WorldWideScience

Sample records for acute vascular rejection

  1. Acute Rejection After Kidney Transplantation Associates With Circulating MicroRNAs and Vascular Injury

    Science.gov (United States)

    Bijkerk, Roel; Florijn, Barend W.; Khairoun, Meriem; Duijs, Jacques M. G. J.; Ocak, Gurbey; de Vries, Aiko P.J.; Schaapherder, Alexander F.; Mallat, Marko J. K.; de Fijter, Johan W.; Rabelink, Ton J.; van Zonneveld, Anton Jan; Reinders, Marlies E. J.

    2017-01-01

    Background Acute rejection (AR) of kidney transplants is associated with the loss of endothelial integrity, microvascular rarefaction and, ultimately, graft dysfunction. Circulating angiogenic microRNAs (miRNAs) may serve as markers for microvascular injury. Here, we investigated the short- and long-term effects of AR after kidney transplantation on systemic vascular injury and the associated circulating miRNA profile. Methods Systemic vascular injury was determined by measuring capillary tortuosity and density within the oral mucosa as well as by assessing circulating levels of angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor and soluble thrombomodulin. After a pilot study, we selected 48 miRNAs to assess the AR- and microvascular injury associated circulating miRNAs. Results In stable transplant recipients (n = 25) and patients with AR (n = 13), which were also studied longitudinally (1, 6, and 12 months post-AR), we found an AR-associated increase in markers of systemic vascular injury, of which vascular endothelial growth factor and soluble thrombomodulin normalized within 1 year after AR. Of the 48 selected miRNAs, 8 were either decreased (miR-135a, miR-199a-3p, and miR-15a) or increased (miR-17, miR-140-3p, miR-130b, miR-122 and miR-192) in AR. Of these, miR-130b, miR-199a, and miR-192 associated with markers of vascular injury, whereas miR-140-3p, miR-130b, miR-122, and miR-192 normalized within 1 year after AR. Conclusions AR after kidney transplantation is characterized by systemic microvascular injury and associates with specific circulating miRNA levels. PMID:28706977

  2. Ultrastructural basis of acute renal allograft rejection

    NARCIS (Netherlands)

    V.D. Vuzevski (Vojislav)

    1976-01-01

    textabstractAn attempt was made: I. to demonstrate the evolution and the time of onset of the ultrastructural morphological changes in the renal parenchyma and blood vessels, as well as the ultrastructural feature of the interstitial cellular infiltration in acute rejection of kidney allografts; 2.

  3. THE DIAGNOSIS OF LIVER ALLOGRAFT ACUTE REJECTION IN LIVER BIOPSIES

    Directory of Open Access Journals (Sweden)

    L. V. Shkalova

    2011-01-01

    Full Text Available We performed histological examination of 80 liver allograft biopsies, the diagnosis of acute rejection was proved in 34 cases. Histological changes in liver biopsies in different grades of acute rejection were estimated according to Banff classification 1995, 1997 and were compared with current literature data. The article deals with the question of morphological value of grading acute rejection on early and late, also we analyze changes in treat- ment tactics after morphological verification of liver allograft acute rejection

  4. Acute antibody-mediated rejection in pancreas and kidney transplantation

    NARCIS (Netherlands)

    Kort, Hanneke de

    2013-01-01

    In this thesis, acute rejection after kidney, simultaneous pancreas and kidney (SPKT), and islets of Langerhans transplantation was addressed. The focus is on acute antibody-mediated rejection (AMR) after transplantation and on a potential strategy using cellular immune modulation to prevent acute

  5. Acute appendicitis mistaken as acute rejection in renal transplant recipients.

    Directory of Open Access Journals (Sweden)

    Talwalkar N

    1994-01-01

    Full Text Available Case histories of 2 renal transplant recipients are reported who had presenting features of fever, leukocytosis and pain/tenderness over right iliac fossa and were diagnosed to be due to acute appendicitis rather than more commonly suspected acute rejection episode which has very similar features. Diagnosis of acute appendicitis was suspected on the basis of rectal examination and later confirmed by laparotomy. The purpose of this communication is to emphasize the need for proper diagnosis in patient with such presentation; otherwise wrong treatment may be received.

  6. Successful reversal of acute vascular rejection and cyclosporine-associated nephrotoxicity in renal allograft with combined sirolimus and mycophenolate mofetil as immunotherapy.

    Science.gov (United States)

    Ołdakowska-Jedynak, U; Paczek, L; Mucha, K; Foroncewicz, B; Perkowska-Ptasińska, A

    2006-01-01

    Cyclosporine (CsA) has substantially improved patient and graft survival rates in solid organ transplantation. In clinical studies, sirolimus has been shown to be as effective as CsA to maintain survival of renal and cardiac allografts without causing nephrotoxicity. Herein we describe a patient with biopsy-proven CsA-associated nephrotoxicity and refractory renal allograft rejection who was converted from steroids, CsA, and azathioprine to steroids, sirolimus (RAPA), and low-dose mycophenolate mofetil (MMF). The follow-up period was 60 months. We observed substantial improvement, even normalization in renal function. Our patient did not give consent to repeat biopsy after conversion. We also observed a beneficial effect of CsA withdrawal on blood pressure control. The spectrum of adverse events induced by sirolimus seemed to be mild relative to the potency of the immunosuppressive effect. The excellent response to combined RAPA and MMF in this patient was probably due to "concerted actions" of these agents on both B- and T-cell functions. The combination enhanced therapeutic efficacy while minimizing the toxicity of individual drugs used in the regimen. These findings suggest that sirolimus, when used as a base therapy in combination with low-dose MMF in a renal allograft recipient, may be an alternative to CsA-based therapy, providing potent immunosuppression of a renal allograft. Sirolimus administration facilitated steroids dose reduction.

  7. The significance of parenchymal changes of acute cellular rejection in predicting chronic liver graft rejection

    NARCIS (Netherlands)

    Gouw, ASH; van den Heuvel, MC; van den Berg, AP; Slooff, NJH; de Jong, KP; Poppema, S

    2002-01-01

    Background. Chronic rejection (CR) in liver allografts shows a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition

  8. Fractal analysis of heart graft acute rejection microscopic images.

    Science.gov (United States)

    Pijet, M; Nozynski, J; Konecka-Mrowka, D; Zakliczynski, M; Hrapkowicz, T; Zembala, M

    2014-10-01

    Endomyocardial biopsy to evaluate rejection in the transplanted heart is accepted at the "gold standard." The complexity of microscopic images suggested using digital methods for precise evaluating of acute rejection episodes with numerical representation. The aim of the present was study to characterize digitally acute rejection of the transplanted heart using complexity/fractal image analysis. Biopsy samples harvested form 40 adult recipients after orthotropic heart transplantation were collected and rejection grade was evaluated according to the International Society for Heart and Lung Transplantation (0, 1a, 1b, or 3a) at transverse and longitudinal sections. Fifteen representative digital microscope images from each grade were collected and analyzed after Sobel edge detection and binarization. Only mean fractal dimension showed a progressive and significant increase and correlation based on rejection grade using longitudinal sections. Lacunarity and number of foreground pixels showed unequivocal results. Mean fractal diameter could serve as auxiliary digital parameter for grading of acute rejection in the transplanted heart.

  9. Acute rejection and humoral sensitization in lung transplant recipients.

    Science.gov (United States)

    Martinu, Tereza; Chen, Dong-Feng; Palmer, Scott M

    2009-01-15

    Despite the recent introduction of many improved immunosuppressive agents for use in transplantation, acute rejection affects up to 55% of lung transplant recipients within the first year after transplant. Acute lung allograft rejection is defined as perivascular or peribronchiolar mononuclear inflammation. Although histopathologic signs of rejection often resolve with treatment, the frequency and severity of acute rejections represent the most important risk factor for the subsequent development of bronchiolitis obliterans syndrome (BOS), a condition of progressive airflow obstruction that limits survival to only 50% at 5 years after lung transplantation. Recent evidence demonstrates that peribronchiolar mononuclear inflammation (also known as lymphocytic bronchiolitis) or even a single episode of minimal perivascular inflammation significantly increase the risk for BOS. We comprehensively review the clinical presentation, diagnosis, histopathologic features, and mechanisms of acute cellular lung rejection. In addition, we consider emerging evidence that humoral rejection occurs in lung transplantation, characterized by local complement activation or the presence of antibody to donor human leukocyte antigens (HLA). We discuss in detail methods for HLA antibody detection as well as the clinical relevance, the mechanisms, and the pathologic hallmarks of humoral injury. Treatment options for cellular rejection include high-dose methylprednisolone, antithymocyte globulin, or alemtuzumab. Treatment options for humoral rejection include intravenous immunoglobulin, plasmapheresis, or rituximab. A greater mechanistic understanding of cellular and humoral forms of rejection and their role in the pathogenesis of BOS is critical in developing therapies that extend long-term survival after lung transplantation.

  10. Acute rejection episodes after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Hamida Fethi

    2009-01-01

    Full Text Available Acute rejection episodes (AREs are a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains, at least partially, the improvement seen in the results of transplantation in recent years. The objectives of this study are to analyze the incidence and severity of AREs, their risk factors and their influence on graft and patient survival. We retrospectively studied 280 kidney transplants performed in adults at the Charles Nicolle Hospital, Tunis, between 1986 and 2004. The diagnosis of ARE was based on clinical data and response to treatment. Allograft biopsies were performed in ten cases. The treatment of AREs consisted of pulse methylprednisolone and anti-thymocyte globulin. There were 186 males (66.4% and 94 females (33.6%, and their mean age was 31 ± 8.9 years. Overall, the 280 study patients experienced a total of 113 AREs. Of them, 85 had only one ARE, 28 had two to three and none had more than three AREs. A total of 68 AREs were completely re-versible, 42 were partially reversible while three could not be reversed with treatment. The mean inci-dence of AREs was 40.4%. The incidence was > 45% between 1986 and 1997, decreased to 20.5% between 1998 and 2000 and to 9% between 2001 and 2004. Graft survival rates in patients with and without AREs were respectively 91% and 93% at three years, 82% and 90% at five years and 73% and 83% at 10 years. We found a decrease in the incidence of AREs in recent years in our study patients, and this was related to the introduction of sensitized cross-match and the newer immunosuppressive agents, particularly MMF. Additionally, AREs had a deleterious impact on late graft survival in our study population.

  11. Mouse model of alloimmune-induced vascular rejection and transplant arteriosclerosis.

    Science.gov (United States)

    Enns, Winnie; von Rossum, Anna; Choy, Jonathan

    2015-05-17

    Vascular rejection that leads to transplant arteriosclerosis (TA) is the leading representation of chronic heart transplant failure. In TA, the immune system of the recipient causes damage of the arterial wall and dysfunction of endothelial cells and smooth muscle cells. This triggers a pathological repair response that is characterized by intimal thickening and luminal occlusion. Understanding the mechanisms by which the immune system causes vasculature rejection and TA may inform the development of novel ways to manage graft failure. Here, we describe a mouse aortic interposition model that can be used to study the pathogenic mechanisms of vascular rejection and TA. The model involves grafting of an aortic segment from a donor animal into an allogeneic recipient. Rejection of the artery segment involves alloimmune reactions and results in arterial changes that resemble vascular rejection. The basic technical approach we describe can be used with different mouse strains and targeted interventions to answer specific questions related to vascular rejection and TA.

  12. Insights from computational modeling in inflammation and acute rejection in limb transplantation.

    Directory of Open Access Journals (Sweden)

    Dolores Wolfram

    Full Text Available Acute skin rejection in vascularized composite allotransplantation (VCA is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection.

  13. Salivary cortisol in response to acute social rejection and acceptance by peers.

    Science.gov (United States)

    Blackhart, Ginette C; Eckel, Lisa A; Tice, Dianne M

    2007-07-01

    Past research indicates that social rejection predicts a wide range of psychological problems (e.g., depression), but laboratory studies examining self-reports of negative affect after social rejection have reported inconsistent results. Salivary cortisol was measured before and after a social rejection/acceptance manipulation for objective assessment of psychological distress subsequent to peer rejection. Rejected participants were predicted to show significantly greater salivary cortisol than accepted or control participants. The present research also examined several factors that may moderate the relationship between acute rejection and cortisol. As predicted, rejected participants exhibited significantly higher cortisol than accepted or control participants. Defensiveness moderated the relationship between rejection and cortisol; highly defensive rejected participants showed significantly lower cortisol than less defensive rejected participants after peer rejection. Results indicate that social rejection causes psychological distress, but highly defensive individuals appear to be less susceptible than less defensive individuals to increases in salivary cortisol after acute social rejection.

  14. Differentiation between Acute Skin Rejection in Allotransplantation and T-Cell Mediated Skin Inflammation Based on Gene Expression Analysis

    Directory of Open Access Journals (Sweden)

    Dolores Wolfram

    2015-01-01

    Full Text Available Advances in microsurgical techniques and immunosuppressive medication have rendered transplantation of vascularized composite allografts possible, when autologous tissue is neither available nor sufficient for reconstruction. However, skin rejection and side effects of long-term immunosuppression still remain a major hurdle for wide adoption of this excellent reconstructive technique. Histopathologic changes during acute skin rejection in vascular composite allotransplantation often mimic inflammatory skin disorders and are hard to distinguish. Hence, the identification of diagnostic and therapeutic markers specific for skin rejection is of particular clinical need. Here we present novel markers allowing for early differentiation between rejection in hind limb allotransplantation and contact hypersensitivity. Assessment of Ccl7, Il18, and Il1b expression is most indicative of distinguishing skin rejection from skin inflammatory disorders. Gene expression levels varied significantly across skin types and regions, indicating localization specific mechanism of leukocyte migration and infiltration. Expression of Il12b, Il17a, and Il1b gene expression levels differed significantly between rejection and inflammation, independent of the skin type. In synopsis of the RNA expression profile and previously assessed protein expression, the Il1 family appears as a promising option for accurate skin rejection diagnosis and, as a following step, for development of novel rejection treatments.

  15. Multiquadrant Subtenon Triamcinolone Injection for Acute Corneal Graft Rejection: A Case Report

    Directory of Open Access Journals (Sweden)

    Sunali Goyal

    2017-05-01

    Full Text Available Background: We report a case of reversal of an acute corneal graft rejection following multiquadrant subtenon triamcinolone injection. Case Presentation: A 19-year-old woman who had acute corneal graft rejection failed to show resolution of the graft rejection after standard treatment with systemic, intravenous, and topical steroids. The graft rejection, however, responded to injection of triamcinolone in multiple subtenon quadrants. Conclusions: For corneal graft rejection, multiquadrant subtenon triamcinolone injections may be a safe adjunct to systemic treatment.

  16. Rejection

    National Research Council Canada - National Science Library

    Black, Mary

    2007-01-01

    .... [...]my long term favourite story comes from Ireland, where in the chaotic, jobless mid-1980s one friend applied for everything going and then wallpapered his bathroom with the rejection letters...

  17. Late Acute Rejection Occuring in Liver Allograft Recipients

    Directory of Open Access Journals (Sweden)

    Eric M Yoshida

    1996-01-01

    Full Text Available To study the effect of immunosuppressive reduction on the incidence and consequence of late acute rejection (LAR in liver allograft recipients, mean daily prednisone dose, mean cyclosporine A (CsA trough and nadir levels were retrospectively reviewed for the nearest 12-week period preceding six episodes of LAR in five liver allograft recipients (group 1. Results were compared with those from a cohort of 12 liver allograft recipients who did not develop LAR (group 2. LAR was defined as acute rejection occurring more than 365 days post-transplantation. Median follow-up for both groups was similar (504 days, range 367 to 1050, versus 511 days, range 365 to 666, not significant. Mean trough CsA levels were lower in patients with LAR compared with those without (224±66 ng/mL versus 233±49 ng/mL but the difference was not statistically significant. In contrast, mean daily prednisone dose (2.5±1.6 mg/ day versus 6.5±2.9 mg/day, P=0.007 and CsA nadir values (129±60 ng/mL versus 186±40 ng/mL, P=0.03 were significantly lower in patients who developed LAR compared with those who did not. Five of six episodes (83% of LAR occurred in patients receiving less than 5 mg/day of prednisone, versus a single LAR episode in only one of 12 patients (8% receiving prednisone 5 mg/day or more (P=0.004. In all but one instance, LAR responded to pulse methylprednisolone without discernible affect on long term graft function. The authors conclude that liver allograft recipients remain vulnerable to acute rejection beyond the first post-transplant year; and reduction of immunosuppressive therapy, particularly prednisone, below a critical, albeit low dose, threshold increases the risk of LAR.

  18. VASCULAR ENDOTHELIAL GROWTH FACTORS IN HEART TRANSPLANT REJECTIONS

    Directory of Open Access Journals (Sweden)

    O. P. Shevchenko

    2015-01-01

    Full Text Available Aim: to determine the clinical significance of vascular endothelial growth factors VEGF-A, VEGF-D, PlGF-1 to assess the risk of cardiovascular complications in heart recipients. Materials and methods. 103 patients, aged 16 to 73 years, 85 males and 18 females. 65 recipients (47 men and 18 women had dilated cardiomyopathy, 38 – coronary heart disease (CHD. The concentration of VEGF-A, VEGF-D, PlGF-1 was measured using xMAP technology with sets of reagents Simplex ProcartaPlex™. Results. After HTx the level of VEGF-A significantly decreased, p = 0.001. There were no correlations between the levels of VEGF-A, VEGF-D and PlGF-1 with age, gender and diagnosis. After HTx VEGF-A level was higher in recipients with ACR than in those without it (p = 0.001. ACR frequency was significantly higher in patients with high VEGF-A level (≥316.5 pg/ml, RR = 5.8 ± 0.5, AUC = 0.779. After HTx PlGF-1 level was higher in recipients with ACR too (p = 0.039. ACR frequency was significantly higher in patients with high PlGF-1 level (≥5.33 pg/ml, RR = 1.8 ± 0.5, AUC = 0.65. There were no correlations between VEGF-D level with ACR and all three biomarkers with AMR. ACR frequency was significantly higher with both high VEGF-A and PlGF-1 levels (RR = 6.4. Conclusion. Serum levels of VEGF-A and PlGF-1 after HTx may be regarded as indicators of increased risk of ACR.

  19. Shotgun Proteomics Identifies Proteins Specific for Acute Renal Transplant Rejection

    Energy Technology Data Exchange (ETDEWEB)

    Sigdel, Tara K.; Kaushal, Amit; Gritsenko, Marina A.; Norbeck, Angela D.; Qian, Weijun; Xiao, Wenzhong; Camp, David G.; Smith, Richard D.; Sarwal, Minnie M.

    2010-01-04

    Acute rejection (AR) remains the primary risk factor for renal transplant outcome; development of non-invasive diagnostic biomarkers for AR is an unmet need. We used shotgun proteomics using LC-MS/MS and ELISA to analyze a set of 92 urine samples, from patients with AR, stable grafts (STA), proteinuria (NS), and healthy controls (HC). A total of 1446 urinary proteins were identified along with a number of NS specific, renal transplantation specific and AR specific proteins. Relative abundance of identified urinary proteins was measured by protein-level spectral counts adopting a weighted fold-change statistic, assigning increased weight for more frequently observed proteins. We have identified alterations in a number of specific urinary proteins in AR, primarily relating to MHC antigens, the complement cascade and extra-cellular matrix proteins. A subset of proteins (UMOD, SERPINF1 and CD44), have been further cross-validated by ELISA in an independent set of urine samples, for significant differences in the abundance of these urinary proteins in AR. This label-free, semi-quantitative approach for sampling the urinary proteome in normal and disease states provides a robust and sensitive method for detection of urinary proteins for serial, non-invasive clinical monitoring for graft rejection after

  20. Changes in the serum levels of interleukin-17/interleukin-23 during acute rejection in liver transplantation.

    Science.gov (United States)

    Fábrega, Emilio; López-Hoyos, Marcos; San Segundo, David; Casafont, Fernando; Pons-Romero, Fernando

    2009-06-01

    Interleukin-23 (IL-23) and T helper 17 (Th17) cells have been cast as major players in autoimmunity, but their role in transplantation immunity remains to be specified. The aim of our study was to investigate the time course of serum levels of IL-23 and IL-17 during hepatic allograft rejection. Serum levels of IL-23 and IL-17 were determined in 20 healthy subjects and 50 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 35 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. The concentrations of IL-23 were similar for the rejection group and nonrejection group at early postoperative times. We observed a significant increase in serum IL-23 levels in the rejection group when a diagnosis of acute rejection had been established. Similarly to IL-23, at the diagnosis of acute rejection, the concentration of IL-17 was significantly higher in the rejection group versus the nonrejection group. The whole transplant group, including those with stable graft function, had higher serum levels of IL-23 and IL-17 than the controls during the entire postoperative period. In conclusion, IL-23 and IL-17 are up-regulated during acute hepatic rejection. These findings suggest a role for Th17 cells in human liver allograft rejection. (c) 2009 AASLD.

  1. Cellular mechanisms underlying acute graft rejection: time for reassessment

    NARCIS (Netherlands)

    Alegre, Maria-Luisa; Florquin, Sandrine; Goldman, Michel

    2007-01-01

    Rejection of transplanted organs depends on an orchestrated immune response to histocompatibility antigens expressed by the grafted tissue. Effector mechanisms primarily responsible for the rejection process classically involve type 1 helper CD4(+) T cells, cytotoxic CD8(+) T cells and antibodies.

  2. Selective treatment of early acute rejection after liver transplantation : Effects on liver, infection rate, and outcome

    NARCIS (Netherlands)

    Klompmaker, IJ; Gouw, ASH; Haagsma, EB; TenVergert, EM; Verwer, R; Slooff, MJH

    To evaluate the results of selective treatment of biopsy-proven mild acute rejection episodes, we retrospectively studied 1-week liver biopsies of 103 patients with a primary liver graft in relation to liver function tests. The overall incidence of rejection was 35 %. In four patients the biopsy

  3. Relationship between acute rejection and cyclosporine or mycophenolic acid levels in Japanese heart transplantation.

    Science.gov (United States)

    Wada, Kyoichi; Takada, Mitsutaka; Ueda, Takashi; Ochi, Hiroyuki; Kotake, Takeshi; Morishita, Hideki; Hanatani, Akihisa; Nakatani, Takeshi

    2007-03-01

    Cyclosporine (CsA), Mycophenolate mofetil (MMF) and prednisolone (PSL) are widely used for the prevention of acute rejection after heart transplantation. Recently, the serum concentration - time curves (AUC) of CsA and MMF have been demonstrated to be precise predictors of acute rejection. Fourteen heart transplant patients were treated concomitantly with CsA, MMF, and PSL between May 1999 and November 2005 at the National Cardiovascular Center and of them 3 had acute rejection episodes [International Society for Heart & Lung Transplantation grade 3a]. Two patients (man in his 30 s; woman in her 40 s) had acute rejection with a mycophenolic acid (MPA) AUC(0-12 h) cardiac allograft rejection even if the MMF was temporarily stopped. These 3 patients were investigated to evaluate the relationship between acute rejection and pharmacokinetic parameters, including the CsA C0, C2, AUC(0-4 h) and MPA AUC(0-12 h). The findings suggest that a high CsA AUC(0-4 h) may prevent rejection of a cardiac allograft, even if MMF is stopped or drastically reduced.

  4. Expression of Mitochondrial-Encoded Genes in Blood Differentiate Acute Renal Allograft Rejection

    Science.gov (United States)

    Roedder, Silke; Sigdel, Tara; Hsieh, Szu-Chuan; Cheeseman, Jennifer; Metes, Diana; Macedo, Camila; Reed, Elaine F.; Gritsch, H. A.; Zeevi, Adriana; Shapiro, Ron; Kirk, Allan D.; Sarwal, Minnie M.

    2017-01-01

    Despite potent immunosuppression, clinical and biopsy confirmed acute renal allograft rejection (AR) still occurs in 10–15% of recipients, ~30% of patients demonstrate subclinical rejection on biopsy, and ~50% of them can show molecular inflammation, all which increase the risk of chronic dysfunction and worsened allograft outcomes. Mitochondria represent intracellular endogenous triggers of inflammation, which can regulate immune cell differentiation, and expansion and cause antigen-independent graft injury, potentially enhancing the development of acute rejection. In the present study, we investigated the role of mitochondrial DNA encoded gene expression in biopsy matched peripheral blood (PB) samples from kidney transplant recipients. Quantitative PCR was performed in 155 PB samples from 115 unique pediatric (21 years) renal allograft recipients at the point of AR (n = 61) and absence of rejection (n = 94) for the expression of 11 mitochondrial DNA encoded genes. We observed increased expression of all genes in adult recipients compared to pediatric recipients; separate analyses in both cohorts demonstrated increased expression during rejection, which also differentiated borderline rejection and showed an increasing pattern in serially collected samples (0–3 months prior to and post rejection). Our results provide new insights on the role of mitochondria during rejection and potentially indicate mitochondria as targets for novel immunosuppression. PMID:29164120

  5. Expression of Mitochondrial-Encoded Genes in Blood Differentiate Acute Renal Allograft Rejection

    Directory of Open Access Journals (Sweden)

    Silke Roedder

    2017-11-01

    Full Text Available Despite potent immunosuppression, clinical and biopsy confirmed acute renal allograft rejection (AR still occurs in 10–15% of recipients, ~30% of patients demonstrate subclinical rejection on biopsy, and ~50% of them can show molecular inflammation, all which increase the risk of chronic dysfunction and worsened allograft outcomes. Mitochondria represent intracellular endogenous triggers of inflammation, which can regulate immune cell differentiation, and expansion and cause antigen-independent graft injury, potentially enhancing the development of acute rejection. In the present study, we investigated the role of mitochondrial DNA encoded gene expression in biopsy matched peripheral blood (PB samples from kidney transplant recipients. Quantitative PCR was performed in 155 PB samples from 115 unique pediatric (<21 years and adult (>21 years renal allograft recipients at the point of AR (n = 61 and absence of rejection (n = 94 for the expression of 11 mitochondrial DNA encoded genes. We observed increased expression of all genes in adult recipients compared to pediatric recipients; separate analyses in both cohorts demonstrated increased expression during rejection, which also differentiated borderline rejection and showed an increasing pattern in serially collected samples (0–3 months prior to and post rejection. Our results provide new insights on the role of mitochondria during rejection and potentially indicate mitochondria as targets for novel immunosuppression.

  6. Impact of the addition of maintenance steroids to a rapid steroid discontinuation immunosuppressive protocol following acute renal transplant rejection.

    Science.gov (United States)

    Arora, Swati; Marcus, Richard J; Dikkala, Sudharani; Sureshkumar, Kalathil K

    2009-12-01

    Rapid steroid discontinuation immunosuppressive protocols are increasingly used in renal transplant. The optimal immunosuppressive regimen in patients who develop acute rejection while on a rapid steroid discontinuation protocol is less clear. We examined our experience of adding maintenance steroid therapy in renal transplant recipients who developed 1 or more acute rejection episode while on a rapid steroid discontinuation protocol. The outcome of 145 patients who underwent renal transplant from 2002 to 2007 and initiated a rapid steroid discontinuation protocol was analyzed. Patients were divided into the following 5 groups: (i): acute rejection X 1 and no maintenance steroids, (ii): acute rejection X 1 and started on maintenance steroids, (iii): acute rejection X 2 and no maintenance steroids (iv): acute rejection X 2 and started on maintenance steroids, and (v): no acute rejection Compared with patients with no acute rejection, graft survival was significantly inferior in patients who experienced 2 or more acute rejection episodes-whether they were started on maintenance steroids (P = .003) or not (P = .006) - but was similar in patients who experienced only 1 episode of acute rejection, and were started either on maintenance steroids (P = .87) or were continued on the rapid steroid discontinuation protocol (P = .69). In patients who sustained 2 episodes of acute rejection, addition of maintenance steroids had no impact on graft survival (P = .97). More than 1 episode of acute rejection in renal transplant recipients on rapid steroid discontinuation protocol is associated with poor, long-term, graft survival, which remains unchanged despite starting maintenance steroids. The use of maintenance steroids may not have a positive impact on graft survival after acute rejection.

  7. Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

    Directory of Open Access Journals (Sweden)

    Mingliang Li

    Full Text Available Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant.Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05. Progressive allograft fibrosis as well as collagen deposition were observed.These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

  8. Ultrasound molecular imaging of acute cardiac transplantation rejection using nanobubbles targeted to T lymphocytes.

    Science.gov (United States)

    Liu, Jinfeng; Chen, Yihan; Wang, Guohua; Lv, Qing; Yang, Yali; Wang, Jing; Zhang, Pingyu; Liu, Jie; Xie, Yu; Zhang, Li; Xie, Mingxing

    2018-02-08

    Clinical surveillance of acute heart transplantation rejection requires repeated invasive endomyocardial biopsies and noninvasive diagnostic techniques are desperately needed. It is acknowledged that T lymphocyte infiltration is the central process of acute rejection. We hypothesized that ultrasound molecular imaging with T lymphocyte-targeted nanobubbles could be used to detect acute rejection in heart transplantation. In this study, nanobubbles bearing anti-CD3 antibody (NB CD3 ) or isotype antibody (NB con ) were prepared and characterized. There was significant adhesion of NB CD3 to T lymphocytes compared with NB con in vitro. The signal intensity of the adherent NB CD3 was significantly higher than that of the NB con in allograft rats, but not significantly different in isograft rats. Furthermore, the signal intensity of NB CD3 in allograft rats was significantly higher than that in isograft rats, indicating more T lymphocyte infiltration in allograft rats compared with isograft rats. These results were further confirmed by immunohistochemistry examination, and the signal intensity of NB CD3 was positively correlated with the number of T lymphocytes in allograft rats. In summary, ultrasound molecular imaging with T lymphocyte-targeted nanobubbles can detect T lymphocyte infiltration in acute rejection and could be used as a noninvasive method in acute rejection detection after cardiac transplantation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation

    Directory of Open Access Journals (Sweden)

    Priscila Cilene León Bueno de Camargo

    2014-08-01

    Full Text Available Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4. The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients.

  10. T cell immunohistochemistry refines lung transplant acute rejection diagnosis and grading.

    Science.gov (United States)

    Cheng, Lin; Guo, Haizhou; Qiao, Xinwei; Liu, Quan; Nie, Jun; Li, Jinsong; Wang, Jianjun; Jiang, Ke

    2013-10-14

    Lung transplant volume has been increasing. However, inaccurate and uncertain diagnosis for lung transplant rejection hurdles long-term outcome due to, in part, interobserver variability in rejection grading. Therefore, a more reliable method to facilitate diagnosing and grading rejection is warranted. Rat lung grafts were harvested on day 3, 7, 14 and 28 post transplant for histological and immunohistochemical assessment. No immunosuppressive treatment was administered. We explored the value of interstitial T lymphocytes quantification by immunohistochemistry and compared the role of T cell immunohistochemistry with H&E staining in diagnosing and grading lung transplant rejection. Typical acute rejection from grade A1 to A4 was found. Rejection severity was heterogeneously distributed in one-third transplanted lungs (14/40): lesions in apex and center were more augmented than in the base and periphery of the grafts, respectively. Immunohistochemistry showed profound difference in T lymphocyte infiltration among grade A1 to A4 rejections. The coincidence rate of H&E and immunohistochemistry was 77.5%. The amount of interstitial T lymphocyte infiltration increased gradually with the upgrading of rejection. The statistical analysis demonstrated that the difference in the amount of interstitial T lymphocytes between grade A2 and A3 was not obvious. However, T lymphocytes in lung tissue of grade A4 were significantly more abundant than in other grades. Rejection severity was heterogeneously distributed within lung grafts. Immunohistochemistry improves the sensitivity and specificity of rejection diagnosis, and interstitial T lymphocyte quantitation has potential value in diagnosing and monitoring lung allograft rejection. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1536075282108217.

  11. Delta Neutrophil Index as a Marker for Differential Diagnosis between Acute Graft Pyelonephritis and Acute Graft Rejection.

    Directory of Open Access Journals (Sweden)

    Dong Ho Shin

    Full Text Available The delta neutrophil index (DNI is the fraction of circulating immature granulocytes, which reflect infectious and/or septic condition. Acute graft pyelonephritis (AGPN versus acute graft rejection is a frequently encountered diagnostic and therapeutic dilemma in kidney transplant recipients, but little is known about the clinical usefulness of DNI value in the differentiation of the two conditions.A total of 90 episodes of AGPN or acute graft rejection were evaluated at the Kangdong Sacred Heart Hospital between 2008 and 2014. We performed retrospective analysis of demographic, clinical, and laboratory parameters data. Receiver operating curves (ROC and multivariate logistic regression were conducted to ascertain the utility of DNI in discriminating between AGPN and acute graft rejection.AGPN group had significantly higher DNI values than acute graft rejection group (2.9% vs. 1.9%, P < 0.001. The area under the ROC curve for DNI value to discriminate between AGPN and acute graft rejection was 0.85 (95% confidence interval [CI]; 0.76-0.92, P < 0.001. A DNI value of 2.7% was selected as the cut-off value for AGPN, and kidney transplant recipients with a DNI value ≥ 2.7% were found to be at a higher risk of infection than those with a DNI < 2.7% (odd ratio [OR] 40.50; 95% CI 8.68-189.08; P < 0.001. In a multivariate logistic regression analysis, DNI was a significant independent factor for predicting AGPN after adjusting age, sex, log WBC count, log neutorphil count, log lymphocyte count, CRP concentration, and procalcitonin concentration (OR 4.32; 95% CI 1.81-10.34, P < 0.001.This study showed that DNI was an effective marker to differentiate between AGPN and acute graft rejection. Thus, these finding suggest that DNI may be a useful marker in the management of these patients.

  12. A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.

    Science.gov (United States)

    Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

    2013-10-21

    Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.

  13. Local production of interleukin-6 during acute rejection in human renal allografts

    NARCIS (Netherlands)

    Raasveld, M. H.; Weening, J. J.; Kerst, J. M.; Surachno, S.; ten Berge, R. J.

    1993-01-01

    Interleukin-6 is involved in T-cell activation and possibly plays a role in the pathogenesis of acute rejection of transplanted organs. This is indicated by elevated levels of interleukin-6 in serum and urine of renal allograft recipients, and elevated amounts of mRNA for interleukin-6 in all

  14. Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons

    NARCIS (Netherlands)

    Tillou, Xavier; Poirier, Nicolas; Le Bas-Bernardet, Stephanie; Hervouet, Jeremy; Minault, David; Renaudin, Karine; Vistoli, Fabio; Karam, Georges; Daha, Mohamed; Soulillou, Jean Paul; Blancho, Gilles

    Acute antibody-mediated rejection is an unsolved issue in transplantation, especially in the context of pretransplant immunization. The deleterious effect of preformed cytotoxic anti-HLA antibodies through complement activation is well proven, but very little is known concerning complement blockade

  15. Interleukin 18 (IL-18) upregulation in acute rejection of kidney allograft

    Czech Academy of Sciences Publication Activity Database

    Stříž, I.; Krásná, E.; Honsová, E.; Lácha, J.; Petříčková, Kateřina; Jarešová, M.; Lodererová, A.; Böhmová, R.; Valhová, Š.; Slavcev, A.; Vitko, S.

    2005-01-01

    Roč. 99, - (2005), s. 30-35 ISSN 0165-2478 R&D Projects: GA MZd NI6843 Institutional research plan: CEZ:AV0Z50200510 Keywords : kidney transplantation * IL-18 * acute rejection Subject RIV: EE - Microbiology, Virology Impact factor: 2.301, year: 2005

  16. DISTINCT PHENOTYPES OF INFILTRATING CELLS DURING ACUTE AND CHRONIC LUNG REJECTION IN HUMAN HEART-LUNG TRANSPLANTS

    NARCIS (Netherlands)

    WINTER, JB; CLELLAND, C; GOUW, ASH; PROP, J

    1995-01-01

    To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung

  17. Serum Levels of Interleukin-34 During Acute Rejection in Liver Transplantation.

    Science.gov (United States)

    San Segundo, D; Ruiz, P; Irure, J; Arias-Loste, M T; Cuadrado, A; Puente, A; Casafont, F; López-Hoyos, M; Crespo, J; Fábrega, E

    2016-11-01

    Accumulating evidence indicates that interleukin (IL)-34 participates in T-cell homeostasis and tolerance due to the ability of IL-34 to trigger apoptosis of Th1, Th17, and Tc1 cells, but spare Th2 cells and Treg. In addition, IL-34 exerts anti-inflammatory effects by impairing leukocyte adhesion and transendothelial migration, and reducing the secretion of proinflammatory cytokines. The aim of our study was to investigate the time course of serum levels of IL-34 during hepatic allograft rejection. Serum levels of IL-34 were determined in 20 healthy subjects and 45 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 30 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. The concentrations of IL-34 were higher in the rejection group vs nonrejection group during the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-34 serum levels than the controls at all times after liver transplantation. Our preliminary results could be related to the recent finding that IL-34 may play an immune-suppressive role in liver transplantation. In our case, although we must be cautious with serum data, increased IL-34 would help to control alloresponse during rejection and protect from graft lost. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Heat Shock Protein 90α Is a Potential Serological Biomarker of Acute Rejection after Renal Transplantation.

    Directory of Open Access Journals (Sweden)

    Takeshi Maehana

    Full Text Available Heat shock protein 90 (HSP90, a molecular chaperone associated with the activation of client proteins, was recently reported to play an important role in immunologic reactions. To date, the role of HSP90 in solid organ transplantations has remained unknown. The aim of this study was to evaluate the relationship between serum HSP90α levels and acute allograft rejection after organ and tissue transplantation using serum samples from kidney allograft recipients, an in vitro antibody-mediated rejection model, and a murine skin transplantation.Serum HSP90α levels were significantly higher in kidney recipients at the time of acute rejection (AR than in those with no evidence of rejection. In most cases with AR, serum HSP90 decreased to baseline after the treatment. On the other hand, serum HSP90α was not elevated as much in patients with chronic rejection, calcineurin inhibitor nephrotoxicity, or BK virus nephropathy as in AR patients. In vitro study showed that HSP90α concentration in the supernatant was significantly higher in the supernatant of human aortic endothelial cells cocultured with specific anti-HLA IgG under complement attack than in that of cells cocultured with nonspecific IgG. In mice receiving skin transplantation, serum HSP90α was elevated when the first graft was rejected and the level further increased during more severe rejection of the second graft.The results suggest that HSP90α is released into the serum by cell damage due to AR in organ and tissue transplantation, and it is potentially a new biomarker to help detect AR in kidney recipients.

  19. The effect of pregnancy on humoral rejection in patients after vascularized organ transplantation.

    Science.gov (United States)

    Cyganek, A; Nowaczyk, M; Sańko-Resmer, J; Pietrzak, B; Grzechocińska, B; Pączek, L; Międzybrodzki, R; Wielgoś, M

    2015-11-01

    The aim of the study was to evaluate the effect of pregnancy on the production of donor- and nondonor-specific anti-human leukocyte antigen antibodies (anti-HLA Abs) in organ allograft recipients. The study group included four pregnant kidney (RT) and four liver (LT) transplant recipients. The genotype of HLA class I (A, B) and class II (DR) antigens was assessed. Anti-HLA antibodies class I and II were evaluated between 36 and 40 weeks' gestation. Two different control groups consisted of the following: group I (n=8) with nonpregnant RT (n=6) and LT recipients (n=2), and group II with healthy pregnant women (n=10) with anti-HLA Abs detected between 38 and 41 weeks' gestation. The HLA genotype was determined in fathers of the fetuses from the study group and group II controls. Half of group II controls had donor-specific anti-HLA (A, B, and/or DR) Abs, while nondonor-specific anti-HLA Abs were detected in all subjects from that group. Anti-HLA Abs were found in all group II controls. In the study group, anti-HLA Abs were found in only two LT recipients and one RT recipient, but they were not confirmed as donor-specific. Anti-HLA antibodies were not detected in the study group, whereas six out of ten group II controls had anti-HLA Abs against the HLA of the child's father. Pregnancy in vascularized organ recipients does not trigger the mechanism of humoral rejection involving anti-HLA class I and II antibodies with a potentially adverse impact on graft function. Copyright © 2015. Published by Elsevier Ireland Ltd.

  20. Presumed serum sickness following thymoglobulin treatment of acute cellular rejection of a cardiac allograft.

    Science.gov (United States)

    Ratushny, Vladimir; Capell, Brian C; Rosenbach, Misha

    2017-09-01

    Serum sickness is a hypersensitivity reaction to proteins in antiserum derived from nonhuman animal sources and can be seen in patients being treated with antiserum to prevent transplant rejection. Serum sickness may display variable clinical presentations. Because cutaneous findings may be the initial symptom in some cases, it is important for dermatologists to be able to recognize this condition given its potentially life-threatening symptoms. We present a case of a 35-year-old man with presumed serum sickness after receiving thymoglobulin for the treatment of acute cellular rejection of a heart transplant. The clinical presentation, laboratory findings, and treatment options are reviewed.

  1. IL-15 is decreased upon CsA and FK506 treatment of acute rejection following heart transplantation in mice.

    Science.gov (United States)

    Yu, Zhiyong; Zhou, Xiaoping; Yu, Songfeng; Xie, Haiyang; Zheng, Shusen

    2015-01-01

    The aim of this study was to investigate the effect of cyclosporine A (CsA) and tacrolimus (FK506) on interleukin-15 (IL-15) production during acute rejection following heart transplantation in mice. Inbred male Balb/c (H‑2d) and C57BL/6 (H-2b) mice were used to establish a heterotopic intra-abdominal cardiac transplantation model. The mice were divided in four groups: syngeneic control, allogeneic acute rejection, allogeneic rejection treated with CsA, and allogeneic rejection treated with FK506. The expression of IL-15, IL-2, and tumor necrosis factor-α (TNF-α) was measured using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. A low level of IL-15 was detected in transplanted hearts of the control group, with a significant increase observed in the allogeneic acute rejection group. Compared to the allogeneic acute rejection group, IL-15 expression was significantly decreased in the CsA- and FK506-treated allogeneic rejection groups. The TNF-α expression pattern was similar to that of IL-15 in all groups. IL-2 expression was increased in the allogeneic acute rejection group and was inhibited in mice treated with CsA and FK506. In conclusion, increased IL-15 expression in rejected murine heart grafts may be reduced by CsA and FK506 in vivo.

  2. Combined strategy of endothelial cells coating, Sertoli cells coculture and infusion improves vascularization and rejection protection of islet graft.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available Improving islet graft revascularization and inhibiting rejection become crucial tasks for prolonging islet graft survival. Endothelial cells (ECs are the basis of islet vascularization and Sertoli cells (SCs have the talent to provide nutritional support and exert immunosuppressive effects. We construct a combined strategy of ECs coating in the presence of nutritious and immune factors supplied by SCs in a co-culture system to investigate the effect of vascularization and rejection inhibition for islet graft. In vivo, the combined strategy improved the survival and vascularization as well as inhibited lymphocytes and inflammatory cytokines. In vitro, we found the combinatorial strategy improved the function of islets and the effect of ECs-coating on islets. Combined strategy treated islets revealed higher levels of anti-apoptotic signal molecules (Bcl-2 and HSP-32, survival and function related molecules (PDX-1, Ki-67, ERK1/2 and Akt and demonstrated increased vascular endothelial growth factor receptor 2 (KDR and angiogenesis signal molecules (FAk and PLC-γ. SCs effectively inhibited the activation of lymphocyte stimulated by islets and ECs. Predominantly immunosuppressive cytokines could be detected in culture supernatants of the SCs coculture group. These results suggest that ECs-coating and Sertoli cells co-culture or infusion synergistically enhance islet survival and function after transplantation.

  3. Impact of animal strain on gene expression in a rat model of acute cardiac rejection

    Directory of Open Access Journals (Sweden)

    Norsworthy Kelly J

    2009-06-01

    Full Text Available Abstract Background The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR. Using a rat heart transplant model and 2 different rat strains (Dark Agouti, and Brown Norway, microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC. Results In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ≥ 3. Only 13 genes were affected by both strain and rejection, which was Conclusion In ACR, genetic background has a large impact on the transcriptome of immune cells, but not heart tissue. Gene expression studies of ACR should avoid study designs that require cross strain comparisons between leukocytes.

  4. Transfer of tolerance to collagen type V suppresses Th-17 lymphocyte mediated acute lung transplant rejection

    Science.gov (United States)

    Braun, Ruedi K.; Molitor-Dart, Melanie; Wigfield, Christopher; Xiang, Zhuzai; Fain, Sean B.; Jankowska-Gan, Ewa; Seroogy, Christine M.; Burlingham, William J.; Wilkes, David S.; Brand, David D.; Torrealba, Jose; Love, Robert B.

    2009-01-01

    Background Rat lung allograft rejection is mediated by collagen type V (col(V)) specific Th17 cells. Adoptive transfer of these cells is sufficient to induce rejection pathology in isografts, whereas tolerance to col(V) suppresses allograft rejection. We therefore tested if regulatory T cells from tolerant rats could suppress the Th17 mediated rejection in the syngeneic model of lung transplantation. Methods Rats were subjected to syngeneic left lung transplantation and acute rejection was induced by adoptive transfer of lymph node cells from col(V)-immunized rats. Tolerance was induced by intravenous (iv) injection of col(V) and spleen lymphocytes were used for adoptive transfer. CD4+ T cells were depleted using magnetic beads. Lung isografts were analyzed using micro-PET imaging and histochemistry. The transvivo delayed type hypersensitivity (TV-DTH) assay was used to analyze the Th17 response. Results Adoptive co-transfer of col(V)-specific effector cells with cells from col(V) tolerized rats suppressed severe vasculitis and bronchiolitis with parenchymal inflammation, and the expression of IL-17 transcripts in mediastinal lymph nodes induced by effector cells alone. Analysis by TV-DTH showed that the reactivity to col(V) was dependent on the presence of TNF-α and IL-17, but not IFN-γ. Depletion of CD4+ T cells from the suppressor cell population abrogated the col(V)-specific protection. Conclusion Th17 mediated acute rejection after lung transplantation is ameliorated by CD4+ col(V)-specific regulatory T cells. The mechanism for this Th17 suppression is consistent with tolerance induction to col(V). The goal of transplantation treatment therefore should target Th17 development and not suppression of T cell activation by suppressing IL-2. PMID:20029330

  5. Successful Treatment of T Cell-Mediated Acute Rejection with Delayed CTLA4-Ig in Mice

    Directory of Open Access Journals (Sweden)

    James S. Young

    2017-09-01

    Full Text Available Clinical observations that kidney transplant recipients receiving belatacept who experienced T cell-mediated acute rejection can be successfully treated and subsequently maintained on belatacept-based immunosuppression suggest that belatacept is able to control memory T cells. We recently reported that treatment with CTLA4-Ig from day 6 posttransplantation successfully rescues allografts from acute rejection in a BALB/c to C57BL/6 heart transplant model, in part, by abolishing B cell germinal centers and reducing alloantibody titers. Here, we show that CTLA4-Ig is additionally able to inhibit established T cell responses independently of B cells. CTLA4-Ig inhibited the in vivo cytolytic activity of donor-specific CD8+ T cells, and the production of IFNγ by graft-infiltrating T cells. Delayed CTLA4-Ig treatment did not reduce the numbers of graft-infiltrating T cells nor prevented the accumulation of antigen-experienced donor-specific memory T cells in the spleen. Nevertheless, delayed CTLA4-Ig treatment successfully maintained long-term graft acceptance in the majority of recipients that had experienced a rejection crisis, and enabled the acceptance of secondary BALB/c heart grafts transplanted 30 days after the first transplantation. In summary, we conclude that delayed CTLA4-Ig treatment is able to partially halt ongoing T cell-mediated acute rejection. These findings extend the functional efficacy of CTLA4-Ig therapy to effector T cells and provide an explanation for why CTLA4-Ig-based immunosuppression in the clinic successfully maintains long-term graft survival after T cell-mediated rejection.

  6. Alteration of Cardiac Deformation in Acute Rejection in Pediatric Heart Transplant Recipients.

    Science.gov (United States)

    Chanana, Nitin; Van Dorn, Charlotte S; Everitt, Melanie D; Weng, Hsin Yi; Miller, Dylan V; Menon, Shaji C

    2017-04-01

    The objective of this study is to assess changes in cardiac deformation during acute cellular- and antibody-mediated rejection in pediatric HT recipients. Pediatric HT recipients aged ≤18 years with at least one episode of biopsy-diagnosed rejection from 2006 to 2013 were included. Left ventricular systolic S (SS) and SR (SSr) data were acquired using 2D speckle tracking on echocardiograms obtained within 12 h of right ventricular endomyocardial biopsy. A mixed effect model was used to compare cardiac deformation during CR (Grade ≥ 1R), AMR (pAMR ≥ 2), and mixed rejection (CR and AMR positive) versus no rejection (Grade 0R and pAMR 0 or 1). A total of 20 subjects (10 males, 50%) with 71 rejection events (CR 35, 49%; AMR 21, 30% and mixed 15, 21%) met inclusion criteria. The median time from HT to first biopsy used for analysis was 5 months (IQR 0.25-192 months). Average LV longitudinal SS and SSr were reduced significantly during rejection (SS: -17.2 ± 3.4% vs. -10.7 ± 4.5%, p < 0.001 and SSr: -1.2 ± 0.2 s(- 1) vs. -0.9 ± 0.3 s(- 1); p < 0.001) and in all rejection types. Average LV short-axis radial SS was reduced only in CR compared to no rejection (p = 0.04), while average LV circumferential SS and SSr were reduced significantly in AMR compared to CR (SS: 18.9 ± 4.2% vs. 20.8 ± 8.8%, p = 0.03 and SSr: 1.35 ± 0.8 s(- 1) vs. 1.54 ± 0.9 s(- 1); p = 0.03). In pediatric HT recipients, LV longitudinal SS and SSr were reduced in all rejection types, while LV radial SS was reduced only in CR. LV circumferential SS and SSr further differentiated between CR and AMR with a significant reduction seen in AMR as compared to CR. This novel finding suggests mechanistic differences between AMR- and CR-induced myocardial injury which may be useful in non-invasively predicting the type of rejection in pediatric HT recipients.

  7. Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms With Acute Rejection in Liver Transplant Recipients.

    Science.gov (United States)

    Azarpira, Negar; Namazi, Soha; Malahi, Sayan; Kazemi, Kourosh

    2016-06-01

    Polymorphisms of the endothelial nitric oxide synthase gene have been associated with altered endothelial nitric oxide synthase activity. The purpose of this study was to investigate the relation between endothelial nitric oxide synthase -786T/C and 894G/T polymorphism and their haplotypes on the occurrence of acute rejection episodes in liver transplant recipients. We conducted a case control study in which 100 liver transplant recipients and 100 healthy controls were recruited from Shiraz Transplant Center. The patients used triple therapy including tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression maintenance. DNA was extracted from peripheral blood and endothelial nitric oxide synthase polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. Patients included 60 men and 40 women (mean age, 32.35 ± 10.2 y). There was a significant association of endothelial nitric oxide synthase 894G/T and acute rejection episode. The GT* gen-otype and acute rejection episodes had a significant association (odds ratio, 2.42; 95% confidence interval, 0.97-6.15; P = .03). The GG and GT* genotype and T* allele frequency were significantly different between patients and control subjects (P = .001). Haplotype TT* was higher in recipients than control subjects (odds ratio, 2.17; 95% confidence interval, 1.12-4.25; P = .01). Haplotype TG was higher in the control group (odds ratio, 0.62; 95% confidence interval, 0.40-0.96; P = .02). Our results suggest a relation between different endothelial nitric oxide synthase geno-types and risk of acute rejection episodes. However, further study is necessary to determine genetic susceptibility for transplant patients.

  8. Acute antibody-mediated rejection after AB0-incomptible kidney transplantation treated successfully with antigen-specific immunoadsorption

    DEFF Research Database (Denmark)

    Just, Søren Andreas; Marcussen, Niels; Sprogøe, Ulrik

    2009-01-01

    -mediated rejection (Banff grade II with IgG deposits) caused by ABO antibodies (anti-B). Anti-rejection treatment with anti-B-specific immunoadsorption, intravenous immunoglobulin and methylprednisolone efficiently cleared deposited IgG from the kidney allograft and re-established normal kidney function. We suggest...... that ABO-incompatible kidney transplantation complicated by acute antibody-mediated rejection, caused by ABO antibodies, may successfully be treated with this regime....

  9. Acute antibody-mediated rejection after ABO-incompatible kidney transplantation treated successfully with antigen-specific immunoadsorption

    DEFF Research Database (Denmark)

    Just, Søren Andreas; Marcussen, Niels; Sprogøe, Ulrik

    2010-01-01

    -mediated rejection (Banff grade II with IgG deposits) caused by ABO antibodies (anti-B). Anti-rejection treatment with anti-B-specific immunoadsorption, intravenous immunoglobulin and methylprednisolone efficiently cleared deposited IgG from the kidney allograft and re-established normal kidney function. We suggest...... that ABO-incompatible kidney transplantation complicated by acute antibody-mediated rejection, caused by ABO antibodies, may successfully be treated with this regime....

