Vascular endothelial growth factor polymorphisms and a synchronized examination of plasma and tissue expression in epithelial ovarian cancers.

Science.gov (United States)

Bhaskari, J; Premalata, C S; Shilpa, V; Rahul, B; Pallavi, V R; Ramesh, G; Krishnamoorthy, Lakshmi

2016-01-01

In this study, we have analyzed six genetic polymorphisms of the VEGF-A gene and correlated the genetic data with plasma and tissue expression of VEGF-A in epithelial ovarian carcinomas. A total of 130 cases including 95 malignant carcinomas, 17 low malignant potential and 18 benign tumours were studied. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were studied by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma levels of VEGF-A were estimated by enzyme-linked immunosorbent assay (ELISA) and tissue expression of VEGF-A by immunohistochemistry (IHC). Four polymorphisms of the above excluding rs699947 and rs3025039 showed significant association with malignancy, and we observed the presence of positive correlation between haplotype CCGGCC and increased expression of VEGF-A in both plasma and tissues which also correlated with poor prognosis and recurrence suggesting a probable increase in resistance to treatment in such carriers. Highly upregulated tissue expression of VEGF-A was seen in all epithelial ovarian carcinomas with intensity of expression increasing from benign to malignant cases. ELISA data from our study showed an increase in circulating levels of VEGF-A in malignancies. VEGF-A plasma levels can be employed as a biomarker for high-grade malignancy in epithelial ovarian cancers alongside tissue expression and CA-125 levels. This study is unique due to the fact that a simultaneous analysis of plasma and tissue expression has been demonstrated and is a first such study in epithelial ovarian cancers and representing the Indian population (South-east Asian) synchronized with genetic polymorphism data as well.

Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors

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Aakhus Svend

2010-01-01

Full Text Available Abstract Background Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2 is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease. Methods Echocardiography was performed in 69 patients with neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher's exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation. Results Mean strain was -21% ± 5. Thirty-three patients had reduced RV function (strain > -20%, mean -16% ± 3. Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR. Thirty-six patients had normal or mildly reduced RV function (strain ≤ -20%, mean -25% ± 3. There was a significant inverse correlation between RV function and plasma CCN2 levels (r = 0.47, p Conclusions Elevated plasma CCN2 levels are associated with RV dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages.

Tissue regenerating functions of coagulation factor XIII

DEFF Research Database (Denmark)

Soendergaard, C; Kvist, P H; Seidelin, J B

2013-01-01

The protransglutaminase factor XIII (FXIII) has recently gained interest within the field of tissue regeneration, as it has been found that FXIII significantly influences wound healing by exerting a multitude of functions. It supports haemostasis by enhancing platelet adhesion to damaged......-receptor 2 and the αVβ3 integrin is important for angiogenesis supporting formation of granulation tissue. Chronic inflammatory conditions involving bleeding and activation of the coagulation cascade have been shown to lead to reduced FXIII levels in plasma. Of particular importance for this review...

Expression and localization of tissue factor pathway inhibitor-2 in normal and atherosclerotic human vessels

NARCIS (Netherlands)

Crawley, James T. B.; Goulding, David A.; Ferreira, Valérie; Severs, Nicholas J.; Lupu, Florea

2002-01-01

Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type, serine protease inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein, plasmin, certain matrix metalloproteinases, and the tissue factor:activated factor VII complex. In this study, we investigated TFPI-2

The assessment of cold atmospheric plasma treatment of DNA in synthetic models of tissue fluid, tissue and cells

Science.gov (United States)

Szili, Endre J.; Gaur, Nishtha; Hong, Sung-Ha; Kurita, Hirofumi; Oh, Jun-Seok; Ito, Masafumi; Mizuno, Akira; Hatta, Akimitsu; Cowin, Allison J.; Graves, David B.; Short, Robert D.

2017-07-01

There is a growing literature database that demonstrates the therapeutic potential of cold atmospheric plasma (herein referred to as plasma). Given the breadth of proposed applications (e.g. from teeth whitening to cancer therapy) and vast gamut of plasma devices being researched, it is timely to consider plasma interactions with specific components of the cell in more detail. Plasma can produce highly reactive oxygen and nitrogen species (RONS) such as the hydroxyl radical (OH•), peroxynitrite (ONOO-) and superoxide (\\text{O}2- ) that would readily modify essential biomolecules such as DNA. These modifications could in principle drive a wide range of biological processes. Against this possibility, the reported therapeutic action of plasmas are not underpinned by a particularly deep knowledge of the potential plasma-tissue, -cell or -biomolecule interactions. In this study, we aim to partly address this issue by developing simple models to study plasma interactions with DNA, in the form of DNA-strand breaks. This is carried out using synthetic models of tissue fluid, tissue and cells. We argue that this approach makes experimentation simpler, more cost-effective and faster than compared to working with real biological materials and cells. Herein, a helium plasma jet source was utilised for these experiments. We show that the plasma jet readily induced DNA-strand breaks in the tissue fluid model and in the cell model, surprisingly without any significant poration or rupture of the phospholipid membrane. In the plasma jet treatment of the tissue model, DNA-strand breaks were detected in the tissue mass after pro-longed treatment (on the time-scale of minutes) with no DNA-strand breaks being detected in the tissue fluid model underneath the tissue model. These data are discussed in the context of the therapeutic potential of plasma.

[Relations between plasma-erythrocyte viscosity factors and ESR].

Science.gov (United States)

Cortinovis, A; Crippa, A; Crippa, M; Bosoni, T; Moratti, R

1992-09-01

The ESR is usually put in relationship: to the real density of the RBCs (erythrocytes) (difference between the RBC specific gravity and the plasma one), and to the resistance that the RBCs meet moving in a medium, which is due to the plasma viscosity and to the total external RBC surface. When the RBCs take shape of aggregates, their external surface is decreased and ESR increases. The most important plasma factor causing changes in ESR is the fibrinogen level followed by the plasma globulins and by the products arising from the tissue damage. The resistance that the RBCs meet moving in the plasma is well expressed by the measurement of the plasma-RBC viscosity considering that is inclusive of both factors that are the plasma viscosity and the external RBC surface. The plasma-RBC viscosity is the resultant of several factors: Fa = Fb - Fe - Fs - Fm, were: Fa is the resultant, Fb the attracting forces due to the proteic macromolecules, Fe the repulsing forces due the negative charges. Fs the repulsing forces due to the shear-stress, Fm the force which opposes itself against the surface tension of the aggregation; it depends on the RBC morphology and on the RBC rigidity. The ESR has been recently used like an index of the RBC aggregation. The Authors study the relationship between several hemorheological parameters and the ESR in infective and inflammatory processes.(ABSTRACT TRUNCATED AT 250 WORDS)

The genetic variation rs6903956 in the novel androgen-dependent tissue factor pathway inhibitor regulating protein (ADTRP) gene is not associated with levels of plasma coagulation factors in the Singaporean Chinese

OpenAIRE

Chang, Xuling; Chin, Hui-Lin; Quek, Swee-Chye; Goh, Daniel Y. T.; Dorajoo, Rajkumar; Friedlander, Yechiel; Heng, Chew-Kiat

2017-01-01

Background Genome-wide association study (GWAS) has reported that rs6903956 within the first intron of androgen-dependent tissue factor pathway inhibitor (TFPI) regulating protein (ADTRP) gene is associated with coronary artery disease (CAD) risk in the Chinese population. Although ADTRP is believed to be involved in the upregulation of TFPI, the underlying mechanism involved is largely unknown. This study investigated the association of rs6903956 with plasma Factor VII coagulant activity (FV...

Tissue and plasma enzyme activities in juvenile green iguanas.

Science.gov (United States)

Wagner, R A; Wetzel, R

1999-02-01

To determine activities of intracellular enzymes in 8 major organs in juvenile green iguanas and to compare tissue and plasma activities. 6 green iguanas iguanas, but high values may not always indicate overt muscle disease. The AMS activity may be specific for the pancreas, but the wide range of plasma activity would likely limit its diagnostic usefulness. Activities of AST and LDH may reflect tissue damage or inflammation, but probably do not reflect damage to specific tissues or organs.

ADIPONECTIN AND C-REACTIVE PROTEIN RELATIONSHIP IN PLASMA AND ADIPOSE TISSUE (STUDY AMONG HEALTHY OBESE EGYPTIAN FEMALES)

International Nuclear Information System (INIS)

SOLIMAN, S.E.T.

2008-01-01

The adipokine, adiponectin inhibits vascular inflammation and acts as an endogenous modulator of obesity - linked diseases. High - sensitive C-reactive protein (hs-CRP) is recently debated as a risk factor and mediator for atherosclerosis. The present study investigated the association between adiponectin and hs-CRP in plasma and adipose tissue, and their relation to body composition and insulin sensitivity in a cohort of normal (30 subjects), obese (30 subjects) and morbidly - obese females (10 subjects). Messenger RNA (mRNA) expression of CRP and adiponectin in human adipose tissue were measured using real-time polymerase chain reaction. Plasma adiponectin and insulin were measured using radioimmunoassay methods, while, plasma hs-CRP was measured using ultrasensitive latex method.Results showed that adiponectin was negatively correlated with weight, BMI and insulin sensitivity index, and positively correlated with HDLc. The plasma hs-CRP levels were negatively correlated with plasma adiponectin. The plasma adiponectin levels being significantly lower and plasma hs-CRP being significantly higher in obese than normal females. Real- Time PCR analysis revealed the expression of CRP m-RNA in human adipose tissue and this was inversely correlated to adiponectin m RNA. These results suggest that elevation of CRP and reduction of adiponectin could emerge as mediators of atherogenesis and insulin resistance

Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

International Nuclear Information System (INIS)

Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y.; Broze, G.J. Jr.

1990-01-01

The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec -1 . The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2 endash-to 3 endash fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia

Plasma rich in growth factors in dentistry

Directory of Open Access Journals (Sweden)

Ana Glavina

2017-06-01

Full Text Available Background Plasma rich in growth factors (PRGF has wider use in many fields of dentistry due to its endogenous biocompatible regenerative potential i.e., their potential to stimulate and accelerate tissue healing and bone regeneration. Aims This review shows the increasing use of PRGF technology in various fields of dentistry. Methods In the last nine years PubMed has been searched in order to find out published articles upon PRGF in dentistry and 36 papers have been included. Results PRGF technology has many advantages with positive clinical and biological outcomes in tissue healing and bone regeneration. Conclusion In order to determine the most effective therapeutic value for patients, further research is required.

Association between plasma metabolites and gene expression profiles in five porcine endocrine tissues

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Bassols Anna

2011-07-01

Full Text Available Abstract Background Endocrine tissues play a fundamental role in maintaining homeostasis of plasma metabolites such as non-esterified fatty acids and glucose, the levels of which reflect the energy balance or the health status of animals. However, the relationship between the transcriptome of endocrine tissues and plasma metabolites has been poorly studied. Methods We determined the blood levels of 12 plasma metabolites in 27 pigs belonging to five breeds, each breed consisting of both females and males. The transcriptome of five endocrine tissues i.e. hypothalamus, adenohypophysis, thyroid gland, gonads and backfat tissues from 16 out of the 27 pigs was also determined. Sex and breed effects on the 12 plasma metabolites were investigated and associations between genes expressed in the five endocrine tissues and the 12 plasma metabolites measured were analyzed. A probeset was defined as a quantitative trait transcript (QTT when its association with a particular metabolic trait achieved a nominal P value Results A larger than expected number of QTT was found for non-esterified fatty acids and alanine aminotransferase in at least two tissues. The associations were highly tissue-specific. The QTT within the tissues were divided into co-expression network modules enriched for genes in Kyoto Encyclopedia of Genes and Genomes or gene ontology categories that are related to the physiological functions of the corresponding tissues. We also explored a multi-tissue co-expression network using QTT for non-esterified fatty acids from the five tissues and found that a module, enriched in hypothalamus QTT, was positioned at the centre of the entire multi-tissue network. Conclusions These results emphasize the relationships between endocrine tissues and plasma metabolites in terms of gene expression. Highly tissue-specific association patterns suggest that candidate genes or gene pathways should be investigated in the context of specific tissues.

Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

Energy Technology Data Exchange (ETDEWEB)

Miller, V., E-mail: vmiller@coe.drexel.edu; Lin, A.; Brettschneider, J.; Fridman, G.; Fridman, A. [AJ Drexel Plasma Institute, Drexel University, Camden, New Jersey 08103 (United States); Kako, F.; Gabunia, K.; Kelemen, S.; Autieri, M. [Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 (United States)

2015-12-15

Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue.

Plasma transthyretin. Tissue sites of degradation and turnover in the rat

International Nuclear Information System (INIS)

Makover, A.; Moriwaki, H.; Ramakrishnan, R.; Saraiva, M.J.; Blaner, W.S.; Goodman, D.S.

1988-01-01

Transthyretin (TTR) is involved in the plasma transport of both retinol and thyroid hormones. TTR is synthesized in the liver and choroid plexus, and in small amounts in several other tissues. A study was conducted to determine the tissue sites of degradation and turnover of TTR in the rat. The study employed TTR labeled with tyramine cellobiose (TC) and the trapped ligand method. Samples of purified rat TTR were labeled either with 125I-TC or directly with 131I. A mixture of the two labeled TTRs was injected intravenously into six rats. Blood samples were collected via a venous catheter for kinetic (turnover) analysis. After 24 or 48 h, the rats were killed, and 23 different tissues/organs were assayed as possible sites of TTR degradation. Derivatization of TTR with TC did not appreciably alter TTR plasma kinetics. Plasma turnover data were best fit by a three-pool model. The mean fractional turnover of plasma TTR was 0.15/h, and of total body TTR 0.04/h. The major sites of TTR degradation were the liver (36-38% of total body TTR degradation, almost all in hepatocytes), muscle (12-15%), and skin (8-10%). Tissues that were sites of 1-8% of body TTR degradation included kidneys, adipose tissue, testes, and the gastrointestinal tract. Less than 1% of total TTR degradation occurred in the other tissues examined. A second study was conducted in which labeled TTR was injected intraventricularly into the cerebrospinal fluid in order to explore the degradation of TTR of choroid plexus origin. The kinetics of the appearance and disappearance of such labeled TTR in plasma were physiologically reasonable, with an estimated turnover of cerebrospinal fluid TTR of the order of 0.33/h. The major tissue sites of degradation of labeled TTR injected into cerebrospinal fluid and into plasma were approximately the same

Adipose tissue extracts plasma ammonia after sprint exercise in women and men

DEFF Research Database (Denmark)

Esbjörnsson, Mona; Bülow, Jens; Norman, Barbara

2006-01-01

This study evaluates a possible contribution of adipose tissue to the elimination of plasma ammonia (NH(3)) after high-intensity sprint exercise. In 14 healthy men and women, repeated blood samples for plasma NH(3) analyses were obtained from brachial artery and from a subcutaneous abdominal vein......) with glutamate resulting in its conversion to glutamine. Adipose tissue may thus play an important physiological role in eliminating plasma NH(3) and thereby reducing the risk of NH(3) intoxication after high-intensity exercise.......This study evaluates a possible contribution of adipose tissue to the elimination of plasma ammonia (NH(3)) after high-intensity sprint exercise. In 14 healthy men and women, repeated blood samples for plasma NH(3) analyses were obtained from brachial artery and from a subcutaneous abdominal vein...... before and after three repeated 30-s cycle sprints separated by 20 min of recovery. Biopsies from subcutaneous abdominal adipose tissue were obtained and analyzed for glutamine and glutamate content. After exercise, both arterial and abdominal venous plasma NH(3) concentrations were lower in women than...

Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

International Nuclear Information System (INIS)

Tormoen, Garth W; Khader, Ayesha; Gruber, András; McCarty, Owen J T

2013-01-01

Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis. (paper)

Activation of factor VII bound to tissue factor: A key early step in the tissue factor pathway of blood coagulation

International Nuclear Information System (INIS)

Rao, L.V.M.; Rapaport, S.I.

1988-01-01

Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. The earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were made with purified factor VII, X, and tissue factor; in some experiments antithrombin III and heparin were added to prevent back-activation of factor VII. Factor X was activated at similar rates in reaction mixtures containing either VII or factor VIIa after an initial 30-sec lag with factor VII. In reaction mixtures with factor VII a linear activation of factor X was established several minutes before cleavage of 125 I-labeled factor VII to the two-chain activated molecule was demonstrable on gel profiles. These data suggest that factor VII/tissue factor cannot activate measurable amounts of factor X over several minutes. Overall, the results support the hypothesis that a rapid preferential activation of factor VII bound to tissue factor by trace amounts of factor Xa is a key early step in tissue factor-dependent blood coagulation

Plasma levels of trefoil factors are increased in patients with advanced prostate cancer

DEFF Research Database (Denmark)

Vestergaard, E.M.; Borregaard, Michael Krabbe; Poulsen, Steen Seier

2006-01-01

Through cDNA array analyses and immunohistochemistry on tissue microarrays, trefoil factor 3 (TFF3) was recently shown to be overexpressed in prostate cancer. The purpose of this study was to test the feasibility of using the levels of trefoil factors as a plasma marker for prostate cancer....

Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation.

OpenAIRE

Rao, L V; Rapaport, S I

1988-01-01

Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and factor IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. Our earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were ma...

YKL-40 tissue expression and plasma levels in patients with ovarian cancer

DEFF Research Database (Denmark)

Høgdall, Estrid V S; Ringsholt, Merete; Høgdall, Claus K

2009-01-01

survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker. METHODS: YKL-40 protein expression was determined by immunohistochemistry...... in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients. RESULTS: YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor...... stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40-3.25, p = 0.0004). CONCLUSION: YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic...

Plasma Rich in Growth Factors for the Treatment of Ocular Surface Diseases.

Science.gov (United States)

Anitua, Eduardo; Muruzabal, Francisco; de la Fuente, María; Merayo, Jesús; Durán, Juan; Orive, Gorka

2016-07-01

The purpose of this work is to describe and review the technology of plasma rich in growth factors (PRGF), a novel blood derivative product, in the treatment of ocular surface disorders. To demonstrate the importance of this technology in the treatment of ocular pathologies, a thorough review of the preclinical and clinical literature results obtained following use of the different therapeutic formulations of PRGF was carried out. A literature search for applications of PGRF plasma in the ophthalmology field was carried out using the PubMed database. PRGF involves the use of patient's own biologically active proteins, growth factors, and biomaterial scaffolds for therapeutic purposes. This procedural technology is gaining interest in regenerative medicine due to its potential to stimulate and accelerate the tissue healing processes. The versatility and biocompatibility of this technology opens the door to a personalized medicine on ocular tissue regeneration. This review discusses the state of the art of the new treatments and technologies developed to promote ocular surface tissue regeneration. The standardized protocol that has been developed to source eye drops from PRGF technology is also described. The preclinical research, together with the most relevant clinical applications are summarized and discussed. The preliminary results suggest that the use of PRGF to enhance ocular tissue regeneration is safe and efficient.

Platelet-rich plasma, plasma rich in growth factors and simvastatin in the regeneration and repair of alveolar bone.

Science.gov (United States)

Rivera, César; Monsalve, Francisco; Salas, Juan; Morán, Andrea; Suazo, Iván

2013-12-01

Platelet preparations promote bone regeneration by inducing cell migration, proliferation and differentiation in the area of the injury, which are essential processes for regeneration. In addition, several studies have indicated that simvastatin (SIMV), widely used for the treatment of hypercholesterolemia, stimulates osteogenesis. The objective of this study was to evaluate the effects of treatment with either platelet-rich plasma (PRP) or plasma rich in growth factors (PRGF) in combination with SIMV in the regeneration and repair of alveolar bone. The jaws of Sprague Dawley rats (n=18) were subjected to rotary instrument-induced bone damage (BD). Animals were divided into six groups: BD/H 2 O (n=3), distilled water without the drug and alveolar bone damage; BD/H 2 O/PRP (n=3), BD and PRP; BD/H 2 O/PRGF (n=3), BD and PRGF; BD/SIMV (n=3), BD and water with SIMV; BD/SIMV/PRP (n=3), BD, PRP and SIMV; and BD/SIMV/PRGF (n=3), BD, PRGF and SIMV. Conventional histological analysis (hematoxylin and eosin staining) revealed that the BD/SIMV group showed indicators for mature bone tissue, while the BD/SIMV/PRP and BD/SIMV/PRGF groups showed the coexistence of indicators for mature and immature bone tissue, with no statistical differences between the platelet preparations. Simvastatin did not improve the effect of platelet-rich plasma and plasma rich in growth factors. It was not possible to determine which platelet preparation produced superior effects.

Coronally advanced flap and connective tissue graft with or without plasma rich in growth factors (PRGF) in treatment of gingival recession.

Science.gov (United States)

Jenabian, Niloofar; Motallebnejad, Mina; Zahedi, Ehsan; Sarmast, Nima D; Angelov, Nikola

2018-05-01

Several researchers have tried to improve the results of gingival recession treatment techniques. One of the methods is to use growth factors The present study was undertaken to evaluate the effect of CAF (coronally advanced flap) + CTG (connective tissue graft) + PRGF (plasma rich in growth factors) in the treatment of Miller Class I buccal gingival recession. Twenty-two teeth with Miller Class I gingival recession in 6 patients 26 ‒ 47 years of age were included in a split-mouth designed randomized controlled trial (RCT). In each patient, one side was treated with CAF + CTG + PRGF (test) and the other side was treated with CAF + CTG (control). The following parameters were measured before surgery and up to 6 months after surgery on the mid-buccal surface of the tooth: keratinized tissue width (KTW), clinical attachment level (CAL), probing depth (PD), vertical recession depth (VRD), recession depth (RD), gingival thickness (GT), root coverage in percentage (RC%) and the distance between the CEJ and mucogingival junction (MGJL). Data were analyzed with paired t-test and repeated measures ANOVA. After 6 months noticeable improvements were observed in both groups in all the variables measured except for PD; however, the differences between the two groups were not significant. RC% was 80 ± 25% and 67 ± 28% in the test and control groups, respectively, after 6 months. Both CAF + CTG + PRGF and CAF + CTG treatment modalities resulted in favorable root coverage; however, the addition of PRGF added no measurable significant effect. Key words: Connective tissue graft, dental root coverage, gingival recession, growth factors, mucogingival surgery, periodontal plastic surgery.

A comparative study of tissue inhibitor of metalloproteinases-1 levels in plasma and tumour tissue from patients with primary breast cancer and in plasma from patients with metastatic breast cancer

DEFF Research Database (Denmark)

Rasmussen, Anne-Sofie Schrohl; Mueller, Volkmar; Christensen, Ib Jarle

2008-01-01

OBJECTIVE: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been investigated as a potential tumour marker in breast cancer. Here we investigated the correlation between TIMP-1 in tumour tissue and plasma to evaluate whether TIMP-1 in plasma is actually a surrogate marker for TIMP-1 in prima...

Peritumoral adipose tissue as a source of inflammatory and angiogenic factors in colorectal cancer.

Science.gov (United States)

Amor, S; Iglesias-de la Cruz, M C; Ferrero, E; García-Villar, O; Barrios, V; Fernandez, N; Monge, L; García-Villalón, A L; Granado, M

2016-02-01

Obesity is a risk factor for the development of human colorectal cancer (CC). The aim of this work is to report the inflammatory and angiogenic scenario in lean (BMI  30 kg/m2) patients with and without CC and to assess the role of peritumoral adipose tissue in CC-induced inflammation. Patients were divided in four experimental groups: obese patients with CC (OB-CC), lean patients with CC (LEAN-CC), obese patients without CC (OB), and lean patients without CC (LEAN). Plasma levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-4, IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in OB-CC patients. Peritumoral adipose tissue (TF) explants and cultured mature adipocytes secreted higher amounts of nitrites and nitrates than did control and non-tumoral (NTF) adipose tissue both alone and in response to lipopolysaccharide (LPS). Nitrite and nitrate secretion was also increased in TF explants from OB-CC patients compared with that from LEAN-CC patients. Gene expression of adiponectin, tumor necrosis factor alpha (TNF-α), insulin-like growth factor type I (IGF-I), cyclooxygenase-2 (COX-2), and peroxisome proliferator-activated receptor γ (PPAR-γ) was increased in TF explants from CC patients. LPS increased the gene expression of IL-6, IL-10, TNF-α, vascular endothelial growth factor (VEGF), and COX-2 in OB and in TF explants from OB-CC patients. COX-2 and PPAR-γ inhibition further increased LPS-induced release of nitrites and nitrates in TF explants and adipocytes from OB-CC patients. In conclusion, OB-CC patients have increased plasma levels of pro-inflammatory and angiogenic factors. TF from OB-CC patients shows an increased secretion of inflammatory markers compared with both TF from LEAN-CC and non-tumoral adipose tissue (AT) through a COX-2- and PPAR-γ-independent mechanism.

Analysis of plasma-mediated ablation in aqueous tissue

International Nuclear Information System (INIS)

Jiao Jian; Guo Zhixiong

2012-01-01

Plasma-mediated ablation using ultrafast lasers in transparent media such as aqueous tissues is studied. It is postulated that a critical seed free electron density exists due to the multiphoton ionization in order to trigger the avalanche ionization which causes ablation and during the avalanche ionization process the contribution of laser-induced photon ionization is negligible. Based on this assumption, the ablation process can be treated as two separate processes - the multiphoton and avalanche ionizations - at different time stages; so that an analytical solution to the evolution of plasma formation is obtained for the first time. The analysis is applied to plasma-mediated ablation in corneal epithelium and validated via comparison with experimental data available in the literature. The critical seed free-electron density and the time to initiate the avalanche ionization for sub-picosecond laser pulses are analyzed. It is found that the critical seed free-electron density decreases as the pulse width increases, obeying a t p -5.65 rule. This model is further extended to the estimation of crater size in the ablation of tissue-mimic polydimethylsiloxane (PDMS). The results match well with the available experimental measurements.

Tissue expression and plasma levels of adrenomedullin in renal cancer patients

DEFF Research Database (Denmark)

Michelsen, Jens; Thiesson, Helle; Walter, Steen

2006-01-01

that AM is increased in CC-RCC tumours and that AM is a plasma biomarker for CC-RCC. Tumours and non-malignant kidney tissue were obtained from patients that underwent unilateral nephrectomy. Blood samples were drawn at the day of surgery, 3-6 days after surgery and 4-5 weeks after surgery. AM m...... conclude that elevated tissue AM is a distinguishing feature of CC-RCC compared with other kidney tumours. Plasma AM is not suited as a tumour marker for this disease....

Air plasma treatment of liquid covered tissue: long timescale chemistry

Science.gov (United States)

Lietz, Amanda M.; Kushner, Mark J.

2016-10-01

Atmospheric pressure plasmas have shown great promise for the treatment of wounds and cancerous tumors. In these applications, the sample is usually covered by a thin layer of a biological liquid. The reactive oxygen and nitrogen species (RONS) generated by the plasma activate and are processed by the liquid before the plasma produced activation reaches the tissue. The synergy between the plasma and the liquid, including evaporation and the solvation of ions and neutrals, is critical to understanding the outcome of plasma treatment. The atmospheric pressure plasma sources used in these procedures are typically repetitively pulsed. The processes activated by the plasma sources have multiple timescales—from a few ns during the discharge pulse to many minutes for reactions in the liquid. In this paper we discuss results from a computational investigation of plasma-liquid interactions and liquid phase chemistry using a global model with the goal of addressing this large dynamic range in timescales. In modeling air plasmas produced by a dielectric barrier discharge over liquid covered tissue, 5000 voltage pulses were simulated, followed by 5 min of afterglow. Due to the accumulation of long-lived species such as ozone and N x O y , the gas phase dynamics of the 5000th discharge pulse are different from those of the first pulse, particularly with regards to the negative ions. The consequences of applied voltage, gas flow, pulse repetition frequency, and the presence of organic molecules in the liquid on the gas and liquid reactive species are discussed.

Monitoring of treatment with vitamin K antagonists: recombinant thromboplastins are more sensitive to factor VII than tissue-extract thromboplastins.

Science.gov (United States)

Biedermann, J S; van den Besselaar, A M H P; de Maat, M P M; Leebeek, F W G; Kruip, M J H A

2017-03-01

Essentials Differences in sensitivity to factor VII (FVII) have been suggested between thromboplastins. FVII-induced International Normalized Ratio (INR) changes differ between commercial reagents. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Thromboplastin choice may affect FVII-mediated INR stability. Background Differences regarding sensitivity to factor VII have been suggested for recombinant human and tissue-extract thromboplastins used for International Normalized Ratio (INR) measurement, but the evidence is scarce. Differences in FVII sensitivity are clinically relevant, as they can affect INR stability during treatment with vitamin K antagonists (VKAs). Objectives To determine whether commercial thromboplastins react differently to changes in FVII. Methods We studied the effect of addition of FVII on the INR in plasma by using three tissue-extract (Neoplastin C1+, Hepato Quick, and Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, and CoaguChek XS) thromboplastins. Three different concentrations of purified human FVII (0.006, 0.012 and 0.062 μg mL -1 plasma), or buffer, were added to five certified pooled plasmas of patients using VKAs (INR of 1.5-3.5). Changes in FVII activity were measured with two bioassays (Neoplastin and Recombiplastin), and relative INR changes were compared between reagents. Results After addition of 0.062 μg mL -1 FVII, FVII activity in the pooled plasmas increased by approximately 20% (Neoplastin) or 32% (Recombiplastin) relative to the activity in pooled normal plasma. All thromboplastins showed dose-dependent INR decreases. The relative INR change in the pooled plasmas significantly differed between the six thromboplastins. No differences were observed among recombinant or tissue-extract thromboplastins. Pooled results indicated that the FVII-induced INR change was greater for recombinant than for tissue-extract thromboplastins. Conclusions Differences

Incorporating Platelet-Rich Plasma into Electrospun Scaffolds for Tissue Engineering Applications

Science.gov (United States)

Wolfe, Patricia S.; Ericksen, Jeffery J.; Simpson, David G.; Bowlin, Gary L.

2011-01-01

Platelet-rich plasma (PRP) therapy has seen a recent spike in clinical interest due to the potential that the highly concentrated platelet solutions hold for stimulating tissue repair and regeneration. The aim of this study was to incorporate PRP into a number of electrospun materials to determine how growth factors are eluted from the structures, and what effect the presence of these factors has on enhancing electrospun scaffold bioactivity. PRP underwent a freeze-thaw-freeze process to lyse platelets, followed by lyophilization to create a powdered preparation rich in growth factors (PRGF), which was subsequently added to the electrospinning process. Release of protein from scaffolds over time was quantified, along with the quantification of human macrophage and adipose-derived stem cell (ADSC) chemotaxis and proliferation. Protein assays demonstrated a sustained release of protein from PRGF-containing scaffolds at up to 35 days in culture. Scaffold bioactivity was enhanced as ADSCs demonstrated increased proliferation in the presence of PRGF, whereas macrophages demonstrated increased chemotaxis to PRGF. In conclusion, the work performed in this study demonstrated that the incorporation of PRGF into electrospun structures has a significant positive influence on the bioactivity of the scaffolds, and may prove beneficial in a number of tissue engineering applications. PMID:21679135

Air plasma treatment of liquid covered tissue: long timescale chemistry

International Nuclear Information System (INIS)

Lietz, Amanda M; Kushner, Mark J

2016-01-01

Atmospheric pressure plasmas have shown great promise for the treatment of wounds and cancerous tumors. In these applications, the sample is usually covered by a thin layer of a biological liquid. The reactive oxygen and nitrogen species (RONS) generated by the plasma activate and are processed by the liquid before the plasma produced activation reaches the tissue. The synergy between the plasma and the liquid, including evaporation and the solvation of ions and neutrals, is critical to understanding the outcome of plasma treatment. The atmospheric pressure plasma sources used in these procedures are typically repetitively pulsed. The processes activated by the plasma sources have multiple timescales—from a few ns during the discharge pulse to many minutes for reactions in the liquid. In this paper we discuss results from a computational investigation of plasma–liquid interactions and liquid phase chemistry using a global model with the goal of addressing this large dynamic range in timescales. In modeling air plasmas produced by a dielectric barrier discharge over liquid covered tissue, 5000 voltage pulses were simulated, followed by 5 min of afterglow. Due to the accumulation of long-lived species such as ozone and N x O y , the gas phase dynamics of the 5000th discharge pulse are different from those of the first pulse, particularly with regards to the negative ions. The consequences of applied voltage, gas flow, pulse repetition frequency, and the presence of organic molecules in the liquid on the gas and liquid reactive species are discussed. (paper)

High-speed photography of plasma during excimer laser-tissue interaction

International Nuclear Information System (INIS)

Murray, Andrea K; Dickinson, Mark R

2004-01-01

During high fluence laser-tissue interaction, ablation of tissue occurs, debris is removed from the ablation site and is then ejected at high velocity. This debris may be observed as a combination of luminous plasma and non-luminous plume, both of which have the potential to shield the ablation site. This study examined the role of ablation debris in shielding the tissue and determined its effects on the ablation rate over a range of laser pulse energies, pulse repetition rates and pulse numbers for dentine; the velocity differences between hard and soft tissues were also examined. High-speed photography was carried out at up to 1 x 10 8 frames per second. A maximum velocity of 2.58 ± 0.52 x 10 4 m s -1 was recorded for dentine debris within the first 10 ns following ejection. The maximum duration of tissue shielding due to a single pulse, determined by attenuation of a probe beam, was found to be ∼7 ms, ∼80 μs of which was due to luminous plasma and the remainder due to the non-luminous plume

Comparison of tissue damage caused by various laser systems with tissue tolerable plasma by light and laser scan microscopy

International Nuclear Information System (INIS)

Vandersee, Staffan; Lademann, Jürgen; Richter, Heike; Patzelt, Alexa; Lange-Asschenfeldt, Bernhard

2013-01-01

Tissue tolerable plasma (TTP) represents a novel therapeutic method with promising capabilities in the field of dermatological interventions, in particular disinfection but also wound antisepsis and regeneration. The energy transfer by plasma into living tissue is not easily educible, as a variety of features such as the medium’s actual molecule-stream, the ions, electrons and free radicals involved, as well as the emission of ultraviolet, visible and infrared light contribute to its increasingly well characterized effects. Thus, relating possible adversary effects, especially of prolonged exposure to a single component of the plasma’s mode of action, is difficult. Until now, severe adverse events connected to plasma exposure have not been reported when conducted according to existing therapeutic protocols. In this study, we have compared the tissue damage-potential of CO 2 and dye lasers with TTP in a porcine model. After exposure of pig ear skin to the three treatment modalities, all specimens were examined histologically and by means of laser scan microscopy (LSM). Light microscopical tissue damage could only be shown in the case of the CO 2 laser, whereas dye laser and plasma treatment resulted in no detectable impairment of the specimens. In the case of TTP, LSM examination revealed only an impairment of the uppermost corneal layers of the skin, thus stressing its safety when used in vivo. (letter)

[Determination of acyclovir in mouse plasma and tissues by reversed-phase high performance liquid chromatography].

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Xu, Y; Zhou, S W; Tang, J L; Huang, L Q

2001-11-01

The aim of this study was to establish an high performance liquid chromatographic method for determining acyclovir (ACV) concentration in mouse plasma and tissues. A solution of 0.25 mL 60 g/L perchloric acid and 0.25 mL acetonitrile was added into 0.2 mL plasma or 0.2 g tissues to precipitate proteins. Following centrifugation, the supernatant obtained was injected into a reversed-phase column. Operating conditions were Hypersil ODS column(250 mm x 4.6 mm i.d., 5 microns), methanol-water-acetic acid(1:99:0.5, volume ratio) solution as mobile phase at a flow rate of 1.5 mL/min, UV detection at 252 nm. The detection limit of ACV concentration in plasma was 20 micrograms/L and that in tissues was 50 ng/g. The standard curves for ACV were linear in plasma and homogenate of tissues (r > 0.99). The precision of the method was good and the recoveries of ACV were higher than 97.5%. So this method is rapid, accurate and convenient for determination of ACV concentrations in plasma and tissues.

YKL-40 tissue expression and plasma levels in patients with ovarian cancer

International Nuclear Information System (INIS)

Høgdall, Estrid VS; Christensen, Lise H; Ringsholt, Merete; Høgdall, Claus K; Christensen, Ib Jarle; Johansen, Julia S; Kjaer, Susanne K; Blaakaer, Jan; Ostenfeld-Møller, Lene; Price, Paul A

2009-01-01

YKL-40 (chitinase-3-like-1) is a member of 'mammalian chitinase-like proteins'. The protein is expressed in many types of cancer cells and the highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker. YKL-40 protein expression was determined by immunohistochemistry in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients. YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor cell expression was higher in OC than in borderline tumors (p = 0.001), and associated with FIGO stage (p < 0.0001) and histological subtype (p = 0.0009). Positive YKL-40 expression (≥ 5% staining) was not associated with reduced survival. Plasma YKL-40 was also higher in patients with OC than in patients with borderline tumors (p < 0.0001), and it was positively correlated to serum CA-125 (p < 0.0001) and FIGO stage (p = 0.0001). Univariate Cox analysis of plasma YKL-40 showed association with overall survival (p < 0.0001). Multivariate Cox analysis, including plasma YKL-40, serum CA125, FIGO stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40–3.25, p = 0.0004). YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic biomarker in patients with OC

Paraneoplastic scleroderma-like tissue reactions in the setting of an underlying plasma cell dyscrasia: a report of 10 cases.

Science.gov (United States)

Magro, Cynthia M; Iwenofu, Hans; Nuovo, Gerard J

2013-07-01

Systemic plasma cell dyscrasias have diverse manifestations in the skin and include an inflammatory paraneoplastic process. We encountered cases of scleroderma and eosinophilic fasciitis in the setting of an underlying plasma cell dyscrasia. Ten cases of scleroderma-like tissue reactions in the setting of an underlying plasma cell dyscrasia were encountered. The biopsies were stained for Transforming growth factor (Transforming growth factor) beta, IgG4, kappa, and lambda. Patients presented with a sclerodermoid reaction represented by eosinophilic fasciitis (5 cases), morphea (3 cases), and systemic scleroderma (2 cases). The mean age of presentation was 70 years with a striking female predominance (4:1). Acral accentuation was noted in 8 cases. In 6 of the cases, the cutaneous sclerosis antedated (4 cases) by weeks to 2 years or occurred concurrently (2 cases) with the initial diagnosis of the plasma cell. The biopsies showed changes typical of eosinophilic fasciitis and/or scleroderma. In 5 cases, light chain-restricted plasma cells were present on the biopsy. There was staining of the plasma cells for Transforming growth factor beta in 3 out of 5 cases tested. In any older patient presenting with a sudden onset of eosinophilic fasciitis or scleroderma especially with acral accentuation, investigations should be conducted in regards to an underlying plasma cell dyscrasia.

Plasma luminescence feedback control system for precise ultrashort pulse laser tissue ablation

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Kim, Beop-Min; Feit, Michael D.; Rubenchik, Alexander M.; Gold, David M.; Darrow, Christopher B.; Marion, John E., II; Da Silva, Luiz B.

1998-05-01

Plasma luminescence spectroscopy was used for precise ablation of bone tissue without damaging nearby soft tissue using an ultrashort pulse laser. Strong contrast of the luminescence spectra between bone marrow and spinal cord provided the real time feedback control so bone tissue is selectively ablated while preserving the spinal cord.

Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

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Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

2016-06-23

The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

Plasma and tissue oxidative stress index in patients with rheumatic and degenerative heart valve disease.

Science.gov (United States)

Rabus, Murat; Demirbağ, Recep; Sezen, Yusuf; Konukoğlu, Oğuz; Yildiz, Ali; Erel, Ozcan; Zeybek, Rahmi; Yakut, Cevat

2008-12-01

We investigated whether patients with rheumatic and degenerative heart valve disease (HVD) differed with regard to plasma and tissue oxidative stress index (OSI). The study included 56 patients who underwent valve replacement due to rheumatic (n=32; 15 males; mean age 47+/-10 years) and degenerative (n=24; 13 males; mean age 55+/-12 years) HVD. Plasma and tissue total oxidative status (TOS) and total antioxidative capacity (TAC) levels were measured and OSI was calculated. Patients with degenerative HVD had significantly higher age, increased interventricular septum thickness, and higher frequency of aortic stenosis, whereas the incidence of mitral stenosis was higher in patients with rheumatic HVD (p0.05). Tissue TAC was significantly lower in patients with rheumatic HVD (p=0.027), whereas tissue TOS and OSI were similar between the two HVD groups (p>0.05). In bivariate analysis, plasma OSI did not show any correlation with clinical, laboratory, and echocardiographic variables (p>0.05). Our data show that plasma and tissue OSI levels are similar in patients with rheumatic and degenerative HVD.

Plasma disappearance, urine excretion, and tissue distribution of ribavirin in rats and rhesus monkeys

International Nuclear Information System (INIS)

Ferrara, E.A.; Oishi, J.S.; Wannemacher, R.W. Jr.; Stephen, E.L.

1981-01-01

Ribavirin has been shown to have broad-spectrum antiviral. To study its tissue distribution and disappearance rate, a single dose of 10 mg/kg which contained 10 microCi of [14C]ribavirin was injected intravenously into rhesus monkeys and intramuscularly into monkeys and rats. Except for peak plasma concentrations and the initial phases of the plasma disappearance and urine excretion curves, no significant difference was observed between plasma, tissue, or urine values for intramuscularly or intravenously injected monkeys. Plasma disappearance curves were triphasic; plasma concentrations of ribavirin were similar for both monkeys and rats. Rats excreted ribavirin in the urine more rapidly and to a greater extent (82% excreted in 24 h) than did monkeys (60% excreted in 72 h). In the rat, only 3% of the injected [14C]ribavirin was detected in expired CO2. Therefore, for both species, urine was the major route for the elimination of labeled ribavirin and its metabolites from the body. In monkeys, the amount of parent drug in blood cells increased through 48 h and remained stable for 72 h, whereas in rats, ribavirin decreased at a rate similar to the plasma disappearance curve. Concentrations of ribavirin at 8 h were consistently higher in monkeys than in rats for all tissues except the brain. Thus, these differences in blood cellular components and organ content and in urine excretion suggested that there was greater tissue retention of ribavirin in monkeys than in rats

The mechanism of plasma-assisted penetration of NO2- in model tissues

Science.gov (United States)

He, Tongtong; Liu, Dingxin; Liu, Zhijie; Liu, Zhichao; Li, Qiaosong; Rong, Mingzhe; Kong, Michael G.

2017-11-01

Cold atmospheric plasmas are reportedly capable of enhancing the percutaneous absorption of drugs, which is a development direction of plasma medicine. This motivated us to study how the enhancement effect was realized. In this letter, gelatin gel films were used as surrogates of human tissues, NaNO2 was used as a representative of small-molecule drugs, and cross-field and linear-field plasma jets were used for the purpose of enhancing the penetration of NaNO2 through the gelatin gel films. The permeability of gelatin gel films was quantified by measuring the NO2- concentration in water which was covered by those films. It was found that the gas flow and electric field of cold plasmas played a crucial role in the permeability enhancement of the model tissues, but the effect of gas flow was mainly confined in the surface layer, while the effect of the electric field was holistic. Those effects might be attributed to the localized squeezing of particles by gas flow and the weakening of the ion-dipole interaction by the AC electric field. The enhancement effect decreases with the increasing mass fraction of gelatin because the macromolecules of gelatin could significantly hinder the penetration of small molecules in the model tissues.

Plasma and tissue osteopontin expression in cutaneous lichen planus and its relation to metabolic syndrome

International Nuclear Information System (INIS)

Awad, M.A.I.

2015-01-01

Lichen planus (LP) is a chronic inflammatory disease that affects the skin, mucous membranes and appendages. Although its pathogenesis is still unclear, some studies showed that autoreactive cytotoxic T lymphocytes are the effector cells which cause degeneration and destruction of keratinocytes. Osteopontin (OPN) is expressed during inflammation by natural killer cells, activated T cells and macrophages and classified as a T-helper type 1 (Th1) cytokine. Plasma OPN has been reported to be a potential clinical marker for prediction of atherosclerosis. The mean values of plasma and tissue OPN in the lesional skin of LP patients were significantly higher than that in the control group (P Values for both plasma and tissue OPN were < 0.001). Correlating levels of plasma OPN in the LP patients to metabolic syndrome parameters showed a statistically significant correlation with dyslipidemia and diabetes mellitus. In conclusion, levels of plasma and tissue OPN were higher in cutaneous lichen planus patients than controls and plasma OPN could be a marker for cardiovascular risk in these patients

Infiltration of plasma rich in growth factors enhances in vivo angiogenesis and improves reperfusion and tissue remodeling after severe hind limb ischemia.

Science.gov (United States)

Anitua, Eduardo; Pelacho, Beatriz; Prado, Roberto; Aguirre, José Javier; Sánchez, Mikel; Padilla, Sabino; Aranguren, Xabier L; Abizanda, Gloria; Collantes, María; Hernandez, Milagros; Perez-Ruiz, Ana; Peñuelas, Ivan; Orive, Gorka; Prosper, Felipe

2015-03-28

PRGF is a platelet concentrate within a plasma suspension that forms an in situ-generated fibrin-matrix delivery system, releasing multiple growth factors and other bioactive molecules that play key roles in tissue regeneration. This study was aimed at exploring the angiogenic and myogenic effects of PRGF on in vitro endothelial cells (HUVEC) and skeletal myoblasts (hSkMb) as well as on in vivo mouse subcutaneously implanted matrigel and on limb muscles after a severe ischemia. Human PRGF was prepared and characterized. Both proliferative and anti-apoptotic responses to PRGF were assessed in vitro in HUVEC and hSkMb. In vivo murine matrigel plug assay was conducted to determine the angiogenic capacity of PRGF, whereas in vivo ischemic hind limb model was carried out to demonstrate PRGF-driven vascular and myogenic regeneration. Primary HUVEC and hSkMb incubated with PRGF showed a dose dependent proliferative and anti-apoptotic effect and the PRGF matrigel plugs triggered an early and significant sustained angiogenesis compared with the control group. Moreover, mice treated with PRGF intramuscular infiltrations displayed a substantial reperfusion enhancement at day 28 associated with a fibrotic tissue reduction. These findings suggest that PRGF-induced angiogenesis is functionally effective at expanding the perfusion capacity of the new vasculature and attenuating the endogenous tissue fibrosis after a severe-induced skeletal muscle ischemia. Copyright © 2015 Elsevier B.V. All rights reserved.

Tissue to plasma capillary permeability of 131I-albumin in the perfused rabbit ear

DEFF Research Database (Denmark)

Bent-Hansen, L; Svendsen, Jesper Hastrup

1991-01-01

The tissue to plasma transfer of 131I-albumin was recorded in perfused rabbit ears (n = 6) following equilibration for 24 hr. 125I-fibrinogen served as the plasma marker, and was introduced intravenously 15 min before clamping. The ears were rollerpump perfused with isotonic diluted plasma...