  10. Kidney Transplant Recipients With Primary Membranous Glomerulonephritis Have a Higher Risk of Acute Rejection Compared With Other Primary Glomerulonephritides

    Directory of Open Access Journals (Sweden)

    Tripti Singh, MD

    2017-11-01

    Conclusions. Patients with MN have higher incidence of acute rejection after kidney transplant but have similar 10-year allograft survival in comparison to the other glomerular diseases like IgAN, FSGS, and LN.

  11. Inhibition of histone methyltransferase EZH2 ameliorates early acute renal allograft rejection in rats.

    Science.gov (United States)

    Li, Long; Zhang, Yi; Xu, Ming; Rong, Ruiming; Wang, Jina; Zhu, Tongyu

    2016-10-26

    Although histone methyltransferases EZH2 has been proved to have significant regulatory effect on the immune rejection after hematopoietic stem cell transplantation, its role in solid-organ transplantation remains uncovered. In this study, we investigate whether histone methylation regulation can impact renal allograft rejection in rat models. Allogeneic rat renal transplantation model (Wistar to Lewis) was established, and the recipients were administrated with EZH2 inhibitor DZNep after transplantation. Renal allografts and peripheral blood were collected on day 5 after transplantation for histological examination and mechanism investigation. We found that inhibition of EZH2 by DZNep after transplantation significantly ameliorated acute rejection (AR), with decreased histological injury and reduced inflammatory infiltration in renal allografts. Attenuation of AR was due to the prohibited activation of alloreactive T cells, the subsequent impaired production of inflammatory cytokines, and also the elevated apoptosis of alloreactive T cells in both renal allografts and periphery. However, inhibition of EZH2 did not increase the regulatory T cells during the AR. Disruption of EZH2 by DZNep suppressed the immune responses of alloreactive T cells and ameliorated AR of renal allografts. This suggests a therapeutic potential of targeting histone methyltransferases EZH2 in treating allograft rejection after solid organ transplantation.

  12. Serum levels of interleukin-9 during acute rejection in liver transplantation.

    Science.gov (United States)

    Fábrega, E; López-Hoyos, M; San Segundo, D; Casafont, F; Angel Mieses, M; Sampedro, B; Pons-Romero, F

    2012-01-01

    Interleukin-9 (IL-9) has been cast as a player in autoimmunity, but its role in liver transplantation remains to be clarified. The aim of our study was to investigate the time course of IL-9 serum levels during hepatic allograft rejection. IL-9 serum levels were determined in 34 healthy subjects and 50 hepatic transplant recipients. The patients were divided into two groups: group I was composed of 15 patients with acute rejection episodes, and group II, 35 patients free of this problem. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. The concentrations of IL-9 were similar in the rejection and nonrejection groups over the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-9 serum levels than the controls at all times after liver transplantation. These preliminary results suggest a lack of participation of IL-9 in human liver allograft rejection. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  13. Rituximab in the treatment of refractory late acute antibody-mediated rejection: Our initial experience

    Directory of Open Access Journals (Sweden)

    M Surendra

    2016-01-01

    Full Text Available Antibody-mediated rejection (AMR is not uncommon after renal transplantation and is harder to handle compared to cell-mediated rejection. When refractory to conventional therapies, rituximab is an attractive option. This study aims to examine the effectiveness of rituximab in refractory late acute AMR. This is a retrospective study involving nine renal transplant recipients. Four doses of rituximab were administered at weekly interval for 4 weeks, at a dose of 375 mg/m 2. The mean age of patients was 35.3 ± 7.38 years. The median period between transplantation and graft dysfunction was 30 ± 20 months. Mean serum creatinine at the time of discharge after transplantation and at the time of acute AMR diagnosis was 1.14 ± 0.19 mg/dl and 2.26 ± 0.57 mg/dl, respectively. After standard therapy, it was 2.68 ± 0.62 mg/dl. One patient died of Pseudomonas sepsis and three patients progressed to end-stage renal disease (ESRD. Four biopsies showed significant plasma cell infiltrations. Mean serum creatinine among non-ESRD patients at the end of 1 year progressed from 2.3 ± 0.4 to 3.8 ± 1.2 mg/dl (P value 0.04. eGFR prior to therapy and at the end of 1 year were 34.4 ± 6.18 and 20.8 ± 7.69 ml/min (P value 0.04, respectively. Only one patient showed improvement in graft function in whom donor-specific antibody (DSA titers showed significant improvement. Rituximab may not be effective in late acute AMR unlike in early acute AMR. Monitoring of DSA has a prognostic role in these patients and plasma cell rich rejection is associated with poor prognosis.

  14. Nebulized cyclosporine for prevention of acute pulmonary allograft rejection in the rat: pharmacokinetic and histologic study.

    Science.gov (United States)

    Blot, F; Tavakoli, R; Sellam, S; Epardeau, B; Faurisson, F; Bernard, N; Becquemin, M H; Frachon, I; Stern, M; Pocidalo, J J

    1995-01-01

    With regard to limiting the systemic effects of cyclosporine A and obtaining better control of acute pulmonary allograft rejection, local immunosuppressive therapy with aerosolized cyclosporine A seems of interest. Given the in situ immunologic mechanisms of acute rejection, as well as the anatomic structure of the lung, this therapy is feasible as previously described by others. The aim of our study is to determine the pharmacokinetic parameters of nebulized cyclosporine A and the best modalities of administration. In a pharmacokinetic study, the cyclosporine A was given either by intramuscular injection (10 mg/kg) or by aerosol at 10 and 25 mg/kg doses; 70 rats were killed at 25 and 50 minutes and 2, 4, 6, 8, 12, 24, or 48 hours after cyclosporine A administration. Cyclosporine A levels were measured in whole blood and in the lung. The areas under the concentration time curves were determined. Twenty-four lung transplantations were then performed. The rats were killed on postoperative day 9. Acute rejection was scored on a scale of 0 to 4, and cyclosporine A trough levels were measured in the lung and in the blood. With a jet nebulizer, the mass median aerodynamic diameter was 2.5 microns, with a standard geometric deviation of 2.3. In blood, the area under the concentration curve was greater for intramuscular (80.6 ng.hr/ml) than for aerosol administrations at 10 (15.1 ng.hr/ml) and 25 mg/kg (41.0 ng.hr/ml) doses. In the lungs, the area under the concentration curve was greater for the aerosol route at 25 mg/kg doses (588 ng.hr/mg) than for the low-dose (200 ng.hr/mg) or intramuscular administration (200 ng.hr/mg). The lung targeting index of cyclosporine A (ratio area under the concentration curve-lungs/area under the concentration curve-blood) was greater for both aerosol administrations than for the intramuscular route. In the study of the prevention of acute rejection, rats without immunosuppression (n = 6), rats receiving daily doses of cyclosporine A

  15. CHALLENGES IN TREATMENT OF RENAL GRAFT ACUTE ANTIBODY-MEDIATED REJECTION

    Directory of Open Access Journals (Sweden)

    A. I. Sushkov

    2016-01-01

    Full Text Available Diagnostic criteria and treatment protocols for acute antibody-mediated rejection (AMR of kidney allograft remain controversial. We report the case of early severe AMR after primary kidney transplantation. The graft removal was considered in the absence of treatment efficacy and in the presence of systemic infl ammatory response syndrome. However, at surgery the graft looked normal and it was not removed. The repeated treatment course (plasmapheresis, antithymocyte globulin, intravenous immunoglobulin and rituximab was effective. The patient has good and stable graft function in 1 year after transplantation. 

  16. Retinal vascular and structural dynamics during acute hyperglycaemia

    DEFF Research Database (Denmark)

    Klefter, Oliver N; Lauritsen, Tina Vilsbøll; Knop, Filip K

    2015-01-01

    PURPOSE: To compare retinal vascular dynamics during acute hyperglycaemia in patients with type 2 diabetes and healthy volunteers. METHODS: Twenty-one patients with type 2 diabetes and 27 healthy controls were examined with fundus photographic measurement of retinal vessel diameters, retinal...

  17. Acute type II cryoglobulinaemic vasculitis mimicking atherosclerotic peripheral vascular disease.

    LENUS (Irish Health Repository)

    Saeed, A

    2012-01-31

    Atherosclerotic peripheral vascular disease is a common presenting cause for digital ischaemia in life long smokers. Acute severe Type II Cryoglobulinaemic vasculitis is a rare yet important cause, which may present with similar clinical features and which if undiagnosed may be rapidly fatal. Following the instigation of therapy with intravenous methylprednisolone and cyclophosphamide this patient made an excellent recovery.

  18. Acute myeloid leukemia in the vascular niche

    NARCIS (Netherlands)

    Cogle, Christopher R.; Bosse, Raphael C.; Brewer, Takae; Migdady, Yazan; Shirzad, Reza; Kampen, Kim Rosalie; Saki, Najmaldin

    2016-01-01

    The greatest challenge in treating acute myeloid leukemia (AML) is refractory disease. With approximately 60-80% of AML patients dying of relapsed disease, there is an urgent need to define and target mechanisms of drug resistance. Unfortunately, targeting cell-intrinsic resistance has failed to

  19. MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaoyou [Department of Organ Transplantation, Zhujiang Hospital, Guangzhou 510282 (China); Dong, Changgui [Institute of Molecular Ecology and Evolution, East China Normal University, Shanghai 200062 (China); Jiang, Zhengyao [Department of Organ Transplantation, Zhujiang Hospital, Guangzhou 510282 (China); Wu, William K.K. [Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); State Key Laboratory of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Chan, Matthew T.V. [Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Zhang, Jie [Department of Organ Transplantation, Zhujiang Hospital, Guangzhou 510282 (China); Li, Haibin; Qin, Ke [Guangxi Key Laboratory for Transplantation Medicine Department of Organ Transplantation in Guangzhou Military Region, Institute of Transplant Medicine, 303 Hospital of People' s Liberation Army, Nanning, Guangxi 530021 (China); Sun, Xuyong, E-mail: sunxuyong0528@163.com [Guangxi Key Laboratory for Transplantation Medicine Department of Organ Transplantation in Guangzhou Military Region, Institute of Transplant Medicine, 303 Hospital of People' s Liberation Army, Nanning, Guangxi 530021 (China)

    2015-04-10

    Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, and chemokine (C–C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. • miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.

  20. Acute regional vascular insufficiency after jellyfish envenomation.

    Science.gov (United States)

    Williamson, J A; Burnett, J W; Fenner, P J; Hach-Wunderle, V; Hoe, L Y; Adiga, K M

    Three cases of jellyfish envenomation which occurred in the Indian Ocean and the Andaman Sea are reported. In each instance the stinging occurred on the upper extremities, and impaired the circulation to the stung limb(s), with absent distal arterial pulses, regional cyanosis, and the threat of distal gangrene. One of the patients is seriously and permanently handicapped, with bilateral upper-limb numbness and paresis; another patient has permanent sensory loss; the third patient, who also had brachial-artery narrowing that was demonstrated by angiography, made an uneventful recovery. The first two patients underwent surgical fasciotomy, whereas surgical exploration was performed on the third patient. Reduced blood flow in the major arteries of the limbs was observed directly in each case. Further, the arterial segment that primarily was affected, in each case, appeared to be that which underlay the actual site of the sting. All patients were young persons with no previous history of vascular disease. These cases corroborate the vascular and neurogenic injury, which previously have been reported in experimental animals and in human patients, that may result from jellyfish venoms.

  1. Acute Rejection in Renal Transplant Patients of a Hospital in Bogota, Colombia.

    Science.gov (United States)

    García, P; Huerfano, M; Rodríguez, M; Caicedo, A; Berrío, F; Gonzalez, C

    2016-01-01

    Renal transplantation is the best treatment for end stage renal disease. Acute graft rejection is one of the main complications and may influence graft survival. To determine the incidence and features of acute cellular rejection (ACR) episodes confirmed by biopsy. We studied a cohort of 175 patients who underwent renal transplantation between 2004 and 2012 to determine the cumulative incidence of ACR confirmed by biopsy and to identify the associated risk factors using multivariate analysis. The one-year patient survival was 96.6%; the graft survival was 93.7%. The incidence of ACR within one year was 14.3%, of which 46% were observed within 6 months following transplantation. The most frequently observed ACR type was 1B according to the Banff classification system (42%). A relationship between ACR and receipt of a kidney from expanded criteria donors was observed, both in univariate and adjusted multiple log-binomial regression analyses, but only 6.3% of patients received extended criteria donor kidneys. No other relationships between variables were found. ACR frequency in this study was similar to that of other cohorts reported previously. We need a bigger sample of renal transplants from expanded criteria donors, PRA and DSA test to support the results.

  2. Towards non-invasive diagnostic techniques for early detection of acute renal transplant rejection: A review

    Directory of Open Access Journals (Sweden)

    Elizabeth Hollis

    2017-03-01

    Full Text Available The kidney is a very important complicated filtering organ of the body. When the kidney reaches stage 5 chronic kidney disease, end stage renal failure, the preeminent therapy is renal transplantation. Although it is the best form of treatment, lack of kidney donors is still challenging. Therefore, all efforts should be employed to prolong the survival rate of the transplanted kidney. However, graft dysfunction (e.g., acute rejection is one of the serious barriers to long term kidney transplant survival. Currently, graft dysfunction’s gold standard of diagnosis is renal biopsy. Although renal biopsy is helpful, it is not preferred due to its invasive nature, high morbidity rates, and expensiveness. Therefore, noninvasive imaging techniques have become the subject of extensive research and interest, giving a strong promise to replace, or at least to decrease, biopsy usage in diagnosing graft dysfunction. This survey will discuss not only the current diagnosis and treatment of graft dysfunction but also the state-of-the-art imaging techniques in detecting acute renal transplant rejection.

  3. A Five-Gene Peripheral Blood Diagnostic Test for Acute Rejection in Renal Transplantation

    Science.gov (United States)

    Li, Li; Khatri, Purveshkumar; Sigdel, Tara K.; Tran, Tim; Ying, Lihua; Vitalone, Matthew; Chen, Amery; Hsieh, Szu-chuan; Dai, Hong; Zhang, Meixia; Naesens, Maarten; Zarkhin, Valeriya; Sansanwal, Poonam; Chen, Rong; Mindrinos, Michael; Xiao, Wenzhong; Benfield, Mark; Ettenger, Robert; Dharnidharka, Vikas; Mathias, Robert; Portale, Anthony; McDonald, Ruth; Harmon, William; Kershaw, David; Vehaskari, V. Matti; Kamil, Elaine; Baluarte, H. Jorge; Warady, Brad; Davis, Ron; Butte, Atul J.; Salvatierra, Oscar; Sarwal, Minnie

    2012-01-01

    Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in gthe NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n=47) and validated on independent test-set (n=198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool. PMID:23009139

  4. Analysis of leukocyte activation during acute rejection of pulmonary allografts in noninfected and cytomegalovirus-infected rats.

    Science.gov (United States)

    Steinmüller, C; Steinhoff, G; Bauer, D; You, X M; Denzin, H; Franke-Ullmann, G; Hausen, B; Bruggemann, C; Wagner, T O; Lohmann-Matthes, M L; Emmendörffer, A

    1997-01-01

    After human lung transplantation acute rejection and cytomegalovirus (CMV) infections may occur, probably contributing to the development of chronic rejection. We established a model of subacute allograft rejection in rats to analyze leukocyte activation and effects of a CMV infection. Histoincompatible lung transplants (BN/LEW) without immunosuppression (group A) and lungs of initially immunosuppressed animals (group B) were analyzed. The production of inflammatory mediators (interleukin-6, tumor necrosis factor alpha, nitric oxides) and the expression of MHC class II antigens by alveolar and lung tissue macrophages were significantly enhanced during the alloresponse. In recipients without immunosuppression (group A) allograft necrosis was detected by day 6, whereas group B allografts were fully rejected by day 25. In allografts of immunosuppressed, CMV-infected animals (group C) the CMV infection was clearly aggravated and the number of activated lung tissue macrophages was increased when compared with noninfected allografts or isografts. The subacute model provides the advantage of allowing us to study mechanisms of acute rejection without the effects of reperfusion injury. Furthermore these findings underline the role of inflammatory mediators produced by macrophages during rejection.

  5. Interleukin-17 positive cells accumulate in renal allografts during acute rejection and are independent predictors of worse graft outcome

    NARCIS (Netherlands)

    Yapici, Ünsal; Kers, Jesper; Bemelman, Fréderike J.; Roelofs, Joris J. T. H.; Groothoff, Jaap W.; van der Loos, Chris M.; van Donselaar-van der Pant, Karlijn A. M. I.; Idu, Mirza M.; Claessen, Nike; ten Berge, Ineke J. M.; Florquin, Sandrine

    2011-01-01

    Interleukin-17 (IL-17) plays an important role in the regulation of cellular and humoral immune responses. Recent studies suggest a role for IL-17 in transplantation. Our study investigated whether quantifying IL-17(+) cells in renal transplant biopsies during acute rejection could have additional

  6. Noninvasive Imaging of Acute Renal Allograft Rejection by Ultrasound Detection of Microbubbles Targeted to T-lymphocytes in Rats.

    NARCIS (Netherlands)

    Grabner, A.; Kentrup, D.; Mühlmeister, M.; Pawelski, H.; Biermann, C.; Bettinger, T.; Pavenstadt, H.; Schlatter, E.; Tiemann, K.; Reuter, S.

    2016-01-01

    PURPOSE: We propose CD3-antibody-mediated contrast-enhanced ultrasonography using human T-lymphocytes for image-based diagnosis of acute allograft rejection (AR) established in a rat renal transplantation model. MATERIALS AND METHODS: 15 minutes after tail vein injection of 30 x 10(6) human

  7. Red Wine Prevents the Acute Negative Vascular Effects of Smoking.

    Science.gov (United States)

    Schwarz, Viktoria; Bachelier, Katrin; Schirmer, Stephan H; Werner, Christian; Laufs, Ulrich; Böhm, Michael

    2017-01-01

    Moderate consumption of red wine is associated with fewer cardiovascular events. We investigated whether red wine consumption counteracts the adverse vascular effects of cigarette smoking. Participants smoked 3 cigarettes alone or after drinking a titrated volume of red wine. Clinical chemistry, blood counts, plasma cytokine enzyme-linked immunosorbent assays, immunomagnetic separation of CD14+ monocytes for gene expression analysis, fluorescence-activated cell sorting for microparticles, and isolation of circulating mononuclear cells to measure telomerase activity were performed, and urine cotinine levels were quantified. Compared with baseline, leukocytosis (P = .019), neutrophilia (P wine consumption. Cigarette smoke results in acute endothelial damage, vascular and systemic inflammation, and indicators of the cellular aging processes in otherwise healthy nonsmokers. Pretreatment with red wine was preventive. The findings underscore the magnitude of acute damage exerted by cigarette smoking in "occasional lifestyle smokers" and demonstrate the potential of red wine as a protective strategy to avert markers of vascular injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-Mediated Rejection.

    Science.gov (United States)

    Tower, Cindy M; Reyes, Morayma; Nelson, Karen; Leca, Nicolae; Kieran, Niamh; Muczynski, Kimberly; Jefferson, Jonathan A; Blosser, Christopher; Kukla, Aleksandra; Maurer, David; Chandler, Wayne; Najafian, Behzad

    2017-09-01

    Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. Currently, AMR diagnosis relies on biopsy which is an invasive procedure. A noninvasive biomarker of acute AMR could lead to early diagnosis and treatment of this condition and improve allograft outcome. Microvesicles are membrane-bound vesicles released from the cell surface after injury. We hypothesized that because AMR is associated with allograft endothelial injury and C4d deposition, plasma microvesicles positive for endothelial (CD144) marker and C4d are increased in this condition. We studied microvesicle concentration in the plasma of 95 kidney transplant patients with allograft dysfunction and compared with 23 healthy volunteers. Biopsy diagnosis and scoring was performed using Banff classification. In the 28 subjects with AMR, the density of C4d+/CD144+ microvesicles was on average 11-fold (P = 0.002) higher than transplant recipients with no AMR and 24-fold (P = 0.008) than healthy volunteers. Densities of C4d+ and C4d+/annexin V+ (C4d+/AVB+) microvesicles were also increased in AMR patients compared with no AMR and healthy subjects. C4d+/AVB+ microvesicles correlated with AMR biopsy severity. Nine patients with acute AMR that received treatment showed a mean 72% decrease (P = 0.01) in C4d+/CD144+ microvesicle concentration compared with pretreatment values. Quantification of plasma C4d+ microvesicles provides information about presence of AMR, its severity and response to treatment in transplant patients.

  9. Changes in the action potential and transient outward potassium current in cardiomyocytes during acute cardiac rejection in rats.

    Science.gov (United States)

    Luo, Wenqi; Jia, Yixin; Zheng, Shuai; Li, Yan; Han, Jie; Meng, Xu

    2017-01-01

    Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential ( AP ) and the transient outward potassium current ( I to ) in cardiomyocytes during acute cardiac rejection. Heterotopic heart transplantation was performed in allogeneic [Brown Norway (BN)-to-Lewis] and isogeneic (BN-to-BN) rats. Twenty models were established in each group. Ten recipients were sacrificed at the 2nd day and the other ten recipients were sacrificed at the 4 th day after the operation in each group. Histopathological examinations of the grafted hearts were performed in half of the recipients in each group randomly. The other half of the grafted hearts were excised rapidly and enzymatically dissociated to obtain single cardiomyocytes. The AP and I to current were recorded using the whole cell patch-clamp technique. Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2 nd day and moderate rejection at the 4 th day in the allogeneic group after cardiac transplantation, while no evidence of histologic lesions of rejection were observed in the isogeneic group. Compared with the isogeneic group, the action potential duration ( APD ) of cardiomyocytes in the allogeneic group was significantly prolonged ( APD 90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2 nd day, P=0.0016; APD 90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4 th day, P=0.0064). The current density of I to was significantly decreased at the 4 th day after cardiac transplantation. The APD of

  10. Acute mesenteric ischemia (Part II) - Vascular and endovascular surgical approaches.

    Science.gov (United States)

    Kärkkäinen, Jussi M; Acosta, Stefan

    2017-02-01

    The modern treatment of acute mesenteric ischemia (AMI) requires seamless collaboration of gastrointestinal surgeons, vascular surgeons, and interventional radiologists. The treatment strategy is straightforward aiming at rapid restoration of blood flow to the intestine. Bowel resection is performed on demand. The first thing to consider is the patient's clinical condition at presentation, whether there are signs of peritonitis or not, and whether the patient is hemodynamically stable or not. Second, there are four etiologies of AMI that need to be distinguished as they differ in treatment: superior mesenteric artery embolism, mesenteric arterial occlusive disease, mesenteric venous thrombosis, and non-occlusive mesenteric ischemia. In this review, we describe the basic vascular and endovascular treatment modalities accompanied by a simple algorithm for the various situations in AMI. Furthermore, the indications for damage control and primary definitive surgery are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Evaluation of Digital PCR as a Technique for Monitoring Acute Rejection in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Hyeseon Lee

    2017-03-01

    Full Text Available Early detection and proper management of kidney rejection are crucial for the long-term health of a transplant recipient. Recipients are normally monitored by serum creatinine measurement and sometimes with graft biopsies. Donor-derived cell-free deoxyribonucleic acid (cfDNA in the recipient's plasma and/or urine may be a better indicator of acute rejection. We evaluated digital PCR (dPCR as a system for monitoring graft status using single nucleotide polymorphism (SNP-based detection of donor DNA in plasma or urine. We compared the detection abilities of the QX200, RainDrop, and QuantStudio 3D dPCR systems. The QX200 was the most accurate and sensitive. Plasma and/or urine samples were isolated from 34 kidney recipients at multiple time points after transplantation, and analyzed by dPCR using the QX200. We found that donor DNA was almost undetectable in plasma DNA samples, whereas a high percentage of donor DNA was measured in urine DNA samples, indicating that urine is a good source of cfDNA for patient monitoring. We found that at least 24% of the highly polymorphic SNPs used to identify individuals could also identify donor cfDNA in transplant patient samples. Our results further showed that autosomal, sex-specific, and mitochondrial SNPs were suitable markers for identifying donor cfDNA. Finally, we found that donor-derived cfDNA measurement by dPCR was not sufficient to predict a patient's clinical condition. Our results indicate that donor-derived cfDNA is not an accurate predictor of kidney status in kidney transplant patients.

  12. Right Ventricular Dysfunction as an Echocardiographic Measure of Acute Rejection Following Heart Transplantation in Children.

    Science.gov (United States)

    Aggarwal, Sanjeev; Blake, Jennifer; Sehgal, Swati

    2017-03-01

    Noninvasive biomarkers of acute allograft rejection (AAR) following orthotopic heart transplantation (OHT) are needed. The aim of this study was to investigate the accuracy of echocardiographic (ECHO) right ventricular (RV) global functional and resistance indices in the detection of AAR. This retrospective chart review included children with biopsy-proven AAR (grade ≥ 2R cellular or CD4 + antibody-mediated rejection) following OHT and an ECHO within 12 h of the biopsy. ECHO measures: (a) ratio of systolic to diastolic duration (S/D), (b) RV myocardial performance index (MPI) and (c) tricuspid regurgitant gradient to RV outflow tract velocity time integral ratio (TRG/VTI), were derived at baseline, during AAR and at two follow-ups. Sixteen patients [56% male, mean (SD) age at OHT 3.5 (4.3) years] had 16 AAR episodes. S/D (1.15 vs. 1.60, p < 0.01), RV MPI (0.19 vs. 0.39, p < 0.01) and TRG/VTI (1.05 vs. 1.7, p = 0.01) deteriorated during AAR and, except for diastolic duration, improved significantly at first follow-up. The negative predictive values for S/D, RV MPI and TRG/VTI at cutoffs of 1.3, 0.31 and 1.3 were 97, 97 and 87%, respectively. RV S/D, MPI and TRG/VTI deteriorated during AAR. Their excellent negative predictive values suggest that their incorporation in surveillance may obviate the need for routine biopsies.

  13. Association between donor-specific antibodies and acute rejection and resolution in small bowel and multivisceral transplantation.

    Science.gov (United States)

    Tsai, Hsin-Lin; Island, Eddie R; Chang, Jei-Wen; Gonzalez-Pinto, Ignacio; Tryphonopoulos, Panagiotis; Nishida, Seigo; Selvaggi, Gennaro; Tekin, Akin; Moon, Jang; Levi, David; Woodle, E Steve; Ruiz, Phillip; Weppler, Debbie; Lee, Oscar K S; Tzakis, Andreas G

    2011-09-27

    Donor-specific antibodies (DSA) are associated with acute kidney graft rejection, but their role in small bowel/multivisceral allograft remains unclear. We carried out a prospective study to understand the impact of DSA in the setting of intestinal allograft rejection. Thirteen patients (15 grafts) were serially evaluated for DSA levels pre- and posttransplant. DSA was determined by Luminex and the results were interpreted as fluorescence intensity (FI), with FI more than 3000 considered positive. The clinical rejection episodes in allografts were significantly associated with the presence of DSA (P=0.041).We obtained 291 biopsy samples from graft ileum and date-matched DSA assay reports. Sixty-three (21.65%) of the biopsies showed acute rejection. The appearance of DSA were preformed (n=5, anti-human leukocyte antigen class II=3, anti-class I and II=2), de novo (n=4, 15.25±4.72 days after transplantation, anti-class II=1, and anti-class I and II=3) and never (n=6). Among the 63 biopsies, 30(47.6%) had significant correlations with positive DSA (kappa=0.30, Ptransplantation patients, there was a high incidence of DSA. The presence of DSA should alert the clinical team of a higher risk of rejection, and reduction of the FI is clinically associated with resolution. Serial endoscopy guided biopsies combined with simultaneous DSA measurement in postintestinal transplantation follow-up is an effective means of screening for cellular and humoral-based forms of acute rejection.

  14. Belatacept for prevention of acute rejection in adult patients who have had a kidney transplant: an update

    Directory of Open Access Journals (Sweden)

    Wojciechowski D

    2012-11-01

    Full Text Available David Wojciechowski, Flavio VincentiKidney Transplant Service, University of California, San Francisco, CA, USAAbstract: In June 2011, the US Food and Drug Administration approved belatacept for the prophylaxis of organ rejection in adult kidney transplant recipients. This review discusses the use of belatacept for the prevention of acute rejection as part of a maintenance immunosuppression regimen. Belatacept is a selective costimulation blocker designed to provide effective immunosuppression while avoiding the toxicities associated with calcineurin inhibitors. Phase III trial data have demonstrated that belatacept is noninferior to cyclosporine in 1-year patient and allograft survival. Three-year data demonstrate an ongoing improvement in mean measured glomerular filtration rate in belatacept-treated versus cyclosporine-treated patients. However, the rate of acute rejection was higher in belatacept-treated patients compared with cyclosporine. Specifically, there was a higher incidence of Banff type II rejections in patients treated with belatacept. Despite the higher Banff grade, rejections on belatacept were not associated with other factors associated with poor outcomes, such as the development of donor-specific antibodies or reduced estimated glomerular filtration rate. One safety issue that must be considered when using belatacept is the potential for increased risk of post-transplant lymphoproliferative disease. There were more cases of post-transplant lymphoproliferative disease in belatacept-treated patients, especially in recipients seronegative for Epstein–Barr virus or patients treated with lymphocyte-depleting agents. Therefore, belatacept can be recommended for use in Epstein–Barr virus antibody-positive recipients.Keywords: belatacept, kidney transplant, acute rejection

  15. Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1

    DEFF Research Database (Denmark)

    Burton, C.M.; Iversen, M.; Carlsen, J.

    2009-01-01

    maximum FEV(1) occurred at a median 183 days post-transplant. Freedom from BOS was 81%, 53%, 38% and 15%, and cumulative incidence of BOS was 18%, 43%, 57% and 77% at 1, 3, 5 and 10 years post-transplantation, respectively. Acute cellular rejection was independently associated with an increased cause......-specific hazard of BOS (hazard ratio 1.4, confidence interval 1.1 to 1.8, p = 0.009). The absolute value of baseline FEV(1) was a significant confounder in all survival and competing risk analyses of BOS (p rejection remains...

  16. Transfer of tolerance to collagen type V suppresses T-helper-cell-17 lymphocyte-mediated acute lung transplant rejection.

    Science.gov (United States)

    Braun, Ruedi K; Molitor-Dart, Melanie; Wigfield, Christopher; Xiang, Zhuzai; Fain, Sean B; Jankowska-Gan, Ewa; Seroogy, Christine M; Burlingham, William J; Wilkes, David S; Brand, David D; Torrealba, Jose; Love, Robert B

    2009-12-27

    Rat lung allograft rejection is mediated by collagen type V (col(V)) specific T-helper-cell 17 (Th17) cells. Adoptive transfer of these cells is sufficient to induce rejection pathology in isografts, whereas tolerance to col(V) suppresses allograft rejection. Therefore, we tested whether regulatory T cells from tolerant rats could suppress the Th17-mediated rejection in the syngeneic model of lung transplantation. Rats were subjected to syngeneic left lung transplantation, and acute rejection was induced by adoptive transfer of lymph node cells from col(V)-immunized rats. Tolerance was induced by intravenous injection of col(V), and spleen lymphocytes were used for adoptive transfer. CD4+ T cells were depleted using magnetic beads. Lung isografts were analyzed using micro-positron emission tomography imaging and histochemistry. The transvivo delayed type hypersensitivity assay was used to analyze the Th17 response. Adoptive cotransfer of col(V)-specific effector cells with cells from col(V)-tolerized rats suppressed severe vasculitis and bronchiolitis with parenchymal inflammation, and the expression of interleukin (IL)-17 transcripts in mediastinal lymph nodes induced by effector cells alone. Analysis by transvivo delayed type hypersensitivity showed that the reactivity to col(V) was dependent on the presence of tumor necrosis factor-alpha and IL-17 but not interferon-gamma. Depletion of CD4+ T cells from the suppressor cell population abrogated the col(V)-specific protection. Th17-mediated acute rejection after lung transplantation is ameliorated by CD4+ col(V)-specific regulatory T cells. The mechanism for this Th17 suppression is consistent with tolerance induction to col(V). The goal of transplantation treatment, therefore, should target Th17 development and not suppression of T-cell activation by suppressing IL-2.

  17. Detection of acute renal allograft rejection by analysis of renal tissue proteomics in rat models of renal transplantation

    Directory of Open Access Journals (Sweden)

    Dai Yong

    2008-01-01

    Full Text Available At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved if rapid, noninvasive and reliable biomarkers of rejection were available. This study is designed to determine whether such protein biomarkers can be found in renal-graft tissue proteomic approach. Orthotopic kidney transplantations were performed using Fisher (F344 or Lewis rats as donors and Lewis rats as recipients. Hence, there were two groups of renal transplant models: one is allograft (from F344 to Lewis rats; another is syngrafts (from Lewis to Lewis rats serving as control. Renal tissues were collected 3, 7 and 14 days after transplantation. As many as 18 samples were analyzed by 2-D Electrophoresis and mass spectrometry (MALDI-TOF-TOF-MS. Eleven differentially expressed proteins were identified between groups. In conclusion, proteomic technology can detect renal tissue proteins associated with acute renal allograft rejection. Identification of these proteins as diagnostic markers for rejection in patients′ urine or sera may be useful and non-invasive, and these proteins might serve as novel therapeutic targets that also help to improve the understanding of mechanism of renal rejection.

  18. Reproducibility of the acute rejection diagnosis in human cardiac allografts. The Stanford Classification and the International Grading System

    DEFF Research Database (Denmark)

    Nielsen, H; Sørensen, Flemming Brandt; Nielsen, B

    1993-01-01

    Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading...... systems have evolved. Most recently, the International Grading System was introduced in The Journal of Heart and Lung Transplantation. In this study the interobserver reproducibility of both the Stanford Classification and the International Grading System is evaluated using Kappa statistics. Three...... observers evaluated 168 endomyocardial biopsy specimens according to the Stanford Classification and 100 endomyocardial biopsy specimens according to the International Grading System. The evaluation was carried out blindly. Kappa values of 54.1% and 51.5%, respectively, were obtained, both significantly...

  19. Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal-transplant recipients using a joint modeling approach.

    OpenAIRE

    Daher-Abdi, Zeinab; Essig, Marie; Rizopoulos, Dimitris; Le Meur, Yannick; Prémaud, Aurélie; Woillard, Jean-Baptiste; Rerolle, Jean-Philippe; Marquet, Pierre; Rousseau, Annick

    2013-01-01

    International audience; This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mixed-effects model to describe the whole pattern of MPA exposure (i.e. area un...

  20. Kidney allograft survival after acute rejection, the value of follow-up biopsies.

    Science.gov (United States)

    El Ters, M; Grande, J P; Keddis, M T; Rodrigo, E; Chopra, B; Dean, P G; Stegall, M D; Cosio, F G

    2013-09-01

    Kidney allografts are frequently lost due to alloimmunity. Still, the impact of early acute rejection (AR) on long-term graft survival is debated. We examined this relationship focusing on graft histology post-AR and assessing specific causes of graft loss. Included are 797 recipients without anti-donor antibodies (DSA) at transplant who had 1 year protocol biopsies. 15.2% of recipients had AR diagnosed by protocol or clinical biopsies. Compared to no-AR, all histologic types of AR led to abnormal histology in 1 and 2 years protocol biopsies, including more fibrosis + inflammation (6.3% vs. 21.9%), moderate/severe fibrosis (7.7% vs. 13.5%) and transplant glomerulopathy (1.4% vs. 8.3%, all p < 0.0001). AR were associated with reduced graft survival (HR = 3.07 (1.92-4.94), p < 0.0001). However, only those AR episodes followed by abnormal histology led to reduced graft survival. Early AR related to more late alloimmune-mediated graft losses, particularly transplant glomerulopathy (31% of losses). Related to this outcome, recipients with AR were more likely to have new DSA class II 1 year posttransplant (no-AR, 11.1%; AR, 21.2%, p = 0.039). In DSA negative recipients, early AR often leads to persistent graft inflammation and increases the risk of new DSA II production. Both of these post-AR events are associated with increased risk of graft loss. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Activation of polymorphonuclear leukocyte oxygen radical production during acute lung rejection in dogs: inhibition by an antiadhesion molecule monoclonal antibody.

    Science.gov (United States)

    Cale, A R; Katzmann, J A; Tazelaar, H D; Miller, V M; McGregor, C G

    1993-01-01

    Monoclonal antibodies against leukocyte adhesion molecules reduce the severity of reperfusion injury and, in some cases, prevent acute allograft rejection. These effects are assumed to be due to prevention of leukocyte-endothelial adhesion. Experiments were designed to study activation of polymorphonuclear leukocytes during acute rejection of canine single lung allografts and to test the ability of an anti-beta 2-integrin monoclonal antibody (R15.7/H4) to regulate leukocyte metabolism independent of leukocyte-endothelial adhesion. Peripheral blood polymorphonuclear leukocytes were obtained by Ficoll-Hypaque centrifugation from unoperated control dogs (n = 10), from dogs with a single lung autotransplant (n = 4), and from dogs after single lung allotransplantation during unmodified rejection (n = 12). Oxygen radicals were measured with luminal-enhanced chemiluminescence of unstimulated polymorphonuclear leukocytes, polymorphonuclear leukocytes stimulated by opsonized-zymosan, and polymorphonuclear leukocytes incubated with anti-beta 2-integrin beta-chain (CD18) monoclonal antibodies before exposure to opsonized zymosan. Polymorphonuclear leukocyte viability was unaffected by the monoclonal antibodies. Polymorphonuclear leukocytes from unoperated and autotransplant dogs did not produce oxygen radicals unless stimulated by opsonized zymosan. Polymorphonuclear leukocytes from rejecting animals produced oxygen radicals in the absence of zymosan, and when stimulated, production of oxygen radicals was significantly greater than that of polymorphonuclear leukocytes from unoperated and autotransplant dogs. Production of oxygen radicals was inhibited significantly by the monoclonal antibodies in polymorphonuclear leukocytes from all three groups. This study shows that rejection activates polymorphonuclear leukocytes and increases the potential to produce activated oxygen species. In addition to inhibiting leukocyte adhesion to endothelial cells, anti-beta 2-integrin

  2. Targeted inhibition of renal Rho kinase reduces macrophage infiltration and lymphangiogenesis in acute renal allograft rejection

    NARCIS (Netherlands)

    Poosti, Fariba; Yazdani, Saleh; Dolman, M. Emmy M.; Kok, Robbert Jan; Chen, Cheng; Ding, Guohua; Lacombe, Marie; Prakash, Jai; van den Born, Jacob; Hillebrands, Jan-Luuk; van Goor, Harry; de Borst, Martin H.

    2012-01-01

    The Rho kinase pathway plays an important role in epithelial dedifferentiation and inflammatory cell infiltration. Recent studies suggest that inflammation promotes lymphangiogenesis, which has been associated with renal allograft rejection. We investigated whether targeted inhibition of the Rho

  3. Rituximab-Related Late-Onset Neutropenia in Kidney Transplant Recipients Treated for Antibody-Mediated Acute Rejection.

    Science.gov (United States)

    Ahmadi, Fatemeh; Dashti-Khavidaki, Simin; Khatami, Mohammad-Reza; Lessan-Pezeshki, Mahboob; Khalili, Hossein; Khosravi, Malihe

    2017-08-01

    Kidney transplant is a new area for use of rituximab, which is being used to treat acute antibody-mediated rejection or as an induction agent in ABO- or HLA-incompatible grafts. We report on late-onset neutropenia in rituximab-treated kidney transplant recipients with antibody-mediated rejection. This observational prospective study was performed on kidney transplant recipients with clinically suspicious or biopsy-proven antibody-mediated rejection treated with plasmapheresis plus intravenous immunoglobulin with (cases) or without (controls) rituximab. Compared with none of the controls, 4 of 6 patients (66.7%) in the rituximab-treated group experienced late-onset neutropenia 35 to 93 days after the last dose of rituximab. The course of neutropenia was complicated by endocarditis in 1 patient, resulting in his death just because of a lack of valvular surgery. Increased use of rituximab to treat antibody-mediated rejection among kidney transplant recipients requires attention to its late-onset adverse event, neutropenia. Although asymptomatic in some patients, kidney transplant recipients treated concomitantly with plasmapheresis and mycophenolate mofetil are predisposed to hypogammaglobulinemia, and monitoring of patients for infections is required.

  4. High Tacrolimus Clearance Is a Risk Factor for Acute Rejection in the Early Phase After Renal Transplantation.

    Science.gov (United States)

    Egeland, Erlend Johannessen; Robertsen, Ida; Hermann, Monica; Midtvedt, Karsten; Størset, Elisabet; Gustavsen, Marte Theie; Reisæter, Anna Varberg; Klaasen, Rolf; Bergan, Stein; Holdaas, Hallvard; Hartmann, Anders; Åsberg, Anders

    2017-08-01

    Patients with high tacrolimus clearance eliminate more drug within a dose interval compared with those with low clearance. Delays in dosing time will result in transient periods of lower concentrations in high versus low clearance patients. Transient subtherapeutic tacrolimus concentrations may induce acute rejection episodes. A retrospective study in all renal transplant patients treated with tacrolimus at our center from 2009 to 2013 was conducted. The association between individually estimated tacrolimus clearance (daily tacrolimus dose [mg]/trough concentration [μg/L]) and biopsy-proven acute rejection (BPAR) the first 90 days posttransplantation was investigated. In total, 638 patients treated with oral tacrolimus were included in the analysis. Eighty-five (13.3%) patients experienced BPAR. Patients were stratified into 4 groups per their estimated clearance. The patients in the high clearance group had significantly higher incidence of BPAR (20.6%) with a hazard ratio of 2.39 (95% confidence interval, 1.30-4.40) compared with the low clearance group. Clearance estimate (as a continuous variable) showed a hazard ratio of 2.25 (95% confidence interval, 1.70-2.99) after adjusting for other risk factors. There were no significant differences in neither trough concentrations the first week after transplantation nor time to target trough concentration between patients later experiencing BPAR or not. High estimated clearance is significantly associated with increased risk of BPAR the first 90 days posttransplantation and may predict an increased risk of rejection in the early phase after renal transplantation.

  5. Platelet-derived or soluble CD154 induces vascularized allograft rejection independent of cell-bound CD154

    OpenAIRE

    Xu, He; Zhang, Xiaojie; Mannon, Roslyn B.; Kirk, Allan D.

    2006-01-01

    CD154 is a cell surface molecule expressed on activated T cells that binds to CD40, an activating molecule on APCs. Its blockade has been shown to prevent allograft rejection, presumably by interrupting interactions between T cells and APCs. It is known that activated human platelets express and shed CD154 and can induce APC activation and other immune processes in vitro. Here we show that platelet-derived CD154 is sufficient to initiate cardiac allograft rejection independent of any cellular...

  6. Defining the burden, scope, and future of vascular acute care surgery.

    Science.gov (United States)

    Harris, Donald G; Herrera, Anthony; Drucker, Charles B; Kalsi, Richa; Menon, Nandakumar; Toursavadkohi, Shahab; Diaz, Jose J; Crawford, Robert S

    2017-11-01

    The paradigm of acute care surgery has revolutionized nonelective general surgery. Similarly, nonelective vascular surgery may benefit from specific management and resource capabilities. To establish the burden and scope of vascular acute care surgery, we analyzed the characteristics and outcomes of patients hospitalized for vascular surgical procedures in Maryland. A retrospective analysis of a statewide inpatient database was performed to identify patients undergoing noncardiac vascular procedures in Maryland from 2009 to 2013. Patients were stratified by admission acuity as elective, urgent, or emergent, with the last two groups defined as acute. The primary outcome was inpatient mortality, and secondary outcomes were critical care and hospital resource requirements. Groups were compared by univariate analyses, with multivariable analysis of mortality based on acuity level and other potential risk factors for death. Of 3,157,499 adult hospital admissions, 154,004 (5%) patients underwent a vascular procedure; most were acute (54% emergent, 13% urgent), whereas 33% were elective. Acute patients had higher rates of critical care morbidity and required more hospital resource utilization. Admission for acute vascular surgery was independently associated with mortality (urgent odds ratio, 2.1; emergent odds ratio, 3.0). The majority of inpatient vascular care in Maryland is for acute vascular surgery, which is an independent risk factor for mortality. Acute vascular surgical care entails greater critical care and hospital resource utilization and-similar to emergency general surgery-may benefit from dedicated training and practice models. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  7. Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood

    NARCIS (Netherlands)

    Kas-Deelen, AM; Harmsen, MC; de Maar, EF; Oost-Kort, WW; Tervaert, JWC; van der Meer, J; van Son, WJ; The, TH

    2000-01-01

    Background. Human cytomegalovirus (HCMV) infections in transplantation patients are associated with vascular endothelial damage. This is reflected by the appearance of cytomegalic endothelial cells (CECs) and noninfected endothelial cells (ECs) in blood. To get more insight in the extent of vascular

  8. Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection

    NARCIS (Netherlands)

    Albrecht, EWJA; van Goor, H; Tiebosch, ATMG; Moshage, H; Tegzess, Adam; Stegeman, CA

    2000-01-01

    Background Nitric oxide (NO) is produced by nitric oxide synthases (NOS), which are either constitutively expressed in the kidney or inducible, in resident and infiltrating cells during inflammation and allograft rejection. NO is rapidly degraded to the stable end products nitrite and nitrate, which

  9. Is lymphocytic bronchiolitis a marker of acute rejection? An analysis of 2,697 transbronchial biopsies after lung transplantation.

    Science.gov (United States)

    Burton, Christopher M; Iversen, Martin; Scheike, Thomas; Carlsen, Jørn; Andersen, Claus B

    2008-10-01

    Guidelines for the diagnosis and grading of lymphocytic bronchiolitis (LB) have been available for more than a decade, but agreement is lacking concerning the clinical implications of this histologic finding. Study goals were to describe the overall prevalence and incidence of LB in a consecutive cohort of lung transplant recipients and identify risk factors for the onset, frequency, and severity of LB. A retrospective analysis was done of 2,697 transbronchial biopsy (TBB) specimens obtained during the first 2 years after transplantation from 299 consecutive patients who underwent transplantation between 1996 and 2006. Full diameter membranous bronchioli were missing in approximately 30% of TBB specimens. The proportion of patients demonstrating LB remained constant during follow-up (trend test, p = 0.2). The cumulative incidence of LB (>or=B2) was 33%, 53%, 62%, and 68% at 1-, 3-, 6-, and 12-months, respectively. Approximately one-quarter and one-half of the patients had a second episode of >or=B2 within 3 months and 2-years of transplantation, respectively. Exposure to LB during the first 2 years after transplantation was independently associated with the frequency and/or severity of acute cellular rejection (p bronchiolitis obliterans (odds ratio, 3.3, 95% confidence interval, 1.5-6.9, p = 0.001). The frequency and severity of LB was associated with the occurrence and severity of acute cellular rejection.

  10. Non-invasive imaging of acute renal allograft rejection in rats using small animal F-FDG-PET.

    Directory of Open Access Journals (Sweden)

    Stefan Reuter

    Full Text Available BACKGROUND: At present, renal grafts are the most common solid organ transplants world-wide. Given the importance of renal transplantation and the limitation of available donor kidneys, detailed analysis of factors that affect transplant survival are important. Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection (AR is still a major risk for graft survival. Nowadays, AR can only be definitively by renal biopsy. However, biopsies carry a risk of renal transplant injury and loss. Most important, they can not be performed in patients taking anticoagulant drugs. METHODOLOGY/PRINCIPAL FINDINGS: We present a non-invasive, entirely image-based method to assess AR in an allogeneic rat renal transplantation model using small animal positron emission tomography (PET and (18F-fluorodeoxyglucose (FDG. 3 h after i.v. injection of 30 MBq FDG into adult uni-nephrectomized, allogeneically transplanted rats, tissue radioactivity of renal parenchyma was assessed in vivo by a small animal PET-scanner (post operative day (POD 1,2,4, and 7 and post mortem dissection. The mean radioactivity (cps/mm(3 tissue as well as the percent injected dose (%ID was compared between graft and native reference kidney. Results were confirmed by histological and autoradiographic analysis. Healthy rats, rats with acute CSA nephrotoxicity, with acute tubular necrosis, and syngeneically transplanted rats served as controls. FDG-uptake was significantly elevated only in allogeneic grafts from POD 1 on when compared to the native kidney (%ID graft POD 1: 0.54+/-0.06; POD 2: 0.58+/-0.12; POD 4: 0.81+/-0.06; POD 7: 0.77+/-0.1; CTR: 0.22+/-0.01, n = 3-28. Renal FDG-uptake in vivo correlated with the results obtained by micro-autoradiography and the degree of inflammatory infiltrates observed in histology. CONCLUSIONS/SIGNIFICANCE: We propose that graft FDG-PET imaging is a new option to non-invasively, specifically, early detect, and follow

  11. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......; the effect of adding mofetil to a steroid-free protocol under cover of high-dose aciclovir prophylaxis on the number of acute rejections, EBV infections and PTLDs after kidney transplantation. Methods: EBV serology was performed in 267 consecutive renal transplantations (1990-1997), All were treated...... or reactivated EBV infection (PREBV) was correlated to acute rejection (treated with OKT3; P

  12. New formulations of tacrolimus and prevention of acute and chronic rejections in adult kidney-transplant recipients.

    Science.gov (United States)

    Jouve, Thomas; Rostaing, Lionel; Malvezzi, Paolo

    2017-07-01

    ​Introduction: As tolerance is not yet achievable, the kidney-transplanted-patients have to take on a daily-basis immunosuppressive drugs in order to avoid acute rejection-AR-. The cornerstone of immunosuppression relies on tacrolimus-therapy which is potentially nephrotoxic. Areas Covered: We identified from the studies published in the recent years those who were reporting on AR in de novo kidney-transplant recipients under tacrolimus-based therapy, as well as those who reported on the attempt to minimize tacrolimus-therapy. There are many formulations of tacrolimus: immediate-release (Prograf®), slow-release (Advagraf®), or extended-release (Envarsus®). All demonstrate a very good efficacy in preventing AR episodes. Studies in which tacrolimus was minimized or even weaned-off have shown that it was unsafe, i.e. in resulting in AR episode and/or de novo donor-specific alloantibodies. Recent data show that Tacrobell®, a generic of tacrolimus, was as efficient as Prograf® in the short- and long-term. Expert-opinion: Tacrolimus-based immunosuppression is very effective in preventing rejection in kidney-transplant recipients. It might be associated with nephrotoxicity, that can be reduced by avoiding tacrolimus trough levels too high in the long-term. Conversely, tacrolimus ultraminimization should not be attempted.

  13. Comparison Between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

    Directory of Open Access Journals (Sweden)

    Ronald W. Day

    2015-03-01

    Full Text Available Objective. Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods. A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21% to 53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21% to 51% oxygen, and 21% to 51% oxygen with 0.05 mg/kg to 0.29 mg/kg intravenous sildenafil of the procedures were compared.Results. Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide, and 21% to 51% oxygen with sildenafil. Mean pulmonary arterial pressure (mm Hg, mean ± standard error of the mean was 38 ± 4 during 21% to 53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21% to 51% oxygen, and 32 ± 2 during 21% to 51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738. Conclusions. Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide cannot be used to predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

  14. Donor and recipient genetic variants in NLRP3 associate with early acute rejection following kidney transplantation

    NARCIS (Netherlands)

    Dessing, Mark C.; Kers, Jesper; Damman, Jeffrey; Navis, Gerjan J.; Florquin, Sandrine; Leemans, Jaklien C.

    2016-01-01

    NLRP3 (NOD-like receptor family, pyrin domain containing 3) is a member of the inflammasome family and is of special interest in renal disease. Experimental studies have shown that Nlrp3 plays a significant role in the induction of renal damage and dysfunction in acute and chronic renal injury.

  15. Association of high HLA-E expression during acute cellular rejection and numbers of HLA class I leader peptide mismatches with reduced renal allograft survival.

    Science.gov (United States)

    Guberina, Hana; Rebmann, Vera; Wagner, Bettina; da Silva Nardi, Fabiola; Dziallas, Phillip; Dolff, Sebastian; Bienholz, Anja; Wohlschlaeger, Jeremias; Bankfalvi, Agnes; Heinemann, Falko M; Witzke, Oliver; Zoet, Yvonne M; Claas, Frans H J; Horn, Peter A; Kribben, Andreas; Doxiadis, Ilias I N

    2017-03-01

    Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed immune responses by interacting with inhibitory NKG2A or by activating NKG2C receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft survival during acute cellular rejection. HLA-E expression was up-regulated in acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal allografts with no rejection-signs. HLA-E up-regulation was correlated with numbers of HLA-class I leader peptide mismatches (p=0.04). CD8+ and CD56+ infiltrating cells correlated with HLA-E expression (pleader peptides might represent additional targets for immune-activating responses. Copyright © 2016 Elsevier GmbH. All rights reserved.

  16. Doppler ultrasound of the hepatic artery and vein performed daily in the first two weeks after orthotopic liver transplantation - Useful for the diagnosis of acute rejection?

    NARCIS (Netherlands)

    Kok, T; Haagsma, EB; Klompmaker, IJ; Zwaveling, JH; Peeters, PMJG; Bijleveld, CMA; Meerman, L; Slooff, MJH

    RATIONALE AND OBJECTIVES. To analyze changes in Doppler ultrasound variables in relation to liver biopsy findings for the diagnosis of acute rejection after orthotopic liver transplantation (OLT), the authors performed in a prospective study 316 Doppler ultrasound examinations in the first 2 weeks

  17. Nontraumatic vascular emergencies: imaging and intervention in acute venous occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Haage, Patrick; Schmitz-Rode, Thomas [Department of Diagnostic Radiology, University of Technology Aachen, Pauwelsstrasse 30, 52057 Aachen (Germany); Krings, Timo [Department of Neuroradiology, University of Technology Aachen, Pauwelsstrasse 30, 52057 Aachen (Germany)

    2002-11-01

    Risk factors for acute venous occlusion range from prolonged immobilization to hypercoagulability syndromes, trauma, and malignancy. The aim of this review article is to illustrate the different imaging options for the diagnosis of acute venous occlusion and to assess the value of interventional strategies for venous thrombosis treatment in an emergency setting. First, diagnosis and treatment of the most common form of venous occlusion, at the level of the lower extremities, is presented, followed by pelvic vein and inferior vena cava occlusion, mesenteric venous thrombosis, upper extremity occlusion, acute cerebral vein thrombosis, and finally acute venous occlusion of hemodialysis access. In acute venous occlusion of the lower extremity phlebography is still the reference gold standard. Presently, duplex ultrasound with manual compression is the most sensitive and specific noninvasive test. Limitations of ultrasonography include isolated distal calf vein occlusion, obesity, and patients with lower extremity edema. If sonography is nondiagnostic, venography should be considered. Magnetic resonance venography can differentiate an acute occlusion from chronic thrombus, but because of its high cost and limited availability, it is not yet used for the routine diagnosis of lower extremity venous occlusion only. Regarding interventional treatment, catheter-directed thrombolysis can be applied to dissolve thrombus in charily selected patients with symptomatic occlusion and no contraindications to therapy. Acute occlusion of the pelvic veins and the inferior vena cava, often due to extension from the femoropopliteal system, represents a major risk for pulmonary embolism. Color flow Doppler imaging is often limited owing to obesity and bowel gas. Venography has long been considered the gold standard for identifying proximal venous occlusion. Both CT scanning and MR imaging, however, can even more accurately diagnose acute pelvis vein or inferior vena cava occlusion. MRI is

  18. High-mobility group box 1 accelerates early acute allograft rejection via enhancing IL-17+ γδ T-cell response.

    Science.gov (United States)

    Xia, Quansong; Duan, Lihua; Shi, Lifeng; Zheng, Fang; Gong, Feili; Fang, Min

    2014-04-01

    Th17 and γδ T cells are the dominant IL-17-producing cell. We previously reported that high-mobility group box 1 (HMGB1) is critical in inducing IL-17-producing alloreactive T cells during early stage of acute allograft rejection. However, the role of γδ T cells during this process and its implication in HMGB1-mediated allograft rejection are not fully understood. Here, we use a murine model of cardiac allograft transplantation to further study the role of HMGB1 and IL-17-producing γδ T cells in acute allograft rejection. It was found that the expression of HMGB1 was increased in allograft, while blockade of HMGB1 suppressed IL-17(+) γδ T-cell response and inhibited the gene transcription of IL-23 and IL-1β. Furthermore, in vitro HMGB1 indirectly promoted the development of IL-17(+) γδ T cells by stimulating dendritic cells to produce IL-23 and IL-1β, meanwhile depletion of γδ T cells in vivo prolonged allograft survival and reduced the level of IL-17 in serum. In conclusion, our findings inferred that increased HMGB1 expression could enhance IL-17(+) γδ T-cell response by promoting the secretion of IL-23 and IL-1β, while IL-17(+) γδ T cells contribute to the early stage of acute allograft rejection. © 2014 Steunstichting ESOT.

  19. Acute vascular effects of waterpipe smoking: Importance of physical activity and fitness status.

    Science.gov (United States)

    Alomari, Mahmoud A; Khabour, Omar F; Alzoubi, Karem H; Shqair, Dana M; Stoner, Lee

    2015-06-01

    While new forms of tobacco, including waterpipe (WP) smoking, continue to gain popularity, limited literature has examined the vascular health consequences. The purpose of the current study was to examine: (i) the acute WP-induced changes in vascular function; (ii) whether acute changes in vascular function are modified by lifestyle behaviors (habitual physical activity, physical fitness). Fifty three (22.7 y, 36% F, 23.4 kg/m(2)) otherwise healthy WP smokers were recruited. Strain-gauge plethysmography was used to measure forearm blood flow, vascular resistance, venous capacitance, and venous outflow at rest and following occlusion. Habitual physical activity was determined using the Arabic version of short-form international physical activity questionnaire, while physical fitness was assessed using the 6 min walk test and handgrip strength. Partial correlations were used to examine the relationships between post-smoking vascular function and lifestyle behaviors, controlling for pre-smoking vascular measures. (i) WP had a small effect on forearm post-occlusion blood flow (d = -0.19), a moderate effect on venous outflow (d = 0.30), and a moderate effect on post-occlusion vascular resistance (d = 0.32). (ii) Total habitual physical activity strongly correlated with resting blood flow (r = 0.50) and moderately with vascular resistance (r = -0.40). Handgrip strength moderately correlated with venous capacitance (r = 0.30) and post-occlusion blood flow (r = 0.30), while 6 min walked distance moderately correlated with resting venous capacitance (r = 0.30). Waterpipe smoking is associated with immediate changes in vascular function, which are exacerbated in individuals with low habitual physical activity and physical fitness levels in young otherwise healthy individuals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. A case of acute bilateral femur fracture with vascular injury

    Directory of Open Access Journals (Sweden)

    Slavisa Zagorac

    2016-01-01

    Full Text Available The femoral fractures remain the great challenge for orthopedic surgeons regarding time of fixation and appropriate fixation techniques. There is a bimodal distribution of fractures occurring most frequently in young males after high-energy trauma (motor vehicle accidents and in elderly females after falls from standing. Young patients with femoral fracture are under the great risk of multiple injuries. Hence, the great significance is optimal time of fixation. We present a case of unusual pattern of injury and fixation technique of bilateral proximal femur fracture associated with vascular injury, with very satisfied outcome.

  1. Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal-transplant recipients using a joint modeling approach.

    Science.gov (United States)

    Daher Abdi, Z; Essig, M; Rizopoulos, D; Le Meur, Y; Prémaud, A; Woillard, J B; Rérolle, J P; Marquet, P; Rousseau, A

    2013-06-01

    This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mixed-effects model to describe the whole pattern of MPA exposure (i.e. area under the concentration-time curve (AUC)) and a survival model. MPA AUC thresholds were determined using time-dependent receiver-operating characteristics (ROC) curves. Data from 490 adult renal-transplant recipients, representative of the general population of adult renal-transplant patients (i.e. including patients considered at low immunological risk-enrolled in the OPERA trial as well as second renal transplant and patients co-treated by either cyclosporine or tacrolimus), were analyzed. A significant association was found between the longitudinal exposure to MPA (MPA AUCs=f(t)) and AR (p=0.0081), and validated by bootstrapping. A significant positive correlation was observed between time post-transplantation and ROC thresholds which increased in average from 35 mg h/L in the first days to 41 mg h/L beyond six months post-transplantation (papproach which recognizes the repeated measures in a same patient, this study supports the association between MPA exposure and AR. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Vascular Physiology according to Clinical Scenario in Patients with Acute Heart Failure: Evaluation using the Cardio-Ankle Vascular Index.

    Science.gov (United States)

    Goto, Toshihiko; Wakami, Kazuaki; Mori, Kento; Kikuchi, Shohei; Fukuta, Hidekatsu; Ohte, Nobuyuki

    2016-09-01

    Increased aortic stiffness may be an important cause of acute heart failure (AHF). Clinical scenario (CS), which classifies the pathophysiology of AHF based on the initial systolic blood pressure (sBP), was proposed to provide the most appropriate therapy for AHF patients. In CS, elevated aortic stiffness, vascular failure, has been considered as a feature of patients categorized as CS1 (sBP > 140 mmHg at initial presentation). However, whether elevated aortic stiffness, vascular failure, is present in such patients has not been fully elucidated. Therefore, we assessed aortic stiffness in AHF patients using the cardio-ankle vascular index (CAVI), which is considered to be independent of instantaneous blood pressure. Sixty-four consecutive AHF patients (mean age, 70.6 ± 12.8 years; 39 men) were classified with CS, based on their initial sBP: CS1: sBP > 140 mmHg (n = 29); CS2: sBP 100-140 mmHg (n = 22); and CS3: sBP < 100 mmHg (n = 13). There were significant group differences in CAVI (CS1 vs. CS2 vs. CS3: 9.7 ± 1.4 vs. 8.4 ± 1.7 vs. 8.3 ± 1.7, p = 0.006, analysis of variance). CAVI was significantly higher in CS1 than in CS2 (p = 0.02) and CS3 (p = 0.04). CAVI did not significantly correlate with sBP at the time of measurement of CAVI (r = 0.24 and p = 0.06). Aortic stiffness assessed using blood pressure-independent methodology apparently increased in CS1 AHF patients. We conclude that vascular failure is a feature of CS1 AHF initiation.

  3. Risk assessment, risk management, and prevention of acute vascular events

    Directory of Open Access Journals (Sweden)

    Gundu H R Rao

    2017-01-01

    Full Text Available South Asians have a very high incidence of cardiometabolic diseases such as hypertension, central abdominal obesity, metabolic syndrome, type 2 diabetes, heart disease, and stroke. In spite of the fact that common risk factors associated with these clinical conditions are known, we do not have point-of-care assays, to monitor the disease of the vessels, and the efficacy of antiplatelet therapy. We have a window of opportunity to develop three-dimensional ultrasound methodologies, to monitor the subclinical atherosclerosis, altered flow velocities of regional vascular beds, as well as plaque progression and regression in the major vessels. We also have opportunities to develop state-of-the-art methodologies for monitoring the efficacy or otherwise of antiplatelet therapies. In this overview, we share our views and strategies for the development of affordable medical technologies in India, for monitoring vessel wall pathology as well as for better management of antiplatelet therapies.

  4. Histological long-term outcomes from acute antibody-mediated rejection following ABO-compatible liver transplantation.

    Science.gov (United States)

    Del Bello, Arnaud; Danjoux, Marie; Congy-Jolivet, Nicolas; Lavayssière, Laurence; Esposito, Laure; Muscari, Fabrice; Kamar, Nassim

    2017-04-01

    Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known. Herein, we describe nine cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination. Two patients presented with aAMR at 10.5 (10, 11) days post-transplantation, caused by preformed donor-specific antibodies. Seven other recipients developed de novo donor-specific antibodies and aAMR at 11.2 (3-24) months post-transplantation. Eight of the nine patients received a B-cell targeting agent (rituximab, with or without plasma exchange), associated with polyclonal antibodies (three patients) or intravenous immunoglobulins (three patients). At the last follow up (i.e. 21 [4-90] months post-aAMR), seven patients were alive, including two patients with normal liver tests. Grafts' survival was 66%. A liver biopsy performed at 11.5 (5-48.5) months after the first biopsy showed no significant improvement in aAMR score (from 2 ± 1.3 to 1.6 ± 1.5, P = 0.6), a significant improvement in chronic AMR score (from 37 ± 9 to 25 ± 8, P = 0.003) and an increase in the Metavir score (1.2 ± 0.6 to 2.1 ± 0.9, P = 0.03). In this study, a B-cell-depleting agent seemed to improve the prognosis of aAMR in selected cases, but several patients kept active lesions antibody-mediated rejection. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  5. Normalizing Rejection.

    Science.gov (United States)

    Conn, Vicki S; Zerwic, Julie; Jefferson, Urmeka; Anderson, Cindy M; Killion, Cheryl M; Smith, Carol E; Cohen, Marlene Z; Fahrenwald, Nancy L; Herrick, Linda; Topp, Robert; Benefield, Lazelle E; Loya, Julio

    2016-02-01

    Getting turned down for grant funding or having a manuscript rejected is an uncomfortable but not unusual occurrence during the course of a nurse researcher's professional life. Rejection can evoke an emotional response akin to the grieving process that can slow or even undermine productivity. Only by "normalizing" rejection, that is, by accepting it as an integral part of the scientific process, can researchers more quickly overcome negative emotions and instead use rejection to refine and advance their scientific programs. This article provides practical advice for coming to emotional terms with rejection and delineates methods for working constructively to address reviewer comments. © The Author(s) 2015.

  6. Hyperosmolar nonketotic hyperglycemic coma induced by methylprednisolone pulse therapy for acute rejection after liver transplantation: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Zhou J

    2014-12-01

    Full Text Available Jian Zhou,* Weiqiang Ju,* Xiaopeng Yuan, Xiaofeng Zhu, Dongping Wang, Xiaoshun HeOrgan Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Hyperosmolar nonketotic hyperglycemic coma (HNKHC is a serious, rare complication induced by methylprednisolone (MP pulse therapy for acute rejection after orthotopic liver transplantation (OLT. Herein, we report an unusual case of a 58-year-old woman who experienced acute rejection at 30 months after OLT, only one case in which HNKHC resulted in MP pulse therapy for acute rejection in all 913 recipients in our center. The general morbidity of HNKHC was 1.09‰ in this study. HNKHC is characterized by rapid onset, rapid progression, and a lack of specific clinical manifestations. High-dose MP management was a clear risk factor. The principle of treatment included rapid rehydration, low-dose insulin infusion, and correcting disorders of electrolytes and acidosis. In conclusion, clinicians considering MP pulse therapy after OLT should be alert to the occurrence of HNKHC. Keywords: liver transplantation, complications, hyperosmolar nonketotic hyperglycemic coma, methylprednisolone pulse therapy, principle of treatment

  7. Spectrum of Retinal Vascular Diseases Associated With Paracentral Acute Middle Maculopathy.

    Science.gov (United States)

    Chen, Xuejing; Rahimy, Ehsan; Sergott, Robert C; Nunes, Renata P; Souza, Eduardo C; Choudhry, Netan; Cutler, Nathan E; Houston, Samuel K S; Munk, Marion R; Fawzi, Amani A; Mehta, Sonia; Hubschman, Jean-Pierre; Ho, Allen C; Sarraf, David

    2015-07-01

    To evaluate the spectrum of retinal diseases that can demonstrate paracentral acute middle maculopathy and isolated ischemia of the intermediate and deep capillary plexus. Retrospective, multicenter, observational case series. This is a retrospective case series review of 9 patients (10 eyes) from 5 centers with paracentral acute middle maculopathy lesions and previously unreported retinal vascular etiologies. Case presentations and multimodal imaging, including color photographs, near-infrared reflectance, fluorescein angiography, spectral-domain optical coherence tomography (SD OCT), and orbital color Doppler imaging, are described. Baseline and follow-up findings are correlated with clinical presentation, demographics, and systemic associations. Five men and 4 women, aged 27-66 years, were included. Isolated band-like hyperreflective lesions in the middle retinal layers, otherwise known as paracentral acute middle maculopathy, were observed in all patients at baseline presentation. Follow-up SD OCT analysis of these paracentral acute middle maculopathy lesions demonstrated subsequent thinning of the inner nuclear layer. Novel retinal vascular associations leading to retinal vasculopathy and paracentral acute middle maculopathy include eye compression injury causing global ocular ischemia, sickle cell crisis, Purtscher's retinopathy, inflammatory occlusive retinal vasculitis, post-H1N1 vaccine, hypertensive retinopathy, migraine disorder, and post-upper respiratory infection. Paracentral acute middle maculopathy lesions may develop in a wide spectrum of retinal vascular diseases. They are best identified with SD OCT analysis and may represent ischemia of the intermediate and deep capillary plexus. These lesions typically result in permanent thinning of the inner nuclear layer and are critical to identify in order to determine the cause of unexplained vision loss. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Delayed Graft Function in Kidney Transplants: Time Evolution, Role of Acute Rejection, Risk Factors, and Impact on Patient and Graft Outcome

    Directory of Open Access Journals (Sweden)

    Martin Chaumont

    2015-01-01

    Full Text Available Background. Although numerous risk factors for delayed graft function (DGF have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipient’s perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2–2.9]. Moreover, we observed two novel risk factors for DGF: patient’s residual diuresis ≤500 mL/d (OR = 2.3 [1.6–3.5] and absence of perioperative saline loading (OR = 3.3 [2.0–5.4]. Area under the curve of the ROC curve (0.77 [0.74–0.81] shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival (P=0.54. However, graft survival is decreased only when rejection was associated with DGF (P<0.001.  Conclusions. Perioperative saline loading efficiently prevents ischemia-reperfusion injury, which is the predominant factor inducing DGF. DGF per se has no influence on patient and graft outcome. Its incidence is currently close to 5% in our centre.

  9. Time elapsed after transplantation influences the relationship between the number of regulatory T cells in lung allograft biopsies and subsequent acute rejection episodes

    DEFF Research Database (Denmark)

    Krustrup, Dorrit; Iversen, Martin; Martinussen, Torben

    2014-01-01

    levels of Tregs/mm2. For biopsies taken 0.5 and 1month after transplantation, a significant correlation between Tregs/mm2 and the degree of acute rejection was found, and logistic regression analysis using updated values for Tregs/mm2 showed a significant relationship between Tregs/mm2 at 2weeks and an A...... indicating a narrow therapeutic window for induction of tolerance by specifically targeting T-cells. The results also indirectly indicate that Tregs early after transplantation could have an impact on the long-term outcome....

  10. A pilot study of steroid-free immunosuppression in the prevention of acute rejection in renal allograft recipients.

    Science.gov (United States)

    Cole, E; Landsberg, D; Russell, D; Zaltzman, J; Kiberd, B; Caravaggio, C; Vasquez, A R; Halloran, P

    2001-09-15

    Corticosteroids have been a mainstay of rejection prophylaxis for several decades, despite the multiple adverse effects of long-term use, including weight gain, hyperlipidemia, diabetes, hypertension, and bone disease. The detrimental effect of steroids on the metabolic profile begins in the early posttransplantation period, and the complete avoidance of steroids in transplantation would therefore be optimal. We hypothesized that the addition of mycophenolate mofetil (MMF) and a humanized monoclonal anti-CD25 antibody (daclizumab) to a cyclosporine (CsA microemulsion)-based immunosuppression protocol would permit transplantation without steroids. Steroid-free renal transplantation was attempted in 57 patients treated with daclizumab, MMF, and CsA. Twenty-eight patients received kidneys from living donors; the remaining 29 received cadaveric grafts. At 1 year, patient and graft survival were 95% and 89%, respectively. Fourteen patients (25%) experienced rejections, of which 13 were readily reversed with steroids; 1 patient required OKT3. Mean serum creatinine at 12 months for patients not experiencing rejection was 149+/-58 micromol/L, compared with 158+/-102 micromol/L for those experiencing rejection. Five patients required hospitalization for infection; no patients developed lymphoproliferative disease. At baseline, 17 patients required 3 or more antihypertensive medications, compared with 2 patients at 1 year. Three of 43 nondiabetic patients developed diabetes during the study. There was no significant reduction in lumbar or femoral bone density. On the basis of these positive results, we believe steroid avoidance with this immunosuppressive regimen merits further study.

  11. Intragraft interleukin 2 mRNA expression during acute cellular rejection and left ventricular total wall thickness after heart transplantation

    NARCIS (Netherlands)

    de Groot-Kruseman, H A; Baan, C C; Hagman, E M; Mol, W M; Niesters, H G; Maat, A P; Zondervan, P E; Weimar, W; Balk, A H

    OBJECTIVE: To assess whether diastolic graft function is influenced by intragraft interleukin 2 (IL-2) messenger RNA (mRNA) expression in rejecting cardiac allografts. DESIGN: 16 recipients of cardiac allografts were monitored during the first three months after transplantation. The presence of IL-2

  12. Do acute effects of exercise on vascular function predict adaptation to training?

    Science.gov (United States)

    Dawson, Ellen A; Cable, N Timothy; Green, Daniel J; Thijssen, Dick H J

    2018-03-01

    No previous study has explored the importance of exercise-induced changes in vascular function to prolonged adaptations. Therefore, the purpose was to explore the within-subject relationship between the acute post-exercise change in brachial artery endothelial function (flow-mediated dilation, FMD) and the change in resting FMD after a 2-week exercise training in healthy volunteers. Twenty one healthy, young men (24 ± 5 years) underwent assessment of brachial artery FMD using high-resolution ultrasound before and after 30-min of moderate-intensity cycle exercise (80% maximal heart rate). Subsequently, subjects performed five 30-min cycle exercise bouts at 80% maximal heart rate across a 2-week period, followed by repeat assessment of resting brachial FMD post-training. Correcting for changes in diameter and shear, FMD did not change after the initial exercise bout (P = 0.26). However, a significant correlation was found between post-exercise changes in FMD and adaptation in resting FMD after training (r = 0.634, P = 0.002), where an acute decrease in post-exercise FMD resulted in a decrease in baseline FMD after 2 weeks and vice versa. We also found a positive correlation between antegrade shear rate during exercise and change in FMD% after acute exercise and after exercise training (r = 0.529 and 0.475, both P < 0.05). Our findings suggest that acute post-exercise changes in vascular function are related to changes in resting FMD after a 2-week endurance exercise training period in healthy men, an effect that may be related to exercise-induced increases in antegrade shear rate. This provides further insight into the relevance of acute changes in shear and FMD for subsequent adaptation.

  13. Biopsy-proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal.

    Science.gov (United States)

    Rodríguez-Perálvarez, Manuel; Rico-Juri, Jose M; Tsochatzis, Emmanuel; Burra, Patrizia; De la Mata, Manuel; Lerut, Jan

    2016-09-01

    Biopsy-proven acute cellular rejection (ACR) is the primary efficacy endpoint in most randomized trials evaluating immunosuppression in liver transplantation. However, ACR is not a major cause of graft loss, and a certain grade of immune activation may be even beneficial for long-term graft acceptance. Validated criteria to select candidates for liver biopsy are lacking, and routine clinical practice relies on liver tests, which are inaccurate markers of ACR. Indeed, both the agreement among clinicians to select candidates for liver biopsy and the correlation between the clinical suspicion of ACR and histological findings are poor. In randomized trials evaluating immunosuppression protocols, this concern grows exponentially due to the open-label and multicenter nature of most studies. Therefore, biopsy-proven ACR is a suboptimal efficacy endpoint given its limited impact on prognosis and the heterogeneous diagnosis, which may increase the risk of bias. Chronic rejection and/or graft loss would be more appropriate endpoints, but would certainly require larger studies with prolonged surveillances. An objective method to select candidates for liver biopsy is therefore urgently needed, and only severe episodes of histological ACR should be considered as potentially harmful. Emerging surrogate markers of ACR and antibody-mediated rejection require further investigation to determine their clinical role. © 2015 Steunstichting ESOT.

  14. Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts. Studies in a heterotopic rat heart model

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Kan (Mie Univ., Tsu (Japan). School of Medicine); Ueda, Keisuke (Saitama Univ. (Japan). Dept. of Surgery); Scheffel, U.; Ravert, H.; Wagner, H.N. Jr. (Johns Hopkins Medical Institutions, Baltimore, MD (USA). Dept. of Radiology); LaFrance, N.D. (Du Pont (E.I.) Co., Inc., North Billerica, MA (USA)); Baumgartner, W.A.; Reitz, B.A.; Herskowitz, A. (Johns Hopkins Medical Institutions, Baltimore, MD (USA). Dept. of Surgery)

    1991-07-01

    {sup 111}In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium 99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and sign of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium 99m pyrophosphate accumulation (r=0.88) but was poorly correlated with labelled antibody uptake (r=0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labeled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium 99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin. (orig.).

  15. Vascular graft employment in the surgical treatment of acute and chronic acromio-clavicular dislocation.

    Science.gov (United States)

    Vitali, Matteo; Pedretti, Alberto; Naim Rodriguez, Nadim; Franceschi, Alessandro; Fraschini, Gianfranco

    2015-10-01

    To show the efficiency and safety of a surgical treatment in both acute and chronic acromio-clavicular junction (ACJ) dislocations. Retrospective. Department of Orthopedics and Traumatology at IRCCS San Raffaele Hospital. This study was performed on 37 subjects classified as Rockwood grade III-V or Tossy III ACJ dislocation. The surgical treatment was carried out by placing a vascular graft (GorePropaten(®)) between the tip of the coracoid process and the mid-lateral side of the clavicle with two temporary percutaneous K-wires positioned in a parallel manner in the AC ligament through the acromion and clavicle for 30 days to improve stability. Outcomes were assessed using the Constant Shoulder (CS) score, DASH score, subjective satisfaction, and stability of AC joint at 24 months. UCLA scores taken preoperatively and at 15-month follow-up were used to perform statistical analysis significance using a control group treated conservatively. Postoperative X-rays were examined to assess joint stability after 24 months. Preoperative CS score was 51 ± 12 in the acute group and 55 ± 15 in the chronic group. Follow-up mean CS score was 88 ± 11 in the acute group and 82 ± 20 in the chronic group at 24 months. Preoperative DASH score was 19 ± 3 in the acute group and 14 ± 5 in the chronic group. Mean DASH score was 3.60 ± 7 in the acute group and 6.42 ± 6 in the chronic group. Preoperative UCLA scores were 14.6 ± 2 and 15 ± 7 in the acute group and chronic group, respectively. At 15-month follow-up, UCLA scores of 28.1 ± 1.9 and 27.7 ± 1 in the acute and chronic group, respectively, showed a significant improvement (p partial re-dislocation at the 24-month X-ray follow-up. No infections, either deep or superficial, or nerve palsies were reported. Given the results obtained during the study and the response of the patients in both acute and chronic groups, the authors found that the employment of a vascular graft combined with temporary percutaneous K-wires is

  16. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study.

    Directory of Open Access Journals (Sweden)

    Christopher Vollmers

    2015-10-01

    Full Text Available It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation.In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412 that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without. We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient's net state of immunosuppression (correlation with tacrolimus level, r = -0.867, 95% CI -0.968 to -0.523, p = 0.0014, as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9% and a specificity of 82.0% (95% CI 72.1% to 89.1% (cell-free donor-derived DNA as noninvasive gold standard. To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several criteria including the

  17. Significance of complement split product C4d in ABO-compatible liver allograft: diagnosing utility in acute antibody mediated rejection.

    Science.gov (United States)

    Ali, Sharif; Ormsby, Adrian; Shah, Veena; Segovia, Maria C; Kantz, Kristin L; Skorupski, Sharon; Eisenbrey, A Bradley; Mahan, Meredith; Huang, Mary Ann Y

    2012-01-01

    Diagnosis of liver allograft antibody-mediated rejection (AMR) is difficult and requires a constellation of clinical, laboratory and histologic features that support the disease and exclude other causes. Histologic features of AMR may intermix with those of biliary obstruction, preservation/reperfusion injury, and graft ischemia. Tissue examination for complement degradation product 4d (C4d) has been proved to support this diagnosis in other allografts. For this reason, we conducted a retrospective review of all ABO compatible/identical re-transplanted liver patients with primary focus on identifying AMR as a possible cause of graft failure and to investigate the utility of C4d in liver allograft specimens. We reviewed 193 liver samples obtained from 53 consecutive ABO-compatible re-transplant patients. 142 specimens were stained with C4d. Anti-donor antibody screening and identification was determined by Luminex100 flow cytometry. For the study analysis, patients were stratified into 3 groups according to time to graft failure: group A, patients with graft failure within 0-7 days (n=7), group B within 8-90 days (n=13) and C >90 days (n=33). Two patients (3.7%) met the diagnostic criteria of acute AMR. Both patients experienced rapid decline of graft function with presence of donor specific antibodies (DSA), morphologic evidence of humoral rejection and C4d deposition in liver specimens. C4d-positive staining was identified in different medical liver conditions i.e., acute cellular rejection (52%), chronic ductopenic rejection (50%), recurrent liver disease (48%), preservation injury (18%), and hepatic necrosis (54%). Univariate analysis showed no significant difference of C4d-positive staining among the 3 patients groups, or patients with DSA (P>.05). In conclusion, AMR after ABO-compatible liver transplantation is an uncommon cause of graft failure. Unlike other solid organ allografts, C4d-positive staining is not a rugged indicator of humoral rejection, thus

  18. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke

    2012-01-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic...... and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3...

  19. Systemic vascular function, measured with forearm flow mediated dilatation, in acute and stable cerebrovascular disease: a case-control study

    Directory of Open Access Journals (Sweden)

    Blacker David

    2010-10-01

    Full Text Available Abstract Background Acute ischaemic stroke is associated with alteration in systemic markers of vascular function. We measured forearm vascular function (using forearm flow mediated dilatation to clarify whether recent acute ischaemic stroke/TIA is associated with impaired systemic vascular function. Methods Prospective case control study enrolling 17 patients with recent acute ischaemic stroke/TIA and 17 sex matched controls with stroke more than two years previously. Forearm vascular function was measured using flow medicated dilatation (FMD. Results Flow mediated dilatation was 6.0 ± 1.1% in acute stroke/TIA patients and 4.7 ± 1.0% among control subjects (p = 0.18. The mean paired difference in FMD between subjects with recent acute stroke and controls was 1.25% (95% CI -0.65, 3.14; p = 0.18. Endothelium independent dilatation was measured in six pairs of participants and was similar in acute stroke/TIA patients (22.6 ± 4.3% and control subjects (19.1 ± 2.6%; p = 0.43. Conclusions Despite the small size of this study, these data indicate that recent acute stroke is not necessarily associated with a clinically important reduction in FMD.

  20. Early blood pressure lowering treatment in acute stroke. Ordinal analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial (SCAST)

    DEFF Research Database (Denmark)

    Jusufovic, Mirza; Sandset, Else Charlotte; Bath, Philip M

    2016-01-01

    OBJECTIVE: Early blood pressure-lowering treatment appears to be beneficial in patients with acute intracerebral haemorrhage and potentially in ischaemic stroke. We used a new method for analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial to see if the effect was depend......OBJECTIVE: Early blood pressure-lowering treatment appears to be beneficial in patients with acute intracerebral haemorrhage and potentially in ischaemic stroke. We used a new method for analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial to see if the effect...... was dependent on the timing of treatment. METHODS: Scandinavian Candesartan Acute Stroke Trial was a randomized controlled and placebo-controlled trial of candesartan within 30 h of ischaemic or haemorrhagic stroke. Of 2029 patients, 231 (11.4%) had a vascular event (vascular death, nonfatal stroke or nonfatal...... logistic regression for analysis and adjusted for predefined prognostic variables. RESULTS: Candesartan had no overall effect on vascular events (adjusted common odds ratio 1.11, 95% confidence interval 0.84-1.47, P = 0.48), and the effects were the same in ischaemic and haemorrhagic stroke. Among...

  1. A critical role for vascular smooth muscle in acute glucocorticoid-induced hypertension.

    Science.gov (United States)

    Goodwin, Julie E; Zhang, Junhui; Geller, David S

    2008-07-01

    Although glucocorticoid (GC)-induced hypertension has commonly been attributed to promiscuous activation of the mineralocorticoid receptor by cortisol, thereby promoting excess reabsorption of sodium and water, numerous lines of evidence indicate that this is not the only or perhaps even the primary mechanism. GC induce a number of effects on vascular smooth muscle (VSM) in vitro that may be pertinent to hypertension, but their contribution in vivo is unknown. To address this question, a mouse model with a tissue-specific knockout (KO) of the GC receptor in the VSM was created and characterized. Similar to control mice, KO mice exhibited normal baseline BP and, interestingly, showed normal circadian variation in BP. When dexamethasone was administered, however, the acute hypertensive response was markedly attenuated in KO mice, and there was a trend toward a decreased chronic hypertensive response. These data suggest that the GC receptor in VSM plays a critical role in the acute hypertensive response to GC in vivo.

  2. Suppression of acute and chronic cardiac allograft rejection in mice by inhibition of chemokine receptor 5 in combination with cyclosporine A.

    Science.gov (United States)

    Li, Jun; Xia, Jiahong; Zhang, Kailun; Xu, Lei

    2009-11-01

    Inhibition of chemokine receptor 5 (CCR5), a chemokine receptor expressed on activated T cells, is an effective antiviral therapy in patients with HIV infection, but its efficacy in modulating inflammation and immunity is only just beginning to be investigated. In this study we examined the inhibition of CCR5 in combination with the treatment with cyclosporine A in acute and chronic rejection in cardiac transplantation. Eighty fully MHC-mismatched murine cardiac allograft models were randomized to four groups. Recipients in group A were treated with anti-CCR5 mAb and CsA, mice in group B were given anti-CCR5 mAb alone, animals in group C were administered only CsA, and group D were the control group with PBS. Acute and chronic rejection was investigated on day 7 and day 45 post-transplant, respectively. Allografts treated with anti-CCR5 mAb plus CsA showed significantly prolonged survival (44.73 +/- 0.258 d, P cardiac graft failure that has not been obviated by conventional immunosuppressive agents.

  3. Orthogonal Comparison of Molecular Signatures of Kidney Transplants With Subclinical and Clinical Acute Rejection: Equivalent Performance Is Agnostic to Both Technology and Platform.

    Science.gov (United States)

    Kurian, S M; Velazquez, E; Thompson, R; Whisenant, T; Rose, S; Riley, N; Harrison, F; Gelbart, T; Friedewald, J J; Charette, J; Brietigam, S; Peysakhovich, J; First, M R; Abecassis, M M; Salomon, D R

    2017-08-01

    We performed orthogonal technology comparisons of concurrent peripheral blood and biopsy tissue samples from 69 kidney transplant recipients who underwent comprehensive algorithm-driven clinical phenotyping. The sample cohort included patients with normal protocol biopsies and stable transplant (sTx) function (n = 25), subclinical acute rejection (subAR, n = 23), and clinical acute rejection (cAR, n = 21). Comparisons between microarray and RNA sequencing (RNA-seq) signatures were performed and demonstrated a strong correlation between the blood and tissue compartments for both technology platforms. A number of shared differentially expressed genes and pathways between subAR and cAR in both platforms strongly suggest that these two clinical phenotypes form a continuum of alloimmune activation. SubAR is associated with fewer or less expressed genes than cAR in blood, whereas in biopsy tissues, this clinical phenotype demonstrates a more robust molecular signature for both platforms. The discovery work done in this study confirms a clear ability to detect gene expression profiles for sTx, subAR, and cAR in both blood and biopsy tissue, yielding equivalent predictive performance that is agnostic to both technology and platform. Our data also provide strong biological insights into the molecular mechanisms underlying these signatures, underscoring their logistical potential as molecular diagnostics to improve clinical outcomes following kidney transplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Acute absolute vasodilatation is associated with a lower vascular wall stiffness in pulmonary arterial hypertension.

    Science.gov (United States)

    Grignola, Juan C; Domingo, Enric; Aguilar, Rio; Vázquez, Manuel; López-Messeguer, Manuel; Bravo, Carlos; Roman, Antonio

    2013-04-05

    Acute vasoreactivity testing (VT) is considered mandatory in the diagnostic work-up of patients with pulmonary arterial hypertension (PAH). We studied the relation between the acute absolute arterial vasodilatation and the severity of vascular remodeling estimated by intravascular ultrasound (IVUS) in patients with idiopathic PAH. Simultaneous right heart catheterization and IVUS of the pulmonary artery (PA) were performed both in basal conditions and during short-term intravenous epoprostenol infusion in nineteen idiopathic PAH patients. Pulmonary vascular resistance (PVRi) and capacitance indexes (stroke volume/pulse pressure, Cp), were calculated. Local pulsatility was estimated by IVUS (IVUSp) (systolic-diastolic lumen area/diastolic lumen area×100; sA-dA/dA) and PA stiffness was assessed by the elastic modulus (E: pulse pressure/IVUSp). Epoprostenol infusion (11±2ng/kg/min) determined a real vasodilatation (increment of dA>10%) in six patients. This vasodilation group presented on average significantly higher cardiac index, stroke volume index and Cp, and lower PVRi and IVUSp (Prights reserved.

  5. Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients

    Science.gov (United States)

    Djamali, Arjang; Muth, Brenda; Ellis, Thomas M.; Mohamed, Maha; Fernandez, Luis; Miller, Karen; Bellingham, Janet; Odorico, Jon; Mezrich, Joshua; Pirsch, John; D’Alessandro, Tony; Vidyasagar, Vijay; Hofmann, R. Michael; Torrealba, Jose; Kaufman, Dixon; Foley, David

    2013-01-01

    In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean calculated panel reactive antibody and MFImax ranged from 10.3% to 57.2%, and 262 to 1691, respectively, between low and high-risk protocols. Mean MFImax increased significantly from transplant to one-week and one-year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32% including 14% cellular, 12% antibody-mediated and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71 to 6.45) and increased donor specific antibodies at 1 week post-transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients. PMID:23447068

  6. Two-stage, in silico deconvolution of the lymphocyte compartment of the peripheral whole blood transcriptome in the context of acute kidney allograft rejection.

    Directory of Open Access Journals (Sweden)

    Casey P Shannon

    Full Text Available Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of

  7. Acute changes in urinary excretion of nitrite + nitrate do not necessarily predict renal vascular NO production.

    Science.gov (United States)

    Sütö, T; Losonczy, G; Qiu, C; Hill, C; Samsell, L; Ruby, J; Charon, N; Venuto, R; Baylis, C

    1995-10-01

    NO2 + NO3 (NOx), the stable oxidation products of NO, and cGMP are widely accepted as indices of in vivo NO production. Whether acute changes in urinary excretion of nitrite + nitrate (UNOXV) can be taken to reflect acute changes in renal and/or systemic NO production is not known. The present studies were conducted in the conscious rat to investigate the effect on acute changes in UNOxV, of maneuvers that (a) enhance NO production and (b) act as diuretics. L-arginine (L-arg) and acetylcholine (Ach) produce equivalent NO dependent falls in renal vascular resistance (RVR), but a much greater increase in UNOX V is seen with L-arg. D-arg does not stimulate NO and has no renal vasodilatory effect, but produces a large rise in UNOX V, and SNP lowers BP but not RVR and results in a reduced UNOX V. None of the diuretics employed should stimulate the NO system or lower RVR; however, the proximally acting agents, acetazolamide and D-arg increased UNOx V, while the loop diuretic furosemide had little effect. H2O diuresis (a distal event) led to a fall in UNOx V. These data suggest that NOx is reabsorbed extensively in the proximal tubule and that inhibition of proximal reabsorption leads to an increase in UNOx V. Also, our results show that the relationship between UNOx V and UcGMP V is unpredictable. Therefore, we conclude that measurements of acute changes in UNOxV and/or UcGMP V should be interpreted cautiously, since they may reflect altered tubular handling of NOx rather than the acute activity of the systemic and/or renal NO systems.

  8. Association of the Number of HLA-DR Mismatches With Early Post-transplant Acute Cellular Rejection Among Heart Transplantation Recipients: A Cohort Study in Japanese Population.

    Science.gov (United States)

    Nitta, D; Kinugawa, K; Imamura, T; Iino, J; Endo, M; Amiya, E; Hatano, M; Kinoshita, O; Nawata, K; Ono, M; Komuro, I

    Although many risk factors are reported about graft rejection after heart transplantation (HTx), the effect of HLA mismatch (MM) still remains unknown, especially in the Japanese population. The aim of the present study was to investigate the influence of HLA MM on graft rejection among HTx recipients in Japan. We retrospectively investigated the association of the number of HLA MM including class I (A, B) and class II (DR) (for each locus MM: 0 to 2, total MM: 0 to 6) and the incidence of moderate to severe acute cellular rejection (ACR) confirmed by endomyocardial biopsy (International Society for Heart and Lung Transplantation grade ≥ 3A/2R) within 1 year after HTx. Between 2007 and 2014, we had 49 HTx cases in our institute. After excluding those with insufficient data and positive donor-specific antigen, finally 35 patients were enrolled. Moderate to severe ACR was observed in 16 (45.7%) patients. The number of HLA-DR MM was significantly associated with the development of ACR (ACR+: 1.50 ± 0.63, ACR-: 1.11 ± 0.46, P = .029). From univariate analysis, DR MM = 2 was the only independent risk factor for ACR episodes (P = .017). The frequency of ACR within 1 year was significantly higher in those with DR MM = 2 (DR MM = 0 to 1: 0.3 ± 0.47, DR MM = 2: 1.17 ± 1.34 times, P = .007). The number of HLA-DR MMs was associated with the development and recurrence of ACR episodes among HTx recipients within 1 year after transplantation in Japanese population. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Sepiapterin decreases acute rejection and apoptosis in cardiac transplants independently of changes in nitric oxide and inducible nitric-oxide synthase dimerization.

    Science.gov (United States)

    Pieper, Galen M; Ionova, Irina A; Cooley, Brian C; Migrino, Raymond Q; Khanna, Ashwani K; Whitsett, Jennifer; Vásquez-Vivar, Jeannette

    2009-06-01

    Tetrahydrobiopterin (BH(4)), a cofactor of inducible nitric-oxide synthase (iNOS), is an important post-translational regulator of NO bioactivity. We examined whether treatment of cardiac allograft recipients with sepiapterin [S-(-)-2-amino-7,8-dihydro-6-(2-hydroxy-1-oxopropyl)-4-(1H)-pteridinone], a precursor of BH(4), inhibited acute rejection and apoptosis in cardiac transplants. Heterotopic cardiac transplantation was performed in Wistar-Furth donor to Lewis recipient strain rats. Recipients were treated daily after transplantation with 10 mg/kg sepiapterin. Grafts were harvested on post-transplant day 6 for analysis of BH(4) (high-performance liquid chromatography), expression of inflammatory cytokines (reverse transcription- and real-time polymerase chain reaction), iNOS (Western blots), and NO (Griess reaction and NO analyzer). Histological rejection grade was scored, and graft function was determined by echocardiography. Apoptosis, protein nitration, and oxidative stress were determined by immunohistochemistry. Treatment of allografts with sepiapterin increased cardiac BH(4) levels by 3-fold without changing protein levels of GTP cyclohydrolase, the enzyme that regulates de novo BH(4) synthesis. Sepiapterin decreased inflammatory cell infiltrate and significantly inhibited histological rejection scores and apoptosis similar in magnitude to cyclosporine. Sepiapterin also decreased nitrative and oxidative stress. Sepiapterin caused a smaller increase in left ventricular mass versus untreated allografts but without improving fractional shortening. Sepiapterin did not alter tumor necrosis factor-alpha and interferon-gamma expression, whereas it decreased interleukin (IL)-2 expression. Sepiapterin did not change total iNOS protein or monomer levels, or plasma and tissue NO metabolites levels. It is concluded that the mechanism(s) of antirejection are due in part to decreased apoptosis, protein nitration, and oxidation of cardiomyocytes, which seems to be

  10. Current clinical and epidemiological portrait of a patient with acute myocardial infarction (by the data of the regional vascular center

    Directory of Open Access Journals (Sweden)

    E. Yu. Kovalchuk

    2015-01-01

    Full Text Available Epidemiological and clinical presentation of acute myocardial infarction based upon the data collected in Regional Vascular Centre of Saint-Petersburg Scientific Research Institute of Emergency Care n. a. I. I. Dzhanelidze in 2009-2012 years. In the article, 4697 cases have been analyzed. Specific features of epidemiology and clinical presentation of acute myocardial infarction at the present stage have been considered.

  11. Preoperative antihypertensive medication intake and acute kidney injury after major vascular surgery.

    Science.gov (United States)

    Duceppe, Emmanuelle; Lussier, Anne-Renee; Beaulieu-Dore, Roxane; LeManach, Yannick; Laskine, Mikhael; Fafard, Josee; Durand, Madeleine

    2018-01-27

    Postoperative acute kidney injury (AKI) is frequent after major vascular surgery and is associated with significant morbidity and mortality. It remains unclear whether the administration of combined oral antihypertensive medications on the day of surgery can increase the risk of postoperative AKI. We performed a retrospective cohort study of hypertensive patients undergoing elective major vascular surgery to determine the association between the number of antihypertensive medications continued on the morning of surgery and AKI at 48 hours postoperatively. A total of 406 patients who had undergone suprainguinal vascular surgery were included, and 10.3% suffered postoperative AKI. In multivariable analysis, the number of antihypertensive medications taken on the morning of surgery was independently associated with AKI (P = .026). Compared with patients who took no medication, taking one medication (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 0.68-3.75) and taking two or more medications (aOR, 2.70; 95% CI, 1.13-6.44) were associated with a 1.6-fold and 2.7-fold increased risk of postoperative AKI, respectively. Other predictors of AKI were suprarenal surgery (aOR, 3.37; 95% CI, 1.53-7.44), age (aOR, 2.29 per 10 years; 95% CI, 1.40-3.74), length of surgery (aOR, 1.40 per 1 hour; 95% CI, 1.10-1.76), hemoglobin drop (aOR, 1.37 per 10 g/L; 95% CI, 1.10-1.74), and history of coronary artery disease (aOR, 2.33; 95% CI, 1.08-5.00). In patients undergoing major vascular surgery who are treated with chronic antihypertensive therapy, the administration of antihypertensive drugs on the morning of surgery is independently associated with an increased risk of postoperative AKI. Further prospective studies are needed to confirm this finding. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  12. Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate

    Science.gov (United States)

    Jaikaransingh, Vishal; MacConmara, Malcolm P.; Parekh, Justin R.; Levea, Swee-Ling; Ariyamuthu, Venkatesh K.; Zhang, Song; Gao, Ang; Ayvaci, Mehmet U.S.; Sandikci, Burhaneddin; Rajora, Nilum; Ahmed, Vaqar; Lu, Christopher Y.; Mohan, Sumit; Vazquez, Miguel A.

    2016-01-01

    Background and objectives IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. Design, setting, participants, & measurements We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post-transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies. Results Median (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P<0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P<0.001, respectively) in the no steroid group. Compared with IL2-RA, PS–weighted and covariate–adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no

  13. Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection.

    Directory of Open Access Journals (Sweden)

    Kazuaki Yamanaka

    Full Text Available The association of complement with the progression of acute T cell mediated rejection (ATCMR is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs in acute T-cell mediated rejection using rat and human renal allografts.We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP by immunohistochemical staining in human renal grafts and their clinical course.qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry, was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.

  14. Vascular Pathology in the Extracranial Vertebral Arteries in Patients with Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Bentsen, L; Nygård, A; Ovesen, C

    2014-01-01

    INTRODUCTION: Vascular pathology in the extracranial vertebral arteries remains among the possible causes in cryptogenic stroke. However, the diagnosis is challenged by the great variety in the anatomy of the vertebral arteries, clinical symptoms and difficulties in the radiological assessments....... METHOD: The analysis was based on 657 consecutive patients with symptoms of acute stroke and a final diagnosis of ischemic stroke or transient ischemic attack. On admission, a noncontrast CT cerebrum and CTA were performed. A senior consultant neuroradiologist, blinded to clinical data, reviewed all CTA...... (2.8%) with pathological findings had an unknown cause of stroke, likely posterior symptoms and no clinical stroke symptoms from the anterior circuit. Of these, 3 cases were kinked arteries (0.5%) and 15 cases (2.3%) were possible dissections. CONCLUSION: We found that in approximately 3...

  15. Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.

    Directory of Open Access Journals (Sweden)

    Elena Crespo

    Full Text Available Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90, to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67. We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction

  16. Activation of adherent vascular neutrophils in the lung during acute endotoxemia

    Directory of Open Access Journals (Sweden)

    Laskin Jeffrey D

    2002-08-01

    Full Text Available Abstract Background Neutrophils constitute the first line of defense against invading microorganisms. Whereas these cells readily undergo apoptosis under homeostatic conditions, their survival is prolonged during inflammatory reactions and they become biochemically and functionally activated. In the present study, we analyzed the effects of acute endotoxemia on the response of a unique subpopulation of neutrophils tightly adhered to the lung vasculature. Methods Rats were treated with 5 mg/kg lipopolysaccharide (i.v. to induce acute endotoxemia. Adherent neutrophils were isolated from the lung vasculature by collagenase digestion and sequential filtering. Agarose gel electrophoresis, RT-PCR, western blotting and electrophoretic mobility shift assays were used to evaluate neutrophil activity. Results Adherent vascular neutrophils isolated from endotoxemic animals exhibited decreased apoptosis when compared to cells from control animals. This was associated with a marked increase in expression of the anti-apoptotic protein, Mcl-1. Cells isolated 0.5–2 hours after endotoxin administration were more chemotactic than cells from control animals and expressed increased tumor necrosis factor-alpha and cyclooxygenase-2 mRNA and protein, demonstrating that they are functionally activated. Endotoxin treatment of the animals also induced p38 and p44/42 mitogen activated protein kinases in the adherent lung neutrophils, as well as nuclear binding activity of the transcription factors, NF-κB and cAMP response element binding protein. Conclusion These data demonstrate that adherent vascular lung neutrophils are highly responsive to endotoxin and that pathways regulating apoptosis and cellular activation are upregulated in these cells.

  17. The kSORT Assay to Detect Renal Transplant Patients at High Risk for Acute Rejection: Results of the Multicenter AART Study

    Science.gov (United States)

    Hsieh, Sue; Dai, Hong; Bestard, Oriol; Metes, Diana; Zeevi, Andrea; Gritsch, Albin; Cheeseman, Jennifer; Macedo, Camila; Peddy, Ram; Medeiros, Mara; Vincenti, Flavio; Asher, Nancy; Salvatierra, Oscar; Shapiro, Ron; Kirk, Allan; Reed, Elaine; Sarwal, Minnie M.

    2014-01-01

    Background Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR) increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR. Methods and Findings We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART) study. Gene expression was assessed by quantitative real-time PCR (QPCR) in one center. A 17-gene set—the Kidney Solid Organ Response Test (kSORT)—was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91–0.98), validated in 124 independent samples (AUC = 0.95; 95% CI 0.88–1.0) and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy). A novel reference-based algorithm (using 13 12-gene models) was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86–0.99). Further validation of kSORT is planned in prospective clinical observational and interventional trials. Conclusions The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants. Please see later in the article for the Editors' Summary PMID

  18. The kSORT assay to detect renal transplant patients at high risk for acute rejection: results of the multicenter AART study.

    Directory of Open Access Journals (Sweden)

    Silke Roedder

    2014-11-01

    Full Text Available Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR.We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART study. Gene expression was assessed by quantitative real-time PCR (QPCR in one center. A 17-gene set--the Kidney Solid Organ Response Test (kSORT--was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91-0.98, validated in 124 independent samples (AUC = 0.95; 95% CI 0.88-1.0 and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy. A novel reference-based algorithm (using 13 12-gene models was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86-0.99. Further validation of kSORT is planned in prospective clinical observational and interventional trials.The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants. Please see later in the article for the Editors' Summary.

  19. High Acute Myeloid Leukemia derived VEGFA levels are associated with a specific vascular morphology in the leukemic bone marrow

    NARCIS (Netherlands)

    Weidenaar, Alida C.; ter Elst, Arja; Koopmans-Klein, Gineke; Rosati, Stefano; den Dunnen, Wilfred F. A.; Meeuwsen-de Boer, Tiny; Kamps, Willem A.; Vellenga, Edo; de Bont, Eveline S. J. M.

    Acute Myeloid Leukemia (AML) bone marrow biopsies at diagnosis display enhanced angiogenesis and increased VEGFA expression. In a xenograft mouse model it was described that availability of free VEGFA versus bound VEGFA is related to different vascular morphology. In this study we investigate the

  20. Acute effects of vascular modifying agents in solid tumors assessed by noninvasive laser Doppler flowmetry and near infrared spectroscopy

    DEFF Research Database (Denmark)

    Kragh, Michael; Quistorff, Bjørn; Horsman, Michael R

    2002-01-01

    that the mechanism of action of CA4DP was vascular shut down with the blood pool trapped in the tumor. NTA caused no change in either tumor perfusion or tumor blood volume. We conclude that noninvasive LDF and NIRS can determine acute effects of vascular modifying agents on tumor perfusion and blood volume.......The potential of noninvasive laser Doppler flowmetry (LDF) and near infrared spectroscopy (NIRS) to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (approximately 200 mm(3)) in the rear foot of CDF1 mice......%, and 78%, respectively. In addition, FAA, DMXAA, and HDZ significantly reduced the blood volume within the tumor, indicating that these compounds to some degree shunted blood from the tumor to adjacent tissue, HDZ being most potent. CA4DP caused no change in the tumor blood volume, indicating...