Platelet-rich plasma derived growth factors contribute to stem cell differentiation in musculoskeletal regeneration

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Qian, Yun; Han, Qixin; Chen, Wei; Song, Jialin; Zhao, Xiaotian; Ouyang, Yuanming; Yuan, Weien; Fan, Cunyi

2017-10-01

Stem cell treatment and platelet-rich plasma (PRP) therapy are two significant issues in regenerative medicine. Stem cells such as bone marrow mesenchymal stem cells, adipose-derived stem cells and periodontal ligament stem cells can be successfully applied in the field of tissue regeneration. PRP, a natural product isolated from whole blood, can secrete multiple growth factors (GFs) for regulating physiological activities. These GFs can stimulate proliferation and differentiation of different stem cells in injury models. Therefore, combination of both agents receives wide expectations in regenerative medicine, especially in bone, cartilage and tendon repair. In this review, we thoroughly discussed the interaction and underlying mechanisms of platelet-rich plasma derived growth factors with stem cells, and assessed their functions in cell differentiation for musculoskeletal regeneration.

Elevated circulating soluble thrombomodulin activity, tissue factor activity and circulating procoagulant phospholipids: new and useful markers for pre-eclampsia?

Science.gov (United States)

Rousseau, Aurélie; Favier, Rémi; Van Dreden, Patrick

2009-09-01

One of the most frequently proposed mechanisms for pre-eclampsia refers to uteroplacental thrombosis. However, the contribution of classical thrombotic risk factors remains questionable. The aims of this study were to investigate the activities of thrombomodulin, tissue factor and procoagulant phospholipids to assess endothelial cell injury in pregnant women with pre-eclampsia and to compare them with other classical markers of vascular injury and thrombotic risk. Using three new functional assays we studied the plasma levels of these new markers in 35 healthy women, 30 healthy pregnant women, and 35 women with pre-eclampsia. We found that plasma levels of thrombomodulin activity, tissue factor activity and procoagulant phospholipids were significantly elevated in women with pre-eclampsia versus normal pregnant and non-pregnant women. It is thus suggested that elevated levels of these parameters in pre-eclampsia may reflect vascular endothelium damage, and may be a more valuable biomarker than antigen for the assessment of endothelial damage in pre-eclampsia. The high increased levels of procoagulant phospholipids and tissue factor activities in pre-eclampsia could suggest that the procoagulant potential may be implicated in this complication and makes these markers very promising for the understanding, follow-up and therapeutic handling of complicated pregnancy.

Concentrations of danofloxacin 18% solution in plasma, milk and tissues after subcutaneous injection in dairy cows

International Nuclear Information System (INIS)

Mestorino, N.; Marchetti, M.L.; Turic, E.; Pesoa, J.; Errecalde, J.

2009-01-01

Danofloxacin is a fluoroquinolone developed for use in veterinary medicine. Its concentrations and pharmacokinetic profile in plasma, milk and tissues of lactating dairy cows were determined, and its milk withdrawal time (WT) calculated. Twenty-one dairy cows received a single subcutaneous administration of 18% mesylate danofloxacin salt (6 mg kg -1 ). Plasma and milk samples were obtained at different times until 48 h. Groups of three animals were sacrificed at different post-administration times and tissue samples (mammary gland, uterus, duodenum, jejunum, ileum, colon and mesenteric lymph nodes) obtained. Danofloxacin concentrations were determined by liquid chromatography with fluorescence detection. The milk WT was calculated by the Time to Safe Concentration method (Software WTM 1.4, EMEA). Danofloxacin was rapidly absorbed and its distribution from plasma to all sampled tissues and milk was extensive. Milk and tissues concentrations were several times above those found in plasma. Plasma area under the curve (AUCp) was 9.69 μg h mL -1 and its elimination half life (T β 1/2 ) was 12.53 h. AUC values for the various tissues and milk greatly exceeded AUCp. T β 1/2 from milk and tissues ranged between 4.57 and 21.91 h and the milk withdrawal time was 73.48 h. The reported results support the potential use of danofloxacin in the treatment of mastitis and other infections in milk cows with 3 days of withdrawal

Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients

Directory of Open Access Journals (Sweden)

Takashi Takeshita

2017-10-01

Full Text Available BACKGROUND: ESR1 mutation in circulating cell-free DNA (cfDNA is emerging as a noninvasive biomarker of acquired resistance to endocrine therapy, but there is a paucity of data comparing the status of ESR1 gene in cfDNA with that in its corresponding tumor tissue. The objective of this study is to validate the degree of concordance of ESR1 mutations between plasma and tumor tissue. METHODS: ESR1 ligand-binding domain mutations Y537S, Y537N, Y537C, and D538G were analyzed using droplet digital PCR in 35 patients with metastatic breast cancer (MBC (35 tumor tissue samples and 67 plasma samples. RESULTS: Of the 35 paired samples, 26 (74.3% were concordant: one patient had detectable ESR1 mutations both plasma (ESR1 Y537S/Y537N and tumor tissue (ESR1 Y537S/Y537C, and 25 had WT ESR1 alleles in both. Nine (25.7% had discordance between the plasma and tissue results: five had mutations detected only in their tumor tissue (two Y537S, one Y537C, one D538G, and one Y537S/Y537N/D538G, and four had mutations detected only in their plasma (one Y537S, one Y537N, and two Y537S/Y537N/D538G. Furthermore, longitudinal plasma samples from 19 patients were used to assess changes in the presence of ESR1 mutations during treatment. Eleven patients had cfDNA ESR1 mutations over the course of treatment. A total of eight of 11 patients with MBC with cfDNA ESR1 mutations (72.7% had the polyclonal mutations. CONCLUSION: We have shown the independent distribution of ESR1 mutations between plasma and tumor tissue in 35 patients with MBC.

A random sampling approach for robust estimation of tissue-to-plasma ratio from extremely sparse data.

Science.gov (United States)

Chu, Hui-May; Ette, Ene I

2005-09-02

his study was performed to develop a new nonparametric approach for the estimation of robust tissue-to-plasma ratio from extremely sparsely sampled paired data (ie, one sample each from plasma and tissue per subject). Tissue-to-plasma ratio was estimated from paired/unpaired experimental data using independent time points approach, area under the curve (AUC) values calculated with the naïve data averaging approach, and AUC values calculated using sampling based approaches (eg, the pseudoprofile-based bootstrap [PpbB] approach and the random sampling approach [our proposed approach]). The random sampling approach involves the use of a 2-phase algorithm. The convergence of the sampling/resampling approaches was investigated, as well as the robustness of the estimates produced by different approaches. To evaluate the latter, new data sets were generated by introducing outlier(s) into the real data set. One to 2 concentration values were inflated by 10% to 40% from their original values to produce the outliers. Tissue-to-plasma ratios computed using the independent time points approach varied between 0 and 50 across time points. The ratio obtained from AUC values acquired using the naive data averaging approach was not associated with any measure of uncertainty or variability. Calculating the ratio without regard to pairing yielded poorer estimates. The random sampling and pseudoprofile-based bootstrap approaches yielded tissue-to-plasma ratios with uncertainty and variability. However, the random sampling approach, because of the 2-phase nature of its algorithm, yielded more robust estimates and required fewer replications. Therefore, a 2-phase random sampling approach is proposed for the robust estimation of tissue-to-plasma ratio from extremely sparsely sampled data.

Content of alpha-linolenic acid in human atrial tissue correlates with plasma levels of alpha-linolenic acid

DEFF Research Database (Denmark)

Gu, Jiwei; Eschen, Rikke Bülow; Andreasen, Annette

and ALA levels were compared by the Pearson correlation coefficient. Results: There was a statistical significant correlation (r=0.54, 95% confidence interval: 0.30-0.71) between levels of ALA in plasma phospholipids and atrial tissue. Conclusion: The content of ALA in plasma phospholipids is a short term...... indicator of intake of ALA and this correlated well with the content of ALA in atrial tissue. Atrial tissue is not readily available but this study shows that determination of plasma phospholipids may be useful to further investigate an antiarrhythmic effect of ALA on AF....

Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

Science.gov (United States)

Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

2009-12-15

Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

Radioimmunoassay of cholecystokinin in human tissue and plasma

International Nuclear Information System (INIS)

Jansen, J.B.M.J.; Lamers, C.B.H.W.

1983-01-01

A highly sensitive radioimmunoassay for cholecystokinin (CCK) without any cross-reactivity with gastrin is described. The antibody was raised in a rabbit by immunisation with 30% CCK and bound to all COOH-terminal CCK-peptides containing at least 14 amino acid residues. The affinity constant of the antibody was 59.4 x 10 10 l/mol. CCK 33 conjugated to [ 125 I]hydroxyphenylpropionic acid-succinimide ester was used as label. The binding between label and antibody was inhibited by 50% (ID 50 ) at a concentration of 2.8 pmol/l cholecystokinin 33. The detection limit of the assay was between 0.5 and 1.0 pmol/l plasma. Concentrations of CCK in aqueous acid extracts of human upper small intestine were 36.5 +- 9.8 pmol/g and of human cerebral cortex 28.2 +- 2.5 pmol/g tissue. Plasma samples were extracted in 96% ethanol prior to assay. No advantage was obtained by adding aprotinin to the tubes. When frozen at -20 0 C plasma CCK was stable for at least 6 months. Basal plasma CCK concentrations in 30 normal subjects were very low, 0.9 +- 0.1 pmol/l, range 0.5 to 3.1 pmol/l. Intraduodenal administration of fat induced significant increases in plasma CCK from 1.1 +- 0.1 to 8.2 +- 1.3 pmol/l (p = 0.01). Infusion of exogenous CCK, resulting in plasma CCK levels slightly lower than those measured during administration of fat, induced pancreatic enzyme secretion and gallbladder contraction. The reliability of this radioimmunoassay for measurements of CCK in human plasma was extensively evaluated. (Auth.)

High plasma concentrations of transforming growth factor-β and tissue inhibitor of metalloproteinase-1. Potential non-invasive predictors for electroanatomical remodeling of atrium in patients with non-valvular atrial fibrillation

International Nuclear Information System (INIS)

Kim, Sook-Kyoung; Park, Jae-Hyung; Kim, Jong-Youn; Joung, Boyoung; Lee, Moon-Hyoung; Kim, Sung-Soon; Pak, Hui-Nam; Choi, Jong Il; Kim, Young-Hoon

2011-01-01

The degree of electroanatomical remodeling of the left atrial (LA) affects the clinical outcome after rhythm control of atrial fibrillation (AF). Our hypothesis was that plasma concentrations of transforming growth factor (TGF)-β and tissue inhibitor of metalloproteinase (TIMP)-1 reflect LA voltage and structural remodeling in patients with non-valvular AF. In the study, 242 patients (male 79.4%, 55.1±11.0 years old) with AF (155 paroxysmal AF, 87 persistent AF) underwent catheter ablation. Pre-ablation plasma concentrations of TGF-β and TIMP-1 and the degree of electroanatomical remodeling quantified by LA voltage map (NavX) and 3D-CT were evaluated. The mean LA voltage and volume were compared in patients with high TGF-β (±10.0 ng/ml, H-TGF) vs. low TGF-β ( 58%. In patients with non-valvular AF, high plasma concentrations TGF-β and TIMP-1 and low ejection fraction were closely related with electroanatomical remodeling of LA. (author)

C-terminal peptides of tissue factor pathway inhibitor are novel host defense molecules.

Science.gov (United States)

Papareddy, Praveen; Kalle, Martina; Kasetty, Gopinath; Mörgelin, Matthias; Rydengård, Victoria; Albiger, Barbara; Lundqvist, Katarina; Malmsten, Martin; Schmidtchen, Artur

2010-09-03

Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C terminus, also modulate cell surface, heparin, and lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the "classic" human antimicrobial peptide LL-37. The killing of E. coli, but not P. aeruginosa, by the C-terminal peptide GGLIKTKRKRKKQRVKIAYEEIFVKNM (GGL27), was enhanced in human plasma and largely abolished in heat-inactivated plasma, a phenomenon linked to generation of antimicrobial C3a and activation of the classic pathway of complement activation. Furthermore, GGL27 displayed anti-endotoxic effects in vitro and in vivo in a mouse model of LPS shock. Importantly, TFPI was found to be expressed in the basal layers of normal epidermis, and was markedly up-regulated in acute skin wounds as well as wound edges of chronic leg ulcers. Furthermore, C-terminal fragments of TFPI were associated with bacteria present in human chronic leg ulcers. These findings suggest a new role for TFPI in cutaneous defense against infections.

Convective transport of highly plasma protein bound drugs facilitates direct penetration into deep tissues after topical application

Science.gov (United States)

Dancik, Yuri; Anissimov, Yuri G; Jepps, Owen G; Roberts, Michael S

2012-01-01

AIMS To relate the varying dermal, subcutaneous and muscle microdialysate concentrations found in man after topical application to the nature of the drug applied and to the underlying physiology. METHODS We developed a physiologically based pharmacokinetic model in which transport to deeper tissues was determined by tissue diffusion, blood, lymphatic and intersitial flow transport and drug properties. The model was applied to interpret published human microdialysis data, estimated in vitro dermal diffusion and protein binding affinity of drugs that have been previously applied topically in vivo and measured in deep cutaneous tissues over time. RESULTS Deeper tissue microdialysis concentrations for various drugs in vivo vary widely. Here, we show that carriage by the blood to the deeper tissues below topical application sites facilitates the transport of highly plasma protein bound drugs that penetrate the skin, leading to rapid and significant concentrations in those tissues. Hence, the fractional concentration for the highly plasma protein bound diclofenac in deeper tissues is 0.79 times that in a probe 4.5 mm below a superficial probe whereas the corresponding fractional concentration for the poorly protein bound nicotine is 0.02. Their corresponding estimated in vivo lag times for appearance of the drugs in the deeper probes were 1.1 min for diclofenac and 30 min for nicotine. CONCLUSIONS Poorly plasma protein bound drugs are mainly transported to deeper tissues after topical application by tissue diffusion whereas the transport of highly plasma protein bound drugs is additionally facilitated by convective blood, lymphatic and interstitial transport to deep tissues. PMID:21999217

Assessment of the biological variation of plasma tissue inhibitor of metalloproteinases-1

DEFF Research Database (Denmark)

Frederiksen, C.B.; Lomholt, Anne Fog; Lottenburger, Tine

2008-01-01

BACKGROUND: Tissue inhibitor of metalloproteinases-1 (TIMP-1) measurements in plasma may be useful for the early detection and prognosis of colorectal cancer (CRC). Data on analytical performance and normal intra- and interindividual biological variation are required in order to interpret...... the utility of TIMP-1 in CRC. The aim of this study was to establish the biological and analytical variation of plasma TIMP-1 in volunteers. MATERIAL AND METHODS: Three separate studies were undertaken. 1: Plasma was collected from 23 volunteers 6 times within a 3-week period, first in September 2004 (round...

Final Report for completed IPP Project:"Development of Plasma Ablation for Soft Tissue and Bone Surgery"

Energy Technology Data Exchange (ETDEWEB)

Brown, Ian

2009-09-01

ArthroCare is a medical device company that develops, manufactures, and markets an advanced surgical tool, a plasma electro-surgical system for cutting and removing tissue. The hand-held electrical discharge device produces plasma in a biocompatible conductive fluid and tissue to which it is applied during surgery. Its products allow surgeons to operate with increased precision and accuracy, limiting damage to surrounding tissue thereby reducing pain and speeding recovery for the patient. In the past, the design of ArthfoCare's plasma wands has been an empirical undertaking. One goal of this R&D program was to put the phenomena involved on a sound scientific footing, allowing optimization of existing plasma based electro-surgery system technology, and the design and manufacture of new and improved kinds of scalpels, in particular for the surgical cutting of bone. Another important related goal of the program was to develop, through an experimental approach, new plasma wand approaches to the cutting ('shaving') of hard bone tissue. The goals of the CRADA were accomplished - computer models were used to predict important parameters of the plasma discharge and the bone environment, and several different approaches to bone-shaving were developed and demonstrated. The primary goal of the project was to develop and demonstrate an atmospheric-pressure plasma tool that is suitable for surgical use for shaving bone in humans. This goal was accomplished, in fact with several different alternative plasma approaches. High bone ablation speeds were measured. The use of probes ('plasma wand' - the surgical tool) with moving active electrodes was also explored, and there are advantages to this method. Another important feature is that the newly-exposed bone surface have only a very thin necrosis layer; this feature was demonstrated. This CRADA has greatly advanced our understanding of bone removal by atmospheric pressure plasmas in liquid, and puts Arthro

Final Report for completed IPP Project: Development of Plasma Ablation for Soft Tissue and Bone Surgery

International Nuclear Information System (INIS)

Brown, Ian

2009-01-01

ArthroCare is a medical device company that develops, manufactures, and markets an advanced surgical tool, a plasma electro-surgical system for cutting and removing tissue. The hand-held electrical discharge device produces plasma in a biocompatible conductive fluid and tissue to which it is applied during surgery. Its products allow surgeons to operate with increased precision and accuracy, limiting damage to surrounding tissue thereby reducing pain and speeding recovery for the patient. In the past, the design of ArthfoCare's plasma wands has been an empirical undertaking. One goal of this R and D program was to put the phenomena involved on a sound scientific footing, allowing optimization of existing plasma based electro-surgery system technology, and the design and manufacture of new and improved kinds of scalpels, in particular for the surgical cutting of bone. Another important related goal of the program was to develop, through an experimental approach, new plasma wand approaches to the cutting ('shaving') of hard bone tissue. The goals of the CRADA were accomplished - computer models were used to predict important parameters of the plasma discharge and the bone environment, and several different approaches to bone-shaving were developed and demonstrated. The primary goal of the project was to develop and demonstrate an atmospheric-pressure plasma tool that is suitable for surgical use for shaving bone in humans. This goal was accomplished, in fact with several different alternative plasma approaches. High bone ablation speeds were measured. The use of probes ('plasma wand' - the surgical tool) with moving active electrodes was also explored, and there are advantages to this method. Another important feature is that the newly-exposed bone surface have only a very thin necrosis layer; this feature was demonstrated. This CRADA has greatly advanced our understanding of bone removal by atmospheric pressure plasmas in liquid, and puts ArthroCare in a good

In vitro evidence of a tissue factor-independent mode of action of recombinant factor VIIa in hemophilia.

Science.gov (United States)

Augustsson, Cecilia; Persson, Egon

2014-11-13

Successful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor (TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients. Thrombin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate factor Xa production. However, (auto)activation of FVII apparently counteracted the negative effect of zymogen binding; a small impact was observed at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amounts of rFVIIa. Moreover, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the range where a physiological level of FVII was capable to downregulate thrombin generation. These data strongly suggest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa is a negligible mechanistic component. © 2014 by The American Society of Hematology.

Systemic factors related to soluble (prorenin receptor in plasma of patients with proliferative diabetic retinopathy.

Directory of Open Access Journals (Sweden)

Keitaro Hase

Full Text Available (Prorenin receptor [(PRR], a new component of the tissue renin-angiotensin system (RAS, plays a crucial role in inflammation and angiogenesis in the eye, thus contributing to the development of proliferative diabetic retinopathy (PDR. In this study, we investigated systemic factors related to plasma levels of soluble form of (PRR [s(PRR] in patients with PDR. Twenty type II diabetic patients with PDR and 20 age-matched, non-diabetic patients with idiopathic macular diseases were enrolled, and plasma levels of various molecules were measured by enzyme-linked immunosorbent assays. Human retinal microvascular endothelial cells were stimulated with several diabetes-related conditions to evaluate changes in gene expression using real-time quantitative PCR. Of various systemic parameters examined, the PDR patients had significantly higher blood sugar and serum creatinine levels than non-diabetic controls. Protein levels of s(PRR, prorenin, tumor necrosis factor (TNF-α, complement factor D (CFD, and leucine-rich α-2-glycoprotein 1 (LRG1 significantly increased in the plasma of PDR subjects as compared to non-diabetes, with positive correlations detected between s(PRR and these inflammatory molecules but not prorenin. Estimated glomerular filtration rate and serum creatinine were also correlated with plasma s(PRR, but not prorenin, levels. Among the inflammatory molecules correlated with s(PRR in the plasma, TNF-α, but not CFD or LRG1, application to retinal endothelial cells upregulated the mRNA expression of (PRR but not prorenin, while stimulation with high glucose enhanced both (PRR and prorenin expression. These findings suggested close relationships between plasma s(PRR and diabetes-induced factors including chronic inflammation, renal dysfunction, and hyperglycemia in patients with PDR.

Platelet-Rich Plasma Derived Growth Factors Contribute to Stem Cell Differentiation in Musculoskeletal Regeneration

OpenAIRE

Yun Qian; Yun Qian; Qixin Han; Wei Chen; Wei Chen; Jialin Song; Jialin Song; Xiaotian Zhao; Yuanming Ouyang; Yuanming Ouyang; Weien Yuan; Cunyi Fan

2017-01-01

Stem cell treatment and platelet-rich plasma (PRP) therapy are two significant issues in regenerative medicine. Stem cells such as bone marrow mesenchymal stem cells, adipose-derived stem cells and periodontal ligament stem cells can be successfully applied in the field of tissue regeneration. PRP, a natural product isolated from whole blood, can secrete multiple growth factors (GFs) for regulating physiological activities. These GFs can stimulate proliferation and differentiation of differen...

Atmospheric pressure plasma jets interacting with liquid covered tissue: touching and not-touching the liquid

International Nuclear Information System (INIS)

Norberg, Seth A; Johnsen, Eric; Tian, Wei; Kushner, Mark J

2014-01-01

In the use of atmospheric pressure plasma jets in biological applications, the plasma-produced charged and neutral species in the plume of the jet often interact with a thin layer of liquid covering the tissue being treated. The plasma-produced reactivity must then penetrate through the liquid layer to reach the tissue. In this computational investigation, a plasma jet created by a single discharge pulse at three different voltages was directed onto a 200 µm water layer covering tissue followed by a 10 s afterglow. The magnitude of the voltage and its pulse length determined if the ionization wave producing the plasma plume reached the surface of the liquid. When the ionization wave touches the surface, significantly more charged species were created in the water layer with H 3 O + aq , O 3 − aq , and O 2 − aq being the dominant terminal species. More aqueous OH aq , H 2 O 2aq , and O 3aq were also formed when the plasma plume touches the surface. The single pulse examined here corresponds to a low repetition rate plasma jet where reactive species would be blown out of the volume between pulses and there is not recirculation of flow or turbulence. For these conditions, N x O y species do not accumulate in the volume. As a result, aqueous nitrites, nitrates, and peroxynitrite, and the HNO 3aq and HOONO aq , which trace their origin to solvated N x O y , have low densities. (paper)

Resistin in Dairy Cows: Plasma Concentrations during Early Lactation, Expression and Potential Role in Adipose Tissue

Science.gov (United States)

Reverchon, Maxime; Ramé, Christelle; Cognié, Juliette; Briant, Eric; Elis, Sébastien; Guillaume, Daniel; Dupont, Joëlle

2014-01-01

Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA) levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6) in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase) in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro. PMID:24675707

Resistin in dairy cows: plasma concentrations during early lactation, expression and potential role in adipose tissue.

Directory of Open Access Journals (Sweden)

Maxime Reverchon

Full Text Available Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP and at five months of gestation (5 MG. We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6 in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase and HSL (hormone-sensitive lipase in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro.

Effects of different concentrations of Platelet-rich Plasma and Platelet-Poor Plasma on vitality and differentiation of autologous Adipose tissue-derived stem cells.

Science.gov (United States)

Felthaus, Oliver; Prantl, Lukas; Skaff-Schwarze, Mona; Klein, Silvan; Anker, Alexandra; Ranieri, Marco; Kuehlmann, Britta

2017-01-01

Autologous fat grafts and adipose-derived stem cells (ASCs) can be used to treat soft tissue defects. However, the results are inconsistent and sometimes comprise tissue resorption and necrosis. This might be due to insufficient vascularization. Platelet-rich plasma (PRP) is a source of concentrated autologous platelets. The growth factors and cytokines released by platelets can facilitate angiogenesis. The simultaneous use of PRP might improve the regeneration potential of fat grafts. The optimal ratio has yet to be elucidated. A byproduct of PRP preparation is platelet-poor plasma (PPP). In this study we investigated the influence of different concentrations of PRP on the vitality and differentiation of ASCs. We processed whole blood with the Arthrex Angel centrifuge and isolated ASCs from the same donor. We tested the effects of different PRP and PPP concentrations on the vitality using resazurin assays and the differentiation of ASCs using oil-red staining. Both cell vitality and adipogenic differentiation increase to a concentration of 10% to 20% PRP. With a PRP concentration of 30% cell vitality and differentiation decrease. Both PRP and PPP can be used to expand ASCs without xenogeneic additives in cell culture. A PRP concentration above 20% has inhibitory effects.

Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies

NARCIS (Netherlands)

Klumpers, Ursula M. H.; Veltman, Dick J.; Boellaard, Ronald; Comans, Emile F.; Zuketto, Cassandra; Yaqub, Maqsood; Mourik, Jurgen E. M.; Lubberink, Mark; Hoogendijk, Witte J. G.; Lammertsma, Adriaan A.

2008-01-01

A single-tissue compartment model with plasma input is the established method for analysing [(11)C]flumazenil ([(11)C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been

In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy

DEFF Research Database (Denmark)

Bladbjerg, E-M; Larsen, L F; Ostergaard, P

2000-01-01

The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII......:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments...

Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells

International Nuclear Information System (INIS)

Thim, L.; Bjoern, S.; Christensen, M.; Nicolaisen, E.M.; Lund-Hansen, T.; Pedersen, A.H.; Hedner, U.

1988-01-01

Blood coagulation factor VII is a vitamin K dependent glycoprotein which in its activated form, factor VII a , participates in the coagulation process by activating factor X and/or factor IX in the presence of Ca 2+ and tissue factor. Three types of potential posttranslational modifications exist in the human factor VII a molecule, namely, 10 γ-carboxylated, N-terminally located glutamic acid residues, 1 β-hydroxylated aspartic acid residue, and 2 N-glycosylated asparagine residues. In the present study, the amino acid sequence and posttranslational modifications of recombinant factor VII a as purified from the culture medium of a transfected baby hamster kidney cell line have been compared to human plasma factor VII a . By use of HPLC, amino acid analysis, peptide mapping, and automated Edman degradation, the protein backbone of recombinant factor VII a was found to be identical with human factor VII a . Asparagine residues 145 and 322 were found to be fully N-glycosylated in human plasma factor VII a . In the recombinant factor VII a , asparagine residue 322 was fully glycosylated whereas asparagine residue 145 was only partially (approximately 66%) glycosylated. Besides minor differences in the sialic acid and fucose contents, the overall carbohydrate compositions were nearly identical in recombinant factor VII a and human plasma factor VII a . These results show that factor VII a as produced in the transfected baby hamster kidney cells is very similar to human plasma factor VII a and that this cell line thus might represent an alternative source for human factor VII a

FABP4 dynamics in obesity: discrepancies in adipose tissue and liver expression regarding circulating plasma levels.

Directory of Open Access Journals (Sweden)

María Isabel Queipo-Ortuño

Full Text Available BACKGROUND: FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. OBJECTIVE: In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. METHODS: The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. RESULTS: In obesity FABP4 expression was down-regulated (at both mRNA and protein levels, with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. CONCLUSION: The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity.

Subepithelial connective tissue graft with and without the use of plasma rich in growth factors for treating root exposure

Science.gov (United States)

Lafzi, Ardeshir; Shirmohammadi, Adileh; Behrozian, Ahmad; Kashefimehr, Atabak; Khashabi, Ehsan

2012-01-01

Purpose The aim of this study was to evaluate the clinical efficiency of the subepithelial connective tissue graft (SCTG) with and without plasma rich in growth factor (PRGF) in the treatment of gingival recessions. Methods Twenty bilateral buccal gingival Miller's Class I and II recessions were selected. Ten of the recessions were treated with SCTG and PRGF (test group). The rest ten of the recessions were treated with SCTG (control group). The clinical parameters including recession depth (RD), percentage of root coverage (RC), mucogingival junction (MGJ) position, clinical attachment level (CAL), and probing depth (PD) were measured at the baseline, and 1 and 3 months later. The data were analyzed using the Wilcoxon signed rank and Mann-Whitney U tests. Results After 3 months, both groups showed a significant improvement in all of the mentioned criteria except PD. Although the amount of improvement was better in the SCTG+PRGF group than the SCTG only group, this difference was not statistically significant. The mean RC was 70.85±12.57 in the test group and 75.83±24.68 in the control group. Conclusions Both SCTG+PRGF and SCTG only result in favorable clinical outcomes, but the added benefit of PRGF is not evident. PMID:23346462

Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

Science.gov (United States)

Tylutki, Zofia; Polak, Sebastian

2015-03-12

Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Plasma membrane proteomic analysis of human Gastric Cancer tissues: revealing flotillin 1 as a marker for Gastric Cancer

International Nuclear Information System (INIS)

Gao, Wen; Xu, Jing; Wang, Fuqiang; Zhang, Long; Peng, Rui; Shu, Yongqian; Wu, Jindao; Tang, Qiyun; Zhu, Yunxia

2015-01-01

Gastric cancer remains the second leading cause of cancer-related deaths in the world. Successful early gastric cancer detection is hampered by lack of highly sensitive and specific biomarkers. Plasma membrane proteins participate and/or have a central role in the metastatic process of cancer cells and are potentially useful for cancer therapy due to easy accessibility of the targets. In the present research, TMT method followed by mass spectrometry analysis was used to compare the relative expression levels of plasma membrane proteins between noncancer and gastric cancer tissues. Of a total data set that included 501 identified proteins, about 35% of the identified proteins were found to be plasma membrane and associated proteins. Among them, 82 proteins were at least 1.5-fold up- or down-regulated in gastric cancer compared with the adherent normal tissues. A number of markers (e.g. annexin A6, caveolin 1, epidermal growth factor receptor, integrin beta 4) were previously reported as biomarkers of GC. Additionally, several potential biomarkers participated in endocytosis pathway and integrin signaling pathways were firstly identified as differentially expressed proteins in GC samples. Our findings also supported the notion that flotillin 1 is a potential biomarker that could be exploited for molecular imaging-based detection of gastric cancer. Together, the results show that subcellular proteomics of tumor tissue is a feasible and promising avenue for exploring oncogenesis. The online version of this article (doi:10.1186/s12885-015-1343-5) contains supplementary material, which is available to authorized users

A novel plasma source for sterilization of living tissues

International Nuclear Information System (INIS)

Martines, E; Zuin, M; Cavazzana, R; Gazza, E; Serianni, G; Spagnolo, S; Spolaore, M; Leonardi, A; Deligianni, V; Brun, P; Aragona, M; Castagliuolo, I; Brun, P

2009-01-01

A source for the production of low-power plasmas at atmospheric pressure, to be used for the nondamaging sterilization of living tissues, is presented. The source, powered by radiofrequency and working with a helium flow, has a specific configuration, studied to prevent the formation of electric arcs dangerous to living matter. It is capable of killing different types of bacteria with a decimal reduction time of 1-2 min; on the contrary, human cells such as conjunctival fibroblasts were found to be almost unharmed by the plasma. A high concentration of OH radicals, likely to be the origin of the sterilizing effect, is detected through their UV emission lines. The effect of the UV and the OH radicals on the fibroblasts was analysed and no significant effects were detected.

Hematology, plasma biochemistry, and tissue enzyme activities of invasive red lionfish captured off North Carolina, USA.

Science.gov (United States)

Anderson, E T; Stoskopf, M K; Morris, J A; Clarke, E O; Harms, C A

2010-12-01

The red lionfish Pterois volitans is important not only in the aquarium trade but also as an invasive species in the western Atlantic. Introduced to waters off the southeastern coast of the United States, red lionfish have rapidly spread along much of the East Coast and throughout Bermuda, the Bahamas, and much of the Caribbean. Hematology and plasma biochemistry were evaluated in red lionfish captured from the offshore waters of North Carolina to establish baseline parameters for individual and population health assessment. Blood smears were evaluated for total and differential white blood cell counts, and routine clinical biochemical profiles were performed on plasma samples. To improve the interpretive value of routine plasma biochemistry profiles, tissue enzyme activities (alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT], lactate dehydrogenase [LD], and creatine kinase [CK]) were analyzed from liver, kidney, skeletal muscle, gastrointestinal tract, and heart tissues from five fish. The hematological and plasma biochemical values were similar to those of other marine teleosts except that the estimated white blood cell counts were much lower than those routinely found in many species. The tissue enzyme activity findings suggest that plasma LD, CK, and AST offer clinical relevance in the assessment of red lionfish.

Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats

DEFF Research Database (Denmark)

Liaset, Bjørn; Madsen, Lise; Hao, Qin

2009-01-01

levels relative to rats fed soy protein or casein. Concomitantly, the saithe FPH fed rats had reduced liver lipids and fasting plasma TAG levels. Furthermore, visceral adipose tissue mass was reduced and expression of genes involved in fatty acid oxidation and energy expenditure was induced in perirenal....../retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism....

Plasma rico en plaquetas vs. plasma rico en factores de crecimiento

OpenAIRE

Carrasco Luna, Joaquín; Bonete Lluch, D.; Gomar Sancho, Francisco

2009-01-01

El desarrollo de los preparados plasmáticos ha generado grandes expectativas en la reparación ósea y han alcanzado gran desarrollo comercial de los kits de obtención del Plasma Rico en Plaquetas (PRP), también conocido como concentrado rico en plaquetas (PRC), gel de plaquetas autólogo, y plasma rico en factores de crecimiento (PRF) y su efecto sobre la regeneración esquelética. La generación de concentrados plasmáticos de plaquetas tiene como objetivo la liberación de factores de...

Relationship between plasma and tissue parameters of leucine metabolism

International Nuclear Information System (INIS)

Vazquez, J.A.; Paul, H.S.; Adibi, S.A.

1986-01-01

Using a primed continuous infusion of [1- 14 C] leucine, the authors investigated parameters of leucine metabolism in plasma, expired air, and tissues of fed and 48-hour starved rats. The ratios of muscle/plasma specific activity of α-ketoisocaproate (KIC) in fed and starved rats, respectively were not significantly different from one (1.07 +/- 0.14 and 0.97 +/- 0.10, mean +/- SE, 7 rats). The ratio of muscle/plasma specific activity of leucine was also not significantly different from one (0.86 +/- 0.11) in fed rats, but was significantly lower than one (0.80 +/- 0.07) in starved rats. The rate of leucine oxidation was approximately 32% higher when calculated based on plasma KIC rather than leucine specific activity. However, starvation significantly increased the rate of leucine oxidation with either specific activity. The rate of leucine incorporation into whole body protein was unaffected by starvation (32.7 +/- 3.5 vs 36.1 +/- 2.5 μmol/100 g/h), but the incorporation into total protein of liver (1350 +/- 140 vs 780 +/- 33 nmol) and of skeletal muscle (1940 +/- 220 vs 820 +/- 60 nmol) was significantly decreased. The authors conclude that a) leucine or KIC specific activity in muscle is better predicted by plasma KIC than leucine specific activity, and b) the tracer infusion technique is valid for the study of leucine oxidation but not for leucine incorporation into whole body protein

Tissue Engineering Using Transfected Growth-Factor Genes

Science.gov (United States)

Madry, Henning; Langer, Robert S.; Freed, Lisa E.; Trippel, Stephen; Vunjak-Novakovic, Gordana

2005-01-01

A method of growing bioengineered tissues includes, as a major component, the use of mammalian cells that have been transfected with genes for secretion of regulator and growth-factor substances. In a typical application, one either seeds the cells onto an artificial matrix made of a synthetic or natural biocompatible material, or else one cultures the cells until they secrete a desired amount of an extracellular matrix. If such a bioengineered tissue construct is to be used for surgical replacement of injured tissue, then the cells should preferably be the patient s own cells or, if not, at least cells matched to the patient s cells according to a human-leucocyteantigen (HLA) test. The bioengineered tissue construct is typically implanted in the patient's injured natural tissue, wherein the growth-factor genes enhance metabolic functions that promote the in vitro development of functional tissue constructs and their integration with native tissues. If the matrix is biodegradable, then one of the results of metabolism could be absorption of the matrix and replacement of the matrix with tissue formed at least partly by the transfected cells. The method was developed for articular chondrocytes but can (at least in principle) be extended to a variety of cell types and biocompatible matrix materials, including ones that have been exploited in prior tissue-engineering methods. Examples of cell types include chondrocytes, hepatocytes, islet cells, nerve cells, muscle cells, other organ cells, bone- and cartilage-forming cells, epithelial and endothelial cells, connective- tissue stem cells, mesodermal stem cells, and cells of the liver and the pancreas. Cells can be obtained from cell-line cultures, biopsies, and tissue banks. Genes, molecules, or nucleic acids that secrete factors that influence the growth of cells, the production of extracellular matrix material, and other cell functions can be inserted in cells by any of a variety of standard transfection techniques.

Effect of an aqueous extract of Scoparia dulcis on plasma and tissue glycoproteins in streptozotocin induced diabetic rats.

Science.gov (United States)

Latha, M; Pari, L

2005-02-01

The influence of Scoparia dulcis, a traditionally used plant for the treatment of diabetes mellitus, was examined in streptozotocin diabetic rats on dearrangement in glycoprotein levels. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin. An aqueous extract of Scoparia dulcis plant was administered orally for 6 weeks. The effect of the Scoparia dulcis extract on blood glucose, plasma insulin, plasma and tissue glycoproteins studied was in comparison to glibenclamide. The levels of blood glucose and plasma glycoproteins were increased significantly whereas the level of plasma insulin was significantly decreased in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of streptozotocin diabetic rats. Oral administration of Scoparia dulcis plant extract (SPEt) to diabetic rats led to decreased levels of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that Scoparia dulcis possesses a significant beneficial effect on glycoproteins in addition to its antidiabetic effect.

Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

Science.gov (United States)

Mast, Alan E

2016-01-01

Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients. © 2015 American Heart Association, Inc.

Platelet-rich plasma to improve the bio-functionality of biomaterials.

Science.gov (United States)

Anitua, Eduardo; Tejero, Ricardo; Alkhraisat, Mohammad H; Orive, Gorka

2013-04-01

Growth factors and cytokines are active players in controlling the different stages of wound healing and tissue regeneration. Recent trends in personalized regenerative medicine involve using patient's own platelet-rich plasma for stimulating wound healing and tissue regeneration. This technology provides a complex cocktail of growth factors and even a fibrin scaffold with multiple biologic effects. In the last few years, an increasing number of studies provide evidence of the potential of combining platelet-rich plasma with different biomaterials in order to improve their properties, including handling, administration, bioactivity, and level of osseointegration, among others. In this review, we discuss the use of platelet-rich plasma as an alternative, easy, cost-effective, and controllable strategy for the release of high concentrations of many endogenous growth factors. Additionally, we provide an overview of the current progress and future directions of research combining different types of biomaterials with platelet-rich plasma in tissue engineering and regenerative medicine.

Immunoradiometric quantitation of tissue plasminogen activator-related antigen in human plasma: crypticity phenomenon and relationship to plasma fibrinolysis

International Nuclear Information System (INIS)

Wun, T.C.; Capuano, A.

1987-01-01

A two-site immunoradiometric assay for tissue plasminogen activator (tPA) antigen has been developed using immunoaffinity purified antibody. Various treatments enhanced the detection of tPA antigen in the plasma samples. Maximum detection was obtained by acidification of plasma to pH 4.8 to 6.5 or addition of 0.5 mol/L of L-lysine or L-arginine. Acidification or addition of lysine to plasma is also required for maximum immunoadsorption of plasma tPA antigen on anti-tPA-Ig-sepharose. These results indicate that plasma tPA antigen is partially cryptic to antibody in untreated plasma. The plasma tPA antigen isolated by immunoadsorption of either untreated plasma or acidified plasma on anti-tPA-Ig-sepharose consists mainly of a 100-kd plasminogen activator species as determined by fibrin-agar zymography. The 100-kd activity is possibly a tPA:inhibitor complex. A standardized sample preparation method was conveniently adopted by mixing 3 vol of plasma and 1 vol of 2 mol/L of L-lysine for the assay. Reconstitution and recovery studies showed that the method is specific and permits full detection of both free tPA and tPA:inhibitor complex. The validity of the assay is further supported by the finding that the spontaneous plasma fibrinolysis previously demonstrated to be dependent on plasma tPA antigen is correlated with tPA antigen content. Using the standardized assay, we found that tPA antigen concentrations in 16 blood bank plasmas are equivalent to 3.7 to 20 ng of 60 kd tPA/mL. In all the plasma tested, more than half of the antigen is undetected unless the plasma is treated as described above

Immunoradiometric quantitation of tissue plasminogen activator-related antigen in human plasma: crypticity phenomenon and relationship to plasma fibrinolysis

Energy Technology Data Exchange (ETDEWEB)

Wun, T.C.; Capuano, A.

1987-05-01

A two-site immunoradiometric assay for tissue plasminogen activator (tPA) antigen has been developed using immunoaffinity purified antibody. Various treatments enhanced the detection of tPA antigen in the plasma samples. Maximum detection was obtained by acidification of plasma to pH 4.8 to 6.5 or addition of 0.5 mol/L of L-lysine or L-arginine. Acidification or addition of lysine to plasma is also required for maximum immunoadsorption of plasma tPA antigen on anti-tPA-Ig-sepharose. These results indicate that plasma tPA antigen is partially cryptic to antibody in untreated plasma. The plasma tPA antigen isolated by immunoadsorption of either untreated plasma or acidified plasma on anti-tPA-Ig-sepharose consists mainly of a 100-kd plasminogen activator species as determined by fibrin-agar zymography. The 100-kd activity is possibly a tPA:inhibitor complex. A standardized sample preparation method was conveniently adopted by mixing 3 vol of plasma and 1 vol of 2 mol/L of L-lysine for the assay. Reconstitution and recovery studies showed that the method is specific and permits full detection of both free tPA and tPA:inhibitor complex. The validity of the assay is further supported by the finding that the spontaneous plasma fibrinolysis previously demonstrated to be dependent on plasma tPA antigen is correlated with tPA antigen content. Using the standardized assay, we found that tPA antigen concentrations in 16 blood bank plasmas are equivalent to 3.7 to 20 ng of 60 kd tPA/mL. In all the plasma tested, more than half of the antigen is undetected unless the plasma is treated as described above.

Alternative pathways of thromboplastin-dependent activation of human factor X in plasma

International Nuclear Information System (INIS)

Marlar, R.A.; Griffin, J.H.

1981-01-01

To determine the interrelationships of the major coagulation pathways, the activation of 3H-labeled factor X in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin and calcium were added to plasma samples containing 3H-factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin, the rate of factor X activation in plasmas deficient in factor VIII or factor IX was 10% of the activation rate of normal plasma or of factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, reconstituted normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these plasma experiments, it is inferred that the dilute thromboplastin-dependent activation of factor X requires factors VII, IX, and VIII. An alternative extrinsic pathway that involves factors IX and VIII may be the physiologic extrinsic pathway and hence help to explain the consistent clinical observations of bleeding diatheses in patients deficient in factors IX or VIII

Determination of piroxicam from rat articular tissue and plasma based on LC-MS/MS.

Science.gov (United States)

Kim, Han Sol; Cho, Ha Ra; Ho, Myoung Jin; Kang, Myung Joo; Choi, Yong Seok

2016-12-01

Osteoarthritis (OA) is the most common type of arthritis. To manage OA, in general, oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) is used. Recently, the analgesic and anti-inflammatory efficacy of piroxicam (PX), a long-acting NSAID, by intra-articular (IA) administration in OA was reported, and the possibility that PX is distributed in articular tissues at a certain concentration was raised. Thus, herein, novel LC-MS/MS methods to detect PX in rat articular tissue and plasma are presented. For articular tissue, solvent extraction with acetonitrile for 12 h was employed and a protein precipitation method was used for the preparation of a plasma sample. The developed methods were validated by following the FDA guidelines, and the validated methods were successfully applied to a PK study of IA PX. The present study presents, to our knowledge, the first method of determining a drug in articular tissue. Additionally, the level of PX in articular tissue after IA PX administration was experimentally confirmed for the first time using the present methods. Therefore, the present methods provide a new direction for in vivo evaluation for IA PX formulations and contribute to the development of alternative IA PX formulations with better effects for the treatment of OA.

Plasma rich in growth factors (PRGF-Endoret) stimulates tendon and synovial fibroblasts migration and improves the biological properties of hyaluronic acid.

Science.gov (United States)

Anitua, E; Sanchez, M; De la Fuente, M; Zalduendo, M M; Orive, G

2012-09-01

Cell migration plays an essential role in development, wound healing, and tissue regeneration. Plasma rich in growth factors (PRGF-Endoret) technology offers a potential source of growth factors involved in tissue regeneration. Here, we evaluate the potential of PRGF-Endoret over tendon cells and synovial fibroblasts migration and study whether the combination of this autologous technology with hyaluronic acid (HA) improves the effect and potential of the biomaterials over the motility of both types of fibroblasts. Migration of primary tendon cells and synovial fibroblasts after culturing with either PRGF or PPGF (plasma poor in growth factors) at different doses was evaluated. Furthermore, the migratory capacity induced by the combination of PPGF and PRGF with HA was tested. PPGF stimulated migration of both types of cells but this effect was significantly higher when PRGF was used. Tendon cells showed an increase of 212% in migratory ability when HA was combined with PPGF and of 335% in the case of HA + PRGF treatment compared with HA alone. PRGF-Endoret stimulates migration of tendon cells and synovial fibroblasts and improves the biological properties of HA.

Fell-Muir lecture: connective tissue growth factor (CCN2) – a pernicious and pleiotropic player in the development of kidney fibrosis

Science.gov (United States)

Mason, Roger M

2013-01-01

Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of matricellular proteins. It interacts with many other proteins, including plasma membrane proteins, modulating cell function. It is expressed at low levels in normal adult kidney cells but is increased in kidney diseases, playing important roles in inflammation and in the development of glomerular and interstitial fibrosis in chronic disease. This review reports the evidence for its expression in human and animal models of chronic kidney disease and summarizes data showing that anti-CTGF therapy can successfully attenuate fibrotic changes in several such models, suggesting that therapies targeting CTGF and events downstream of it in renal cells may be useful for the treatment of human kidney fibrosis. Connective tissue growth factor stimulates the development of fibrosis in the kidney in many ways including activating cells to increase extracellular matrix synthesis, inducing cell cycle arrest and hypertrophy, and prolonging survival of activated cells. The relationship between CTGF and the pro-fibrotic factor TGFβ is examined and mechanisms by which CTGF promotes signalling by the latter are discussed. No specific cellular receptors for CTGF have been discovered but it interacts with and activates several plasma membrane proteins including low-density lipoprotein receptor-related protein (LRP)-1, LRP-6, tropomyosin-related kinase A, integrins and heparan sulphate proteoglycans. Intracellular signalling and downstream events triggered by such interactions are reviewed. Finally, the relationships between CTGF and several anti-fibrotic factors, such as bone morphogenetic factor-4 (BMP4), BMP7, hepatocyte growth factor, CCN3 and Oncostatin M, are discussed. These may determine whether injured tissue heals or progresses to fibrosis. PMID:23110747

Increased tissue factor, MMP-8, and D-dimer expression in diabetic patients with unstable advanced carotid atherosclerosis

Directory of Open Access Journals (Sweden)

Jerzy Krupinski

2007-09-01

Full Text Available Jerzy Krupinski1,2, Marta M Turu1,2, M Angels Font1, Nesser Ahmed3, Matthew Sullivan3, Ana Luque1,2, Francisco Rubio1, Lina Badimon2, Mark Slevin31Department of Neurology, Stroke Unit, University Hospital of Bellvitge (HUB, Fundacio IDIBELL, Barcelona, Spain; 2Cardiovascular Research Centre, IIBB/CSIC-HSCSP-UAB, Barcelona, Spain; 3School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester, United KingdomAbstract: Advanced atherogenesis is characterized by the presence of markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and by clinical conditions associated with defective coagulation. Diabetes may be associated with enhanced lesion instability and atherosclerotic plaque rupture. Plaques obtained from 206 patients undergoing carotid endarterectomy were divided into diabetic (type 2 and nondiabetic and analyzed by Western blotting and immunohistochemistry to detect tissue factor (TF, metalloproteinases (MMP-2, -8, -9, and fibrin/fibrinogen related antigens, and in situ zymography to detect MMP activity. Plasma samples were quantified for TF procoagulant activity, C-reactive protein, fibrinogen and D-dimer. Diabetic and symptomatic patients with hypoechogenic plaques had increased plasma TF activity and D-dimer, compared with those with hyperechogenic plaques (p = 0.03, p = 0.007, respectively. Diabetic, symptomatic patients had higher plasma D-dimer levels than asymptomatic patients (p = 0.03. There was a significant correlation between intramural TF levels and D-dimer in diabetic patients with symptomatic disease (p = 0.001, r2 = 0.4. In diabetic patients, plasma fibrinogen levels were higher in patients with hypoechogenic plaques (p = 0.007. Diabetic patients with ulcerated plaques had higher plasma D-dimer and MMP-8 levels than those with fibrous plaques (p = 0.02, p = 0.01, respectively. This data suggests that currently available circulating markers may be clinically useful to select

Determining potential adverse effects in marine fish exposed to pharmaceuticals and personal care products with the fish plasma model and whole-body tissue concentrations

International Nuclear Information System (INIS)

Meador, James P.; Yeh, Andrew; Gallagher, Evan P.

2017-01-01

The Fish Plasma Model (FPM) was applied to water exposure and tissue concentrations in fish collected from two wastewater treatment plant impacted estuarine sites. In this study we compared predicted fish plasma concentrations to Cmax values for humans, which represents the maximum plasma concentration for the minimum therapeutic dose. The results of this study show that predictions of plasma concentrations for a variety of pharmaceutical and personal care products (PPCPs) from effluent concentrations resulted in 37 compounds (54%) exceeding the response ratio (RR = Fish [Plasma]/1%Cmax total ) of 1 compared to 3 compounds (14%) detected with values generated with estuarine receiving water concentrations. When plasma concentrations were modeled from observed whole-body tissue residues, 16 compounds out of 24 detected for Chinook (67%) and 7 of 14 (50%) for sculpin resulted in an RR tissue value greater than 1, which highlights the importance of this dose metric over that using estuarine water. Because the tissue residue approach resulted in a high percentage of compounds with calculated response ratios exceeding a value of unity, we believe this is a more accurate representation for exposure in the field. Predicting plasma concentrations from tissue residues improves our ability to assess the potential for adverse effects in fish because exposure from all sources is captured. Tissue residues are also more likely to represent steady-state conditions compared to those from water exposure because of the inherent reduction in variability usually observed for field data and the time course for bioaccumulation. We also examined the RR in a toxic unit approach to highlight the importance of considering multiple compounds exhibiting a similar mechanism of action. - Highlights: • Fish Plasma Model (FPM) to assess risk based on water and fish tissue concentrations. • Plasma levels predicted with receiving water concentrations underestimate exposure for feral fish. �

Efficacy of Tissue Tolerable Plasma (TTP against Ixodes ricinus

Directory of Open Access Journals (Sweden)

Bender, Claudia

2014-03-01

Full Text Available [english] The efficacy of Tissue Tolerable Plasma (TTP against ticks was tested, as data from the literature has demonstrated its efficacy against other acari.The study was carried out by using the KINPen09 (Argon as carrier gas on (n=24. Treatment times of 1 and 3 minutes led to a reversible inactivation of the ticks. After 5 min of treatment, they died.Thanks to the acaricidal effect of TPP, a new treatment strategy using the KINPen09 for tick-infested pets is now available.

Pharmacokinetic study of arctigenin in rat plasma and organ tissue by RP-HPLC method.

Science.gov (United States)

He, Fan; Dou, De-Qiang; Hou, Qiang; Sun, Yu; Kang, Ting-Guo

2013-01-01

A high-performance liquid chromatography (HPLC) technique was developed for the determination of arctigenin in plasma and various organs of rats after the oral administration of 30, 50 and 70 mgkg(-1) of arctigenin to the Sprague-Dawley rats. Results showed that the validated HPLC method was simple, fast, reproducible and suitable to the determination of arctigenin in rat plasma and organ tissue and one-compartmental model with zero-order absorption process can well describe the changes of arctigenin concentration in the plasma. The concentration of compound was highest in the spleen, less in the liver and the least in the lung.

Effect of experimentally increased protein supply to postpartum dairy cows on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis.

Science.gov (United States)

Larsen, M; Røntved, C M; Theil, P K; Khatun, M; Lauridsen, C; Kristensen, N B

2017-05-01

The effect of experimentally increasing the postpartum protein supply on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis was studied using 8 periparturient Holstein cows in a complete randomized design. At calving, cows were assigned to abomasal infusion of water (CTRL) or casein (CAS) in addition to a lactation diet. Casein infusion was gradually decreased from 696 ± 1 g/d at +2 d relative to calving (DRTC) to 212 ± 10 g/d at +29 DRTC to avoid excessive supply. Synthesis rate of plasma proteins was measured at -14, +4, +15, and +29 DRTC by measuring [C]Phe isotopic enrichment in arterial plasma free Phe, total plasma proteins, and albumin after 3, 5, and 7 h of jugular ring[C]Phe infusion. Plasma volume was determined at +4 and +29 DRTC by dilution of a [I]BSA dose. Synthesis rate of tissue protein in biopsied rumen papillae was determined by measuring [C]Phe isotopic enrichment, and mRNA expression of selected genes was measured by real-time qPCR. Total and differential leukocyte counts were performed and immune responsiveness of monocytes was evaluated by tumor necrosis factor ɑ (TNFɑ) concentration on ex vivo whole blood stimulation with Escherichia coli lipopolysaccharide (LPS) and responsiveness of T-lymphocytes by interferon γ (IFNγ) concentration on stimulation with Staphylococcus aureus enterotoxin β (SEB). Further, ELISA plasma concentrations of IgM, IgA, and IgG were determined. The DRTC affected the majority of investigated parameters as expected. The CAS treatment increased milk protein yield (P = 0.04), and tended to lower TNFɑ (P = 0.06), and lowered IFNγ (P = 0.03) responsiveness per monocyte and lymphocyte, respectively, compared with CTRL. Further, fractional synthesis rate of albumin was greater at +4 DRTC for CAS compared with CTRL but did not differ by +29 DRTC (interaction: P = 0.01). In rumen papillae, synthesis rate of tissue protein was greater for CAS compared with CTRL (P protein supply seem to

Canine adiponectin: cDNA structure, mRNA expression in adipose tissues and reduced plasma levels in obesity.

Science.gov (United States)

Ishioka, K; Omachi, A; Sagawa, M; Shibata, H; Honjoh, T; Kimura, K; Saito, M

2006-04-01

Adiponectin is a protein synthesized and secreted by adipocytes. Decreased adiponectin is responsible for insulin resistance and atherosclerosis associated with human obesity. We obtained a cDNA clone corresponding to canine adiponectin, whose nucleotide and deduced amino acid sequences were highly identical to those of other species. Adiponectin mRNA was detected in adipose tissues, but not in other tissues, of dogs. When 22 adult beagles were given a high-energy diet for 14 weeks, they became obese, showing heavier body weights, higher plasma leptin concentrations, but lower plasma adiponectin concentrations. The adiponectin concentrations of plasma samples collected from 71 dogs visiting veterinary practices were negatively correlated to plasma leptin concentrations, being lower in obese than non-obese dogs. These results are compatible with those reported in other species, and suggest that adiponectin is an index of adiposity and a target molecule for studies on diseases associated with obesity in dogs.

Plasma oxalic acid and calcium levels in oxalate poisoning

Science.gov (United States)

Zarembski, P. M.; Hodgkinson, A.

1967-01-01

Observations are reported on five cases of suicide or attempted suicide by poisoning with oxalic acid or ethylene glycol. Elevated oxalic acid levels were observed in the plasma, stomach contents, and a number of tissues. Raised oxalic acid levels in plasma were associated with reduced total and ultrafilterable calcium levels. It is suggested that the reduction in plasma total calcium level is due mainly to the deposition of calcium oxalate in the soft tissues, but inhibition of the parathyroid glands may be a contributory factor. Microscopic examination of various tissues indicated that oxalic acid is deposited in the tissues in two forms: (1) crystalline calcium oxalate dihydrate in the kidney and (2) a non-crystalline complex of calcium oxalate and lipid in liver and other tissues. PMID:5602563

Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

NARCIS (Netherlands)

Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

2017-01-01

Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor beta induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

NARCIS (Netherlands)

Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

2017-01-01

Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue fluid using in vivo ultrafiltration.

Science.gov (United States)

Messenger, K M; Wofford, J A; Papich, M G

2016-02-01

Measurement of unbound drug concentrations at their sites of action is necessary for accurate PK/PD modeling. The objective of this study was to determine the unbound concentration of carprofen in canine interstitial fluid (ISF) using in vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen concentrations between inflamed and control tissue sites. We hypothesized that active concentrations of carprofen would exhibit different dispositions in ISF between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed subcutaneously in six healthy Beagle dogs 12 h prior to induction of inflammation. Two milliliters of either 2% carrageenan or saline control was injected subcutaneously at each probe site, 12 h prior to intravenous carprofen (4 mg/kg) administration. Plasma and ISF samples were collected at regular intervals for 72 h, and carprofen concentrations were determined using HPLC. Prostaglandin E2 (PGE2 ) concentrations were quantified in ISF using ELISA. Unbound carprofen concentrations were higher in ISF compared with predicted unbound plasma drug concentrations. Concentrations were not significantly higher in inflamed ISF compared with control ISF. Compartmental modeling was used to generate pharmacokinetic parameter estimates, which were not significantly different between sites. Terminal half-life (T½) was longer in the ISF compared with plasma. PGE2 in ISF decreased following administration of carprofen. In vivo ultrafiltration is a reliable method to determine unbound carprofen in ISF, and that disposition of unbound drug into tissue is much higher than predicted from unbound drug concentration in plasma. However, concentrations and pharmacokinetic parameter estimates are not significantly different in inflamed vs. un-inflamed tissues. © 2015 John Wiley & Sons Ltd.

The importance of residues 195-206 of human blood clotting factor VII in the interaction of factor VII with tissue factor

International Nuclear Information System (INIS)

Wildgoose, P.; Kisiel, W.; Kazim, A.L.

1990-01-01

Previous studies indicated that human and bovine factor VII exhibit 71% amino acid sequence identity. In the present study, competition binding experiments revealed that the interaction of human factor VII with cell-surface human tissue factor was not inhibited by 100-fold molar excess of bovine factor VII. This finding indicated that bovine and human factor VII are not structurally homologous in the region(s) where human factor VII interacts with human tissue factor. On this premise, the authors synthesized three peptides corresponding to regions of human factor VII that exhibited marked structural dissimilarity to bovine factor VII; these regions of dissimilarity included residues 195-206, 263-274, and 314-326. Peptide 195-206 inhibited the interaction of factor VII with cell-surface tissue factor and the activation of factor X by a complex of factor VIIa and tissue factor half-maximally at concentrations of 1-2 mM. A structurally rearranged form of peptide 195-206 containing an aspartimide residue inhibited these reactions half-maximally at concentrations of 250-300 μM. In contrast, neither peptide 263-274 nor peptide 314-326, at 2 mM concentration, significantly affected either factor VIIa interaction with tissue factor or factor VIIa-mediated activation of factor X. The data provide presumptive evidence that residues 195-206 of human factor VII are involved in the interaction of human factor VII with the extracellular domain of human tissue factor apoprotein

Plasma needle treatment of bacteria known to cause infections of the soft tissue of the oral region and bones

Science.gov (United States)

Maletic, Dejan; Lazovic, Sasa; Puac, Nevena; Malovic, Gordana; Petrovic, Zoran Lj.; Miletic, Maja P.; Pavlica, Dusan B.; Jovanovic, Milena Z.; Milenkovic, Pavle

2009-10-01

Plasma needle can be used for non-contact disinfection of dental cavities and wounds, minimum-destructive precise treatment, as well as the removal of damaged tissue. The effect of bacterial deactivation is probably caused by reactive oxygen species while nitric oxide provided by plasma plays major role in many processes in the organism. Mass spectrometry was done to provide better insight into plasma-cell interactions. Our measurements were performed on a plasma needle that we originally used for the treatment of plant cells.Our research was done on species that are known to cause primary and secondary infections of the soft tissue of the oral region, as well as bones. The bacteria cultures used are bacterial reference culture species Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922. We investigated the effect of the plasma needle discharge on different concentration of bacteria using several exposure times and power transmitted to the plasma. It was found that excellent removal of this and other bacteria may be achieved by the plasma needle treatment.

Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

Directory of Open Access Journals (Sweden)

Xiaolin He

Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

Monoclonal anti-human factor VII antibodies. Detection in plasma of a second protein antigenically and genetically related to factor VII.

OpenAIRE

Broze, G J; Hickman, S; Miletich, J P

1985-01-01

Several murine monoclonal anti-human Factor VII antibodies were produced using hybridoma technology. Two noncompetitive monoclonal antibodies were used to examine by Western blotting the Factor VII cross-reactive material (CRM) in normal human plasma and three commercially available congenitally Factor VII-deficient plasmas, and to construct a facile "sandwich" immunoassay for plasma Factor VII. A second, previously undescribed, form of Factor VII CRM was detected in human plasma, which on We...

Age-related changes in factor VII proteolysis in vivo.

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Ofosu, F A; Craven, S; Dewar, L; Anvari, N; Andrew, M; Blajchman, M A

1996-08-01

Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

Matrix- and plasma-derived peptides promote tissue-specific injury responses and wound healing in diabetic swine.

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Sheets, Anthony R; Massey, Conner J; Cronk, Stephen M; Iafrati, Mark D; Herman, Ira M

2016-07-02

Non-healing wounds are a major global health concern and account for the majority of non-traumatic limb amputations worldwide. However, compared to standard care practices, few advanced therapeutics effectively resolve these injuries stemming from cardiovascular disease, aging, and diabetes-related vasculopathies. While matrix turnover is disrupted in these injuries, debriding enzymes may promote healing by releasing matrix fragments that induce cell migration, proliferation, and morphogenesis, and plasma products may also stimulate these processes. Thus, we created matrix- and plasma-derived peptides, Comb1 and UN3, which induce cellular injury responses in vitro, and accelerate healing in rodent models of non-healing wounds. However, the effects of these peptides in non-healing wounds in diabetes are not known. Here, we interrogated whether these peptides stimulate healing in a diabetic porcine model highly reminiscent of human healing impairments in type 1 and type 2-diabetes. After 3-6 weeks of streptozotocin-induced diabetes, full-thickness wounds were surgically created on the backs of adult female Yorkshire swine under general anesthesia. Comb1 and UN3 peptides or sterile saline (negative control) were administered to wounds daily for 3-7 days. Following sacrifice, wound tissues were harvested, and quantitative histological and immunohistochemical analyses were performed for wound closure, angiogenesis and granulation tissue deposition, along with quantitative molecular analyses of factors critical for angiogenesis, epithelialization, and dermal matrix remodeling. Comb1 and UN3 significantly increase re-epithelialization and angiogenesis in diabetic porcine wounds, compared to saline-treated controls. Additionally, fluorescein-conjugated Comb1 labels keratinocytes, fibroblasts, and vascular endothelial cells in porcine wounds, and Far western blotting reveals these cell populations express multiple fluorescein-Comb1-interacting proteins in vitro. Further

Plasma extravasation mediated by lipopolysaccharide-induction of kinin B1 receptors in rat tissues

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Paulo Roberto Wille

2001-01-01

Full Text Available The present study was performed to: (a evaluate the effects of kinin B1 (Sar{D-Phe8}-des-Arg9-BK; 10 nmol/kg and B2 (bradykinin (BK; 10 nmol/kg receptor agonists on plasma extravasation in selected rat tissues; (b determine the contribution of a lipopolysaccharide (LPS (100 μ g/kg to the effects triggered by B1 and B2 agonists; and (c characterize the selectivity of B1 ({Leu8}desArg9-BK; 10 nmol/kg and B2 (HOE 140; 10 nmol/kg antagonists as inhibitors of this kinin-induced phenomenon. B1 and B2 agonists were shown to increase plasma extravasation in the duodenum, ileum and also in the urinary bladder of the rat. LPS pretreatment enhanced the plasma extravasation mediated only by the B1 agonist in the duodenum, ileum, trachea, main and segmentar bronchi. These effects were prevented by the B1. but not the B2 antagonist. In normal rats, the B2 antagonist inhibited the effect of B2 agonist in all the tissues analyzed. However, in LPS-treated rats, the B2 antagonist was ineffective in the urinary bladder.

Study on the plasma leptin level and leptin mRNA expression in cancerous breast tissue in patients with breast carcinoma complicated with obesity

International Nuclear Information System (INIS)

Li Chunrui; Liu Wenli; Sun Hanying; Zhou Jianfeng

2006-01-01

Objective: To study the plasma leptin level and leptin mRNA expression in cancerous breast tissue in patients with breast cancer complicated with obesity. Methods: Plasma leptin levels were measured with RIA in 48 breast cancer patients with obesity, 36 patients with various benign breast disorders and obesity and 40 controls (with simple obesity only). The leptin mRNA expression in the surgical specimens from the 84 patients with breast disease was also examined with RT-PCR, Results: The plasma leptin levels in the breast cancer patients (12.02 ± 1.23 μg/L) were significantly higher than those in patients with benign breast disorders (9.84 ± 0.98 μg/L) and controls (9.79 ± 1.16 μg/L) (both P<0.05). The expression levels of leptin mRNA in specimens from malignant breast disease (0.71 ± 0.32), were significantly higher than those in specimens from benign breast diseases (0.41 ± 0.26) (P<0.05), The plasma leptin levels and the tissue leptin mRNA expression levels were mutually positively correlated (r=0.4220 ,P 0.0180). These levels were not correlated with the presence of axillary metastasis, TMN stage, menstrual status, pathological classification and other parameters. Conclusion: Leptin might be a promotive factor in the development of breast cancer. (authors)

Neutron kerma factors, and water equivalence of some tissue substitutes

International Nuclear Information System (INIS)

Singh, V. P.; Badiger, N. M.; Vega C, H. R.

2014-08-01

The kerma factors and kerma relative to air and water of 24 compounds used as tissue substitutes were calculated for neutron energy from 2.53 x 10 -8 up to 29 MeV. The kerma ratio of the tissue substitutes relative to air and water were calculated by the ratio of kerma factors of the tissue substitute to air and water respectively. The water equivalence of the selected tissue substitutes was observed above neutron energies 100 eV. Kerma ratio relative to the air for Poly-vinylidene fluoride and Teflon are found to be nearest to unity in very low energy (up to 1 eV) and above 63 eV respectively. It was found that the natural rubber as a water equivalent tissue substitute compound. The results of the kerma factors in our investigation shows a very good agreement with those published in ICRU-44. We found that at higher neutron energies, the kerma factors and kerma ratios of the selected tissue substitute compounds are approximately same, but differences are large for energies below 100 eV. (Author)

Time- and space-resolved spectroscopic characterization of laser-induced swine muscle tissue plasma

Energy Technology Data Exchange (ETDEWEB)

Camacho, J.J. [Departamento de Química-Física Aplicada, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Diaz, L., E-mail: luis.diaz@csic.es [Instituto de Estructura de la Materia, CFMAC, CSIC, Serrano 121, 28006 Madrid (Spain); Martinez-Ramirez, S. [Instituto de Estructura de la Materia, CFMAC, CSIC, Serrano 121, 28006 Madrid (Spain); Caceres, J.O. [Departamento de Química Analítica, Facultad de Ciencias Químicas, Universidad Complutense, Cuidad Universitaria, 28040 Madrid (Spain)

2015-09-01

The spatial-temporal evolution of muscle tissue sample plasma induced by a high-power transversely excited atmospheric (TEA) CO{sub 2} pulsed laser at vacuum conditions (0.1–0.01 Pa) has been investigated using high-resolution optical emission spectroscopy (OES) and imaging methods. The induced plasma shows mainly electronically excited neutral Na, K, C, Mg, H, Ca, N and O atoms, ionized C{sup +}, C{sup 2+}, C{sup 3+}, Mg{sup +}, Mg{sup 2+}, N{sup +}, N{sup 2+}, Ca{sup +}, O{sup +} and O{sup 2+} species and molecular band systems of CN(B{sup 2}Σ{sup +}–X{sup 2}Σ{sup +}), C{sub 2}(d{sup 3}Π{sub g}–a{sup 3}Π{sub u}), CH(B{sup 2}Σ{sup −}–X{sup 2}Π; A{sup 2}Δ–X{sup 2}Π), NH(A{sup 3}Π–X{sup 3}Σ{sup −}), OH(A{sup 2}Σ{sup +}–X{sup 2} Σ{sup +}), and CaOH(B{sup 2}Σ{sup +}–X{sup 2}Σ{sup +}; A{sup 2}Π–X{sup 2}Σ{sup +}). Time-resolved two-dimensional emission spectroscopy is used to study the expanded distribution of different species ejected during ablation. Spatial and temporal variations of different atoms and ionic excited species are reported. Plasma parameters such as electron density and temperature were measured from the spatio-temporal analysis of different species. Average velocities of some plasma species were estimated. - Highlights: • LIBS of swine muscle tissue sample generated by CO{sub 2} laser pulses has been done for the first time. • Average velocities of some plasma species have been calculated from spatial and temporally resolved 2D OES images. • Electron density (~ 9 × 10{sup 17} cm{sup -3}) has been studied with spatial and temporal resolution. • Temporal evolution of the plasma temperature has been calculated by means of Boltzmann plots.

Plasma triacylglycerol and coagulation factor concentrations predict the anticoagulant effect of dietary fish oil in overweight subjects

DEFF Research Database (Denmark)

Vanschoonbeek, Kristof; Feijge, Marion A H; Saris, Wim H M

2007-01-01

fish-oil effects. In study 1, 54 overweight subjects consumed 3.1 g (n-3) PUFA daily. In study 2, which involved 42 overweight patients with type 2 diabetes, 20 subjects consumed (n-3) PUFA, whereas 22 others ingested a preparation rich in (n-6) PUFA. Tissue factor-induced thrombin generation (thrombin...... potential) was determined as an integrated measure of plasma coagulant activity. In both studies, multivariate analysis indicated a strong clustering of fasting concentrations of triacylglycerols, prothrombin, factor V, factor VII, and factor X with one another at baseline. This cluster of factors......-induced lowering of triacylglycerol and coagulation factor V, VII, and X concentrations, and thrombin generation. We conclude that high fasting triacylglycerol concentrations predict high procoagulant activity and a lowering of thrombin potential with dietary fish oil....

Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs.

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Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

2014-01-01

In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, pplatelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors.

A paradigm shift in pharmacokinetic-pharmacodynamic (PKPD) modeling: rule of thumb for estimating free drug level in tissue compared with plasma to guide drug design.

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Poulin, Patrick

2015-07-01

A basic assumption in pharmacokinetics-pharmacodynamics research is that the free drug concentration is similar in plasma and tissue, and, hence, in vitro plasma data can be used to estimate the in vivo condition in tissue. However, in a companion manuscript, it has been demonstrated that this assumption is violated for the ionized drugs. Nonetheless, these observations focus on in vitro static environments and do not challenge data with an in vivo dynamic system. Therefore, an extension from an in vitro to an in vivo system becomes the necessary next step. The objective of this study was to perform theoretical simulations of the free drug concentration in tissue and plasma by using a physiologically based pharmacokinetics (PBPK) model reproducing the in vivo conditions in human. Therefore, the effects of drug ionization, lipophilicity, and clearance have been taken into account in a dynamic system. This modeling exercise was performed as a proof of concept to demonstrate that free drug concentration in tissue and plasma may also differ in a dynamic system for passively permeable drugs that are ionized at the physiological pH. The PBPK model simulations indicated that free drug concentrations in tissue cells and plasma significantly differ for the ionized drugs because of the pH gradient effect between cells and interstitial space. Hence, a rule of thumb for potentially performing more accurate PBPK/PD modeling is suggested, which states that the free drug concentration in tissue and plasma will differ for the ionizable drugs in contrast to the neutral drugs. In addition to the pH gradient effect for the ionizable drugs, lipophilicity and clearance effects will increase or decrease the free drug concentration in tissue and plasma for each class of drugs; thus, higher will be the drug lipophilicity and clearance, lower would be the free drug concentration in plasma, and, hence, in tissue, in a dynamic in vivo system. Therefore, only considering the value of free

Monoclonal antibodies to human factor VII: production of immunodepleted plasma for VII:C assays.

OpenAIRE

Takase, T; Tuddenham, E G; Chand, S; Goodall, A H

1988-01-01

A high affinity monoclonal antibody to factor VII (RFF-VII/1), coupled to sepharose, was used to immunodeplete factor VII from normal plasma. The plasma could be used as a substrate in a one stage coagulation assay and performed as well as, or better than, commercially available factor VII deficient plasma or plasma from congenitally deficient factor VII patients. Plasma from normal donors (n = 20), patients with liver disease (n = 20), and patients receiving warfarin (n = 20), or congenitall...

Bioassay of procoagulant albumin in human plasma.

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Grosset, A; Liu, L; Parker, C J; Rodgers, G M

1994-09-01

Procoagulant albumin (P-Al) is present in normal human plasma and increases monocyte and endothelial cell expression of tissue factor activity. To develop a bioassay for P-Al, we partially purified plasma from healthy volunteers and several patient groups using BaCl2 and (NH4)2SO4 precipitation. The samples were assayed for tissue factor (TF) inducing activity, expressed as a percentage increase compared to a serum-free media control. Over six months, the assay was reproducible in stored samples and in serial samples from normal volunteers. The plasma P-Al activities of 35 volunteers averaged 141 +/- 8.2% (SEM). There was no diurnal variation. There was no difference in the P-Al activity after a 12 hour fast and 2 hours after a large meal in 4 healthy volunteers. There was no increase in activity (r = 0.16) with the subject's age. The average activity from 16 poorly-controlled diabetics was 131 +/- 11% (SEM). No alteration in activity was seen with samples from patients with uremia, liver dysfunction, hemophilia, thrombotic events, or adenocarcinoma. These results indicate that P-Al activity can be bioassayed in individual patient samples; however, pathologic states associated with abnormal P-Al-induced tissue factor activity presently remain unidentified.

Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine frompatients with bladder cancer

DEFF Research Database (Denmark)

Holten Andersen, MN; Brunner, N; Nielsen, HJ

2006-01-01

Aim: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. Methods: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...... (n=3) or adenocarcinoma (n=7). Results: Free and total TIMP-1 in plasma were weakly but significantly correlated with age; urinary TIMP-1 was not. A strong correlation between free and total TIMP-1 in plasma was observed, with an average ratio of 0.85. No correlation between total TIMP-1 in urine...... and plasma was found (p=0.55). No significant differences in free or total TIMP-1 in plasma were found between healthy individuals, patients with cystitis or bladder cancer (p=0.4). Urinary TIMP-1 levels were significantly increased in patients with cystitis (p=0.001). No apparent differences in TIMP-1...

Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI.

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Cristina Puy

Full Text Available Factor (F XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα, in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin.Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma.Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP.

Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration

DEFF Research Database (Denmark)

Hjortoe, Gertrud M; Petersen, Lars C; Albrektsen, Tatjana

2004-01-01

Tissue factor (TF), the cellular receptor for factor VIIa (FVIIa), besides initiating blood coagulation, is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Like TF, the chemokine interleukin-8 (IL-8) is shown to play a critical role...... in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 m......RNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene...

Gene expression of tumour necrosis factor and insulin signalling-related factors in subcutaneous adipose tissue during the dry period and in early lactation in dairy cows.

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Sadri, H; Bruckmaier, R M; Rahmani, H R; Ghorbani, G R; Morel, I; van Dorland, H A

2010-10-01

Gene expression of adipose factors, which may be part of the mechanisms that underlie insulin sensitivity, were studied in dairy cows around parturition. Subcutaneous fat biopsies and blood samples were taken from 27 dairy cows in week 8 antepartum (a.p.), on day 1 postpartum (p.p.) and in week 5 p.p. In the adipose tissue samples, mRNA was quantified by real-time reverse transcription polymerase chain reaction for tumour necrosis factor alpha (TNFα), insulin-independent glucose transporter (GLUT1), insulin-responsive glucose transporter (GLUT4), insulin receptor, insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), regulatory subunit of phosphatidylinositol-3 kinase (p85) and catalytic subunit of phosphatidylinositol-3 kinase. Blood plasma was assayed for concentrations of glucose, β-hydroxybutyric acid, non-esterified fatty acids (NEFA) and insulin. Plasma parameters followed a pattern typically observed in dairy cows. Gene expression changes were observed, but there were no changes in TNFα concentrations, which may indicate its local involvement in catabolic adaptation of adipose tissue. Changes in GLUT4 and GLUT1 mRNA abundance may reflect their involvement in reduced insulin sensitivity and in sparing glucose for milk synthesis in early lactation. Unchanged gene expression of IRS1, IRS2 and p85 over time may imply a lack of their involvement in terms of insulin sensitivity dynamics. Alternatively, it may indicate that post-transcriptional modifications of these factors came into play and may have concealed an involvement. © 2010 Blackwell Verlag GmbH.

Therapeutic efficacy of connective tissue autotransplants with periosteum and platelet rich plasma in the management of gingival recession

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Jovičić Bojan

2013-01-01

Full Text Available Background/Aim. Gingival recession progression in clinical practaice has influenced the development of various surgical procedures and techniques for solving esthetic imperfections and subjective difficulties coused by gingival recession. The aim of this study was to verify efficacy of surgical procedures and to compare both of surgical procedures through the keratinized tissue width. Methods. The study included 20 teeth with gingival recesion, Müller class I and II. Ten teeth with gingival recession were treated with connective tissue autotransplants with periosteum in combination with coronary guided surgical flap (CTG group. On the contralateral side 10 teeth with gingival recession were treated with the same surgical procedures but in combination with platelet-rich plasma (CTGPRP group. We measured the keratinized tissue width. For statistical significance we used the Student's t-test. Results. The study reveled a statistical significance in reducing vertical deepress of recession by both used treatments. Root deepness in CTG and CTG-PRP group was 90% and 93.5%, respectively. With both surgical techniques we achieved larger zone of keratinized gingiva but with a wide zone of keratinized tissue in CTG - the PRP group. Conclusion. The concept regeneration technique with PRP and with the stimulating influence of platele activated growth factors results in the regeneration of deep periodontal tissue as an important prerequisite for the successful treatment of gingival recession.

Risk factors contributing to a low darunavir plasma concentration

NARCIS (Netherlands)

Daskapan, Alper; Stienstra, Ymkje; Kosterink, Jos G.W.; Bierman, Wouter F.W.; van der Werf, Tjip S.; Touw, Daan J.; Alffenaar, Jan Willem C.

Darunavir is an efficacious drug; however, pharmacokinetic variability has been reported. The objective of this study was to find predisposing factors for low darunavir plasma concentrations in patients starting the once- or twice-daily dosage. Darunavir plasma concentrations from January 2010 till

Determining potential adverse effects in marine fish exposed to pharmaceuticals and personal care products with the fish plasma model and whole-body tissue concentrations.

Science.gov (United States)

Meador, James P; Yeh, Andrew; Gallagher, Evan P

2017-11-01

The Fish Plasma Model (FPM) was applied to water exposure and tissue concentrations in fish collected from two wastewater treatment plant impacted estuarine sites. In this study we compared predicted fish plasma concentrations to Cmax values for humans, which represents the maximum plasma concentration for the minimum therapeutic dose. The results of this study show that predictions of plasma concentrations for a variety of pharmaceutical and personal care products (PPCPs) from effluent concentrations resulted in 37 compounds (54%) exceeding the response ratio (RR = Fish [Plasma]/1%Cmax total ) of 1 compared to 3 compounds (14%) detected with values generated with estuarine receiving water concentrations. When plasma concentrations were modeled from observed whole-body tissue residues, 16 compounds out of 24 detected for Chinook (67%) and 7 of 14 (50%) for sculpin resulted in an RR tissue value greater than 1, which highlights the importance of this dose metric over that using estuarine water. Because the tissue residue approach resulted in a high percentage of compounds with calculated response ratios exceeding a value of unity, we believe this is a more accurate representation for exposure in the field. Predicting plasma concentrations from tissue residues improves our ability to assess the potential for adverse effects in fish because exposure from all sources is captured. Tissue residues are also more likely to represent steady-state conditions compared to those from water exposure because of the inherent reduction in variability usually observed for field data and the time course for bioaccumulation. We also examined the RR in a toxic unit approach to highlight the importance of considering multiple compounds exhibiting a similar mechanism of action. Published by Elsevier Ltd.

Proteomics of plasma membranes from poplar trees reveals tissue distribution of transporters, receptors, and proteins in cell wall formation.

Science.gov (United States)

Nilsson, Robert; Bernfur, Katja; Gustavsson, Niklas; Bygdell, Joakim; Wingsle, Gunnar; Larsson, Christer

2010-02-01

By exploiting the abundant tissues available from Populus trees, 3-4 m high, we have been able to isolate plasma membranes of high purity from leaves, xylem, and cambium/phloem at a time (4 weeks after bud break) when photosynthesis in the leaves and wood formation in the xylem should have reached a steady state. More than 40% of the 956 proteins identified were found in the plasma membranes of all three tissues and may be classified as "housekeeping" proteins, a typical example being P-type H(+)-ATPases. Among the 213 proteins predicted to be integral membrane proteins, transporters constitute the largest class (41%) followed by receptors (14%) and proteins involved in cell wall and carbohydrate metabolism (8%) and membrane trafficking (8%). ATP-binding cassette transporters (all members of subfamilies B, C, and G) and receptor-like kinases (four subfamilies) were two of the largest protein families found, and the members of these two families showed pronounced tissue distribution. Leaf plasma membranes were characterized by a very high proportion of transporters, constituting almost half of the integral proteins. Proteins involved in cell wall synthesis (such as cellulose and sucrose synthases) and membrane trafficking were most abundant in xylem plasma membranes in agreement with the role of the xylem in wood formation. Twenty-five integral proteins and 83 soluble proteins were exclusively found in xylem plasma membranes, which identifies new candidates associated with cell wall synthesis and wood formation. Among the proteins uniquely found in xylem plasma membranes were most of the enzymes involved in lignin biosynthesis, which suggests that they may exist as a complex linked to the plasma membrane.

A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation.

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Bjørndal, Bodil; Berge, Christ; Ramsvik, Marie Sannes; Svardal, Asbjørn; Bohov, Pavol; Skorve, Jon; Berge, Rolf K

2013-10-07

There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis factor alpha (hTNFα). hTNFα mice (C57BL/6 hTNFα) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma. The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of ∆6 and ∆9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-γ level was observed. Plasma carnitine and the carnitine precursor γ-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal β-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice. The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin.

Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells.

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Mellado-López, Maravillas; Griffeth, Richard J; Meseguer-Ripolles, Jose; Cugat, Ramón; García, Montserrat; Moreno-Manzano, Victoria

2017-01-01

Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100  μ M of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

Science.gov (United States)

Spreen, William; Ford, Susan L; Chen, Shuguang; Wilfret, David; Margolis, David; Gould, Elizabeth; Piscitelli, Stephen

2014-12-15

GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

Effects of experimentally increased protein supply to postpartum dairy cows on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis

DEFF Research Database (Denmark)

Larsen, Mogens; Røntved, Christine Maria; Theil, Peter Kappel

2017-01-01

The effect of experimentally increasing the postpartum protein supply on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis was studied using 8 periparturient Holstein cows in a complete randomized design. At calving, cows were assigned to abomasal infusion of water (CTRL......) or casein (CAS) in addition to a lactation diet. Casein infusion was gradually decreased from 696 ± 1 g/d at +2 d relative to calving (DRTC) to 212 ± 10 g/d at +29 DRTC to avoid excessive supply. Synthesis rate of plasma proteins was measured at –14, +4, +15, and +29 DRTC by measuring [13C]Phe isotopic...... enrichment in arterial plasma free Phe, total plasma proteins, and albumin after 3, 5, and 7 h of jugular ring[13C]Phe infusion. Plasma volume was determined at +4 and +29 DRTC by dilution of a [125I]BSA dose. Synthesis rate of tissue protein in biopsied rumen papillae was determined by measuring [13C...

Growth factor effects on costal chondrocytes for tissue engineering fibrocartilage

Science.gov (United States)

Johns, D.E.; Athanasiou, K.A.

2010-01-01

Tissue engineered fibrocartilage could become a feasible option for replacing tissues like the knee meniscus or temporomandibular joint disc. This study employed five growth factors insulin-like growth factor-I, transforming growth factor-β1, epidermal growth factor, platelet-derived growth factor-BB, and basic fibroblast growth factor in a scaffoldless approach with costal chondrocytes, attempting to improve biochemical and mechanical properties of engineered constructs. Samples were quantitatively assessed for total collagen, glycosaminoglycans, collagen type I, collagen type II, cells, compressive properties, and tensile properties at two time points. Most treated constructs were worse than the no growth factor control, suggesting a detrimental effect, but the IGF treatment tended to improve the constructs. Additionally, the 6wk time point was consistently better than 3wks, with total collagen, glycosaminoglycans, and aggregate modulus doubling during this time. Further optimization of the time in culture and exogenous stimuli will be important in making a more functional replacement tissue. PMID:18597118

Gene therapy with growth factors for periodontal tissue engineering–A review

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Gupta, Shipra; Mahendra, Aneet

2012-01-01

The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. The aim of this paper is to review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Various such materials have been formulated into devices that can be used as vehicles for delivery of cells, growth factors and DNA. Different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral and tooth supporting structure. Key words: Periodontal disease, gene therapy, regeneration, tissue repair, growth factors, tissue engineering. PMID:22143705

Quantification of tissue inhibitor of metalloproteinases 2 in plasma from healthy donors and cancer patients

DEFF Research Database (Denmark)

Larsen, M. B.; Stephens, R. W.; Brünner, Nils

2005-01-01

Tissue inhibitor of metalloproteinases (TIMP)-2 is a highly conserved molecule, which binds both active and latent matrix metalloproteinase (MMP)-2. TIMP-2 is also involved in the activation of MMP-2 on the cell surface. A quantitative enzyme-linked immunosorbent assay (ELISA) was established...... and optimized for measurement of TIMP-2 in plasma. The capturing antibody in the ELISA was a monoclonal, while the detecting antibody was a chicken polyclonal antibody recognizing the native form of human TIMP-2. The levels of TIMP-2 were measured in ethylenediaminetetraacetic acid (EDTA) and citrate plasma...... from healthy donors. The median values were determined as 163 ng/ml (n = 186) with a range of 109-253 ng/ml for EDTA plasma and 139 ng/ml (n = 77) with a range of 95-223 ng/ml for citrate plasma. The TIMP-2 concentration in citrate plasma from 15 patients with advanced, stage IV breast cancer had...

Combined effect of protein and oxygen on reactive oxygen and nitrogen species in the plasma treatment of tissue

Science.gov (United States)

Gaur, Nishtha; Szili, Endre J.; Oh, Jun-Seok; Hong, Sung-Ha; Michelmore, Andrew; Graves, David B.; Hatta, Akimitsu; Short, Robert D.

2015-09-01

The influence of protein and molecular, ground state oxygen (O2) on the plasma generation, and transport of reactive oxygen and nitrogen species (RONS) in tissue are investigated. A tissue target, comprising a 1 mm thick gelatin film (a surrogate for real tissue), is placed on top of a 96-well plate; each well is filled with phosphate buffered saline (PBS, pH 7.4) containing one fluorescent or colorimetric reporter that is specific for one of three RONS (i.e., H2O2, NO2-, or OH•) or a broad spectrum reactive oxygen species reporter (2,7-dichlorodihydrofluorescein). A helium cold atmospheric plasma (CAP) jet contacts the top of the gelatin surface, and the concentrations of RONS generated in PBS are measured on a microplate reader. The data show that H2O2, NO2-, or OH• are generated in PBS underneath the target. Independently, measurements are made of the O2 concentration in the PBS with and without the gelatin target. Adding bovine serum albumin protein to the PBS or gelatin shows that protein either raises or inhibits RONS depending upon the O2 concentration. Our results are discussed in the context of plasma-soft tissue interactions that are important in the development of CAP technology for medicine, biology, and food manufacturing.

Dietary (n-6 : n-3 Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

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Amira Abdulbari Kassem

2012-01-01

Full Text Available The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO: 50% cod liver oil (CLO (1 : 1, 84% SBO: 16% CLO (6 : 1, 96% SBO: 4% CLO (30 : 1. Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.

Dietary (n-6 : n-3) fatty acids alter plasma and tissue fatty acid composition in pregnant Sprague Dawley rats.

Science.gov (United States)

Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

2012-01-01

The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.

Dietary (n-6 : n-3) Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

Science.gov (United States)

Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

2012-01-01

The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat. PMID:22489205

On the search for new anticancer drugs 14: the plasma pharmacokinetics and tissue distribution of spin-labeled thio-TEPA (SL-O-TT).

Science.gov (United States)

Gutierrez, P L; Cohen, B E; Sosnovsky, G; Davis, T A; Egorin, M J

1985-01-01

We defined the plasma and tissue concentrations and pharmacokinetics of SL-O-TT, a spin-labeled analog of thio-TEPA, in 35-44-g male Swiss Webster mice that had received spin-labeled thio-TEPA at a dosage of 10 mg/kg. Concentrations of spin-labeled thio-TEPA in ethyl acetate extracts of tissue and plasma were determined by gas-liquid chromatography and electron spin resonance spectroscopy. Plasma concentrations of spin-labeled thio-TEPA declined in a biexponential fashion that was well described by the equation: Ct = 21.5e-0.276t + 2.30e-0.026t indicating a half-life alpha of 2.5 min and a half-life beta of 26.6 min. After 2 h there was still spin-labeled thio-TE-PA in plasma, but not in tissues. In tissues, no spin-labeled thio-TEPA was detected with gas-liquid chromatography 15 min after injection, but with electron-spin resonance label was found in lung and skeletal muscle. The main metabolite of spin-labeled thio-TEPA is spin-labeled TEPA, where oxidative desulfurization is invoked as the main metabolic mechanism. Reduction of the spin label to the hydroxylamine was also observed with time.

Growth factor-enriched autologous plasma improves wound healing after surgical debridement in odontogenic necrotizing fasciitis: a case report

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Martinez-Fong Daniel

2011-03-01

Full Text Available Abstract Background Odontogenic necrotizing fasciitis of the neck is a fulminant infection of odontogenic origin that quickly spreads along the fascial planes and results in necrosis of the affected tissues. It is usually polymicrobial, occurs frequently in immunocompromised patients, and has a high mortality rate. Case presentation A 69-year old Mexican male had a pain in the maxillar right-canine region and a swelling of the submental and submandibular regions. Our examination revealed local pain, tachycardia, hyperthermia (39°C, and the swelling of bilateral submental and submandibular regions, which also were erythematous, hyperthermic, crepitant, and with a positive Godet sign. Mobility and third-degree caries were seen in the right mandibular canine. Bacteriological cultures isolated streptococcus pyogenes and staphylococcus aureus. The histopathological diagnosis was odontogenic necrotizing fasciitis of the submental and submandibular regions. The initial treatment was surgical debridement and the administration of antibiotics. After cultures were negative, the surgical wound was treated with a growth factor-enriched autologous plasma eight times every third day until complete healing occurred. Conclusions The treatment with a growth factor-enriched autologous plasma caused a rapid healing of an extensive surgical wound in a patient with odontogenic necrotizing fasciitis. The benefits were rapid tissue regeneration, an aesthetic and a functional scar, and the avoidance of further surgery and possible complications.

In vivo transfer of cholesteryl ester from high and low density plasma lipoproteins into human aortic tissue

International Nuclear Information System (INIS)

Stender, S.; Hjelms, E.

1988-01-01

For the study of cholesteryl ester transfer from different plasma lipoproteins into human aortic tissue, patients scheduled for reconstructive aortic surgery were intravenously injected with autologous in vitro labeled lipoproteins 20 to 24 hours before aortic intima-media samples were obtained during the operation. The injectate contained high density lipoproteins (d greater than 1.063) labeled with 3H-cholesteryl ester and lipoproteins of lower density (d less than 1.063) labeled with 14C-cholesteryl ester or lipoproteins with the opposite labeling. In 16 aortic tissue samples (some with visible atherosclerosis) from 11 normocholesterolemic patients, the aortic influx of total cholesteryl ester was 1 to 50 nmol x cm-2 x day-1. Some 39% +/- 3% (mean +/- SEM) of the influx was derived from high density lipoproteins, which in plasma accounted for only 22% +/- 2% (mean +/- SEM) of the esterified cholesterol. The findings suggest that: 1) esterified cholesterol from the two lipoprotein fractions in plasma enter the aortic intima by the same mechanism, and 2) influx of cholesteryl ester from the smaller, high density lipoproteins is greater than influx from the larger, lower density lipoproteins considering their concentrations in plasma. In some patients, the cholesterol content in the intima-media tissue with no visible atherosclerosis corresponded to only a few months of continuous cholesteryl ester influx. This time is short considering the age of the patients and, therefore, indicates that removal of esterified cholesterol from the intima-media is of major importance in preventing cholesterol deposition in the arterial wall

The Synergistic Effect between Electrical and Chemical Factors in Plasma Gene/Molecule-Transfection

Science.gov (United States)

Jinno, Masafumi

2016-09-01

This study has been done to know what kind of factors in plasma and processes on cells promote plasma gene/molecule transfection. We have discovered a new plasma source using a microcapillary electrode which enables high transfection efficiency and high cell survivability simultaneously. However, the mechanism of the transfection by plasma was not clear. To clarify the transfection mechanisms by micro plasma, we focused on the effects of electrical (current, charge, field, etc.) and chemical (radicals, RONS, etc.) factors generated by the micro plasma and evaluated the contribution weight of three groups of the effects and processes, i.e. electrical, chemical and biochemical ones. At first, the necessity of the electrical factors was estimated by the laser produced plasma (LPP). Mouse L-929 fibroblast cell was cultured on a 96-well plate or 12-well micro slide chamber. Plasmids pCX-EGFP in Tris-EDTA buffer was dropped on the cells and they were exposed to the capillary discharge plasma (CDP) or the LPP. In the case of the CDP, the plasma was generated between the tip of the capillary electrode and the cells so that both electrical and chemical factors were supplied to the cells. In this setup, about 20% of average transfection efficiency was obtained. In the case of the LPP, the plasma was generated apart from the cells so that electrical factors were not supplied to the cells. In this setup, no transfection was observed. These results show that the electrical factors are necessary for the plasma gene transfection. Next, the necessity of the chemical factors was estimated the effect of catalase to remove H2O2 in CDP. The transfection efficiency decreased to 0.4 by scavenging H2O2 with catalase. However, only the solution of H2O2 caused no gene transfection in cells. These results shows that H2O2 is important species to cause gene/molecule transfection but still needs a synergistic effect with electrical or other chemical factors. This work was partly supported by

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.