  1. Acute black tea consumption improves cutaneous vascular function in healthy middle-aged humans.

    Science.gov (United States)

    Woodward, Kirsty A; Hopkins, Nicola D; Draijer, Richard; de Graaf, Young; Low, David A; Thijssen, Dick H J

    2016-12-22

    Dietary flavonoids, such as those present in black tea, are associated with reduced risk of cardiovascular disease (CVD), possibly through improving nitric oxide (NO) mediated vascular function. The aim of this study was to examine the effect of acute black tea ingestion on cutaneous microvascular function. Twenty healthy participants (58 ± 5 y, 9 men) attended two experimental trials (tea, placebo), 7-days apart in a randomised, controlled, double-blind, cross-over design. Participants ingested a single dose of 200 ml black tea or placebo, followed by assessment of forearm cutaneous perfusion using laser-Doppler flowmetry (LDF) using three distinct heating protocols, enabling us to distinguish between axon- and endothelium-dependent vasodilation: 1. rapid 42°C, 2. rapid 39°C and 3. gradual 42°C. On the contralateral arm, full-field laser perfusion imaging (FLPI) was used to assess forearm perfusion during gradual 42°C. Data were presented as cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC (%CVCmax). Rapid local heating to 39°C or 42°C demonstrated no effect of tea for flux, CVC or %CVCmax (all P > 0.05). Gradual local heating to 42 °C, however, produced a higher skin blood flow following black tea ingestion for absolute CVC (P = 0.04) when measured by LDF, and higher absolute flux (P < 0.001) and CVC (P < 0.001) measured with FLPI. No effect of tea was found for %CVCmax when assessed by either LDF or FLPI. Acute tea ingestion enhanced cutaneous vascular responses to gradual local heating to 42 °C in healthy, middle-aged participants, possibly through a mechanism related to activation of endothelium-derived chemical mediators, such as NO. These improvements may contribute to the cardiovascular health benefits of regular tea ingestion. Copyright © 2016. Published by Elsevier Ltd.

  2. Basiliximab treatment for steroid-resistant rejection in pediatric patients following liver transplantation for acute liver failure.

    Science.gov (United States)

    Shigeta, Takanobu; Sakamoto, Seisuke; Uchida, Hajime; Sasaki, Kengo; Hamano, Ikumi; Kanazawa, Hiroyuki; Fukuda, Akinari; Kawai, Toshinao; Onodera, Masafumi; Nakazawa, Atsuko; Kasahara, Mureo

    2014-12-01

    An IL-2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6-12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno-occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Urinary metabolomics for noninvasive detection of borderline and acute T cell-mediated rejection in children after kidney transplantation.

    Science.gov (United States)

    Blydt-Hansen, T D; Sharma, A; Gibson, I W; Mandal, R; Wishart, D S

    2014-10-01

    The goal of this study was to evaluate the utility of urinary metabolomics for noninvasive diagnosis of T cell-mediated rejection (TCMR) in pediatric kidney transplant recipients. Urine samples (n = 277) from 57 patients with surveillance or indication kidney biopsies were assayed for 134 unique metabolites by quantitative mass spectrometry. Samples without TCMR (n = 183) were compared to borderline tubulitis (n = 54) and TCMR (n = 30). Partial least squares discriminant analysis identified distinct classifiers for TCMR (area under receiver operating characteristic curve [AUC] = 0.892; 95% confidence interval [CI] 0.827-0.957) and borderline tubulitis (AUC = 0.836; 95% CI 0.781-0.892), respectively. Application of the TCMR classifier to borderline tubulitis samples yielded a discriminant score (-0.47 ± 0.33) mid-way between TCMR (-0.20 ± 0.34) and No TCMR (-0.80 ± 0.32) (p metabolomics is a sensitive, specific and noninvasive tool for TCMR identification that is superior to serum creatinine, with minimal confounding by other allograft injury processes. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. The number of regulatory T cells in transbronchial lung allograft biopsies is related to FoxP3 mRNA levels in bronchoalveolar lavage fluid and to the degree of acute cellular rejection

    DEFF Research Database (Denmark)

    Krustrup, Dorrit; Madsen, Caroline B; Iversen, Martin

    2013-01-01

    the number of lymphocytes expressing FoxP3 in transbronchial biopsies from lung allografts with the FoxP3 expression in bronchoalveolar lavage fluid (BALF). In addition, we aimed to correlate the number of FoxP3+ cells in transbronchial biopsies with the degree of acute cellular rejection in lung allografts....

  5. Endovascular Acute Stroke Treatment Performed by Vascular Interventional Radiologists: Is It Safe and Efficacious?

    Energy Technology Data Exchange (ETDEWEB)

    Fjetland, Lars, E-mail: lars.fjetland@lyse.net; Roy, Sumit; Kurz, Kathinka D. [Stavanger University Hospital, Department of Radiology (Norway); Larsen, Jan Petter; Kurz, Martin W. [Stavanger University Hospital, Norwegian Centre for Movement Disorders (Norway)

    2012-10-15

    Purpose: To evaluate the safety and efficacy of neurointerventional procedures in acute stroke patients performed by a team of vascular interventional radiologists in close cooperation with diagnostic neuroradiologists and stroke neurologists and to compare the results with those of previous reports from centres with specialised interventional neuroradiologists. Material and Methods: A total of 39 patients with acute ischemic stroke due to large-vessel occlusion not responding to or not eligible for intravenous thrombolysis were treated with either intra-arterial thrombolysis or mechanical thrombectomy (Penumbra System or solitaire FR thrombectomy system, respectively) and included in our prospective study. Outcomes were measured using the modified Rankin scale after 90 days, and recanalization was assessed by thrombolysis using the myocardial infarction score. Results: Mean patient age was 68.3 {+-} 14.2 years; the average National Institutes of Health Stroke Scale score at hospital admission was 17.2 (SD = 6.2 [n = 38]). Successful recanalization was achieved in 74.4 % of patients. Median time from clinical onset to recanalization was 5 h 11 min. Procedure-related complications occurred in 5 % of patients, and 7.5 % had a symptomatic intracerebral hemorrhage. Of the patients, 22.5 % died within the first 90 postprocedural days, 5 % of these from cerebral causes. Patients who were successfully recanalized had a clinical better outcome at follow-up than those in whom treatment failed. Of the patients, 35.9 % had an mRS score {<=}2 after 90 days. Conclusion: Our results are in line with those in the published literature and show that a treatment strategy with general interventional radiologists performing neurointerventional procedures in acute stroke patients with large vessel occlusions can be achieved to the benefit of patients.

  6. Asthma is a risk factor for acute chest syndrome and cerebral vascular accidents in children with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Scott Paul J

    2005-01-01

    Full Text Available Abstract Background Asthma and sickle cell disease are common conditions that both may result in pulmonary complications. We hypothesized that children with sickle cell disease with concomitant asthma have an increased incidence of vaso-occlusive crises that are complicated by episodes of acute chest syndrome. Methods A 5-year retrospective chart analysis was performed investigating 48 children ages 3–18 years with asthma and sickle cell disease and 48 children with sickle cell disease alone. Children were matched for age, gender, and type of sickle cell defect. Hospital admissions were recorded for acute chest syndrome, cerebral vascular accident, vaso-occlusive pain crises, and blood transfusions (total, exchange and chronic. Mann-Whitney test and Chi square analysis were used to assess differences between the groups. Results Children with sickle cell disease and asthma had significantly more episodes of acute chest syndrome (p = 0.03 and cerebral vascular accidents (p = 0.05 compared to children with sickle cell disease without asthma. As expected, these children received more total blood transfusions (p = 0.01 and chronic transfusions (p = 0.04. Admissions for vasoocclusive pain crises and exchange transfusions were not statistically different between cases and controls. SS disease is more severe than SC disease. Conclusions Children with concomitant asthma and sickle cell disease have increased episodes of acute chest syndrome, cerebral vascular accidents and the need for blood transfusions. Whether aggressive asthma therapy can reduce these complications in this subset of children is unknown and requires further studies.

  7. Small RNA-seq during acute maximal exercise reveal RNAs involved in vascular inflammation and cardiometabolic health: brief report.

    Science.gov (United States)

    Shah, Ravi; Yeri, Ashish; Das, Avash; Courtright-Lim, Amanda; Ziegler, Olivia; Gervino, Ernest; Ocel, Jeffrey; Quintero-Pinzon, Pablo; Wooster, Luke; Bailey, Cole Shields; Tanriverdi, Kahraman; Beaulieu, Lea M; Freedman, Jane E; Ghiran, Ionita; Lewis, Gregory D; Van Keuren-Jensen, Kendall; Das, Saumya

    2017-12-01

    Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. We performed plasma small RNA sequencing in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry. We found changes in miRNAs and other ex-RNAs with exercise (e.g., Y RNAs and tRNAs) implicated in cardiovascular disease. In two independent cohorts of acute maximal exercise, we identified miR-181b-5p as a key ex-RNA increased in plasma after exercise, with validation in a separate cohort. In a mouse model of acute exercise, we found significant increases in miR-181b-5p expression in skeletal muscle after acute exercise in young (but not older) mice. Previous work revealed a strong role for miR-181b-5p in vascular inflammation in obesity, insulin resistance, sepsis, and cardiovascular disease. We conclude that circulating ex-RNAs were altered in plasma after acute exercise target pathways involved in inflammation, including miR-181b-5p. Further investigation into the role of known (e.g., miRNA) and novel (e.g., Y RNAs) RNAs is warranted to uncover new mechanisms of vascular inflammation on exercise-mediated benefits on health.NEW & NOTEWORTHY How exercise provides benefits to cardiometabolic health remains unclear. We performed RNA sequencing in plasma during exercise to identify the landscape of small noncoding circulating transcriptional changes. Our results suggest a link between inflammation and exercise, providing rich data on circulating noncoding RNAs for future studies by the scientific community. Copyright © 2017 the American Physiological Society.

  8. Dual-phase CT for the assessment of acute vascular injuries in high-energy blunt trauma: the imaging findings and management implications.

    Science.gov (United States)

    Iacobellis, Francesca; Ierardi, Anna M; Mazzei, Maria A; Magenta Biasina, Alberto; Carrafiello, Gianpaolo; Nicola, Refky; Scaglione, Mariano

    2016-01-01

    Acute vascular injuries are the second most common cause of fatalities in patients with multiple traumatic injuries; thus, prompt identification and management is essential for patient survival. Over the past few years, multidetector CT (MDCT) using dual-phase scanning protocol has become the imaging modality of choice in high-energy deceleration traumas. The objective of this article was to review the role of dual-phase MDCT in the identification and management of acute vascular injuries, particularly in the chest and abdomen following multiple traumatic injuries. In addition, this article will provide examples of MDCT features of acute vascular injuries with correlative surgical and interventional findings.

  9. LATE RENAL GRAFT REJECTION: PATHOLOGY AND PROGNOSIS

    Directory of Open Access Journals (Sweden)

    E.S. Stolyarevich

    2014-01-01

    Full Text Available Rejection has always been one of the most important cause of late renal graft dysfunction. Aim of the study was to analyze the prevalence of different clinico-pathological variants of rejection that cause late graft dysfunction, and evaluate their impact on long-term outcome. Materials and methods. This is a retrospective study that analyzed 294 needle core biopsy specimens from 265 renal transplant recipients with late (48,8 ± 46,1 months after transplantation allograft dysfunction caused by late acute rejection (LAR, n = 193 or chronic rejection (CR, n = 78 or both (n = 23. C4d staining was performed by immunofl uorescence (IF on frozen sections using a standard protocol. Results. Peritubular capillary C4d deposition was identifi ed in 36% samples with acute rejection and in 62% cases of chronic rejection (including 67% cases of transplant glomerulopathy, and 50% – of isolated chronic vasculopathy. 5-year graft survival for LAR vs CR vs their combination was 47, 13 and 25%, respectively. The outcome of C4d– LAR was (p < 0,01 better than of C4d+ acute rejection: at 60 months graft survival for diffuse C4d+ vs C4d− was 33% vs 53%, respectively. In cases of chronic rejection C4d+ vs C4d– it was not statistically signifi cant (34% vs 36%. Conclusion. In long-term allograft biopsy C4d positivity is more haracteristic for chronic rejection than for acute rejection. Only diffuse C4d staining affects the outcome. C4d– positivity is associated with worse allograft survival in cases of late acute rejection, but not in cases of chronic rejection

  10. Clinical significance of the ratio between FOXP3 positive regulatory T cell and interleukin-17 secreting cell in renal allograft biopsies with acute T-cell-mediated rejection

    Science.gov (United States)

    Chung, Byung H; Oh, Hye J; Piao, Shang G; Hwang, Hyeon S; Sun, In O; Choi, Sun R; Park, Hoon S; Choi, Bum S; Choi, Yeong J; Park, Cheol W; Kim, Yong-Soo; Cho, Mi-La; Yang, Chul W

    2012-01-01

    The aim of this study is to investigate the clinical significance of the ratio between interleukin-17 (IL-17) secreting cell and FOXP3-positive regulatory T cell (FOXP3+ Treg) infiltration in renal allograft tissues with acute T-cell-mediated rejection (ATCMR). Fifty-six patients with biopsy-proven ATCMR were included. Infiltration of FOXP3+ Treg and IL-17-secreting cells was evaluated with immunostaining for FOXP3 or IL-17 on the biopsy specimens, and the patients were divided into the FOXP3 high group (Log FOXP3/IL-17 > 0·45) or the IL-17 high group (Log FOXP3/IL-17 IL-17 high group, allograft function was significantly decreased compared with the FOXP3 high group (P IL-17 high group was higher than the FOXP3 high group (P IL-17 high group than in the FOXP3 high group (all indicators, P IL-17 high group showed lower 1-year (54% versus 90%, P IL-17 ratio was a significant predictor for allograft outcome. The FOXP3/IL-17 ratio is a useful indicator for representing the severity of tissue injury, allograft dysfunction and for predicting the clinical outcome of ATCMR. PMID:22444300

  11. Acute Antibody-Mediated Rejection in Presence of MICA-DSA and Successful Renal Re-Transplant with Negative-MICA Virtual Crossmatch.

    Directory of Open Access Journals (Sweden)

    Yingzi Ming

    Full Text Available The presence of donor-specific alloantibodies (DSAs against the MICA antigen results in high risk for antibody-mediated rejection (AMR of a transplanted kidney, especially in patients receiving a re-transplant. We describe the incidence of acute C4d+ AMR in a patient who had received a first kidney transplant with a zero HLA antigen mismatch. Retrospective analysis of post-transplant T and B cell crossmatches were negative, but a high level of MICA alloantibody was detected in sera collected both before and after transplant. The DSA against the first allograft mismatched MICA*018 was in the recipient. Flow cytometry and cytotoxicity tests with five samples of freshly isolated human umbilical vein endothelial cells demonstrated the alloantibody nature of patient's MICA-DSA. Prior to the second transplant, a MICA virtual crossmatch and T and B cell crossmatches were used to identify a suitable donor. The patient received a second kidney transplant, and allograft was functioning well at one-year follow-up. Our study indicates that MICA virtual crossmatch is important in selection of a kidney donor if the recipient has been sensitized with MICA antigens.

  12. Higher tacrolimus trough levels on days 2-5 post-renal transplant are associated with reduced rates of acute rejection.

    LENUS (Irish Health Repository)

    O'Seaghdha, C M

    2011-04-06

    We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng\\/mL (n = 122, range 2-13.5 ng\\/mL), Group 2: median 17 ng\\/mL (n = 123, range 14-20 ng\\/mL), Group 3: median 24 ng\\/mL (n = 108, range 20.5-27 ng\\/mL) and Group 4: median 33.5 ng\\/mL (n = 116, range 27.5-77.5 ng\\/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.

  13. Effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Anne-Christin Stöwhas

    Full Text Available Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown.To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.In 51 healthy male subjects with a mean (SD age of 26.9 (9.3 years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL particle size, insulin resistance (HOMA-index, highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich and during two days at 2590 m, (Davos Jakobshorn, Switzerland in randomized order. The largest differences in outcomes between the two altitudes are reported.Mean (SD oxygen saturation was significantly lower at 2590 m, 91.0 (2.0%, compared to 490 m, 96.0 (1.0%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001 and heart rate (mean difference +3.3 bpm, p<0.001 were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides -0.14 mmol/l, p=0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio -0.25, p=0.001, LDL particle size increased (median difference +0.45 nm, p=0.048 and hsCRP decreased (median difference -0.18 mg/l, p=0.024 compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m.Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism.ClinicalTrials.gov NCT01130948.

  14. Central nervous system involvement in acute lymphoblastic leukemia is mediated by vascular endothelial growth factor.

    Science.gov (United States)

    Münch, Vera; Trentin, Luca; Herzig, Julia; Demir, Salih; Seyfried, Felix; Kraus, Johann M; Kestler, Hans A; Köhler, Rolf; Barth, Thomas F E; Te Kronnie, Geertruy; Debatin, Klaus-Michael; Meyer, Lüder H

    2017-08-03

    In acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is a major clinical concern. Despite nondetectable CNS leukemia in many cases, prophylactic CNS-directed conventional intrathecal chemotherapy is required for relapse-free survival, indicating subclinical CNS manifestation in most patients. However, CNS-directed therapy is associated with long-term sequelae, including neurocognitive deficits and secondary neoplasms. Therefore, molecular mechanisms and pathways mediating leukemia-cell entry into the CNS need to be understood to identify targets for prophylactic and therapeutic interventions and develop alternative CNS-directed treatment strategies. In this study, we analyzed leukemia-cell entry into the CNS using a primograft ALL mouse model. We found that primary ALL cells transplanted onto nonobese diabetic/severe combined immunodeficiency mice faithfully recapitulated clinical and pathological features of meningeal infiltration seen in patients with ALL. ALL cells that had entered the CNS and were infiltrating the meninges were characterized by high expression of vascular endothelial growth factor A (VEGF). Although cellular viability, growth, proliferation, and survival of ALL cells were found to be independent of VEGF, transendothelial migration through CNS microvascular endothelial cells was regulated by VEGF. The importance of VEGF produced by ALL cells in mediating leukemia-cell entry into the CNS and leptomeningeal infiltration was further demonstrated by specific reduction of CNS leukemia on in vivo VEGF capture by the anti-VEGF antibody bevacizumab. Thus, we identified a mechanism of ALL-cell entry into the CNS, which by targeting VEGF signaling may serve as a novel strategy to control CNS leukemia in patients, replacing conventional CNS-toxic treatment. © 2017 by The American Society of Hematology.

  15. ACE2 Antagonizes VEGFa to Reduce Vascular Permeability During Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Xiaobo Yu

    2016-03-01

    Full Text Available Background/Aims: Angiotensin converting enzyme 2 (ACE2 treatment suppresses the severity of acute lung injury (ALI, through antagonizing hydrolyzing angiotensin II (AngII and the ALI-induced apoptosis of pulmonary endothelial cells. Nevertheless, the effects of ACE2 on vessel permeability and its relationship with vascular endothelial growth factor a (VEGFa remain ill-defined. In the current study, we examined the relationship between ACE2 and VEGFa in ALI model in mice. Methods: Here, we used a previously published bleomycin method to induce ALI in mice, and treated the mice with ACE2. We analyzed the levels of VEGFa in these mice. The mouse lung vessel permeability was determined by a fluorescence pharmacokinetic assay following i.v. injection of 62.5µg/kg Visudyne. VEGFa pump or SU5416 pump was given to increase or decrease VEGFa effects, respectively. The long-term effects on lung function were determined by measurement of lung resistance using methacholine. Results: ACE2 treatment did not alter VEGFa levels in lung, but antagonized the effects of VEGFa on increases of lung vessel permeability. Ectogenic VEGFa abolished the antagonizing effects of ACE2 on the vessel permeability against VEGFa. On the other hand, suppression of VEGF signaling mimicked the effects of ACE2 on the vessel permeability against VEGFa. The suppression of vessel permeability resulted in improvement of lung function after ALI. Conclusion: ACE2 may antagonize the VEGFa-mediated increases in lung vessel permeability during ALI, resulting in improvement of lung function after ALI.

  16. PML-RARa modulates the vascular signature of extracellular vesicles released by acute promyelocytic leukemia cells.

    Science.gov (United States)

    Fang, Yi; Garnier, Delphine; Lee, Tae Hoon; D'Asti, Esterina; Montermini, Laura; Meehan, Brian; Rak, Janusz

    2016-01-01

    Oncogenic transformation is believed to impact the vascular phenotype and microenvironment in cancer, at least in part, through mechanisms involving extracellular vesicles (EVs). We explored these questions in the context of acute promyelocytic leukemia cells (NB4) expressing oncogenic fusion protein, PML-RARa and exquisitely sensitive to its clinically used antagonist, the all-trans retinoic acid (ATRA). We report that NB4 cells produce considerable numbers of EVs, which are readily taken up by cultured endothelial cells triggering their increased survival. NB4 EVs contain PML-RARa transcript, but no detectable protein, which is also absent in endothelial cells upon the vesicle uptake, thereby precluding an active intercellular trafficking of this oncogene in this setting. ATRA treatment changes the emission profile of NB4-related EVs resulting in preponderance of smaller vesicles, an effect that occurs in parallel with the onset of cellular differentiation. ATRA also increases IL-8 mRNA and protein content in NB4 cells and their EVs, while decreasing the levels of VEGF and tissue factor (TF). Endothelial cell uptake of NB4-derived EVs renders these cells more TF-positive and procoagulant, and this effect is diminished by pre-treatment of EV donor cells with ATRA. Profiling angiogenesis-related transcripts in intact and ATRA-treated APL cells and their EVs reveals multiple differences attributable to cellular responses and EV molecular packaging. These observations point to the potential significance of changes in the angiogenic signature and activity associated with EVs released from tumor cells subjected to targeted therapy.

  17. Effects of candesartan in acute stroke on vascular events during long-term follow-up: results from the Scandinavian Candesartan Acute Stroke Trial (SCAST).

    Science.gov (United States)

    Hornslien, Astrid G; Sandset, Else C; Igland, Jannicke; Terént, Andreas; Boysen, Gudrun; Bath, Philip M W; Murray, Gordon D; Berge, Eivind

    2015-08-01

    Randomized-controlled trials have shown no beneficial short-term effects of blood pressure lowering treatment in the acute phase of stroke. We aimed to see whether blood pressure lowering treatment with candesartan in the acute phase can lead to benefits that become apparent over a longer period of follow-up. The Scandinavian Candesartan Acute Stoke Trial was a randomized- and placebo-controlled trial of candesartan in 2,029 patients with acute stroke and systolic blood pressure ≥140 mmHg. Trial treatment was given for seven-days, and the primary follow-up period was six-months. We have used the national patient registries and the cause of death registries in the Scandinavian countries to collect data on vascular events and deaths up to three-years from randomization. The primary end-point was the composite of stroke, myocardial infarction, or vascular death, and we used Cox proportional hazards regression model for analysis. Long-term data were available for 1,256 of the 1,286 patients (98%) from Scandinavia. The risk of the primary composite end-point did not differ significantly between the groups (candesartan 178/632 events, placebo 203/624 events, hazard ratio = 0·87, 95% confidence interval 0·71-1·07). There were also no statistically significant differences for the secondary end-points stroke and all-cause death, or in any of the pre-specified subgroups. Treatment with candesartan in the acute phase of stroke was not associated with clear long-term clinical benefits. This result supports the conclusion from trials with short-term follow-up, that blood pressure lowering treatment with candesartan should not be given routinely to patients with acute stroke and raised blood pressure. © 2015 World Stroke Organization.

  18. Trends in open vascular surgery for trauma: implications for the future of acute care surgery.

    Science.gov (United States)

    Forrester, Joseph D; Weiser, Thomas G; Maggio, Paul; Browder, Timothy; Tennakoon, Lakshika; Spain, David; Staudenmayer, Kristan

    2016-09-01

    Trauma patients with vascular injuries have historically been within a general surgeon's operative ability. Changes in training and decline in operative trauma have decreased trainees' exposure to these injuries. We sought to determine how frequently vascular procedures are performed at US trauma centers to quantify the need for general surgeons trained to manage vascular injuries. We conducted a retrospective analysis of the National Trauma Data Base (NTDB) from 2012 compared with 2002. Patients with general surgical and vascular procedures were identified using International Classification of Diseases, Ninth Revision, procedure codes 38.0-39.99, excluding 38.9-38.99. General surgery or vascular operations were performed on 12,099 (24%) of 50,248 severely injured adult patients in 2002 and 21,854 (16%) of 138,009 injured patients in 2012. Nineteen percent to 26% of all patients underwent vascular procedures. Patients with combined general surgery and vascular procedures were less likely to be discharged home and more likely to die. In 2002, 6% of severely injured adult trauma patients underwent open vascular procedures at level III/IV trauma centers; by 2012, only 1% of vascular surgery procedures were performed at level III/IV centers (P surgery remains common for severely injured patients. Future trauma systems and surgical training programs will need to account for the need for open vascular skills. The findings suggest that there is already a trend away from open vascular procedures at level III/IV trauma centers, which may be a sign of system compensation for changes in the workforce. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Age-specific risk of renal graft loss from late acute rejection or noncompliance in the adolescent and young adult period.

    Science.gov (United States)

    Ritchie, Angus G; Clayton, Philip A; McDonald, Stephen P; Kennedy, Sean E

    2017-04-27

    To identify if an age-specific high-risk window for graft loss is present in Australia and New Zealand and identify the aetiology for such graft loss using the ANZDATA registry. Retrospective cohort analysis of all renal transplants performed in Australia and New Zealand during 1985-2010 in which the graft survived >3 months and the patient spent at least some time aged 10-30y inclusive while the graft was functioning. Calculation of adjusted hazard ratio (aHR) for graft loss according to age, sex, race, cause of end-stage kidney disease, transition, era of transplantation, donor type and Human Leucocyte Antigen mismatch calculated using an extended Cox proportional hazards model. Analysis of age-specific aHR of graft loss from any cause or late acute rejection (LAR) or non-compliance. 3289 grafts in 3048 recipients were included. 757 grafts failed including 110 (15%) from LAR or non-compliance. Age was strongly associated with graft loss from LAR or non-compliance (p risk of graft loss from LAR or non-compliance was significantly increased from 16-24y, peaking at 19-21y (aHR 11.3, 95%CI 1.5-84.3, p non-compliance (aHR 3.5, 95%CI 2.1-5.6), whereas paediatric-to-adult transition with a functioning transplant was not (aHR 1.2, 95%CI 0.4-3.5, p = 0.68). The high risk of graft loss during adolescence and young adulthood is primarily due to LAR or non-compliance. The elevated risk continues well into the 20s and is independent of paediatric-to-adult transition. This article is protected by copyright. All rights reserved.

  20. Both absolute and relative quantification of urinary mRNA are useful for non-invasive diagnosis of acute kidney allograft rejection.

    Directory of Open Access Journals (Sweden)

    Jung-Woo Seo

    Full Text Available Urinary mRNA analysis with three-gene set (18S rRNA, CD3ε, and IP-10 has been suggested as a non-invasive biomarker of acute rejection (AR in kidney transplant recipients using quantitative real-time PCR (qPCR. Application of droplet digital PCR (ddPCR, which has been suggested to provide higher sensitivity, accuracy, and absolute quantification without standard curves, could be a useful method for the quantifying low concentration of urinary mRNA. We investigated the urinary expression of these three genes in Korean patients with kidney transplantation and also evaluated the usefulness of ddPCR. 90 urine samples were collected at time of allograft biopsy in kidney recipients (n = 67 and from patients with stable renal function more than 10 years (n = 23. Absolute quantification with both PCR system showed significant higher mRNA levels of CD3ε and IP-10 in AR patients compared with stable transplants (STA, but there was no difference in 18S rRNA expression across the patient groups. To evaluate discrimination between AR and STA, ROC curve analyses of CTOT-4 formula yielded area under the curve values of 0.72 (95% CI 0.60-0.83 and 0.77 (95% CI 0.66-0.88 for qPCR and ddPCR, respectively. However, 18S normalization of absolute quantification and relative quantification with 18S showed better discrimination of AR from STA than those of the absolute method. Our data indicate that ddPCR system without standard curve would be useful to determine the absolute quantification of urinary mRNA from kidney transplant recipients. However, comparative method also could be useful and convenient in both qPCR and ddPCR analysis.

  1. Multiparametric cardiovascular magnetic resonance surveillance of acute cardiac allograft rejection and characterisation of transplantation-associated myocardial injury: a pilot study.

    Science.gov (United States)

    Miller, Christopher A; Naish, Josephine H; Shaw, Steven M; Yonan, Nizar; Williams, Simon G; Clark, David; Bishop, Paul W; Ainslie, Mark P; Borg, Alex; Coutts, Glyn; Parker, Geoffrey J M; Ray, Simon G; Schmitt, Matthias

    2014-07-20

    Serial surveillance endomyocardial biopsies are performed in patients who have recently undergone heart transplantation in order to detect acute cardiac allograft rejection (ACAR) before symptoms occur, however the biopsy process is associated with a number of limitations. This study aimed to prospectively and longitudinally evaluate the performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting and monitoring ACAR in the early phase post-transplant, and characterize graft recovery following transplantation. All patients receiving a heart transplant at a single UK centre over a period of 25 months were approached within one month of transplantation. Multiparametric CMR was prospectively performed on the same day as biopsy on four separate occasions (6 weeks, 10 weeks, 15 weeks and 20 weeks post-transplant). CMR included assessment of global and regional ventricular function, myocardial tissue characterization (T1 mapping, T2 mapping, extracellular volume, LGE) and pixel-wise absolute myocardial blood flow quantification. CMR parameters were compared with biopsy findings. As is standard, grade 2R or higher ACAR was considered significant. 88 CMR-matched biopsies were performed in 22 patients. Eight (9%) biopsies in 5 patients demonstrated significant ACAR. Significant ACAR was associated with a reduction in circumferential strain (-12.7±2.5% vs. -13.7±3.6%, p=0.047) but there was considerable overlap between groups. Whilst trends were observed between ACAR and proposed CMR markers of oedema, particularly after adjusting for primary graft dysfunction, differences were not significant. Significant improvements were seen in markers of graft structure and contractility, oedema and microvascular function over the period studied, although few parameters normalised. This study provides novel insight into the myocardial injury associated with transplantation, and its recovery, however multiparametric CMR was not able to accurately detect ACAR

  2. [Correlation of severity classification of acute respiratory distress syndrome by the Berlin definition with extra vascular lung water index and pulmonary vascular permeability index].

    Science.gov (United States)

    Zhu, Jinyuan; Wang, Xiaohong; Yang, Xiaojun; Wang, Xiaoqi; Ma, Xigang

    2015-05-19

    To explore the correlation of severity classification of acute respiratory distress syndrome (ARDS) by the Berlin definition with extra vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). A total of 70 cases with ARDS at intensive care unit of our hospital from July 2012 to July 2014 were divided into three groups of mild (n = 20), moderate (n = 30) and severe (n = 20) according to the Berlin definition. The scores of acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) within 24 h of admission were recorded. And the values of EVLWI and PVPI of three groups from Day 1-4 were monitored by pulse indicator continuous cardiac output (PiCCO). Receiver operating characteristic (ROC) curve was drawn for these parameters and the area under curve was compared. Meanwhile blood gas was analyzed and oxygenation index (OI) calculated. And the correlations of EVLWI and PVPI with OI were analyzed. Comparisons of EVLWI, PVPI and OI were made for three groups at different timepoints: As the severity of ARDS aggravated, EVLWI and PVPI of three groups increased significantly at any timepoint while OI decreased sharply (P 0.05). There was no sharp decline of EVLWI or PVPI in severe ARDS group (P > 0.05). And OI increased significantly from Day 1-4 in three groups (P 2.95 at Day 4 of admission was used as the best threshold value for judging prognosis. And the sensitivity was 70% and specificity 92%. OI had negative correlation with EVLWI and PVPI in three groups from Day 1-4 [(r = -0.685, P = 0.000) and (r = -0.631, P = 0.000)]. Both EVLWI and PVPI reflect adequately the severity of ARDS by the Berlin definition. And the dynamic trend of PVPI is superior to that of EVLWI.

  3. Adipose-derived cellular therapies in solid organ and vascularized-composite allotransplantation.

    Science.gov (United States)

    Stivers, Katlin B; Beare, Jason E; Chilton, Paula M; Williams, Stuart K; Kaufman, Christina L; Hoying, James B

    2017-10-01

    Controlling acute allograft rejection following vascularized composite allotransplantation requires strict adherence to courses of systemic immunosuppression. Discovering new methods to modulate the alloreactive immune response is essential for widespread application of vascularized composite allotransplantation. Here, we discuss how adipose-derived cellular therapies represent novel treatment options for immune modulation and tolerance induction in vascularized composite allotransplantation. Adipose-derived mesenchymal stromal cells are cultured from autologous or allogeneic adipose tissue and possess immunomodulatory qualities capable of prolonging allograft survival in animal models of vascularized composite allotransplantation. Similar immunosuppressive and immunomodulatory effects have been observed with noncultured adipose stromal-vascular-fraction-derived therapies, albeit publication of in-vivo stromal vascular fraction cell modulation in transplantation models is lacking. However, both stromal vascular fraction and adipose derived mesenchymal stem cell therapies have the potential to effectively modulate acute allograft rejection via recruitment and induction of regulatory immune cells. To date, most reports focus on adipose derived mesenchymal stem cells for immune modulation in transplantation despite their phenotypic plasticity and reliance upon culture expansion. Along with the capacity for immune modulation, the supplemental wound healing and vasculogenic properties of stromal vascular fraction, which are not shared by adipose derived mesenchymal stem cells, hint at the profound therapeutic impact stromal vascular fraction-derived treatments could have on controlling acute allograft rejection and tolerance induction in vascularized composite allotransplantation. Ongoing projects in the next few years will help design the best applications of these well tolerated and effective treatments that should reduce the risk/benefit ratio and allow more patients

  4. The Role of Acute Intermittent Hypoxia in Neutrophil-Generated Superoxide, Sympathovagal Balance, and Vascular Function in Healthy Subjects.

    Science.gov (United States)

    Almeida, Germana P L; Trombetta, Ivani C; Cepeda, Felipe X; Hatanaka, Elaine; Curi, Rui; Mostarda, Cristiano; Irigoyen, Maria C; Barreto-Filho, José A S; Krieger, Eduardo M; Consolim-Colombo, Fernanda M

    2017-01-01

    Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPX-reoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 ± 2 years; 22.3 ± 0.46 kg/m(2)), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 ± 50 vs. 741 ± 135, P intermittent HPX not only increased superoxide generation in neutrophils, but also impaired cardiac sympathovagal balance in healthy subjects. These data reinforce the role of intermittent HPX in superoxide generation on neutrophils, which may

  5. Diagnostics of vascular diseases as a cause for acute abdomen; Diagnostik vaskulaerer Erkrankungen als Ursache fuer das akute Abdomen

    Energy Technology Data Exchange (ETDEWEB)

    Juchems, M.S. [Universitaetsklinikum Ulm, Klinik fuer Diagnostische und Interventionelle Radiologie, Ulm (Germany); Aschoff, A.J. [Klinikum Kempten-Oberallgaeu, Abteilung fuer Radiologie, Kempten (Germany)

    2010-03-15

    Vascular pathologies are rare causes of an acute abdomen. If the cause is a vascular disease a rapid diagnosis is desired as vascular pathologies are associated with high mortality. A differentiation must be made between arterial and venous diseases. An occlusion of the superior mesenteric artery is the most common reason for acute mesenteric ischemia but intra-abdominal arterial bleeding is also of great importance. Venous pathologies include thrombotic occlusion of the portal vein, the mesenteric vein and the vena cava. Multi-detector computed tomography (MDCT) is predestined for the diagnostics of vascular diseases of the abdomen. Using multiphasic contrast protocols enables reliable imaging of the arterial and venous vessel tree and detection of disorders with high sensitivity and specificity. Although conventional angiography has been almost completely replaced by MDCT as a diagnostic tool, it is still of high importance for minimally invasive interventions, for example in the management of gastrointestinal bleeding. (orig.) [German] Vaskulaere Pathologien sind seltene Ursachen fuer den klinischen Zustand eines akuten Abdomens. Liegt eine vaskulaere Erkrankung vor, ist jedoch aufgrund der hohen Mortalitaet eine zuegige Diagnostik von grosser Wichtigkeit. Bei den Erkrankungen der abdominellen Gefaesse sind arterielle von venoesen Ursachen zu unterscheiden. Ein Verschluss der A. mesenterica superior ist die haeufigste Ursache fuer die akute Mesenterialischaemie, daneben sind Blutungen in den abdominellen Gefaessprovinzen des arteriellen Gefaessbaums von Bedeutung. Venoese Pathologien betreffen thrombotische Verschluesse der Pfortader, der V. mesenterica und der V. cava. Die Multidetektor-CT (MDCT) ist zur Diagnostik vaskulaerer Erkrankungen des Abdominalraums praedestiniert. Mit mehrphasigen Untersuchungsprotokollen gelingt es, den arteriellen und venoesen Gefaessbaum zuverlaessig darzustellen und Erkrankungen mit hoher Sensitivitaet und Spezifitaet zu

  6. Time Course of Flow-Mediated Dilation and Vascular Endothelial Growth Factor following Acute Stroke.

    Science.gov (United States)

    Billinger, Sandra A; Sisante, Jason-Flor V; Whitaker, Alicen A; Abraham, Michael G

    2017-11-30

    People after stroke demonstrate alterations in vascular endothelial function measured by flow-mediated dilation. Limited information is available in the literature on possible protective factors following stroke. The aims of the secondary analysis were (1) to characterize the time course of vascular endothelial function using flow-mediated dilation at 72 hours after stroke and 1 week later during inpatient stroke rehabilitation and (2) to determine whether flow-mediated dilation was related to vascular endothelial growth factor, brain-derived neurotrophic factor, or estimated prestroke peak oxygen uptake. Flow-mediated dilation using Doppler ultrasound was assessed in bilateral brachial arteries at the defined time points. Flow-mediated dilation and blood draws occurred on the same day between 7:30 am and 9:00 am following an overnight fast. Enzyme-linked immunosorbent assay was used to quantify plasma vascular endothelial growth factor and brain-derived neurotrophic factor values. A nonexercise estimate was used to calculate prestroke peak oxygen uptake. We have shown that between-limb differences are evident within 72 hours after stroke and remain 1 week later during inpatient rehabilitation. Higher values for vascular endothelial growth factor were associated with increased flow-mediated dilation at both time points. Higher estimated prestroke peak oxygen uptake was related to flow-mediated dilation. Brain-derived neurotrophic factor was not related to any outcome measures. Unique vascular adaptations start early after stroke in the stroke-affected limb and remain through inpatient stroke rehabilitation. Vascular endothelial growth factor and prestroke physical activity may have a protective role in vascular function following stroke. Future work should focus on mechanistic pathways for preservation of vascular health. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  7. Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure.

    Science.gov (United States)

    Haynes, Andrew; Linden, Matthew D; Chasland, Lauren C; Nosaka, Kazunori; Maiorana, Andrew; Dawson, Ellen A; Dembo, Lawrence H; Naylor, Louise H; Green, Daniel J

    2017-06-01

    Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF are scant. Eccentric (ECC) cycling is a novel exercise modality that may be particularly suited to patients with CHF, but the acute impacts of ECC cycling on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow-mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC cycling increased baseline artery diameter (pre: 4.0 ± 0.8 mm vs. post: 4.2 ± 0.7 mm; P = 0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for, the decrease in FMD post-ECC cycling was no longer significant. No changes were apparent after CON. Neither ECC nor CON cycling resulted in changes to any platelet-function measures (all P > 0.05). These results suggest that both ECC and CON cycling, at a moderate intensity and short duration, can be performed by patients with HFrEF without detrimental impacts on vascular or platelet function. NEW & NOTEWORTHY This is the first evidence to indicate that eccentric (ECC) cycling can be performed relatively safely by patients with chronic heart failure (CHF), as it did not result in impaired vascular or platelet function compared with conventional cycling

  8. Vascular Risk Factors and Diseases Modulate Deficits of Reward-Based Reversal Learning in Acute Basal Ganglia Stroke.

    Directory of Open Access Journals (Sweden)

    Ulla K Seidel

    Full Text Available Besides motor function, the basal ganglia have been implicated in feedback learning. In patients with chronic basal ganglia infarcts, deficits in reward-based reversal learning have previously been described.We re-examined the acquisition and reversal of stimulus-stimulus-reward associations and acquired equivalence in eleven patients with acute basal ganglia stroke (8 men, 3 women; 57.8±13.3 years, whose performance was compared eleven healthy subjects of comparable age, sex distribution and education, who were recruited outside the hospital. Eleven hospitalized patients with a similar vascular risk profile as the stroke patients but without stroke history served as clinical control group.In a neuropsychological assessment 7±3 days post-stroke, verbal and spatial short-term and working memory and inhibition control did not differ between groups. Compared with healthy subjects, control patients with vascular risk factors exhibited significantly reduced performance in the reversal phase (F[2,30] = 3.47; p = 0.044; post-hoc comparison between risk factor controls and healthy controls: p = 0.030, but not the acquisition phase (F[2,30] = 1.01; p = 0.376 and the acquired equivalence (F[2,30] = 1.04; p = 0.367 tasks. In all tasks, the performance of vascular risk factor patients closely resembled that of basal ganglia stroke patients. Correlation studies revealed a significant association of the number of vascular risk factors with reversal learning (r = -0.33, p = 0.012, but not acquisition learning (r = -0.20, p = 0.121 or acquired equivalence (r = -0.22, p = 0.096.The previously reported impairment of reward-based learning may be attributed to vascular risk factors and associated diseases, which are enriched in stroke patients. This study emphasizes the necessity of appropriate control subjects in cognition studies.

  9. The acute effect of smoking a single cigarette on vascular status, SpO2, and stress level.

    Science.gov (United States)

    MiYang, Jeon; HyeonCheol, Jeong; Lee, KyoungSoon; Yim, JongEun

    2014-04-12

    Tobacco use is a major cause of cardiovascular and respiratory disease and cancer. It is controversial whether smoking helps relieve stress. This study investigated the acute effect of smoking a single cigarette on vascular status, SpO2, and stress level. 38 non-smokers and 29 smokers were selected as subjects to measure BVOP (Blood Vessel Output Power), BVT (Blood Vessel Tension), RBV (Remained Blood Volume), BVAL (Blood Vessel Aging Level), SpO2, resistance to stress, and stress score. Pre- and post-experiment changes were recorded during a 20-min interval, with smokers being recorded 5 min after smoking for the post-experiment. The smoker group showed a significant decrease in vascular status (BVOP, RBV, BVAL) compared with the non-smoker group. SpO2 showed no difference between the smoker group and the non-smoker group. Smoking showed no effect on stress reduction compared to non-smoking. The results of the study indicate that smoking causes a negative effect on vascular status and is not beneficial to stress reduction. Therefore, quitting smoking is encouraged for better physical and mental health.

  10. EXPERIMENTAL ACUTE NEPHRITIS: THE VASCULAR REACTIONS AND THE ELIMINATION OF NITROGEN

    Science.gov (United States)

    Pearce, Richard M.; Hill, Miner C.; Eisenbrey, Arthur B.

    1910-01-01

    By combining physiological and anatomical methods in the study of experimental nephritis it is possible to distinguish types of nephritis in which either tubular or vascular changes predominate, and are essentially characteristic of the lesion produced, but it is not possible to say that a given poison produces exclusively tubular or exclusively vascular lesions. The so-called epithelial poisons (potassium chromate, uranium nitrate and corrosive sublimate) present anatomical evidence of extensive tubular injury, and in the early stages show, on physiological study, no evidence of vascular injury other than exaggerated contraction and dilatation of the vessels and increased diuresis. On the other hand, the vascular poisons, arsenic and cantharidin, which produce but little injury to the tubules, tend to cause anuria and are characterized by minimal contraction and dilatation of the vessels and little or no flow of urine. From the physiological point of view these two types may be, for practical purposes, considered as examples of tubular and vascular nephritis. They are not, however, pure types; for the increased diuresis of the early tubular type is in itself evidence of vessel irritability and similar to the increased irritability caused by small doses of vascular poisons, and on the other hand, this essentially vascular lesion is accompanied by slight morphological changes in the tubular epithelium. Furthermore, the tubular lesions of chromium and uranium and corrosive sublimate pass into a stage closely resembling the vascular type, if not identical with it. Two forms of late tubular nephritis may be recognized. One of these, the anuric form, is accompanied by severe gastro-intestinal disturbance and evidence of approaching anuria; physiological tests show diminished power of dilatation of the vessels and corresponding inhibition of diuresis. The second form, the polyuric, is characterized by a condition of polyuria up to the moment of anesthesia; physiological

  11. Acute Effects of Vascular Modifying Agents in Solid Tumors Assessed by Noninvasive Laser Doppler Flowmetry and Near Infrared Spectroscopy

    Directory of Open Access Journals (Sweden)

    Michael Kragh

    2002-01-01

    Full Text Available The potential of noninvasive laser Doppler flowmetry (LDF and near infrared spectroscopy (NIRS to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (∼200 mm3 in the rear foot of CDF1 mice were treated with flavone acetic acid (FAA, 150 mg/kg, 5,6-dimethylxanthenone-4acetic acid (DMXAA, 20 mg/kg, combretastatin A-4 disodium phosphate (CAMP, 250 mg/kg, hydralazine (HDZ, 5 mg/kg, or nicotinamide (NTA, 500 mg/kg. Tumor perfusion before and after treatment was evaluated by noninvasive LDF, using a 41°C heated custombuilt LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by MRS, using light guide coupled reflectance measurements at 800±10 nm. FAA, DMXAA, CAMP, and HDZ significantly decreased tumor perfusion by 50%, 47%, 73%, and 78%, respectively. In addition, FAA, DMXAA, and HDZ significantly reduced the blood volume within the tumor, indicating that these compounds to some degree shunted blood from the tumor to adjacent tissue, HDZ being most potent. CAMP caused no change in the tumor blood volume, indicating that the mechanism of action of CAMP was vascular shut down with the blood pool trapped in the tumor. NTA caused no change in either tumor perfusion or tumor blood volume. We conclude that noninvasive LDF and MRS can determine acute effects of vascular modifying agents on tumor perfusion and blood volume.

  12. Protective vascular effects of quercitrin in acute TNBS-colitis in rats: the role of nitric oxide.

    Science.gov (United States)

    Romero, Miguel; Vera, Beatriz; Galisteo, Milagros; Toral, Marta; Gálvez, Julio; Perez-Vizcaino, Francisco; Duarte, Juan

    2017-08-01

    Quercitrin (quercetin 3-rhamnoside) is a bioflavonoid with anti-inflammatory activity in experimental colitis. Several studies have suggested that vascular injury might be a primary process in Crohn's disease, but there is no information about the function of the mesenteric bed in the experimental models of colitis. The aims of this study were to analyse whether the reactivity to vasoconstrictor agents is altered in the mesenteric vascular bed from animals with colitis induced by administration of trinitrobenzenesulfonic acid (TNBS) in the early stages of this pathology, and to determine the effects of quercitrin on such vascular alterations. Contraction of mesenteric beds produced by vasoconstrictor agents such as noradrenaline and KCl is reduced in rats in the early stages of experimental TNBS-induced colitis. This alteration was partially reverted by non-selective nitric oxide synthase (NOS) inhibition with N-nitro-l-arginine methylester, and enhanced by non-selective cyclooxygenase (COX) inhibition with indomethacin. However, the endothelium-dependent relaxant responses to acetylcholine were not significantly altered. iNOS, COX-2, NOX-1, tumor necrosis factor α (TNFα) and interleukin 1β (IL1β) expressions were higher in the mesenteric arteries from TNBS-treated rats, without changes in both eNOS expression and eNOS-Ser1177 phosphorylation. The in vivo pre-treatment with 5 mg kg-1 of the flavonoid quercitrin reverts both the early hyporesponse of mesenteric arteries to noradrenaline and the up-regulation of iNOS, COX2, NOX1, TNFα and IL1β in colitic rats. In conclusion, quercitrin improves the impaired mesenteric vascular reactivity in the acute phase of this colitis model, at least in part by reducing NO overproduction from iNOS.

  13. Inflammation and vascular responses to acute mental stress : implications for the triggering of myocardial infarction

    NARCIS (Netherlands)

    Paine, N.J.; Bosch, J.A.; Veldhuijzen Van Zanten, J.J.C.S.

    2012-01-01

    There is evidence that mental stress can trigger myocardial infarction. Even though the underlying mechanisms remain to be determined, both inflammation and vascular responses to mental stress have been implicated as contributing factors. This review explores the effects of inflammation on the

  14. Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study

    NARCIS (Netherlands)

    Dower, James I.; Geleijnse, Marianne; Kroon, Paul A.; Philo, Mark; Mensink, Marco; Kromhout, Daan; Hollman, Peter C.H.

    2016-01-01

    Scope: Cocoa, rich in flavan-3-ols, improves vascular function, but the contribution of specific flavan-3-ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan-3-ol, and chocolate. Methods and results: In a randomized crossover study, twenty healthy men (40-80 years)

  15. Failure to down-regulate intragraft cytokine mRNA expression shortly after clinical heart transplantation is associated with high incidence of acute rejection

    NARCIS (Netherlands)

    de Groot-Kruseman, H A; Baan, C C; Loonen, E H; Mol, W M; Niesters, H G; Maat, A P; Balk, A H; Weimar, W

    BACKGROUND: Brain-death, ischemia and reperfusion damage have been implicated as initial factors that lead to a cascade of immunologic events that result in allograft rejection in experimental animals. Cytokines are thought to play a central role in this process. Therefore, we evaluated intragraft

  16. Light Microscopic Evaluation of Cardio-vasculare System in Alloksan-induced Diabetic Rats in Acute Period

    Directory of Open Access Journals (Sweden)

    Selen Bahçeci

    2007-01-01

    Full Text Available Diabetic cardiomyopathy is one of the chronic complication of diabetes and acute effects of diabetes on heart and aorta is not clear. We aimed to determine acute effects of diabetes on cardio-vasculare system with light microscopy. We used 20 Spraque-Dawley rats and applied 150 mg/kg alloxan, intraperitoneally for inducing diabetes and 1 ml SF in control group. After 24 hours, venous blood samples were measured. Blood glucose levels higher than 250 mg/dl were accepted as DM and treated with 4 IU/d human insülin. After 7 days rats were sacrified under ketamin anaesthesia. Heart and aorta were fixed in 10 % buffered formalin. The sectiones were embedded in paraffin and were serially sectioned at 5 m thickness, then stained with Hematoxyline-Eosine (H&E and Heidenhein’s Azan modification.There was no histopathological changes in cardiac muscle cells in control group. But there was a heterogen appearance in cardiac muscle cells and we determined some hydropic degenerations in some of the cardiac muscle cells and a minimal fibrosis in perivasculare and interstitial area in diabetic group. All histological stratums of aorta were seen normally in control group. In diabetic group, there was a clear anisostosis in smooth muscle cells and decreased in nucleus of smooth muscle cells in tunica media. We concluted that DM is caused degeneration and fibrosis in cardiac muscle cells and effective on smooth muscle cells in aorta in acute period.

  17. Decreased vascular endothelial growth factor response to acute hypoglycemia in type 2 diabetic patients with hypoglycemic coma.

    Science.gov (United States)

    Arnalich, Francisco; Maldifassi, Maria Constanza; Atienza, Gema; Ciria, Enrique; Quesada, Angustias; Cedillo, José Luis; Renart, Jaime; Codoceo, Rosa; Herruzo, Rafael; Montiel, Carmen

    2012-03-01

    Plasma vascular endothelial growth factor (VEGF) was shown to increase during acute hypoglycemia and could mediate rapid adaptation of the brain. In this study we examined the neuroendocrine response in patients with type 2 diabetes mellitus (T2DM) in hypoglycemic coma or with acute neuroglycopenic symptoms. We prospectively studied 135 consecutive T2DM patients admitted for severe hypoglycemia during a 2-year period. We collected clinical variables and measured plasma concentrations of VEGF, epinephrine, norepinephrine, cortisol and growth hormone at admission and 30min afterwards. Thirty two patients developed hypoglycemic coma and 103 did not lose consciousness. Median plasma VEGF level of coma patients was 3.1-fold lower at baseline than that of non-coma patients, and even 5.3-fold lower 30min afterwards. Plasma epinephrine concentration was significantly lower just at baseline in coma patients. On the contrary, there were no differences in concentrations of the other hormones. Multivariate logistic regression analysis showed that VEGF concentration (OR 0.68; CI 0.51-0.95) was a protective factor against the development of coma. VEGF and epinephrine responses to acute hypoglycemia are reduced in T2DM patients who develop hypoglycemic coma. An increased plasma VEGF concentration appeared to be a protective factor against the development of hypoglycemic coma. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. The Open Lung Approach Improves Pulmonary Vascular Mechanics in an Experimental Model of Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Santos, Arnoldo; Lucchetta, Luca; Monge-Garcia, M Ignacio; Borges, Joao Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-03-01

    To test whether positive end-expiratory pressure consistent with an open lung approach improves pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressures in experimental acute respiratory distress syndrome. Experimental study. Animal research laboratory. Ten pigs, 35 ± 5.2 kg. Acute respiratory distress syndrome was induced combining saline lung lavages with injurious mechanical ventilation. The positive end-expiratory pressure level resulting in highest compliance during a decremental positive end-expiratory pressure trial after lung recruitment was determined. Thereafter, three positive end-expiratory pressure levels were applied in a random order: hyperinflation, 6 cm H2O above; open lung approach, 2 cm H2O above; and collapse, 6 cm H2O below the highest compliance level. High fidelity pressure and flow sensors were placed at the main pulmonary artery for measuring pulmonary artery resistance (Z0), effective arterial elastance, compliance, and reflected pressure waves. After inducing acute respiratory distress syndrome, Z0 and effective arterial elastance increased (from 218 ± 94 to 444 ± 115 dyn.s.cm and from 0.27 ± 0.14 to 0.62 ± 0.22 mm Hg/mL, respectively; p mechanics compared with higher or lower positive end-expiratory pressure settings.