Correlation of virus load in plasma and lymph node tissue in human immunodeficiency virus infection. INCAS Study Group. Italy, Netherlands, Canada, Australia, and (United) States.

Science.gov (United States)

Harris, M; Patenaude, P; Cooperberg, P; Filipenko, D; Thorne, A; Raboud, J; Rae, S; Dailey, P; Chernoff, D; Todd, J; Conway, B; Montaner, J S

1997-11-01

The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted from homogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12-18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.

Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

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Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

2015-02-01

Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Blood BDNF concentrations reflect brain-tissue BDNF levels across species

DEFF Research Database (Denmark)

Klein, Anders B; Williamson, Rebecca; Santini, Martin A

2011-01-01

Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

Blood BDNF concentrations reflect brain-tissue BDNF levels across species

DEFF Research Database (Denmark)

Klein, Anders B; Williamson, Rebecca; Santini, Martin A

2011-01-01

no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from......Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)—Patient Version

Science.gov (United States)

Plasma cell neoplasms occur when abnormal plasma cells or myeloma cells form tumors in the bones or soft tissues of the body. Multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are different types of plasma cell neoplasms. Find out about risk factors, symptoms, diagnostic tests, prognosis, and treatment for these diseases.

Controlled Systemic Delivery by Polymeric Implants Enhances Tissue and Plasma Curcumin Levels Compared with Oral Administration

Science.gov (United States)

Bansal, Shyam S.; Kausar, Hina; Vadhanam, Manicka V.; Ravoori, Srivani; Gupta, Ramesh C.

2012-01-01

Curcumin possess potent anti-inflammatory and anti-proliferative activities but with poor biopharmaceutical attributes. To overcome these limitations, curcumin implants were developed and tissue (plasma, brain and liver) curcumin concentrations were measured in female ACI rats for 3 months. Biological efficacy of tissue levels achieved was analyzed by modulation of hepatic cytochromes. Curcumin implants exhibited diffusion-mediated biphasic release pattern with ~2-fold higher in vivo release as compared to in vitro. Plasma curcumin concentration from implants was ~3.3 ng/ml on day 1 which dropped to ~0.2 ng/ml after 3 months whereas only 0.2–0.3 ng/ml concentration was observed from 4–12 days with diet and was undetected subsequently. Almost 10 fold higher curcumin levels were observed in brain on day 1 from implants compared with diet (30.1±7.3 vs 2.7±0.8 ng/g) and were higher even after 90 days (7.7±3.8 vs 2.2±0.8 ng/g). Although, curcumin levels were similar in liver from both the routes (~25–30 ng/g from day 1–4 and ~10–15 ng/g at 90 days), implants were more efficacious in altering hepatic CYP1A1 levels and CYP3A4 activity at ~28 fold lower doses. Curcumin implants provided much higher plasma and tissue concentrations and are a viable alternative for delivery of curcumin to various organs like brain. PMID:22227368

Ovulation-inducing factor: a protein component of llama seminal plasma

Directory of Open Access Journals (Sweden)

Huanca Wilfredo

2010-05-01

Full Text Available Abstract Background Previously, we documented the presence of ovulation-inducing factor (OIF in the seminal plasma of llamas and alpacas. The purpose of the study was to define the biochemical characteristics of the molecule(s in seminal plasma responsible for inducing ovulation. Methods In Experiment 1, llama seminal plasma was centrifuged using filtration devices with nominal molecular mass cut-offs of 30, 10 and 5 kDa. Female llamas (n = 9 per group were treated i.m. with whole seminal plasma (positive control, phosphate-buffered saline (negative control, or the fraction of seminal plasma equal or higher than 30 kDa, 10 to 30 kDa, 5 to 10 kDa, or Results In Experiment 1, all llamas in the equal or higher than 30 kDa and positive control groups ovulated (9/9 in each, but none ovulated in the other groups (P Conclusions We conclude that ovulation-inducing factor (OIF in llama seminal plasma is a protein molecule that is resistant to heat and enzymatic digestion with proteinase K, and has a molecular mass of approximately equal or higher than 30 kDa.

A hypothesis: factor VII governs clot formation, tissue repair and apoptosis.

Science.gov (United States)

Coleman, Lewis S

2007-01-01

A hypothesis: thrombin is a "Universal Enzyme of Energy Transduction" that employs ATP energy in flowing blood to activate biochemical reactions and cell effects in both hemostasis and tissue repair. All cells possess PAR-1 (thrombin) receptors and are affected by thrombin elevations, and thrombin effects on individual cell types are determined by their unique complement of PAR-1 receptors. Disruption of the vascular endothelium (VE) activates a tissue repair mechanism (TRM) consisting of the VE, tissue factor (TF), and circulating Factors VII, IX and X that governs localized thrombin elevations to activate clot formation and cellular effects that repair tissue damage. The culmination of the repair process occurs with the restoration of the VE followed by declines in thrombin production that causes Apoptosis ("programmed cell death") in wound-healing fibroblasts, which functions as a mechanism to draw wound edges together. The location and magnitude of TRM activity governs the location and magnitude of Factor VIII activity and clot formation, but the large size of Factor VIII prevents it from penetrating the clot formed by its activity, so that its effects are self-limiting. Factors VII, IX and X function primarily as tissue repair enzymes, while Factor VIII and Factor XIII are the only serine protease enzymes in the "Coagulation Cascade" that are exclusively associated with hemostasis.

Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes.

Science.gov (United States)

Gould, Travis J; Lysov, Zakhar; Swystun, Laura L; Dwivedi, Dhruva J; Zarychanski, Ryan; Fox-Robichaud, Alison E; Liaw, Patricia C

2016-12-01

Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone-treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.

An In Vitro Investigation of Platelet-Rich Plasma-Gel as a Cell and Growth Factor Delivery Vehicle for Tissue Engineering

OpenAIRE

Jalowiec, Jagoda M.; D'Este, Matteo; Bara, Jennifer Jane; Denom, Jessica; Menzel, Ursula; Alini, Mauro; Verrier, Sophie; Herrmann, Marietta

2015-01-01

Platelet-rich plasma (PRP) has been used for different applications in human and veterinary medicine. Many studies have shown promising therapeutic effects of PRP; however, there are still many controversies regarding its composition, properties, and clinical efficacy. The aim of this study was to evaluate the influence of different platelet concentrations on the rheological properties and growth factor (GF) release profile of PRP-gels. In addition, the viability of incorporated bone marrow-d...

SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods.

Science.gov (United States)

Schuitemaker, Alie; van Berckel, Bart N M; Kropholler, Marc A; Veltman, Dick J; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A; Boellaard, Ronald

2007-05-01

(R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to interobserver variation. In addition, results are only obtained for predefined areas and (unexpected) signals in undefined areas may be missed. On the other hand, standard pharmacokinetic models are too sensitive to noise to calculate (R)-[11C]PK11195 binding on a voxel-by-voxel basis. Linearised versions of both plasma input and reference tissue models have been described, and these are more suitable for parametric imaging. The purpose of this study was to compare the performance of these plasma input and reference tissue parametric methods on the outcome of statistical parametric mapping (SPM) analysis of (R)-[11C]PK11195 binding. Dynamic (R)-[11C]PK11195 PET scans with arterial blood sampling were performed in 7 younger and 11 elderly healthy subjects. Parametric images of volume of distribution (Vd) and binding potential (BP) were generated using linearised versions of plasma input (Logan) and reference tissue (Reference Parametric Mapping) models. Images were compared at the group level using SPM with a two-sample t-test per voxel, both with and without proportional scaling. Parametric BP images without scaling provided the most sensitive framework for determining differences in (R)-[11C]PK11195 binding between younger and elderly subjects. Vd images could only demonstrate differences in (R)-[11C]PK11195 binding when analysed with proportional scaling due to intersubject variation in K1/k2 (blood-brain barrier transport and non-specific binding).

Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect.

Science.gov (United States)

Mathijssen, Natascha C J; Masereeuw, Rosalinde; Holme, Pal Andre; van Kraaij, Marian G J; Laros-van Gorkom, Britta A P; Peyvandi, Flora; van Heerde, Waander L

2013-08-01

Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. Ten factor VII deficient patients were treated with either recombinant activated (20 μg/kg) or plasma-derived (25 IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236 ml/kg; 175 ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206 ml/kg; 64 ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright © 2013 Elsevier Ltd. All rights reserved.

Connective tissue activation. XVII

International Nuclear Information System (INIS)

Weiss, J.J.; Donakowski, C.; Anderson, B.; Meyers, S.; Castor, C.W.

1980-01-01

The platelet-derived connective tissue activating peptide (CTAP-III) has been shown to be an important factor stimulating the metabolism and proliferation of human connective tissue cell strains, including synovial tissue cells. The quantities of CTAP-III affecting the cellular changes and the amounts in various biologic fluids and tissues are small. The objectives of this study were to develop a radioimmunoassay (RIA) for CTAP-III and to ascertain the specificities of the anti-CTAP-III sera reagents. The antisera were shown not to cross-react with a number of polypeptide hormones. However, two other platelet proteins β-thromboglobulin and low affinity platelet factor-4, competed equally as well as CTAP-III for anti-CTAP-III antibodies in the RIA system. Thus, the three platelet proteins are similar or identical with respect to those portions of the molecules constituting the reactive antigenic determinants. The levels of material in normal human platelet-free plasma that inhibited anti-CTAP-III- 125 I-CTAP-III complex formation were determined to be 34+-13 (S.D.) ng/ml. (Auth.)

Regulation of plasma von Willebrand factor [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Karl C Desch

2018-01-01

Full Text Available Von Willebrand factor (VWF is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.

Plasma tissue inhibitor of metalloproteinases-1 as a biological marker? Pre-analytical considerations

DEFF Research Database (Denmark)

Lomholt, Anne Fog; Frederiksen, Camilla; Christensen, Ib Jarle

2007-01-01

Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) may be a valuable biological marker in Colorectal Cancer (CRC). However, prospective validation of TIMP-1 as a biological marker should include a series of pre-analytical considerations. TIMP-1 is stored in platelets, which may degranulate during ...... collection and storage. The aim of this study was to evaluate the influence of platelet TIMP-1 contamination on plasma TIMP-1 levels in healthy volunteers....

Effects of argon plasma coagulation on human stomach tissue: An ex vivo study.

Science.gov (United States)

Gong, Eun Jeong; Ahn, Ji Yong; Jung, Hwoon-Yong; Park, Young Soo; Na, Hee Kyong; Jung, Kee Wook; Kim, Do Hoon; Lee, Jeong Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Kim, Jin-Ho

2017-05-01

Argon plasma coagulation (APC) is a safe alternative treatment for gastrointestinal neoplasms and precancerous lesions. However, the extent of thermal damage after APC is difficult to predict. We investigated the effects of APC on human stomach tissue. Argon plasma coagulation was performed on 10 freshly resected human stomachs that were obtained after total gastrectomy. The effects on tissue were compared across power settings (40, 60, and 80 W), durations (5, 10, 15, 20, and 25 s), and between injection (submucosal injection of normal saline) and control (without injection) groups. Success was defined as complete mucosal necrosis without damaging the muscularis propria. Without submucosal injection, the incidence of damaging the muscularis propria increased as the power and duration increased. Tissue damage in the injection group was mostly confined to the submucosa, even when using the high-power setting. In the injection group, ablations at 40 W for 20 s, 60 W for 15 s, and 80 W for 15 or 20 s produced success rates ≥80%. In the control group, ablations at 60 W for 10 s, and 80 W for 5, or 10 s produced success rates ≥80%. The optimal energy levels to achieve complete mucosal and submucosal necrosis without damaging the muscularis propria were 800-1600 and 600-800 J in the injection and control groups, respectively. Application of APC produces good results with a low risk of perforation. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells

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Maravillas Mellado-López

2017-01-01

Full Text Available Adipose-derived stem cells (ASCs are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100 μM of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

Tissue localization of human trefoil factors 1, 2, and 3

DEFF Research Database (Denmark)

Madsen, Jens; Nielsen, Ole; Tornøe, Ida

2007-01-01

Trefoil factors (TTFs) are small, compact proteins coexpressed with mucins in the gastrointestinal tract. Three trefoil factors are known in mammals: TFF1, TFF2, and TFF3. They are implicated to play diverse roles in maintenance and repair of the gastrointestinal channel. We compared the expression...... pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised...... against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more...

Do methodological differences account for the current controversy on tissue factor expression in platelets?

Science.gov (United States)

Brambilla, Marta; Rossetti, Laura; Zara, Chiara; Canzano, Paola; Giesen, Peter L A; Tremoli, Elena; Camera, Marina

2018-06-01

Tissue factor (TF), the key activator of the blood coagulation cascade and of thrombus formation, is also expressed by circulating human platelets. Despite the documented in-depth characterization of platelet TF carried out in the past 15 years, some authors still fail to identify TF in platelets, especially when assessment in platelet-rich plasma (PRP) or washed platelets is carried out. This study aims to extend the characterization of the subset of TF-positive platelets in PRP from healthy subjects and to verify how different centrifugation forces, used to prepare the PRP, could affect the analysis of TF-positive platelets. Data indicate that large-size platelets express significantly higher amount of TF compared to small-size cells, in terms of both TF protein and TF mRNA. Upon stimulation, large platelets readily expose on the cell membrane TF, which is functionally active, i.e., able to generate factor Xa (FXa) as well as thrombin. By contrast, TF activity in small platelets is almost completely quenched by tissue factor pathway inhibitor (TFPI), becoming indeed detectable only after treatment with an anti-TFPI antibody. Our data highlight that particular attention must be paid to the preparation and collection of the PRP since such preanalytical variables may influence the platelet recovery and in turn affect subsequent analysis, whether it is flow cytometry, functional activity tests, proteome, or transcriptome analysis. Indeed, the TF-positive subset of large platelets can easily be lost if centrifugation protocols are not optimized, thus erroneously leading to a false-negative result.

Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

Science.gov (United States)

van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

2012-10-01

The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

Concentration of Potassium in Plasma, Erythrocytes, and Muscle Tissue in Cows with Decreased Feed Intake and Gastrointestinal Ileus.

Science.gov (United States)

Schneider, S; Müller, A; Wittek, T

2016-01-01

Healthy cows consume large amounts of potassium and a sudden loss in appetite can lead to hypokalemia. The routine method to evaluate potassium homeostasis is the measurement of the extracellular potassium in plasma or serum, but this does not provide information about the intracellular potassium pool. To evaluate potassium homeostasis by comparing the extracellular and intracellular potassium concentration in cows with reduced feed intake and gastrointestinal ileus. Twenty cows 1-3 days postpartum (group 1) and 20 cows with gastrointestinal ileus (group 2). Observational cross-sectional study. Plasma potassium was measured by using an ion-sensitive electrode. Intracellular potassium was measured in erythrocytes and muscle tissue (muscle biopsy) by using inductively coupled plasma optical emission spectroscopy. Cows of group 1 did not have hypokalemia. Overall cows with gastrointestinal ileus were hypokalemic (mean ± SD, 2.9 mmol/L ± 0.78), but potassium concentration in erythrocytes and muscle tissue was not lower than in postpartum cows. Intracellular potassium in erythrocytes varied very widely; group 1: 3497-10735 mg/kg (5559 ± 2002 mg/kg), group 2: 4139-21678 mg/kg (7473 ± 4034 mg/kg). Potassium in muscle tissue did not differ between group 1 (3356 ± 735 mg/kg wet weight) and group 2 (3407 ± 1069 mg/kg wet weight). No association between extracellular and intracellular potassium concentrations was detected. That measurement of plasma potassium concentration is not sufficient to evaluate potassium metabolism of cows. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Tissue Factor and Tissue Factor Pathway Inhibitor in the Wound-Healing Process After Neurosurgery.

Science.gov (United States)

Ślusarz, Robert; Głowacka, Mariola; Biercewicz, Monika; Barczykowska, Ewa; Haor, Beata; Rość, Danuta; Gadomska, Grażyna

2016-03-01

The aim of the study was to assess the concentrations of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the blood of patients with a postoperative wound after neurosurgery. Participants included 20 adult patients who underwent neurosurgery because of degenerative spine changes. The concentration of TF and TFPI in the patients' blood serum was measured 3 times: before surgery, during the first 24 hr after surgery, and between the 5th and 7th days after surgery. The control group comprised 20 healthy volunteers similar to the patient group with respect to gender and age. A statistically significant difference was observed between TF concentration at all three measurement time points in the research group and TF concentration in the control group (p = .018, p = .010, p = .001). A statistically significant difference was found between TFPI concentration at the second time point in the research group and TFPI concentration in the control group (p = .041). No statistically significant within-subject difference was found between TF concentrations before and after surgery. A statistically significant within-subject difference was found between TFPI concentrations within 24 hr after surgery and 5-7 days after surgery (p = .004). High perioperative concentrations of TF indicate not only the presence of thrombophilia but also the importance of TF in the wound-healing process. Perioperative changes in TFPI concentrations are related to its compensatory influence on hemostasis in thrombophilic conditions. © The Author(s) 2015.

Validation of the IDS Octeia ELISA for the determination of insulin-like growth factor 1 in equine serum and tendon tissue extracts

DEFF Research Database (Denmark)

Lygren, Tone; Schjerling, Peter; Jacobsen, Stine

2013-01-01

BACKGROUND: Insulin-like growth factor (IGF-1) is an important mediator of tissue repair in horses. OBJECTIVES: The aim of the study was to evaluate whether IGF-1 could be measured reliably in equine serum and tendon tissue extracts, using an IGF-1 ELISA kit developed for human serum and plasma...... diluted equine serum samples and tendon tissue extracts. The recovery of IGF-1 was evaluated in serum and tendon tissue extracts spiked with known amounts of IGF-1. RESULTS: The range of IGF-1 released using the manufacturer's pretreatment was between 23% and 56% of the amount released using the gly...... with serum, and 72 ± 15% when diluted with PBS. The recovery after dilution was 108 ± 17% in tendon tissue extracts. Recovery from serum spiked with a fixed amount of IGF-1 was 101 ± 5% and 99 ± 7% from tendon tissue samples. CONCLUSIONS: The IDS Octeia IGF-1 ELISA kit can be used for measuring IGF-1...

Effects of spontaneously hypertensive rat plasma on blood pressure and tail artery calcium uptake in normotensive rats

International Nuclear Information System (INIS)

Lewanczuk, R.Z.; Wang, J.; Zhang, Z.R.; Pang, P.K.

1989-01-01

Previous studies have described the presence of humoral hypertensive factors in spontaneously hypertensive rats (SHR). Other studies have described factors that increase calcium uptake in vascular tissue. In this study, we attempted to confirm, and thereby correlate, the presence of both types of factors in SHR plasma. Intravenous infusion or bolus administration of dialyzed SHR plasma consistently induced an increase in blood pressure in normotensive rats. This hypertensive response was somewhat delayed, with peak blood pressures occurring 45 minutes after bolus administration and 90 minutes after infusion of SHR plasma. Spontaneously hypertensive rat plasma also increased 45 Ca uptake in isolated normotensive rat tail arteries in a dose-dependent manner, with a time course similar to that for the hypertensive response to bolus administration. These findings suggest, therefore, that a substance exists in SHR plasma that can increase intracellular calcium in vascular tissues and thereby increase blood pressure

Determination of the neuropharmacological drug nodakenin in rat plasma and brain tissues by liquid chromatography tandem mass spectrometry: Application to pharmacokinetic studies.

Science.gov (United States)

Song, Yingshi; Yan, Huiyu; Xu, Jingbo; Ma, Hongxi

2017-09-01

A rapid and sensitive liquid chromatography tandem mass spectrometry detection using selected reaction monitoring in positive ionization mode was developed and validated for the quantification of nodakenin in rat plasma and brain. Pareruptorin A was used as internal standard. A single step liquid-liquid extraction was used for plasma and brain sample preparation. The method was validated with respect to selectivity, precision, accuracy, linearity, limit of quantification, recovery, matrix effect and stability. Lower limit of quantification of nodakenin was 2.0 ng/mL in plasma and brain tissue homogenates. Linear calibration curves were obtained over concentration ranges of 2.0-1000 ng/mL in plasma and brain tissue homogenates for nodakenin. Intra-day and inter-day precisions (relative standard deviation, RSD) were <15% in both biological media. This assay was successfully applied to plasma and brain pharmacokinetic studies of nodakenin in rats after intravenous administration. Copyright © 2017 John Wiley & Sons, Ltd.

Benefits of plasma rich in growth factors (PRGF) in skin photodamage: clinical response and histological assessment.

Science.gov (United States)

Díaz-Ley, B; Cuevast, J; Alonso-Castro, L; Calvo, M I; Ríos-Buceta, L; Orive, G; Anitua, E; Jaén, P

2015-01-01

Skin ageing is characterized by small and fine wrinkles, roughness, laxity, and pigmentation as a result of epidermal thinning, collagen degradation, dermal atrophy, and fewer fibroblasts. Plasma rich in growth factors (PRGF) is an autologous plasma preparation enriched in proteins obtained from patient's own blood aimed at accelerating tissue repair and regeneration. To evaluate the benefits of PRGF in skin photodamage, 10 healthy volunteers were treated with three consecutive intradermal injections of PRGF in the facial area. Clinical outcomes and histological analysis were performed. A statistically significant increase in the epidermis and papillary dermis thickness was seen after PRGF treatment (p PRGF treatment, a reduction of the average area fraction of solar elastosis was observed in patients with clinical and histological signs of skin photodamage (p PRGF use was 0.75 (9/12) for the group of patients with signs of skin photodamage. Intradermal PRGF infiltration appears to be an effective treatment for the photodamaged skin. © 2015 Wiley Periodicals, Inc.

Experimental validation of a Lyapunov-based controller for the plasma safety factor and plasma pressure in the TCV tokamak

Science.gov (United States)

Mavkov, B.; Witrant, E.; Prieur, C.; Maljaars, E.; Felici, F.; Sauter, O.; the TCV-Team

2018-05-01

In this paper, model-based closed-loop algorithms are derived for distributed control of the inverse of the safety factor profile and the plasma pressure parameter β of the TCV tokamak. The simultaneous control of the two plasma quantities is performed by combining two different control methods. The control design of the plasma safety factor is based on an infinite-dimensional setting using Lyapunov analysis for partial differential equations, while the control of the plasma pressure parameter is designed using control techniques for single-input and single-output systems. The performance and robustness of the proposed controller is analyzed in simulations using the fast plasma transport simulator RAPTOR. The control is then implemented and tested in experiments in TCV L-mode discharges using the RAPTOR model predicted estimates for the q-profile. The distributed control in TCV is performed using one co-current and one counter-current electron cyclotron heating actuation.

Platelet-Rich Plasma Derived Growth Factors Contribute to Stem Cell Differentiation in Musculoskeletal Regeneration

Directory of Open Access Journals (Sweden)

Yun Qian

2017-10-01

Full Text Available Stem cell treatment and platelet-rich plasma (PRP therapy are two significant issues in regenerative medicine. Stem cells such as bone marrow mesenchymal stem cells, adipose-derived stem cells and periodontal ligament stem cells can be successfully applied in the field of tissue regeneration. PRP, a natural product isolated from whole blood, can secrete multiple growth factors (GFs for regulating physiological activities. These GFs can stimulate proliferation and differentiation of different stem cells in injury models. Therefore, combination of both agents receives wide expectations in regenerative medicine, especially in bone, cartilage and tendon repair. In this review, we thoroughly discussed the interaction and underlying mechanisms of PRP derived GFs with stem cells, and assessed their functions in cell differentiation for musculoskeletal regeneration.

Effect of hypocaloric diet-induced weight loss in obese women on plasma apelin and adipose tissue expression of apelin and APJ.

Science.gov (United States)

Castan-Laurell, Isabelle; Vítkova, Michaela; Daviaud, Danièle; Dray, Cédric; Kováciková, Michaela; Kovacova, Zuzana; Hejnova, Jindriska; Stich, Vladimir; Valet, Philippe

2008-06-01

Apelin is a novel adipokine acting on APJ receptor, regulated by insulin and tumor necrosis factor-alpha (TNF-alpha) in adipose tissue (AT). Plasma apelin levels are increased in obese hyperinsulinemic subjects. The aim was to investigate whether the hypocaloric diet associated with weight loss modifies the elevated plasma apelin levels and the expression of apelin and APJ receptor in AT in obese women. Fasting plasma levels of apelin and TNF-alpha as well as mRNA levels of apelin and APJ in AT were measured before and after a 12-week hypocaloric weight-reducing diet in 20 obese women (body mass index (BMI) before diet 32.2+/-6.4 kg/m(2)). Twelve healthy women with a BMI of 20.7+/-0.6 kg/m(2) served as reference. Plasma levels of apelin and TNF-alpha were higher in obese compared with lean controls. The hypocaloric diet resulted in a significant decrease of BMI to 29.8+/-6.3 kg/m(2), plasma insulin (8.16+/-0.73 to 6.58+/-0.66 mU/l), apelin (369+/-25 pg/ml to 257+/-12 pg/ml), TNF-alpha levels (0.66+/-0.04 pg/ml to 0.56+/-0.04 pg/ml), and AT mRNAs of apelin and APJ. In addition, changes in AT mRNA apelin were related to changes in AT mRNA APJ levels. The hypocaloric diet associated with weight loss reduces the increased plasma and AT expression of apelin in obese women. This reduced apelin expression in AT could contribute to decreased circulating apelin levels.

Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB.

Science.gov (United States)

Sun, Qi; Chen, Ling; Gao, Mengyu; Jiang, Wenwen; Shao, Fangxian; Li, Jingjing; Wang, Jun; Kou, Junping; Yu, Boyang

2012-01-01

Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis. Copyright © 2011 Elsevier B.V. All rights reserved.

Treatment of Ebola Virus Infection With a Recombinant Inhibitor of Factor Vlla/Tissue Factor: A Study in Rhesus Monkeys

National Research Council Canada - National Science Library

Geisbert, Thomas W; Hensley, Lisa E; Jahrling, Peter B; Larsen, Tom; Geisbert, Joan B

2003-01-01

Infection with the Ebola virus induces overexpression of the procoagulant tissue factor in primate monocytes and macrophages, suggesting that inhibition of the tissue-factor pathway could ameliorate...

Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

Science.gov (United States)

Koizume, Shiro; Miyagi, Yohei

2015-01-01

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

Preparation and application of an innovative thrombocyte/leukocyte-enriched plasma to promote tissue repair in chelonians.

Directory of Open Access Journals (Sweden)

Francesco Di Ianni

Full Text Available Platelet concentrates are widely used in mammalian regenerative medicine to improve tissue healing. Chelonians (Testudines would benefit from the application of thrombocyte preparations to regenerate damaged tissues, since traumatic injuries are leading causes of morbidity and mortality for both wild-living and domesticated animals. The aim of this study was to establish a protocol that optimized the recovery of the thrombocytes from blood samples and to show the efficacy of thrombocyte-enriched plasma in chelonians. Peripheral blood samples were obtained from Testudo spp. (n = 12 and Trachemys scripta elegans (n = 10. Blood cells were fractionated by sodium diatrizoate-sodium polysucrose density gradient using a two-step centrifugation protocol. Thrombocytes and leukocytes were isolated and resuspended to obtain thrombocyte-leucocyte rich plasma (TLRP. The mean recovery of leukocytes and thrombocytes was 48.9% (±4.0 SEM, n = 22 of the whole blood cell content. No statistically significant difference was observed between blood samples collected from different turtle species. The ability of TLRP to form a gel was evaluated by adding variable concentrations of calcium gluconate at room temperature and at 37°C. A reliable and consistent clotting of the TLRP was obtained in glass tubes and dishes by adding 5-20% v/v of a 100 mg/ml solution of calcium gluconate. Furthermore, in order to test the clinical efficacy of TLRP, a preliminary evaluation was performed on four turtles (Testudo spp. with traumatic injuries. In all the four animals, a successful clinical outcome was observed. The results demonstrated that a thrombocyte-enriched plasma, comparable to mammalian platelet rich plasma, can be prepared from chelonian blood samples. Furthermore, although the low number of cases presented does not allow definitive conclusions from a clinical point of view, their outcome suggests that TLRP application could be further investigated to improve the

Preparation and Application of an Innovative Thrombocyte/Leukocyte-Enriched Plasma to Promote Tissue Repair in Chelonians

Science.gov (United States)

Di Ianni, Francesco; Merli, Elisa; Burtini, Francesca; Conti, Virna; Pelizzone, Igor; Di Lecce, Rosanna; Parmigiani, Enrico; Squassino, Gian Paolo; Del Bue, Maurizio; Lucarelli, Enrico; Ramoni, Roberto; Grolli, Stefano

2015-01-01

Platelet concentrates are widely used in mammalian regenerative medicine to improve tissue healing. Chelonians (Testudines) would benefit from the application of thrombocyte preparations to regenerate damaged tissues, since traumatic injuries are leading causes of morbidity and mortality for both wild-living and domesticated animals. The aim of this study was to establish a protocol that optimized the recovery of the thrombocytes from blood samples and to show the efficacy of thrombocyte-enriched plasma in chelonians. Peripheral blood samples were obtained from Testudo spp. (n = 12) and Trachemys scripta elegans (n = 10). Blood cells were fractionated by sodium diatrizoate-sodium polysucrose density gradient using a two-step centrifugation protocol. Thrombocytes and leukocytes were isolated and resuspended to obtain thrombocyte-leucocyte rich plasma (TLRP). The mean recovery of leukocytes and thrombocytes was 48.9% (±4.0 SEM, n = 22) of the whole blood cell content. No statistically significant difference was observed between blood samples collected from different turtle species. The ability of TLRP to form a gel was evaluated by adding variable concentrations of calcium gluconate at room temperature and at 37°C. A reliable and consistent clotting of the TLRP was obtained in glass tubes and dishes by adding 5-20% v/v of a 100 mg/ml solution of calcium gluconate. Furthermore, in order to test the clinical efficacy of TLRP, a preliminary evaluation was performed on four turtles (Testudo spp.) with traumatic injuries. In all the four animals, a successful clinical outcome was observed. The results demonstrated that a thrombocyte-enriched plasma, comparable to mammalian platelet rich plasma, can be prepared from chelonian blood samples. Furthermore, although the low number of cases presented does not allow definitive conclusions from a clinical point of view, their outcome suggests that TLRP application could be further investigated to improve the healing process of

A Loss in the Plasma Membrane ATPase Activity and Its Recovery Coincides with Incipient Freeze-Thaw Injury and Postthaw Recovery in Onion Bulb Scale Tissue 1

Science.gov (United States)

Arora, Rajeev; Palta, Jiwan P.

1991-01-01

Plasma membrane ATPase has been proposed to be functionally altered during early stages of injury caused by a freeze-thaw stress. Complete recovery from freezing injury in onion cells during the postthaw period provided evidence in support of this proposal. During recovery, a simultaneous decrease in ion leakage and disappearance of water soaking (symptoms of freeze-thaw injury) has been noted. Since reabsorption of ions during recovery must be an active process, recovery of plasma membrane ATPase (active transport system) functions has been implicated. In the present study, onion (Allium cepa L. cv Downing Yellow Globe) bulbs were subjected to a freeze-thaw stress which resulted in a reversible (recoverable) injury. Plasma membrane ATPase activity in the microsomes (isolated from the bulb scales) and ion leakage rate (efflux/hour) from the same scale tissue were measured immediately following thawing and after complete recovery. In injured tissue (30-40% water soaking), plasma membrane ATPase activity was reduced by about 30% and this was paralleled by about 25% higher ion leakage rate. As water soaking disappeared during recovery, the plasma membrane ATPase activity and the ion leakage rate returned to about the same level as the respective controls. Treatment of freeze-thaw injured tissue with vanadate, a specific inhibitor of plasma membrane ATPase, during postthaw prevented the recovery process. These results indicate that recovery of freeze-injured tissue depends on the functional activity of plasma membrane ATPase. PMID:16668063

Distribution of chloramphenicol to tissues, plasma and urine in pigs after oral intake of low doses.

Science.gov (United States)

Aspenström-Fagerlund, Bitte; Nordkvist, Erik; Törnkvist, Anna; Wallgren, Per; Hoogenboom, Ron; Berendsen, Bjorn; Granelli, Kristina

2016-09-01

Toxic effects of chloramphenicol in humans caused the ban for its use in food-producing animals in the EU. A minimum required performance level (MRPL) was specified for chloramphenicol at 0.3 μg kg(-1) for various matrices, including urine. In 2012, residues of chloramphenicol were found in pig urine and muscle without signs of illegal use. Regarding its natural occurrence in straw, it was hypothesised that this might be the source, straw being compulsory for use as bedding material for pigs in Sweden. Therefore, we investigated if low daily doses of chloramphenicol (4, 40 and 400 μg/pig) given orally during 14 days could result in residues in pig tissues and urine. A dose-related increase of residues was found in muscle, plasma, kidney and urine (showing the highest levels), but no chloramphenicol was found in the liver. At the lowest dose, residues were below the MRPL in all tissues except in the urine. However, in the middle dose, residues were above the MRPL in all tissues except muscle, and at the highest dose in all matrices. This study proves that exposure of pigs to chloramphenicol in doses occurring naturally in straw could result in residues above the MRPL in plasma, kidney and especially urine.

Effect of plasma-rich in platelet-derived growth factors on peri-implant bone healing: An experimental study in canines

Science.gov (United States)

Birang, Reza; Torabi, Alireza; Shahabooei, Mohammad; Rismanchian, Mansour

2012-01-01

Background: Tissue engineering principles can be exploited to enhance alveolar and peri-implant bone reconstruction by applying such biological factors as platelet-derived growth factors. The objective of the present study is to investigate the effect of autologous plasma-rich in growth factors (on the healing of peri-implant bone in canine mandible). Materials and Methods: In this prospective experimental animal study, two healthy canines of the Iranian mix breed were selected. Three months after removing their premolar teeth on both sides of the mandible, 12 implants of the Osteo Implant Corporationsystem, 5 mm in diameter and 10 mm in length, were selected to be implanted. Plasma rich in growth factors (PRGF) were applied on six implants while the other six were used as plain implants without the plasma. The implants were installed in osteotomy sites on both sides of the mandible to be removed after 4 weeks with the surrounding bones using a trephine bur. Mesio-distal sections and implant blocks, 50 μ in diameter containing the peri-implant bone, were prepared By basic fuchin toluidine-bluefor histological and histomorphometric evaluation by optical microscope. The data were analyzed using Mann-Whitney Test (PPRGF and control groups had no statistically significant differences (P=0.261, P=0.2) although the parameters showed higher measured values in the PRGF group. However, compared to the control, application of PRGF had significantly increased bone-to-implant contact (P=0.028) Conclusion: Based on the results, it may be concluded that application of PRGF on the surface of implant may enhance bone-to-implant contact. PMID:22363370

Human tissue factor: cDNA sequence and chromosome localization of the gene

International Nuclear Information System (INIS)

Scarpati, E.M.; Wen, D.; Broze, G.J. Jr.; Miletich, J.P.; Flandermeyer, R.R.; Siegel, N.R.; Sadler, J.E.

1987-01-01

A human placenta cDNA library in λgt11 was screened for the expression of tissue factor antigens with rabbit polyclonal anti-human tissue factor immunoglobulin G. Among 4 million recombinant clones screened, one positive, λHTF8, expressed a protein that shared epitopes with authentic human brain tissue factor. The 1.1-kilobase cDNA insert of λHTF8 encoded a peptide that contained the amino-terminal protein sequence of human brain tissue factor. Northern blotting identified a major mRNA species of 2.2 kilobases and a minor species of ∼ 3.2 kilobases in poly(A) + RNA of placenta. Only 2.2-kilobase mRNA was detected in human brain and in the human monocytic U937 cell line. In U937 cells, the quantity of tissue factor mRNA was increased several fold by exposure of the cells to phorbol 12-myristate 13-acetate. Additional cDNA clones were selected by hybridization with the cDNA insert of λHTF8. These overlapping isolates span 2177 base pairs of the tissue factor cDNA sequence that includes a 5'-noncoding region of 75 base pairs, an open reading frame of 885 base pairs, a stop codon, a 3'-noncoding region of 1141 base pairs, and a poly(a) tail. The open reading frame encodes a 33-kilodalton protein of 295 amino acids. The predicted sequence includes a signal peptide of 32 or 34 amino acids, a probable extracellular factor VII binding domain of 217 or 219 amino acids, a transmembrane segment of 23 acids, and a cytoplasmic tail of 21 amino acids. There are three potential glycosylation sites with the sequence Asn-X-Thr/Ser. The 3'-noncoding region contains an inverted Alu family repetitive sequence. The tissue factor gene was localized to chromosome 1 by hybridization of the cDNA insert of λHTF8 to flow-sorted human chromosomes

Effects of neutron-gamma or gamma irradiations on plasma clotting factors. Effect of a treatment by substituted factors

International Nuclear Information System (INIS)

Mestries, J.C.; Martin, S.; Janodet, D.; Herodin, F.; Gourmelon, P.; Fatome, M.

1991-01-01

Neutron-gamma irradiation of the baboon at lethal dose altered the plasma clotting factors and induced a fibrinoformation alteration which occurred shortly before death. These disturbances, which were not found after gamma irradiation, could explain the importance of the haemorrhagic syndrome. Treatment by P.P.S.B. (factors II, VII, X and IX) counteracted the alterations of the plasma clotting factors, but had no influence on the lethality nor on the fibrinoformation alteration which seems to be an important cause of death [fr

Plasma thromboplastin antecedent (PTA, factor XI): a specific and sensitive radioimmunoassay

International Nuclear Information System (INIS)

Saito, H.; Goldsmith, G.H. Jr.

1977-01-01

A specific, sensitive, and reproducible radioimmunoassay for human plasma thromboplastin antecedent (PTA, factor XI) has been developed with purified PTA and monospecific rabbit antiserum. Precise measurements of PTA antigen were possible for concentrations as low as 0.3% of that in normal pooled plasma. Normal plasma contained approximately 6 μg PTA/ml. A good correlation (correlation coefficient 0.68) existed between the PTA procoagulant assays and radioimmunoassays among 50 normal adults (25 males and 25 females). PTA antigen was markedly reduced in plasma of 13 patients with congenital homozygous PTA deficiency (range <0.003-0.128 U/ml) and 9 patients with hepatic cirrhosis (0.35 +- 0.17 U/ml), but was normal in those of 9 patients under treatment with warfarin, 8 patients with disseminated intravascular coagulation and 16 patients with other congenital clotting factor abnormalities, including prekallikrein deficiency (Fletcher trait) and high molecular weight kininogen deficiency

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

Science.gov (United States)

Knapp, Paweł; Bodnar, Lubomir; Błachnio-Zabielska, Agnieszka; Świderska, Magdalena; Chabowski, Adrian

2017-10-01

The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100μl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100μl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100μl (AUC:0.77, P=0.0136) was noticed. Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The Effect of Plasma Exposure on Tail Regeneration of Tadpoles Xenopus Laevis

Science.gov (United States)

June, Joyce; Rivie, Adonis; Ezuduemoih, Raphael; Menon, Jaishri; Martus, Kevin

2014-03-01

Wound healing requires a balanced combination of nutrients and growth factors for healing and tissue regeneration. The effect of plasma exposure on tail regeneration of tadpoles, Xenopus laevis is investigated. The exposure of the wound to the helium plasma immediately followed the amputation of 40% of the tail. Amputation of the tail initiates regeneration of spinal cord, muscle, notochord, skin and connective tissues. By 24 h, the wound was covered by wound epithelium and blastema was formed by day 5. There was increased angiogenesis in plasma exposed tail regenerate compared to the control following 5 d post amputation. Observed was an increase in NO production in the regenerate of plasma exposed tadpoles was derived from increased activity of nNOS and iNOS. Western blot analysis for vascular endothelial growth factor showed stronger bands for the protein in amputated tadpoles of both the groups. Analysis of the composition and characteristics of the plasma using optical emission spectroscopy indicates excited state species consisting of N2, N2+,and OH is present in the plasma. This study was supported, in part, by the NSF Grant 1040108.

Relationship between expression of leptin receptors mRNA in breast tissue, plasma leptin level in breast cancer patients with obesity and clinical pathologic data

International Nuclear Information System (INIS)

Li Chunrui; Liu Wenli; Sun Hanying; Zhou Jianfeng

2007-01-01

In order to investigate the expression of leptin receptors mRNA in breast tissue and plasma leptin levels in breast cancer patients with obesity and their relationship with clinical pathologic data, 124 subjects who were either obesity or had suffered from breast benign disease with obesity, or breast cancer with obesity were entered into this study. The levels of plasma leptin in all subjects were determined and leptin receptors mRNA expression levels were measured by RT-PCR in breast tissue of breast cancer patients with obesity and breast benign disease with obesity. The results showed that plasma leptin levels in breast cancer patients with obesity were significantly higher than those in breast benign disease with obesity and obesity patients alone (P<0.05). The expression of the leptin receptor long form [-Lep-R(L)-] mRNA and the leptin receptor short form [-Lep-R(S)-] mRNA in breast tissue of breast cancer patients with obesity were significantly higher than that in breast tissue of breast benign disease patients with obesity (P<0.05). The plasma leptin level had remarkable positive correlation with the expressions of the Lep-R(L) mRNA and the Lep-R(S) mRNA. The plasma leptin level and leptin receptors mRNA expression levels in patients were not correlated with the axillary node metastasis, menopause, the TNM stage or pathological type. Therefore, leptin may have a promoting effect on the carcinogenesis of breast cancer. (authors)

Freeze-dried plasma enhances clot formation and inhibits fibrinolysis in the presence of tissue plasminogen activator similar to pooled liquid plasma.

Science.gov (United States)

Huebner, Benjamin R; Moore, Ernest E; Moore, Hunter B; Sauaia, Angela; Stettler, Gregory; Dzieciatkowska, Monika; Hansen, Kirk; Banerjee, Anirban; Silliman, Christopher C

2017-08-01

Systemic hyperfibrinolysis is an integral part of trauma-induced coagulopathy associated with uncontrolled bleeding. Recent data suggest that plasma-first resuscitation attenuates hyperfibrinolysis; however, the availability, transport, storage, and administration of plasma in austere environments remain challenging and have limited its use. Freeze-dried plasma (FDP) is a potential alternative due to ease of storage, longer shelf life, and efficient reconstitution. FDP potentially enhances clot formation and resists breakdown better than normal saline (NS) and albumin and similar to liquid plasma. Healthy volunteers underwent citrated blood draw followed by 50% dilution with NS, albumin, pooled plasma (PP), or pooled freeze-dried plasma (pFDP). Citrated native and tissue plasminogen activator (t-PA)-challenge (75 ng/mL) thrombelastography were done. Proteins in PP, pFDP, and albumin were analyzed by mass spectroscopy. pFDP and PP had superior clot-formation rates (angle) and clot strength (maximum amplitude) compared with NS and albumin in t-PA-challenge thrombelastographies (angle: pFDP, 67.9 degrees; PP, 67.8 degrees; NS, 40.6 degrees; albumin, 35.8 degrees; maximum amplitude: pFDP, 62.4 mm; PP, 63.5 mm; NS, 44.8 mm; albumin, 41.1 mm). NS and albumin dilution increased susceptibility to t-PA-induced hyperfibrinolysis compared with pFDP and PP (NS, 62.4%; albumin, 62.6%; PP, 8.5%; pFDP, 6.7%). pFDP was similar to PP in the attenuation of t-PA-induced fibrinolysis. Most proteins (97%) were conserved during the freeze-dry process, with higher levels in 12% of pFDP proteins compared with PP. pFDP enhances clot formation and attenuates hyperfibrinolysis better than NS and albumin and is a potential alternative to plasma resuscitation in the treatment of hemorrhagic shock. © 2017 AABB.

NS3 protease resistance-associated substitutions in liver tissue and plasma samples from patients infected by hepatitis C virus genotype 1A or 1B.

Science.gov (United States)

Morsica, Giulia; Andolina, Andrea; Merli, Marco; Messina, Emanuela; Hasson, Hamid; Lazzarin, Adriano; Uberti-Foppa, Caterina; Bagaglio, Sabrina

2017-08-01

The presence of naturally occurring resistance-associated substitutions (RASs) in the HCV-protease domain has been poorly investigated in the liver, the main site of HCV replication. We evaluated the natural resistance of the virus to NS3 protease inhibitors in liver tissue and plasma samples taken from HCV-infected patients. RASs were investigated by means of viral population sequencing in liver tissue samples from 18 HCV-infected patients harbouring genotype 1a or genotype 1b; plasma samples from 12 of these patients were also available for virological investigation. A discordant genotype was found in two of the 12 patients (16.6%) who provided samples from both compartments. Sequence analysis of the NS3 protease domain showed the presence of RASs in four of the 18 liver tissue samples (22.2%), two of which showed cross-resistance to protease inhibitors in clinical use or phase 2-3 trials. The analysis of the 12 paired tissues and plasma samples excluded the presence of RASs in the plasma compartment. The dominance of discordant genotypes in the paired liver and plasma samples of some HCV-infected patients suggests mixed infection possibly leading to the selective advantage of different genotype in the two compartments. The presence of RASs at intra-hepatic level is not uncommon and may lead to the early emergence of cross-resistant strains.

Use of fibroblast growth factor 2 for expansion of chondrocytes and tissue engineering

Science.gov (United States)

Vunjak-Novakovic, Gordana (Inventor); Martin, Ivan (Inventor); Freed, Lisa E. (Inventor); Langer, Robert (Inventor)

2003-01-01

The present invention provides an improved method for expanding cells for use in tissue engineering. In particular the method provides specific biochemical factors to supplement cell culture medium during the expansion process in order to reproduce events occurring during embryonic development with the goal of regenerating tissue equivalents that resemble natural tissues both structurally and functionally. These specific biochemical factors improve proliferation of the cells and are capable of de-differentiation mature cells isolated from tissue so that the differentiation potential of the cells is preserved. The bioactive molecules also maintain the responsiveness of the cells to other bioactive molecules. Specifically, the invention provides methods for expanding chondrocytes in the presence of fibroblast growth factor 2 for use in regeneration of cartilage tissue.

Determination of lead in bone tissues by axially viewed inductively coupled plasma multichannel-based emission spectrometry.

Science.gov (United States)

Grotti, Marco; Abelmoschi, Maria Luisa; Dalla Riva, Simona; Soggia, Francesco; Frache, Roberto

2005-04-01

A new procedure for determining low levels of lead in bone tissues has been developed. After wet acid digestion in a pressurized microwave-heated system, the solution was analyzed by inductively coupled plasma multichannel-based emission spectrometry. Internal standardization using the Co 228.615 nm reference line was chosen as the optimal method to compensate for the matrix effects from the presence of calcium and nitric acid at high concentration levels. The detection limit of the procedure was 0.11 microg Pb g(-1) dry mass. Instrumental precision at the analytical concentration of approximately 10 microg l(-1) ranged from 6.1 to 9.4%. Precision of the sample preparation step was 5.4%. The concentration of lead in SRM 1486 (1.32+/-0.04 microg g(-1)) found using the new procedure was in excellent agreement with the certified level (1.335+/-0.014 microg g(-1)). Finally, the method was applied to determine the lead in various fish bone tissues, and the analytical results were found to be in good agreement with those obtained through differential pulse anodic stripping voltammetry. The method is therefore suitable for the reliable determination of lead at concentration levels of below 1 microg g(-1) in bone samples. Moreover, the multi-element capability of the technique allows us to simultaneously determine other major or trace elements in order to investigate inter-element correlation and to compute enrichment factors, making the proposed procedure particularly useful for investigating lead occurrence and pathways in fish bone tissues in order to find suitable biomarkers for the Antarctic marine environment.

Biochemical characterization of the plasma membrane H+ - ATPase from red beet (Beta vulgaris) hypocotyl tissue

International Nuclear Information System (INIS)

Oleski, N.A.

1986-01-01

Several biochemical techniques including selective solubilization followed by gel filtration or various types of affinity chromatography, and antibody production were employed in an attempt to purify the plasma membrane H + - ATPase from red beet hypocotyl tissue. While the enzyme could not be purified using any of these methods, it was possible to successfully conduct a more detailed biochemical analysis of the H + - ATPase. The molecular weight and isoelectric point of the enzyme were determined using N,N'dicyclohexylcarbodiimide (DCCD) and a H + - ATPase antibody. When plasma membrane vesicles were incubated with 20 μM [ 14 C]-DCCD at 0 C, a single 97,000 dalton protein was apparent on a fluorograph. A close correlation between [ 14 C]-DCCD labelling of the 97,000 dalton protein and the extent of ATPase inhibition over a range of DCCD concentrations suggests that this 97,000 dalton protein is a component of the plasma membrane H + - ATPase. An antibody raised against the plasma membrane H + - ATPase of Neurospora crassa cross-reacted with the 97,000 dalton DCCD-binding protein, further supporting the identity of this protein. Immunoblots of two dimensional gels of red beet plasma membrane vesicles indicated the isoelectric point of the enzyme to be pH 6.5

Oral Ultramicronized Palmitoylethanolamide: Plasma and Tissue Levels and Spinal Anti-hyperalgesic Effect

Directory of Open Access Journals (Sweden)

Stefania Petrosino

2018-03-01

Full Text Available Palmitoylethanolamide (PEA is a pleiotropic lipid mediator with established anti-inflammatory and anti-hyperalgesic activity. Ultramicronized PEA (PEA-um has superior oral efficacy compared to naïve (non-micronized PEA. The aim of the present study was two-fold: (1 to evaluate whether oral PEA-um has greater absorbability compared to naïve PEA, and its ability to reach peripheral and central tissues under healthy and local inflammatory conditions (carrageenan paw edema; (2 to better characterize the molecular pathways involved in PEA-um action, particularly at the spinal level. Rats were dosed with 30 mg/kg of [13C]4-PEA-um or naïve [13C]4-PEA by oral gavage, and [13C]4-PEA levels quantified, as a function of time, by liquid chromatography/atmospheric pressure chemical ionization/mass spectrometry. Overall plasma levels were higher in both healthy and carrageenan-injected rats administered [13C]4-PEA-um as compared to those receiving naïve [13C]4-PEA, indicating the greater absorbability of PEA-um. Furthermore, carrageenan injection markedly favored an increase in levels of [13C]4-PEA in plasma, paw and spinal cord. Oral treatment of carrageenan-injected rats with PEA-um (10 mg/kg confirmed beneficial peripheral effects on paw inflammation, thermal hyperalgesia and tissue damage. Notably, PEA-um down-regulated distinct spinal inflammatory and oxidative pathways. These last findings instruct on spinal mechanisms involved in the anti-hyperalgesic effect of PEA-um in inflammatory pain.

In vivo bioimaging with tissue-specific transcription factor activated luciferase reporters.

OpenAIRE

Buckley, SM; Delhove, JM; Perocheau, DP; Karda, R; Rahim, AA; Howe, SJ; Ward, NJ; Birrell, MA; Belvisi, MG; Arbuthnot, P; Johnson, MR; Waddington, SN; McKay, TR

2015-01-01

The application of transcription factor activated luciferase reporter cassettes in vitro is widespread but potential for in vivo application has not yet been realized. Bioluminescence imaging enables non-invasive tracking of gene expression in transfected tissues of living rodents. However the mature immune response limits luciferase expression when delivered in adulthood. We present a novel approach of tissue-targeted delivery of transcription factor activated luciferase reporter lentiviruse...

Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin.

Science.gov (United States)

Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F

1999-04-01

Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

Computer modeling the boron compound factor in normal brain tissue

International Nuclear Information System (INIS)

Gavin, P.R.; Huiskamp, R.; Wheeler, F.J.; Griebenow, M.L.

1993-01-01

The macroscopic distribution of borocaptate sodium (Na 2 B 12 H 11 SH or BSH) in normal tissues has been determined and can be accurately predicted from the blood concentration. The compound para-borono-phenylalanine (p-BPA) has also been studied in dogs and normal tissue distribution has been determined. The total physical dose required to reach a biological isoeffect appears to increase directly as the proportion of boron capture dose increases. This effect, together with knowledge of the macrodistribution, led to estimates of the influence of the microdistribution of the BSH compound. This paper reports a computer model that was used to predict the compound factor for BSH and p-BPA and, hence, the equivalent radiation in normal tissues. The compound factor would need to be calculated for other compounds with different distributions. This information is needed to design appropriate normal tissue tolerance studies for different organ systems and/or different boron compounds

Increased and correlated expression of connective tissue growth factor and transforming growth factor beta 1 in surgically removed periodontal tissues with chronic periodontitis.

Science.gov (United States)

Mize, T W; Sundararaj, K P; Leite, R S; Huang, Y

2015-06-01

Both gingival tissue destruction and regeneration are associated with chronic periodontitis, although the former overwhelms the latter. Studies have shown that transforming growth factor beta 1 (TGF-β1), a growth factor largely involved in tissue regeneration and remodeling, is upregulated in chronic periodontitis. However, the gingival expression of connective tissue growth factor (CTGF or CCN2), a TGF-β1-upregulated gene, in patients with periodontitis remains undetermined. Although both CTGF/CCN2 and TGF-b1 increase the production of extracellular matrix, they have many different biological functions. Therefore, it is important to delineate the impact of periodontitis on gingival CTGF/CCN2 expression. Periodontal tissue specimens were collected from seven individuals without periodontitis (group 1) and from 14 with periodontitis (group 2). The expression of CTGF and TGFβ1 mRNAs were quantified using real-time PCR. Analysis using the nonparametric Mann-Whitney U-test showed that the levels of expression of both CTGF/CCN2 and TGFβ1 mRNAs were significantly increased in individuals with periodontitis compared with individuals without periodontitis. Furthermore, analysis using a nonparametric correlation (Spearman r) test showed a positive correlation between TGFβ1 and CTGF/CCN2 mRNAs. The gingival expression levels of CTGF/CCN2 and TGFβ1 mRNAs in individuals with periodontitis are upregulated and correlated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Partitioning the variability of fasting plasma glucose levels in pedigrees. Genetic and environmental factors.

Science.gov (United States)

Boehnke, M; Moll, P P; Kottke, B A; Weidman, W H

1987-04-01

Fasting plasma glucose measurements made in 1972-1977 on normoglycemic individuals in three-generation Caucasian pedigrees from Rochester, Minnesota were analyzed. The authors determined the contributions of polygenic loci and environmental factors to fasting plasma glucose variability in these pedigrees. To that end, fasting plasma glucose measurements were normalized by an inverse normal scores transformation and then regressed separately for males and females on measured concomitants including age, body mass index (weight/height2), season of measurement, sex hormone use, and diuretic use. The authors found that 27.7% of the variability in normalized fasting plasma glucose in these pedigrees is explained by these measured concomitants. Subsequent variance components analysis suggested that unmeasured polygenic loci and unmeasured shared environmental factors together account for at least an additional 36.7% of the variability in normalized fasting plasma glucose, with genes alone accounting for at least 27.3%. These results are consistent with the known familiality of diabetes, for which fasting plasma glucose level is an important predictor. Further, these familial factors provide an explanation for at least half the variability in normalized fasting plasma glucose which remains after regression on known concomitants.

Ionization-potential depression and dynamical structure factor in dense plasmas

Science.gov (United States)

Lin, Chengliang; Röpke, Gerd; Kraeft, Wolf-Dietrich; Reinholz, Heidi

2017-07-01

The properties of a bound electron system immersed in a plasma environment are strongly modified by the surrounding plasma. The modification of an essential quantity, the ionization energy, is described by the electronic and ionic self-energies, including dynamical screening within the framework of the quantum statistical theory. Introducing the ionic dynamical structure factor as the indicator for the ionic microfield, we demonstrate that ionic correlations and fluctuations play a critical role in determining the ionization potential depression. This is, in particular, true for mixtures of different ions with large mass and charge asymmetry. The ionization potential depression is calculated for dense aluminum plasmas as well as for a CH plasma and compared to the experimental data and more phenomenological approaches used so far.

Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors.

Science.gov (United States)

Amable, Paola Romina; Carias, Rosana Bizon Vieira; Teixeira, Marcus Vinicius Telles; da Cruz Pacheco, Italo; Corrêa do Amaral, Ronaldo José Farias; Granjeiro, José Mauro; Borojevic, Radovan

2013-06-07

Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed. PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure. Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 10(6) to 1.9 × 10(6) platelets/μl). Platelets were highly purified, because only platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-β3 and IFNγ were not detected in any studied fraction. Clots obtained after platelet coagulation retained a high concentration of several growth factors, including platelet-derived growth factor and TGF. Our study resulted in a consistent PRP preparation method that yielded a cytokine and growth factor pool

Uptake and Tissue Distribution of Pharmaceuticals and Personal Care Products in Wild Fish from Treated-Wastewater-Impacted Streams.

Science.gov (United States)

Tanoue, Rumi; Nomiyama, Kei; Nakamura, Haruna; Kim, Joon-Woo; Isobe, Tomohiko; Shinohara, Ryota; Kunisue, Tatsuya; Tanabe, Shinsuke

2015-10-06

A fish plasma model (FPM) has been proposed as a screening technique to prioritize potential hazardous pharmaceuticals to wild fish. However, this approach does not account for inter- or intraspecies variability of pharmacokinetic and pharmacodynamic parameters. The present study elucidated the uptake potency (from ambient water), tissue distribution, and biological risk of 20 pharmaceutical and personal care product (PPCP) residues in wild cyprinoid fish inhabiting treated-wastewater-impacted streams. In order to clarify the uncertainty of the FPM for PPCPs, we compared the plasma bioaccumulation factor in the field (BAFplasma = measured fish plasma/ambient water concentration ratio) with the predicted plasma bioconcentration factor (BCFplasma = fish plasma predicted by use of theoretical partition coefficients/ambient water concentration ratio) in the actual environment. As a result, the measured maximum BAFplasma of inflammatory agents was up to 17 times higher than theoretical BCFplasma values, leading to possible underestimation of toxicological risk on wild fish. When the tissue-blood partition coefficients (tissue/blood concentration ratios) of PPCPs were estimated, higher transportability into tissues, especially the brain, was found for psychotropic agents, but brain/plasma ratios widely varied among individual fish (up to 28-fold). In the present study, we provide a valuable data set on the intraspecies variability of PPCP pharmacokinetics, and our results emphasize the importance of determining PPCP concentrations in possible target organs as well as in the blood to assess the risk of PPCPs on wild fish.

Additive Effect of Plasma Rich in Growth Factors With Guided Tissue Regeneration in Treatment of Intrabony Defects in Patients With Chronic Periodontitis: A Split-Mouth Randomized Controlled Clinical Trial.

Science.gov (United States)

Ravi, Sheethalan; Malaiappan, Sankari; Varghese, Sheeja; Jayakumar, Nadathur D; Prakasam, Gopinath

2017-09-01

Periodontal regeneration can be defined as complete restoration of lost periodontal tissues to their original architecture and function. A variety of treatment modalities have been proposed to achieve it. Plasma rich in growth factors (PRGF) is a concentrated suspension of growth factors that promotes restoration of lost periodontal tissues. The objective of the present study is to assess the effect of PRGF associated with guided tissue regeneration (GTR) versus GTR only in the treatment of intrabony defects (IBDs) in patients with chronic periodontitis (CP). Patients with CP (n = 14) with 42 contralateral 2- and 3-walled defects were randomly assigned to test (PRGF+GTR) and control (GTR alone) treatment groups. Clinical and radiographic assessments performed at baseline and after 6 months were: 1) gingival index (GI), 2) probing depth (PD), 3) clinical attachment level (CAL), 4) radiologic defect depth, and 5) bone fill. Comparison of parameters measured at baseline and after 6 months showed mean PD reduction of 3.37 ± 1.62 mm in the control group (P <0.001) and 4.13 ± 1.59 mm in the test group (P <0.001). There was a significant difference in mean change in CAL (P <0.001) in the control group (5.42 ± 1.99) and the test group (5.99 ± 1.77). Mean change in GI was 1.89 ± 0.32 and 1.68 ± 0.58 in the control group and test group, respectively, and the difference was statistically significant (P <0.001). When compared between groups, clinical parameters did not show any statistically significant variations. Mean radiographic bone fill was 1.06 ± 0.81 and 1.0 ± 0.97 in the control group and test group, respectively. However, the difference was not statistically significant. PRGF with GTR, as well as GTR alone, was effective in improving clinical and radiographic parameters of patients with CP at the 6-month follow-up. There was no additive effect of PRGF when used along with GTR in the treatment of IBDs in patients with CP in terms of both clinical and

Plasma levels of hypoxia-regulated factors in patients with age-related macular degeneration.

Science.gov (United States)

Ioanna, Zygoula; Christian, Schori; Christian, Grimm; Daniel, Barthelmes

2018-02-01

Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA). The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients. nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.

Assay of Plasma Membrane H+-ATPase in Plant Tissues under Abiotic Stresses.

Science.gov (United States)

Janicka, Małgorzata; Wdowikowska, Anna; Kłobus, Grażyna

2018-01-01

Plasma membrane (PM) H + -ATPase, which generates the proton gradient across the outer membrane of plant cells, plays a fundamental role in the regulation of many physiological processes fundamental for growth and development of plants. It is involved in the uptake of nutrients from external solutions, their loading into phloem and long-distance transport, stomata aperture and gas exchange, pH homeostasis in cytosol, cell wall loosening, and cell expansion. The crucial role of the enzyme in resistance of plants to abiotic and biotic stress factors has also been well documented. Such great diversity of physiological functions linked to the activity of one enzyme requires a suitable and complex regulation of H + -ATPase. This regulation comprises the transcriptional as well as post-transcriptional levels. Herein, we describe the techniques that can be useful for the analysis of the plasma membrane proton pump modifications at genetic and protein levels under environmental factors.

Quantification of Epstein-Barr virus DNA load, interleukin-6, interleukin-10, transforming growth factor-β1 and stem cell factor in plasma of patients with nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Tan, Eng-lai; Selvaratnam, G; Kananathan, R; Sam, Choon-kook

2006-01-01

Nasopharyngeal carcinoma (NPC) is a common epithelial neoplasm among the Chinese populations in Southern China and South East Asia. Epstein-Barr virus (EBV) is known to be an important etiologic agent of NPC and the viral gene products are frequently detected in NPC tissues along with elevated antibody titres to the viral proteins (VCA and EA) in a majority of patients. Elevated plasma EBV DNA load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the levels of certain interleukins and growth factors have also been implicated in NPC. The objectives of the present study are, 1) to investigate the correlations between plasma EBV DNA load and the levels of interleukin (IL)-6, IL-10, TGF-β1 and SCF (steel factor) and 2) to relate these parameters to the stages of NPC and the effect of treatment. A total of 78 untreated NPC patients were enrolled in this study. Of these, 51 were followed-up after treatment. The remaining patients had irregular or were lost to follow-up. Plasma EBV DNA was quantified using real-time quantitative PCR. The levels of plasma interleukins and growth factors were quantified using ELISA. A significant decrease in EBV DNA load was detected in plasma of untreated NPC patients (1669 ± 637 copies/mL; n = 51) following treatment (57 ± 37 copies/mL, p < 0.05); n = 51). Plasma EBV DNA load was shown to be a good prognosticator for disease progression and clinical outcome in five of the follow-up patients. A significant difference in IL-6 levels was noted between the untreated patients (164 ± 37 pg/mL; n = 51) and following treatment (58 ± 16 pg/mL, p < 0.05; n = 51). Positive correlations between EBV DNA load and IL-10 (r(49) = 0.535, p < 0.01), between IL6 and IL-10 (r(49) = 0.474, p < 0.01) and between TGF and SCF (r(49) = 0.464, p < 0.01) were observed in patients following treatment. None of the parameters tested including Ig

Indian values of tissue weighting factors for internal dosimetry

International Nuclear Information System (INIS)

Mehta, S.K.

1995-01-01

In the present work the induced cancer component of detriment by the relative risk (RR) as well as US National Institute of Health (NIH) models using Indian organ based baseline cancer data and the all-causes mortality of the Indian population has been estimated. The Indian values of tissue weighting factors (W T ) have been worked out by the ICRP-60 methodology. The Indian values of detriment from the exposure of principal organs stomach, lung, colon and bone marrow are factors of 1.5 to 2.5 lower than the corresponding ICRP values. The Indian values of W T differ significantly from the ICRP five population average values. A tissue weighting factor of 0.08 for breast, colon, lung and stomach for the Indian population is more appropriate than the ICRP assigned factors of 0.05, 0.12, 0.12 and 0.12 respectively for these organs. For gonads, the appropriate Indian factor is 0.29 instead of the ICRP value of 0.20. The use of appropriate Indian values of W T is advocated for the Indian population in special investigation cases requiring regulatory intervention. (author). 11 refs., 11 figs., 4 tabs

Factors affecting the tissues composition of pork belly.

Science.gov (United States)

Duziński, K; Knecht, D; Lisiak, D; Janiszewski, P

2015-11-01

Bellies derived from the commercial population of pig carcasses are diverse in terms of tissue composition. Knowledge of the factors influencing it and the expected results, permits quick and easy evaluation of raw material. The study was designed to determine the factors affecting the tissues composition of pork bellies and to estimate their lean meat content. The research population (n=140 pig carcasses) was divided into groups according to sex (gilts, barrows), half-carcass mass (meat content class: S (⩾60%), E (55% to 60%), U (50% to 55%), R (meat content affected the growth of the fat and skin mass in a linear way. No differences were observed between class S and E in terms of belly muscle mass. A 0.37% higher share of belly in the half-carcass was found for barrows (Pmeat content in bellies, suggesting they may be used directly in the production line.

Fabrication and characterization of platelet-rich plasma scaffolds for tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Sadeghi-Ataabadi, Mahmoud [Tissue engineering Lab, Anatomy department, Medical School, Shiraz University of Medical Sciences (Iran, Islamic Republic of); Mostafavi-pour, Zohreh [Recombinant protein lab, Department of Biochemistry, Medical School, Shiraz University of Medical Sciences (Iran, Islamic Republic of); Vojdani, Zahra; Sani, Mahsa [Tissue engineering Lab, Anatomy department, Medical School, Shiraz University of Medical Sciences (Iran, Islamic Republic of); Latifi, Mona [Tissue Engineering Department, National Institute of Genetic Engineering and Biotechnoloy (Iran, Islamic Republic of); Tissue engineering Lab, Anatomy department, Medical School, Shiraz University of Medical Sciences (Iran, Islamic Republic of); Talaei-Khozani, Tahereh, E-mail: talaeit@sums.ac.ir [Tissue engineering Lab, Anatomy department, Medical School, Shiraz University of Medical Sciences (Iran, Islamic Republic of)

2017-02-01

Platelet-Rich Plasma (PRP), as a rich source of growth factor, can form a fibrin gel that recapitulates the extracellular matrix of the tissues. The aim of this study was to evaluate the effects of different concentrations of CaCl{sub 2} on the PRP scaffold structure which in turn could change the cell's behavior. PRP was mixed with 2.5, 5 and 10% (w/v) CaCl{sub 2}. Then, the tensile strength, biodegradability and water content of the scaffolds were evaluated. We also performed immunostaining for assessment of the actin stress fiber orientation and SEM for detecting the cell phenotype and physical properties of the fibers. Cell viability, attachment and migration were also evaluated. The highest cell attachment and short term proliferation rate was observed on the scaffolds with 2.5% CaCl{sub 2}. The cells cultured on the scaffold with higher CaCl{sub 2} concentration had fusiform phenotype with few cell processes and parallel arrangement of stress fibers while those cultured on the other scaffolds were fibroblast-like with more processes and net-like stress fibers. The scaffolds with 10% CaCl{sub 2} demonstrated the highest osmolarity (358.75 ± 4.99 mOsmole), fiber thickness (302.1 ± 54.3 nm), pore size (332.1 ± 118.9 nm{sup 2}) and the longest clotting time (12.2 ± 0.776 min) compared with the other scaffolds. Water content, branching angle, porosity, orientation and tensile strength did not change by gelation with different CaCl{sub 2} concentrations. In conclusion, the cell shape, viability and proliferation were modified by culturing on the PRP scaffolds prepared with various concentrations of CaCl{sub 2}, and as a result, the scaffolds showed different physical and biological properties - Highlights: Platelet rich plasma (PRP) can be considered as an autologous source for tissue engineering applications. Cell shape, function and differentiation fate are influenced by the mechanical and physical features of the scaffolds. Different CaCl2

Fabrication and characterization of platelet-rich plasma scaffolds for tissue engineering applications

International Nuclear Information System (INIS)

Sadeghi-Ataabadi, Mahmoud; Mostafavi-pour, Zohreh; Vojdani, Zahra; Sani, Mahsa; Latifi, Mona; Talaei-Khozani, Tahereh

2017-01-01

Platelet-Rich Plasma (PRP), as a rich source of growth factor, can form a fibrin gel that recapitulates the extracellular matrix of the tissues. The aim of this study was to evaluate the effects of different concentrations of CaCl 2 on the PRP scaffold structure which in turn could change the cell's behavior. PRP was mixed with 2.5, 5 and 10% (w/v) CaCl 2 . Then, the tensile strength, biodegradability and water content of the scaffolds were evaluated. We also performed immunostaining for assessment of the actin stress fiber orientation and SEM for detecting the cell phenotype and physical properties of the fibers. Cell viability, attachment and migration were also evaluated. The highest cell attachment and short term proliferation rate was observed on the scaffolds with 2.5% CaCl 2 . The cells cultured on the scaffold with higher CaCl 2 concentration had fusiform phenotype with few cell processes and parallel arrangement of stress fibers while those cultured on the other scaffolds were fibroblast-like with more processes and net-like stress fibers. The scaffolds with 10% CaCl 2 demonstrated the highest osmolarity (358.75 ± 4.99 mOsmole), fiber thickness (302.1 ± 54.3 nm), pore size (332.1 ± 118.9 nm 2 ) and the longest clotting time (12.2 ± 0.776 min) compared with the other scaffolds. Water content, branching angle, porosity, orientation and tensile strength did not change by gelation with different CaCl 2 concentrations. In conclusion, the cell shape, viability and proliferation were modified by culturing on the PRP scaffolds prepared with various concentrations of CaCl 2 , and as a result, the scaffolds showed different physical and biological properties - Highlights: Platelet rich plasma (PRP) can be considered as an autologous source for tissue engineering applications. Cell shape, function and differentiation fate are influenced by the mechanical and physical features of the scaffolds. Different CaCl2 concentrations modified some features of the PRP

Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3.

Science.gov (United States)

Kapacee, Zoher; Yeung, Ching-Yan Chloé; Lu, Yinhui; Crabtree, David; Holmes, David F; Kadler, Karl E

2010-10-01

Tendon-like tissue generated from stem cells in vitro has the potential to replace tendons and ligaments lost through injury and disease. However, thus far, no information has been available on the mechanism of tendon formation in vitro and how to accelerate the process. We show here that human mesenchymal stem cells (MSCs) and bone marrow-derived mononuclear cells (BM-MNCs) can generate tendon-like tissue in 7days mediated by transforming growth factor (TGF) β3. MSCs cultured in fixed-length fibrin gels spontaneously synthesized narrow-diameter collagen fibrils and exhibited fibripositors (actin-rich, collagen fibril-containing plasma membrane protrusions) identical to those that occur in embryonic tendon. In contrast, BM-MNCs did not synthesize tendon-like tissue under these conditions. We performed real-time PCR analysis of MSCs and BM-MNCs. MSCs upregulated genes encoding type I collagen, TGFβ3, and Smad2 at the time of maximum contraction of the tendon-like tissue (7days). Western blot analysis showed phosphorylation of Smad2 at maximum contraction. The TGFβ inhibitor SB-431542, blocked the phosphorylation of Smad2 and stopped the formation of tendon-like tissue. Quantitative PCR showed that BM-MNCs expressed very low levels of TGFβ3 compared to MSCs. Therefore we added exogenous TGFβ3 protein to BM-MNCs in fibrin gels, which resulted in phosphorylation of Smad2, synthesis of collagen fibrils, the appearance of fibripositors at the plasma membrane, and the formation of tendon-like tissue. In conclusion, MSCs that self-generate TGFβ signaling or the addition of TGFβ3 protein to BM-MNCs in fixed-length fibrin gels spontaneously make embryonic tendon-like tissue in vitro within 7days. Copyright © 2010 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Immunolocalization of transforming growth factor alpha in normal human tissues

DEFF Research Database (Denmark)

Christensen, M E; Poulsen, Steen Seier

1996-01-01

anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

Science.gov (United States)

Chen, Guobao; Lv, Yonggang

2015-01-01

Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

High-throughput proteomic characterization of plasma rich in growth factors (PRGF-Endoret)-derived fibrin clot interactome.

Science.gov (United States)

Anitua, Eduardo; Prado, Roberto; Azkargorta, Mikel; Rodriguez-Suárez, Eva; Iloro, Ibon; Casado-Vela, Juan; Elortza, Felix; Orive, Gorka

2015-11-01

Plasma rich in growth factors (PRGF®-Endoret®) is an autologous technology that contains a set of proteins specifically addressed to wound healing and tissue regeneration. The scaffold formed by using this technology is a clot mainly composed of fibrin protein, forming a three-dimensional (3D) macroscopic network. This biomaterial is easily obtained by biotechnological means from blood and can be used in a range of situations to help wound healing and tissue regeneration. Although the main constituent of this clot is the fibrin scaffold, little is known about other proteins interacting in this clot that may act as adjuvants in the healing process. The aim of this study was to characterize the proteins enclosed by PRGF-Endoret scaffold, using a double-proteomic approach that combines 1D-SDS-PAGE approach followed by LC-MS/MS, and 2-DE followed by MALDI-TOF/TOF. The results presented here provide a description of the catalogue of key proteins in close contact with the fibrin scaffold. The obtained lists of proteins were grouped into families and networks according to gene ontology. Taken together, an enrichment of both proteins and protein families specifically involved in tissue regeneration and wound healing has been found. Copyright © 2013 John Wiley & Sons, Ltd.

The regulation of the factor VII-dependent coagulation pathway: rationale for the effectiveness of recombinant factor VIIa in refractory bleeding disorders

NARCIS (Netherlands)

van't Veer, C.; Mann, K. G.

2000-01-01

We have explored the molecular basis of the clinical therapeutic effect of factor VIIa in hemophilia A using empirical reconstituted in vitro thrombin generation models. Tissue factor acts as a receptor and activator of preexistent but virtually inactive two-chain plasma factor VIIa. However, most

REGENERATIVE PECULIARITIES OF LIVER TISSUE AFTER HEMOSTASIS BY NONEQUILIBRIUM PLASMA ON 90TH AND 180TH DAY (EXPERIMENTAL STUDY

Directory of Open Access Journals (Sweden)

Ye. V. Semichev

2014-01-01

Full Text Available Liver damages occur to 17.8% of blunt abdominal trauma cases. Postoperative mortality in liver damage is a high. It amounts to 4–10% in case of stab wounds, to 30.4–35,2% in case of closed injury, to 39.3% in case of concomitant injury. Complete hemostasis without damage to organ parenchyma is needed for liver surgical operation.The aim of research is to evaluate the regenerative characteristics of liver tissue after hemostasis by nonequilibrium plasma in a long-term period.Material and methods. Research was performed on 20 laboratory rats, 3 experimental groups. 10 intact animals and 5 animals in groups on 90th and 180th day. Surgery is resection of liver left lobe and coagulation with cold plasma coagulator. The biochemical control (glucose, ALT, AST, total bilirubin, direct, alkaline phosphatase, total protein, urea, α-amylase, CRP, fibrinogen, aPTT, PTT, INR, morphological study of rat liver were performed.Results. After surgery with cold plasma hemostasis animals are active, early begin to eat. Fatal cases are not. Analysis of biochemical markers doesn't reveal statistically significant differences from the norm for the majority of indicators. Decrease of glucose concentration in the blood serum is observed in a long-term period. Histological analysis reveals an increase of the central and interlobular veins and moderate signs of edema on the 90th day. Hepatocytes with pronounced signs of protein and fatty degeneration are identified. Liver histology corresponds to the usual structure and is represented by liver lobules, separated by a small layer of connective tissue on the 180th day.Conclusion. Cold plasma coagulation in liver surgery showed effective hemostasis, minimal trauma of organ parenchyma, the lack of systemic effect and the subsequent complete regeneration of liver tissue in the treatment area.

Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-beta1-Induced myodifferentiation.

Science.gov (United States)

Anitua, Eduardo; Sanchez, Mikel; Merayo-Lloves, Jesus; De la Fuente, Maria; Muruzabal, Francisco; Orive, Gorka

2011-08-01

Plasma rich in growth factors (PRGF-Endoret) technology is an autologous platelet-enriched plasma obtained from patient's own blood, which after activation with calcium chloride allows the release of a pool of biologically active proteins that influence and promote a range of biological processes including cell recruitment, and growth and differentiation. Because ocular surface wound healing is mediated by different growth factors, we decided to explore the potential of PRGF-Endoret technology in stimulating the biological processes related with fibroblast-induced tissue repair. Furthermore, the anti-fibrotic properties of this technology were also studied. Blood from healthy donors was collected, centrifuged and, whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were drawn off, avoiding the buffy coat. Primary human cells including keratocytes and conjunctival fibroblasts were used to perform the "in vitro" investigations. The potential of PRGF-Endoret in promoting wound healing was evaluated by means of a proliferation and migration assays. Fibroblast cells were induced to myofibroblast differentiation after the treatment with 2.5 ng/mL of TGF-β1. The capability of WP and F3 to prevent and inhibit TGF-β1-induced differentiation was evaluated. Results show that this autologous approach significantly enhances proliferation and migration of both keratocytes and conjunctival fibroblasts. In addition, plasma rich in growth factors prevents and inhibits TGF-β1-induced myofibroblast differentiation. No differences were found between WP and F3 plasma fractions. These results suggest that PRGF-Endoret could reduce scarring while stimulating wound healing in ocular surface. F3 or whole plasma column show similar biological effects in keratocytes and conjunctival fibroblast cells.

Initial plasma disappearance and tissue uptake of 131I-albumin in normal rabbits

International Nuclear Information System (INIS)

Bent-Hansen, L.

1991-01-01

The simultaneous plasma disappearance curves of 131I-albumin and 125I-fibrinogen were recorded in normal rabbits for 1 hr. Using fibrinogen as a plasma reference, the disappearance curves of albumin were shown to contain two separate phases of efflux: one fast from zero to 10 min. comprising 8% of the total tracer; and one slow appearing in the interval of 10 to 60 min. containing another 9% of the tracer. Total albumin escape was analyzed to yield an initial slope of 0.024 ± 0.004 min-1, corresponding to a wholebody unidirectional albumin clearance (Cl(0)) of 0.090 ± 0.009 ml(min*100 g)-1. The distribution of efflux was assessed by biopsy uptakes using the same tracers in spleen, kidney, heart, lung, liver, intestine, skin, muscle, and brain. The disappearance curve generally reflects a biphasic pattern of uptake in peripheral tissue, predominantly by muscle and lung. The rapid phase has contributions from the fast near equilibration of liver, and intestine and skin are significant codeterminants of the slow phase. Due to their low body masses highly perfused organs such as kidney, spleen, and heart have little influence on the plasma disappearance. In accordance, the Cl(0) determined for the wholebody was higher than initial clearances found in skin (0.053 ml(min*100 g)-1) and muscle (0.054 ml(min*100 g)-1), but much lower than those found in the highly perfused organs. The initial (unidirectional) rates of peripheral albumin transfer demonstrated, ranged from 10 to 30 times higher than estimates of lymphatic return, suggesting that transcapillary albumin exchange is mediated by high-rate bidirectional diffusion. The rapid decrease of net albumin exchange rates suggests a second, highly significant barrier located within the interstitial matrix, which restricts plasma escape and reduces plasma to lymph albumin transport

Association of intraoperative tissue oxygenation with suspected risk factors for tissue hypoxia.

Science.gov (United States)

Spruit, R J; Schwarte, L A; Hakenberg, O W; Scheeren, T W L

2013-10-01

Tissue hypoxia may cause organ dysfunction, but not much is known about tissue oxygenation in the intraoperative setting. We studied microcirculatory tissue oxygen saturation (StO₂) to determine representative values for anesthetized patients undergoing urological surgery and to test the hypothesis that StO₂ is associated with known perioperative risk factors for morbidity and mortality, conventionally monitored variables, and hypotension requiring norepinephrine. Using near-infrared spectroscopy, we measured StO₂ on the thenar eminence in 160 patients undergoing open urological surgery under general anesthesia (FiO2 0.35-0.4), and calculated its correlations with age, risk level for general perioperative complications and mortality (high if age ≥70 and procedure is radical cystectomy), mean arterial pressure (MAP), hemoglobin concentration (Hb), central venous oxygen saturation (ScvO₂), and norepinephrine use. The time averaged StO₂ was 86 ± 6 % (mean ± SD). In the multivariate analysis, Hb [standardized coefficient (SC) 0.21, p = 0.003], ScvO₂ (SC 0.53, p SStO₂ was partly dependent on MAP only when this was below 65 mmHg (lowest MAP SC 0.20, p = 0.006, MAP area under the curve <65 mmHg SC 0.03, p = 0.02). Finally, StO₂ was slightly lower in patients requiring norepinephrine (85 ± 6 vs. 89 ± 6 %, p = 0.001). Intraoperative StO₂ in urological patients was comparable to that of healthy volunteers breathing room air as reported in the literature and correlated with known perioperative risk factors. Further research should investigate its association with outcome and the effect of interventions aimed at optimizing StO₂.

Quantum shielding effects on the Gamow penetration factor for nuclear fusion reaction in quantum plasmas

Science.gov (United States)

Lee, Myoung-Jae; Jung, Young-Dae

2017-01-01

The quantum shielding effects on the nuclear fusion reaction process are investigated in quantum plasmas. The closed expression of the classical turning point for the Gamow penetration factor in quantum plasmas is obtained by the Lambert W-function. The closed expressions of the Gamow penetration factor and the cross section for the nuclear fusion reaction in quantum plasmas are obtained as functions of the plasmon energy and the relative kinetic energy by using the effective interaction potential with the WKB analysis. It is shown that the influence of quantum screening suppresses the Sommerfeld reaction factor. It is also shown that the Gamow penetration factor increases with an increase of the plasmon energy. It is also shown that the quantum shielding effect enhances the deuterium formation by the proton-proton reaction in quantum plasmas. In addition, it is found that the energy dependences on the reaction cross section and the Gamow penetration factor are more significant in high plasmon-energy domains.

Estimation of anisotropy factor spectrum for determination of optical properties in biological tissues

Science.gov (United States)

Iwamoto, Misako; Honda, Norihiro; Ishii, Katsunori; Awazu, Kunio

2017-07-01

Spectroscopic setup for measuring anisotropy factor g spectrum of biological tissues was constructed. g of chicken liver tissue was lower than chicken breast tissue. High absorption of hemoglobin can have an influence on g spectrum.

Plasma brain-derived neurotrophic factor and reverse dipping pattern of nocturnal blood pressure in patients with cardiovascular risk factors.

Directory of Open Access Journals (Sweden)

Manabu Kadoya

Full Text Available Basic studies have shown that brain-derived neurotrophic factor (BDNF has critical roles in the survival, growth, maintenance, and death of central and peripheral neurons, while it is also involved in regulation of the autonomic nervous system. Furthermore, recent clinical studies have suggested potential role of plasma BDNF in the circulatory system.We investigated the mutual relationships among plasma BDNF, patterns of nocturnal blood pressure changes (dippers, non-dippers, extra-dippers, and reverse-dippers, and cardiac autonomic function as determined by heart rate variability (HRV.This was a cross-sectional study of patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA Study from October 2010 to November 2012.Two-hundred fifty patients with 1 or more cardiovascular risk factor(s (obesity, smoking, presence of cardiovascular event history, hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease were enrolled.Plasma BDNF levels (natural logarithm transformed were significantly (p = 0.001 lower in reverse-dipper patients (7.18±0.69 pg/ml, mean ± SD, n = 36 as compared to dippers (7.86±0.86 pg/ml, n = 100. Multiple logistic regression analysis showed that BDNF (odds ratios: 0.417, 95% confidence interval: 0.228-0.762, P = 0.004 was the sole factor significantly and independently associated with the reverse-dippers as compared with dippers. Furthermore, plasma BDNF level was significantly and positively correlated with the time-domain (SDNN, SDANN5, CVRR and frequency-domain (LF of HRV parameters. Finally, multiple logistic regression analyses showed that the relationship between plasma BDNF and the reverse-dippers was weakened, yet remained significant or borderline significant even after adjusting for HRV parameters.Low plasma BDNF was independently associated with patients showing a reverse-dipper pattern of nocturnal blood pressure, in which an imbalance of cardiac autonomic function

Ectopic bone formation during tissue-engineered cartilage repair using autologous chondrocytes and novel plasma-derived albumin scaffolds.

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Robla Costales, David; Junquera, Luis; García Pérez, Eva; Gómez Llames, Sara; Álvarez-Viejo, María; Meana-Infiesta, Álvaro

2016-10-01

The aims of this study were twofold: first, to evaluate the production of cartilaginous tissue in vitro and in vivo using a novel plasma-derived scaffold, and second, to test the repair of experimental defects made on ears of New Zealand rabbits (NZr) using this approach. Scaffolds were seeded with chondrocytes and cultured in vitro for 3 months to check in vitro cartilage production. To evaluate in vivo cartilage production, a chondrocyte-seeded scaffold was transplanted subcutaneously to a nude mouse. To check in vivo repair, experimental defects made in the ears of five New Zealand rabbits (NZr) were filled with chondrocyte-seeded scaffolds. In vitro culture produced mature chondrocytes with no extracellular matrix (ECM). Histological examination of redifferentiated in vitro cultures showed differentiated chondrocytes adhered to scaffold pores. Subcutaneous transplantation of these constructs to a nude mouse produced cartilage, confirmed by histological study. Experimental cartilage repair in five NZr showed cartilaginous tissue repairing the defects, mixed with calcified areas of bone formation. It is possible to produce cartilaginous tissue in vivo and to repair experimental auricular defects by means of chondrocyte cultures and the novel plasma-derived scaffold. Further studies are needed to determine the significance of bone formation in the samples. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods

NARCIS (Netherlands)

Schuitemaker, Alie; van Berckel, Bart N. M.; Kropholler, Marc A.; Veltman, Dick J.; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A.; Boellaard, Ronald

2007-01-01

(R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to

Effects of Plasma Rich in Growth Factors and Platelet-Rich Fibrin on Proliferation and Viability of Human Gingival Fibroblasts

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Vahabi, Surena; Vaziri, Shahram; Torshabi, Maryam

2015-01-01

Objectives: Platelet preparations are commonly used to enhance bone and soft tissue regeneration. Considering the existing controversies on the efficacy of platelet products for tissue regeneration, more in vitro studies are required. The aim of the present study was to compare the in vitro effects of plasma rich in growth factors (PRGF) and platelet-rich fibrin (PRF) on proliferation and viability of human gingival fibroblasts (HGFs). Materials and Methods: Anitua’s PRGF and Choukran’s PRF were prepared according to the standard protocols. After culture periods of 24, 48 and 72 hours, proliferation of HGFs was evaluated by the methyl thiazol tetrazolium assay. Statistical analysis was performed using one-way ANOVA followed by Tukey-Kramer’s multiple comparisons and P-valuesPRGF treatment induced statistically significant (PPRGF than in PRF group (PPRGF had a strong stimulatory effect on HGF cell viability and proliferation compared to PRF. PMID:26877740

Hypoxia-Inducible Factor-1α: A Potential Factor for the Enhancement of Osseointegration between Dental Implants and Tissue-Engineered Bone

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Duohong Zou

2011-07-01

Full Text Available Introduction: Tissue-engineered bones are widely utilized to protect healthy tissue, reduce pain, and increase the success rate of dental implants. one of the most challenging obstacles lies in obtaining effective os-seointegration between dental implants and tissue-engineered structures. Deficiencies in vascularization, osteogenic factors, oxygen, and other nutrients inside the tissue-engineered bone during the early stages following implantation all inhibit effective osseointe-gration. Oxygen is required for aerobic metabolism in bone and blood vessel tissues, but oxygen levels inside tissue-engineered bone are not suf-ficient for cell proliferation. HIF-1α is a pivotal regulator of hypoxic and ischemic vascular responses, driving transcriptional activation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, and osteogenesis.The hypothesis: Hypoxia-Inducible Factor-1α seems a potential factor for the enhancement of osseointegration between dental implants and tissue-engineered bone.Evaluation of the hypothesis: Enhancement of HIF-1α protein expression is recognized as the most promising approach for angiogenesis, because it can induce multiple angiogenic targets in a coordinated manner. Therefore, it will be a novel potential therapeutic methods targeting HIF-1α expression to enhance osseointegration be-tween dental implants and tissue-engineered bone.

Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors.

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Orgeur, Mickael; Martens, Marvin; Leonte, Georgeta; Nassari, Sonya; Bonnin, Marie-Ange; Börno, Stefan T; Timmermann, Bernd; Hecht, Jochen; Duprez, Delphine; Stricker, Sigmar

2018-03-29

Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development. © 2018. Published by The Company of Biologists Ltd.

Effect of platelet activating factor on endothelial permeability to plasma macromolecules

International Nuclear Information System (INIS)

Handley, D.A.; Arbeeny, C.M.; Lee, M.L.; Van Valen, R.G.; Saunders, R.N.

1984-01-01

The effect of intrajugular administration of platelet activating factor (PAF-C16) on vascular permeability was examined in the guinea pig. To examine the loss of selective endothelial permeability, the extravasative effect of PAF was assessed by monitoring hemoconcentration and the plasma loss of 125 I-albumin (6.7 nm), 125 I-low density lipoproteins (22.0 nm) or 125 I-very low density lipoproteins (62.1 nm). Extravasation was dose-dependent and began 1 min after PAF administration, continuing for 5-7 min. During extravasation, there was no evidence for selective plasma retention of any of the labeled plasma tracers, as measured by plasma radioactivity. These results suggest that PAF-induced extravasation is dose-dependent, with increases in vascular permeability sufficient to permit similar plasma efflux rates of albumin, low density lipoproteins and very low density lipoproteins

Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors

Science.gov (United States)

2013-01-01

Introduction Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed. Methods PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure. Results Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 106 to 1.9 × 106 platelets/μl). Platelets were highly purified, because only blood cells and leukocytes was present in the final PRP preparation. We also quantified growth factors, cytokines and chemokines secreted by the concentrated platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-β3 and IFNγ were not detected in any studied fraction. Clots obtained after platelet coagulation retained a high concentration of

The impact of plasma rich in growth factors on clinical and biological factors involved in healing processes after third molar extraction.

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Mozzati, Marco; Martinasso, Germana; Pol, Renato; Polastri, Carolina; Cristiano, Antonio; Muzio, Giuliana; Canuto, Rosa

2010-12-01

Extraction of an impacted mandibular third molar is a common surgical procedure, although it still leads to several postoperative symptoms and complications. The study assessed the efficacy of autologous plasma rich in growth factors (PRGF) in the healing process by checking the difference of tissue cytokines and other healing factors produced by the mucosa after extraction between sites treated with PRGF and control sites and, at the same time, by evaluating the clinical efficacy of PRGF in terms of reduced pain and facial swelling. This study was a split-mouth study, in which the patient becomes his/her own control, to eliminate any individual response differences toward PRGF treatment. The parameters regarding inflammation and subsequent wound healing were all significantly higher at PRGF sites than at control sites. The increase at PRGF sites of the two proinflammatory cytokines evaluated, interleukin (IL)-1β and IL-6, was accompanied by the increase of two anti-inflammatory cytokines, IL-10 and transforming growth factor-β. Furthermore, IL-1β and IL-6 induce fibroblast and keratinocyte proliferation, important events in wound healing. Postoperative pain and the swelling, measured at all experimental times, were reduced in the presence of PRGF. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

Graft Product for Autologous Peripheral Blood Stem Cell Transplantation Enhances Thrombin Generation and Expresses Procoagulant Microparticles and Tissue Factor.

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Sidibe, Fatoumata; Spanoudaki, Anastasia; Vanneaux, Valerie; Mbemba, Elisabeth; Larghero, Jerome; Van Dreden, Patrick; Lotz, Jean-Pierre; Elalamy, Ismail; Larsen, Annette K; Gerotziafas, Grigoris T

2018-05-01

The beneficial effect of autologous peripheral blood stem cell transplantation (APBSCT) may be compromised by acute vascular complications related to hypercoagulability. We studied the impact of graft product on thrombin generation of normal plasma and the expression of tissue factor (TF) and procoagulant platelet-derived procoagulant microparticles (Pd-MPs) in samples of graft products. Graft products from 10 patients eligible for APBSCT were mixed with platelet-poor plasma (PPP) or platelet-rich plasma (PRP) from healthy volunteers and assessed for in vitro thrombin generation. In control experiments, thrombin generation was assessed in (1) PPP and PRP without any exogenous TF and/or procoagulant phospholipids, (2) PPP with the addition of TF (5 pM) and procoagulant phospholipids (4 μM), (3) in PRP with the addition of TF (5 pM). Graft products were assessed with Western blot assay for TF expression, with a specific clotting assay for TF activity and with flow cytometry assay for Pd-MPs. The graft product enhanced thrombin generation and its procoagulant activity was related to the presence of Pd-MPs and TF. The concentration of Pd-MPs in the graft product was characterized by a significant interindividual variability. The present study reveals the need for a thorough quality control of the graft products regarding their procoagulant potential.