  19. Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease.

    Science.gov (United States)

    de Matthaeis, Angela; Greco, Antonio; Dagostino, Mariangela Pia; Paroni, Giulia; Fontana, Andrea; Vinciguerra, Manlio; Mazzoccoli, Gianluigi; Seripa, Davide; Vendemiale, Gianluigi

    2014-01-01

    Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO) concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD), a common medical condition in the elderly. Flow-mediated dilation (FMD), a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1) and after (phase 2) standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001), pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001), pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001), FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001) and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001). FMD values were positively correlated with pCO2 values (r=0.294, P=0.004) at baseline. A significant correlation was also found between relative changes in FMD and pCO2 levels, passing from phase 1 to phase 2 (r=0.23, P=0.023). Patients with higher baseline endothelium-dependent vasodilation as evaluated by FMD showed greater modification with regard to pCO2 changes (2.6±1.39 versus 1.59±1.4, P=0.012). In conclusion, endothelium-dependent vasodilation as evaluated by FMD was elevated during hypercapnia, and varied significantly according to pCO2 changes in patients with higher baseline levels, suggesting that vascular reactivity in acute COPD exacerbations in the elderly depends on integrity of the vascular endothelium.

  20. Acute Heart Failure Exacerbation with Cardiogenic Shock and Elevated Systemic Vascular Resistance Treated with a Combination of Nicardipine and Dobutamine Therapy

    Directory of Open Access Journals (Sweden)

    Lydia E. Issac

    2017-01-01

    Full Text Available Acute heart failure is a common reason for hospital admission and is usually caused by decreased cardiac output either as a result of an intrinsic cardiac issue or as a result of severe hypertension with elevated afterload. We present a patient with a history of HFrEF who presented with acute heart failure, found to have hypotension requiring Dobutamine support and an elevated systemic vascular resistance requiring Nicardipine drip, with subsequent recovery of cardiac function.

  1. Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study.

    Science.gov (United States)

    Dower, James I; Geleijnse, Johanna M; Kroon, Paul A; Philo, Mark; Mensink, Marco; Kromhout, Daan; Hollman, Peter C H

    2016-11-01

    Cocoa, rich in flavan-3-ols, improves vascular function, but the contribution of specific flavan-3-ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan-3-ol, and chocolate. In a randomized crossover study, twenty healthy men (40-80 years) were supplemented with: (1) 70g dark chocolate (150 mg epicatechin) with placebo capsules; (2) pure epicatechin capsules (2 × 50 mg epicatechin) with 75g white chocolate; and (3) placebo capsules with 75 g white chocolate (0 mg epicatechin). Vascular function (flow-mediated dilation (FMD) and augmentation index (AIx)) were measured before and 2 hours after interventions. Epicatechin metabolites time-profiles were measured in blood to calculate the bioavailability. Pure epicatechin did not significantly improve FMD (+0.75%; p = 0.10) or AIx (-2.2%; p = 0.23) compared to placebo. Dark chocolate significantly improved FMD (+0.96%; p = 0.04) and AIx (-4.6%; p = 0.02). Differences in improvements in FMD (+ 0.21%; p = 0.65) or Aix (-2.4%; p = 0.20) between pure epicatechin and dark chocolate were not significant. The bioavailability of epicatechin did not differ between pure epicatechin and dark chocolate (p = 0.14). Despite differences in epicatechin dose, improvements in vascular function after pure epicatechin and chocolate were similar and the bioavailability did not differ, suggesting a role for epicatechin. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Plasma cytokines eotaxin, MIP-1α, MCP-4, and vascular endothelial growth factor in acute lower respiratory tract infection

    DEFF Research Database (Denmark)

    Relster, Mette Marie; Holm, Anette; Pedersen, Court

    2017-01-01

    ), monocyte chemoattractant protein 4 (MCP-4), and vascular endothelial growth factor (VEGF) in 40 patients hospitalized with acute lower respiratory tract infections (LRTI). The cytokines contribute to the pathogenesis of several inflammatory respiratory diseases, indicating a potential as markers for LRTI....... Patients were stratified according to etiology and severity of LRTI, based on baseline C-reactive protein and CURB-65 scores. Using a multiplex immunoassay of plasma, levels of eotaxin and MCP-4 were shown to increase from baseline until day 6 after admission to hospital. The four cytokines were unable...... the full potential of eotaxin, MCP-4, MIP-1α, and VEGF as biomarkers for LRTI because of their low predictive power and a high interindividual variation of cytokine levels....

  3. Access to primary health care for acute vascular events in rural low income settings: a mixed methods study.

    Science.gov (United States)

    Ahmed, Shyfuddin; Chowdhury, Muhammad Ashique Haider; Khan, Md Alfazal; Huq, Nafisa Lira; Naheed, Aliya

    2017-01-18

    Cardiovascular diseases (CVDs) are the leading cause of global mortality. Among the CVDs, acute vascular events (AVE) mainly ischemic heart diseases and stroke are the largest contributors. To achieve 25% reduction in preventable deaths from CVDs by 2025, health systems need to be equipped with extended service coverage in order to provide person-centered care. The overall goal of this proposed study is to assess access to health care in-terms of service availability, care seeking patterns and barriers to access care after AVE in rural Bangladesh. We will consider myocardial infarction (MI) and stroke as acute vascular events. We will conduct a mixed methods study in rural Matlab, Bangladesh. This study will comprise of a) health facility survey, b) structured questionnaire interview and c) qualitative study. We will assess service availabilities by creating an inventory of public and private health facilities. Readiness of the facilities to deliver services for AVE will be assessed through a health facility survey using 'service availability and readiness assessment' (SARA) tools of the World Health Organization (WHO). We will interview survivors of AVE and caregivers (present and accompanied the person during the event) of person who died from AVE for exploring patterns of care seeking during an AVE. For exploring barriers to access care for AVE, we will conduct in-depth interview with survivors of AVE and caregivers of the person who died from AVE. We will also conduct key informant interviews with the service providers at primary health care (PHC) facilities and government high level officials at central health administration of Bangladesh. This study will provide a comprehensive picture of access to primary health care services during acute cardiovascular events as stroke & MI in rural context of Bangladesh. It will explore available service facilities in rural area for management, utilization of services and barriers to access care during an acute emergency

  4. Abdominal aortic occlusion and vascular compromise secondary to acute gastric dilatation in a patient with bulimia.

    Science.gov (United States)

    Elsharif, M; Doulias, T; Aljundi, W; Balchandra, S

    2014-11-01

    Acute gastric dilation is a rare but recognised complication in patients with bulimia and anorexia following binge episodes owing to decreased bowel motility. We present a rare case of acute gastric dilation secondary to bulimia in an otherwise healthy 18-year-old female patient that resulted in compression and complete occlusion of the abdominal aorta, leading to acute mesenteric and bilateral lower limb ischaemia. This resolved immediately following a laparotomy and gastric decompression. Management of these patients is very challenging owing to the lack of a successful precedent. To our knowledge, such a catastrophic complication has only ever been reported once in the literature and the outcome was fatal. Our case is of additional importance as it offers a successful management strategy for these patients.

  5. Improvement of vascular function by acute and chronic treatment with the GPR30 agonist G1 in experimental diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Zi-lin Li

    Full Text Available The G-protein coupled estrogen receptor 30 (GPR30 is a seven-transmembrane domain receptor that mediates rapid estrogen responses in a wide variety of cell types. This receptor is highly expressed in the cardiovascular system, and exerts vasodilatory effects. The objective of the present study was to investigate the effects of GPR30 on vascular responsiveness in diabetic ovariectomized (OVX rats and elucidate the possible mechanism involved. The roles of GPR30 were evaluated in the thoracic aorta and cultured endothelial cells. The GPR30 agonist G1 induced a dose-dependent vasodilation in the thoracic aorta of the diabetic OVX rats, which was partially attenuated by the nitric oxide synthase (NOS inhibitor, nitro-L-arginine methylester (L-NAME and the GPR30-selective antagonist G15. Dose-dependent vasoconstrictive responses to phenylephrine were attenuated significantly in the rings of the thoracic aorta following the acute G1 administration in the diabetic OVX rats. This effect of G1 was abolished partially by L-NAME and G15. The acute administration of G1 increased significantly the eNOS activity and the concentration of NO in the endothelial cells exposed to high glucose. G1 treatment induced an enhanced endothelium-dependent relaxation to acetylcholine (Ach in the diabetic OVX rats. Further examination revealed that G1 induced vasodilation in the diabetic OVX rats by increasing the phosphorylation of eNOS. These findings provide preliminary evidence that GPR30 activation leads to eNOS activation, as well as vasodilation, to a certain degree and has beneficial effects on vascular function in diabetic OVX rats.

  6. Acute effects of different types of oil consumption on endothelial function, oxidative stress status and vascular inflammation in healthy volunteers.

    Science.gov (United States)

    Tousoulis, Dimitris; Papageorgiou, Nikolaos; Antoniades, Charalambos; Giolis, Anastasios; Bouras, George; Gounari, Panagiota; Stefanadi, Elli; Miliou, Antigoni; Psaltopoulou, Theodora; Stefanadis, Christodoulos

    2010-01-01

    Consumption of different types of oil may have different effects on cardiovascular risk. The exact role of maize oil, cod liver oil, soya oil and extra virgin olive oil on endothelial function, oxidative stress and inflammation is unknown. We evaluated the effect of acute consumption of these types of oil on endothelial function, oxidative stress and inflammation in healthy adults. Thirty-seven healthy volunteers were randomised to receive an oral amount of each type of oil or water. Endothelial function was evaluated by gauge-strain plethysmography at baseline and 1, 2 and 3 h after consumption. Oxidative stress status was determined by total lipid peroxides (PEROX), while inflammatory process was estimated by measuring the soluble form of vascular adhesion molecule 1. Serum levels of the two previous markers were measured at baseline and 3 h after oil consumption. Reactive hyperaemia (RH) was significantly decreased after maize oil consumption compared with controls (P consumption of cod liver oil and soya oil induced a significant improvement of RH after 1 h, compared with controls (P consumption on endothelium-independent dilatation, total lipid PEROX and vascular adhesion molecule 1 serum levels. Consumption of maize oil leads to impaired endothelial function, while soya oil and cod liver oil slightly improve endothelial function. However, all types of oils did not affect inflammatory process and systemic oxidative stress, suggesting that their effect on endothelial function may not be mediated by free radicals bioavailability.

  7. Microalbuminuria indicates long-term vascular risk in patients after acute stroke undergoing in-patient rehabilitation

    Directory of Open Access Journals (Sweden)

    Sander Dirk

    2012-09-01

    Full Text Available Abstract Background Patients in neurologic in-patient rehabilitation are at risk of cardio- and cerebrovascular events. Microalbuminuria (MAU is frequent and an important risk predictor but has not been validated in in-patient rehabilitation. We therefore aimed to examine MAU as an indicator of risk and predictor of vascular events in a prospective study. Methods The INSIGHT (INvestigation of patients with ischemic Stroke In neuroloGic reHabiliTation registry is the first to provide large scale data on 1,167 patients with acute stroke (χ2 or Mann–Whitney-U Test. Relative risks (RR with 95% confidence intervals (CI were estimated using log-binominal models. To evaluate the association between MAU and new vascular events as well as mortality, we calculated hazard ratios (HR using Cox proportional hazard regression. Results A substantial proportion of patients was MAU positive at baseline (33.1%. Upon univariate analysis these patients were about 4 years older (69 vs. 65 years; p 2; p = 0.03 and increased waist circumference (79.5 vs. 50.4% for women [p  Conclusions INSIGHT demonstrated a significant association between MAU and polyvascular disease and further supports previous findings that MAU predicts cardio-/cerebrovascular events in patients recovering from ischemic stroke. This biomarker may also be used in patients during neurologic in-patient rehabilitation, opening a window of opportunity for early intervention in this patient group at increased risk for recurrent events.

  8. Natural antioxidant ice cream acutely reduces oxidative stress and improves vascular function and physical performance in healthy individuals.

    Science.gov (United States)

    Sanguigni, Valerio; Manco, Melania; Sorge, Roberto; Gnessi, Lucio; Francomano, Davide

    2017-01-01

    The formation of reactive oxygen species (ROS) contributes to the pathogenesis and progression of several diseases. Polyphenols have been shown to be beneficial against ROS. The aim of this study was to evaluate the effects of a natural antioxidant ice cream on oxidative stress, vascular function, and physical performance. In this controlled, single-blind, crossover study, 14 healthy individuals were randomized to consume 100 g of either antioxidant ice cream containing dark cocoa powder and hazelnut and green tea extracts or milk chocolate ice cream (control ice cream). Participants were studied at baseline and 2 h after ingesting ice cream. Serum polyphenols, antioxidant status (ferric-reducing ability of plasma [FRAP]), nitric oxide (NOx) bioavailability, markers of oxidative stress (determination of reactive oxygen metabolites [d-ROMs] and hydrogen peroxide [H2O2]), endothelium function (flow-mediated dilation [FMD] and reactive hyperemia index [RHI]), and exercise tolerance (stress test) were assessed, and the double product was measured. Serum polyphenols (P ice cream ingestion. No changes were found after control ice cream ingestion. To our knowledge, this is the first study to demonstrate that a natural ice cream rich in polyphenols acutely improved vascular function and physical performance in healthy individuals through a reduction in oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Mast cell dependent vascular changes associated with an acute response to cold immersion in primary contact urticaria.

    Directory of Open Access Journals (Sweden)

    Joseph Meyer

    Full Text Available While a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation.To characterize the microcirculatory events that follow mast cell degranulation.Perturbations in dermal blood flow, temperature and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI challenge in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the histamine-associated vascular response accompanying mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an antihistamine.Monitoring the hemodynamic responses within tissues that are associated with mast cell degranulation provides additional insight into the evolution of the acute inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention.

  10. Vascular endothelial growth factor secretion is an independent prognostic factor for relapse-free survival in pediatric acute myeloid leukemia patients

    NARCIS (Netherlands)

    de Bont, ESJM; Fidler, [No Value; Meeuwsen, T; Scherpen, F; Hahlen, K; Kamps, WA

    Substantial improvements in long-term survival have been made with acute myeloid leukemia (AML). However, the overall success rate in treatment of AML is around 50%, despite intensive chemotherapeutic regimens. AML cell survival seems to be related to vascular endothelial growth factor (VEGF). The

  11. Use of tacrolimus in rescue therapy of acute and chronic rejection in liver transplantation Uso de tacrolimus na terapia de resgate de rejeições agudas e crônicas no transplante de fígado

    Directory of Open Access Journals (Sweden)

    Fabricio Ferreira Coelho

    2003-01-01

    Full Text Available PURPOSE: To study the indications and results of tacrolimus as rescue therapy for acute cellular or chronic rejection in liver transplantation. PATIENTS AND METHODS: Eighteen liver transplant recipients who underwent rescue therapy with tacrolimus between March 1995 and August 1999 were retrospectively studied. The treatment indication, patients, and graft situation were recorded as of October 31st, 1999. The response to tacrolimus was defined as patient survival with a functional graft and histological reversal of acute cellular, or for chronic rejection, bilirubin serum levels decreasing to up to twice the upper normal limit. RESULTS: Fourteen cases (77.8% presented a good response. The response rate for the different indications was: (1 acute cellular + sepsis - 0/1 case; (2 recurrent acute cellular - 1/1 case; (3 OKT3-resistant acute cellular - 2/2 cases; (4 steroid-resistant acute cellular + active viral infection - 3/3 cases; (5 chronic rejection - 8/11 cases (72.7% response rate. The 4 patients who did not respond died. CONCLUSION: Tacrolimus rescue therapy was successful in most cases of acute cellular and chronic rejection in liver transplantation.OBJETIVO: Estudar os critérios de indicação e o resultado do uso de tacrolimus na terapia de resgate de rejeições agudas ou crônicas no transplante de fígado. CASUÍSTICA E MÉTODO: Foram estudados 18 pacientes transplantados de fígado, submetidos a terapia de resgate com tacrolimus entre março de 1995 e agosto de 1999. Foram registradas a indicação do tratamento e a situação de pacientes e enxertos em 31/10/1999. Considerou-se "respondendores" pacientes vivos, com enxerto funcionante e regressão histológica da terapia de resgate de rejeições agudas, ou com bilirrubina até 2 vezes o valor normal, no caso de terapia de resgate de rejeições crônicas. RESULTADO: Observou-se resposta em 14 casos (77,8%. A taxa de resposta nas diferentes indicações foi: (1 terapia de resgate

  12. Dimethylfumarate attenuates restenosis after acute vascular injury by cell-specific and Nrf2-dependent mechanisms

    Directory of Open Access Journals (Sweden)

    Chang Joo Oh

    2014-01-01

    Full Text Available Excessive proliferation of vascular smooth muscle cells (VSMCs and incomplete re-endothelialization is a major clinical problem limiting the long-term efficacy of percutaneous coronary angioplasty. We tested if dimethylfumarate (DMF, an anti-psoriasis drug, could inhibit abnormal vascular remodeling via NF−E2-related factor 2 (Nrf2-NAD(PH quinone oxidoreductase 1 (NQO1 activity. DMF significantly attenuated neointimal hyperplasia induced by balloon injury in rat carotid arteries via suppression of the G1 to S phase transition resulting from induction of p21 protein in VSMCs. Initially, DMF increased p21 protein stability through an enhancement in Nrf2 activity without an increase in p21 mRNA. Later on, DMF stimulated p21 mRNA expression through a process dependent on p53 activity. However, heme oxygenase-1 (HO-1 or NQO1 activity, well-known target genes induced by Nrf2, were dispensable for the DMF induction of p21 protein and the effect on the VSMC proliferation. Likewise, DMF protected endothelial cells from TNF-α-induced apoptosis and the dysfunction characterized by decreased eNOS expression. With knock-down of Nrf2 or NQO1, DMF failed to prevent TNF-α-induced cell apoptosis and decreased eNOS expression. Also, CD31 expression, an endothelial specific marker, was restored in vivo by DMF. In conclusion, DMF prevented abnormal proliferation in VSMCs by G1 cell cycle arrest via p21 upregulation driven by Nrf2 and p53 activity, and had a beneficial effect on TNF-α-induced apoptosis and dysfunction in endothelial cells through Nrf2–NQO1 activity suggesting that DMF might be a therapeutic drug for patients with vascular disease.

  13. Vascular Reactivity: Evaluation of an acute suprasystolic occlusion with impedance plethysmography

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, M C [Departamento de BioingenierIa, Facultad de Ciencias Exactas y TecnologIa, Universidad Nacional de Tucuman e INSIBIO, CONICET, Tucuman (Argentina); Bonaudo, M; Conde, A [Carrera de Ingenieria de Biomedica, Facultad de Ciencias Exactas y TecnologIa, Universidad Nacional de Tucuman (Argentina); Palavecino, L [Carrera de Ingenieria de Biomedica, Facultad de Ciencias Exactas y TecnologIa, Universidad Nacional de Tucuman (Argentina)

    2007-11-15

    In the clinical set, the evaluation of endothelium- dependent vasodilator response of large vessels is carried out using ultrasound equipment for vascular flow determinations and during administration of vasoactive drugs. This work proposes to use a substantially cheaper technique and a sustained cuff arterial occlusion in order to cause vasodilation. Impedance plethysmography is used to detect the arterial pulse wave over radial artery while the forearm is occluded by above the recording site. From these plethysmographic waves, three indexes and their changes -between control and maximal response post-occlusion- were calculated. 33 complete records obtained from healthy low-risk volunteers were analyzed. Between control and post-occlusion maximal response, 'average percentual change of pulse wave amplitude' were (35{+-}13)%, 'stiffness index' did not show significant differences (6,38{+-}0,98 vs 6,38{+-}0,94 and 'reflection index' was significant lower (58{+-}15 vs 35{+-}16)%. These results indicate that: 1- cuff occlusion maneuver was effective to cause endothelium-dependent vasodilation, 2-changes of pulse wave amplitude and reflection index could be used as markers of athero-arteriosclerotic damage in the vascular bed, even in sub-clinical conditions.

  14. Vascular Reactivity: Evaluation of an acute suprasystolic occlusion with impedance plethysmography

    Science.gov (United States)

    Herrera, M. C.; Bonaudo, M.; Conde, A.; Palavecino, L.

    2007-11-01

    In the clinical set, the evaluation of endothelium- dependent vasodilator response of large vessels is carried out using ultrasound equipment for vascular flow determinations and during administration of vasoactive drugs. This work proposes to use a substantially cheaper technique and a sustained cuff arterial occlusion in order to cause vasodilation. Impedance plethysmography is used to detect the arterial pulse wave over radial artery while the forearm is occluded by above the recording site. From these plethysmographic waves, three indexes and their changes -between control and maximal response post-occlusion- were calculated. 33 complete records obtained from healthy low-risk volunteers were analyzed. Between control and post-occlusion maximal response, "average percentual change of pulse wave amplitude" were (35±13)%, "stiffness index" did not show significant differences (6,38±0,98 vs 6,38±0,94 and "reflection index" was significant lower (58±15 vs 35±16)%. These results indicate that: 1- cuff occlusion maneuver was effective to cause endothelium-dependent vasodilation, 2-changes of pulse wave amplitude and reflection index could be used as markers of athero-arteriosclerotic damage in the vascular bed, even in sub-clinical conditions.

  15. Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    de Matthaeis A

    2014-05-01

    Full Text Available Angela de Matthaeis,1 Antonio Greco,2,* Mariangela Pia Dagostino,2 Giulia Paroni,2 Andrea Fontana,3 Manlio Vinciguerra,1,4,5 Gianluigi Mazzoccoli,1,* Davide Seripa,2 Gianluigi Vendemiale61Division of Internal Medicine and Chronobiology Unit, 2Geriatrics Unit and Gerontology, Geriatrics Research Laboratory, Department of Medical Sciences, 3Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, 4Euro-Mediterranean Institute of Sciences and Technology, Palermo, Italy; 5University College London, Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, London, UK; 6Geriatrics Unit, University of Foggia, Foggia, Italy*These authors contributed equally to this workAbstract: Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD, a common medical condition in the elderly. Flow-mediated dilation (FMD, a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1 and after (phase 2 standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001, pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001, pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001, FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001 and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001. FMD values were

  16. Acute Impact of Tobacco vs Electronic Cigarette Smoking on Oxidative Stress and Vascular Function.

    Science.gov (United States)

    Carnevale, Roberto; Sciarretta, Sebastiano; Violi, Francesco; Nocella, Cristina; Loffredo, Lorenzo; Perri, Ludovica; Peruzzi, Mariangela; Marullo, Antonino G M; De Falco, Elena; Chimenti, Isotta; Valenti, Valentina; Biondi-Zoccai, Giuseppe; Frati, Giacomo

    2016-09-01

    The vascular safety of electronic cigarettes (e-Cigarettes) must still be clarified. We compared the impact of e-Cigarettes vs traditional tobacco cigarettes on oxidative stress and endothelial function in healthy smokers and nonsmoker adults. A crossover, single-blind study was performed in 40 healthy subjects (20 smokers and 20 nonsmokers, matched for age and sex). First, all subjects smoked traditional tobacco cigarettes. One week later, the same subjects smoked an e-Cigarette with the same nominal nicotine content. Blood samples were drawn just before and after smoking, and markers of oxidative stress, nitric oxide bioavailability, and vitamin E levels were measured. Flow-mediated dilation (FMD) was also measured. Smoking both e-Cigarettes and traditional cigarettes led to a significant increase in the levels of soluble NOX2-derived peptide and 8-iso-prostaglandin F2α and a significant decrease in nitric oxide bioavailability, vitamin E levels, and FMD. Generalized estimating equation analysis confirmed that all markers of oxidative stress and FMD were significantly affected by smoking and showed that the biologic effects of e-Cigarettes vstraditional cigarettes on vitamin E levels (P = .413) and FMD (P = .311) were not statistically different. However, e-Cigarettes seemed to have a lesser impact than traditional cigarettes on levels of soluble NOX2-derived peptide (P = .001), 8-iso-prostaglandin F2α (P = .046), and nitric oxide bioavailability (P = .001). Our study showed that both cigarettes have unfavorable effects on markers of oxidative stress and FMD after single use, although e-Cigarettes seemed to have a lesser impact. Future studies are warranted to clarify the chronic vascular effects of e-Cigarette smoking. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  17. Local Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance Induction Protocol

    Science.gov (United States)

    2016-10-01

    Provide adjunctive local immunosuppression with PLDS in a non-human model Validate design architecture for digital ear canal volumetric shape Comments...optimizing a fabrication method, and developing characterization methods to test the pharmacokinetics after drug loading. To this end, the team...synthesized and characterized a batch of the chosen tyrosine-derived polymer formulation, E1218(1k), and moved forward in finalizing the fabrication

  18. Inhibition of Secretory Phospholipase A(2) in Patients with Acute Coronary Syndromes: Rationale and Design of the Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 Weeks (VISTA-16) Trial

    NARCIS (Netherlands)

    Nicholls, Stephen J.; Cavender, Matthew A.; Kastelein, John J. P.; Schwartz, Gregory; Waters, David D.; Rosenson, Robert S.; Bash, Dianna; Hislop, Colin

    2012-01-01

    Background The action of secretory phospholipase A(2) (sPLA(2)) on lipoproteins may render them more susceptible to oxidation, thereby promoting vascular inflammation and increasing cardiovascular risk. Patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events

  19. Post-operative acute kidney injury in non-suprainguinal vascular surgery patients with a pre-operative history of hypertension

    Science.gov (United States)

    Moodley, Yoshan; Biccard, Bruce M.

    2015-01-01

    Hypertension is an independent predictor of acute kidney injury (AKI) in non-cardiac surgery patients. There are a few published studies which report AKI following non-suprainguinal vascular procedures, but these studies have not investigated predictors of AKI, including anti-hypertensive medications and other comorbidities, in the hypertensive population alone. We sought to identify independent predictors of post-operative AKI in non-suprainguinal vascular surgery patients with a pre-operative history of hypertension. We performed univariate (chi-squared, or Fisher's exact testing) and multivariate (binary logistic regression) statistical analysis of prospectively collected data from 243 adult hypertensive patients who underwent non-suprainguinal vascular surgery (lower limb amputation or peripheral artery bypass surgery) at a tertiary hospital between 2008 and 2011 in an attempt to identify possible associations between comorbidity, acute pre-operative antihypertensive medication administration, and post-operative AKI (a post-operative increase in serum creatinine of ≥ 25 % above the pre-operative measurement) in these patients. The incidence of post-operative AKI in this study was 5.3 % (95 % Confidence Interval: 3.2-8.9 %). Acute pre-operative β-blocker administration was independently associated with post-operative AKI in non-suprainguinal vascular surgery patients with a pre-operative history of hypertension (Odds Ratio: 3.24; 95 % Confidence Interval: 1.03-10.25). The acute pre-operative administration of β-blockers should be carefully considered in non-suprainguinal vascular surgery patients with a pre-operative history of hypertension, in lieu of an increased risk of potentially poor post-operative renal outcomes. PMID:26966428

  20. Assessment of mesenteric vascular steno-occlusive lesion in acute mesenteric ischemia: comparison between CT angiography and digital subtraction angiography

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Sang Soo; Jeong, Yong Yeon; Yoon, Woong; Lim, Hyo Soon; Song, Sang Gook; Jang Nam Kyu; Kim, Jae Kyu; Kang, Heoung Keun [Chonnam National University, Gwangju (Korea, Republic of); Shen, Yu Lan [YanBian Canner Hospital, Peijing (China)

    2005-09-15

    Acute mesenteric ischemia (AMI) is one of the most dramatic abdominal emergencies. The most common cause of AMI is a thrombo-embolism of the mesenteric artery or vein. The aim of this study was to evaluate the feasibility of CT angiography for evaluating mesenteric vascular steno-occlusive lesion in AMI. Fifteen patients with clinically and angiographically proven AMI underwent a two-phase CT. The CT angiographic images were reconstructed using a 3D rendering algorithm, such as the maximum intensity projection and volume-rendering. All the CT angiographic images were reviewed with respect to stenosis or occlusion of mesenteric vessel by the consensus of two radiologists, and were correlated with the findings of digital subtraction angiography. Digital subtraction angiography (DSA) visualized 60 mesenteric vessels including the superior mesenteric artery (n=15) and vein (n=15), and the inferior mesenteric artery (n=15) and vein (n=15). DSA showed steno-occlusive lesions in 16 mesenteric vessels (13 superior mesenteric arteries, two superior mesenteric vein, and one inferior mesenteric artery). CT angiography detected steno-occlusive lesions in 16 mesenteric vessels (12 superior mesenteric arteries, one superior mesenteric vein, and three inferior mesenteric arteries). The sensitivity, specificity, and accuracy of CT angiography for evaluating mesenteric vascular steno-occlusive lesion were 87.5%, 95.4%, and 93.3%, respectively. CT angiography is an useful adjunct to abdominal CT in an AMI setting on account of its ability to detect the causes of AMI such as a steno-occlusive lesion of the mesenteric vessel.

  1. Human cord blood progenitors with high aldehyde dehydrogenase activity improve vascular density in a model of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Creer Michael H

    2010-03-01

    Full Text Available Abstract Human stem cells from adult sources have been shown to contribute to the regeneration of muscle, liver, heart, and vasculature. The mechanisms by which this is accomplished are, however, still not well understood. We tested the engraftment and regenerative potential of human umbilical cord blood-derived ALDHhiLin-, and ALDHloLin- cells following transplantation to NOD/SCID or NOD/SCID β2m null mice with experimentally induced acute myocardial infarction. We used combined nanoparticle labeling and whole organ fluorescent imaging to detect human cells in multiple organs 48 hours post transplantation. Engraftment and regenerative effects of cell treatment were assessed four weeks post transplantation. We found that ALDHhiLin- stem cells specifically located to the site of injury 48 hours post transplantation and engrafted the infarcted heart at higher frequencies than ALDHloLin- committed progenitor cells four weeks post transplantation. We found no donor derived cardiomyocytes and few endothelial cells of donor origin. Cell treatment was not associated with any detectable functional improvement at the four week endpoint. There was, however, a significant increase in vascular density in the central infarct zone of ALDHhiLin- cell-treated mice, as compared to PBS and ALDHloLin- cell-treated mice. Conclusions Our data indicate that adult human stem cells do not become a significant part of the regenerating tissue, but rapidly home to and persist only temporarily at the site of hypoxic injury to exert trophic effects on tissue repair thereby enhancing vascular recovery.

  2. Pig specific vascular anatomy allows acute infrarenal aortic occlusion without hind limb ischemia and stepwise occlusion without clinical signs.

    Science.gov (United States)

    Haacke, N; Unger, J K; Haidenhein, C; Russ, M; Hiebl, B; Niehues, S M

    2011-01-01

    In a porcine, aortic graft model we found 5 animals to develop and survive unnoticed, complete infrarenal aortic occlusion and 2 pigs with an acute occlusion but rather unspecific clinical symptoms. We investigated the pigs' vascular system to classify the anatomic capabilities to compensate for an acute abdominal aortic occlusion. Retrospective analysis of CT scans and clinical data to specify unexpected results in a case series of infrarenal occlusion in a porcine model. Collaborative study of experimental and clinical departments. Fifteen healthy female minipigs. All pigs underwent an infrarenal aortic graft intervention. Anesthesia and perioperative management of the animals were preformed along the standard operating procedures of the local Department of Experimental Medicine. All animals received perioperative antibiotics, ASS, and carprofen for postoperative analgesia. Arterial pressure, heart rate, body temperature, and diuresis were monitored during surgery and therapeutic interventions. Contrast media based computed tomography (CT) with total body scans were performed at 1, 4, 10, 12 weeks after surgery. Comparable scans of cardiovascular healthy subjects (humans and pigs) and patients with a Leriche's syndrome were analyzed. Neither acute (within the first 12 h after surgery) nor stepwise total aortic occlusion show unmistakable clinical signs. In pigs, the epigastric artery (EGA) - which is in connection with suprarenal lumbal arteries, subclavian and external iliac artery - is highly developed associated to the high number of mammary glands of about 7 on one side. In humans, the ratio of aortic to EGA-diameter is 1 : 0.15. In minipigs we found a ratio of 1 : 0.43 which changed during aortic occlusion resulting in a ratio of 1 : 0.58. Pigs with a slowly developing occlusion demonstrated an enlargement of the ureteric artery of about 210% completing a sufficient collateral system. While in the human Leriche's syndrome months are needed to enlarge the

  3. Acute Peanut Consumption Alters Postprandial Lipids and Vascular Responses in Healthy Overweight or Obese Men.

    Science.gov (United States)

    Liu, Xiaoran; Hill, Alison M; West, Sheila G; Gabauer, Rachel M; McCrea, Cindy E; Fleming, Jennifer A; Kris-Etherton, Penny M

    2017-05-01

    Background: Postprandial hyperlipidemia is associated with impaired endothelial function. Peanut consumption favorably affects the lipid and lipoprotein profile; however, the effects on endothelial function remain unclear.Objective: The purpose of the study was to evaluate the effects of acute peanut consumption as part of a high-fat meal on postprandial endothelial function.Methods: We conducted a randomized, controlled, crossover postprandial study to evaluate the effect of acute peanut consumption on postprandial lipids and endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery in 15 healthy overweight or obese men [mean age: 26.7 y; mean body mass index (in kg/m(2)): 31.4]. Participants consumed, in a randomized order, a peanut meal containing 3 ounces (85 g) ground peanuts (1198 kcal; 40.0% carbohydrate, 47.7% fat, 19.4% saturated fat, 13.2% protein) and a control meal matched for energy and macronutrient content. Meals were in the form of a shake, scheduled ≥1 wk apart. Lipids, lipoproteins, glucose, and insulin were measured at baseline (0 min) and at 30, 60, 120, and 240 min after shake consumption. FMD was measured at baseline and at 240 min.Results: Acute peanut consumption blunted the serum triglyceride (TG) response 120 and 240 min after consumption compared with the control meal (means ± SEMs-120 min: 188.9 ± 19.4 compared with 197.5 ± 20.7 mg/dL; 240 min: 189.9 ± 24.3 compared with 197.3 ± 18.4 mg/dL; P 150 mg/dL) and LDL (>100 mg/dL)-cholesterol concentrations showed a significant decrease in FMD after the control meal (-1.8%, P = 0.017; -2.0%, P = 0.038), whereas the peanut meal maintained endothelial function in all participants irrespective of total- and LDL-cholesterol concentrations.Conclusion: The inclusion of 85 g peanuts (3 ounces) as part of a high-fat meal improved the postprandial TG response and preserved endothelial function in healthy overweight or obese men. This trial was registered at

  4. Corneal Graft Rejection: Incidence and Risk Factors

    Directory of Open Access Journals (Sweden)

    Alireza Baradaran-Rafii

    2008-12-01

    Full Text Available

    PURPOSE: To determine the incidence and risk factors of late corneal graft rejection after penetrating keratoplasty (PKP. METHODS: Records of all patients who had undergone PKP from 2002 to 2004 without immunosuppressive therapy other than systemic steroids and with at least one year of follow up were reviewed. The role of possible risk factors such as demographic factors, other host factors, donor factors, indications for PKP as well as type of rejection were evaluated. RESULTS: During the study period, 295 PKPs were performed on 286 patients (176 male, 110 female. Mean age at the time of keratoplasty was 38±20 (range, 40 days to 90 years and mean follow up period was 20±10 (range 12-43 months. Graft rejection occurred in 94 eyes (31.8% at an average of 7.3±6 months (range, 20 days to 39 months after PKP. The most common type of rejection was endothelial (20.7%. Corneal vascularization, regrafting, anterior synechiae, irritating sutures, active inflammation, additional anterior segment procedures, history of trauma, uncontrolled glaucoma, prior graft rejection, recurrence of herpetic infection and eccentric grafting increased the rate of rejection. Patient age, donor size and bilateral transplantation had no significant influence on graft rejection. CONCLUSION: Significant risk factors for corneal graft rejection include

  5. Serum Soluble Vascular-Cell Adhesion Molecule-1 (VCAM-1 in Patients with Acute and Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Mario Pirisi

    1996-01-01

    Full Text Available Our ai m was to ascertai n the degree of variation of serum soluble vascular cell adhesion moleculeI (VCAM-1 concentrations according to the nature and the severity of an underl ying liver disease . One-hundred forty sera collected from 123 patients (83 male, 40 female with acute hepatitis (n=14. mi Id chronic Ii ver disease (n=52 or cirrhosis (n=57 of different etiologies as well as from 17 healthy blood donors (8 male, 9 female were studied. Soluble VCAM-I concentration was measured immunoenzymatically. One-way analysis of variance revealed a significant variability of the mean values of soluble VCAM-1 among groups (F=80.02, p <0.000 I. All groups of patients had higher soluble VCAM-I than controls; moreover, patients with acute hepatitis and patients with cirrhosis had higher soluble VCAM-1 levels than patients with mild chronic liver disease (Bonferroni's test. p <0.(1. These results did not change after stratification of patients according to the etiology (viral or toxic of liver disease (two-way analysis of variance: grouping factor diagnosis, F=60.39, p <0.000 I; grouping factor etiology. F= 1.73, p NS. Cholinesterase, total bilirubin, circulating thrombocytes and blood urea nitrogen were the independent predictors of the concentration of soluble VCAM-1. In conclusion, patients with liver disease have high serum soluble VCAM-1, which seems to reflect more the severity of impairment of liver function rather than the etiologic nature of the disease.

  6. Inhibition of vascular endothelial growth factor signaling facilitates liver repair from acute ethanol-induced injury in zebrafish

    Directory of Open Access Journals (Sweden)

    Changwen Zhang

    2016-11-01

    Full Text Available Alcoholic liver disease (ALD results from alcohol overconsumption and is among the leading causes of liver-related morbidity and mortality worldwide. Elevated expression of vascular endothelial growth factor (VEGF and its receptors has been observed in ALD, but how it contributes to ALD pathophysiology is unclear. Here, we investigated the impact of VEGF signaling inhibition on an established zebrafish model of acute alcoholic liver injury. Kdrl activity was blocked by chemical inhibitor treatment or by genetic mutation. Exposing 4-day-old zebrafish larvae to 2% ethanol for 24 h induced hepatic steatosis, angiogenesis and fibrogenesis. The liver started self-repair once ethanol was removed. Although inhibiting Kdrl did not block the initial activation of hepatic stellate cells during ethanol treatment, it suppressed their proliferation, extracellular matrix protein deposition and fibrogenic gene expression after ethanol exposure, thus enhancing the liver repair. It also ameliorated hepatic steatosis and attenuated hepatic angiogenesis that accelerated after the ethanol treatment. qPCR showed that hepatic stellate cells are the first liver cell type to increase the expression of VEGF ligand and receptor genes in response to ethanol exposure. Both hepatic stellate cells and endothelial cells, but not hepatic parenchymal cells, expressed kdrl upon ethanol exposure and were likely the direct targets of Kdrl inhibition. Ethanol-induced steatosis and fibrogenesis still occurred in cloche mutants that have hepatic stellate cells but lack hepatic endothelial cells, and Kdrl inhibition suppressed both phenotypes in the mutants. These results suggest that VEGF signaling mediates interactions between activated hepatic stellate cells and hepatocytes that lead to steatosis. Our study demonstrates the involvement of VEGF signaling in regulating sustained liver injuries after acute alcohol exposure. It also provides a proof of principle of using the

  7. Effect of Acetazolamide and Gingko Biloba on the Human Pulmonary Vascular Response to an Acute Altitude Ascent

    Science.gov (United States)

    Ke, Tao; Wang, Jiye; Swenson, Erik R.; Zhang, Xiangnan; Hu, Yunlong; Chen, Yaoming; Liu, Mingchao; Zhang, Wenbin; Zhao, Feng; Shen, Xuefeng; Yang, Qun

    2013-01-01

    Abstract Ke, Tao, Jiye Wang, Erik R. Swenson, Xiangnan Zhang, Yunlong Hu, Yaoming Chen, Mingchao Liu, Wenbin Zhang, Feng Zhao, Xuefeng Shen, Qun Yang, Jingyuan Chen, and Wenjing Luo. Effect of acetazolamide and gingko biloba on the human pulmonary vascular response to an acute altitude ascent. High Alt Med Biol 14:162–167, 2013.—Acetazolamide and gingko biloba are the two most investigated drugs for the prevention of acute mountain sickness (AMS). Evidence suggests that they may also reduce pulmonary artery systolic pressure (PASP). To investigate whether these two drugs for AMS prevention also reduce PASP with rapid airlift ascent to high altitude, a randomized controlled trial was conducted on 28 healthy young men with acetazolamide (125 mg bid), gingko biloba (120 mg bid), or placebo for 3 days prior to airlift ascent (397 m) and for the first 3 days at high altitude (3658 m). PASP, AMS, arterial oxygen saturation (Sao2), mean arterial pressure (MAP), heart rate (HR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF) were assessed both at 397 m and 3658 m. HR, PEF, and PASP increased with altitude exposure (pbiloba (mean at 3658 m, 33.7 mm Hg, p=0.001; incremental change, 13.1 mm Hg, 95%CI., 9.6–16.5 mm Hg, p=0.002), and with placebo (mean at 3658 m, 34.7 mm Hg, pgingko biloba, mitigates the early increase of PASP in a quick ascent profile. PMID:23795737

  8. Adipose stromal vascular fraction cell construct sustains coronary microvascular function after acute myocardial infarction

    Science.gov (United States)

    LeBlanc, Amanda J.; Touroo, Jeremy S.; Hoying, James B.

    2012-01-01

    A three-dimensional tissue construct was created using adipose-derived stromal vascular fraction (SVF) cells and evaluated as a microvascular protection treatment in a myocardial infarction (MI) model. This study evaluated coronary blood flow (BF) and global left ventricular function after MI with and without the SVF construct. Fischer-344 rats were separated into four groups: sham operation (sham), MI, MI Vicryl patch (no cells), and MI SVF construct (MI SVF). SVF cells were labeled with green fluorescent protein (GFP). Immediately postinfarct, constructs were implanted onto the epicardium at the site of ischemia. Four weeks postsurgery, the coronary BF reserve was significantly decreased by 67% in the MI group and 75% in the MI Vicryl group compared with the sham group. The coronary BF reserve of the sham and MI SVF groups in the area at risk was not significantly different (sham group: 83 ± 22% and MI SVF group: 57 ± 22%). Griffonia simplicifolia I and GFP-positive SVF immunostaining revealed engrafted SVF cells around microvessels in the infarct region 4 wk postimplant. Overall heart function, specifically ejection fraction, was significantly greater in MI SVF hearts compared with MI and MI Vicryl hearts (MI SVF: 66 ± 4%, MI: 37 ± 8%, and MI Vicryl: 29 ± 6%). In conclusion, adipose-derived SVF cells can be used to construct a novel therapeutic modality for treating microvascular instability and ischemia through implantation on the epicardial surface of the heart. The SVF construct implanted immediately after MI not only maintains heart function but also sustains microvascular perfusion and function in the infarct area by sustaining the coronary BF reserve. PMID:22140045

  9. Consumption of a flavonoid-rich acai meal is associated with acute improvements in vascular function and a reduction in total oxidative status in healthy overweight men

    OpenAIRE

    Alqurashi, Randah M.; Galante, Laura A.; Rowland, Ian R.; Spencer, Jeremy P.; Commane, Danny M.

    2016-01-01

    Background: Acai (Euterpe oleracea) is a polyphenol-rich fruit marketed as beneficial for health. Experimental data showing improvements in health markers arising from acai consumption in humans is limited.\\ud Objective: The objective of the present study was to investigate the effect of acai consumption on acute changes in vascular function and on other disease risk markers, including postprandial plasma insulin, glucose, and oxidative stress.\\ud Design: Twenty-three healthy male volunteers,...

  10. Heavy Proteinuria as a Manifestation of Acute Allograft Rejection Presenting Early after Kidney Transplantation: A Retrospective, Single-Center Case Series

    Science.gov (United States)

    2009-01-01

    Abstract: The differential diagnosis of heavy proteinuria presenting early after kidney transplantation has generally included de novo or recurrent...SUPPLEMENTARY NOTES 14. ABSTRACT The differential diagnosis of heavy proteinuria presenting early after kidney transplantation has generally included de novo...26 The Open Transplantation Journal, 2009, 3, 26-30 1874-4184/09 2009 Bentham Open Open Access Heavy Proteinuria as a Manifestation of Acute

  11. Visualizing the Acute Effects of Vascular-Targeted Therapy In Vivo Using Intravital Microscopy and Magnetic Resonance Imaging: Correlation with Endothelial Apoptosis, Cytokine Induction, and Treatment Outcome

    Directory of Open Access Journals (Sweden)

    Mukund Seshadri

    2007-02-01

    Full Text Available The acute effects of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA were investigated in vivo using intravital microscopy (IVM and magnetic resonance imaging (MRI. Changes in vascular permeability and blood flow of syngeneic CT-26 murine colon adenocarcinomas were assessed at 4 and 24 hours after DMXAA treatment (30 mg/kg, i.p. and correlated with induction of tumor necrosis factor-α (TNF-α, endothelial damage [CD31/terminal deoxynucleotidyl transferase (TdT], and treatment outcome. Intravital imaging revealed a marked increase in vascular permeability 4 hours after treatment, consistent with increases in intratumoral mRNA and protein levels of TNF-α. Parallel contrast-enhanced MRI studies showed a ~ 4-fold increase in longitudinal relaxation rates (ΔR1, indicative of increased contrast agent accumulation within the tumor. Dualimmunostained tumor sections (CD31/TdT revealed evidence of endothelial apoptosis at this time point. Twenty-four hours after treatment, extensive hemorrhage and complete disruption of vascular architecture were observed with IVM, along with a significant reduction in ΔR1 and virtual absence of CD31 immunostaining. DMXAA-induced tumor vascular damage resulted in significant long-term (60-day cures compared to untreated controls. Multimodality imaging approaches are useful in visualizing the effects of antivascular therapy in vivo. Such approaches allow cross validation and correlation of findings with underlying molecular changes contributing to treatment outcome.

  12. VEGF receptor antagonist Cyclo-VEGI reduces inflammatory reactivity and vascular leakiness and is neuroprotective against acute excitotoxic striatal insult

    Directory of Open Access Journals (Sweden)

    McLarnon James G

    2008-05-01

    Full Text Available Abstract Background Excitotoxic brain insult is associated with extensive neuronal damage but could also cause inflammatory reactivity and vascular remodeling. The effects of the vascular endothelial growth factor (VEGF inhibitor, Cyclo-VEGI on expression of VEGF, microgliosis and astrogliosis, blood-brain barrier (BBB integrity and neuronal viability have been studied following intra-striatal injection of the excitotoxin, quinolinic acid (QUIN. The purpose of this study was to examine VEGF-dependent inflammatory responses in excitotoxin-injected brain and their dependence on pharmacological antagonism of VEGF receptors. Methods Single and double immunofluorescence staining of cellular (microglia, astrocyte, neuron responses and dye and protein infiltration of blood-brain barrier have been applied in the absence, and presence, of pharmacological modulation using a VEGF receptor antagonist, Cyclo-VEGI. Dunn-Bonferroni statistical analysis was used to measure for significance between animal groups. Results Detailed analysis, at a single time point of 1 d post-QUIN injection, showed excitotoxin-injected striatum to exhibit marked increases in microgliosis (ED1 marker, astrogliosis (GFAP marker and VEGF expression, compared with PBS injection. Single and double immunostaining demonstrated significant effects of Cyclo-VEGI treatment of QUIN-injected striatum to inhibit microgliosis (by 38%, ED1/VEGF (by 42% and VEGF striatal immunoreactivity (by 43%; astrogliosis and GFAP/VEGF were not significantly altered with Cyclo-VEGI treatment. Leakiness of BBB was indicated by infiltration of Evans blue dye and plasma protein fibrinogen into QUIN-injected striatum with barrier permeability restored by 62% (Evans blue permeability and 49% (fibrinogen permeability with Cyclo-VEGI application. QUIN-induced toxicity was demonstrated with loss of striatal neurons (NeuN marker and increased neuronal damage (Fluoro-Jade marker with significant neuroprotection

  13. [Vascular trauma].

    Science.gov (United States)

    Furuya, T; Nobori, M; Tanaka, N

    1999-07-01

    Vascular trauma is essentially acute arterial obstruction, often combined with hemorrhage, fracture, and infection. It can be both life-threatening and limb-threatening and needs an emergency operation. In vascular trauma patient, multiple fracture and organ injury, such as brain, lung, liver, spleen, kidney, or gastrointestinal tract should be evaluated to decide treatment priority. When the pulse distal from the injured site is absent or diminished, vascular trauma is most likely and reconstruction should be accomplished within "the golden time (6-8 hours)". Intimal damage followed by platelet aggregation and thrombus formation will necessitate resection and repair of the site instead of simple thrombectomy. Although autogenous vein is the first choice, artificial graft can be implanted for short segment in non-infected field.

  14. Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Santos, Arnoldo; Gomez-Peñalver, Eva; Monge-Garcia, M Ignacio; Retamal, Jaime; Borges, João Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-11-01

    To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

  15. Long-term outcome of patients with persistent vascular obstruction on computed tomography pulmonary angiography 6 months after acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Golpe, Rafael; Llano, Luis A. Perez de; Olalla, Castro-Anon [The Respiratory Service, Hospital Lucus Augusti, Lugo (Spain)], e-mail: Rafael.golpe.gomez@sergas.es; Vazquez-Caruncho, Manuel [The Radiology Service, Hospital Lucus Augusti, Lugo (Spain); Gonzalez-Juanatey, Carlos [The Cardiology Service, Hospital Lucus Augusti, Lugo (Spain); Farinas, Maria Carmen [Internal Medicine Dept., Hospital Univ. Marques de Valdecilla, Santander (Spain)

    2012-09-15

    Background: The incidence and clinical significance of pulmonary residual thrombosis 6 months after an acute pulmonary embolism (PE) are still not well-known. Purpose: To evaluate the association between residual vascular obstruction and the risk of venous thromboembolism (VTE) recurrence or death. Material and Methods: Computed tomography pulmonary angiography (CTPA) was repeated in 97 consecutive patients 6 months after an acute episode of hemodynamically stable pulmonary embolism. We assessed the long-term consequences of residual thrombosis on vital status and incidence of recurrent VTE. Results: Six patients were lost for follow-up. The remaining 91 patients were classified according to the presence (Group 1: 18 cases) or absence (Group 2: 73 cases) of residual pulmonary vascular obstruction. After a mean {+-}SD of 2.91 {+-}0.99 years, there were eight (8.8%) deaths and 11 (12.1%) VTE recurrences. Groups 1 and 2 did not differ in the incidence of death or VTE recurrence. Conclusion: Persistent pulmonary vascular obstruction on 6-month CTPA did not predict long-term adverse outcome events.

  16. Value of endothelin in cellular rejection after liver transplantation.

    Science.gov (United States)

    Fábrega, E; Figols, J; Dueñas, C; Crespo, J; Casafont, F; Sanchez-Antolín, G; de las Heras, G; Amado, J A; Pons-Romero, F

    1997-02-01

    Endothelin-1 is a vasoconstrictor peptide released by the vascular endothelium by various chemical and mechanical factors. Cellular rejection is one of the most common complications following orthotopic liver transplantation, endotheliitis being its most specific and consistent histological feature. To assess the role of endothelin in cellular hepatic rejection, we studied 21 cirrhotic patients undergoing elective liver transplantation. These patients were divided in two groups: Group I comprised 10 patients without cellular rejection, and Group II comprised 11 patients with cellular rejection. Endothelin was measured on day 7 after transplantation, on the day of liver biopsy, and after treatment for rejection. We found a significant increase in the plasma endothelin levels in the early postoperative period in the patients with moderate or severe cellular rejection compared with the non-rejection group. It remained significantly elevated until the clinical diagnosis of rejection was made. This value returned to baseline with successful treatment. So, the monitorization of this peptide may be of help in the diagnosis of rejection, its severity, and the evaluation of its resolution.

  17. [Effect of emodin on rejection of liver transplantation in rats].

    Science.gov (United States)

    Jing, He; Lin, Shengzhang; Yang, Xiao

    2009-06-01

    To investigate the mechanism of Emodin on the role of acute rejection in rat liver transplantation. Forty-eight pairs of orthotopic liver transplantation model were established with inbred rats which were randomly divided into 3 groups: Control group (BN --> BN), acute rejection group (Lewis --> BN) and emodin group (Lewis --> BN). Six recipients in each group were randomly collected and contents of TNF-alpha and IL-10 in the peripheral blood were detected with ELISA on Day 1, 3, 5 and 7 separately after transplantation and histopathological evaluation was made to detect the differences among groups after the livers were taken out on day 7. The other 10 in each group were protected to evaluate the animation and life time. The average meso-life time in emodin group (25.6 days) is significantly longer (P < 0.05) than acute rejection group (10.9 days). Compared with the acute rejection group, Emodin group shows up less rejection in the histopathological evaluation (P < 0.01), less TNF-alpha (P < 0.05) and a significant up-regulation of IL-10 in the peripheral blood (P < 0.05 after day 3). Emodin can inhibit the acute rejection of liver transplantation in rats model effectively and it may play the role with reduction of TNF-alpha and upregulation of IL-10.