Platelet Rich Plasma- mechanism of action and clinical applications

OpenAIRE

Cristina N. Cozma; Laura Raducu; Cristian R. Jecan

2016-01-01

Platelet-rich plasma (PRP) is a blood-derived fraction containing high level of platelets, a high concentration of leukocytes and growth factors. PRP therapy has been growing as a viable treatment alternative for a number of clinical applications and has a potential benefit for use in wound healing. Nowadays platelet rich plasma is used in stimulating wound healing in skin and soft tissue ulcerations, accelerating wound healing in diabetic patients and facilitating bone proliferation in ortho...

Biocompatibility of plasma-treated poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nanofiber mats modified by silk fibroin for bone tissue regeneration

Energy Technology Data Exchange (ETDEWEB)

Unalan, Irem [Biomedical Technologies Department, Graduate School of Natural and Applied Sciences, Dokuz Eylul University, Izmir (Turkey); Colpankan, Oylum [Metallurgical and Materials Engineering Department, Faculty of Engineering, Dokuz Eylul University, Izmir (Turkey); Albayrak, Aylin Ziylan, E-mail: aylin.albayrak@deu.edu.tr [Metallurgical and Materials Engineering Department, Faculty of Engineering, Dokuz Eylul University, Izmir (Turkey); Gorgun, Cansu [Biomedical Technologies Department, Graduate School of Natural and Applied Sciences, Ege University, Izmir (Turkey); Urkmez, Aylin Sendemir [Biomedical Technologies Department, Graduate School of Natural and Applied Sciences, Ege University, Izmir (Turkey); Bioengineering Department, Faculty of Engineering, Ege University, Izmir (Turkey)

2016-11-01

The objective of this study was to produce biocompatible plasma-treated and silk-fibroin (SF) modified poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofiber mats. The mats were plasma-treated using O{sub 2} or N{sub 2} gas to increase their hydrophilicity followed by SF immobilization for the improvement of biocompatibility. Contact angle measurements and SEM showed increased hydrophilicity and no disturbed morphology, respectively. Cell proliferation assay revealed that SF modification together with N{sub 2} plasma (PS/N{sub 2}) promoted higher osteoblastic (SaOs-2) cell viability. Although, O{sub 2} plasma triggered more mineral formation on the mats, it showed poor cell viability. Consequently, the PS/N{sub 2} nanofiber mats would be a potential candidate for bone tissue engineering applications. - Highlights: • N{sub 2}-plasma treated and silk fibroin modified mats do not show hydrophobic recovery. • Biomineralization is better on O{sub 2}-plasma treated and silk fibroin modified mats. • SaOS-2 cells like to proliferate on N{sub 2}-plasma treated surfaces.

Computer simulations of plasma-biomolecule and plasma-tissue interactions for a better insight in plasma medicine

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Neyts, Erik C.; Yusupov, Maksudbek; Verlackt, Christof C.; Bogaerts, Annemie

2014-07-01

Plasma medicine is a rapidly evolving multidisciplinary field at the intersection of chemistry, biochemistry, physics, biology, medicine and bioengineering. It holds great potential in medical, health care, dentistry, surgical, food treatment and other applications. This multidisciplinary nature and variety of possible applications come along with an inherent and intrinsic complexity. Advancing plasma medicine to the stage that it becomes an everyday tool in its respective fields requires a fundamental understanding of the basic processes, which is lacking so far. However, some major advances have already been made through detailed experiments over the last 15 years. Complementary, computer simulations may provide insight that is difficult—if not impossible—to obtain through experiments. In this review, we aim to provide an overview of the various simulations that have been carried out in the context of plasma medicine so far, or that are relevant for plasma medicine. We focus our attention mostly on atomistic simulations dealing with plasma-biomolecule interactions. We also provide a perspective and tentative list of opportunities for future modelling studies that are likely to further advance the field.

Tissue factor-expressing tumor cells can bind to immobilized recombinant tissue factor pathway inhibitor under static and shear conditions in vitro.

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Sara P Y Che

Full Text Available Mammary tumors and malignant breast cancer cell lines over-express the coagulation factor, tissue factor (TF. High expression of TF is associated with a poor prognosis in breast cancer. Tissue factor pathway inhibitor (TFPI, the endogenous inhibitor of TF, is constitutively expressed on the endothelium. We hypothesized that TF-expressing tumor cells can bind to immobilized recombinant TFPI, leading to arrest of the tumor cells under shear in vitro. We evaluated the adhesion of breast cancer cells to immobilized TFPI under static and shear conditions (0.35 - 1.3 dyn/cm2. We found that high-TF-expressing breast cancer cells, MDA-MB-231 (with a TF density of 460,000/cell, but not low TF-expressing MCF-7 (with a TF density of 1,400/cell, adhered to recombinant TFPI, under static and shear conditions. Adhesion of MDA-MB-231 cells to TFPI required activated factor VII (FVIIa, but not FX, and was inhibited by a factor VIIa-blocking anti-TF antibody. Under shear, adhesion to TFPI was dependent on the TFPI-coating concentration, FVIIa concentration and shear stress, with no observed adhesion at shear stresses greater than 1.0 dyn/cm2. This is the first study showing that TF-expressing tumor cells can be captured by immobilized TFPI, a ligand constitutively expressed on the endothelium, under low shear in vitro. Based on our results, we hypothesize that TFPI could be a novel ligand mediating the arrest of TF-expressing tumor cells in high TFPI-expressing vessels under conditions of low shear during metastasis.

Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

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Federica Novelli

Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

LHRH-pituitary plasma membrane binding: the presence of specific binding sites in other tissues.

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Marshall, J C; Shakespear, R A; Odell, W D

1976-11-01

Two specific binding sites for LHRH are present on plasma membranes prepared from rat and bovine anterior pituitary glands. One site is of high affinity (K = 2X108 1/MOL) and the second is of lower affinity (8-5X105 1/mol) and much greater capacity. Studies on membrane fractions prepared from other tissues showed the presence of a single specific site for LHRH. The kinetics and specificity of this site were similar to those of the lower affinity pituitary receptor. These results indicate that only pituitary membranes possess the higher affinity binding site and suggest that the low affinity site is not of physiological importance in the regulation of gonadotrophin secretion. After dissociation from membranes of non-pituitary tissues 125I-LHRH rebound to pituitary membrane preparations. Thus receptor binding per se does not result in degradation of LHRH and the function of these peripheral receptors remains obscure.

Accurate determination of silver nanoparticles in animal tissues by inductively coupled plasma mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Veverková, Lenka [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Hradilová, Šárka [Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Milde, David, E-mail: david.mlde@upol.cz [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Panáček, Aleš [Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Skopalová, Jana [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Kvítek, Libor [Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Petrželová, Kamila [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); National Reference Laboratory for Chemical Elements, Department of Residues in Kroměříž, State Veterinary Institute Olomouc, Hulínská 2286, CZ 767 60 Kroměříž (Czech Republic); and others

2014-12-01

This study examined recoveries of silver determination in animal tissues after wet digestion by inductively coupled plasma mass spectrometry. The composition of the mineralization mixture for microwave assisted digestion was optimized and the best recoveries were obtained for mineralization with HNO{sub 3} and addition of HCl promptly after digestion. The optimization was performed on model samples of chicken meat spiked with silver nanoparticles and a solution of ionic silver. Basic calculations of theoretical distribution of Ag among various silver-containing species were implemented and the results showed that most of the silver is in the form of soluble complexes AgCl{sub 2}{sup −} and AgCl{sub 3}{sup 2−} for the optimized composition of the mineralization mixture. Three animal tissue certified reference materials were then analyzed to verify the trueness and precision of the results. - Highlights: • We performed detailed optimization of microwave assisted digestion procedure of animal tissue used prior to Ag determination by ICP-MS. • We provide basic equilibrium calculations to give theoretical explanation of results from optimization of tested mineralization mixtures. • Results from method validation that was done by analysis of several matrix CRMs are presented.

Expression of cyclooxygenase-1 and cyclooxygenase-2, syndecan-1 and connective tissue growth factor in benign and malignant breast tissue from premenopausal women.

Science.gov (United States)

Fahlén, M; Zhang, H; Löfgren, L; Masironi, B; von Schoultz, E; von Schoultz, B; Sahlin, L

2017-05-01

Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues. The COX-2 mRNA level was lower in the malignant tumor than in the normal tissue, while CTGF mRNA did not differ between the groups. COX-1 immunostaining was higher in stroma from malignant tumors than in benign tissues, whereas COX-2 immunostaining was higher in the malignant tissue. Glandular S-1 immunostaining was lower in malignant tumors compared to benign and normal tissues, and the opposite was found in stroma. Conclusively, mRNA levels of COX-1 and COX-2 were oppositely regulated, with COX-1 being increased in the malignant tumor while COX-2 was decreased. S-1 protein localization switched from glandular to stromal cells in malignant tissues. Thus, these markers are, in premenopausal women, localized and regulated differently in normal/benign breast tissue as compared to the malignant tumor.

Some growth factors in neoplastic tissues of brain tumors of different histological structure

Directory of Open Access Journals (Sweden)

O. I. Kit

2016-01-01

Full Text Available Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis, and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015 play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement.Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas.Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area by the method of immunoassay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria, VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria, EGF (Biosource, USA, IFR-1 and IFR-2 (Mediagnost, USA, TGF

The measurement of insulin-like growth factor 1 in sheep plasma.

Science.gov (United States)

Bruce, L A; Atkinson, T; Hutchinson, J S; Shakespear, R A; MacRae, J C

1991-02-01

A method is described for the radioimmunoassay (RIA) of insulin-like growth factor 1 (IGF-1) in neutralised formic acid-ethanol extracts of sheep plasma. The ability of the acid-ethanol pretreatment to remove the IGF-1 binding proteins (BPs), which interfere in the assay has been examined. Comparative plasma IGF-1 concentrations determined by the method correlated closely (P less than 0.001) with corresponding values where BPs were removed by acid gel filtration. The method has been applied to studies in which sheep were given exogenous growth hormone and indicated that plasma IGF-1 levels respond rapidly to the onset and termination of treatment.

Methadone Recycling Sustains Drug Reservoir in Tissue.

Science.gov (United States)

Linares, Oscar A; Fudin, Jeffrey; Daly, Annemarie; Schiesser, William E; Boston, Raymond C

2015-09-01

We hypothesize that there is a tissue store of methadone content in humans that is not directly accessible, but is quantifiable. Further, we hypothesize the mechanism by which methadone content is sustained in tissue stores involves methadone uptake, storage, and release from tissue depots in the body (recycling). Accordingly, we hypothesize that such tissue stores, in part, determine plasma methadone levels. We studied a random sample of six opioid-naïve healthy subjects. We performed a clinical trial simulation in silico using pharmacokinetic modeling. We found a large tissue store of methadone content whose size was much larger than methadone's size in plasma in response to a single oral dose of methadone 10 mg. The tissue store measured 13-17 mg. This finding could only be explained by the contemporaneous storage of methadone in tissue with dose recycling. We found that methadone recycles 2-5 times through an inaccessible extravascular compartment (IAC), from an accessible plasma-containing compartment (AC), before exiting irreversibly. We estimate the rate of accumulation (or storage) of methadone in tissue was 0.029-7.29 mg/h. We predict 39 ± 13% to 83 ± 6% of methadone's tissue stores "spillover" into the circulation. Our results indicate that there exists a large quantifiable tissue store of methadone in humans. Our results support the notion that methadone in humans undergoes tissue uptake, storage, release into the circulation, reuptake from the circulation, and re-release into the circulation, and that spillover of methadone from tissue stores, in part, maintain plasma methadone levels in humans.

Thyroid hormones and deiodinase activity in plasma and tissues in relation to high levels of organohalogen contaminants in East Greenland polar bears (Ursus maritimus).

Science.gov (United States)

Gabrielsen, Kristin Møller; Krokstad, Julie Stene; Villanger, Gro Dehli; Blair, David A D; Obregon, Maria-Jesus; Sonne, Christian; Dietz, Rune; Letcher, Robert J; Jenssen, Bjørn Munro

2015-01-01

Previous studies have shown relationships between organohalogen contaminants (OHCs) and circulating levels of thyroid hormones (THs) in arctic wildlife. However, there is a lack of knowledge concerning the possible functional effects of OHCs on TH status in target tissues for TH-dependent activity. The relationships between circulating (plasma) levels of OHCs and various TH variables in plasma as well as in liver, muscle and kidney tissues from East Greenland sub-adult polar bears (Ursus maritimus) sampled in 2011 (n=7) were therefore investigated. The TH variables included 3.3',5.5'-tetraiodothyronine or thyroxine (T4), 3.3',5-triiodothyronine (T3) and type 1 (D1) and type 2 (D2) deiodinase activities. Principal component analysis (PCA) combined with correlation analyses demonstrated negative relationships between individual polychlorinated biphenyls (PCBs) and their hydroxylated (OH-) metabolites and T4 in both plasma and muscle. There were both positive and negative relationships between individual OHCs and D1 and D2 activities in muscle, liver and kidney tissues. In general, PCBs, OH-PCBs and polybrominated dipehenyl ethers (PBDEs) were positively correlated to D1 and D2 activities, whereas organochlorine pesticides and byproducts (OCPs) were negatively associated with D1 and D2 activities. These results support the hypothesis that OHCs can affect TH status and action in the target tissues of polar bears. TH levels and deiodinase activities in target tissues can be sensitive endpoints for exposure of TH-disrupting compounds in arctic wildlife, and thus, tissue-specific responses in target organs should be further considered when assessing TH disruption in wildlife studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Factors influencing plasma transfusion practices in paediatric intensive care units around the world

DEFF Research Database (Denmark)

Karam, Oliver; Demaret, Pierre; Duhamel, Alain

2017-01-01

investigators of the 101 participating centres, in February 2016. Four areas were explored: beliefs regarding plasma transfusion, patients' case-mix in each unit, unit's characteristics, and local blood product transfusion policies and processes. RESULTS: The response rate was 82% (83/101). 43...... transfusions (P = 0·02 and P = 0·04, respectively). Case-mix, centre characteristics or local transfusion services were not identified as significant relevant factors. CONCLUSION: Factors influencing plasma transfusion practices reflect beliefs about indications and the efficacy of transfusion...

Plasma fibrinogen and factor VII concentrations in adults after prenatal exposure to famine

NARCIS (Netherlands)

Roseboom, T. J.; van der Meulen, J. H.; Ravelli, A. C.; Osmond, C.; Barker, D. J.; Bleker, O. P.

2000-01-01

To assess the effect of maternal malnutrition during different stages of gestation on plasma concentrations of fibrinogen and factor VII, we investigated 725 people, aged 50 years, born around the time of the Dutch famine 1944-5. After adjustment for sex, plasma fibrinogen concentrations differed by

Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.

Science.gov (United States)

Wojtukiewicz, Marek Z; Sierko, Ewa; Skalij, Piotr; Kamińska, Magda; Zimnoch, Lech; Brekken, Ralf A; Thorpe, Philip E

2016-01-01

Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco. G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR). Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs. The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.

Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic Disorders

Science.gov (United States)

Pakradouni, Jihane; Le Goff, Wilfried; Calmel, Claire; Antoine, Bénédicte; Villard, Elise; Frisdal, Eric; Abifadel, Marianne; Tordjman, Joan; Poitou, Christine; Bonnefont-Rousselot, Dominique; Bittar, Randa; Bruckert, Eric; Clément, Karine; Fève, Bruno; Martinerie, Cécile; Guérin, Maryse

2013-01-01

Objective Evidence points to a founder of the multifunctional CCN family, NOV/CCN3, as a circulating molecule involved in cardiac development, vascular homeostasis and inflammation. No data are available on the relationship between plasma NOV/CCN3 levels and cardiovascular risk factors in humans. This study investigated the possible relationship between plasma NOV levels and cardiovascular risk factors in humans. Methods NOV levels were measured in the plasma from 594 adults with a hyperlipidemia history and/or with lipid-lowering therapy and/or a body mass index (BMI) >30 kg/m2. Correlations were measured between NOV plasma levels and various parameters, including BMI, fat mass, and plasma triglycerides, cholesterol, glucose, and C-reactive protein. NOV expression was also evaluated in adipose tissue from obese patients and rodents and in primary cultures of adipocytes and macrophages. Results After full multivariate adjustment, we detected a strong positive correlation between plasma NOV and BMI (r = 0.36 p<0.0001) and fat mass (r = 0.33 p<0.0005). According to quintiles, this relationship appeared to be linear. NOV levels were also positively correlated with C-reactive protein but not with total cholesterol, LDL-C or blood glucose. In patients with drastic weight loss induced by Roux-en-Y bariatric surgery, circulating NOV levels decreased by 28% (p<0.02) and 48% (p<0.0001) after 3 and 6 months, respectively, following surgery. In adipose tissue from obese patients, and in human primary cultures NOV protein was detected in adipocytes and macrophages. In mice fed a high fat diet NOV plasma levels and its expression in adipose tissue were also significantly increased compared to controls fed a standard diet. Conclusion Our results strongly suggest that in obese humans and mice plasma NOV levels positively correlated with NOV expression in adipose tissue, and support a possible contribution of NOV to obesity-related inflammation. PMID:23785511

Kininase enzymes of cat eye tissues

International Nuclear Information System (INIS)

Ryan, J.W.; Anderson, D.R.

1986-01-01

Eye tissues contain kininase activities, including an angiotensin converting enzyme (ACE)-like activity. The authors have begun further to characterize the ACE-like activity and to examine for another reputed kininase, carboxypeptidase N (CPN). Homogenates of tissues of 6 cat eyes and paired plasmas were assayed for ACE using 3 acyl-tripeptide substrates, 3 H-benzoylated F-A-P, F-G-P and A-G-P (respectively, BFAP, BFGP and BAGP). CPN was assayed using 3 H-benzoyl-A-R. All eye tissues and fluids contained ACE- and CPN-like activities. The ACE activity was clearly owing to ACE: relative values of Kc/Km for BFAP, BFGP and BAGP were those for pure ACE (2.213, 1.751 and 1.0); reactivities with inhibitors were as expected (Ki for captopril, MK 422 and RAC-X-65: 2.7, 0.62 and 0.31 nM). EDTA inhibited both ACE and CPN (I 50 's: 43 and 47 μM). CPN activity was inhibited by 2-mercaptomethyl-3-guanidinoethylthiopropionate (Ki 2.4 nM). However, distributions of the two enzymes differed markedly. Virtually all tissues contained ACE at specific activities higher than that of plasma. Specific activities appeared to be a function of tissue vascularity (for choroid, ciliary body, iris, retina and plasma: 7.31, 2.57, 1.98, 1.53 and 0.21 pmol/mg protein). Only iris contained more CPN that did plasma (23.0 v. 7.21 pmol/mg protein). The tissue distribution of ACE is that expected for an endothelial-associated enzyme. Plasma may be the major source of CPN in eye tissues other than iris

Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

DEFF Research Database (Denmark)

Bladbjerg, E-M; Skouby, S O.; Andersen, L F

2002-01-01

BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen......: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed...

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

Science.gov (United States)

Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

2016-03-01

Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

High plasma apolipoprotein B identifies obese subjects who best ameliorate white adipose tissue dysfunction and glucose-induced hyperinsulinemia after a hypocaloric diet.

Science.gov (United States)

Bissonnette, Simon; Saint-Pierre, Nathalie; Lamantia, Valerie; Leroux, Catherine; Provost, Viviane; Cyr, Yannick; Rabasa-Lhoret, Remi; Faraj, May

2018-06-18

To optimize the prevention of type 2 diabetes (T2D), high-risk obese subjects with the best metabolic recovery after a hypocaloric diet should be targeted. Apolipoprotein B lipoproteins (apoB lipoproteins) induce white adipose tissue (WAT) dysfunction, which in turn promotes postprandial hypertriglyceridemia, insulin resistance (IR), and hyperinsulinemia. The aim of this study was to explore whether high plasma apoB, or number of plasma apoB lipoproteins, identifies subjects who best ameliorate WAT dysfunction and related risk factors after a hypocaloric diet. Fifty-nine men and postmenopausal women [mean ± SD age: 58 ± 6 y; body mass index (kg/m2): 32.6 ± 4.6] completed a prospective study with a 6-mo hypocaloric diet (-500 kcal/d). Glucose-induced insulin secretion (GIIS) and insulin sensitivity (IS) were measured by 1-h intravenous glucose-tolerance test (IVGTT) followed by a 3-h hyperinsulinemic-euglycemic clamp, respectively. Ex vivo gynoid WAT function (i.e., hydrolysis and storage of 3H-triolein-labeled triglyceride-rich lipoproteins) and 6-h postprandial plasma clearance of a 13C-triolein-labeled high-fat meal were measured in a subsample (n = 25). Postintervention first-phase GIISIVGTT and total C-peptide secretion decreased in both sexes, whereas second-phase and total GIISIVGTT and clamp IS were ameliorated in men (P hypocaloric diet. We propose that subjects with high plasma apoB represent an optimal target group for the primary prevention of T2D by hypocaloric diets. This trial was registered at BioMed Central as ISRCTN14476404.

Impact of pre-analytical factors on the proteomic analysis of formalin-fixed paraffin-embedded tissue.

Science.gov (United States)

Thompson, Seonaid M; Craven, Rachel A; Nirmalan, Niroshini J; Harnden, Patricia; Selby, Peter J; Banks, Rosamonde E

2013-04-01

Formalin-fixed paraffin-embedded (FFPE) tissue samples represent a tremendous potential resource for biomarker discovery, with large numbers of samples in hospital pathology departments and links to clinical information. However, the cross-linking of proteins and nucleic acids by formalin fixation has hampered analysis and proteomic studies have been restricted to using frozen tissue, which is more limited in availability as it needs to be collected specifically for research. This means that rare disease subtypes cannot be studied easily. Recently, improved extraction techniques have enabled analysis of FFPE tissue by a number of proteomic techniques. As with all clinical samples, pre-analytical factors are likely to impact on the results obtained, although overlooked in many studies. The aim of this review is to discuss the various pre-analytical factors, which include warm and cold ischaemic time, size of sample, fixation duration and temperature, tissue processing conditions, length of storage of archival tissue and storage conditions, and to review the studies that have considered these factors in more detail. In those areas where investigations are few or non-existent, illustrative examples of the possible importance of specific factors have been drawn from studies using frozen tissue or from immunohistochemical studies of FFPE tissue. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plasma fractionation for blood products: isolation and purification of coagulating factors, albumin and immunoglobulin

International Nuclear Information System (INIS)

Siti Najila Mohd Janib; Shaharuddin Mohd; Wan Hamirul Bahrin Wan Kamal

2005-01-01

Approximately 12 million liters of human plasma are fractionated world-wide annually. However, with the market for clotting factors and other haemoderivatives steadily increasing from year to year, the amount processed will also increase correspondingly to keep up with the demand. In Malaysia, part of the need for the blood products are obtained commercially but a major portion of the requirement involves sending the plasma collected by the National Blood Centre to Australia for processing. Following purification and isolation of the blood products, they are sent back to Malaysia for local consumption. As yet there are no plasma fractionation plants in the South East Asia region, it would be advantageous to establish a local fractionation plant as it would be able to cater for local demands of the haemoderivatives and thus reduces the cost of importing these products. Besides, this facility will be able to provide contract fractionation services to the surrounding region. Early work in MINT has started in trying to purify plasma obtained from rats. Purification of the plasma was performed by using Sephadex G-25 column. Short term objective of this project is to develop the technique of extraction, fractionation and purification of blood products such as albumin, globulin and clotting factors (Factor VIII and Factor IX). The long term emphasis will be to scale up the production facility to a pilot plant stage and eventually to a national fractionation and purification plant. (Author)

Recombinant nematode anticoagulant protein c2, an inhibitor of tissue factor/factor VIIa, attenuates coagulation and the interleukin-10 response in human endotoxemia

NARCIS (Netherlands)

de Pont, A. C. J. M.; Moons, A. H. M.; de Jonge, E.; Meijers, J. C. M.; Vlasuk, G. P.; Rote, W. E.; Büller, H. R.; van der Poll, T.; Levi, M. [=Marcel M.

2004-01-01

The tissue factor-factor (F)VIIa complex (TF/FVIIa) is responsible for the initiation of blood coagulation under both physiological and pathological conditions. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of TF/FVIIa. mechanistically distinct from tissue factor

The influence of platelet- derived products on angiogenesis and tissue repair: a concise update

Directory of Open Access Journals (Sweden)

Constanza E Martínez

2015-10-01

Full Text Available Platelet degranulation allows the release of a large amount of soluble mediators, is an essential step for wound healing initiation, and stimulates clotting and angiogenesis. The latter process is one of the most critical biological events observed during tissue repair,increasing the growth of blood vessels in the maturing wound. Angiogenesis requires the action of a variety of growth factors that act in an appropriate physiological ratio to assure functional blood vessel restoration. Platelets release main regulators of angiogenesis: Vascular Endothelial Growth Factors (VEGFs, basic fibroblast growth factor (FGF-2, and Platelet derived growth factors (PDGFs, among others. In order to stimulate tissue repair, platelet derived fractions have been used as an autologous source of growth factors and biomolecules, namely Platelet Rich Plasma (PRP, Platelet Poor Plasma (PPP and Platelet Rich Fibrin(PRF. The continuous release of these growth factors has been proposed to promote angiogenesis both in vitro and in vivo. Considering the existence of clinical trials currently evaluating the efficacy of autologous PRP, the present review analyses fundamental questions regarding the putative role of platelet derived fractions as regulators of angiogenesis and evaluates the possible clinical implications of these formulations.

Associations of Plasma Nitrite, L-Arginine and Asymmetric Dimethylarginine with Morbidity and Mortality in Patients with Necrotizing Soft Tissue Infections

DEFF Research Database (Denmark)

Hansen, Marco Bo; Rasmussen, Lars Simon; Garred, Peter

2017-01-01

BACKGROUND: The nitric oxide system could play an important role in the pathophysiology related to necrotizing soft tissue infection (NSTI). Accordingly, we investigated the association between plasma nitrite level at admission and the presence of septic shock in patients with NSTI. We also evalu...

Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice.

Science.gov (United States)

McLachlan, Stela; Page, Kathryn E; Lee, Seung-Min; Loguinov, Alex; Valore, Erika; Hui, Simon T; Jung, Grace; Zhou, Jie; Lusis, Aldons J; Fuqua, Brie; Ganz, Tomas; Nemeth, Elizabeta; Vulpe, Chris D

2017-11-01

Iron homeostasis is tightly regulated, and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex- and strain-dependent differences in mRNA and serum levels of hepcidin and reported conflicting data on the relationship between hepcidin ( Hamp1 ) mRNA levels and iron status. Our aim was to clarify the relationships between strain, sex, and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains. Two studies were done: first, Hamp1 mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, Hamp1 mRNA and plasma hepcidin levels in both sexes and iron levels in the heart, kidneys, liver, pancreas, and spleen in males were measured in nine inbred/recombinant inbred strains raised on an iron-sufficient or high-iron diet. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). However, liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice fed iron-sufficient or high-iron diets, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males. We also measured plasma erythroferrone, performed RNA-sequencing analysis of liver samples from six inbred strains fed the iron-sufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. NEW & NOTEWORTHY Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). Liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least

Recovery from Bell Palsy after Transplantation of Peripheral Blood Mononuclear Cells and Platelet-Rich Plasma

OpenAIRE

Seffer, Istvan; Nemeth, Zoltan

2017-01-01

Summary: Peripheral blood mononuclear cells (PBMCs) are multipotent, and plasma contains growth factors involving tissue regeneration. We hypothesized that transplantation of PBMC-plasma will promote the recovery of paralyzed facial muscles in Bell palsy. This case report describes the effects of PBMC-plasma transplantations in a 27-year-old female patient with right side Bell palsy. On the affected side of the face, the treatment resulted in both morphological and functional recovery includi...

Connective tissue growth factor immunohistochemical expression is associated with gallbladder cancer progression.

Science.gov (United States)

Garcia, Patricia; Leal, Pamela; Alvarez, Hector; Brebi, Priscilla; Ili, Carmen; Tapia, Oscar; Roa, Juan C

2013-02-01

Gallbladder cancer (GBC) is an aggressive neoplasia associated with late diagnosis, unsatisfactory treatment, and poor prognosis. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. Connective tissue growth factor (CTGF) is thought to play a role in the pathologic processes and is overexpressed in several human cancers, including GBC. No information is available about CTGF expression in early stages of gallbladder carcinogenesis. Objective.- To evaluate the expression level of CTGF in benign and malignant lesions of gallbladder and its correlation with clinicopathologic features and GBC prognosis. Connective tissue growth factor protein was examined by immunohistochemistry on tissue microarrays containing tissue samples of chronic cholecystitis (n = 51), dysplasia (n = 15), and GBC (n = 169). The samples were scored according to intensity of staining as low/absent and high CTGF expressers. Statistical analysis was performed using the χ(2) test or Fisher exact probability test with a significance level of P Connective tissue growth factor expression showed a progressive increase from chronic cholecystitis to dysplasia and then to early and advanced carcinoma. Immunohistochemical expression (score ≥2) was significantly higher in advanced tumors, in comparison with chronic cholecystitis (P < .001) and dysplasia (P = .03). High levels of CTGF expression correlated with better survival (P = .04). Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.

Resistin in Dairy Cows: Plasma Concentrations during Early Lactation, Expression and Potential Role in Adipose Tissue

OpenAIRE

Reverchon, Maxime; Ramé, Christelle; Cognié, Juliette; Briant, Eric; Elis, Sébastien; Guillaume, Daniel; Dupont, Joëlle

2014-01-01

Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigat...

Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

International Nuclear Information System (INIS)

Sawada, Keigo; Takedachi, Masahide; Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki; Lee, Chun Man; Okura, Hanayuki; Matsuyama, Akifumi; Kitamura, Masahiro; Murakami, Shinya

2015-01-01

Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation

Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

Energy Technology Data Exchange (ETDEWEB)

Sawada, Keigo [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Takedachi, Masahide, E-mail: takedati@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Lee, Chun Man [Medical Center for Translational Research, Osaka University Hospital, Osaka (Japan); Okura, Hanayuki; Matsuyama, Akifumi [Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka (Japan); Kitamura, Masahiro; Murakami, Shinya [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan)

2015-08-14

Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

[Conservative treatment using plasma rich in growth factors (PRGF) for injury to the ligamentous complex of the ankle].

Science.gov (United States)

Frei, R; Biosca, F E; Handl, M; Trc, T

2008-02-01

The authors describe the therapeutic utilization of separated/isolated autologous growth factors in semiconservative treatment of type III injury to the ankle ligamentous complex. Between October 2004 and March 2005 a group of 11 patients, two women and nine men, aged 18 to 41 (average, 25.09) years with acute injury to the lateral ligamentous complex of the ankle were treated by plasma rich in growth factors (PRGF) infiltration. On functional radiographic examination, the post-traumatic lateral opening of the tibiotalar intraarticular space was 17.45 degrees (range, 12.0-30.0; s = 5.68). The injured patients were clinically examined and standard forced inversion radiographs were made using topical anesthesia. Autologous PRGF activated with calcium chloride was used to infiltrate the injured tissues. The treatment was followed by immobilization of the joint and its subsequent rehabilitation. Clinical examination of injured tissues was carried out at 4 and 6 weeks of follow-up, using stability assessment tests and functional radiography of the ankle. Physical therapy included standard procedures, but faster regeneration of the soft tissues allowed for more exercises. The average time of healing was 5.18 weeks. Five patients showed no signs of instability at 4 weeks after therapy and could return to their previous sports activities. One patient had lateral ankle instability at 5 weeks and therefore the therapy continued with prolonged immobilization and then rehabilitation at a slower pace. The average lateral opening of the tibiotalar intra-articular space at 4 or 6 follow-up weeks was 4.73 degrees (range, 3.0 - 7.0; s = 1.19). At 6 weeks after therapy, 90.9% of the patients resumed their full sports activities. Ankle distortion with swelling, hematoma and pain, but with no radiographic findings of ligament lesions, is usually treated conservatively by ankle immobilization and early rehabilitation. When an injury to the fibular ankle ligaments occurs (i.e., opening

Effects of Socio demographic factors on plasma ascorbic acid and alpha tocopherol anti oxidants during pregnancy

International Nuclear Information System (INIS)

Sylvester, I.E.; Paul, A.

2010-01-01

Objectives: To assess the plasma levels of vitamins C and E at the various stages of pregnancy and to correlate their plasma levels with the socio-demographic factors of pregnant Nigerians. Methodology: The pregnant cases (n=180) were randomly selected according to gestational ages. And the controls (n=20) were non-pregnant women of the same age. Plasma levels of both vitamins were assayed with well established laboratory methods. Results: The mean plasma vitamins C and E in the pregnant cases was lower (by 17-23%) than controls across the three trimesters, p<0.0001. The correlation of vitamin C versus maternal age was significant; r = - 0.59, p<0.05; the mean plasma level of vitamin C declined by 57% as the maternal age increases from 22-37 years. Conclusion: The mean plasma Ascorbic acid and Alpha-tocopherol are reduced during pregnancy and socio-demographic factors have mild effects on the plasma levels of these vitamins. (author)

Fast and sensitive HPLC/UV method for cefazolin quantification in plasma and subcutaneous tissue microdialysate of humans and rodents applied to pharmacokinetic studies in obese individuals.

Science.gov (United States)

Palma, Eduardo Celia; Laureano, João Victor; de Araújo, Bibiana Verlindo; Meinhardt, Nelson Guardiola; Stein, Airton Tetelbom; Dalla Costa, Teresa

2018-04-14

Antimicrobial prophylactic dosing of morbidly obese patients may differ from normal weighted individuals owing to alterations in drug tissue distribution. Drug subcutaneous tissue distribution can be investigated by microdialysis patients and animals. The need for cefazolin prophylactic dose adjustment in obese patients remains under discussion. The paper describes the validation of an HPLC-UV method for cefazolin quantification in plasma and microdialysate samples from clinical and pre-clinical studies. A C 18 column with an isocratic mobile phase was used for drug separation, with detection at 272 nm. Total and unbound cefazolin lower limit of quantitation was 5 μg/mL in human plasma, 2 μg/mL in rat plasma, and 0.5 and 0.025 μg/mL in human and rat microdialysate samples, respectively. The maximum intra- and inter-day imprecisions were 10.7 and 8.1%, respectively. The inaccuracy was <9.7%. The limit of quantitation imprecision and inaccuracy were < 15%. Cefazolin stability in the experimental conditions was confirmed. Cefazolin plasma concentrations and subcutaneous tissue penetration were determined by microdialysis in morbidly obese patients (2 g i.v. bolus) and diet-induced obese rats (30 mg/kg i.v. bolus) using the method. This method has the main advantages of easy plasma clean-up and practicability and has proven to be useful in cefazolin clinical and pre-clinical pharmacokinetic investigations. Copyright © 2018 John Wiley & Sons, Ltd.

Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

OpenAIRE

Koizume, Shiro; Miyagi, Yohei

2015-01-01

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are...

The influence of tethered epidermal growth factor on connective tissue progenitor colony formation

OpenAIRE

Marcantonio, Nicholas A.; Boehm, Cynthia A.; Rozic, Richard J.; Au, Ada; Wells, Alan; Muschler, George F.; Griffith, Linda G.

2009-01-01

Strategies to combine aspirated marrow cells with scaffolds to treat connective tissue defects are gaining increasing clinical attention and use. In situations such as large defects where initial survival and proliferation of transplanted connective tissue progenitors (CTPs) are limiting, therapeutic outcomes might be improved by using the scaffold to deliver growth factors that promote the early stages of cell function in the graft. Signaling by the epidermal growth factor receptor (EGFR) pl...

Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

DEFF Research Database (Denmark)

Sidelmann, Johannes Jakobsen; Skouby, Sven O.; Kluft, Cornelis

2011-01-01

progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P≤0.001). OC use increased FSAP antigen by 25% and FSAP activity......Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... by 59% (P0.05). The relative increase in FSAP activity was significantly higher in women carrying the 1601GG genotype (63%) than in women carrying 1601GA genotype (50%) (P=0.01) and was associated with an increased activation of FVII. In conclusion: OC use increases the plasma measures of FSAP...

Trefoil factors in saliva and gingival tissues of patients with chronic periodontitis

DEFF Research Database (Denmark)

Chaiyarit, Ponlatham; Chayasadom, Anek; Wara-Aswapati, Nawarat

2012-01-01

BACKGROUND: Trefoil factors (TFFs) are secreted molecules that are involved in cytoprotection against tissue damage and the immune response. TFFs have been detected in saliva and oral tissues, but their clinical significance has never been investigated in patients with chronic periodontitis....... The objective of this study is to determine whether TFF expression in saliva and gingival tissues is associated with periodontal pathology. METHODS: Saliva and gingival tissue samples were collected from 25 non-periodontitis individuals and 25 patients with chronic periodontitis (CP). Enzyme...... observed in patients with CP (P = 0.003 and P periodontal pathology and number of Porphyromonas gingivalis...

Cancer therapy using non-thermal atmospheric pressure plasma with ultra-high electron density

International Nuclear Information System (INIS)

Tanaka, Hiromasa; Mizuno, Masaaki; Toyokuni, Shinya; Maruyama, Shoichi; Kodera, Yasuhiro; Terasaki, Hiroko; Adachi, Tetsuo; Kato, Masashi; Kikkawa, Fumitaka; Hori, Masaru

2015-01-01

Cancer therapy using non-thermal atmospheric pressure plasma is a big challenge in plasma medicine. Reactive species generated from plasma are key factors for treating cancer cells, and thus, non-thermal atmospheric pressure plasma with high electron density has been developed and applied for cancer treatment. Various cancer cell lines have been treated with plasma, and non-thermal atmospheric plasma clearly has anti-tumor effects. Recent innovative studies suggest that plasma can both directly and indirectly affect cells and tissues, and this observation has widened the range of applications. Thus, cancer therapy using non-thermal atmospheric pressure plasma is promising. Animal experiments and understanding the mode of action are essential for clinical application in the future. A new academic field that combines plasma science, the biology of free radicals, and systems biology will be established

Cancer therapy using non-thermal atmospheric pressure plasma with ultra-high electron density

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Hiromasa [Institute of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan); Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550 (Japan); Mizuno, Masaaki [Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550 (Japan); Toyokuni, Shinya [Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550 (Japan); Maruyama, Shoichi [Department of Nephrology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550 (Japan); Kodera, Yasuhiro [Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550 (Japan); Terasaki, Hiroko [Department of Ophthalmology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550 (Japan); Adachi, Tetsuo [Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 501-1196 Gifu (Japan); Kato, Masashi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550 (Japan); Kikkawa, Fumitaka [Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550 (Japan); Hori, Masaru [Institute of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan)

2015-12-15

Cancer therapy using non-thermal atmospheric pressure plasma is a big challenge in plasma medicine. Reactive species generated from plasma are key factors for treating cancer cells, and thus, non-thermal atmospheric pressure plasma with high electron density has been developed and applied for cancer treatment. Various cancer cell lines have been treated with plasma, and non-thermal atmospheric plasma clearly has anti-tumor effects. Recent innovative studies suggest that plasma can both directly and indirectly affect cells and tissues, and this observation has widened the range of applications. Thus, cancer therapy using non-thermal atmospheric pressure plasma is promising. Animal experiments and understanding the mode of action are essential for clinical application in the future. A new academic field that combines plasma science, the biology of free radicals, and systems biology will be established.

Monte Carlo study of voxel S factor dependence on tissue density and atomic composition

Energy Technology Data Exchange (ETDEWEB)

Amato, Ernesto, E-mail: eamato@unime.it [University of Messina, Department of Biomedical Sciences and of Morphologic and Functional Imaging, Section of Radiological Sciences, via Consolare Valeria, 1, I-98125 Messina (Italy); Italiano, Antonio [INFN – Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Messina (Italy); Baldari, Sergio [University of Messina, Department of Biomedical Sciences and of Morphologic and Functional Imaging, Section of Radiological Sciences, via Consolare Valeria, 1, I-98125 Messina (Italy)

2013-11-21

Voxel dosimetry is a common approach to the internal dosimetry of non-uniform activity distributions in nuclear medicine therapies with radiopharmaceuticals and in the estimation of the radiation hazard due to internal contamination of radionuclides. Aim of the present work is to extend our analytical approach for the calculation of voxel S factors to materials different from the soft tissue. We used a Monte Carlo simulation in GEANT4 of a voxelized region of each material in which the source of monoenergetic electrons or photons was uniformly distributed within the central voxel, and the energy deposition was scored over the surrounding 11×11×11 voxels. Voxel S factors were obtained for the following standard ICRP materials: Adipose tissue, Bone cortical, Brain, Lung, Muscle skeletal and Tissue soft with 1 g cm{sup −3} density. Moreover, we considered the standard ICRU materials: Bone compact and Muscle striated. Voxel S factors were represented as a function of the “normalized radius”, defined as the ratio between the source–target voxel distance and the voxel side. We found that voxel S factors and related analytical fit functions are mainly affected by the tissue density, while the material composition gives only a slight contribution to the difference between data series, which is negligible for practical purposes. Our results can help in broadening the dosimetric three-dimensional approach based on voxel S factors to other tissues where diagnostic and therapeutic radionuclides can be taken up and radiation can propagate.

Monte Carlo study of voxel S factor dependence on tissue density and atomic composition

International Nuclear Information System (INIS)

Amato, Ernesto; Italiano, Antonio; Baldari, Sergio

2013-01-01

Voxel dosimetry is a common approach to the internal dosimetry of non-uniform activity distributions in nuclear medicine therapies with radiopharmaceuticals and in the estimation of the radiation hazard due to internal contamination of radionuclides. Aim of the present work is to extend our analytical approach for the calculation of voxel S factors to materials different from the soft tissue. We used a Monte Carlo simulation in GEANT4 of a voxelized region of each material in which the source of monoenergetic electrons or photons was uniformly distributed within the central voxel, and the energy deposition was scored over the surrounding 11×11×11 voxels. Voxel S factors were obtained for the following standard ICRP materials: Adipose tissue, Bone cortical, Brain, Lung, Muscle skeletal and Tissue soft with 1 g cm −3 density. Moreover, we considered the standard ICRU materials: Bone compact and Muscle striated. Voxel S factors were represented as a function of the “normalized radius”, defined as the ratio between the source–target voxel distance and the voxel side. We found that voxel S factors and related analytical fit functions are mainly affected by the tissue density, while the material composition gives only a slight contribution to the difference between data series, which is negligible for practical purposes. Our results can help in broadening the dosimetric three-dimensional approach based on voxel S factors to other tissues where diagnostic and therapeutic radionuclides can be taken up and radiation can propagate

Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR)

DEFF Research Database (Denmark)

Christensen, Anders; Kiss, Katalin; Lelkaitis, Giedrius

2017-01-01

Background: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhib...... with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer....

Synergistic and additive effects of hydrostatic pressure and growth factors on tissue formation.

Directory of Open Access Journals (Sweden)

Benjamin D Elder

2008-06-01

Full Text Available Hydrostatic pressure (HP is a significant factor in the function of many tissues, including cartilage, knee meniscus, temporomandibular joint disc, intervertebral disc, bone, bladder, and vasculature. Though studies have been performed in assessing the role of HP in tissue biochemistry, to the best of our knowledge, no studies have demonstrated enhanced mechanical properties from HP application in any tissue.The objective of this study was to determine the effects of hydrostatic pressure (HP, with and without growth factors, on the biomechanical and biochemical properties of engineered articular cartilage constructs, using a two-phased approach. In phase I, a 3x3 full-factorial design of HP magnitude (1, 5, 10 MPa and frequency (0, 0.1, 1 Hz was used, and the best two treatments were selected for use in phase II. Static HP at 5 MPa and 10 MPa resulted in significant 95% and 96% increases, respectively, in aggregate modulus (H(A, with corresponding increases in GAG content. These regimens also resulted in significant 101% and 92% increases in Young's modulus (E(Y, with corresponding increases in collagen content. Phase II employed a 3x3 full-factorial design of HP (no HP, 5 MPa static, 10 MPa static and growth factor application (no GF, BMP-2+IGF-I, TGF-beta1. The combination of 10 MPa static HP and TGF-beta1 treatment had an additive effect on both H(A and E(Y, as well as a synergistic effect on collagen content. This group demonstrated a 164% increase in H(A, a 231% increase in E(Y, an 85% increase in GAG/wet weight (WW, and a 173% increase in collagen/WW, relative to control.To our knowledge, this is the first study to demonstrate increases in the biomechanical properties of tissue from pure HP application, using a cartilage model. Furthermore, it is the only study to demonstrate additive or synergistic effects between HP and growth factors on tissue functional properties. These findings are exciting as coupling HP stimulation with growth

Combinatorial regulation of tissue specification by GATA and FOG factors

Science.gov (United States)

Chlon, Timothy M.; Crispino, John D.

2012-01-01

The development of complex organisms requires the formation of diverse cell types from common stem and progenitor cells. GATA family transcriptional regulators and their dedicated co-factors, termed Friend of GATA (FOG) proteins, control cell fate and differentiation in multiple tissue types from Drosophila to man. FOGs can both facilitate and antagonize GATA factor transcriptional regulation depending on the factor, cell, and even the specific gene target. In this review, we highlight recent studies that have elucidated mechanisms by which FOGs regulate GATA factor function and discuss how these factors use these diverse modes of gene regulation to control cell lineage specification throughout metazoans. PMID:23048181

Deep-Dive Targeted Quantification for Ultrasensitive Analysis of Proteins in Nondepleted Human Blood Plasma/Serum and Tissues

Energy Technology Data Exchange (ETDEWEB)

Nie, Song [Biological Sciences Division; Shi, Tujin [Biological Sciences Division; Fillmore, Thomas L. [Biological Sciences Division; Schepmoes, Athena A. [Biological Sciences Division; Brewer, Heather [Biological Sciences Division; Gao, Yuqian [Biological Sciences Division; Song, Ehwang [Biological Sciences Division; Wang, Hui [Biological Sciences Division; Rodland, Karin D. [Biological Sciences Division; Qian, Wei-Jun [Biological Sciences Division; Smith, Richard D. [Biological Sciences Division; Liu, Tao [Biological Sciences Division

2017-08-11

Mass spectrometry-based targeted proteomics (e.g., selected reaction monitoring, SRM) is emerging as an attractive alternative to immunoassays for protein quantification. Recently we have made significant progress in SRM sensitivity for enabling quantification of low ng/mL to sub-ng/mL level proteins in nondepleted human blood plasma/serum without affinity enrichment. However, precise quantification of extremely low abundant but biologically important proteins (e.g., ≤100 pg/mL in blood plasma/serum) using targeted proteomics approaches still remains challenging. To address this need, we have developed an antibody-independent Deep-Dive SRM (DD-SRM) approach that capitalizes on multidimensional high-resolution reversed-phase liquid chromatography (LC) separation for target peptide enrichment combined with precise selection of target peptide fractions of interest, significantly improving SRM sensitivity by ~5 orders of magnitude when compared to conventional LC-SRM. Application of DD-SRM to human serum and tissue has been demonstrated to enable precise quantification of endogenous proteins at ~10 pg/mL level in nondepleted serum and at <10 copies per cell level in tissue. Thus, DD-SRM holds great promise for precisely measuring extremely low abundance proteins or protein modifications, especially when high-quality antibody is not available.

Tissue Factor and Thrombin in Sickle Cell Anemia

OpenAIRE

Chantrathammachart, Pichika; Pawlinski, Rafal

2012-01-01

Sickle cell anemia is an inherited hematologic disorder associated with hemolytic and vaso-occlusive complications. An activation of coagulation is also a prominent feature of sickle cell anemia. Growing evidence indicates that coagulation may contribute to the inflammation and vascular injury in sickle cell anemia. This review focuses on tissue factor expression and its contribution to the activation of coagulation, thrombosis and vascular inflammation in sickle cell anemia.

Plasma and adipose tissue level of angiopoietin-like 7 (ANGPTL7) are increased in obesity and reduced after physical exercise.

Science.gov (United States)

Abu-Farha, Mohamed; Cherian, Preethi; Al-Khairi, Irina; Madhu, Dhanya; Tiss, Ali; Warsam, Samia; Alhubail, Asma; Sriraman, Devarajan; Al-Refaei, Faisal; Abubaker, Jehad

2017-01-01

ANGPTL7 is a member of the Angiopoietin-like (ANGPTL) protein family that is composed of eight proteins (1-8). Increasing evidence is associating ANGPTL proteins to obesity and insulin resistance. The biological role of ANGPTL7 is yet to be understood except for a recently proposed role in the pathophysiology of glaucoma. This study was designed to shed light on the function of ANGPTL7 in obesity and its modulation by physical exercise as well as its potential association with lipid profile. A total of 144 subjects were enrolled in this study and finished three months of physical exercise. The participants were classified based on their BMI, 82 subjects were non-obese and 62 obese. ANGPTL7 levels in plasma and adipose tissue were measured by ELISA, RT-PCR and immunohistochemistry. In this study, we showed that ANGPTL7 level was increased in the plasma of obese subjects (1249.05± 130.39 pg/mL) as compared to non-obese (930.34 ± 87.27 pg/mL) (p-Value = 0.032). ANGPTL7 Gene and protein expression levels in adipose tissue also showed over two fold increase. Physical exercise reduced circulating level of ANGPTL7 in the obese subjects to 740.98± 127.18 pg/mL, (p-Value = 0.007). ANGPTL7 expression in adipose tissue was also reduced after exercise. Finally, ANGPTL7 circulating level showed significant association with TG level in the obese subjects (R2 = 0.183, p-Value = 0.03). In conclusion, our data shows for the first time that obesity increases the level of ANGPTL7 in both plasma and adipose tissue. Increased expression of ANGPTL7 might play a minor role in the regulation of TG level in obese subjects either directly or through interaction with other ANGPTL protein members. Physical exercise reduced the level of ANGPTL7 highlighting the potential for targeting this protein as a therapeutic target for regulating dyslipidemia.

Dynamic changes in plasma tissue plasminogen activator, plasminogen activator inhibitor-1 and beta-thromboglobulin content in ischemic stroke.

Science.gov (United States)

Zhuang, Ping; Wo, Da; Xu, Zeng-Guang; Wei, Wei; Mao, Hui-ming

2015-07-01

The aim of this paper is to investigate the corresponding variations of plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities, and beta-thromboglobulin (β-TG) content in patients during different stages of ischemic stroke. Ischemic stroke is a common disease among aging people and its occurrence is associated with abnormalities in the fibrinolytic system and platelet function. However, few reports focus on the dynamic changes in the plasma fibrinolytic system and β-TG content in patients with ischemic stroke. Patients were divided into three groups: acute, convalescent and chronic. Plasma t-PA and PAI-1 activities were determined by chromogenic substrate analysis and plasma β-TG content was detected by radioimmunoassay. Patients in the acute stage of ischemic stroke had significantly increased levels of t-PA activity and β-TG content, but PAI-1 activity was significantly decreased. Negative correlations were found between plasma t-PA and PAI-1 activities and between plasma t-PA activity and β-TG content in patients with acute ischemic stroke. There were significant differences in plasma t-PA and PAI-1 activities in the aged control group, as well as in the acute, convalescent and chronic groups. It can be speculated that the increased activity of t-PA in patients during the acute stage was the result of compensatory function, and that the increase in plasma β-TG level not only implies the presence of ischemic stroke but is likely a cause of ischemic stroke. During the later stages of ischemic stroke, greater attention is required in monitoring levels of PAI-1. Copyright © 2015 Elsevier Ltd. All rights reserved.

Determination of 6258-70, a new semi-synthetic taxane, in rat plasma and tissues: Application to the pharmacokinetics and tissue distribution study

Directory of Open Access Journals (Sweden)

Simin Zhao

2016-08-01

Full Text Available Cancer is the leading cause of death all over the world. Among the chemotherapy drugs, taxanes play an important role in cancer treatment. 6258-70 is a new semi-synthetic taxane which has a broad spectrum of antitumor activity. A fast and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS method was developed for quantification of 6258-70 in rat plasma and tissues in this paper. After extraction by liquid-liquid extraction method with methyl tert-butyl ether, the samples were separated on a Kinetex C18 column (50 mm×2.1 mm, 2.6 µm, Phenomenex, USA within 3 min. The method was fully validated with the matrix effect between 87.7% and 99.5% and the recovery ranging from 80.3% to 90.1%. The intra- and inter-day precisions were less than 9.5% and the accuracy ranged from −3.8% to 6.5%. The reliable method was successfully applied to the pharmacokinetics and tissue distribution studies of 6258-70 after intravenous administration in rats. The pharmacokinetic results indicated that the pharmacokinetic behavior of 6258-70 in rats was in accordance with linear features within tested dosage of 1 to 4 mg/kg, and there was no significant difference between the two genders. The tissue distribution study showed that 6258-70 had an effective penetration, spread widely and rapidly and could cross blood-brain barrier. The results of pharmacokinetics and tissue distribution may provide a guide for future study.

Platelet concentration of plateletrich plasma from dogs, obtained through three centrifugation speeds

Directory of Open Access Journals (Sweden)

Vanessa Couto de Magalhães Ferraz

2007-12-01

Full Text Available The platelets release at least 4 growth factors (Platelet Derived Growth Factor. ²1 and ²2 Transforming Growth Factors and Insulin-like Growth Factor which are responsible for the migration and activation of cells that will start the reparation of soft tissues and bones. The Platelet Rich Plasma is an autogenous source for Growth Factors, obtained by platelet concentration by centrifuging total blood. This study aimed the comparison of platelet concentrations in plasma centrifuged in three different centrifugation speeds (1300, 1600 e 3200rpm, for the production of platelet rich plasma. Blood was drowned from 15 dogs, 40ml of each, and these were divided into four groups and centrifuged at 800rpm. Then the first group was centrifuged at 1300rpm, the second at 1600rpm, the third at 3200rpm and the last was used as control, named plasma. The mean percentage increase in the platelet concentration for each technique was: 1300 - 183%, 1600 - 210% and 3200 - 222%. But in centrifugation at 3200 rpm, platelets presented altered morphology and different sizes in every sample studied, which was understood as severe cell damage. It was concluded that the best technique for the preparation of the platelet rich plasma in dogs consisted of the previous centrifugation of the blood at 800rpm for ten minutes, and then the plasma should be separated. This plasma is then submitted to a second centrifugation of 1600rpm for 10 minutes, and the platelet poor plasma is separated and discharged.

Plasma Ceramides as Prognostic Biomarkers and Their Arterial and Myocardial Tissue Correlates in Acute Myocardial Infarction

Directory of Open Access Journals (Sweden)

Leonardo P. de Carvalho, MD, PhD

2018-04-01

Full Text Available Summary: We identified a plasma signature of 11 C14 to C26 ceramides and 1 C16 dihydroceramide predictive of major adverse cardiovascular events in patients with acute myocardial infarction (AMI. Among patients undergoing coronary artery bypass surgery, those with recent AMI, compared with those without recent AMI, showed a significant increase in 5 of the signature’s 12 ceramides in plasma but not simultaneously-biopsied aortic tissue. In contrast, a rat AMI model, compared with sham control, showed a significant increase in myocardial concentrations of all 12 ceramides and up-regulation of 3 ceramide-producing enzymes, suggesting ischemic myocardium as a possible source of this ceramide signature. Key Words: acute coronary syndrome, ceramides, dihydroceramides, major adverse cardiovascular and cerebrovascular events, prognosis, risk prediction

Proteomic Changes of Tissue-Tolerable Plasma Treated Airway Epithelial Cells and Their Relation to Wound Healing.

Science.gov (United States)

Lendeckel, Derik; Eymann, Christine; Emicke, Philipp; Daeschlein, Georg; Darm, Katrin; O'Neil, Serena; Beule, Achim G; von Woedtke, Thomas; Völker, Uwe; Weltmann, Klaus-Dieter; Jünger, Michael; Hosemann, Werner; Scharf, Christian

2015-01-01

The worldwide increasing number of patients suffering from nonhealing wounds requires the development of new safe strategies for wound repair. Recent studies suggest the possibility of nonthermal (cold) plasma application for the acceleration of wound closure. An in vitro wound healing model with upper airway S9 epithelial cells was established to determine the macroscopically optimal dosage of tissue-tolerable plasma (TTP) for wound regeneration, while a 2D-difference gel electrophoresis (2D-DIGE) approach was used to quantify the proteomic changes in a hypothesis-free manner and to evaluate the balance of beneficial and adverse effects due to TTP application. Plasma doses from 30 s up to 360 s were tested in relation to wound closure after 24 h, 48 h, 72 h, 96 h, and 120 h, in which lower doses (30, 60, and 120 s) resulted in dose-dependent improved wound healing rate compared to untreated cells. Thereby, the 120 s dose caused significantly the best wound healing properties after 96 and 120 h. The proteome analysis combined with IPA revealed that a lot of affected stress adaptation responses are linked to oxidative stress response emphasizing oxidative stress as a possible key event in the regeneration process of epithelial cells as well as in the adaptation to plasma exposure. Further cellular and molecular functions like proliferation and apoptosis were significantly up- or downregulated by all TTP treatments but mostly by the 120 s dose. For the first time, we were able to show plasma effects on cellular adaptation of upper airway epithelial S9 cells improving wound healing. This is of particular interest for plasma application, for example, in the surgery field of otorhinolaryngology or internal medicine.

The development and application of a cold atmospheric plasma generator for treatment of skin and soft-tissue injuries in animals

Science.gov (United States)

Emelyanov, O. A.; Petrova, N. O.; Smirnova, N. V.; Shemet, M. V.

2017-08-01

We describe a device for obtaining cold plasma in air at atmospheric pressure using a system of positive high-voltage pin electrodes, which is intended for the treatment of skin and soft-tissue injuries in animals. Plasma is generated due to the development of periodic pulsed discharge of nanosecond duration at current pulse amplitudes 10-20 mA, characteristic frequencies 10-20 kHz, and applied voltages within 8-10 kV. The high efficacy of the proposed device and method is confirmed by the good clinical results of treating large domestic animals with traumatic injuries.

Risk factors for pedicled flap necrosis in hand soft tissue reconstruction: a multivariate logistic regression analysis.

Science.gov (United States)

Gong, Xu; Cui, Jianli; Jiang, Ziping; Lu, Laijin; Li, Xiucun

2018-03-01

Few clinical retrospective studies have reported the risk factors of pedicled flap necrosis in hand soft tissue reconstruction. The aim of this study was to identify non-technical risk factors associated with pedicled flap perioperative necrosis in hand soft tissue reconstruction via a multivariate logistic regression analysis. For patients with hand soft tissue reconstruction, we carefully reviewed hospital records and identified 163 patients who met the inclusion criteria. The characteristics of these patients, flap transfer procedures and postoperative complications were recorded. Eleven predictors were identified. The correlations between pedicled flap necrosis and risk factors were analysed using a logistic regression model. Of 163 skin flaps, 125 flaps survived completely without any complications. The pedicled flap necrosis rate in hands was 11.04%, which included partial flap necrosis (7.36%) and total flap necrosis (3.68%). Soft tissue defects in fingers were noted in 68.10% of all cases. The logistic regression analysis indicated that the soft tissue defect site (P = 0.046, odds ratio (OR) = 0.079, confidence interval (CI) (0.006, 0.959)), flap size (P = 0.020, OR = 1.024, CI (1.004, 1.045)) and postoperative wound infection (P < 0.001, OR = 17.407, CI (3.821, 79.303)) were statistically significant risk factors for pedicled flap necrosis of the hand. Soft tissue defect site, flap size and postoperative wound infection were risk factors associated with pedicled flap necrosis in hand soft tissue defect reconstruction. © 2017 Royal Australasian College of Surgeons.

Implementation of a more physiological plasma rich in growth factor (PRGF) protocol: Anticoagulant removal and reduction in activator concentration.

Science.gov (United States)

Anitua, Eduardo; Prado, Roberto; Troya, María; Zalduendo, Mar; de la Fuente, María; Pino, Ander; Muruzabal, Francisco; Orive, Gorka

2016-07-01

Plasma rich in growth factors (PRGF) is a biological therapy that uses patient's own growth factors for promoting tissue regeneration. Given the current European regulatory framework in which anticoagulant solution in blood extraction tubes could be considered as a medicinal product, a new PRGF protocol has been developed. The actual protocol (PRGF-A) and the new one (PRGF-B) have been performed and compared under Good Laboratory Practices. PRGF-A protocol uses extraction tubes with 0.9 mL of trisodium citrate as anticoagulant and 50 μL of calcium chloride/mL PRGF to activate it. The PRGF-B reduces the amount of sodium citrate and calcium chloride to 0.4 mL and to 20 μL, respectively. Basic hematological parameters, platelet function, the scaffold obtaining process, growth factors content, and the biological effect were compared between both PRGF obtaining protocols. PRGF-B protocol led to a statistically significant higher enrichment and recovery of platelets regarding to the PRGF-A. Hypotonic stress response by platelets was significantly better in the new protocol. A statistically significant decrease in the basal platelet activation status of PRGF-B compared to PRGF-A was also observed. The duration of the lag phase in the platelet aggregation assay was statistically lower for the PRGF-B protocol. Both the clotting and the clot retraction time were significantly reduced in the B protocol. A higher growth factor concentration was detected in the plasma obtained using the PRGF-B protocol. The new PRGF obtaining protocol, with a reduction in the amount of anticoagulant and activator, has even improved the actual one.

A system model of the effects of exercise on plasma Interleukin-6 dynamics in healthy individuals: Role of skeletal muscle and adipose tissue.

Science.gov (United States)

Morettini, Micaela; Palumbo, Maria Concetta; Sacchetti, Massimo; Castiglione, Filippo; Mazzà, Claudia

2017-01-01

Interleukin-6 (IL-6) has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution. This study aimed at developing and validating a system model of exercise's effects on plasma IL-6 dynamics in healthy humans, combining the contributions of both adipose tissue and skeletal muscle. A two-compartment description was adopted to model plasma IL-6 changes in response to oxygen uptake's variation during an exercise bout. The free parameters of the model were estimated by means of a cross-validation procedure performed on four different datasets. A low coefficient of variation (dynamics during exercise and post-exercise were consistent with literature data from exercise protocols differing in intensity, duration and modality. The model successfully emulated the physiological effects of exercise on plasma IL-6 levels and provided a reliable description of the role of skeletal muscle and adipose tissue on the dynamics of plasma IL-6. The system model here proposed is suitable to simulate IL-6 response to different exercise modalities. Its future integration with existing models of GLP-1-induced insulin secretion might provide a more reliable description of exercise's effects on glucose homeostasis and hence support the definition of more tailored interventions for the treatment of type 2 diabetes.

Plasma-Modified and Polyethylene Glycol-Grafted Polymers for Potential Tissue Engineering Applications

Czech Academy of Sciences Publication Activity Database

Švorčík, V.; Makajová, Z.; Kasálková-Slepičková, N.; Kolská, Z.; Bačáková, Lucie

2012-01-01

Roč. 12, č. 8 (2012), s. 6665-6671 ISSN 1533-4880 R&D Projects: GA ČR(CZ) GAP108/10/1106; GA AV ČR(CZ) KAN400480701 Grant - others:GA AV ČR(CZ) KAN200100801 Program:KA Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : polymers * plasma treatment * cells adhesion and proliferation Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.149, year: 2012

Plasma IGF-1 and IGFBP-3 may be imprecise surrogates for breast concentrations: an analysis of healthy women

Science.gov (United States)

Llanos, Adana A.; Brasky, Theodore M.; Dumitrescu, Ramona G.; Marian, Catalin; Makambi, Kepher H.; Kallakury, Bhaskar V. S.; Spear, Scott L.; Perry, David J.; Convit, Rafael J.; Platek, Mary E.; Adams-Campbell, Lucile L.; Freudenheim, Jo L.; Shields, Peter G.

2013-01-01

We investigated insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 concentrations in histologically normal breast tissues and assessed their association with plasma concentrations, and breast cancer risk factors. IGF-1 and IGFBP-3 were assessed in plasma and breast tissues of 90 women with no history of any cancer and undergoing reduction mammoplasty. Pearson correlations and ANOVAs were used to describe plasma-breast associations and biomarker differences by breast cancer risk factors, respectively. Multivariable regression models were used to determine associations between risk factors, and breast IGF-1 and IGFBP-3. The mean age of the study sample was 37.3 years, 58 % were white, and generally these women were obese (mean BMI = 30.8 kg/m2). We observed no plasma-breast correlation for IGF-1, IGFBP-3, or IGF-1/IGFBP-3 (r = −0.08, r = 0.14, and r = 0.03, respectively; p-values >0.05). Through age- and BMI-adjusted analysis, BMI and years of oral contraceptive (OC) use were inversely associated with breast IGF-1 (p-values = 0.02 and 0.003, respectively) and age was associated with breast IGFBP-3 (p = 0.01), while breast IGF-1/IGFBP-3 was higher in blacks than whites (1.08 vs. 0.68, p = 0.04) and associated with age and BMI (p-values = 0.03 and 0.002, respectively). In multivariable-adjusted models, some breast cancer risk factors studied herein explained 24, 10, and 15 % of the variation in breast IGF-1, IGFBP-3, and IGF-1/IGFBP-3, respectively. While reasons for the lack of plasma-breast hormone correlations in these cancer-free women are unknown, several factors were shown to be associated with breast concentrations. The lack of correlation between blood and tissue IGF-1 and IGFBP-3 suggests that studies of breast cancer risk assessing blood IGF-1 and IGFBP-3 may have important limitations in understanding their role in breast carcinogenesis. PMID:23456194

Increased uncoupling protein-2 mRNA abundance and glucocorticoid action in adipose tissue in the sheep fetus during late gestation is dependent on plasma cortisol and triiodothyronine

Science.gov (United States)

Gnanalingham, MG; Mostyn, A; Forhead, AJ; Fowden, AL; Symonds, ME; Stephenson, T

2005-01-01

The endocrine regulation of uncoupling protein-2 (UCP2), an inner mitochondrial protein, in fetal adipose tissue remains unclear. The present study aimed to determine if fetal plasma cortisol and triiodothyronine (T3) influenced the mRNA abundance of UCP2, glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 2 (11βHSD2) in fetal adipose tissue in the sheep during late gestation. Perirenal–abdominal adipose tissue was sampled from ovine fetuses to which either cortisol (2–3 mg kg−1 day−1) or saline was infused for 5 days up to 127–130 days gestation, or near term fetuses (i.e. 142–145 days gestation) that were either adrenalectomised (AX) or remained intact. Fetal plasma cortisol and T3 concentrations were higher in the cortisol infused animals and lower in AX fetuses compared with their corresponding control group, and increased with gestational age. UCP2 and GR mRNA abundance were significantly lower in AX fetuses compared with age-matched controls, and increased with gestational age and by cortisol infusion. Glucocorticoid action in fetal adipose tissue was augmented by AX and suppressed by cortisol infusion, the latter also preventing the gestational increase in 11βHSD1 mRNA and decrease in 11βHSD2 mRNA. When all treatment groups were combined, both fetal plasma cortisol and T3 concentrations were positively correlated with UCP2, GR and 11βHSD2 mRNA abundance, but negatively correlated with 11βHSD1 mRNA abundance. In conclusion, plasma cortisol and T3 are both required for the late gestation rise in UCP2 mRNA and differentially regulate glucocorticoid action in fetal adipose tissue in the sheep during late gestation. PMID:15961419

A strategy for extending the applicability of a validated plasma calibration curve to quantitative measurements in multiple tissue homogenate samples: a case study from a rat tissue distribution study of JI-101, a triple kinase inhibitor.

Science.gov (United States)

Gurav, Sandip Dhondiram; Jeniffer, Sherine; Punde, Ravindra; Gilibili, Ravindranath Reddy; Giri, Sanjeev; Srinivas, Nuggehally R; Mullangi, Ramesh

2012-04-01

A general practice in bioanalysis is that, whatever the biological matrix the analyte is being quantified in, the validation is performed in the same matrix as per regulatory guidelines. In this paper, we are presenting the applicability of a validated LC-MS/MS method in rat plasma for JI-101, to estimate the concentrations of JI-101 in various tissues that were harvested in a rat tissue distribution study. A simple protein precipitation technique was used to extract JI-101 and internal standard from the tissue homogenates. The recovery of JI-101 in all the matrices was found to be >70%. Chromatographic separation was achieved using a binary gradient using mobile phase A (acetonitrile) and B (0.2% formic acid in water) at a flow rate of 0.30 mL/min on a Prodigy ODS column with a total run time of 4.0 min. The MS/MS ion transitions monitored were 466.1 → 265 for JI-101 and 180.1 → 110.1 for internal standard. The linearity range was 5.02-4017 ng/mL. The JI-101 levels were quantifiable in the various tissue samples harvested in this study. Therefore, the use of a previously validated JI-101 assay in plasma circumvented the tedious process of method development/validation in various tissue matrices. Copyright © 2011 John Wiley & Sons, Ltd.

The effects of plasma rich in growth factors (PRGF-Endoret) on healing of medial collateral ligament of the knee.

Science.gov (United States)

Yoshioka, Tomokazu; Kanamori, Akihiro; Washio, Toshikatsu; Aoto, Katsuya; Uemura, Kenta; Sakane, Masataka; Ochiai, Naoyuki

2013-08-01

Platelet-rich plasma (PRP) has been increasingly used in sports-related injuries for therapeutic applications. However, there are numerous manufacturing procedures and treatment protocols of PRP use, which make difficult to assess its real efficacy for tissue healing. This study addressed to evaluate the therapeutic effects of locally delivered plasma rich in growth factors (PRGF-Endoret) on the early healing of medial collateral ligament (MCL) in rabbit knees. Thirty-one Japanese white rabbits were subjected to a mop-end tear in the MCL of the left knee. PRGF-Endoret was prepared using Anitua's technique. Two groups were set up. In 17 knees, prepared 1.0 ml of PRGF-Endoret after clotting was applied on the tear site, while in 14 knees the tear site was untreated serving as a control. Quantitative aspects of PRGF-Endoret, the concentration of platelets, leukocytes and erythrocytes and therapeutic growth factors such as PDGF-BB and TGF-β1 were measured. Rabbits were sacrificed at 3 and 6 weeks after the operation and histological and biomechanical evaluation were performed. No leukocytes were measured and certain amount of growth factors such as PDGF-BB and TGF-β1 were confirmed in the PRGF-Endoret. PRGF-Endoret stimulated proliferation of fibroblasts and neovascularization, and induced statistically better structural properties in repaired MCL. Our findings provide evidence that local administration of PRGF-Endoret promotes early steps in ligament healing and the repair of structural properties in a rabbit model. PRGF-Endoret would be a useful product in clinical treatment of ligament injuries.

A key inactivation factor of HeLa cell viability by a plasma flow

Energy Technology Data Exchange (ETDEWEB)

Sato, Takehiko; Yokoyama, Mayo [Institute of Fluid Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Johkura, Kohei, E-mail: sato@ifs.tohoku.ac.jp [Department of Histology and Embryology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621 (Japan)

2011-09-21

Recently, a plasma flow has been applied to medical treatment using effects of various kinds of stimuli such as chemical species, charged particles, heat, light, shock wave and electric fields. Among them, the chemical species are known to cause an inactivation of cell viability. However, the mechanisms and key factors of this event are not yet clear. In this study, we focused on the effect of H{sub 2}O{sub 2} in plasma-treated culture medium because it is generated in the culture medium and it is also chemically stable compared with free radicals generated by the plasma flow. To elucidate the significance of H{sub 2}O{sub 2}, we assessed the differences in the effects of plasma-treated medium and H{sub 2}O{sub 2}-added medium against inactivation of HeLa cell viability. These two media showed comparable effects on HeLa cells in terms of the survival ratios, morphological features of damage processes, permeations of H{sub 2}O{sub 2} into the cells, response to H{sub 2}O{sub 2} decomposition by catalase and comprehensive gene expression. The results supported that among chemical species generated in a plasma-treated culture medium, H{sub 2}O{sub 2} is one of the main factors responsible for inactivation of HeLa cell viability. (fast track communication)

Effects of molecular size and chemical factor on plasma gene transfection

Science.gov (United States)

Ikeda, Yoshihisa; Motomura, Hideki; Kido, Yugo; Satoh, Susumu; Jinno, Masafumi

2016-07-01

In order to clarify the mechanism of plasma gene transfection, the relationship between transfection efficiency and transferred molecular size was investigated. Molecules with low molecular mass (less than 50 kDa; dye or dye-labeled oligonucleotide) and high molecular mass (more than 1 MDa; plasmid DNA or fragment of plasmid DNA) were transferred to L-929 cells. It was found that the transfection efficiency decreases with increasing in transferred molecular size and also depends on the tertiary structure of transferred molecules. Moreover, it was suggested the transfection mechanism is different between the molecules with low (less than 50 kDa) and high molecular mass (higher than 1 MDa). For the amount of gene transfection after plasma irradiation, which is comparable to that during plasma irradiation, it is shown that H2O2 molecules are the main contributor. The transfection efficiency decreased to 0.40 ± 0.22 upon scavenging the H2O2 generated by plasma irradiation using the catalase. On the other hand, when the H2O2 solution is dropped into the cell suspension without plasma irradiation, the transfection efficiency is almost 0%. In these results, it is also suggested that there is a synergetic effect of H2O2 with electrical factors or other reactive species generated by plasma irradiation.

Investigation of the differentiation of ex vivo nerve and fat tissues using laser-induced breakdown spectroscopy (LIBS): Prospects for tissue-specific laser surgery.

Science.gov (United States)

Mehari, Fanuel; Rohde, Maximillian; Kanawade, Rajesh; Knipfer, Christian; Adler, Werner; Klämpfl, Florian; Stelzle, Florian; Schmidt, Michael

2016-10-01

In the present study, the elemental compositions of fat and nerve tissue during their plasma mediated laser ablation are studied in the context of tissue differentiation for laser surgery applications by using Laser-Induced Breakdown Spectroscopy (LIBS). Tissue samples of porcine fat and nerve were prepared as ex vivo experimental objects. Plasma mediated laser ablation is performed using an Nd : YAG laser in open air and under normal stray light conditions. The performed measurements suggest that the two tissue types show a high similarity in terms of qualitative elemental composition while at the same time revealing a distinct difference in the concentration of the constituent elements. Different analysis approaches are evaluated and discussed to optimize the tissue-differentiation performance of the LIBS approach. Plasma mediated laser tissue ablation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

H+-ATPase activity from storage tissue of Beta vulgaris. IV. N,N'-dicyclohexylcarbodiimide binding and inhibition of the plasma membrane H+-ATPase

International Nuclear Information System (INIS)

Oleski, N.A.; Bennett, A.B.

1987-01-01

The molecular weight and isoelectric point of the plasma membrane H + -ATPase from red beet storage tissue were determined using N,N'-dicyclohexylcarbodiimide (DCCD) and a H + -ATPase antibody. When plasma membrane vesicles were incubated with 20 micromolar [ 14 C]-DCCD at 0 0 C, a single 97,000 dalton protein was visualized on a fluorography of a sodium dodecyl sulfate polyacrylamide gel. A close correlation between [ 14 C]DCCD labeling of the 97,000 dalton protein and the extent of ATPase inhibition over a range of DCCD concentration suggests that this 97,000 dalton protein is a component of the plasma membrane H + -ATPase. An antibody raised against the plasma membrane H + -ATPase of Neurospora crassa cross-reacted with the 97,000 dalton DCCD-binding protein, further supporting the identity of this protein. Immunoblots of two-dimensional gels of red beet plasma membrane vesicles indicated the isoelectric point of the H + -ATPase to be 6.5

Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer.

Science.gov (United States)

Cui, X Y; Tinholt, M; Stavik, B; Dahm, A E A; Kanse, S; Jin, Y; Seidl, S; Sahlberg, K K; Iversen, N; Skretting, G; Sandset, P M

2016-02-01

ESSENTIALS: A hypoxic microenvironment is a common feature of tumors that may influence activation of coagulation. MCF-7 and SK-BR-3 breast cancer cells and breast cancer tissue samples were used. The results showed transcriptional repression of tissue factor pathway inhibitor expression in hypoxia. Hypoxia-inducible factor 1α may be a target for the therapy of cancer-related coagulation and thrombosis. Activation of coagulation is a common finding in patients with cancer, and is associated with an increased risk of venous thrombosis. As a hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia-inducible factor (HIF)-1α in breast cancer cells and their correlation in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. Time-dependent and dose-dependent downregulation of TFPI mRNA (quantitative RT-PCR) and of free TFPI protein (ELISA) were observed in hypoxia. Western blotting showed parallel increases in the levels of HIF-1α protein and TF. HIF-1α inhibitor abolished or attenuated the hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and HIF-1α overexpression caused strong repression of TFPI promoter activity. Subsequent chromatin immunoprecipitation and mutagenesis analysis demonstrated a functional hypoxia response element within the TFPI promoter, located at -1065 to -1060 relative to the transcriptional start point. In breast cancer tissue samples, gene expression analyses showed a positive correlation between the mRNA expression of TFPI and that of HIF-1α. This study demonstrates that HIF-1α is involved in the transcriptional regulation of the TFPI gene, and suggests that a hypoxic microenvironment inside a breast tumor may

Dissociation between plasma concentrations of thyroxine and insulin-like growth factor-I.

Science.gov (United States)

Dauncey, M J; Morovat, A; Rudd, B T; Shakespear, R A

1990-09-01

The relation between plasma concentrations of thyroxine (T4) and insulin-like growth factor-I (IGF-I) has been examined in young, growing pigs under controlled conditions of energy intake. Compared with euthyroid controls, plasma levels of IGF-I were significantly elevated (P less than 0.005) both in hypothyroid animals on the same food intake and in hyperthyroid animals on double the food intake. There was however no increase in IGF-I in a hyperthyroid group on the control level of intake. Contrary to previous reports in which energy intake was not controlled, it is concluded that there is no simple correlation between plasma concentrations of T4 and IGF-I.

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions.

Science.gov (United States)

Zhang, Dong-Mei; Jiao, Rui-Qing; Kong, Ling-Dong

2017-03-29

High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

Directory of Open Access Journals (Sweden)

Dong-Mei Zhang

2017-03-01

Full Text Available High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2 and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG, free fatty acid (FFA, uric acid (UA and methylglyoxal (MG. Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

A validated UPLC-MS/MS method for the analysis of linezolid and a novel oxazolidinone derivative (PH027) in plasma and its application to tissue distribution study in rabbits.

Science.gov (United States)

Hedaya, Mohsen A; Thomas, Vidhya; Abdel-Hamid, Mohamed E; Kehinde, Elijah O; Phillips, Oludotun A

2017-01-01

Linezolid is the first approved oxazolidinone antibacterial agent, whereas PH027 is a novel compound of the same class that exhibits good in vitro antibacterial activity. The objective of this study was to develop an UPLC-MS/MS assay for the analysis of linezolid and PH027 in plasma and to apply the method for comparative pharmacokinetic and tissue distribution studies of both compounds. Plasma samples and calibrators were extracted with diethyl ether after addition of the internal standard solution. After evaporation of the ether layer, the residue was reconstituted in mobile phase and injected into UPLC-MS/MS. The mobile phase consisted of 2mM ammonium acetate buffer solution and acetonitrile (70:30) at a flow rate of 0.2ml/min. Separation was achieved using UPLC BEH C 18 column, and quantitative determination of the analytes was performed using multiple-reaction monitoring (MRM) scanning mode. The method was validated by analyzing quality control tissue homogenate samples, and was applied to analyze tissue homogenate samples obtained following IV injections of linezolid and PH027 in rabbits. The developed UPLC-MS/MS method was linear in the concentration range of 50-5000ng/ml. Validation of the method proved that the method's precision, selectivity and stability were all within the acceptable limits. Linezolid and PH027 concentrations were accurately determined in the quality control tissue homogenate samples, and analysis of samples obtained following IV administration of the two compounds showed that the tissue to plasma concentration ratio of PH027 was higher than that of linezolid probably due to its higher lipophilicity. The developed UPLC-MS/MS method for the analysis of linezolid and PH027 in rabbit's plasma can accurately determine the concentrations of these compounds in different tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptive plasma for cancer therapy: physics, mechanism and applications

Science.gov (United States)

Keidar, Michael

2017-10-01

One of the most promising applications of cold atmospheric plasma (CAP) is the cancer therapy. The uniqueness of plasma is in its ability to change composition in situ. Plasma self-organization could lead to formation of coherent plasma structures. These coherent structures tend to modulate plasma chemistry and composition, including reactive species, the electric field and charged particles. Formation of coherent plasma structures allows the plasma to adapt to external boundary conditions, such as different cells types and their contextual tissues. In this talk we will explore possibilities and opportunities that the adaptive plasma therapeutic system might offer. We shall define such an adaptive system as a plasma device that is able to adjust the plasma composition to obtain optimal desirable outcomes through its interaction with cells and tissues. The efficacy of cold plasma in a pre-clinical model of various cancer types such as lung, bladder, breast, head, neck, brain and skin has been demonstrated. Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. Recently mechanism of plasma selectivity based on aquaporin hypothesis has been proposed. Aquaporins (AQPs) are the confirmed membrane channels of H2O2 and other large molecules. We have demonstrated that the anti-cancer capacity of plasma could be inhibited by silencing the expression of AQPs. Additional possible cell feedback mechanism was recently discovered. It is associated with production of reactive species during direct CAP treatment by cancer cells. Selective production of hydrogen peroxide by different cells can lead to adaptation of chemistry at the plasma-cell interface based on the cellular input. In particular we have found that the discharge voltage is an important factor affecting the ratio of reactive oxygen species to reactive nitrogen species in the gas phase and this correlates well with effect of hydrogen peroxide production by cells. This work was

Modern concepts for basic radiobiological factors characterizing tumor tissue radiosensitivity

International Nuclear Information System (INIS)

Gocheva, L.; Sergieva, K.

2002-01-01

Traditionally radiotherapy is prescribed at doses consistent with the expected therapeutic response and tolerance of tumor and normal tissues without consideration to individual differences in radiosensitivity. However, the basic radiobiological knowledge and clinical experience along this line point to significant variations in the observed therapeutic results. It has been established that cells and tissues under experimental and clinical conditions manifest a wide spectrum of individual radiosensitivity. The aim of this survey is to outline the current concepts for the basic radiobiological factors influencing tumor radiosensitivity. A thorough discussion is done of the essence, mechanisms of action, methods of determination and measurement, and effect on the prognosis in patients with malignant diseases of a number of radiobiological factors, such as: tumor-cell proliferation, apoptosis, tumor hypoxia and neovascularization. Although the knowledge of the mechanisms of radiosensitivity is constantly expanding, its clinical implementation is still rather limited. The true role of radiosensitivity in predicting the therapeutic response should be more accurately defined. (authors)

[Expression of connective tissue growth factor in colorectal cancer and its association with prognosis].

Science.gov (United States)

Sun, Zheng; Yang, Ping; Liang, Li-yuan; Zhang, Tong; Zhang, Wei-jian; Cao, Jie

2012-11-01

To investigate the expression of connective tissue growth factor (CTGF) in colorectal cancer(CRC) and its association with clinicopathologic parameters and overall survival rate. Fresh tumor tissues and matched distal normal colon tissues were collected from 92 patients diagnosed as CRC by surgical operation. The expression level of CTGF mRNA was quantified by quantitative reverse transcription PCR. Thirty out of 92 pairs of tissue specimens were selected randomly to detect CTGF protein by immunohistochemistry. All the cases were followed up to identify prognostic factors for survival. CTGF mRNA expression was up-regulated in CRC. The positive rate of CTGF protein expression tissues (73.3%) was significantly higher than that in the corresponding normal tissues (23.3%, Ptissues was classified into high and low expression groups. The 5-year cumulative survival rate was lower in patients with low CTGF expression (29.3%) as compared to those with high CTGF expressions (68.3%) (P<0.01). Cox regression analysis revealed that the relative expression level of CTGF was independent factor of overall survival (RR=2.960, 95%CI:1.491-1.587, P<0.01). ROC curve analysis showed that sensitivity and specificity of CTGF mRNA expression for prediction of 5-year survival were 64.9% and 74.5%, respectively. The aberrant expression of CTGF is associated with the malignant biological behaviors of CRC. Low expression of CTGF is associated with worse prognosis of CRC.

Quantitative images of metals in plant tissues measured by laser ablation inductively coupled plasma mass spectrometry

International Nuclear Information System (INIS)

Becker, J.S.; Dietrich, R.C.; Matusch, A.; Pozebon, D.; Dressler, V.L.

2008-01-01

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used for quantitative imaging of toxic and essential elements in thin sections (thickness of 30 or 40 μm) of tobacco plant tissues. Two-dimensional images of Mg, Fe, Mn, Zn, Cu, Cd, Rh, Pt and Pb in leaves, shoots and roots of tobacco were produced. Sections of the plant tissues (fixed onto glass slides) were scanned by a focused beam of a Nd:YAG laser in a laser ablation chamber. The ablated material was transported with argon as carrier gas to the ICP ion source at a quadrupole ICP-MS instrument. Ion intensities of the investigated elements were measured together with 13 C + , 33 S + and 34 S + within the entire plant tissue section. Matrix matching standards (prepared using powder of dried tobacco leaves) were used to constitute calibration curves, whereas the regression coefficient of the attained calibration curves was typically 0.99. The variability of LA-ICP-MS process, sample heterogeneity and water content in the sample were corrected by using 13 C + as internal standard. Quantitative imaging of the selected elements revealed their inhomogeneous distribution in leaves, shoots and roots

Angiogenesis is not impaired in connective tissue growth factor (CTGF) knock-out mice

NARCIS (Netherlands)

Kuiper, Esther J.; Roestenberg, Peggy; Ehlken, Christoph; Lambert, Vincent; van Treslong-de Groot, Henny Bloys; Lyons, Karen M.; Agostini, Hans-Jürgen T.; Rakic, Jean-Marie; Klaassen, Ingeborg; van Noorden, Cornelis J. F.; Goldschmeding, Roel; Schlingemann, Reinier O.

2007-01-01

Connective tissue growth factor (CTGF) is a member of the CCN family of growth factors. CTGF is important in scarring, wound healing, and fibrosis. It has also been implicated to play a role in angiogenesis, in addition to vascular endothelial growth factor (VEGF). In the eye, angiogenesis and

The suprachiasmatic nucleus drives day-night variations in postprandial triglyceride uptake into skeletal muscle and brown adipose tissue.

Science.gov (United States)

Moran-Ramos, Sofía; Guerrero-Vargas, Natali N; Mendez-Hernandez, Rebeca; Basualdo, Maria Del Carmen; Escobar, Carolina; Buijs, Ruud M

2017-12-01

What is the central question of this study? What are the factors influencing day-night variations in postprandial triglycerides? What is the main finding and its importance? Rats show low postprandial plasma triglyceride concentrations early in the active period that are attributable to a higher uptake by skeletal muscle and brown adipose tissue. We show that these day-night variations in uptake are driven by the suprachiasmatic nucleus, probably via a Rev-erbα-mediated mechanism and independent of locomotor activity. These findings highlight that the suprachiasmatic nucleus has a major role in day-night variations in plasma triglycerides and that disturbances in our biological clock might be an important risk factor contributing to development of postprandial hyperlipidaemia. Energy metabolism follows a diurnal pattern, mainly driven by the suprachiasmatic nucleus (SCN), and disruption of circadian regulation has been linked to metabolic abnormalities. Indeed, epidemiological evidence shows that night work is a risk factor for cardiovascular disease, and postprandial hyperlipidaemia is an important contributor. Therefore, the aim of this work was to investigate the factors that drive day-night variations in postprandial triglycerides (TGs). Intact and SCN-lesioned male Wistar rats were subjected to an oral fat challenge during the beginning of the rest phase (day) or the beginning of the active phase (night). The plasma TG profile was evaluated and tissue TG uptake assayed. After the fat challenge, intact rats showed lower postprandial plasma TG concentrations early in the night when compared with the day. However, no differences were observed in the rate of intestinal TG secretion between day and night. Instead, there was a higher uptake of TG by skeletal muscle and brown adipose tissue early in the active phase (night) when compared with the rest phase (day), and these variations were abolished in rats bearing bilateral SCN lesions. Rev-erbα gene expression

Beneifcial effect of reifned red palm oil on lipid peroxidation and monocyte tissue factor in HCV-related liver disease：a randomized controlled study

Institute of Scientific and Technical Information of China (English)

Roberto Catanzaro; Nicola Zerbinati; Umberto Solimene; Massimiliano Marcellino; Dheeraj Mohania; Angelo Italia; Antonio Ayala; Francesco Marotta

2016-01-01

BACKGROUND: A large amount of endotoxin can be detected in the peripheral venous blood of patients with liver cirrhosis, contributing to the pathogenesis of hepatotoxicity because of its role in oxidative stress. The present study aimed to test the effect of the supplementation with red palm oil (RPO), which is a natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat-soluble tocopherols, tocotrienols and carot-enoids, on lipid peroxidation and endotoxemia with plasma endotoxin-inactivating capacity, proinlfammatory cytokines proifle, and monocyte tissue factor in patients with chronic liver disease. METHODS: The study group consisted of sixty patients (34 males and 26 females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related cirrhosis without a history of ethanol consumption, randomly enrolled into an 8-week oral daily treatment with either vitamin E or RPO. All patients had undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them showed esophageal varices. RESULTS: Both treatments signiifcantly decreased erythro-cyte malondialdehyde and urinary isoprostane output, only RPO signiifcantly affected macrophage-colony stimulating fac-tor and monocyte tissue factor. Liver ultrasound imaging did not show any change. CONCLUSIONS: RPO beneifcially modulates oxidative stress and, not least, downregulates macrophage/monocyte inlfam-matory parameters. RPO can be safely advised as a valuable nutritional implementation tool in the management of chron-ic liver diseases.

The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis.

Science.gov (United States)

Wang, F-M; Yu, F; Tan, Y; Liu, G; Zhao, M-H

2014-06-01

The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, plupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, plupus nephritis (63.3 ± 63.4 ng/ml vs. 38.3 ± 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, plupus nephritis (plupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Epicardial adipose tissue and cardiometabolic risk factors in overweight and obese children and adolescents.

Science.gov (United States)

Schusterova, I; Leenen, F H H; Jurko, A; Sabol, F; Takacova, J

2014-02-01

What is already known about this subject The prevalence of childhood obesity has increased markedly in the past 2 decades. Abdominal fat is a better predictor of risk than body mass index. Waist circumference (WC) as a measure of abdominal fat has limited sensitivity and specificity. What this study adds Epicardial adipose tissue (EAT) as measured by echocardiography represents a simple and reliable marker of visceral adiposity. In children, both body mass index and EAT show a similar or better correlation with markers of cardiometabolic risk than does waist circumference. Epicardial adipose tissue (EAT) is the visceral fat deposit around the heart and is commonly increased in obese subjects. EAT is related to cardiometabolic risk factors and non-alcoholic fatty liver disease (NAFLD) in adults, but this relationship is not well known in children. Echocardiographic assessment of EAT and its association with cardiometabolic risk factors in overweight and obese children. In 25 (mean age 13.0 ± 2.3) overweight and obese subjects and 24 lean controls, blood pressure (BP), WC, fasting plasma glucose and insulin, lipids, uric acid and hepatic enzymes were measured. EAT thickness was measured by transthoracic echocardiography. In overweight and obese subjects, EAT was significantly higher compared to normal weight children. Overweight and obese children had significantly higher body mass index (BMI), WC, BP, triglycerides (TAG), low-density lipoprotein and total cholesterol, hepatic enzymes alanine aminotransferase (ALT) and γ-glutamyl transferase, and lower high-density lipoprotein cholesterol (HDL-C). EAT correlated significantly with BP, TAG, uric acid, HDL-C, apoprotein B and ALT. Correlation coefficients were similar or better than for WC, but similar or lower than for BMI. EAT thickness in children is associated with an unfavourable cardiometabolic risk profile including biochemical signs of NAFLD and hyperuricaemia, but is not a stronger indicator than BMI. �

The effect of platelet-rich plasma on composite graft survival.

Science.gov (United States)

Jeon, Yeo Reum; Kang, Eun Hye; Yang, Chae Eun; Yun, In Sik; Lee, Won Jai; Lew, Dae Hyun

2014-08-01

Composite grafts are suitable for facial reconstruction because of good color matching, low donor-site morbidity, acceptable texture, and easy surgical techniques. However, their use is limited to small defects and by unpredictable survival rates. As platelet-rich plasma contains large numbers of growth factors and has been widely used for tissue regeneration, this study aimed to investigate platelet-rich plasma as an adjuvant to enhance composite graft survival. Twenty New Zealand White rabbits were used, and chondrocutaneous composite grafts were applied to their ears. The grafts were then returned to their original positions after rotation to block the original circulation from the base of the graft. Each of the individual ears was assigned randomly into one of two groups: experimental (n=20; platelet-rich plasma group) or control (n=20; control group). The surrounding skin of the composite graft was injected with either 1.0 ml of platelet-rich plasma derived from autologous whole blood in the platelet-rich plasma group or normal saline in the control group. Graft survival, cutaneous blood flow, CD31-stained vessels, and vascular endothelial growth factor protein levels were examined. Twelve days after surgery, graft viability in the platelet-rich plasma group was higher than in the control group. Blood perfusion was also higher in the platelet-rich plasma group. Compared with the control group, the number of CD31 blood vessels and vascular endothelial growth factor expression levels were significantly increased in the platelet-rich plasma group. The authors' results suggest that platelet-rich plasma restores the perfusion of composite grafts by enhancing revascularization and may exert therapeutic effects on the survival of composite grafts.