  18. Incidence, risk factors, and outcome of antithymocyte globulin treatment of steroid-resistant rejection after liver transplantation

    NARCIS (Netherlands)

    Bijleveld, CGE; Klompmaker, IJ; vandenBerg, AP; Gouw, ASH; Hepkema, BG; Haagsma, EB; Slooff, MJH

    1996-01-01

    We retrospectively analyzed the incidence and outcome of steroid-resistant rejection (SRR) during the first 6 months after OLT in 126 patients receiving triple immunosuppression. A total of 95 patients either did not experience acute rejection at all or had acute rejection that subsided without

  19. The influence of genotype on vascular endothelial growth factor and regulation of myocardial collateral blood flow in patients with acute and chronic coronary heart disease

    DEFF Research Database (Denmark)

    Ripa, R.S.; Jorgensen, E.; Baldazzi, F.

    2009-01-01

    OBJECTIVE: To test the hypothesis that mutations in the vascular endothelial growth factor (VEGF) gene are associated with plasma concentration of VEGF and subsequently the ability to influence coronary collateral arteries in patients with coronary heart disease (CHD). METHODS: Blood samples from...... patients with chronic ischemic heart disease (n=53) and acute coronary syndrome (n=61) were analysed. Coronary collaterals were scored from diagnostic biplane coronary angiograms. RESULTS: The plasma concentration of VEGF was increased in patients with acute compared to chronic CHD (p=0.01). The genotype......-1154 and coronary collateral size (p=0.03) and a significant association between the VEGF plasma concentration and the collateral size (p=0.03). CONCLUSION: VEGF plasma concentration seems related to coronary collateral function in patients with CHD. The results did not support the hypothesis...

  20. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification and vascular territory of ischemic stroke lesions diagnosed by diffusion-weighted imaging.

    Science.gov (United States)

    Chung, Jong-Won; Park, Su Hyun; Kim, Nayoung; Kim, Wook-Joo; Park, Jung Hyun; Ko, Youngchai; Yang, Mi Hwa; Jang, Myung Suk; Han, Moon-Ku; Jung, Cheolkyu; Kim, Jae Hyoung; Oh, Chang Wan; Bae, Hee-Joon

    2014-08-11

    The association between the location and the mechanism of a stroke lesion remains unclear. A diffusion-weighted imaging study may help resolve this lack of clarity. We studied a consecutive series of 2702 acute ischemic stroke patients whose stroke lesions were confirmed by diffusion-weighted imaging and who underwent a thorough etiological investigation. The vascular territory in which an ischemic lesion was situated was identified using standard anatomic maps of the dominant arterial territories. Stroke subtype was based on the Trial of ORG 10172 in Acute Stroke Treatment, or TOAST, classification. Large-artery atherosclerosis (37.3%) was the most common stroke subtype, and middle cerebral artery (49.6%) was the most frequently involved territory. Large-artery atherosclerosis was the most common subtype for anterior cerebral, middle cerebral, vertebral, and anterior and posterior inferior cerebellar artery territory infarctions. Small vessel occlusion was the leading subtype in basilar and posterior cerebral artery territories. Cardioembolism was the leading cause in superior cerebellar artery territory. Compared with carotid territory stroke, vertebrobasilar territory stroke was more likely to be caused by small vessel occlusion (21.4% versus 30.1%, Pterritory infarction was frequently caused by cardioembolism (44.2%) in carotid territory and by large-artery atherosclerosis (52.1%) in vertebrobasilar territory. Information on vascular territory of a stroke lesion may be helpful in timely investigation and accurate diagnosis of stroke etiology. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  1. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Classification and Vascular Territory of Ischemic Stroke Lesions Diagnosed by Diffusion‐Weighted Imaging

    Science.gov (United States)

    Chung, Jong‐Won; Park, Su Hyun; Kim, Nayoung; Kim, Wook‐Joo; Park, Jung Hyun; Ko, Youngchai; Yang, Mi Hwa; Jang, Myung Suk; Han, Moon‐Ku; Jung, Cheolkyu; Kim, Jae Hyoung; Oh, Chang Wan; Bae, Hee‐Joon

    2014-01-01

    Background The association between the location and the mechanism of a stroke lesion remains unclear. A diffusion‐weighted imaging study may help resolve this lack of clarity. Methods and Results We studied a consecutive series of 2702 acute ischemic stroke patients whose stroke lesions were confirmed by diffusion‐weighted imaging and who underwent a thorough etiological investigation. The vascular territory in which an ischemic lesion was situated was identified using standard anatomic maps of the dominant arterial territories. Stroke subtype was based on the Trial of ORG 10172 in Acute Stroke Treatment, or TOAST, classification. Large‐artery atherosclerosis (37.3%) was the most common stroke subtype, and middle cerebral artery (49.6%) was the most frequently involved territory. Large‐artery atherosclerosis was the most common subtype for anterior cerebral, middle cerebral, vertebral, and anterior and posterior inferior cerebellar artery territory infarctions. Small vessel occlusion was the leading subtype in basilar and posterior cerebral artery territories. Cardioembolism was the leading cause in superior cerebellar artery territory. Compared with carotid territory stroke, vertebrobasilar territory stroke was more likely to be caused by small vessel occlusion (21.4% versus 30.1%, Pterritory infarction was frequently caused by cardioembolism (44.2%) in carotid territory and by large‐artery atherosclerosis (52.1%) in vertebrobasilar territory. Conclusions Information on vascular territory of a stroke lesion may be helpful in timely investigation and accurate diagnosis of stroke etiology. PMID:25112556

  2. Acute response of circulating vascular regulating microRNAs during and after high-intensity and high-volume cycling in children

    Directory of Open Access Journals (Sweden)

    Yvonne eKilian

    2016-03-01

    Full Text Available Aim: The aim of the present study was to analyze the response of vascular circulating microRNAs (miRNAs; miR-16, miR-21, miR-126 and the VEGF mRNA following an acute bout of HIIT and HVT in children. Methods: Twelve healthy competitive young male cyclists (14.4 ± 0.8 yrs; 57.9 ± 9.4 ml·min-1·kg-1 peak oxygen uptake performed one session of high intensity 4x4 min intervals (HIIT at 90-95% peak power output, each interval separated by 3 min of active recovery, and one high volume session (HVT consisting of a constant load exercise for 90 min at 60% peak power output. Capillary blood from the earlobe was collected under resting conditions, during exercise (d1 = 20 min, d2 = 30 min, d3 = 60 min, and 0, 30, 60, 180 min after the exercise to determine miR-16, -21, -126 and VEGF mRNA.Results: HVT significantly increased miR-16 and miR-126 during and after the exercise compared to pre values, whereas HIIT showed no significant influence on the miRNAs compared to pre values. VEGF mRNA significantly increased during and after HIIT (d1, 30`, 60`, 180` and HVT (d3, 0`, 60`. Conclusion: Results of the present investigation suggest a volume dependent exercise regulation of vascular regulating miRNAs (miR-16, miR-21, miR-126 in children. In line with previous data, our data show that acute exercise can alter circulating miRNAs profiles that might be used as novel biomarkers to monitor acute and chronic changes due to exercise in various tissues.

  3. Adeno-associated viral vector 2.9 thymosin ß4 application attenuates rejection after heart transplantation: results of a preclinical study in the pig.

    Science.gov (United States)

    Postrach, Johannes; Schmidt, Maximilian; Thormann, Michael; Thein, Eckart; Burdorf, Lars; Reichart, Bruno; Sotlar, Karl; Walz, Christoph; Faber, Claudius; Bauer, Andreas; Schmoeckel, Michael; Kupatt, Christian; Hinkel, Rabea

    2014-10-27

    Graft survival is the most important factor for morbidity and mortality in cardiac transplantation. Improved immunosuppression significantly reduced early graft rejection. However, acute rejection may predispose to chronic rejection. Targeting both phases of the recipient's immune-reactivity by means of long-acting recombinant adeno-associated viral vectors (AAVs) encoding anti-inflammatory and cardioprotective factors appears to be a promising therapeutic approach. We investigate thymosin ß4 (Tß4) possessing anti-inflammatory and prosurvival abilities, as a means for pretransplant gene therapy. Heterotopic, abdominal transplantation of cardiac allografts into landrace or into Munich mini pigs (n=5 per group) was performed. Transplants were transduced with AAV2.9 before transplantation by means of in situ perfusion of the donor organ. Vascuar endothelial growth factor and AAV2.9.Tß4 or AAV2.9.LacZ were added to the autologous blood used for perfusing the grafts for a period of 45 min. Immunosuppression was applied for 10 days after the operation. Transgene expression, capillary density, graft function, survival, and rejection were assessed. The AAV2.9 transduction induced robust overexpression of the transgene. In addition, Tß4 ameliorated inflammation, necrosis, vascular reaction (acute rejection) and in parallel improved capillary density. In addition, graft survival was significantly prolonged (10±3 days AAV2.9.LacZ vs. 31±4 days AAV2.9.Tß4). In the mini pig model, regional myocardial function of the grafts was improved by Tß4 transduction compared to LacZ (9.1%±0.9% subendocardial segment shortening in AAV2.9.LacZ vs. 15.8%±2.3% in AAV2.9.Tß4). In situ AAV2.9-mediated gene transfer of thymosin β4 attenuated graft rejection in a heterotopic heart transplantation model. Perioperative cardioprotection by means of gene therapy might improve graft survival in cardiac allotransplantation.

  4. VASCULAR DEMENTIA

    Directory of Open Access Journals (Sweden)

    Maria Alekseyevna Cherdak

    2010-01-01

    vascular cognitive disorders and vascular dementia (VD. The heterogeneity of vascular cognitive disorders, concurrence of vascular and neurodegenerative diseases are discussed. Data from studies of specific therapy for VD are given.

  5. Role of Multidetector CT in Evaluation of Acute Chest Pain: Non-Cardiac Vascular and Pulmonary Causes

    OpenAIRE

    Rania S Sayed *, Hisham M Mansour **, Mohammad H Khaleel ***, Sherif H Abo Gamra ** and Merhan A Nasr

    2013-01-01

    Background: Triage of patients with acute chest pain is one of the most important issues currently facing physicians in the emergency department. Acute chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. The causes of acute chest pain range from non-serious to life threatening. A rapid, accurate and cost-effective approach for the evaluation of emergency department patients with chest pain is needed. Aim of the work: This work aims to...

  6. The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome.

    Science.gov (United States)

    Kushimoto, Shigeki; Taira, Yasuhiko; Kitazawa, Yasuhide; Okuchi, Kazuo; Sakamoto, Teruo; Ishikura, Hiroyasu; Endo, Tomoyuki; Yamanouchi, Satoshi; Tagami, Takashi; Yamaguchi, Junko; Yoshikawa, Kazuhide; Sugita, Manabu; Kase, Yoichi; Kanemura, Takashi; Takahashi, Hiroyuki; Kuroki, Yuichi; Izumino, Hiroo; Rinka, Hiroshi; Seo, Ryutarou; Takatori, Makoto; Kaneko, Tadashi; Nakamura, Toshiaki; Irahara, Takayuki; Saito, Nobuyuki; Watanabe, Akihiro

    2012-12-11

    Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95). PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates. UMIN-CTR ID UMIN000003627.

  7. Role of the PKCβII/JNK signaling pathway in acute glucose fluctuation-induced apoptosis of rat vascular endothelial cells.

    Science.gov (United States)

    Wu, Na; Shen, Haitao; Wang, Yanjun; He, Bing; Zhang, Yongyan; Bai, Yu; Du, Runyu; Du, Qiang; Han, Ping

    2017-08-01

    The purpose of this study was to investigate the mechanism of vascular endothelial cell apoptosis induced by acute blood glucose fluctuation. Thirty rats were assigned to three groups: normal saline (SAL group), constant high glucose (CHG group) and acute blood glucose fluctuation (AFG) group. Other forty rats were assigned to SAL group, AFG group, LY group (PKCβ inhibitor LY333531 was injected intragastrically to the rats who were under acute blood glucose fluctuation) and SP group (JNK inhibitor SP600125 was injected intraperitoneally to the rats who were under acute blood glucose fluctuation). Oxidative stress and inflammatory cytokines were detected. TUNEL was performed to detect apoptosis. Pro-caspase-3, caspase-3 p17, JNK, PKC-βII and insulin signaling-related protein expression were tested by Western blotting. After administration of LY333531, AFG-induced membrane translocation of PKCβII protein was inhibited, but SP600125 failed to affect AFG-induced PKCβII membrane translocation. After administration of LY333531, the AFG-induced increase in JNK activity was significantly compromised. LY333531 inhibited AFG-induced oxidative stress. However, SP600125 only slightly inhibited AFG-induced oxidative stress reaction (P > 0.05). Both LY333531 and SP600125 can reverse AFG-induced endothelial cell apoptosis increase, inflammatory cytokines levels rise and insulin signaling impairment. It is necessary to actively control blood glucose and avoid significant glucose fluctuation. PKCβII/JNK may serve as a target, and inhibitors of PKCβII/JNK may be used to help prevent cardiovascular diseases in patients with poor glucose control or significant glucose fluctuation.

  8. Acute and chronic effects of flavanol-rich cocoa on vascular function in subjects with coronary artery disease: a randomized double-blind placebo-controlled study.

    Science.gov (United States)

    Farouque, H M Omar; Leung, Michael; Hope, Sarah A; Baldi, Mauro; Schechter, Clyde; Cameron, James D; Meredith, Ian T

    2006-07-01

    Evidence suggests that flavonoid-containing diets reduce cardiovascular risk, but the mechanisms responsible are unclear. In the present study, we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD (coronary artery disease). Forty subjects (61+/-8 years; 30 male) with CAD were recruited to a 6-week randomized double-blind placebo-controlled study. Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily (total flavanols, 444 mg/day) or matching isocaloric placebos daily (total flavanols, 19.6 mg/day) for 6 weeks. Brachial artery FMD (flow-mediated dilation) and SAC (systemic arterial compliance) were assessed at baseline, 90 min following the first beverage and after 3 and 6 weeks of daily consumption. Soluble cellular adhesion molecules and FBF (forearm blood flow) responses to ACh (acetylcholine chloride; 3-30 microg/min) and SNP (sodium nitroprusside; 0.3-3 microg/min) infusions, forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks. FMD, SAC and FBF responses did not differ between groups at baseline. No acute or chronic changes in FMD or SAC were seen in either group. No difference in soluble cellular adhesion molecules, FBF responses to ischaemia, exercise, SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks. These data suggest that over a 6-week period, flavanol-rich cocoa does not modify vascular function in patients with established CAD.

  9. Repression of Vascular Endothelial Growth Factor Expression by the Runt-Related Transcription Factor 1 in Acute Myeloid Leukemia

    NARCIS (Netherlands)

    ter Elst, Arja; Ma, Bin; Scherpen, Frank J. G.; de Jonge, Hendrik J. M.; Douwes, Jenny; Wierenga, Albertus T. J.; Schuringa, Jan Jacob; Kamps, Willem A.; de Bont, Eveline S. J. M.

    2011-01-01

    VEGFA is considered one of the most important regulators of tumor-associated angiogenesis in cancer. In acute myeloid leukemia (AML) VEGFA is an independent prognostic factor for reduced overall and relapse-free survival. Transcriptional activation of the VEGFA promoter, a core mechanism for VEGFA

  10. Acute effect of tea, wine, beer, and polyphenols on ecto-alkaline phosphatase activity in human vascular smooth muscle cells.

    Science.gov (United States)

    Negrão, Maria R; Keating, Elisa; Faria, Ana; Azevedo, Isabel; Martins, Maria J

    2006-07-12

    Alkaline phosphatase (ALP) is an ecto-enzyme widely distributed across species. It modulates a series of transmembranar transport systems, has an important role in bone mineralization, and can also be involved in vascular calcification. Polyphenol-rich diets seem to have protective effects on human health, namely, in the prevention of cardiovascular diseases. We aimed to investigate the effects of polyphenols and polyphenol-rich beverages upon membranar alkaline phosphatase (ecto-ALP) activity in intact human vascular smooth muscle cells (AALTR). The ecto-ALP activity was determined at pH 7.8, with p-nitrophenyl phosphate as the substrate, by absorbance spectrophotometry at 410 nm. Cell viability was assessed by the lactate dehydrogenase (LDH) method, and the polyphenol content of beverages was assessed using the Folin-Ciocalteu reagent. All polyphenols tested inhibited ecto-ALP activity, in a concentration-dependent way. Teas, wines, and beers also inhibited ecto-ALP activity, largely according to their polyphenol content. All tested compounds and beverages improved or did not change AALTR cell viability. Stout beer was an exception to the described behavior. Although more studies must be done, the inhibition of AALTR ecto-ALP activity by polyphenolic compounds and polyphenol-containing beverages may contribute to their cardiovascular protective effects.

  11. Clinical value of detection on ser um monocyte chemotactant protein-1 and vascular endothelial cadher in levels in patients with acute cerebral infarction

    Directory of Open Access Journals (Sweden)

    Xia Zhou

    2016-11-01

    Full Text Available Objective: To study the correlation of serum monocyte chemotactant protein-1 (MCP-1 and vascular endothelia cadherin (VE-cadherin levels in patients with acute cerebral infarction, and nerve injury molecules, interleukins and matrix metalloproteinases. Methods: A total of 86 patients with acute cerebral infarction treated in our hospital from April 2012 to October 2015 were selected as the observation group and 50 healthy subjects in the same period treated in our hospital were selected as the control group. The serums were collected and the contents of MCP-1, VE-cadherin, heart-type fatty acid binding protein (H-FABP, S100 calcium binding protein B (S100B, neuron-specific enolase (NSE, interleukin-lb (IL-1b, IL-6, IL-17, IL-18, matrix metalloproteinase-2 (MMP2, MMP3 and MMP9 were measured. Results: The serum contents of MCP-1, VE-cadherin, H-FABP, S100B, NSE, IL-1b, IL- 6, IL-17, IL-18, MMP2, MMP3 and MMP9 in observation group were significantly higher than those of control group. Carotid artery plaque formation and unstable plaque properties will increase the serum contents of MCP-1, VE-cadherin, H-FABP, S100B, NSE, IL-1b, IL-6, IL-17, IL-18, MMP2, MMP3 and MMP9 in patients with cerebral infarction. The serum levels of MCP-1, VE-cadherin and the contents of H-FABP, S100B, NSE, IL-1b, IL-6, IL-17, IL-18, MMP2, MMP3 and MMP9 were positively correlated. Conclusions: The serum levels of VE-cadherin and MCP-1 were significantly increased in patients with acute cerebral infarction. MCP-1 and VE-cadherin can increase the secretion of interleukins and matrix metalloproteinases, which can result in the carotid artery plaque formation, unstable plaque properties and the injury of nerve function.

  12. Private Information and Insurance Rejections.

    Science.gov (United States)

    Hendren, Nathaniel

    2013-09-01

    Across a wide set of non-group insurance markets, applicants are rejected based on observable, often high-risk, characteristics. This paper argues that private information, held by the potential applicant pool, explains rejections. I formulate this argument by developing and testing a model in which agents may have private information about their risk. I first derive a new no-trade result that theoretically explains how private information could cause rejections. I then develop a new empirical methodology to test whether this no-trade condition can explain rejections. The methodology uses subjective probability elicitations as noisy measures of agents beliefs. I apply this approach to three non-group markets: long-term care, disability, and life insurance. Consistent with the predictions of the theory, in all three settings I find significant amounts of private information held by those who would be rejected; I find generally more private information for those who would be rejected relative to those who can purchase insurance; and I show it is enough private information to explain a complete absence of trade for those who would be rejected. The results suggest private information prevents the existence of large segments of these three major insurance markets.

  13. Primary HHV 6 infection after liver transplantation with acute graft rejection and multi-organ failure: successful treatment with a 2.5-fold dose of cidofovir and reduction of immunosuppression

    NARCIS (Netherlands)

    Dohna-Schwake, C.; Fiedler, M.; Gierenz, N.; Gerner, P.; Ballauf, A.; Breddemann, A.; Laer, S.; Baba, H.A.; Hoyer, P.F.

    2011-01-01

    HHV type 6 has been reported with enhanced pathogenicity in immunocompromised patients. Herein, we report about a two-yr-old girl who experienced primary HHV 6 infection after liver transplantation. She clinically presented with graft rejection and necrotic hepatitis as well as high fever,

  14. Explaining the paradoxical rejection-aggression link: the mediating effects of hostile intent attributions, anger, and decreases in state self-esteem on peer rejection-induced aggression in youth

    NARCIS (Netherlands)

    Reijntjes, A.; Thomaes, S.; Kamphuis, J.H.; Bushman, B.J.; Orobio de Castro, B.; Telch, M.J.

    2011-01-01

    People are strongly motivated to feel accepted by others. Yet when faced with acute peer rejection they often aggress against the very peers they desire acceptance from, which may lead to further rejection. The present experiment tests three potential mediators of aggressive responses to acute peer

  15. Explaining the paradoxical rejection-aggression link: The mediating effects of hostile intent attributions, anger, and decreases in state self-esteem on peer rejection-induced aggression in youth

    NARCIS (Netherlands)

    Reijntjes, A.H.A.; Thomaes, S.C.E.; Kamphuis, J.H.; Bushman, B. J.; Orobio de Castro, B.; Telch, M.J.

    2011-01-01

    People are strongly motivated to feel accepted by others. Yet when faced with acute peer rejection they often aggress against the very peers they desire acceptance from, which may lead to further rejection. The present experiment tests three potential mediators of aggressive responses to acute peer

  16. Explaining the paradoxical rejection-aggression link: The mediating effects of hostile intent attributions, anger, and decreases in state self-esteem on peer rejection-related aggression in youth

    NARCIS (Netherlands)

    Reijntjes, A.; Thomaes, S.; Kamphuis, J.H.; Bushman, B.J.; Orobio de Castro, B.; Telch, M. J.

    2011-01-01

    People are strongly motivated to feel accepted by others. Yet when faced with acute peer rejection they often aggress against the very peers they desire acceptance from, which may lead to further rejection. The present experiment tests three potential mediators of aggressive responses to acute peer

  17. Lack of nephrotoxicity of gadopentetate dimeglumine-enhanced non-vascular MRI and MRI without contrast agent in patients at high-risk for acute kidney injury.

    Science.gov (United States)

    Gok Oguz, Ebru; Kiykim, Ahmet; Turgutalp, Kenan; Olmaz, Refik; Ozhan, Onur; Muslu, Necati; Horoz, Mehmet; Bardak, Simge; Sungur, Mehmet Ali

    2013-11-06

    Gadolinium chelates (GCs) have been traditionally considered as non-nephrotoxic magnetic resonance imaging (MRI) contrast materials. However, it has been suggested in some recent articles that GCs may have a nephrotoxic potential, but most of these reports are retrospective. However, the evaluated contrast agents, their doses, and the tests used to determine the kidney function were not consistent across studies. We aimed to investigate the effect of magnetic field and an MRI contrast agent, gadopentetate dimeglumine (GD), on renal functions in patients at high risk for acute kidney injury (AKI). We designed a prospective case-control study with 2 age- and sex-matched groups of patients at high-risk for AKI (n=72 for each group). Patients in Group 1 received a fixed dose of (0.2 mmol/kg) GD-enhanced non-vascular MRI and patients in Group 2 received MRI without GD. Before the MRI and at 6, 24, 72, and 168 hours after the MRI, biochemical tests, estimated glomerular filtration rate (eGFR), albumin/creatinine ratio in spot urine, and early AKI biomarkers (cystatin C, N-Acetyl-Glucosaminidase [NAG], Neutrophil gelatinase-associated lipocalin [NGAL]) were measured. Serum creatinine, albumin/creatinine ratio, and eGFR were not different between Group 1 and 2 (p>0.05). There were no significant changes in renal function tests and AKI biomarkers (∆serum creatinine, ∆albumin/creatinine ratio, ∆GFR, ∆cystatin C, ∆NAG, and ∆NGAL) for either groups 6, 24, 72, and 168 hours after the procedures (p>0.05). MRI without contrast agent and non-vascular contrast-enhanced (GD, 0.2 mmol/kg) MRI are not nephrotoxic procedures for patients at high risk for AKI.

  18. Acute Effects of Nitrate-Rich Beetroot Juice on Blood Pressure, Hemostasis and Vascular Inflammation Markers in Healthy Older Adults: A Randomized, Placebo-Controlled Crossover Study

    Directory of Open Access Journals (Sweden)

    Kyle Raubenheimer

    2017-11-01

    Full Text Available Aging is associated with a vasoconstrictive, pro-coagulant, and pro-inflammatory profile of arteries and a decline in the bioavailability of the endothelium-derived molecule nitric oxide. Dietary nitrate elicits vasodilatory, anti-coagulant and anti-inflammatory effects in younger individuals, but little is known about whether these benefits are evident in older adults. We investigated the effects of 140 mL of nitrate-rich (HI-NI; containing 12.9 mmol nitrate versus nitrate-depleted beetroot juice (LO-NI; containing ≤0.04 mmol nitrate on blood pressure, blood coagulation, vascular inflammation markers, plasma nitrate and nitrite before, and 3 h and 6 h after ingestion in healthy older adults (five males, seven females, mean age: 64 years, age range: 57–71 years in a randomized, placebo-controlled, crossover study. Plasma nitrate and nitrite increased 3 and 6 h after HI-NI ingestion (p < 0.05. Systolic, diastolic and mean arterial blood pressure decreased 3 h relative to baseline after HI-NI ingestion only (p < 0.05. The number of blood monocyte-platelet aggregates decreased 3 h after HI-NI intake (p < 0.05, indicating reduced platelet activation. The number of blood CD11b-expressing granulocytes decreased 3 h following HI-NI beetroot juice intake (p < 0.05, suggesting a shift toward an anti-adhesive granulocyte phenotype. Numbers of blood CD14++CD16+ intermediate monocyte subtypes slightly increased 6 h after HI-NI beetroot juice ingestion (p < 0.05, but the clinical implications of this response are currently unclear. These findings provide new evidence for the acute effects of nitrate-rich beetroot juice on circulating immune cells and platelets. Further long-term research is warranted to determine if these effects reduce the risk of developing hypertension and vascular inflammation with aging.

  19. Electrocardiographic abnormalities in acute cerebro-vascular accidents and their correlation with cerebro-spinal fluid pressure and serum electrolytes

    Directory of Open Access Journals (Sweden)

    Gambhir M

    1978-01-01

    Full Text Available Electrocardiographic studies have been carried out in 50 patients with acute cerebrovascular accidents. These cases included 31 cases from non-haemorrhagic group and 19 cases from haemor-rhagic group. `T′ or T-U wave abnormalities were seen in 63.1% of cases in haemorrhagic group and in 35.4% of cases from non-hae-morrhagic group. Abnormal prolongation of QTc interval (105% of normal i.e. 0.45 Secs. was observed in 73.6% cases from haemorrhagic group and in 35.4% of cases from non-haemorrhagic group. On comparing these two groups it was found that QTc was signi-ficantly more prolonged in patiens of haemorrhagic group than non--haemorrhagic group. The CSF pressure was found to be signi-ficantly more in patients with ECG abnormalities. However, there teas no correlation between serum electrolyte levels and ECG abnormalities. After 2 weeks, the ECG abnormalities disappeared, except in two cases from haemorrhagic group. There was no signi-ficant difference in the incidence of mortality between patient having ECG abnormalities and the patients without ECG abnormalities. In the light of these findings the probable mechanism of production of ECG changes in acute cerebrovascular accidents is discussed.

  20. FLAIR-hyperintense vessel sign, diffusion-perfusion mismatch and infarct growth in acute ischemic stroke without vascular recanalisation therapy.

    Science.gov (United States)

    Gawlitza, Matthias; Gragert, Jasmin; Quäschling, Ulf; Hoffmann, Karl Titus

    2014-10-01

    To investigate the relation between DWI-PWI mismatch and FLAIR-hyperintense vessel (FHV) sign and their influence on the prediction of the infarct growth in stroke patients without vessel recanalising therapy. Thirty-three patients with non-lacunar acute stroke and not eligible for recanalisation therapy received cerebral MRI at the day of admission and after 7±1 days. DWI and PWI lesion volumes, DWI-PWI mismatch volumes, infarct growth, relative mismatch and relative infarct growth were assessed. FHV sign was subdivided into (i) proximal or (ii) distal, the latter graded as either (i) prominent or (ii) subtle. FHV sign did not predict absolute or relative infarct growth. Significantly larger DWI lesions, PWI lesions and mismatch volumes were observed in FHV-positive infarcts. There were significant correlations between the degree of FHV sign and PWI lesion volume (r=0.52; PPWI mismatch and relative infarct growth (r=0.91; PPWI lesion volumes and DWI-to-PWI mismatch volumes in acute stroke and thus seems to be an indicator of collateral flow. However, it is unsuitable to predict infarct growth. The latter occurred when DWI-to-PWI mismatches were present with bigger relative mismatch volumes making subsequent infarct growth more likely. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans

    Science.gov (United States)

    Perkins, Jennifer M.; Joy, Nino G.; Tate, Donna B.

    2015-01-01

    We investigated the separate and combined effects of hyperglycemia and hyperinsulinemia on markers of endothelial function, proinflammatory and proatherothrombotic responses in overweight/obese nondiabetic humans. Twenty-two individuals (13 F/9 M, BMI 30.1 ± 4.1 kg/m2) were studied during four randomized, single-blind protocols. The pancreatic clamp technique was combined with 4-h glucose clamps consisting of either 1) euinsulinemia-euglycemia, 2) euinsulinemia-hyperglycemia, 3) hyperinsulinemia-hyperglycemia, or 4) hyperinsulinemia-euglycemia. Insulin levels were higher (998 ± 66 vs. 194 ± 22 pmol/l) during hyperinsulinemia compared with euinsulinemia. Glucose levels were 11.1 mmol/l during hyperinsulinemia compared with 5.1 ± 0.1 mmol/l during euglycemia. VCAM, ICAM, P-selectin, E-selectin, IL-6, adiponectin, and PAI-1 responses were all increased (P hyperglycemia compared with other protocols. Hyperinsulinemia in the presence of hyperglycemia prevented the increase in proinflammatory and proatherothrombotic markers while also normalizing vascular endothelial function. We conclude that 4 h of moderate hyperglycemia can result in increases of proinflammatory markers (ICAM, VCAM, IL-6, E-selectin), platelet activation (P-selectin), reduced fibrinolytic balance (increased PAI-1), and disordered endothelial function in a group of obese and overweight individuals. Hyperinsulinemia prevents the actions of moderate hyperglycemia to reduce endothelial function and increase proinflammatory and proatherothrombotic markers. PMID:26015434

  2. [Flow cytometry controlled induction therapy with ATG and noninvasive monitoring of rejection--a modern management concept after heart transplantation].

    Science.gov (United States)

    Wagner, F M; Tugtekin, S M; Matschke, K; Platzbecker, U; Gulielmos, V; Schüler, S

    1998-01-01

    We introduce our concept of non-invasive transplant monitoring. The introduction of individualized immunosuppression by means of flow cytometry leads to a lower incidence of acute graft rejection and preserves immuncompetence. With the simultaneous use of echocardiography and intramyocardial electrogram (IMEG) acute graft rejections can be safely identified without using any invasive method.

  3. Low CD4/CD8 Ratio in Bronchus-Associated Lymphoid Tissue Is Associated with Lung Allograft Rejection.

    Science.gov (United States)

    Shenoy, K V; Solomides, C; Cordova, F; Rogers, T J; Ciccolella, D; Criner, G J

    2012-01-01

    Background. Bronchus-associated lymphoid tissue (BALT) has been associated with lung allograft rejection in rat transplant models. In human transplant recipients, BALT has not been linked to clinically significant rejection. We hypothesize that the immunohistochemical composition of BALT varies with the presence of acute lung allograft rejection. Methods. We retrospectively examined 40 human lung allograft recipients transplanted from 3/1/1999 to 6/1/2008. Patients were grouped by frequency and severity of acute rejection based on International Society of Heart Lung Transplant (ISHLT) criteria. Transbronchial biopsies were reviewed for BALT by a blinded pathologist. BALT if present was immunohistochemically stained to determine T-and B-cell subpopulations. Results. BALT presence was associated with an increased frequency of acute rejection episodes in the first year after transplantation. Patients with a lower CD4/CD8 ratio had an increased rejection rate; however, BALT size or densities of T-cell and B-cell subpopulations did not correlate with rejection rate. Conclusion. The presence of BALT is associated with an increased frequency of rejection one year after transplant. The lower the CD4/CD8 ratio, the more acute rejection episodes occur in the first year after transplantation. The immunohistochemical composition of BALT may predict patients prone to frequent episodes of acute cellular rejection.

  4. Low CD4/CD8 Ratio in Bronchus-Associated Lymphoid Tissue Is Associated with Lung Allograft Rejection

    Directory of Open Access Journals (Sweden)

    K. V. Shenoy

    2012-01-01

    Full Text Available Background. Bronchus-associated lymphoid tissue (BALT has been associated with lung allograft rejection in rat transplant models. In human transplant recipients, BALT has not been linked to clinically significant rejection. We hypothesize that the immunohistochemical composition of BALT varies with the presence of acute lung allograft rejection. Methods. We retrospectively examined 40 human lung allograft recipients transplanted from 3/1/1999 to 6/1/2008. Patients were grouped by frequency and severity of acute rejection based on International Society of Heart Lung Transplant (ISHLT criteria. Transbronchial biopsies were reviewed for BALT by a blinded pathologist. BALT if present was immunohistochemically stained to determine T-and B-cell subpopulations. Results. BALT presence was associated with an increased frequency of acute rejection episodes in the first year after transplantation. Patients with a lower CD4/CD8 ratio had an increased rejection rate; however, BALT size or densities of T-cell and B-cell subpopulations did not correlate with rejection rate. Conclusion. The presence of BALT is associated with an increased frequency of rejection one year after transplant. The lower the CD4/CD8 ratio, the more acute rejection episodes occur in the first year after transplantation. The immunohistochemical composition of BALT may predict patients prone to frequent episodes of acute cellular rejection.

  5. Does borderline kidney allograft rejection always require treatment?

    Science.gov (United States)

    Németh, Dorottya; Ovens, Jörg; Opelz, Gerhard; Sommerer, Claudia; Döhler, Bernd; Becker, Luis E; Gross, Marie-Luise; Waldherr, Rüdiger; Mieth, Markus; Sadeghi, Mahmoud; Schmidt, Jan; Langer, Robert M; Zeier, Martin; Süsal, Caner

    2010-08-27

    Borderline rejection (Bord-R) is a frequent diagnosis in renal transplantation, and there is increasing evidence that regulatory T lymphocytes are involved in its pathogenesis. Current histopathologic practice does not differentiate between graft-protecting and -damaging T lymphocytes, and patients with Bord-R routinely receive rejection treatment. We analyzed Treg-associated forkhead box P3 (Foxp3) gene expression in Bord-R and more severe forms of acute rejection episodes (ARE). Foxp3 transcripts were measured in 520 serial peripheral blood samples from 177 kidney graft recipients obtained during the first 20 days posttransplantation. The highest Foxp3 transcripts were observed in patients with Bord-R or without rejection and the lowest in patients with ARE. Patients with Bord-R on posttransplant days 5 to 7 showed an increased Foxp3 transcript level of 156%, which increased to 302% by posttransplant days 14 to 16. In contrast, patients with ARE demonstrated significantly lower Foxp3 gene expression than that observed in Bord-R, nonrejectors, or acute tubular necrosis patients (P=0.001, PBord-R. This finding questions the appropriateness of rejection treatment in all patients with the histopathologic diagnosis "Bord-R".

  6. Fragmentation of care threatens patient safety in peripheral vascular catheter management in acute care--a qualitative study.

    Science.gov (United States)

    Castro-Sánchez, Enrique; Charani, Esmita; Drumright, Lydia N; Sevdalis, Nick; Shah, Nisha; Holmes, Alison H

    2014-01-01

    The use of peripheral vascular catheters (PVCs) is an extremely common and necessary clinical intervention, but inappropriate PVC care poses a major patient safety risk in terms of infection. Quality improvement initiatives have been proposed to reduce the likelihood of adverse events, but a lack of understanding about factors that influence behaviours of healthcare professionals limits the efficacy of such interventions. We undertook qualitative interviews with clinical staff from a large group of hospitals in order to understand influences on PVC care behaviors and subsequent patient safety. Ten doctors, ten clinical pharmacists, 18 nurses and one midwife at a National Health Service hospital group in London (United Kingdom) were interviewed between December 2010 and July 2011 using qualitative methods. Responses were analysed using a thematic framework. FOUR KEY THEMES EMERGED: 1) Fragmentation of management and care, demonstrated with a lack of general overview and insufficient knowledge about expected standards of care or responsibility of different professionals; 2) feelings of resentment and frustration as a result of tensions in the workplace, due to the ambiguity about professional responsibilities; 3) disregard for existing hospital policy due to perceptions of flaws in the evidence used to support it; and 4) low-risk perception for the impact of PVC use on patient safety. Fragmentation of practice resulted in ill-defined responsibilities and interdisciplinary resentment, which coupled with a generally low perception of risk of catheter use, appeared to result in lack of maintaining policy PVC standards which could reduced patient safety. Resolution of these issues through clearly defining handover practice, teaching interdisciplinary duties and increasing awareness of PVC risks could result in preventing thousands of BSIs and other PVC-related infections annually.

  7. The Relationship of Anti-MICA Antibodies and MICA Expression with Heart Allograft Rejection

    National Research Council Canada - National Science Library

    Suarez-Alvarez, B; Lopez-Vazquez, A; Gonzalez, M. Zapico; Fdez-Morera, J. L; Diaz-Molina, B; Blanco-Gelaz, M. A; Pascual, D; Martinez-Borra, J; Muro, M; Alvarez-Lopez, M. R; Lopez-Larrea, C

    2007-01-01

    The role of MICA antibodies in acute heart allograft rejection was examined utilizing 190 pre- and post-transplant serum samples from 44 patients collected during the first year after transplantation...

  8. Analysis of Sera of Recipients with Allograft Rejection Indicates That Keratin 1 Is the Target of Anti-Endothelial Antibodies

    OpenAIRE

    Xuli Guo; Juan Hu; Weiguang Luo; Qizhi Luo; Jing Guo; Fang Tian; Yingzi Ming; Yizhou Zou

    2017-01-01

    Anti-endothelial cell antibodies (AECAs) are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera...

  9. Optical coherence tomography based microangiography for quantitative monitoring of structural and vascular changes in a rat model of acute uveitis in vivo: a preliminary study.

    Science.gov (United States)

    Choi, Woo June; Pepple, Kathryn L; Zhi, Zhongwei; Wang, Ruikang K

    2015-01-01

    Uveitis models in rodents are important in the investigation of pathogenesis in human uveitis and the development of appropriate therapeutic strategies for treatment. Quantitative monitoring of ocular inflammation in small animal models provides an objective metric to assess uveitis progression and/or therapeutic effects. We present a new application of optical coherence tomography (OCT) and OCT-based microangiography (OMAG) to a rat model of acute anterior uveitis induced by intravitreal injection of a killed mycobacterial extract. OCT/OMAG is used to provide noninvasive three-dimensional imaging of the anterior segment of the eyes prior to injection (baseline) and two days post-injection (peak inflammation) in rats with and without steroid treatments. OCT imaging identifies characteristic structural and vascular changes in the anterior segment of the inflamed animals when compared to baseline images. Characteristics of inflammation identified include anterior chamber cells, corneal edema, pupillary membranes, and iris vasodilation. In contrast, no significant difference from the control is observed for the steroid-treated eye. These findings are compared with the histology assessment of the same eyes. In addition, quantitative measurements of central corneal thickness and iris vessel diameter are determined. This pilot study demonstrates that OCT-based microangiography promises to be a useful tool for the assessment and management of uveitis in vivo.

  10. Optical coherence tomography based microangiography for quantitative monitoring of structural and vascular changes in a rat model of acute uveitis in vivo: a preliminary study

    Science.gov (United States)

    Choi, Woo June; Pepple, Kathryn L.; Zhi, Zhongwei; Wang, Ruikang K.

    2015-01-01

    Uveitis models in rodents are important in the investigation of pathogenesis in human uveitis and the development of appropriate therapeutic strategies for treatment. Quantitative monitoring of ocular inflammation in small animal models provides an objective metric to assess uveitis progression and/or therapeutic effects. We present a new application of optical coherence tomography (OCT) and OCT-based microangiography (OMAG) to a rat model of acute anterior uveitis induced by intravitreal injection of a killed mycobacterial extract. OCT/OMAG is used to provide noninvasive three-dimensional imaging of the anterior segment of the eyes prior to injection (baseline) and two days post-injection (peak inflammation) in rats with and without steroid treatments. OCT imaging identifies characteristic structural and vascular changes in the anterior segment of the inflamed animals when compared to baseline images. Characteristics of inflammation identified include anterior chamber cells, corneal edema, pupillary membranes, and iris vasodilation. In contrast, no significant difference from the control is observed for the steroid-treated eye. These findings are compared with the histology assessment of the same eyes. In addition, quantitative measurements of central corneal thickness and iris vessel diameter are determined. This pilot study demonstrates that OCT-based microangiography promises to be a useful tool for the assessment and management of uveitis in vivo.

  11. Erythropoietin does not have effects on the ventilatory and pulmonary vascular response to acute hypoxia in men and women.

    Science.gov (United States)

    Berendsen, Remco R; Lindeman, Rob C; Boom, Merel; Aarts, Leon P H J; van Dorp, Eveline L A; Teppema, Luc J

    2016-07-13

    Sustained and chronic hypoxia lead to a rise in pulmonary ventilation (hypoxic ventilatory response, HVR) and to an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction, HPV). In this study, we examined the effect of a clinical intravenous dose of recombinant human erythropoietin (rHuEPO,50 IU kg(-1) ) on the isocapnic HVR and HPV in 7 male and 7 female subjects by exposing them to hypoxia for 20 min (end-tidal PO2  ∼ 50 mmHg) while measuring their ventilation and estimating pulmonary arterial pressure from the maximal velocity of the regurgitant jet over the tricuspid valve during systole (ΔPmax) with echocardiography. In placebo, after 5 and 20 min, men responded with a rise in ventilation by 0.0056 and 0.0023 l/min/kg/%SpO2 , respectively, indicating the presence of hypoxic ventilatory depression. In women, the rise in ventilation was 0.0067 and 0.0047 l/min/kg/%SpO2 , respectively. In both sexes, EPO did not alter these responses significantl . In placebo, mean ΔPmax rose by 6.1 ± 0.7 mmHg in men P = 0.035) and by 8.4 ± 1.4 mmHg in women (P = 0.020) during the hypoxic exposure whereby women had a ∼5 mmHg lower end-tidal PCO2 . EPO did not alter these responses: in men a rise in ΔPmax by 7.5 ± 1.1 mmHg (NS vs. placebo) and in women by 9.7 ± 2.2 mmHg (NS vs. placebo). We conclude that women tended to have a greater HPV in placebo and that a clinical dose of EPO has no effect on the HVR and HPV in either sex This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

    Science.gov (United States)

    Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y.; Castoldi, Ângela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

    2012-01-01

    Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA. PMID:22952850

  13. Heat Shock Protein A12B Protects Vascular Endothelial Cells Against Sepsis-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Yi Chen

    2017-05-01

    Full Text Available Background: Pulmonary endothelial injury is a critical process in the pathogenesis of acute lung injury (ALI during sepsis. Heat shock protein A12B (HSPA12B is mainly expressed in endothelial cells and protects against several harmful factors. However, the effects of HSPA12B in sepsis-induced ALI and its potential mechanisms of action remain unclear. Methods: For in vivo experiments, C57BL/6 mice were randomly divided into four groups (n=15: a sham operation group, a cecal ligation and puncture (CLP group, a HSPA12B siRNA-CLP group and a negative control (NC siRNA-CLP group. The mice were treated by nasal inhalation of 2-OMe-modified HSPA12B siRNA or NC siRNA. Sepsis was induced by CLP. Samples were harvested 24 and 48 hours post-CLP surgery. Pathological changes and scoring of lung tissue samples were monitored using hematoxylin and eosin staining. Levels of pro-inflammatory cytokines (e.g., interleukin (IL-1β, tumor necrosis factor (TNF-α, and IL-6 and myeloperoxidase activity in bronchoalveolar lavage fluid were analyzed by ELISA. Pulmonary edema was assessed using a wet-to-dry weight ratio. Neutrophils and alveolar macrophages were counted using flow cytometry. Pulmonary endothelial cell apoptosis was detected by TUNEL staining. Expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blot analysis. In addition, 7-day survival was recorded. For in vitro experiments, human umbilical vein endothelial cells were pre-transfected with HSPA12B siRNA or pIRES2-EGFP-HSPA12B-Flag plasmid and treated with lipopolysaccharide; subsequently, the expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blotting. Results: Nasal inhalation of nano-polymer-encapsulated HSPA12B siRNA specifically downregulated mRNA and protein expression levels of HSPA12B in lung tissues. The administration of HSPA12B siRNA aggravated lung pathological injury, upregulated pro-inflammatory cytokine (e

  14. Acute and 3-month effects of calcium carbonate on the calcification propensity of serum and regulators of vascular calcification: secondary analysis of a randomized controlled trial.

    Science.gov (United States)

    Bristow, S M; Gamble, G D; Pasch, A; O'Neill, W C; Stewart, A; Horne, A M; Reid, I R

    2016-03-01

    Calcium supplements have been associated with increased cardiovascular risk, but the mechanism is unknown. We investigated the effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50). Changes in serum calcium were related to changes in T50. Calcium supplements have been associated with increased cardiovascular risk; however, it is unknown whether this is related to an increase in vascular calcification. We investigated the acute and 3-month effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50), and on three possible regulators of calcification: fetuin-A, pyrophosphate and fibroblast growth factor-23 (FGF23). We randomized 41 postmenopausal women to 1 g/day of calcium as carbonate, or to a placebo containing no calcium. Measurements were performed at baseline and then 4 and 8 h after their first dose, and after 3 months of supplementation. Fetuin-A, pyrophosphate and FGF23 were measured in the first 10 participants allocated to calcium carbonate and placebo who completed the study. T50 declined in both groups, the changes tending to be greater in the calcium group. Pyrophosphate declined from baseline in the placebo group at 4 h and was different from the calcium group at this time point (p = 0.04). There were no other significant between-groups differences. The changes in serum total calcium from baseline were significantly related to changes in T50 at 4 h (r = -0.32, p = 0.05) and 8 h (r = -0.39, p = 0.01), to fetuin-A at 3 months (r = 0.57, p = 0.01) and to pyrophosphate at 4 h (r = 0.61, p = 0.02). These correlative findings suggest that serum calcium concentrations modulate the propensity of serum to calcify (T50), and possibly produce counter-regulatory changes in pyrophosphate and fetuin-A. This provides a possible mechanism by which

  15. Vascular Cures

    Science.gov (United States)

    ... is the first national program to bring the power of the patient to vascular research and care. ... Our recent national Vascular Research Summit brought together leaders from 31 institutions to generate collaborative projects for ...

  16. Association between a gain-of-function variant of PTPN22 and rejection in liver transplantation.

    Science.gov (United States)

    Dullin, Raphael; Koch, Martina; Sterneck, Martina; Nashan, Björn; Thude, Hansjörg

    2015-02-01

    The protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) encodes a strong T-cell regulator called lymphoid protein tyrosine phosphatase. Previously, PTPN22 was described as a susceptibility gene for autoimmunity because it contains single nucleotide polymorphisms (SNPs) associated with several autoimmune diseases. One SNP (rs2476601; 1858G>A) has emerged as a particularly potent risk factor for autoimmunity. We address the question whether PTPN22 polymorphisms are also associated with acute rejection after liver transplantation. We investigated the influence of six PTPN22 SNPs on the susceptibility to acute liver allograft rejection. Consequently, we carried out a retrospective study genotyping 345 German liver recipients at six SNP loci, which include rs2488457 (-1123G>C), rs33996649 (788C>T), rs2476601 (1858G>A), rs1310182 (-852A>G), rs1217388 (-2200G>A), rs3789604 (64434T>G). Our study enrolled 165 recipients who did not develop rejection, 123 who showed one rejection episode, and 57 patients who suffered from multiple acute rejections after transplantation. The 1858A allele containing genotypes (GA+AA) and the 1858A allele had a significantly higher frequency in the group of patients with multiple rejection episodes (35.1% and 18.4%) compared to rejection-free patients (15.8% and 7.9%; P=0.022 and 0.023). In contrast, we could not detect any association between rejection and the other tested SNPs. Additionally, we identified one haplotype contributing to risk of multiple rejections, however, exhibiting no stronger impact than the 1858A allele alone. We conclude that the 1858G>A SNP may confer susceptibility to multiple acute liver transplant rejections in the German population.

  17. Prognostic value of blood glucose in emergency room and glycosylated hemoglobin in patients who have suffered an acute cerebro-vascular event.

    Science.gov (United States)

    Ernaga Lorea, Ander; Hernández Morhain, María Cecilia; Ollero García-Agulló, María Dolores; Martínez de Esteban, Juan Pablo; Iriarte Beroiz, Ana; Gállego Culleré, Jaime

    2017-07-07

    Stress hyperglycemia has been associated with a worse prognosis in patients hospitalized in critical care units. The aim of this study is to evaluate the impact of blood glucose and glycosylated hemoglobin (HbA1c) levels on the mortality of patients suffering a acute cerebro-vascular event, and to determine if this relationship depends on the presence of diabetes. A retrospective analysis of 255 patients admitted to the ER for stroke was performed. Venous plasma glucose levels in the emergency room and HbA1c levels within the first 48hours were analyzed. The presence of diabetes was defined in terms of the patients' medical history, as well as their levels of fasting plasma glucose and HbA1c. Mortality was assessed within the first 30 months after the onset of the acute event. 28.2% of patients had diabetes. Higher mortality was observed in patients who had been admitted with plasma glucose levels≥140mg/dl (hazard ratio [HR]=2.22, 95% CI: 1.18-4.16, P=.013) after adjusting for various factors. This relationship was not confirmed in diabetic patients (HR=2.20, 95% CI: 0.66-7.40, P=.201) and was in non-diabetics (HR=2.55, 95% CI: 1.11-5.85, P=.027). In diabetics, HbA1c≥7% was not associated with poor prognosis (HR=0.68, 95% CI: 0.23-1.98, P=.475), whereas non-diabetics with admission levels of HbA1c falling within the pre-diabetes range (5.7% -6.4%) had a higher mortality (HR=2.62, 95% CI: 1.01-6.79, P=.048). Admission hyperglycemia is associated with a worse prognosis in patients without diabetes admitted for stroke, but this relationship was not seen in diabetics. In non-diabetic patients, HbA1c levels in the pre-diabetes range is associated with higher mortality. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  18. Early vascular healing after titanium-nitride-oxide-coated stent versus platinum-chromium everolimus-eluting stent implantation in patients with acute coronary syndrome.

    Science.gov (United States)

    Varho, Ville; Kiviniemi, Tuomas O; Nammas, Wail; Sia, Jussi; Romppanen, Hannu; Pietilä, Mikko; Airaksinen, Juhani K; Mikkelsson, Jussi; Tuomainen, Petri; Perälä, Anssi; Karjalainen, Pasi P

    2016-07-01

    Data on early vascular healing response of novel stent designs are scarce. In this randomized prospective trial, we sought to compare early neointimal coverage of cobalt-chromium-based titanium-nitride-oxide-coated bioactive stents (CoCr-BAS) versus platinum-chromium everolimus-eluting stents (PtCr-EES) at 2-month follow-up in patients with acute coronary syndrome (ACS). Forty patients with ACS were randomized to receive either CoCr-BAS (n = 19) or PtCr-EES (n = 21). Neointimal strut coverage and strut apposition were examined by optical coherence tomography; and coronary flow reserve (CFR), fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) were assessed using a coronary pressure wire at 2 months. Two patients in the PtCr-EES underwent OCT out of the time frame of the study, and were excluded from analysis. At 63 ± 8 days, 302 cross-sections (3412 struts) were analysed in the CoCr-BAS group, and 324 cross-sections (3460 struts) in the PtCr-EES group. Median [IQR] neointimal thickness was 203 [108] µm and 42.2 [41] µm for CoCr-BAS and PtCr-EES, respectively (p  0.05 for all). CoCr-BAS showed earlier and more adequate neointimal coverage of struts at 2 months, compared with PtCr-EES, but with more neointimal hyperplasia. Functional healing as assessed by CFR, FFR, and IMR was similar between the two stent arms.

  19. After acute coronary syndrome, diabetic patients with peripheral vascular disease remain at high risk of cardiovascular events despite secondary prevention measures.