Concentrations of trimethoprim and sulphadoxine in tissues from goats and a cow

Energy Technology Data Exchange (ETDEWEB)

Nielsen, P; Rasmussen, F [Kongelige Veterinaer- og Landbohoejskole, Copenhagen (Denmark)

1975-01-01

The concentration of trimethoprim and sulphadoxine in plasma and tissue from goats and a cow have been determined after a single intravenous injection. Furthermore, the concentration of the two drugs and their metabolites in plasma and tissues have been determined after continuous intravenous infusion for 2 1/2 - 3 hrs. Trimethoprim was present in all tissues but brain at higher concentrations than in plasma while the concentration of sulphadoxine in the different tissues were lower than in plasma. The highest concentration of the 2 drugs and their metabolites was found in the kidney. The distribution pattern of trimethoprim and sulphadoxine was similar in cow and goats.

Concentrations of trimethoprim and sulphadoxine in tissues from goats and a cow

International Nuclear Information System (INIS)

Nielsen, P.; Rasmussen, F.

1975-01-01

The concentration of trimethoprim and sulphadoxine in plasma and tissue from goats and a cow have been determined after a single intravenous injection. Furthermore, the concentration of the two drugs and their metabolites in plasma and tissues have been determined after continuous intravenous infusion for 2 1/2 - 3 hrs. Trimethoprim was present in all tissues but brain at higher concentrations than in plasma while the concentration of sulphadoxine in the different tissues were lower than in plasma. The highest concentration of the 2 drugs and their metabolites was found in the kidney. The distribution pattern of trimethoprim and sulphadoxine was similar in cow and goats. (author)

Energy absorption buildup factors of human organs and tissues at energies and penetration depths relevant for radiotherapy and diagnostics

DEFF Research Database (Denmark)

Manohara, S. R.; Hanagodimath, S. M.; Gerward, Leif

2011-01-01

Energy absorption geometric progression (GP) fitting parameters and the corresponding buildup factors have been computed for human organs and tissues, such as adipose tissue, blood (whole), cortical bone, brain (grey/white matter), breast tissue, eye lens, lung tissue, skeletal muscle, ovary......, testis, soft tissue, and soft tissue (4-component), for the photon energy range 0.015-15 MeV and for penetration depths up to 40 mfp (mean free path). The chemical composition of human organs and tissues is seen to influence the energy absorption buildup factors. It is also found that the buildup factor...... of human organs and tissues changes significantly with the change of incident photon energy and effective atomic number, Zeff. These changes are due to the dominance of different photon interaction processes in different energy regions and different chemical compositions of human organs and tissues...

Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation.

Science.gov (United States)

Akar, Banu; Jiang, Bin; Somo, Sami I; Appel, Alyssa A; Larson, Jeffery C; Tichauer, Kenneth M; Brey, Eric M

2015-12-01

Gradients of soluble factors play an important role in many biological processes, including blood vessel assembly. Gradients can be studied in detail in vitro, but methods that enable the study of spatially distributed soluble factors and multi-cellular processes in vivo are limited. Here, we report on a method for the generation of persistent in vivo gradients of growth factors in a three-dimensional (3D) biomaterial system. Fibrin loaded porous poly (ethylene glycol) (PEG) scaffolds were generated using a particulate leaching method. Platelet derived growth factor BB (PDGF-BB) was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres which were placed distal to the tissue-material interface. PLGA provides sustained release of PDGF-BB and its diffusion through the porous structure results in gradient formation. Gradients within the scaffold were confirmed in vivo using near-infrared fluorescence imaging and gradients were present for more than 3 weeks. The diffusion of PDGF-BB was modeled and verified with in vivo imaging findings. The depth of tissue invasion and density of blood vessels formed in response to the biomaterial increased with magnitude of the gradient. This biomaterial system allows for generation of sustained growth factor gradients for the study of tissue response to gradients in vivo. Published by Elsevier Ltd.

Isolation of cDNA clones coding for human tissue factor: primary structure of the protein and cDNA

International Nuclear Information System (INIS)

Spicer, E.K.; Horton, R.; Bloem, L.

1987-01-01

Tissue factor is a membrane-bound procoagulant protein that activates the extrinsic pathway of blood coagulation in the presence of factor VII and calcium. λ Phage containing the tissue factor gene were isolated from a human placental cDNA library. The amino acid sequence deduced from the nucleotide sequence of the cDNAs indicates that tissue factor is synthesized as a higher molecular weight precursor with a leader sequence of 32 amino acids, while the mature protein is a single polypeptide chain composed of 263 residues. The derived primary structure of tissue factor has been confirmed by comparison to protein and peptide sequence data. The sequence of the mature protein suggests that there are three distinct domains: extracellular, residues 1-219; hydrophobic, residues 220-242; and cytoplasmic, residues 243-263. Three potential N-linked carbohydrate attachment sites occur in the extracellular domain. The amino acid sequence of tissue factor shows no significant homology with the vitamin K-dependent serine proteases, coagulation cofactors, or any other protein in the National Biomedical Research Foundation sequence data bank (Washington, DC)

Lyapunov-based distributed control of the safety-factor profile in a tokamak plasma

International Nuclear Information System (INIS)

Bribiesca Argomedo, Federico; Witrant, Emmanuel; Prieur, Christophe; Brémond, Sylvain; Nouailletas, Rémy; Artaud, Jean-François

2013-01-01

A real-time model-based controller is developed for the tracking of the distributed safety-factor profile in a tokamak plasma. Using relevant physical models and simplifying assumptions, theoretical stability and robustness guarantees were obtained using a Lyapunov function. This approach considers the couplings between the poloidal flux diffusion equation, the time-varying temperature profiles and an independent total plasma current control. The actuator chosen for the safety-factor profile tracking is the lower hybrid current drive, although the results presented can be easily extended to any non-inductive current source. The performance and robustness of the proposed control law is evaluated with a physics-oriented simulation code on Tore Supra experimental test cases. (paper)

Changes of plasma angiogenic factors during chronic resistance exercise in type 1 diabetic rats

International Nuclear Information System (INIS)

Esfahani, S.P.; Gharakhanlou, R.

2012-01-01

Objective: Exercise has several beneficial effects on cardiovascular system. However, the exact mechanism is unclear. The purpose of this study was to evaluate the effects of chronic resistance exercise on some plasma angiogenic factors in type 1 diabetic rats. Methodology: Thirty male Wistar rats were divided into three groups of control, diabetic and diabetic trained (n = 10 each). Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg). The rats in the trained group undertook one training session per day, 3 days/week, for 4 weeks. Blood samples were taken and the concentrations of plasma glucose, lipid profile, nitric oxide (NO), vascular endothelial growth factor (VEGF) and soluble form of VEGF receptor-1 (sFlt-1) were determined. Results: We found a significant reduction in plasma NO concentrations in diabetic rats compared to the controls (p 0.05). There were no significant differences in plasma VEGF and sFlt-1 concentrations between diabetic sedentary and trained groups (p > 0.05). Moreover, VEGF/sFlt-1 ratios in diabetic animals were lower than the control group and resistance exercise could not increase this ratio in diabetic animals (p > 0.05) Conclusion: Resistance exercise could not change plasma VEGF, sFlt-1 and VEGF/sFlt-1 ratio. However, it increased plasma NO concentrations in diabetic animals. More studies are needed to determine the effects of this type of exercise on the angiogenesis process. (author)

Model of a ternary complex between activated factor VII, tissue factor and factor IX.

Science.gov (United States)

Chen, Shu-wen W; Pellequer, Jean-Luc; Schved, Jean-François; Giansily-Blaizot, Muriel

2002-07-01

Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.

Ultra-performance liquid chromatography tandem mass spectrometry for simultaneous determination of natural steroid hormones in sea lamprey (Petromyzon marinus) plasma and tissues.

Science.gov (United States)

Wang, Huiyong; Bussy, Ugo; Chung-Davidson, Yu-Wen; Li, Weiming

2016-01-15

This study aims to provide a rapid, sensitive and precise UPLC-MS/MS method for target steroid quantitation in biological matrices. We developed and validated an UPLC-MS/MS method to simultaneously determine 16 steroids in plasma and tissue samples. Ionization sources of Electrospray Ionization (ESI) and Atmospheric Pressure Chemical Ionization (APCI) were compared in this study by testing their spectrometry performances at the same chromatographic conditions, and the ESI source was found up to five times more sensitive than the APCI. Different sample preparation techniques were investigated for an optimal extraction of steroids from the biological matrices. The developed method exhibited excellent linearity for all analytes with regression coefficients higher than 0.99 in broad concentration ranges. The limit of detection (LOD) was from 0.003 to 0.1ng/mL. The method was validated according to FDA guidance and applied to determine steroids in sea lamprey plasma and tissues (fat and testes) by the developed method. Copyright © 2015. Published by Elsevier B.V.

Destructive, granulating lesion in the temporal bone after elevated plasma homocysteine

DEFF Research Database (Denmark)

Bonding, Per; Skriver, Elisabeth; Helin, Pekka

2004-01-01

lesion in the left temporal bone was discovered; repeated histologic examination only showed simple granulation tissue. After 6 months, a part of the bony cochlea was extruded. With approximately 8 months' delay and after the patient had had postoperative lung embolism, plasma homocysteine was found...... to be significantly elevated, a condition known as an independent risk factor for thromboembolic lesions. In the acquired form, it is most often caused by nutritional deficiency of vitamin B cofactors. Accordingly, the patient was treated with folic acid, which rapidly normalized plasma homocysteine. Subsequently...

Platelet Rich Plasma and Knee Surgery

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Mikel Sánchez

2014-01-01

Full Text Available In orthopaedic surgery and sports medicine, the knee joint has traditionally been considered the workhorse. The reconstruction of every damaged element in this joint is crucial in achieving the surgeon’s goal to restore the knee function and prevent degeneration towards osteoarthritis. In the last fifteen years, the field of regenerative medicine is witnessing a boost of autologous blood-derived platelet rich plasma products (PRPs application to effectively mimic and accelerate the tissue healing process. The scientific rationale behind PRPs is the delivery of growth factors, cytokines, and adhesive proteins present in platelets and plasma, as well as other biologically active proteins conveyed by the plasma such as fibrinogen, prothrombin, and fibronectin; with this biological engineering approach, new perspectives in knee surgery were opened. This work describes the use of PRP to construct and repair every single anatomical structure involved in knee surgery, detailing the process conducted in ligament, meniscal, and chondral surgery.

Plasma tumor necrosis factor-a (TNF-a) levels in Gaucher disease

NARCIS (Netherlands)

Michelakakis, H.; Spanou, C.; Kondyli, A.; Dimitriou, E.; van Weely, S.; Hollak, C. E.; van Oers, M. H.; Aerts, J. M.

1996-01-01

Tumor necrosis factor-a (TNF-a) levels were measured in the plasma of patients with different types of Gaucher disease (GD) and patients with other lysosomal storage diseases. The highest TNF-a levels were observed in the most severe neuronopathic type of GD, exceeding those found in healthy

Plasma rico en plaquetas Platelet -rich plasma

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J. González Lagunas

2006-04-01

Full Text Available El Plasma Rico en Plaquetas es una suspensión concentrada de la sangre centrifugada que contiene elevadas concentraciones de trombocitos. Durante los últimos años, este producto ha aparecido de forma repetida en publicaciones científicas y en medios de comunicación generales como un producto que por sus características induce la curación y regeneración de los tejidos. La premisa de su uso es que las elevadas concentraciones de plaquetas en el PRP, liberan cantidades significativas de factores de crecimiento. En este artículo se van a recoger las evidencias científicas que se han presentado en la literatura médica con respecto al PRP y a la curación ósea, así como las diferentes aplicaciones clínicas que se han sugerido.Platelet-rich plasma is a by-product of centrifuged whole blood that contains high levels of thrombocytes. In the last decade, scientific and media interest has been generated by this product that apparently has the capacity of inducing and promoting tissue healing and regeneration. The premise of its use is that the large number of platelets in PRP release significant amounts of growth factors. In this paper, a critical review of the medical literature regarding PRP and bone healing will be presented. Also, the suggested clinical applications of the product will be addressed.

Clastogenic factors in the plasma of children exposed at Chernobyl

International Nuclear Information System (INIS)

Emerit, I.; Levy, A.; Cernjavski, L.; Alaoui-Youssefi, A.; Pogossian, A.; Quastel, M.; Goldsmith, J.; Merkin, L.; Riklis, E.

1997-01-01

Clastogenic factors (CFs), as they were described previously in accidentally or therapeutically irradiated persons, in A-bomb survivors and in liquidators of the Chernobyl nuclear power plant, were also detected in the plasma of Chernobyl-exposed children. A high percentage of plasma ultrafiltrates from 170 children, immigrated to Israel in 1990, exerted clastogenic effects in test cultures set up with blood from healthy donors. The differences were highly significant in comparison to children immigrated from 'clean' cities of the former Soviet Union or children born in Israel. The percentage of CF-positive children and the mean values of the adjusted clastogenic scores (ACS) were higher for those coming from Gomel and Mozyr, which are high exposure sites (IAEA measurements), compared to those coming from Kiev. There was no correlation between residual 137-Caesium body burden and presence of CFs. However, both measurements were not done at the same time (in 1990 and 1992-1994, respectively). Also no relationship could be revealed between enlargement of the thyroid gland and CF-positivity. CFs are not only observed after irradiation, but in a variety of chronic inflammatory diseases with autoimmune reactions. They were also described in the congenital breakage syndromes, which are hereditary diseases with the highest cancer incidence in humans. Whether the clastogenic effects continuously produced by circulating CFs represent a risk factor for malignant late effects deserves further study and follow-up. Since CF formation and CF action are mediated by superoxide radicals, prophylactic treatment with antioxidants may be suggested for Chernobyl-exposed children, whose plasma induces a strongly positive CF-test

COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

International Nuclear Information System (INIS)

Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

2011-01-01

Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue

COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

Directory of Open Access Journals (Sweden)

Lagerstedt Kristina

2011-06-01

Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

Plasma intact fibroblast growth factor 23 levels in women with anorexia nervosa

Directory of Open Access Journals (Sweden)

Otani Makoto

2008-04-01

Full Text Available Abstract Background Fibroblast growth factor (FGF23 is a novel phosphaturic factor associated with inorganic phosphate homeostasis. Previous human studies have shown that serum FGF23 levels increase in response to a high phosphate diet. For anorexia nervosa (AN patients, inorganic phosphate homeostasis is important in the clinical course, such as in refeeding syndrome. The purpose of this study was to determine plasma levels of intact FGF23 (iFGF23 in restricting-type AN (AN-R patients, binge-eating/purging-type AN (AN-BP patients, and healthy controls. Methods The subjects consisted of 6 female AN-R patients, 6 female AN-BP patients, and 11 healthy female controls; both inpatients and outpatients were included. Plasma iFGF23, 1,25-dihydroxyvitamin D (1,25-(OH2D, and 25-hydroxyvitamin D (25-OHD levels were measured. Data are presented as the median and the range. A two-tailed Mann-Whitney U-test with Bonferroni correction was used to assess differences among the three groups, and a value of p Results There were no differences between AN-R patients and controls in the iFGF23 and 1,25-(OH2D levels. In AN-BP patients, the iFGF23 level (41.3 pg/ml; range, 6.1–155.5 pg/ml was significantly higher than in controls (3.8 pg/ml; range, not detected-21.3 pg/ml; p = 0.001, and the 1,25-(OH2D was significantly lower in AN-BP patients (7.0 pg/ml; range, 4.2–33.7 pg/ml than in controls (39.7 pg/ml; range, 6.3–58.5 pg/ml; p = 0.015. No differences in plasma 25-OHD levels were observed among the groups. Conclusion This preliminary study is the first to show that plasma iFGF23 levels are increased in AN-BP patients, and that these elevated plasma FGF23 levels might be related to the decrease in plasma 1,25-(OH2D levels.

Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration

Directory of Open Access Journals (Sweden)

Ye-Rang Yun

2010-01-01

Full Text Available Fibroblast growth factors (FGFs that signal through FGF receptors (FGFRs regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain optimal outcomes in vivo, it is important to enhance the half-life of FGFs and their biological stability. Future applications of FGFs are expected when the biological functions of FGFs are potentiated through the appropriate use of delivery systems and scaffolds. This review will introduce the biology and cellular functions of FGFs and deal with the biomaterials based delivery systems and their current applications for the regeneration of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve tissues.

Control of exogenous factors affecting plasma homovanillic acid concentration.

Science.gov (United States)

Davidson, M; Giordani, A B; Mohs, R C; Mykytyn, V V; Platt, S; Aryan, Z S; Davis, K L

1987-04-01

Measurements of plasma homovanillic acid (pHVA) concentrations appear to be a valid research strategy in psychiatric disorders in which a central dopamine (DA) abnormality has been implicated. This study provides guidance about the control of some of the exogenous factors affecting pHVA concentrations. Fasting for 14 hours eliminates the dietary effects on pHVA in healthy human subjects. Changing position, walking for 30 minutes, or smoking two cigarettes has no effect on pHVA concentrations.

Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

DEFF Research Database (Denmark)

Sidelmann, Johannes J; Skouby, Sven O; Kluft, Cornelis

2011-01-01

Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P=0.001). OC use increased FSAP antigen by 25% and FSAP activity...

Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

DEFF Research Database (Denmark)

Nossent, Anne Yaël; Robben, J H; Deen, P M T

2010-01-01

SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

Plasmas for medicine

Science.gov (United States)

von Woedtke, Th.; Reuter, S.; Masur, K.; Weltmann, K.-D.

2013-09-01

Plasma medicine is an innovative and emerging field combining plasma physics, life science and clinical medicine. In a more general perspective, medical application of physical plasma can be subdivided into two principal approaches. (i) “Indirect” use of plasma-based or plasma-supplemented techniques to treat surfaces, materials or devices to realize specific qualities for subsequent special medical applications, and (ii) application of physical plasma on or in the human (or animal) body to realize therapeutic effects based on direct interaction of plasma with living tissue. The field of plasma applications for the treatment of medical materials or devices is intensively researched and partially well established for several years. However, plasma medicine in the sense of its actual definition as a new field of research focuses on the use of plasma technology in the treatment of living cells, tissues, and organs. Therefore, the aim of the new research field of plasma medicine is the exploitation of a much more differentiated interaction of specific plasma components with specific structural as well as functional elements or functionalities of living cells. This interaction can possibly lead either to stimulation or inhibition of cellular function and be finally used for therapeutic purposes. During recent years a broad spectrum of different plasma sources with various names dedicated for biomedical applications has been reported. So far, research activities were mainly focused on barrier discharges and plasma jets working at atmospheric pressure. Most efforts to realize plasma application directly on or in the human (or animal) body for medical purposes is concentrated on the broad field of dermatology including wound healing, but also includes cancer treatment, endoscopy, or dentistry. Despite the fact that the field of plasma medicine is very young and until now mostly in an empirical stage of development yet, there are first indicators of its enormous

Nuclear exclusion of transcription factors associated with apoptosis in developing nervous tissue

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R. Linden

1999-07-01

Full Text Available Programmed cell death in the form of apoptosis involves a network of metabolic events and may be triggered by a variety of stimuli in distinct cells. The nervous system contains several neuron and glial cell types, and developmental events are strongly dependent on selective cell interactions. Retinal explants have been used as a model to investigate apoptosis in nervous tissue. This preparation maintains the structural complexity and cell interactions similar to the retina in situ, and contains cells in all stages of development. We review the finding of nuclear exclusion of several transcription factors during apoptosis in retinal cells. The data reviewed in this paper suggest a link between apoptosis and a failure in the nucleo-cytoplasmic partition of transcription factors. It is argued that the nuclear exclusion of transcription factors may be an integral component of apoptosis both in the nervous system and in other types of cells and tissues.

Recovery from Bell Palsy after Transplantation of Peripheral Blood Mononuclear Cells and Platelet-Rich Plasma.

Science.gov (United States)

Seffer, Istvan; Nemeth, Zoltan

2017-06-01

Peripheral blood mononuclear cells (PBMCs) are multipotent, and plasma contains growth factors involving tissue regeneration. We hypothesized that transplantation of PBMC-plasma will promote the recovery of paralyzed facial muscles in Bell palsy. This case report describes the effects of PBMC-plasma transplantations in a 27-year-old female patient with right side Bell palsy. On the affected side of the face, the treatment resulted in both morphological and functional recovery including voluntary facial movements. These findings suggest that PBMC-plasma has the capacity of facial muscle regeneration and provides a promising treatment strategy for patients suffering from Bell palsy or other neuromuscular disorders.

Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery.

Science.gov (United States)

Anitua, E; Muruzabal, F; Alcalde, I; Merayo-Lloves, J; Orive, G

2013-10-01

This study evaluated the efficacy of Plasma rich in growth factors (PRGF-Endoret) on the corneal wound healing process after Photorefractive keratectomy (PRK). To address this, blood from three healthy donors was collected, centrifuged and, the whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were collected. The effects of F3 and WP on the proliferation and migration of human corneal epithelial cells (HCE) were analyzed. PRK was performed on C57BL/6 mice. Animals were divided in three treatment groups: Control, F3, and WP. Corneal wound healing and haze formation were evaluated macroscopically. Eyes were collected at 1, 2, 3, and 7 days after surgery, and were processed for histological studies. Immunofluorescence was used to assess cellular proliferation, apoptosis and myofibroblast transformation in the mouse cornea. Results showed a significant increased on proliferation and wound healing after F3 and WP treatment when compared with control group. In vivo studies showed significant reduction on haze formation in mice treated with both PRGF-Endoret formulations (F3 and WP). Histological studies showed an increase of epithelial cell proliferation in corneas of control group, promoting an epithelial hyperplasia. The number of SMA-positive cells (corresponding to myofibroblast differentiation) was significantly lower in the PRGF-Endoret group than in the control group, correlating with the higher transparence results observed macroscopically in both PRGF-Endoret groups. According to this, it can be concluded that PRGF-Endoret accelerates corneal tissue regeneration after PRK, reducing haze formation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gamma-ray energy absorption and exposure buildup factor studies in some human tissues with endometriosis

Energy Technology Data Exchange (ETDEWEB)

Kurudirek, Murat, E-mail: mkurudirek@gmail.co [Faculty of Science, Department of Physics, Ataturk University, 25240 Erzurum (Turkey); Dogan, Bekir [Faculty of Science, Department of Physics, Ataturk University, 25240 Erzurum (Turkey); Ingec, Metin [Faculty of Medicine, Department of Obstetrics and Gynecology, Ataturk University, 25240 Erzurum (Turkey); Ekinci, Neslihan; Ozdemir, Yueksel [Faculty of Science, Department of Physics, Ataturk University, 25240 Erzurum (Turkey)

2011-02-15

Human tissues with endometriosis have been analyzed in terms of energy absorption (EABF) and exposure (EBF) buildup factors using the five-parameter geometric progression (G-P) fitting formula in the energy region 0.015-15 MeV up to a penetration depth of 40 mfp (mean free path). Chemical compositions of the tissue samples were determined using a wavelength dispersive X-ray fluorescence spectrometer (WDXRFS). Possible conclusions were drawn due to significant variations in EABF and EBF for the selected tissues when photon energy, penetration depth and chemical composition changed. Buildup factors so obtained may be of use when the method of choice for treatment of endometriosis is radiotherapy.

Bilateral sinus elevation evaluating plasma rich in growth factors technology: a report of five cases.

Science.gov (United States)

Anitua, Eduardo; Prado, Roberto; Orive, Gorka

2012-03-01

The purpose of this study was to evaluate the potential effects of plasma rich in growth factors (PRGF) technology and its autologous formulations in five consecutive patients in which bilateral sinus lift augmentation was carried out. Five consecutive patients received bilateral sinus floor augmentation. All patients presented a residual bone height of class D (1-3 mm). The effects of PRGF combined with bovine anorganic bone (one side) were compared with the biomaterial alone (contralateral side). The effects of using liquid PRGF to maintain the bone window and autologous fibrin membrane to seal the defect were evaluated. A complete histological and histomorphometrical analysis was performed 5 months after surgery. One patient was excluded from the study as the Schneiderian membrane of the control side was perforated during the surgery. In two patients, the biopsies obtained from the control sides 5 months postsurgery were not acceptable for processing. PRGF technology facilitated the surgical approach of sinus floor elevation. The control area was more inflamed than the area treated with PRGF technology. Patients referred also to an increased sensation of pain in the control area. PRGF-treated samples had more new vital bone than controls. In patient number 1, image processing revealed 21.4% new vital bone in the PRGF area versus 8.4% in the control area, whereas in patient number 2, 28.4% new vital bone was quantified in the PRGF area compared with the 8.2% of the control side. The immunohistochemical processing of the biopsies revealed that the number of blood vessels per square millimeter of connective tissue was 116 vessels in the PRGF sample versus 7 in the control biopsy. These preliminary results suggest that from a practical point of view, PRGF may present a role in reducing tissue inflammation after surgery, increasing new bone formation and promoting the vascularization of bone tissue. © 2010 Wiley Periodicals, Inc.

The biology of platelet-rich plasma and its application in oral surgery: literature review.

NARCIS (Netherlands)

Nikolidakis, D.; Jansen, J.A.

2008-01-01

Platelet-rich plasma (PRP) is a new approach in tissue regeneration and a developing area for clinicians and researchers. It is used in various surgical fields, including oral and maxillofacial surgery. PRP is prepared from the patient's own blood and contains growth factors that influence wound

Transforming growth factor-β1/Smad/connective tissue growth factor axis: The main pathway in radiation-induced fibrosis of osteoradionecrosis?

Directory of Open Access Journals (Sweden)

Qian Wei Zhuang

2013-01-01

Full Text Available Introduction: Osteoradionecrosis (ORN of the mandible is a serious complication following radiation therapy for malignancies of the head and neck. Radiation-induced fibrosis (RIF is a new theory that accounts for the damage to normal tissues after radiotherapy, and the radiation-induced fibroatrophic mechanism includes the free-radical formation, endothelial dysfunction, inflammation, microvascular thrombosis, fibrosis and remodeling, and finally bone and tissue necrosis. The Hypothesis: Previous studies revealed that transforming growth factor-β1 (TGF-β1 is the master switch cytokine responsible for the regulation of fibroblast proliferation and differentiation that result in RIF. Among the targets of TGF-β1, connective tissue growth factor (CTGF is a downstream mediator through the Smad3/4 pathway and plays an important role in connective tissue homeostasis and fibroblast proliferation. Studies have proved that the TGF-β1/Smad/CTGF signaling pathway is involved in the RIF of soft tissues, so the authors put forward a hypothesis that the TGF-β1/Smad/CTGF axis is also the main pathway in RIF of ORN. Evaluation of the Hypothesis: The validation of our hypothesis may provide new insights for better understanding the pathogenesis of ORN and open new perspectives for anti-fibrotic therapies, and pioneer novel approaches to treat ORN.

Plasma pharmacokinetics, tissue distribution and excretion of MnDPDP in the rat and dog after intravenous administration

International Nuclear Information System (INIS)

Hustvedt, S.O.

1997-01-01

Purpose: To investigate distribution and excretion of mangafodipir (MnDPDP, Teslascan) in the rat and dog. Material and Methods: Formulations of either 14 C-MnDPDP or 54 MnDPDP were injected intravenously at near clinical doses in rats and dogs. Results: The manganese (Mn) moeity is rapidly removed from plasma with an elimination half-life of less than 25 min in both species, reflecting a rapid distribution to the tissues and an early excretion. The plasma clearance of the DPDP moeity is slower than that of Mn and it appears to distribute into the extracellular fluid. Mn is distributed largely to the liver, pancreas and kidneys, and in pregnant rats, also to foetal liver and bones. No transplacental passage of DPDP could be detected. The metal is mainly excreted by the faecal route, with a small fraction eliminated early in the urine. DPDP is rapidly and essentially completely excreted in the urine, consistent with the glomerular filtration rate. (orig./AJ)

Redox Stimulation of Human THP-1 Monocytes in Response to Cold Physical Plasma

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Sander Bekeschus

2016-01-01

Full Text Available In plasma medicine, cold physical plasma delivers a delicate mixture of reactive components to cells and tissues. Recent studies suggested a beneficial role of cold plasma in wound healing. Yet, the biological processes related to the redox modulation via plasma are not fully understood. We here used the monocytic cell line THP-1 as a model to test their response to cold plasma in vitro. Intriguingly, short term plasma treatment stimulated cell growth. Longer exposure only modestly compromised cell viability but apparently supported the growth of cells that were enlarged in size and that showed enhanced metabolic activity. A significantly increased mitochondrial content in plasma treated cells supported this notion. On THP-1 cell proteome level, we identified an increase of protein translation with key regulatory proteins being involved in redox regulation (hypoxia inducible factor 2α, differentiation (retinoic acid signaling and interferon inducible factors, and cell growth (Yin Yang 1. Regulation of inflammation is a key element in many chronic diseases, and we found a significantly increased expression of the anti-inflammatory heme oxygenase 1 (HMOX1 and of the neutrophil attractant chemokine interleukin-8 (IL-8. Together, these results foster the view that cold physical plasma modulates the redox balance and inflammatory processes in wound related cells.

Redox Stimulation of Human THP-1 Monocytes in Response to Cold Physical Plasma.

Science.gov (United States)

Bekeschus, Sander; Schmidt, Anke; Bethge, Lydia; Masur, Kai; von Woedtke, Thomas; Hasse, Sybille; Wende, Kristian

2016-01-01

In plasma medicine, cold physical plasma delivers a delicate mixture of reactive components to cells and tissues. Recent studies suggested a beneficial role of cold plasma in wound healing. Yet, the biological processes related to the redox modulation via plasma are not fully understood. We here used the monocytic cell line THP-1 as a model to test their response to cold plasma in vitro. Intriguingly, short term plasma treatment stimulated cell growth. Longer exposure only modestly compromised cell viability but apparently supported the growth of cells that were enlarged in size and that showed enhanced metabolic activity. A significantly increased mitochondrial content in plasma treated cells supported this notion. On THP-1 cell proteome level, we identified an increase of protein translation with key regulatory proteins being involved in redox regulation (hypoxia inducible factor 2α), differentiation (retinoic acid signaling and interferon inducible factors), and cell growth (Yin Yang 1). Regulation of inflammation is a key element in many chronic diseases, and we found a significantly increased expression of the anti-inflammatory heme oxygenase 1 (HMOX1) and of the neutrophil attractant chemokine interleukin-8 (IL-8). Together, these results foster the view that cold physical plasma modulates the redox balance and inflammatory processes in wound related cells.

Application of inductively coupled plasma mass spectrometry for multielement analysis in small sample amounts of thyroid tissue from Chernobyl area

International Nuclear Information System (INIS)

Becker, J.S.; Dietze, H.J.; Boulyga, S.F.; Bazhanova, N.N.; Kanash, N.V.; Malenchenko, A.F.

2000-01-01

As a result of the Chernobyl nuclear power plant accident in 1986, thyroid pathologies occurred among children in some regions of belarus. Besides the irradiation of children's thyroids by radioactive iodine and caesium nuclides, toxic elements from fallout are a direct risk to health. Inductively coupled plasma quadrupole-based mass spectrometry (Icp-Ms) and instrumental neutron activation analysis (IAA) were used for multielement determination in small amounts (I-10 mg) of human thyroid tissue samples. The accuracy of the applied analytical technique for small biological sample amounts was checked using NIST standard reference material oyster tissue (SRM 1566 b). Almost all essential elements as well as a number of toxic elements such as Cd, Pb, Hg, U etc. Were determined in a multitude of human thyroid tissues by quadrupole-based Icp-Ms using micro nebulization. In general, the thyroid tissue affected by pathology is characterized by higher calcium content. Some other elements, among them Sr, Zn, Fe, Mn, V, As, Cr, Ni, Pb, U, Ba, Sb, were also Accumulated in such tissue. The results obtained will be used as initial material for further specific studies of the role of particular elements in thyroid pathology development

Chemically reactive species in liquids generated by atmospheric-pressure plasmas and their roles in plasma medicine

International Nuclear Information System (INIS)

Hamaguchi, Satoshi

2013-01-01

Plasmas whose gas temperatures are close to room temperature may be generated in ambient air or a gas at atmospheric pressure with the use of low-frequency high voltage or low-power radio-frequency (RF) or microwave power applied to electrodes. Such plasmas can serve as a powerful source of free radicals and/or chemically reactive species that arise from atoms and molecules of the ambient gas. Recently use of such plasmas for medical purposes has attracted much attention as they can be implemented in possible medical devices that can cause blood coagulation, heal wounds, facilitate angiogenesis, sterilize surgical devices as well as living tissues without harming healthy cells, and selectively inactivate cancer cells. Especially of interest among reactive species generated by atmospheric-pressure plasmas (APP) are reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are generated in liquid phase. Since most living tissues and cells are immersed in liquids (such as blood or culture media), reactive species generated by APPs in the gas phase are transported to the liquid phase and possibly converted to different types of reactive species therein before causing some influence on the tissues or cells. In this study, the rate equations are solved to evaluate concentrations of various reactive species in pure water that are originated by plasma reactions in atmosphere and possible effects of such species (including ROS/RNS) on living tissues and cells are discussed

Chemically reactive species in liquids generated by atmospheric-pressure plasmas and their roles in plasma medicine

Energy Technology Data Exchange (ETDEWEB)

Hamaguchi, Satoshi [Center for Atomic and Molecular Technologies, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan)

2013-07-11

Plasmas whose gas temperatures are close to room temperature may be generated in ambient air or a gas at atmospheric pressure with the use of low-frequency high voltage or low-power radio-frequency (RF) or microwave power applied to electrodes. Such plasmas can serve as a powerful source of free radicals and/or chemically reactive species that arise from atoms and molecules of the ambient gas. Recently use of such plasmas for medical purposes has attracted much attention as they can be implemented in possible medical devices that can cause blood coagulation, heal wounds, facilitate angiogenesis, sterilize surgical devices as well as living tissues without harming healthy cells, and selectively inactivate cancer cells. Especially of interest among reactive species generated by atmospheric-pressure plasmas (APP) are reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are generated in liquid phase. Since most living tissues and cells are immersed in liquids (such as blood or culture media), reactive species generated by APPs in the gas phase are transported to the liquid phase and possibly converted to different types of reactive species therein before causing some influence on the tissues or cells. In this study, the rate equations are solved to evaluate concentrations of various reactive species in pure water that are originated by plasma reactions in atmosphere and possible effects of such species (including ROS/RNS) on living tissues and cells are discussed.

Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

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Halima Rakhila

Full Text Available Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2, cell adhesion (αv and β3 integrins, survival (B-cell lymphoma-2 and angiogenic (vascular endothelial cell growth factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

Science.gov (United States)

Rakhila, Halima; Girard, Karine; Leboeuf, Mathieu; Lemyre, Madeleine; Akoum, Ali

2014-01-01

Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

Polychlorinated biphenyl concentrations, congener profiles, and ratios in the fat tissue, eggs, and plasma of snapping turtles (Chelydra s. serpentina) from the Ohio Basin of Lake Erie, USA.

Science.gov (United States)

Dabrowska, H; Fisher, S W; Estenik, J; Kidekhel, R; Stromberg, P

2006-08-01

Concentrations and profiles of polychlorinated biphenyls (PCBs) were determined in three tissues of adult snapping turtles (Chelydra serpentina serpentina) from six locations in the Ohio Basin of Lake Erie to characterize tissue variation and geographic trends. The locations included the Ohio Areas of Concern, i.e., the Ashtabula, Black, and Maumee Rivers; the Ottawa River near Toledo; and two reference sites. Mean total PCBs were greatest in turtles from the Ottawa River followed by the Maumee, Ashtabula, and Black Rivers. All three types of samples-fat tissue (FT), eggs, and plasma-showed the same geographic trend in PCB levels. On a wet-weight basis, mean concentrations ranged from 2,148 to 18,669 ng/g in FT, from 183 to 3,683 ng/g in eggs, and from 18 to 201 ng/g in plasma. Across all sites, total PCB concentrations between the tissues were significantly correlated (0.001 40 congeners (0.001 < p < 0.05). The distribution ratios determined for these congeners from the slope of the regression lines averaged 1.235 +/- 0.279, 0.430 +/- 0.170, and 0.387 +/- 0.115, respectively. The plasma wet weight-FT lipid-normalized concentration ratios for these congeners averaged 0.012 +/- 0.006. Both egg-FT and plasma wet weight-FT lipid-normalized ratios regressed against log K(ow) showed significant decreases, with increasing log K(ow), indicating greater accumulation of highly chlorinated congeners in FT than in other compartments. The estimated 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents ranged from 0.007 ng/g at reference sites to 0.060 ng/g at contaminated sites and from 0.099 to 1.992 ng/g in plasma and eggs, respectively. In both plasma and eggs, coplanar-CBs were the major contributors to total toxic equivalents (TEQs). Eggs from all contaminated sites had TEQs that exceeded the lowest observed effect level TEQs proposed for bald eagle chicks, in addition to high SigmaPCB levels at some of these sites, especially the Ottawa and Maumee River sites, indicate

Plasma Adiponectin, clinical factors, and patient outcomes during the acute respiratory distress syndrome.

Directory of Open Access Journals (Sweden)

Allan J Walkey

Full Text Available Adiponectin (APN is an anti-inflammatory hormone derived from adipose tissue that attenuates acute lung injury in rodents. In this study, we investigated the association between circulating APN and outcomes among patients with acute respiratory distress syndrome (ARDS.We performed a retrospective cohort study using data and plasma samples from participants in the multicenter ARDS Network Fluid and Catheter Treatment Trial.Plasma APN concentrations were measured in 816 (81.6% trial participants at baseline and in 568 (56.8% subjects at both baseline and day 7 after enrollment. Clinical factors associated with baseline APN levels in multivariable-adjusted models included sex, body mass index, past medical history of cirrhosis, and central venous pressure (model R2 = 9.7%. We did not observe an association between baseline APN and either severity of illness (APACHE III or extent of lung injury (Lung Injury Score. Among patients who received right heart catheterization (n = 384, baseline APN was inversely related to mean pulmonary artery pressure (β = -0.015, R2 1.5%, p = 0.02; however, this association did not persist in multivariable models (β = -0.009, R2 0.5%, p = 0.20. Neither baseline APN levels [HR per quartile1.04 (95% CI 0.91-1.18, p = 0.61], nor change in APN level from baseline to day 7 [HR 1.04 (95% CI 0.89-1.23, p = 0.62] were associated with 60 day mortality in Cox proportional hazards regression models. However, subgroup analysis identified an association between APN and mortality among patients who developed ARDS from extra-pulmonary etiologies [HR per quartile 1.31 (95% CI 1.08-1.57]. APN levels did not correlate with mortality among patients developing ARDS in association with direct pulmonary injury [HR 0.96 (95% CI 0.83-1.13], pinteraction = 0.016.Plasma APN levels did not correlate with disease severity or mortality in a large cohort of patients with ARDS. However, higher APN levels were

Factors which affect operation of a plasma focus in various gases

International Nuclear Information System (INIS)

Smith, A.J.

1987-06-01

It is shown that the axial transit time t a and γ, the ratio of specific heats, are the main factors which affect the operation of a plasma focus in various gases. An energy balance theory is used to explore this dependence. The results are consistent with previous calculations and with experiment. (author). 12 refs

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

Science.gov (United States)

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

2018-01-01

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

Preclinical pharmacokinetics, tissue distribution and plasma protein binding of sodium (±-5-bromo-2-(α-hydroxypentyl benzoate (BZP, an innovative potent anti-ischemic stroke agent

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Xin Tian

2016-08-01

Full Text Available Sodium (±-5-bromo-2-(α-hydroxypentyl benzoate (BZP is a potential cardiovascular drug and exerts potent neuroprotective effect against transient and long-term ischemic stroke in rats. BZP could convert into 3-butyl-6-bromo-1(3H-isobenzofuranone (Br-NBP in vitro and in vivo. However, the pharmacokinetic profiles of BZP and Br-NBP still have not been evaluated. For the purpose of investigating the pharmacokinetic profiles, tissue distribution and plasma protein binding of BZP and Br-NBP, a rapid, sensitive and specific method based on liquid chromatography coupled to mass spectrometry (LC-MS/MS has been developed for determination of BZP and Br-NBP in biological samples. The results indicated that BZP and Br-NBP showed a short elimination half-life, and pharmacokinetic profile in rats (3, 6 and 12 mg/kg; i.v. and beagle dogs (1, 2 and 4 mg/kg; i.v.gtt were obtained after single dosing of BZP. After multiple dosing of BZP, there was no significant accumulation of BZP and Br-NBP in the plasma of rats and beagle dogs. Following i.v. single dose (6 mg/kg to rats, BZP and Br-NBP were distributed rapidly into all tissues examined, with the highest concentrations of BZP and Br-NBP in lung and kidney, respectively. The brain distribution of Br-NBP in middle cerebral artery occlusion (MCAO rats was more than in normal rats (P<0.05. The plasma protein binding degree of BZP at three concentrations (8000, 20000 and 80000 ng/mL from rat, beagle dog and human plasma were 98.1~98.7%, 88.9~92.7% and 74.8%~83.7% respectively. In conclusion, both BZP and Br-NBP showed short half-life, good dose-linear pharmacokinetic profile, wide tissue distribution and different degree protein binding to various species plasma. This was the first preclinical pharmacokinetic investigation of BZP and Br-NBP in both rats and beagle dogs, which provided vital guidance for further preclinical research and the subsequent clinical trials.

Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients.

Science.gov (United States)

Diaz, Alba; Alós, Llúcia; León, Agathe; Mozos, Anna; Caballero, Miguel; Martinez, Antonio; Plana, Montserrat; Gallart, Teresa; Gil, Cristina; Leal, Manuel; Gatell, Jose M; García, Felipe

2010-08-24

The factors associated with fibrosis in lymphoid tissue in long-term treated HIV-infected patients and their correlation with immune reconstitution were assessed. Tonsillar biopsies were performed in seven antiretroviral-naive patients and 29 successfully treated patients (median time on treatment, 61 months). Twenty patients received protease inhibitors-sparing regimens and nine protease inhibitor-containing regimens. Five tonsillar resections of HIV-negative individuals were used as controls. Lymphoid tissue architecture, collagen deposition (fibrosis) and the mean interfollicular CD4(+) cell count per mum were assessed. Naive and long-term treated HIV-infected patients had a higher proportion of fibrosis than did HIV-uninfected persons (P lymphoid tissue (P = 0.03) and smaller increase in peripheral CD4(+) T cells (r = -0.40, P = 0.05). The factors independently associated with fibrosis in lymphoid tissue were age (P lymphoid tissue viral load when compared with patients with undetectable lymphoid tissue viral load (median 5 vs. 12%, respectively, P = 0.017) and patients receiving a protease inhibitor-sparing vs. a protease inhibitor-containing regimen (median 8 vs. 2.5%, respectively, P = 0.04). Fibrosis in lymphoid tissue was associated with a poor reconstitution of CD4(+) T cells and long-term antiretroviral therapy did not reverse this abnormality. HIV infection, older age, a detectable level of lymphoid tissue viral load in treated patients and protease inhibitor-sparing regimens seem to favour fibrosis in lymphoid tissue.

Plasma rico en plaquetas: fundamentos biológicos y aplicaciones en cirugía maxilofacial y estética facial Platelet-rich plasma: biology and applications in maxillofacial surgery and facial aesthetics

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Jordi Rodríguez Flores

2012-03-01

Full Text Available Esta revisión presenta el uso del preparado de plasma rico en plaquetas (PRP como una herramienta potenciadora de ciertas características histológicas de los tejidos conformados por células con receptores para los factores de crecimiento plaquetarios. Se ha realizado una revisión sobre el plasma rico en plaquetas de la literatura publicada en PubMed. Se describen los fundamentos biológicos del PRP a nivel celular, la técnica de obtención, y sus usos clínicos en la actualidad.This review shows platelet-rich-plasma (PRP as an enhancer of the histological characteristics of the tissues with platelet-derived growth factor receptors. A review has been made of the literature on the platelet-rich plasma published in PubMed. The article describes the cellular biology of PRP, the technique for obtaining it, and its clinical applications.

Total levels of tissue inhibitor of metalloproteinases 1 in plasma yield high diagnostic sensitivity and specificity in patients with colon cancer

DEFF Research Database (Denmark)

Holten-Andersen, Mads N; Christensen, Ib Jarle; Nielsen, Hans Jørgen

2002-01-01

: Total TIMP-1 plasma levels were measured by ELISA in blood samples from two different blood donor populations from IBD patients, and preoperative samples from patients with primary colon cancer (CC), rectal cancer (RC), or breast cancer. RESULTS: There were no significant differences in plasma TIMP-1......PURPOSE: The purpose of this study was to measure total levels of tissue inhibitor of metalloproteinases (TIMP-1) by ELISA in plasma from blood donors, patients with inflammatory bowel disease (IBD), and patients with cancer and to correlate the results to patient diagnosis. EXPERIMENTAL DESIGN...... levels between healthy donors and IBD or breast cancer patients, whereas patients with CC or RC had significantly elevated TIMP-1 levels. Total TIMP-1 levels identified patients with CC with a sensitivity of 63% at 98% specificity, patients with early CC (Dukes' A+B) with a sensitivity of 56% at 98...

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.

Science.gov (United States)

Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

2015-01-01

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

Tissue factor pathway inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study.

Directory of Open Access Journals (Sweden)

Aurélie Di Bartolomeo

Full Text Available The study aimed to evaluate if the rate of tissue factor pathway inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women.This was a prospective multicentre cohort study of 200 patients at a high risk of occurrence or recurrence of placenta-mediated adverse pregnancy outcomes conducted between June 2008 and October 2010. Measurements of tissue factor pathway inhibitor resistance (normalized ratio and tissue factor pathway inhibitor activity were performed for the last 72 patients at 20, 24, 28, 32, and 36 weeks of gestation and during the postpartum period.Overall, 15 patients presented a placenta-mediated adverse pregnancy outcome. There was no difference in normalized tissue factor pathway inhibitor ratios between patients with and without placenta-mediated adverse pregnancy outcomes during pregnancy and in the post-partum period. Patients with placenta-mediated adverse pregnancy outcomes had tissue factor pathway inhibitor activity rates that were significantly higher than those in patients without at as early as 24 weeks of gestation. The same results were observed following delivery.Among high-risk women, the tissue factor pathway inhibitor activity of patients with gestational vascular complications is higher than that in other patients. Hence, these markers could augment a screening strategy that includes an analysis of angiogenic factors as well as clinical and ultrasound imaging with Doppler measurement of the uterine arteries.

Growth/differentiation factor-I5 is an abundant cytokine in human seminal plasma

Czech Academy of Sciences Publication Activity Database

Souček, Karel; Slabáková, Eva; Ovesná, P.; Malenovská, A.; Kozubík, Alois; Hampl, Aleš

2010-01-01

Roč. 25, č. 12 (2010), s. 2962-2971 ISSN 0268-1161 R&D Projects: GA MZd NS9600 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50390703 Keywords : seminal plasma * growth/differentiation factor-15 (GDF-15/MIC-1) * FOXP3 Subject RIV: BO - Biophysics Impact factor: 4.357, year: 2010

Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model.

Science.gov (United States)

Pawlinski, Rafal; Pedersen, Brian; Kehrle, Bettina; Aird, William C; Frank, Rolf D; Guha, Mausumee; Mackman, Nigel

2003-05-15