    Science.gov (United States)

    Lafitte, Marianne; Barandon, Laurent; Pucheu, Yann; Pillois, Xavier; Gin, Henri; Bonnet, Jacques; Couffinhal, Thierry

    2010-02-01

    Peripheral vascular disease (PVD) is associated with a high risk of cardiovascular events after an acute coronary syndrome (ACS). The impact of suboptimal risk-factor control and drug prescription on morbidity and mortality rates in patients with PVD following an ACS remains to be established. To assess whether a global atherosclerosis management programme and optimal secondary prevention could benefit high-risk PVD patients after an ACS. A total of 851 ACS patients underwent an intensified intervention focusing on evaluating risk factors and atherosclerosis lesions, and on optimizing treatment and education. We compared its impact on long-term risk factors, medication observance and cardiovascular outcomes in patients with coronary artery disease (CAD) alone (n=715, 84.0%) and with both CAD and PVD (n=136). At a median follow-up of 18.6months, both groups reached recommended secondary prevention goals and showed no significant differences in rates of drug prescription. PVD was not associated with minor cardiovascular events (hazard ratio [HR] 1.32, 95% confidence interval [CI] 0.57-3.02) but remained independently associated with major (HR 2.15, 95% CI 1.12-4.13) and total (HR 1.76, 95% CI 1.05-2.93) cardiovascular events. Compared to patients with CAD alone, this risk was significantly higher in CAD patients with both PVD and diabetes (HR 2.87, 95% CI 1.52-5.43), but not in PVD patients without diabetes (HR 1.35, 95% CI 0.71-2.56) or diabetic patients without PVD (HR 1.11, 95% CI 0.68-1.81). Despite optimization of risk-factor control and drug prescription after ACS, patients with both PVD and diabetes carry a 2.9-fold higher risk of cardiovascular events at 18-month follow-up versus patients with CAD alone. This excess risk was not significant in PVD patients without diabetes or in diabetic patients without PVD.

  20. Cardio-Ankle Vascular Index and C-Reactive Protein Are Useful Parameters for Identification of Ischemic Heart Disease in Acute Heart Failure Patients.

    Science.gov (United States)

    Kiuchi, Shunsuke; Hisatake, Shinji; Kabuki, Takayuki; Oka, Takashi; Dobashi, Shintaro; Fujii, Takahiro; Ikeda, Takanori

    2017-05-01

    The most common cause of heart failure (HF) is ischemic heart disease (IHD). Evaluation of IHD with non-invasive examinations is useful for the treatment of HF, and cardio-ankle vascular index (CAVI) is a good parameter for detecting systemic arteriosclerosis. However, the relationship between IHD and CAVI in acute HF (AHF) patients is still unclear. Therefore, we investigated the effect of non-invasive examinations, including CAVI to detect IHD. We studied 53 consecutive patients (average age of 66.5 ± 10.9 years old, 36 males) with AHF from January 2009 to December 2012. These patients were classified into the IHD group (n = 19) and non-IHD group (n = 34) according to the coronary artery angiography results. We evaluated the vital signs, laboratory findings and CAVI. According to the laboratory findings, the C-reactive protein (CRP) in IHD group was significantly higher than non-IHD group (1.5 ± 2.1 mg/dL vs. 0.4 ± 0.4 mg/dL, P = 0.002). CAVI in IHD group was significantly higher than non-IHD group (9.58 ± 1.73 vs. 7.83 ± 1.86, P < 0.001). In the receiver operating characteristic (ROC) curve for discriminating the probability of IHD, the cut-off point of the CRP plus CAVI was 9.00. At that cut-off point, the sensitivity and the specificity were 69.7% and 89.5%, respectively. The mean area under the ROC curve (AUC) defined by the CRP plus CAVI was the greatest at all parameters. The CRP and CAVI were useful parameters for the identification of IHD in patients with AHF.

  1. Current perspectives on antibody-mediated rejection after lung transplantation

    Directory of Open Access Journals (Sweden)

    Witt CA

    2014-10-01

    Full Text Available Chad A Witt, Ramsey R Hachem Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO, USA Abstract: The role of donor-specific antibodies (DSA to human leukocyte antigens and the burden of antibody-mediated rejection (AMR in lung transplantation remain enigmatic. Over the past several years, evidence has been emerging that humoral immunity plays an important role in the development of both acute and chronic lung allograft dysfunction (CLAD. Multiple case reports and case series have identified lung allograft recipients with clinical findings consistent with acute AMR. However, there is currently no widely accepted definition for AMR in lung transplantation, and this has been a significant barrier to furthering our understanding of this form of rejection. Nonetheless, the development of DSA after transplantation has consistently been identified as an independent risk factor for persistent and high-grade acute cellular rejection and CLAD. This has raised the possibility that chronic AMR may be a distinct phenotype of CLAD although evidence supporting this paradigm is still lacking. Additionally, antibodies to lung-restricted self-antigens (collagen V and K-α 1 tubulin have been associated with primary graft dysfunction early and the development of CLAD late after transplantation, and emerging evidence underscores significant interactions between autoimmunity and alloimmunity after transplantation. There is currently an active International Society for Heart and Lung Transplantation working group that is developing an operational definition for AMR in lung transplantation. This will be critical to improve our understanding of this form of rejection and conduct clinical trials to identify optimal treatment strategies. This review will summarize the literature on DSA and AMR in lung transplantation and discuss the impact of antibodies to self-antigens on lung

  2. Nucleic Acid Drugs for Prevention of Cardiac Rejection

    Directory of Open Access Journals (Sweden)

    Jun-ichi Suzuki

    2009-01-01

    Full Text Available Heart transplantation has been broadly performed in humans. However, occurrence of acute and chronic rejection has not yet been resolved. Several inflammatory factors, such as cytokines and adhesion molecules, enhance the rejection. The graft arterial disease (GAD, which is a type of chronic rejection, is characterized by intimal thickening comprised of proliferative smooth muscle cells. Specific treatments that target the attenuation of acute rejection and GAD formation have not been well studied in cardiac transplantation. Recent progress in the nucleic acid drugs, such as antisense oligodeoxynucleotides (ODNs to regulate the transcription of disease-related genes, has important roles in therapeutic applications. Transfection of cis-element double-stranded DNA, named as “decoy,” has been also reported to be a useful nucleic acid drug. This decoy strategy has been not only a useful method for the experimental studies of gene regulation but also a novel clinical strategy. In this paper, we reviewed the experimental results of NF-κB, E2F, AP-1, and STAT-1 decoy and other ODNs using the experimental heart transplant models.

  3. Rejection sensitivity and symptom severity in patients with borderline personality disorder: effects of childhood maltreatment and self-esteem.

    Science.gov (United States)

    Bungert, Melanie; Liebke, Lisa; Thome, Janine; Haeussler, Katrin; Bohus, Martin; Lis, Stefanie

    2015-01-01

    Interpersonal dysfunction in Borderline Personality Disorder (BPD) is characterized by an 'anxious preoccupation with real or imagined abandonment' (DSM-5). This symptom description bears a close resemblance to that of rejection sensitivity, a cognitive affective disposition that affects perceptions, emotions and behavior in the context of social rejection. The present study investigates the level of rejection sensitivity in acute and remitted BPD patients and its relation to BPD symptom severity, childhood maltreatment, and self-esteem. Data were obtained from 167 female subjects: 77 with acute BPD, 15 with remitted BPD, and 75 healthy controls who were matched with the patients for age and education. The instruments used for assessment were the Rejection Sensitivity Questionnaire, the short version of the Borderline Symptom List, the Childhood Trauma Questionnaire, and the Rosenberg Self-Esteem Scale. Both acute and remitted BPD patients had higher scores on the Rejection Sensitivity Questionnaire than did healthy controls. Lower self-esteem was found to be positively correlated with both increased BPD symptom severity and higher rejection sensitivity, and mediated the relation between the two. History of childhood maltreatment did not correlate with rejection sensitivity, BPD symptom severity, or self-esteem. Our findings support the hypothesis that rejection sensitivity is an important component in BPD, even for remitted BPD patients. Level of self-esteem appears to be a relevant factor in the relationship between rejection sensitivity and BPD symptom severity. Therapeutic interventions for BPD would do well to target rejection sensitivity.

  4. Anti-LFA-1 Therapy in a Nonhuman Primate Renal Transplant Model of Costimulation Blockade Resistant Rejection

    Science.gov (United States)

    Anderson, Douglas J.; Lo, Denise J.; Leopardi, F.; Song, Mingqing; Turgeon, Nicole A.; Strobert, Elizabeth A.; Jenkins, Joe B.; Wang, Rijian; Reimann, Keith A.; Larsen, Christian P.; Kirk, Allan D.

    2016-01-01

    Costimulation blockade with the fusion protein belatacept provides a desirable side-effect profile and improvement in renal function compared to calcineurin inhibition in renal transplantation. This comes at the cost of increased rates of early acute rejection. Blockade of the integrin molecule LFA-1 has been shown to be an effective adjuvant to costimulation blockade in a rigorous non-human primate (NHP) model of islet transplantation. We therefore sought to test this combination in an NHP renal transplant model. Rhesus macaques received belatacept maintenance therapy with or without the addition of LFA-1 blockade, achieved using a murine derived LFA-1 specific antibody, TS1/22. Additional experiments were performed using chimeric, rhesus IgG1 (TS1/22R1) or IgG4 (TS1/22R4) variants, each engineered to limit antibody clearance. Despite evidence of proper binding to the target molecule and impaired cellular egress from the intravascular space indicative of a therapeutic effect similar to prior islet studies, LFA-1 blockade failed to significantly prolong graft survival. Furthermore, evidence of impaired protective immunity against CMV was observed. These data highlight the difficulties in translating treatment regimens between organ models, and suggest that the primarily vascularized renal model is more robust with regard to belatacept resistant rejection than the islet model. PMID:26602755

  5. Perturbations in the Urinary Exosome in Transplant Rejection

    Energy Technology Data Exchange (ETDEWEB)

    Sigdel, Tara K.; NG, Yolanda; Lee, Sangho; Nicora, Carrie D.; Qian, Weijun; Smith, Richard D.; Camp, David G.; Sarwal, Minnie M.

    2015-01-05

    Background: Urine exosomes, vesicles exocytosed into urine by all renal epithelial cell types, occur under normal physiologic and disease states. Exosome contents may mirror disease-specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed and for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Methods: Urine exosomes were isolated by centrifugal filtration from mid-stream, second morning void, urine samples collected from kidney transplant recipients with and without biopsy matched acute rejection. The proteomes of unfractionated whole urine (Uw) and urine exosomes (Uexo) underwent mass spectrometry-based quantitative proteomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR). Results: Identifications of 1018 and 349 proteins, Uw and Uexo fractions, respectively, demonstrated a 279 protein overlap between the two urinary compartments with 25%(70) of overlapping proteins unique to Uexoand represented membrane bound proteins (p=9.31e-7). Of 349 urine exosomal proteins identified in transplant patients 220 were not previously identified in the normal urine exosomal fraction. Uexo proteins (11), functioning in the inflammatory / stress response, were more abundant in patients with biopsy-confirmed acute rejection, 3 of which were exclusive to Uexo. Uexo AR-specific biomarkers (8) were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. Conclusions: A rapid urinary exosome isolation method and quantitative measurement of enriched Uexo proteins was applied. Urine proteins specific to the exosomal fraction were detected either in unfractionated urine (at low abundances) or by Uexo fraction analysis. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were

  6. Neovascularização retiniana secundária a obstrução vascular em retinocoroidite por toxoplasmose em paciente HIV positivo: relato de caso Retinal vascular occlusion and neovascularization in acute toxoplasmic retinochoroiditis in a patient with AIDS: case report

    Directory of Open Access Journals (Sweden)

    Vânia Ewert

    2004-08-01

    Full Text Available Apresentar e discutir o caso de paciente infectado pelo HIV, que desenvolveu quadro de obstrução vascular seguido de neovascularização retiniana e de papila, durante o tratamento específico para retinocoroidite por toxoplasmose e que evoluiu com resolução espontânea da neovascularização sem a necessidade de tratamento associado. Paciente com retinocoroidite por toxoplasmose, que após 4 semanas de tratamento específico (sulfadiazina e pirimetamina desenvolveu quadro de obstrução vascular, seguido de neovascularização retiniana, apresentou involução espontânea, não havendo necessidade de fotocoagulação a laser, ou de outro tratamento adicional. As lesões retinianas ativas de toxoplasmose podem cursar com complicações vasculares, mesmo na vigência de tratamento específico, e geralmente apresentam bom prognóstico com regressão espontânea dos neovasos, sem necessidade de tratamentos adicionais.To present a case of an HIV-infected patient, who presented with active chorioretinal inflammatory lesion suggestive of toxoplasmosis, that during the specific treatment developed a retinal vascular occlusion, and adjacent neovascularization. 35-year-old AIDS patient that, presented with toxoplasmic retinochoroiditis and after 4 weeks of the specific therapy (pyrimethamine and sulfadiazine developed a vascular occlusion and retinal neovascularization that healed without the need for phototocoagulation or other adjunctive therapy. This case demonstrates that acute toxoplasmic retinochoroiditis that develops vascular complications may present a good result with the specific treatment without the need for adjunctive therapy.

  7. Gender and age peculiarities of content changes of protein C, von Willebrand factor, vascular cell adhesion molecules sVCAM-1 in patients with acute left ventricle Q-wave myocardial infarction

    Directory of Open Access Journals (Sweden)

    S. M. Kyselov

    2015-04-01

    Full Text Available Markers of hemostasis have an influence on the state of postinfarction remodeling processes. Aim. In order to study the gender and age peculiarities, to determine the predictive value of the protein C, von Willebrand factor and vascular cell adhesion molecules sVCAM-1 concentration, we examined 76 patients with acute Q-wave myocardial infarction. Methods and results. On the 1st day of the disease, higher concentrations of protein C were detected in young women, vascular cell adhesion molecules sVCAM-1 - in men of any age. On the 10th day of the disease, both in men and women increase in the content of protein C, reducing the concentration of von Willebrand factor and vascular cell adhesion molecules sVCAM-1 were detected. Conclusion. Protein C has the highest prognostic potential in relation to the formation of heart aneurysm after Q-wave myocardial infarction in women of young age, and von Willebrand factor and vascular cell adhesion molecules sVCAM-1 - in older men.

  8. Cognitive improvement after treatment of depressive symptoms in the acute phase of stroke Melhora cognitiva com tratamento antidepressivo na fase aguda do acidente vascular cerebral

    Directory of Open Access Journals (Sweden)

    Samuel Simis

    2006-06-01

    Full Text Available The outcome of antidepressant treatment for depressive symptoms and cognitive impairment at the acute phase of stroke is controversial. We investigated 93 patients, treating with citalopram 36 with severe depressive symptoms (HAM-D: Hamilton Depression Rating Scale >18, whilst 19 patients with mild depressive symptoms, and 38 non-depressed patients, remained untreated. At baseline (two weeks after stroke, patients with severe depressive symptoms had lower scores in total Dementia Rating Scale (DRS and in the attention and memory DRS subscales, than the non-depressed patients (pOs resultados do tratamento com antidepressivo para os sintomas depressivos e comprometimento cognitivo da fase aguda do acidente vascular cerebral não estão estabelecidos. Investigamos 93 pacientes, 36 com sintomas depressivos graves (HAM-D: Escala de Depressão de Hamilton >18 foram tratados com citalopram, enquanto 19 pacientes com sintomas depressivos leves e 38 não-deprimidos não foram tratados. Ao início do tratamento (duas semanas depois do icto, pacientes com sintomas depressivos graves tinham escores mais baixos na Escala de Avaliação de Demência (DRS total e nas subescalas de atenção e de memória da DRS do que os pacientes não-deprimidos (p<0,001. Ao fim de três meses de acompanhamento essas diferenças tinham desaparecido, mas pacientes que inicialmente tinham sintomas depressivos leves passaram a ter escores mais altos no HAM-D do que os não-deprimidos (p=0,015, e escores mais baixos nas subescalas de atenção e memória da DRS (p<0,01 do que os pacientes tratados com citalopram. O tratamento associou-se a melhora de humor, memória e atenção, e demonstra que é necessário um estudo controlado com placebo para o tratamento de sintomas depressivos leves.

  9. Huoxue Anxin Recipe () promotes myocardium angiogenesis of acute myocardial infarction rats by up-regulating miR-210 and vascular endothelial growth factor.

    Science.gov (United States)

    Wang, Jie; Zhang, Yun; Liu, Yong-Mei; Guo, Li-Li; Wu, Ping; Dong, Yu; Wu, Guang-Jun

    2016-09-01

    To investigate the microRNAs (miRNAs) expression profile of acute myocardial infarction (AMI) rats and the regulating effects of Huoxue Anxin Recipe (, HAR) on angiogenesis-related miRNAs and genes. Forty-five Wistar rats were randomly assigned to 3 groups according to a random number table: sham, AMI, and AMI+HAR groups (15 in each group). AMI rats were established by ligation of the left descending coronary artery. HAR was intragastrically administered to rats of the AMI+HAR group for successive 21 days since modeling, meanwhile the same volume of 0.9% normal saline was administered to rats of the sham and AMI groups. Doppler echocardiography was used for noninvasive cardiac function test. Hematoxylin and eosin staining was used to observe the histopathological change. miRNAs expression profile was detected by quantitative realtime polymerase chain reaction (qRT-PCR). The mRNA and protein expressions of vascular endothelial growth factor (VEGF), and a target gene of miR-210 was further detected by qRT-PCR and Western blot, respectively. The microvessels density of myocardium was evaluated by CD31 immunostaining. Compared with the sham group, ejection fraction (EF) and fractional shortening (FS) values were decreased significantly in the AMI group (Pinfarction area and the interstitial collagen deposition were increased obviously. As for the AMI+HAR group, EF and FS values were increased significantly (Pinfarction area was reduced and the interstitial collagen deposition were alleviated significantly. Total of 23 miRNAs in the AMI group expressed differently by at least 1.5 folds compared with those in the sham group; 5 miRNAs in the AMI+HAR group expressed differently by at least 1.5 folds compared with those in the AMI group. Among them, miR-210 was low in the AMI group and high in the AMI+HAR group. The relative mRNA and protein expressions of VEGF were decreased significantly in the AMI group (Pinfarction area, alleviate the interstitial fibrosis and improve

  10. Experimental autologous substitute vascular graft for transplantation surgery

    NARCIS (Netherlands)

    Kobori, L; Dallos, G; Gouw, ASH; Nemeth, T; Nemes, B; Fehervari, I; Tegzess, Adam; Slooff, MJH; Perner, F; De Jong, KP

    2000-01-01

    Vascular complications in fiver transplantation are a major cause of graft failure and mortality. The aim of the study was to create autologous vascular graft without risk of rejection. Posterior rectus fascia sheath lined with peritoneum was used for iliac artery replacement in seven mongrel dogs.

  11. Consumption of a flavonoid-rich açai meal is associated with acute improvements in vascular function and a reduction in total oxidative status in healthy overweight men.

    Science.gov (United States)

    Alqurashi, Randah M; Galante, Laura A; Rowland, Ian R; Spencer, Jeremy Pe; Commane, Daniel M

    2016-11-01

    Açai (Euterpe oleracea) is a polyphenol-rich fruit marketed as beneficial for health. Experimental data showing improvements in health markers arising from açai consumption in humans is limited. The objective of the present study was to investigate the effect of açai consumption on acute changes in vascular function and on other disease risk markers, including postprandial plasma insulin, glucose, and oxidative stress. Twenty-three healthy male volunteers, aged 30-65 y and with a body mass index (in kg/m2) of 25-30, completed a randomized, controlled, high-fat challenge, double-blind, crossover, acute dietary intervention trial. The volunteers consumed either an açai-based smoothie (AS) or a macronutrient-matched control smoothie (PS) together with a high-fat breakfast meal challenge. The primary endpoint was the assessment of endothelial function in the brachial artery by flow-mediated dilatation (FMD). The acute consumption of an AS containing 694 mg total phenolics improved vascular function, with postprandial increases in FMD from baseline of 1.4% at 2 h compared with 0.4% after consumption of the PS (P = 0.001) and increases at 6 h of 0.8% for the AS compared with -0.3% for the PS (P study in overweight men, açai consumption was associated with improvements in vascular function, which may lower the risk of a cardiovascular event. Future intervention studies, perhaps with a chronic design, in wider populations and with other biomarkers of disease risk are needed to fully elucidate the benefits of açai to health. This trial was registered at clinicaltrials.gov as NCT02292329. © 2016 American Society for Nutrition.

  12. Social Causes and Consequences of Rejection Sensitivity

    Science.gov (United States)

    London, Bonita; Downey, Geraldine; Bonica, Cheryl; Paltin, Iris

    2007-01-01

    Predictions from the Rejection Sensitivity (RS) model concerning the social causes and consequences of RS were examined in a longitudinal study of 150 middle school students. Peer nominations of rejection, self-report measures of anxious and angry rejection expectations, and social anxiety, social withdrawal, and loneliness were assessed at two…

  13. Peer Group Rejection and Children's Outgroup Prejudice

    Science.gov (United States)

    Nesdale, Drew; Durkin, Kevin; Maass, Anne; Kiesner, Jeff; Griffiths, Judith; Daly, Josh; McKenzie, David

    2010-01-01

    Two simulation studies examined the effect of peer group rejection on 7 and 9 year old children's outgroup prejudice. In Study 1, children (n = 88) pretended that they were accepted or rejected by their assigned group, prior to competing with a lower status outgroup. Results indicated that rejected versus accepted children showed increased…

  14. 7 CFR 58.136 - Rejected milk.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rejected milk. 58.136 Section 58.136 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Milk § 58.136 Rejected milk. A plant shall reject specific milk from a producer if the milk fails to...

  15. [Vascular dementia

    NARCIS (Netherlands)

    Leeuw, H.F. de; Gijn, J. van

    2004-01-01

    Vascular dementia is one of the most frequently occurring dementia syndromes. Its prevalence is about 5% among subjects above 85 years of age. Elevated blood pressure and atherosclerosis are the most important risk factors. According to international criteria, vascular dementia usually occurs within

  16. Estudo das alterações das citocinas inflamatórias na rejeição aguda do transplante intestinal em ratos Cytokine participation in the acute rejection of intestinal transplantation in rats

    Directory of Open Access Journals (Sweden)

    André Dong Won Lee

    2004-06-01

    patients with short bowel syndrome, aiming the reintroduction of oral diet. However, the major obstacle in this procedure is the strong rejection. Delay in rejection diagnosis may be irreversible and lethal. AIM: To define method for early diagnosis of rejection based on the presence of interleucin-6 (IL-6 e interferon- gamma (IFN-gamma from intestinal allograft. MATERIAL AND METHODS: Isogenic rats Brown-Norway (BN and Lewis (LEW were submitted to intestinal heterotopic allotransplantation and divided in two groups: LEW donor to LEW recipient isograft group (C and BN donor to LEW recipient allograft group (Tx. According to the day of sacrifice, Tx group were subdivided in three subgroups with eight animals each as follow: Tx3- sacrificed at third postoperative day (POD, Tx5 - sacrificed at fifth POD and Tx7 - sacrificed at seventh POD. Eight animals from control group were subdivided in three moments according to the time of biopsy from the graft as follow: C³ - biopsy at third POD; C5 - biopsy at fifth POD and C7 - biopsy at seventh POD. All animals from control group were sacrificed at seventh POD. Rejection parameters were compared between the control groups (C3 vs C5, C3 vs C7 and C5 vs C7, and allograft group (Tx3 vs Tx5, Tx3 vs Tx7 and Tx5 vs Tx7. The same parameters were analyzed between the control group and allograft groups ( C3 vs Tx3, C5 vs Tx5 and C7 vs Tx7. RESULTS: In C group no statistical significant difference regarding the immunoexpression of the cytokines, while in Tx group, immunoexpression of IL-6 and IFN-gamma were remarkable since the fifth postoperative day.

  17. Vascular effects of a single high salt meal

    Directory of Open Access Journals (Sweden)

    Mohamed Abdel Kader Abdel Wahab

    2016-09-01

    Conclusion: High salt intake may acutely impair vascular function in different vascular beds independent of the increase of blood pressure. Plasma sodium increase may be one of the underlying mechanisms.

  18. Patterns of Early Rejection in Renal Retransplantation: A Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Lan Zhu

    2016-01-01

    Full Text Available It has been reported that kidney retransplant patients had high rates of early acute rejection due to previous sensitization. In addition to the acute antibody-mediated rejection (ABMR that has received widespread attention, the early acute T-cell-mediated rejection (TCMR may be another important issue in renal retransplantation. In the current single-center retrospective study, we included 33 retransplant patients and 90 first transplant patients with similar protocols of induction and maintenance therapy. Analysis focused particularly on the incidence and patterns of early acute rejection episodes, as well as one-year graft and patient survival. Excellent short-term clinical outcomes were obtained in both groups, with one-year graft and patient survival rates of 93.9%/100% in the retransplant group and 92.2%/95.6% in the first transplant group. Impressively, with our strict immunological selection and desensitization criteria, the retransplant patients had a very low incidence of early acute ABMR (6.1%, which was similar to that in the first transplant patients (4.4%. However, a much higher rate of early acute TCMR was observed in the retransplant group than in the first transplant group (30.3% versus 5.6%, P<0.001. Acute TCMR that develops early after retransplantation should be monitored in order to obtain better transplant outcomes.

  19. Efeitos agudos dos estrogênios associados a progestogênios sobre a trigliceridemia e reatividade vascular pós-prandial Acute effects of the use of estrogens in association with progestogens on postprandial triglyceridemia and vascular reactivity

    Directory of Open Access Journals (Sweden)

    Silvio C.M. Santos

    2004-11-01

    Full Text Available OBJETIVO: Avaliar se a terapia de reposição hormonal com estrogênios e progestogênios, em mulheres hipertensas na pós-menopausa, modifica a trigliceridemia e a reatividade vascular pós-prandial. MÉTODOS: Estudo controlado, duplo cego, cruzado contra placebo em 15 mulheres na pós-menopausa (idade de 50 a 70, média = 61,6 ± 6 anos, sorteadas para 2 semanas de placebo ou ingestão oral de 0,625 mg de estrogênios conjugados eqüinos e 2,5 mg de medroxiprogesterona e alimentadas com refeição rica em gorduras (897 calorias; 50,1% de gorduras. Foi medida a reatividade vascular (RV - % de variação dos diâmetros do vaso entre o jejum e 2h após a alimentação, usando-se método ultra-sonográfico automatizado. Foram também determinados o perfil lipídico e a glicose, em jejum e 2h após a alimentação rica em gorduras. RESULTADOS: Com o placebo, a reatividade vascular (RV diminuiu de 3,20 ± 17% em jejum para -2,1 ± 30%, 2h após a alimentação (p = 0,041, e com terapia de reposição hormonal, a reatividade vascular diminuiu de 6,14 ± 27% em jejum para -0,05±18%, 2h após a alimentação (p=NS. A trigliceridemia pós-prandial aumentou, 35 ± 25% com o placebo, e 12 ± 10% com a terapia de reposição hormonal (P OBJECTIVE: To assess whether hormone replacement therapy with estrogens in association with progestogens in postmenopausal hypertensive women alters postprandial triglyceridemia and vascular reactivity. METHODS: A double-blind, placebo-controlled, crossover study was carried out with 15 postmenopausal women (age range: 50 to 70 years, mean = 61.6 ± 6 years randomly assigned to 2 weeks of placebo or oral ingestion of 0.625 mg of equine conjugated estrogens and 2.5 mg of medroxyprogesterone, fed a high-fat diet (897 calories; 50.1% fat. Vascular reactivity (VR - % of vessel diameter variation in the fasting period and 2 hours after meals was measured by using the automated ultrasound method. Lipid profile and glycemia

  20. Induction Therapy, Rejection, and Graft Outcomes in Pediatric and Adolescent Kidney Transplant Recipients.

    Science.gov (United States)

    Mincham, Christine Marie; Wong, Germaine; Teixeira-Pinto, Armando; Kennedy, Sean; Alexander, Stephen; Larkins, Nicholas; Lim, Wai H

    2017-09-01

    Although the clinical benefit of interleukin-2-receptor antibody (IL-2RAb) induction in reducing the risk of acute rejection in adult kidney transplant recipients is well established, a similar benefit in pediatric recipients remains controversial. The aim of this study is to evaluate the efficacy of IL-2RAb in reducing acute rejection in pediatric and adolescent recipients aged 21 years or younger using Australia and New Zealand Dialysis and Transplant registry. The association between IL-2RAb induction and risk of acute rejection was examined using adjusted logistic regression and propensity score analyses, whereby the associations between induction, graft loss, and incident cancer were examined using adjusted Cox regression analysis. There were 658 recipients followed up for a median of 5.5 years between 2001 and 2012. The use of IL-2RAb induction was associated with adjusted odds ratios of 0.61 (95% confidence interval [CI], 0.41-0.91; P = 0.007) for any rejection and 0.57 (95% CI, 0.35-0.92; P = 0.020) for early rejection occurring in the first 6 months after transplant. These associations were attenuated in the propensity score analysis but remained statistically significant with adjusted odds ratio of 0.65 (95% CI, 0.49-0.87) for any rejection and 0.64 (95% CI, 0.44-0.93) for early rejection. There were no associations between induction, graft loss, and incident cancer. Induction treatment of IL-2RAb in pediatric and adolescent kidney transplant recipients is associated with at least a 40% reduction in the odds of acute rejection, independent of age, era, immunological status, and initial immunosuppression.

  1. Profile of the Pleximmune blood test for transplant rejection risk prediction

    OpenAIRE

    Sindhi, Rakesh; Ashokkumar, Chethan; Higgs, Brandon W; Levy, Samantha; Soltys, Kyle; Bond, Geoffrey; Mazariegos, George; Ranganathan, Sarangarajan; Zeevi, Adriana

    2016-01-01

    The Pleximmune? test (Plexision Inc., Pittsburgh, PA, USA) is the first cell-based test approved by the US FDA, which predicts acute cellular rejection in children with liver- or intestine transplantation. The test addresses an unmet need to improve management of immunosuppression, which incurs greater risks of opportunistic infections and Epstein?Barr virus-induced malignancy during childhood. High-dose immunosuppression and recurrent rejection after intestine transplantation also result in ...

  2. Renal vascular and thrombotic effects of cyclosporine.

    Science.gov (United States)

    Remuzzi, G; Bertani, T

    1989-04-01

    Cyclosporine A (CyA) given to prevent xenograft rejection induces renal function impairment. In the last few years many studies have been devoted to understanding the mechanism(s) of CyA-induced renal insufficiency. In humans, several specific findings--interstitial fibrosis, toxic tubulopathy, peritubular capillary congestion, arteriolopathy--have been associated with CyA administration. It is now recognized that CyA renal toxicity mainly manifests under three different syndromes: (1) acute reversible decrease in glomerular filtration rate (GFR), (2) acute microvascular disease with the pattern of thrombotic microangiopathy, and (3) chronic irreversible renal damage. This review analyzes the available evidence that the clinical syndromes of CyA nephrotoxicity are related to changes induced by CyA on renal vessels. Experimental studies have failed to document that the activation of renin-angiotensin axis or sympathetic nervous system plays a relevant role in the development of CyA-associated renal vasoconstriction, which is the main causal factor of acute reversible decrease in GFR, whereas it is possible that changes in arachidonic acid metabolites with vasoactive properties contribute to this CyA-induced phenomenon. In this context, findings of increased urinary TxB2 and protective effect of TxA2 receptor blocking are of particular interest. Since the introduction of CyA in clinical practice, a syndrome of thrombotic microangiopathy resembling hemolytic uremic syndrome/thrombotic thrombocytopenic purpura has been recognized in humans and reproduced in experimental animals. This is a rare form of vascular toxicity attributed to CyA which may have a poor prognosis and possibly results from a direct toxic effect of CyA on vascular endothelium. The syndrome of chronic progressive deterioration of renal function associated with CyA was first recognized in humans. Until recently the possibility of reproducing this syndrome in animals in order to better understand its

  3. Vascular ring

    DEFF Research Database (Denmark)

    Schmidt, Anne Mette S; Larsen, Signe H; Hjortdal, Vibeke E

    2018-01-01

    BACKGROUND: Vascular ring is a rare cause of recurrent respiratory infections, dysphagia and stridor. Surgical repair is considered safe but the long-term outcomes are unclear. The purpose of this study was to investigate the mortality and morbidity following vascular ring surgery in a single...... age of 1.4 years (range 0.008-64 years) were operated for vascular ring. Median follow-up was 6.8 years (range 2.4-34 years). Presenting symptoms were stridor (52%), dysphagia or vomiting (52%) and recurrent respiratory infections (48%). There were no early or late deaths. Three months postoperatively...

  4. Vascular anomalies

    Directory of Open Access Journals (Sweden)

    Murthy Jyotsna

    2005-01-01

    Full Text Available Management of vascular anomalies is an emerging multidisciplinary, super-specialisation field involving several surgical, medical and radiological specialties. Over the years, development in this field has been limited because of complex nomenclature and lack of consensus on the best practice for treatment of some of the more complex vascular anomalies. It was only in 1996 that the International Society of the Study of Vascular Anomalies defined nomenclature for the anomalies and gave clear guidelines on management, allowing for improved clinical practices. As in all fields of clinical medicine, the correct diagnosis of the vascular anomalies is essential to choose the appropriate treatment. This paper gives clear guidelines for diagnosis, understanding of the anomalies and discusses their management.

  5. Vascular Dementia

    OpenAIRE

    Maria Alekseyevna Cherdak; O V Uspenskaya

    2015-01-01

    This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/S0140-6736(15)00463-8 Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the e...

  6. Vascular Vertigo

    Directory of Open Access Journals (Sweden)

    Mazyar Hashemilar

    2017-02-01

    Full Text Available Vertigo is a common complaint in neurology and medicine. The most common causes of vertigo are benign paroxysmal positional vertigo, vestibular neuritis, Meniere’s disease, and vascular disorders. Vertigo of vascular origin is usually limited to migraine, transient ischemic attacks, and ischemic or hemorrhagic stroke. Vascular causes lead to various central or peripheral vestibular syndromes with vertigo. This review provides an overview of epidemiology and clinical syndromes of vascular vertigo. Vertigo is an illusion of movement caused by asymmetrical involvement of the vestibular system by various causes. Migraine is the most frequent vascular disorder that causes vertigo in all age groups. Vertigo may occur in up to 25% of patients with migraine. The lifetime prevalence of migrainous vertigo is almost 1%. Cerebrovascular disorders are estimated to account for 3% to 7% of patients with vertigo. Vestibular paroxysmia has been diagnosed in 1.8% to 4% of cases in various dizziness units. Vasculitic disorders are rare in the general population, but vertigo may be seen in almost up to 50% of patients with different vasculitic syndromes. Conclusions: Migraine, cerebrovascular disorders especially involving the vertebrobasilar territory, cardiocirculatory diseases, neurovascular compression of the eighth nerve, and vasculitis are vascular causes of vertigo syndromes.

  7. Recurrence and rejection in liver transplantation for primary sclerosing cholangitis

    Science.gov (United States)

    Fosby, Bjarte; Karlsen, Tom H; Melum, Espen

    2012-01-01

    Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to fibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can influence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible influence of rejection on the risk of recurrent disease in the allograft. PMID:22228965

  8. Vascular Access Procedures

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Vascular Access Procedures A vascular access procedure inserts a flexible, ... the limitations of Vascular Access Procedures? What are Vascular Access Procedures? A vascular access procedure involves the insertion ...

  9. Vascular Access for Hemodialysis

    Science.gov (United States)

    ... Adequacy Eating & Nutrition for Hemodialysis Vascular Access for Hemodialysis What is a vascular access? A vascular access ... Set Up the Vascular Access Well before Starting Hemodialysis Patients should set up a vascular access well ...

  10. What Is Vascular Disease?

    Science.gov (United States)

    ... Policy What Is Vascular Disease? What Is Vascular Disease? Vascular disease is any abnormal condition of the blood ... Privacy Policy × Your ticket for the: What Is Vascular Disease? Title What Is Vascular Disease? USD Close Print

  11. Pulmonary vascular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fedullo, P.F.; Shure, D.

    1987-03-01

    A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques.

  12. Extended Active Disturbance Rejection Controller

    Science.gov (United States)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2016-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  13. Serum exosomal protein profiling for the non-invasive detection of cardiac allograft rejection.

    Science.gov (United States)

    Kennel, Peter J; Saha, Amit; Maldonado, Dawn A; Givens, Raymond; Brunjes, Danielle L; Castillero, Estibaliz; Zhang, Xiaokan; Ji, Ruiping; Yahi, Alexandre; George, Isaac; Mancini, Donna M; Koller, Antonius; Fine, Barry; Zorn, Emmanuel; Colombo, Paolo C; Tatonetti, Nicholas; Chen, Emily I; Schulze, P Christian

    2017-07-19

    Exosomes are cell-derived circulating vesicles that play an important role in cell-cell communication. Exosomes are actively assembled and carry messenger RNAs, microRNAs and proteins. The "gold standard" for cardiac allograft surveillance is endomyocardial biopsy (EMB), an invasive technique with a distinct complication profile. The development of novel, non-invasive methods for the early diagnosis of allograft rejection is warranted. We hypothesized that the exosomal proteome is altered in acute rejection, allowing for a distinction between non-rejection and rejection episodes. Serum samples were collected from heart transplant (HTx) recipients with no rejection, acute cellular rejection (ACR) and antibody-mediated rejection (AMR). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of serum exosome was performed using a mass spectrometer (Orbitrap Fusion Tribrid). Principal component analysis (PCA) revealed a clustering of 3 groups: (1) control and heart failure (HF); (2) HTx without rejection; and (3) ACR and AMR. A total of 45 proteins were identified that could distinguish between groups (q < 0.05). Comparison of serum exosomal proteins from control, HF and non-rejection HTx revealed 17 differentially expressed proteins in at least 1 group (q < 0.05). Finally, comparisons of non-rejection HTx, ACR and AMR serum exosomes revealed 15 differentially expressed proteins in at least 1 group (q < 0.05). Of these 15 proteins, 8 proteins are known to play a role in the immune response. Of note, the majority of proteins identified were associated with complement activation, adaptive immunity such as immunoglobulin components and coagulation. Characterizing of circulating exosomal proteome in different cardiac disease states reveals unique protein expression patterns indicative of the respective pathologies. Our data suggest that HTx and allograft rejection alter the circulating exosomal protein content. Exosomal protein analysis could be a novel approach

  14. Expression of vascular endothelial growth factor, stromal cell-derived factor-1, and CXCR4 in human limb muscle with acute and chronic ischemia

    NARCIS (Netherlands)

    Weel, V. van; Seghers, L.; Vries, M.R. de; Kuiper, E.J.; Schlingemann, R.O.; Bajema, I.M.; Lindeman, J.H.N.; Delis-Diemen, P.M. van; Hinsbergh, V.W.M. van; Bockel, J.H. van; Quax, P.H.A.

    2007-01-01

    OBJECTIVE - Vascular endothelial growth factor (VEGF)-induced stromal cell-derived factor-1 (SDF-1) has been implicated in angiogenesis in ischemic tissues by recruitment of CXCR4-positive bone marrow-derived circulating cells with paracrine functions in preclinical models. Here, evidence for this

  15. Pediatric vascularized composite allotransplantation.

    Science.gov (United States)

    Doumit, Gaby; Gharb, Bahar Bassiri; Rampazzo, Antonio; Papay, Francis; Siemionow, Maria Z; Zins, James E

    2014-10-01

    Vascularized composite allotransplantation (VCA) has experienced a growing acceptance, which has led to a debate centered on extending the indications of the procedure to include pediatric patients. The aim of this article was to discuss such indications based on the evidence in pediatric solid organ transplantation, reconstructive surgery in children, and VCA in adult patients. Papers published on the outcomes of pediatric solid organ transplantation, growth after replantation of extremities, vascularized autologous tissue transfer, craniofacial surgery, orthognathic procedures, facial fractures, and outcomes after repair of peripheral nerves in children were reviewed. Although the outcomes of solid organ transplantation in children have improved, the transplanted organs continue to have a limited lifespan. Long-term immunosuppressive therapy exposes the patients to an increased lifetime risk of infections, diabetes, hypertension, dyslipidemia, cardiovascular disease, and malignancy. Growth impairment and learning disabilities are other relevant drawbacks, which affect the pediatric recipients. Nonadherence to medication is a common cause of graft dysfunction and loss among the adolescent transplant recipients. Rejection episodes, hospitalizations, and medication adverse effects contribute negatively to the quality of life of the patients. Although normal growth after limb transplantation could be expected, pediatric facial transplant recipients may present with arrest of growth of transplanted midfacial skeleton. Considering the non-life-threatening nature of the conditions that lead to eligibility for VCA, it is suggested that it is premature to extend the indications of VCA to include pediatric patients under the currently available immunosuppressive protocols.

  16. Indicators of rejection in groups of children

    Directory of Open Access Journals (Sweden)

    Vera Regina Miranda Gomes da Silva

    2001-12-01

    Full Text Available The issue of rejection is motivating countless researchers due to the close relationship between peer rejection and difficulties in future adjustment. The study of this issue can contribute towards the detection of factors that trigger rejection, consequently making possible preventive interventions. This text is intended to provide a summary of the research undertaken by the author as part of her Master's Degree, the aim of which was to detect indicators of rejection in the final year of a private primary school in Curitiba (n=52. In this study, “indicators of rejection” are understood to be criteria that lead children to exclude each other from their recreation and working activities, within the context of the school. The study used one instrument designed to collect data from the children (“voting for the least popular” and “tag” and another aimed at obtaining data from the teachers (“teacher's card”. The analysis and cross-referencing of the data obtained indicated that children tend to reject their peers based on their inadequate behaviour (bossiness, disruptive behaviour, and this perception was reinforced by the data obtained from the teachers. On the other hand, children tend to chose other children who frequently demonstrate sociable behaviour to be their peers. Keywords: Rejection, rejected children, peer rejection, recognition of rejection.

  17. Vascular ultrasound for atherosclerosis imaging

    NARCIS (Netherlands)

    C.L. de Korte (Chris); H.H.G. Hansen (Hendrik); A.F.W. van der Steen (Ton)

    2011-01-01

    textabstractCardiovascular disease is a leading cause of death in the Western world. Therefore, detection and quantification of atherosclerotic disease is of paramount importance to monitor treatment and possible prevention of acute events. Vascular ultrasound is an excellent technique to assess the

  18. The Glu298Asp single nucleotide polymorphism in the endothelial nitric oxide synthase gene differentially affects the vascular response to acute consumption of fruit and vegetable puree based drinks.

    Science.gov (United States)

    George, Trevor W; Waroonphan, Saran; Niwat, Chutamat; Gordon, Michael H; Lovegrove, Julie A

    2012-07-01

    Diets low in fruits and vegetables (FV) are responsible for 2.7 million deaths from cardiovascular diseases (CVD) and certain cancers annually. Many FV and their juices contain flavonoids, some of which increase endothelial nitric oxide synthase (eNOS) activity. A single nucleotide polymorphism in the eNOS gene, where thymine (T) replaces guanine (G) at position 894 predicting substitution of glutamate for aspartate at codon 298 (Glu298Asp), has been associated with increased CVD risk due to effects on nitric oxide synthesis and subsequently vascular reactivity. Individuals can be homozygous for guanine (GG), thymine (TT) or heterozygous (GT). We investigated the effects of acute ingestion of a FV-puree-based-drink (FVPD) on vasodilation and antioxidant status in subjects retrospectively genotyped for this polymorphism. Healthy volunteers (n = 24; 11 GG, 11 GT, 2 TT) aged 30-70 were recruited to a randomized, controlled, crossover, acute study. We showed that acute consumption of 400 mL FVPD differentially affected individuals depending on their genotype. There was a significant genotype interaction for endothelium-dependent vasodilation measured by laser Doppler imaging with iontophoresis (P puree-based drink. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Perturbations in the Urinary Exosome in Transplant Rejection

    Directory of Open Access Journals (Sweden)

    Tara eSigdel

    2015-01-01

    Full Text Available Urine exosomes are small vesicles exocytosed into the urine by all renal epithelial cell types under normal physiologic and disease states. Urine exosomal proteins may mirror disease specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Urine exosomes were isolated by centrifugal filtration of urine samples collected from kidney transplant patients with and without acute rejection, which were biopsy matched. The proteomes of unfractionated whole urine (Uw and urine exosomes (Ue underwent mass spectroscopy-based quantitative proteonomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR. A total of 1018 proteins were identified in Uw and 349 proteins in Ue. 279 overlapped between the two urinary compartments and 70 proteins were unique to the Ue compartment. Of 349 exosomal proteins identified from transplant patients,220 had not been previously identified in the normal Ue fraction. 11 Ue proteins, functionally involved in an inflammatory and stress response, were more abundant in urine samples from patients with acute rejection, 3 of which are exclusive to the Ue fraction. Ue AR-specific biomarkers(8 were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. A rapid urinary exosome isolation method and quantitative measurement of enriched Ue proteins was applied. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were specific to inflammatory responses, and were not observed in the Ue fraction from normal healthy subjects. Ue specific protein alterations in renal disease provide potential mechanistic insights and offer a unique panel of sensitive biomarkers for monitoring AR.

  20. Vascular dementia.

    Science.gov (United States)

    O'Brien, John T; Thomas, Alan

    2015-10-24

    Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the exact nature of the relation between cerebrovascular pathology and cognitive impairment, and the paucity of identifiable tractable treatment targets. Although there is an established relation between vascular and degenerative Alzheimer's pathology, the mechanistic link between the two has not yet been identified. This Series paper critiques some of the key areas and controversies, summarises treatment trials so far, and makes suggestions for what progress is needed to advance our understanding of pathogenesis and thus maximise opportunities for the search for new and effective management approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Análise da remodelação vascular na isquemia pulmonar experimental, nas fases aguda e crônica Analysis of acute and chronic vascular remodeling in an experimental model of pulmonary ischemia

    Directory of Open Access Journals (Sweden)

    Wanderley M. Bernardo

    2005-02-01

    Full Text Available INTRODUÇÃO: Alterações estruturais da circulação pulmonar traduzem processo de remodelação vascular e têm relação provável com variações locais de fluxo e isquemia. OBJETIVO: Definir as alterações histológicas na circulação pulmonar após obstrução experimental da artéria pulmonar. Correlacioná-las com os padrões de redistribuição sangüínea e remodelação vascular. MÉTODO: Foram submetidos à toracotomia esquerda 48 ratos Wistar, alocados aleatoriamente em dois grupos, com ligadura da artéria pulmonar e controle, e sacrificados com 1, 7, 30 e 60 dias. Nos pulmões retirados avaliou-se presença de sinais de injúria no parênquima e mensurou-se diâmetro externo e espessura da parede das arteríolas de bronquíolos terminais, respiratórios e alveolares. Diâmetro interno e porcentagem de espessura da parede foram calculados. RESULTADOS: Só ocorreu infarto, necrose e hemorragia no pulmão isquêmico. No não isquêmico houve aumento mantido dos diâmetros externo e interno das arteríolas, com redução inicial da espessura no 1º dia e valores semelhantes aos do grupo controle no 60º dia. No pulmão isquêmico houve redução transitória nos diâmetros externo e interno das arteríolas de bronquíolos terminais e respiratórios, com aumento, inicial e transitório, na sua espessura. As arteríolas alveolares apresentaram aumento do diâmetro externo e espessura da parede, com redução do diâmetro interno, mantida e progressiva. CONCLUSÃO: Este modelo reproduz arteriopatia distal em pacientes com tromboembolismo pulmonar crônico. A resposta vascular no pulmão não isquêmico é compatível com padrão de remodelação de hiperfluxo; a no pulmão isquêmico com hipofluxo e isquemia. Nas arteríolas de bronquíolos terminais e respiratórios a resposta foi transitória. Nas alveolares foi progressiva e mantida, pela provável ocorrência tardia de hiperfluxo local.BACKGROUND: Structural alterations to the

  2. Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Kupchak Brian R

    2009-07-01

    Full Text Available Abstract Background Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47 increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. Methods A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10 and women (n = 10 (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m2 participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47 or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD and venous occlusion strain gauge plethysmography. Results Baseline peak FMD was not different for Placebo (7.7% and NOP-47 (7.8%. Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P P = 0.008 for time × trial interaction. Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25% compared to NOP-47 (-18%. Conclusion These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.

  3. Not all rejections are alike : Competence and warmth as a fundamental distinction in social rejection

    NARCIS (Netherlands)

    Celik, P.; Lammers, J.; van Beest, I.; Bekker, M.H.J.; Vonk, R.

    2013-01-01

    Social rejection can lead to a variety of emotions. Two studies show that specific emotional reactions to social rejection can be understood by relying on the fundamental distinction between competence and warmth. Rejection that is perceived to be due to incompetence leads to anger, whereas

  4. Factors Influencing the Cure Rate in the Corneal Graft Rejection with Survival Analysis

    Directory of Open Access Journals (Sweden)

    Feizi S.

    2009-11-01

    Full Text Available AbstractBackground and Objectives: Immunologic rejection of the transplanted cornea is the major cause of human allograft failure with several risk factors contributing to it. Since in the corneal graft, most individuals do not reject the graft, we used the survival analysis with cure rate for the assessment of the factors influencing the cure rate at the time of data analysis. The main aim of this study was to evaluate the cure rate and assess the risk factors for corneal graft rejection in the keratoconus disease in Labafinejad Hospital, Tehran, Iran. Methods: This was a routine data base study in which the data were gathered from keratoconus patients’ files that had undergone penetrating keratoplasty operation. In the survival analysis, individuals who didn’t reject corneal were considered cured. To study the factors influencing the cure rate, we used the Weibull distribution for survival function and the logistic link function for the cure rate because of their tractability and accuracy.Results: Out of 119 patients 31 patients (26% rejected grafts. Among the factors influencing cure rate, only in vascularization and in persons older than 25 years of age was ameaningful effect on decreasing cure rate. With this cure model, the expected cure rate in the non-vascularization and less than 25 year- old patients was 81, in non-vascularization and more than 25 year- olds it is 64, in the vascularization and less than 25 year- olds, the cure rate is 19 and in the vascularization and more than 25 years of age, the cure rate is 9 percent and the observed cure rate for Kaplan-Meier product limit estimator was 79, 61, 27 and 0 percent, respectively. The results showed that the estimate of cure rate in the survival analysis was near the Kaplan-Meier product-limits estimator.Conclusion: One of the benefits of modeling is its ability to generalize the results; using them in the prediction. According to the results obtained from the fitting cure model

  5. 21 CFR 1230.47 - Rejected containers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rejected containers. 1230.47 Section 1230.47 Food... FEDERAL CAUSTIC POISON ACT Imports § 1230.47 Rejected containers. (a) In all cases where the containers... notification to the importer that the containers must be exported under customs supervision within 3 months...

  6. VASCULAR SURGERY

    African Journals Online (AJOL)

    Venous thromboembolism (VTE) is a complex and serious condition encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), usually in the lower extremities.1,2. Thromboses can result from venous stasis, vascular injury or hypercoagulability, and those involving the deep veins proximal to the knee are ...

  7. Fractional active disturbance rejection control.

    Science.gov (United States)

    Li, Dazi; Ding, Pan; Gao, Zhiqiang

    2016-05-01

    A fractional active disturbance rejection control (FADRC) scheme is proposed to improve the performance of commensurate linear fractional order systems (FOS) and the robust analysis shows that the controller is also applicable to incommensurate linear FOS control. In FADRC, the traditional extended states observer (ESO) is generalized to a fractional order extended states observer (FESO) by using the fractional calculus, and the tracking differentiator plus nonlinear state error feedback are replaced by a fractional proportional-derivative controller. To simplify controller tuning, the linear bandwidth-parameterization method has been adopted. The impacts of the observer bandwidth ωo and controller bandwidth ωc on system performance are then analyzed. Finally, the FADRC stability and frequency-domain characteristics for linear single-input single-output FOS are analyzed. Simulation results by FADRC and ADRC on typical FOS are compared to demonstrate the superiority and effectiveness of the proposed scheme. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  8. An Evolutionary Perspective on Mate Rejection.

    Science.gov (United States)

    Kelly, Ashleigh J; Dubbs, Shelli L; Barlow, Fiona Kate

    2016-01-01

    We argue that mate rejection and ex-partner relationships are important, multifaceted topics that have been underresearched in social and evolutionary psychology. Mate rejection and relationship dissolution are ubiquitous and form integral parts of the human experience. Both also carry with them potential risks and benefits to our fitness and survival. Hence, we expect that mate rejection would have given rise to evolved behavioral and psychological adaptations. Herein, we outline some of the many unanswered questions in evolutionary psychology on these topics, at each step presenting novel hypotheses about how men and women should behave when rejecting a mate or potential mate or in response to rejection. We intend these hypotheses and suggestions for future research to be used as a basis for enriching our understanding of human mating from an evolutionary perspective.

  9. Intrathymic immune modulation prevents acute rejection but not the development of graft arteriosclerosis (chronic rejection)

    NARCIS (Netherlands)

    Hillebrands, JL; Raue, HP; Klatter, FA; Hylkema, MN; Platteel, [No Value; Hardonk-Wubbena, A; Nieuwenhuis, P; Rozing, J

    2001-01-01

    Background. We showed previously that our intrathymic immune modulation protocol induces virtually permanent graft survival of simultaneously transplanted cardiac allografts in MHC-incompatible rat strain combinations. It is, however, unknown whether this procedure prevents the development of graft

  10. Explaining the paradoxical rejection-aggression link: the mediating effects of hostile intent attributions, anger, and decreases in state self-esteem on peer rejection-induced aggression in youth.

    Science.gov (United States)

    Reijntjes, Albert; Thomaes, Sander; Kamphuis, Jan H; Bushman, Brad J; de Castro, Bram Orobio; Telch, Michael J

    2011-07-01

    People are strongly motivated to feel accepted by others. Yet when faced with acute peer rejection they often aggress against the very peers they desire acceptance from, which may lead to further rejection. The present experiment tests three potential mediators of aggressive responses to acute peer rejection in the critical developmental stage of early adolescence. Participants (N=185, M(age)=11.5 years) completed personal profiles that were allegedly evaluated online by peers. After receiving negative or neutral peer feedback, participants could aggress against the same peers who had evaluated them. Rejected participants attributed more hostile intent to the peers, were angrier, showed a greater reduction in state self-esteem, and were more aggressive. Mediational analyses showed that hostile intent attributions mediated the acute peer rejection-aggression relationship, whereas increases in anger and decreases in state self-esteem did not. Thus, acute peer rejection evokes hostile intent attributions that, in turn, lead to aggressive reactions. © 2011 by the Society for Personality and Social Psychology, Inc

  11. Expression of class II major histocompatibility complex antigens (HLA-DR) and lymphocyte subset immunotyping in chronic pulmonary transplant rejection.

    Science.gov (United States)

    Hasegawa, S; Ockner, D M; Ritter, J H; Patterson, G A; Trulock, E P; Cooper, J D; Wick, M R

    1995-05-01

    Currently, the bronchiolitis obliterans syndrome (BOS) of chronic airway rejection represents the most significant obstacle to the long-term function of isolated pulmonary allografts in humans. Between 20% and 30% of recipients are affected by this condition. To define the possible pathogenetic role of altered expression of class II major histocompatibility complex antigens (ie, HLA-DR) in BOS, the authors studied well-characterized examples of this process immunohistologically. Eleven BOS specimens were compared with seven controls, represented by allografts with no pathologic abnormalities taken from patients with normal posttransplant respiratory function, as well as 14 biopsies showing acute rejection. In addition, immunophenotypic subtyping of lymphocytes in all specimens was undertaken. Control tissues exhibited variable but weak expression of HLA-DR in bronchiolar epithelium and alveolar pneumocytes. In comparison, immunostaining for class II major histocompatibility complex antigens in BOS showed no statistically significant differences, whereas the 14 examples of acute rejection manifested intense HLA-DR expression in epithelia and endothelial cells. The numbers of intrabronchiolar and peribronchiolar lymphocytes were clearly higher in both acute rejection and BOS than in controls, but these cells differed in lineage in the two rejection states. Acute rejection showed an obvious preponderance of CD43-positive T lymphocytes, whereas lymphoid cells in BOS were a relatively equal mixture of CD20-positive B cells and CD43-positive T cells. Moreover, incipient peribronchiolar B-cell follicles were observed in BOS. Natural killer (CD57-positive) lymphocytes were rare in all specimens. These data suggest that alterations in HLA-DR expression probably do not play a central role in the genesis of BOS, as they do in acute rejection. In contrast, the results of lymphocyte immunophenotyping and correlative histologic findings in BOS suggest that both T cells and B

  12. Somatostatin receptor scintigraphy predicts impending cardiac allograft rejection before endomyocardial biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Aparici, C.M.; Martin, J.C.; Tembl, A.; Flotats, A.; Estorch, M.; Catafau, A.M.; Berna, L.; Carrio, I. [Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Narula, J.; Puig, M.; Camprecios, M.; Ballester, M. [Cardiology Department, Sant Pau Hospital, Barcelona (Spain)

    2000-12-01

    The invasive nature of endomyocardial biopsy has led to a search for alternative diagnostic modalities for the detection of cardiac allograft rejection. To date, no non-invasive test meets all the requirements for the detection of acute and chronic rejection. The rejection process usually presents with lymphocyte infiltration with or without myocyte necrosis, which indicates the severity of cardiac allograft rejection and the necessity of treatment. Activated lymphocytes express somatostatin receptors; thus somatostatin receptor imaging could be used to target them. The aim of this study was to assess the feasibility of using somatostatin receptor imaging to target activated lymphocytes in the process of cardiac allograft rejection. Thirteen somatostatin receptor imaging studies were performed on ten cardiac allograft recipients 12-4745 days after transplantation, simultaneously with endomyocardial biopsy, to assess the imaging of activated lymphocytes in comparison with histological findings. Somatostatin receptor imaging was performed 4 h after the injection of 110 MBq of the somatostatin analogue indium-111 pentetreotide. {sup 111}In-pentetreotide uptake was visually scored and semi-quantitatively estimated by the calculation of a heart-to-lung ratio (HLR). The visual score correlated with the HLR. Intense/moderate uptake on visual assessment and an HLR >1.6 was observed in eight studies. In three of these studies there was significant rejection in the simultaneous endomyocardial biopsy [International Society of Heart and Lung Transplantation (ISHLT) rejection grade 3A/4]. Intense/moderate uptake was associated with mild or no rejection in the remaining five patients, and in four of them the next endomyocardial biopsy performed 1 week later demonstrated significant rejection requiring treatment. Two patients with low uptake and an HLR <1.6 had no evidence of rejection either in the simultaneous endomyocardial biopsy or in the endomyocardial biopsy performed the

  13. Somatostatin receptor scintigraphy predicts impending cardiac allograft rejection before endomyocardial biopsy.

    Science.gov (United States)

    Aparici, C M; Narula, J; Puig, M; Camprecios, M; Martín, J C; Tembl, A; Flotats, A; Estorch, M; Catafau, A M; Bernà, L; Ballester, M; Carrió, I

    2000-12-01

    The invasive nature of endomyocardial biopsy has led to a search for alternative diagnostic modalities for the detection of cardiac allograft rejection. To date, no non-invasive test meets all the requirements for the detection of acute and chronic rejection. The rejection process usually presents with lymphocyte infiltration with or without myocyte necrosis, which indicates the severity of cardiac allograft rejection and the necessity of treatment. Activated lymphocytes express somatostatin receptors; thus somatostatin receptor imaging could be used to target them. The aim of this study was to assess the feasibility of using somatostatin receptor imaging to target activated lymphocytes in the process of cardiac allograft rejection. Thirteen somatostatin receptor imaging studies were performed on ten cardiac allograft recipients 12-4,745 days after transplantation, simultaneously with endomyocardial biopsy, to assess the imaging of activated lymphocytes in comparison with histological findings. Somatostatin receptor imaging was performed 4 h after the injection of 110 MBq of the somatostatin analogue indium-111 pentetreotide. 111In-pentetreotide uptake was visually scored and semi-quantitatively estimated by the calculation of a heart-to-lung ratio (HLR). The visual score correlated with the HLR. Intense/moderate uptake on visual assessment and an HLR >1.6 was observed in eight studies. In three of these studies there was significant rejection in the simultaneous endomyocardial biopsy [International Society of Heart and Lung Transplantation (ISHLT) rejection grade 3A/4]. Intense/moderate uptake was associated with mild or no rejection in the remaining five patients, and in four of them the next endomyocardial biopsy performed 1 week later demonstrated significant rejection requiring treatment. Two patients with low uptake and an HLR <1.6 had no evidence of rejection either in the simultaneous endomyocardial biopsy or in the endomyocardial biopsy performed the

  14. Corneal Graft Rejection Ten Years after Penetrating Keratoplasty in the Cornea Donor Study

    Science.gov (United States)

    Dunn, Steven P.; Gal, Robin L.; Kollman, Craig; Raghinaru, Dan; Dontchev, Mariya; Blanton, Christopher L.; Holland, Edward J; Lass, Jonathan H.; Kenyon, Kenneth R.; Mannis, Mark J; Mian, Shahzad I.; Rapuano, Christopher J.; Stark, Walter J.; Beck, Roy W.

    2015-01-01

    Purpose To assess the effect of donor and recipient factors on corneal allograft rejection and evaluate whether a rejection event was associated with graft failure. Methods 1,090 subjects undergoing penetrating keratoplasty for a moderate risk condition (principally Fuchs’ dystrophy or pseudophakic corneal edema) were followed for up to 12 years. Associations of baseline recipient and donor factors with the occurrence of a rejection event were assessed in univariate and multivariate proportional hazards models. Results Among 651 eyes with a surviving graft at 5 years, the 10-year graft failure (± 99% CI) rates were 12% ± 4% among eyes with no rejection events in the first 5 years, 17% ± 12% in eyes with at least one probable, but no definite rejection event, and 22% ± 20% in eyes with at least one definite rejection event. The only baseline factor significantly associated with a higher risk of definite graft rejection was a preoperative history of glaucoma, particularly when prior glaucoma surgery had been performed and glaucoma medications were being used at time of transplant (10-year incidence 35% ± 23% compared with 14% ± 4% in eyes with no history of glaucoma/intraocular pressure treatment, p=0.008). Conclusion Those patients who experienced a definite rejection event frequently went on to graft failure raising important questions as to how we might change acute and long-term corneal graft management. Multivariate analysis indicated that the prior use of glaucoma medications and glaucoma filtering surgery was a significant risk factor related to a definite rejection event. PMID:25119961

  15. Immune response and histology of humoral rejection in kidney transplantation.

    Science.gov (United States)

    González-Molina, Miguel; Ruiz-Esteban, Pedro; Caballero, Abelardo; Burgos, Dolores; Cabello, Mercedes; Leon, Miriam; Fuentes, Laura; Hernandez, Domingo

    2016-01-01

    The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded. The special coexistence of binding and unbinding between antibodies and antigens of the endothelial cell membranes has been the cause of the delay in demonstrating the humoral allogenic response. The endothelium, the target tissue of antibodies, has a high turnover, and antigen-antibody binding is non-covalent. If endothelial cells are attacked by the humoral response, immunoglobulins are rapidly removed from their surface by shedding and/or internalization, as well as degrading the components of the complement system by the action of MCP, DAF and CD59. Thus, the presence of complement proteins in the membrane of endothelial cells is transient. In fact, the acute form of antibody-mediated rejection was not demonstrated until C4d complement fragment deposition was identified, which is the only component that binds covalently to endothelial cells. This review examines the relationship between humoral immune response and the types of acute and chronic histological lesion shown on biopsy of the transplanted organ. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Anaesthesia for vascular emergencies.

    Science.gov (United States)

    Ellard, L; Djaiani, G

    2013-01-01

    Patients presenting with vascular emergencies including acute aortic syndrome, ruptured thoracic or abdominal aortic aneurysms, thoracic aortic trauma and acute lower limb ischaemia have a high risk of peri-operative morbidity and mortality. Although anatomical suitability is not universal, endovascular surgery may improve mortality and the results of ongoing randomised controlled trials are awaited. Permissive hypotension pre-operatively should be the standard of care with the systolic blood pressure kept to 50-100 mmHg as long as consciousness is maintained. The benefit of local anaesthesia over general anaesthesia is not definitive and this decision should be tailored for a given patient and circumstance. Cerebrospinal fluid drainage for prevention of paraplegia is often impractical in the emergency setting and is not backed by strong evidence; however, it should be considered postoperatively if symptoms develop. We discuss the pertinent anaesthetic issues when a patient presents with a vascular emergency and the impact that endovascular repair has on anaesthetic management. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  17. Acute Gain in Minimal Lumen Area Following Implantation of Everolimus-Eluting ABSORB Biodegradable Vascular Scaffolds or Xience Metallic Stents: Intravascular Ultrasound Assessment From the ABSORB II Trial.

    Science.gov (United States)

    Sotomi, Yohei; Ishibashi, Yuki; Suwannasom, Pannipa; Nakatani, Shimpei; Cho, Yun-Kyeong; Grundeken, Maik J; Zeng, Yaping; Tateishi, Hiroki; Smits, Pieter C; Barragan, Paul; Kornowski, Ran; Gershlick, Anthony H; Windecker, Stephan; van Geuns, Robert-Jan; Bartorelli, Antonio L; de Winter, Robbert J; Tijssen, Jan; Serruys, Patrick W; Onuma, Yoshinobu

    2016-06-27

    The study compared, by intravascular ultrasound (IVUS), acute gain (AG) at the site of the pre-procedural minimal lumen area (MLA) achieved by either the Absorb (Abbott Vascular, Santa Clara, California) scaffold or the Xience stent and identified the factors contributing to the acute performance of these devices. It is warranted that the acute performance of Absorb matches that of metallic stents; however, concern exists about acute expansion and lumen gain with the use of Absorb. Of a total of 501 patients (546 lesions) in the ABSORB II (ABSORB II Randomized Controlled Trial) randomized trial, 445 patients with 480 lesions were investigated by IVUS pre- and post-procedure. Comparison of MLA pre- and post-procedure was performed at the MLA site by matching pre- and post-procedural IVUS pullbacks. Lower AG on IVUS (lowest tertile) occurred more frequently in the Absorb arm than in the Xience arm (3.46 mm(2) vs. 4.27 mm(2), respectively; p < 0.001; risk ratio: 3.04; 95% confidence interval: 1.94 to 4.76). The plaque morphology at the MLA cross-section was not independently associated with IVUS acute gain. The main difference in AG in MLD by angiography was observed at the time of device implantation (Xience vs. Absorb, Δ+1.50 mm vs. Δ+1.23 mm, respectively), whereas the gain from post-dilation was similar between the 2 arms (Δ+0.16 mm vs. Δ+0.16 mm) when patients underwent post-dilation, although expected balloon diameter was smaller in the Absorb arm than in the Xience arm (p = 0.003) during post-dilation. At the site of the pre-procedural MLA, the increase of the lumen post-procedure was smaller in the Absorb-arm than in the Xience arm. To achieve equivalent AG to Xience, the implantation of Absorb may require more aggressive strategies at implantation, pre- and post-dilation than the technique used in the ABSORB II trial. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281). Copyright © 2016 American College of Cardiology Foundation. Published

  18. Profile of the Pleximmune blood test for transplant rejection risk prediction

    Science.gov (United States)

    Sindhi, Rakesh; Ashokkumar, Chethan; Higgs, Brandon W; Levy, Samantha; Soltys, Kyle; Bond, Geoffrey; Mazariegos, George; Ranganathan, Sarangarajan; Zeevi, Adriana

    2016-01-01

    Summary The Pleximmune™ test (Plexision Inc., Pittsburgh, PA, USA) is the first cell-based test approved by the US FDA, which predicts acute cellular rejection in children with liver- or intestine transplantation. The test addresses an unmet need to improve management of immunosuppression, which incurs greater risks of opportunistic infections and Epstein–Barr virus-induced malignancy during childhood. High-dose immunosuppression and recurrent rejection after intestine transplantation also result in a 5-year graft loss rate of up to 50%. Such outcomes seem increasingly unacceptable because children can experience rejection-free survival with reduced immunosuppression. Pleximmune test sensitivity and specificity for predicting acute cellular rejection is 84% and 81% respectively in training set–validation set testing of 214 children. Among existing gold standards, the biopsy detects but cannot predict rejection. Anti-donor antibodies, which presage antibody-mediated injury, reflect late-stage allosensitization as a downstream effect of engagement between recipient and donor cells. Therefore, durable graft and patient outcomes also require an accurate management of cellular immune responses in clinical practice. PMID:26760313

  19. Predicting cellular rejection with a cell-based assay: Pre-clinical evaluation in children

    Science.gov (United States)

    Ashokkumar, Chethan; Soltys, Kyle; Mazariegos, George; Bond, Geoffrey; Higgs, Brandon W.; Ningappa, Mylarappa; Sun, Qing; Brown, Amanda; White, Jaimie; Levy, Samantha; Fazzolare, Tamara; Remaley, Lisa; Dirling, Katie; Harris, Patti; Hartle, Tara; Kachmar, Pam; Nicely, Megan; O'Toole, Lindsay; Boehm, Brittany; Jativa, Nicole; Stanley, Paula; Jaffe, Ronald; Ranganathan, Sarangarajan; Zeevi, Adriana; Sindhi, Rakesh

    2015-01-01

    Background Allospecific CD154+T-cytotoxic memory cells (CD154+TcM) predict acute cellular rejection (ACR) after liver or intestine transplantation (LTx, ITx) in small cohorts of children and can enhance immunosuppression management, but await validation and clinical implementation. Methods To establish safety and probable benefit, CD154+TcM were measured in cryopreserved samples from 214 children 1 implies increased rejection-risk. Results Training and validation set subjects were demographically similar. Mean coefficient of test variation was <10% under several conditions. Logistic regression incorporating several confounding variables identified separate pre-transplant and post-transplant IR thresholds for prediction of rejection in respective training set samples. An IR ≥ 1.1 in post-transplant training samples, and IR ≥1.23 in pre-transplant training samples predicted LTx or ITx rejection in corresponding validation set samples in the 60-day post-sampling period with sensitivity, specificity, positive and negative predictive values of 84%, 80%, 64%, and 92%, respectively (AUC 0.792), and 57%, 89%, 78%, and 74%, respectively (AUC 0.848). No adverse events were encountered due to phlebotomy. Conclusions Allospecific CD154+T-cytotoxic memory cells predict acute cellular rejection after liver or intestine transplantation in children. Adjunctive use can enhance clinical outcomes. PMID:26950712

  20. Structural Decoupling and Disturbance Rejection in a Distillation Column

    DEFF Research Database (Denmark)

    Bahar, Mehrdad; Jantzen, Jan; Commault, C.

    1996-01-01

    Introduction, distillation column model, input-output decoupling, disturbance rejection, concluding remarks, references.......Introduction, distillation column model, input-output decoupling, disturbance rejection, concluding remarks, references....

  1. Comparing reports of peer rejection: associations with rejection sensitivity, victimization, aggression, and friendship.

    Science.gov (United States)

    Zimmer-Gembeck, Melanie J; Nesdale, Drew; McGregor, Leanne; Mastro, Shawna; Goodwin, Belinda; Downey, Geraldine

    2013-12-01

    Perceiving that one is rejected is an important correlate of emotional maladjustment. Yet, self-perceptions can substantially differ from classmate-reports of who is rejected. In this study, discrepancies between self- and classmate-reports of rejection were identified in 359 Australian adolescents (age 10-12 years). As expected, adolescents who overestimated rejection reported more rejection sensitivity and felt more victimized by their peers, but were not seen by peers as more victimized. Adolescents who underestimated rejection identified themselves as high in overt aggression, and their peers identified them as high in overt and relational aggression and low in prosocial behavior. Yet, underestimators' feelings of friendship satisfaction did not seem to suffer and they reported low rejection sensitivity. Results suggest that interventions to promote adolescent health should explicitly recognize the different needs of those who do and do not seem to perceive their high rejection, as well as adolescents who overestimate their rejection. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  2. A bypass case due to an acute inferior myocardial infarction caused by vascular occlusion of the left subclavian artery and left anterior descending artery

    Directory of Open Access Journals (Sweden)

    Altas Y

    2016-07-01

    Full Text Available Yakup Altas, Ali Veysel Ulugg Department of Cardiology, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, Turkey Abstract: ST segment elevation is the most common electrocardiographic finding in acute myocardial infarction. ST elevation in chest leads generally represents left anterior descending artery occlusion, while elevation in DII and III, and aVF represents right coronary and circumflex artery occlusion. A female patient aged 66 years was admitted to our emergency service with ST elevation in leads DIII and aVF. A diagnosis of acute inferior myocardial infarction was made. The patient’s history included coronary artery bypass graft involving the left internal mammary artery to the left anterior descending coronary artery and aorta to the right coronary artery. The patient was taken to the cardiac catheterization laboratory for primary percutaneous coronary intervention and a lesion in the left anterior descending artery was identified. Additionally, the left subclavian artery was totally occluded. Following intervention to the lesion, the patient was discharged on day 4 of admission. Keywords: electrocardiography, myocardial infarction, coronary circulation

  3. The fate of triaged and rejected manuscripts.

    Science.gov (United States)

    Zoccali, Carmine; Amodeo, Daniela; Argiles, Angel; Arici, Mustafa; D'arrigo, Graziella; Evenepoel, Pieter; Fliser, Danilo; Fox, Jonathan; Gesualdo, Loreto; Jadoul, Michel; Ketteler, Markus; Malyszko, Jolanta; Massy, Ziad; Mayer, Gert; Ortiz, Alberto; Sever, Mehmet; Vanholder, Raymond; Vinck, Caroline; Wanner, Christopher; Więcek, Andrzej

    2015-12-01

    In 2011, Nephrology Dialysis and Transplantation (NDT) established a more restrictive selection process for manuscripts submitted to the journal, reducing the acceptance rate from 25% (2008-2009) to currently about 12-15%. To achieve this goal, we decided to score the priority of manuscripts submitted to NDT and to reject more papers at triage than in the past. This new scoring system allows a rapid decision for the authors without external review. However, the risk of such a restrictive policy may be that the journal might fail to capture important studies that are eventually published in higher-ranked journals. To look into this problem, we analysed random samples of papers (∼10%) rejected by NDT in 2012. Of the papers rejected at triage and those rejected after regular peer review, 59 and 61%, respectively, were accepted in other journals. A detailed analysis of these papers showed that only 4 out of 104 and 7 out of 93 of the triaged and rejected papers, respectively, were published in journals with an impact factor higher than that of NDT. Furthermore, for all these papers, independent assessors confirmed the evaluation made by the original reviewers. The number of citations of these papers was similar to that typically obtained by publications in the corresponding journals. Even though the analyses seem reassuring, previous observations made by leading journals warn that the risk of 'big misses', resulting from selective editorial policies, remains a real possibility. We will therefore continue to maintain a high degree of alertness and will periodically track the history of manuscripts rejected by NDT, particularly papers that are rejected at triage by our journal. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  4. Image rejects in general direct digital radiography

    Science.gov (United States)

    Rosanowsky, Tine Blomberg; Jensen, Camilla; Wah, Kenneth Hong Ching

    2015-01-01

    Background The number of rejected images is an indicator of image quality and unnecessary imaging at a radiology department. Image reject analysis was frequent in the film era, but comparably few and small studies have been published after converting to digital radiography. One reason may be a belief that rejects have been eliminated with digitalization. Purpose To measure the extension of deleted images in direct digital radiography (DR), in order to assess the rates of rejects and unnecessary imaging and to analyze reasons for deletions, in order to improve the radiological services. Material and Methods All exposed images at two direct digital laboratories at a hospital in Norway were reviewed in January 2014. Type of examination, number of exposed images, and number of deleted images were registered. Each deleted image was analyzed separately and the reason for deleting the image was recorded. Results Out of 5417 exposed images, 596 were deleted, giving a deletion rate of 11%. A total of 51.3% were deleted due to positioning errors and 31.0% due to error in centering. The examinations with the highest percentage of deleted images were the knee, hip, and ankle, 20.6%, 18.5%, and 13.8% respectively. Conclusion The reject rate is at least as high as the deletion rate and is comparable with previous film-based imaging systems. The reasons for rejection are quite different in digital systems. This falsifies the hypothesis that digitalization would eliminates rejects. A deleted image does not contribute to diagnostics, and therefore is an unnecessary image. Hence, the high rates of deleted images have implications for management, training, education, as well as for quality. PMID:26500784

  5. Ferulic Acid Improves Functional Recovery after Acute Spinal Cord Injury in Rats by Inducing Hypoxia to Inhibit microRNA-590 and Elevate Vascular Endothelial Growth Factor Expressions.

    Science.gov (United States)

    Li, Zhenjie; Wang, Shengyun; Li, Wenfang; Yuan, Hongbin

    2017-01-01

    Spinal cord injury (SCI) is the leading cause of paralysis, disability and even death in severe cases, and neural stem cells (NSCs) transplant has been employed for repairing SCI. Ferulic acid (FA) is able to promote neurogenesis in various stem cell therapies. We aimed to investigate the effect of FA on NSC transplant therapy, and the underlying mechanism, in improving functional recovery in SCI rat model. A rat model of SCI was established, which then received transplant of NSCs with or without FA pre-treatment. Functional recovery of the SCI rats was then evaluated, in terms of spinal cord water content, myeloperoxidase activity and behavioral assessments. Effect of FA in inducing hypoxia in NSCs was also assessed, followed by identifying the hypoxic regulated microRNA and the subsequent target gene. Transplant of FA pre-treated NSCs improved functional recovery of SCI rats to a more significant extent than NSCs without FA pre-treatment. The beneficial effects of FA in repairing SCI was mediated by inducing hypoxia in NSCs, which in turn inhibited microRNA-590 to elevate vascular endothelial growth factor expression. Our findings support the clinical potential of FA in improving efficacy of NSC transplant therapy for treatment of SCI.

  6. Acute glucoregulatory and vascular outcomes of three strategies for interrupting prolonged sitting time in postmenopausal women: A pilot, laboratory-based, randomized, controlled, 4-condition, 4-period crossover trial.

    Directory of Open Access Journals (Sweden)

    Jacqueline Kerr

    Full Text Available Prolonged sitting is associated with cardiometabolic and vascular disease. Despite emerging evidence regarding the acute health benefits of interrupting prolonged sitting time, the effectiveness of different modalities in older adults (who sit the most is unclear.In preparation for a future randomized controlled trial, we enrolled 10 sedentary, overweight or obese, postmenopausal women (mean age 66 years ±9; mean body mass index 30.6 kg/m2 ±4.2 in a 4-condition, 4-period crossover feasibility pilot study in San Diego to test 3 different sitting interruption modalities designed to improve glucoregulatory and vascular outcomes compared to a prolonged sitting control condition. The interruption modalities included: a 2 minutes standing every 20 minutes; b 2 minutes walking every hour; and c 10 minutes standing every hour. During each 5-hr condition, participants consumed two identical, standardized meals. Blood samples, blood pressure, and heart rate were collected every 30 minutes. Endothelial function of the superficial femoral artery was measured at baseline and end of each 5-hr condition using flow-mediated dilation (FMD. Participants completed each condition on separate days, in randomized order. This feasibility pilot study was not powered to detect statistically significant differences in the various outcomes, however, analytic methods (mixed models were used to test statistical significance within the small sample size.Nine participants completed all 4 study visits, one participant completed 3 study visits and then was lost to follow up. Net incremental area under the curve (iAUC values for postprandial plasma glucose and insulin during the 5-hr sitting interruption conditions were not significantly different compared to the control condition. Exploratory analyses revealed that the 2-minute standing every 20 minutes and the 2-minute walking every hour conditions were associated with a significantly lower glycemic response to the second

  7. Acute glucoregulatory and vascular outcomes of three strategies for interrupting prolonged sitting time in postmenopausal women: A pilot, laboratory-based, randomized, controlled, 4-condition, 4-period crossover trial.

    Science.gov (United States)

    Kerr, Jacqueline; Crist, Katie; Vital, Daniela G; Dillon, Lindsay; Aden, Sabrina A; Trivedi, Minaxi; Castellanos, Luis R; Godbole, Suneeta; Li, Hongying; Allison, Matthew A; Khemlina, Galina L; Takemoto, Michelle L; Schenk, Simon; Sallis, James F; Grace, Megan; Dunstan, David W; Natarajan, Loki; LaCroix, Andrea Z; Sears, Dorothy D

    2017-01-01

    Prolonged sitting is associated with cardiometabolic and vascular disease. Despite emerging evidence regarding the acute health benefits of interrupting prolonged sitting time, the effectiveness of different modalities in older adults (who sit the most) is unclear. In preparation for a future randomized controlled trial, we enrolled 10 sedentary, overweight or obese, postmenopausal women (mean age 66 years ±9; mean body mass index 30.6 kg/m2 ±4.2) in a 4-condition, 4-period crossover feasibility pilot study in San Diego to test 3 different sitting interruption modalities designed to improve glucoregulatory and vascular outcomes compared to a prolonged sitting control condition. The interruption modalities included: a) 2 minutes standing every 20 minutes; b) 2 minutes walking every hour; and c) 10 minutes standing every hour. During each 5-hr condition, participants consumed two identical, standardized meals. Blood samples, blood pressure, and heart rate were collected every 30 minutes. Endothelial function of the superficial femoral artery was measured at baseline and end of each 5-hr condition using flow-mediated dilation (FMD). Participants completed each condition on separate days, in randomized order. This feasibility pilot study was not powered to detect statistically significant differences in the various outcomes, however, analytic methods (mixed models) were used to test statistical significance within the small sample size. Nine participants completed all 4 study visits, one participant completed 3 study visits and then was lost to follow up. Net incremental area under the curve (iAUC) values for postprandial plasma glucose and insulin during the 5-hr sitting interruption conditions were not significantly different compared to the control condition. Exploratory analyses revealed that the 2-minute standing every 20 minutes and the 2-minute walking every hour conditions were associated with a significantly lower glycemic response to the second meal

  8. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection.

    Science.gov (United States)

    Stewart, Susan; Winters, Gayle L; Fishbein, Michael C; Tazelaar, Henry D; Kobashigawa, Jon; Abrams, Jacki; Andersen, Claus B; Angelini, Annalisa; Berry, Gerald J; Burke, Margaret M; Demetris, Anthony J; Hammond, Elizabeth; Itescu, Silviu; Marboe, Charles C; McManus, Bruce; Reed, Elaine F; Reinsmoen, Nancy L; Rodriguez, E Rene; Rose, Alan G; Rose, Marlene; Suciu-Focia, Nicole; Zeevi, Adriana; Billingham, Margaret E

    2005-11-01

    In 1990, an international grading system for cardiac allograft biopsies was adopted by the International Society for Heart Transplantation. This system has served the heart transplant community well, facilitating communication between transplant centers, especially with regard to patient management and research. In 2004, under the direction of the International Society for Heart and Lung Transplantation (ISHLT), a multidisciplinary review of the cardiac biopsy grading system was undertaken to address challenges and inconsistencies in its use and to address recent advances in the knowledge of antibody-mediated rejection. This article summarizes the revised consensus classification for cardiac allograft rejection. In brief, the revised (R) categories of cellular rejection are as follows: Grade 0 R--no rejection (no change from 1990); Grade 1 R--mild rejection (1990 Grades 1A, 1B and 2); Grade 2 R--moderate rejection (1990 Grade 3A); and Grade 3 R--severe rejection (1990 Grades 3B and 4). Because the histologic sub-types of Quilty A and Quilty B have never been shown to have clinical significance, the "A" and "B" designations have been eliminated. Recommendations are also made for the histologic recognition and immunohistologic investigation of acute antibody-mediated rejection (AMR) with the expectation that greater standardization of the assessment of this controversial entity will clarify its clinical significance. Technical considerations in biopsy processing are also addressed. This consensus revision of the Working Formulation was approved by the ISHLT Board of Directors in December 2004.

  9. Total hepatectomy model in pigs: Revised method for vascular reconstruction using a rigid vascular prosthesis

    NARCIS (Netherlands)

    Sosef, M. N.; van Gulik, T. M.

    2004-01-01

    Total hepatectomy in animals provides an irreversible model of acute liver failure. Vascular reconstruction in this model of acute liver failure was modified and characterized for the use of assessment of liver support systems. Pigs underwent total hepatectomy and a rigid three-way transparent

  10. Human polyclonal anti-hepatitis B surface antigen immunoglobulin reduces the frequency of acute rejection after liver transplantation for chronic hepatitis B A imunoglobulina policlonal humana anti-antígeno de superfície da hepatite B reduz a freqüência da rejeição aguda após transplante de fígado

    Directory of Open Access Journals (Sweden)

    Claudia Alves COUTO

    2001-12-01

    Full Text Available BACKGROUND: Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg has been shown to reduce hepatitis B virus (HBV recurrence after liver transplantation (LT and to decrease the frequency of acute cellular rejection (ACR. However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM: To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS: 260 patients (158 males, 43 ± 14 years old submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12 that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10. Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS: HBIg-treated patients (group I had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS: Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT.INTRODUÇÃO: O emprego da imunoglobulina policlonal anti-antígeno de superfície da hepatite B (HBIg tem reduzido a recorrência da hepatite B após transplante hepático (TH, assim como também a freqüência de rejeição celular aguda (RCA. No entanto, o papel protetor da HBIg contra a RCA permanece controverso, pois a própria infecção por vírus B foi também associada a menor incidência de RCA. OBJETIVOS: Verificar a relação entre HBIg e a freqüência de RCA após TH. MÉTODOS: 260 pacientes (158 do sexo masculino, com 43 ± 14 anos submetidos a TH foram avaliados, retrospectivamente, e divididos em três grupos de acordo com a presença de AgHBs e uso de

  11. Understanding Rejection between First-and-Second-Grade Elementary Students through Reasons Expressed by Rejecters

    Science.gov (United States)

    García Bacete, Francisco J.; Carrero Planes, Virginia E.; Marande Perrin, Ghislaine; Musitu Ochoa, Gonzalo

    2017-01-01

    Objective: The aim of this research was to obtain the views of young children regarding their reasons for rejecting a peer. Method: To achieve this goal, we conducted a qualitative study in the context of theory building research using an analysis methodology based on Grounded Theory. The collected information was extracted through semi-structured individual interviews from a sample of 853 children aged 6 from 13 urban public schools in Spain. Results: The children provided 3,009 rejection nominations and 2,934 reasons for disliking the rejected peers. Seven reason categories emerged from the analysis. Four categories refer to behaviors of the rejected children that have a cost for individual peers or peer group such as: direct aggression, disturbance of wellbeing, problematic social and school behaviors and dominance behaviors. A further two categories refer to the identities arising from the preferences and choices of rejected and rejecter children and their peers: personal identity expressed through preferences and disliking, and social identity expressed through outgroup prejudices. The “no-behavior or no-choice” reasons were covered by one category, unfamiliarity. In addition, three context categories were found indicating the participants (interpersonal–group), the impact (low–high), and the subjectivity (subjective–objective) of the reason. Conclusion: This study provides researchers and practitioners with a comprehensive taxonomy of reasons for rejection that contributes to enrich the theoretical knowledge and improve interventions for preventing and reducing peer rejection. PMID:28421008

  12. Peer Rejection as a Social Antecedent to Rejection Sensitivity in Youth: The Role of Relational Valuation.

    Science.gov (United States)

    Wang, Jennifer; McDonald, Kristina L; Rubin, Kenneth H; Laursen, Brett

    2012-11-01

    Although much is known about the consequences of rejection sensitivity (RS), less is known about its social antecedents, particularly during development. Despite research demonstrating the role of peer rejection in the development and maintenance of problematic social schema like RS, little is known about why some youth are more susceptible to these negative consequences than others. We examined how relational valuation might moderate the effects of peer rejection on RS in a sample of 294 youth (138 boys) who made the transition from middle to high school. Results from path analysis revealed that 8th grade peer rejection was most highly associated with 9th grade RS for youth who held high regard for social relationships. Findings demonstrate the importance of examining cognitive moderators in the links between negative social experiences and problematic social schema, and highlight the need to move beyond simple main effects models for understanding the heterogeneity of rejection.

  13. Large Solar-Rejection Filter

    Science.gov (United States)

    Roberts, William; Sheikh, David; Patrick, Brian

    2007-01-01

    times solar, and sulfur is 20 times solar. From its previously observed optical emission lines, P831-57 (WD 0334 6400 or Ret 1 in A Catalog and Atlas of Cataclysmic Variables: Living Edition) has been suspected to contain an accretion disk associated with a companion star in orbit around a subdwarf star with a temperature T is greater than 21,000K. P831-57 has therefore been classified as a nova-like. However, our present observations show it to be a DA + dMe binary. The analysis of its Far Ultraviolet Spectroscopic Explorer (FUSE) spectrum (continuum and lines) reveal an average mass white dwarf (Log(g) approximately equals 7.8 plus or minus 0.1)with a temperature T approximately equals 37,000 plus or minus 500K, an extremely low projected rotational velocity, and a distance of about 115 plus or minus 5pc. The photosphere contains C, N, Si, and S (at about 1% of solar abundances). The dMe star is seen as a flux excess in near-infrared photometry and appears to show occasional flaring of about one magnitude as seen in the Harvard plates. There is no evidence of periodic variability in the spectroscopic or photometric data. We find no evidence of a an accretion disk, instead we find evidence of wind accretion as the stellar carbon abundance (N(C)/N(H) = 2.5 x 10 (exp -6) is about ten times larger than predicted by radiative levitation for such a gravity and temperature. The power needs and solutions for the space exploration and lunar mobility program are discussed. Long term missions in space and on the lunar surface require high energy batteries. Rechargeable batteries for mobility systems and portable utility pallet are needed for successful exploration missions. Nanomaterial usage increases the energy density of the cells apart from increasing the power density. The symptoms and threats from acute mountain sickness (AMS) are discussed. The underlying assumptions concerning spacecraft atmosphere mean there is a potential risk to astronauts. The baseline worst case

  14. Successful management of immunological rejection following allogeneic simple limbal epithelial transplantation (SLET) for bilateral ocular burns.

    Science.gov (United States)

    Bhalekar, Swapnil; Basu, Sayan; Sangwan, Virender S

    2013-03-14

    A 41-year-old woman presented with bilateral total limbal stem cell deficiency, one year after chemical injury. She underwent allogeneic simple limbal epithelial transplantation (SLET) from a cadaveric donor in her right eye. One month later her unaided visual acuity (VA) improved to 20/100 from hand-motions. The corneal surface was avascular and epithelialised. Three months later, she presented with acute pain in right eye with peripheral corneal neovascularisation encircling the transplants, engorged and tortuous perilimbal vessels and diffuse epithelial haze. For a diagnosis of allograft rejection, pulse doses of intravenous methyl prednisolone with intensive topical steroids were administered. Her symptoms resolved in a week, confirming the diagnosis. She recovered her pre-rejection VA. She was maintained on systemic immunosuppressive agents. Her ocular surface continues to be stable. This case describes hitherto unknown clinical features of allograft rejection following SLET and emphasises the importance of continued immunosuppression in allogeneic limbal transplantation.

  15. Cerebrospinal fluid and plasma concentration of soluble intercellular adhesion molecule1, vascular cell adhesion molecule1 and endothelial leukocyte adhesion molecule in patients with acute ischemic b

    Directory of Open Access Journals (Sweden)

    Selaković Vesna M.

    2003-01-01

    Full Text Available Background. Leukocyte migration into the ischemic area is a complex process controlled by adhesion molecules (AM in leukocytes and endothelium, by migratory capacity of leukocytes and the presence of hemotaxic agents in the tissue. In this research it was supposed that in the blood and cerebrospinal fluid (CSF of patients in the acute phase of ischemic brain disease (IBD there were relevant changes in the concentration of soluble AM (sICAM-1 sVCAM-1 and sE-selectin, that could have been the indicators of the intensity of damaging processes in central nervous system (CNS. Methods. The study included 45 IBD patients, 15 with transient ischemic attack (TIA 15 with reversible ischemic attack (RIA, and 15 with brain infarction (BI of both sexes, mean age 66±7. Control group consisted of 15 patients with radicular lesions of discal origin, subjected to diagnostic radiculography without the signs of interruption in the passage of CSF. Changes of selected biochemical parameters were determined in all patients in frame 72 hours since the occurence of an ischemic episode. Concentrations of soluble AM were determined in plasma and CSF by ELISA. Total number of leukocytes (TNL in peripheral blood was determined by hematological analyzer. Results. The results showed that during the first 72 hrs of IBD significant increases occured in TNL and that the increase was progressive compared to the severeness of the disease. Significant increase of soluble AM concentration was shown in plasma of IBD patients. The increase was highest in BI somewhat lower in RIA and the lowest in TIA patients compared to the control. In CSF concentrations of sICAM-1, sVCAM-1 and sE-selectin demonstrated similar increasing trend as in plasma. Conclusion. TNL, as well as the soluble AM concentrations in plasma and CSF, were increased during the acute IBD phase and progressive in relation to the severeness of the disease, so that they might have been the indicators of CNS inflammatory

  16. Transesophageal echocardiography (TEE) vs. transthoracic echocardiography (TTE) in assessing cardio-vascular sources of emboli in patients with acute ischemic stroke.

    Science.gov (United States)

    Blum, Arnon; Reisner, Shimon; Farbstein, Yakov

    2004-09-01

    Transesophageal echocardiography (TEE) is a valuable tool in the evaluation of ischemic stroke patients. However, the real clinical impact of additional TEE data remains to be defined. Our purpose was to evaluate the impact of TEE on the management of patients at low risk for cardiogenic embolism. We studied 68 patients (57+/-10 years old) with ischemic stroke at low-risk for cardiogenic embolism. Each patient underwent bilateral carotid ultrasound Doppler study, trans-thoracic echocardiography (TTE) and TEE in order to find out left atrial spontaneous echo contrast or intracavitary thrombi, communication or aneurysm of the inter-atrial septum, ventricular septal defect, patent foramen ovale, and the presence of intra-aortic atherosclerotic plaques or thrombi. In 28 out of 68 patients TEE found an abnormal lesion that has not been detected by TTE: there were 23 diffuse (>5mm) atherosclerotic atheromas in the aortic arch, 5 patent foramen ovale (PFO) lesions, 3 left atrial thrombi, 1 ventricular septal defect (VSD), and 1 atrial septal defect (ASD). 6 patients had more than 1 finding. These findings changed the management, and all 28 patients started to be treated with Coumadine instead of Aspirin. Patients with PFO were sent to close the shunt with a patch. In half of the patients TEE (but not TTE) found a significant lesion that changed our policy of management. None of these lesions were detected by TTE. It seems that TEE is mandatory in the evaluation of patients with acute ischemic stroke.

  17. Administration of Antithymocyte Globulin (Rabbit) to Treat a Severe, Mixed Rejection Episode in a Pregnant Renal Transplant Recipient.

    Science.gov (United States)

    Kutzler, Heather L; Ye, Xiaoyi; Rochon, Caroline; Martin, Spencer T

    2016-04-01

    Pregnancy in solid organ transplant recipients carries numerous risks to the mother such as increased risk of rejection, gestational diabetes mellitus, and preeclampsia. The developing fetus is subjected to risks such as birth defects, preterm delivery, and low birth weight. Typically, these risks can be managed through intensive, multidisciplinary prenatal care and a proper immunosuppressive regimen. In the setting of rejection, however, little data are available to suggest safe and effective treatment of acute cellular rejection, antibody-mediated rejection, or mixed rejection episodes in the pregnant solid organ transplant recipient. We describe the first case, to our knowledge, in which antithymocyte globulin (rabbit) was used to successfully treat a pregnant renal transplant recipient who experienced a mixed rejection episode. A 22-year-old, African American woman with stage 6 chronic kidney disease received a deceased donor renal transplant after undergoing hemodialysis for 3 years. Her maintenance immunosuppressive regimen at the time of transplantation consisted of tacrolimus, prednisone, and mycophenolate mofetil. Despite counseling efforts on the importance of having a planned pregnancy after kidney transplantation so that her immunosuppressive medications could be optimized, the patient became pregnant 12 months later; her mycophenolate mofetil was changed to azathioprine to reduce the risk of fetal deformities or death. Three months later, the patient was admitted for biopsy of her transplanted kidney and was evaluated for possible kidney rejection. After confirmation of a mixed 1B acute cellular rejection and antibody-mediated rejection episode, the patient decided to pursue resolution of her rejection episode and continue the pregnancy despite the potential risks to the fetus. She was treated with high-dose corticosteroids, intravenous immunoglobulin, plasmapheresis, and antithymocyte globulin (rabbit). Twenty-nine months after transplantation, the

  18. VASCULAR COMPLICATIONS AFTER KIDNEY TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    M. Sh. Khubutia

    2013-01-01

    Full Text Available Aim: evaluation of the incidence and the pattern of vessel complications, efficacy of the prophylactic anticoagulation therapy after kidney transplantation. Materials and methods. From March 2007 till January 2013 421 patients: 230 men (54,6% and 191 women (45,4%; mean age 43,07 ± 11,62 undergone 429 kidney transplantations in the department of pancreas and kidney transplantation of the Scientific-Research Institute of Emergency Care named after N.V. Sklifosovsky. In order to evaluate the condition and the function of the kidney transplant ultrasound investigation (daily andacquisition(weekly wereused. In cases of kidney dysfunction and assumption of vessel complications we used computerized tomography. Besides, we used daily analysis of biochemical and clinical parameters of blood and urine. Results. The most common vessel complication was the thrombosis of the microvasculature of the kidney transplant due to acute humoral and combined rejection resistant to antirejection therapy (n = 9; 2,1%; in 4 cases there was a breakage of the transplant due to the acute rejection and the urgent transplantatectomy in an effort to save the patient; thrombosis of the transplantat artery occurred in 1 case (0,23%; we observed 2 cases (0,46% of the artery stenosis and 2 cases (0,46% of venous thrombosis. Conclusion. Summary frequency of vessel complications in our clinic, including thrombosis due to rejection, was 3,49%. It fully corresponds with data obtained from the global medical community. The incidence of great vessel thrombosis was less than 1% which indicates the adequate prophylactic anticoagulation therapy. For the benefit of early diacrisis of complications Doppler sonography is needed. In case of assumption of vessel complications urgent acquisition, computerized tomography and/ or angiography are to be held. 

  19. Comparison of Ticagrelor Versus Prasugrel for Inflammation, Vascular Function, and Circulating Endothelial Progenitor Cells in Diabetic Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Requiring Coronary Stenting: A Prospective, Randomized, Crossover Trial.

    Science.gov (United States)

    Jeong, Han Saem; Hong, Soon Jun; Cho, Sang-A; Kim, Jong-Ho; Cho, Jae Young; Lee, Seung Hun; Joo, Hyung Joon; Park, Jae Hyoung; Yu, Cheol Woong; Lim, Do-Sun

    2017-08-28

    This study compared adenosine-associated pleiotropic effects of the 2 P2Y12 receptor antagonists on vascular function, systemic inflammation, and circulating endothelial progenitor cells (EPCs). Both ticagrelor and prasugrel have potent antiplatelet effects. However, only ticagrelor inhibits cellular uptake of adenosine. Using a randomized, crossover design with 10-week follow-up ticagrelor or prasugrel was administered to type 2 diabetic patients with non-ST-segment elevation acute coronary syndrome requiring stent implantation. A total of 62 patients underwent randomization in a 1:1 ratio to receive ticagrelor or prasugrel for 5 weeks followed by a direct cross over to the alternative treatment for 5 additional weeks. Brachial artery flow-mediated dilation, inflammatory markers, and number of circulating EPCs were compared. Improvement in brachial artery flow-mediated dilation was greater in the ticagrelor group (0.15 ± 0.19 mm vs. -0.03 ± 0.18 mm; p ticagrelor compared with prasugrel decreased interleukin 6 (-0.58 ± 0.43 pg/ml vs. -0.05 ± 0.24 pg/ml; p Ticagrelor compared with prasugrel significantly increased absolute numbers of circulating EPCs CD34+/KDR+ (42.5 ± 37.8 per μl vs. -28.2 ± 23.7 per μl; p ticagrelor significantly decreased inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha and increased circulating EPCs, contributing to improved arterial endothelial function in diabetic non-ST-segment elevation acute coronary syndrome patients. Thus, data support that pleiotropic effects of ticagrelor beyond its potent antiplatelet effects could contribute to additional clinical benefits. (Comparison of Ticagrelor vs. Prasugrel on Inflammation, Arterial Stiffness, Endothelial Function, and Circulating Endothelial Progenitor Cells in Diabetic Patients With Non-ST Elevation Acute Coronary Syndrome [NSTE-ACS] Requiring Coronary Stenting; NCT02487732). Copyright © 2017 American College of Cardiology Foundation. Published

  20. Waste heat rejection from geothermal power stations

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, R.C.

    1978-12-01

    This study of waste heat rejection from geothermal power stations is concerned only with the heat rejected from the power cycle. The heat contained in reinjected or otherwise discharged geothermal fluids is not included with the waste heat considered here. The heat contained in the underflow from the flashtanks in such systems is not considered as part of the heat rejected from the power cycle. By following this definition of the waste heat to be rejected, various methods of waste heat dissipation are discussed without regard for the particular arrangement to obtain heat from the geothermal source. Recent conceptual design studies made for 50-MW(e) geothermal power stations at Heber and Niland, California, are of particular interst. The former uses a flashed-steam system and the latter a binary cycle that uses isopentane. In last-quarter 1976 dollars, the total estimated capital costs were about $750/kW and production costs about 50 mills/kWhr. If wet/dry towers were used to conserve 50% of the water evaporation at Heber, production costs would be about 65 mills/kWhr.

  1. Ferrite grade iron oxides from ore rejects

    Indian Academy of Sciences (India)

    Unknown

    Abstract. Iron oxyhydroxides and hydroxides were synthesized from chemically beneficiated high SiO2/Al2O3 low-grade iron ore (57⋅49% Fe2O3) rejects and heated to get iron oxides of 96–99⋅73% purity. The infrared band positions, isothermal weight loss and thermogravimetric and chemical analysis established the ...

  2. Ferrite grade iron oxides from ore rejects

    Indian Academy of Sciences (India)

    Iron oxyhydroxides and hydroxides were synthesized from chemically beneficiated high SiO2/Al2O3 low-grade iron ore (57.49% Fe2O3) rejects and heated to get iron oxides of 96–99.73% purity. The infrared band positions, isothermal weight loss and thermogravimetric and chemical analysis established the chemical ...

  3. Development of enhanced sulfur rejection processes

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, R.H.; Luttrell, G.H.; Adel, G.T.; Richardson, P.E.

    1996-03-01

    Research at Virginia Tech led to the development of two complementary concepts for improving the removal of inorganic sulfur from many eastern U.S. coals. These concepts are referred to as Electrochemically Enhanced Sulfur Rejection (EESR) and Polymer Enhanced Sulfur Rejection (PESR) processes. The EESR process uses electrochemical techniques to suppress the formation of hydrophobic oxidation products believed to be responsible for the floatability of coal pyrite. The PESR process uses polymeric reagents that react with pyrite and convert floatable middlings, i.e., composite particles composed of pyrite with coal inclusions, into hydrophilic particles. These new pyritic-sulfur rejection processes do not require significant modifications to existing coal preparation facilities, thereby enhancing their adoptability by the coal industry. It is believed that these processes can be used simultaneously to maximize the rejection of both well-liberated pyrite and composite coal-pyrite particles. The project was initiated on October 1, 1992 and all technical work has been completed. This report is based on the research carried out under Tasks 2-7 described in the project proposal. These tasks include Characterization, Electrochemical Studies, In Situ Monitoring of Reagent Adsorption on Pyrite, Bench Scale Testing of the EESR Process, Bench Scale Testing of the PESR Process, and Modeling and Simulation.

  4. Accept & Reject Statement-Based Uncertainty Models

    NARCIS (Netherlands)

    E. Quaeghebeur (Erik); G. de Cooman; F. Hermans (Felienne)

    2015-01-01

    textabstractWe develop a framework for modelling and reasoning with uncertainty based on accept and reject statements about gambles. It generalises the frameworks found in the literature based on statements of acceptability, desirability, or favourability and clarifies their relative position. Next

  5. Rejection Pathways in Heart Transplant Recipients

    NARCIS (Netherlands)

    N.M. van Besouw (Nicole)

    1999-01-01

    textabstractSince the beginning of this century experimental heart transplantations in animal studies were performed.' These studies were started in Rotterdam in the seventies to compare heterotopic and orthotopic heart transplantations, and to study the process of chronic rejection. The history of

  6. Music genre recognition with risk and rejection

    DEFF Research Database (Denmark)

    Sturm, Bob L.

    2013-01-01

    We explore risk and rejection for music genre recognition (MGR) within the minimum risk framework of Bayesian classification. In this way, we attempt to give an MGR system knowledge that some misclassifications are worse than others, and that deferring classification to an expert may be a better...

  7. CD28 Family and Chronic Rejection: “To Belatacept...and Beyond!”

    Directory of Open Access Journals (Sweden)

    Marcos V. Silva

    2012-01-01

    Full Text Available Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.

  8. The outcast-lash-out effect in youth: alienation increases aggression following peer rejection.

    Science.gov (United States)

    Reijntjes, Albert; Thomaes, Sander; Bushman, Brad J; Boelen, Paul A; de Castro, Bram Orobio; Telch, Michael J

    2010-10-01

    Although there are good theoretical reasons to believe that youth who are high in alienation (i.e., estranged from society, significant others, and themselves) are prone to behave aggressively, empirical evidence is lacking. The present experiment tested whether alienation moderates the effects of acute peer rejection on aggression in youth. Participants (N = 121; mean age = 11.5 years) completed a personal profile (e.g., "How do you describe yourself?") that was allegedly evaluated online by a panel of peer judges. After randomly receiving negative or positive feedback from peer judges, participants were given the opportunity to aggress against them (i.e., by reducing their monetary reward and by posting negative comments about them online). As predicted, alienation increased participants' aggression against peers who had rejected them, but not against peers who had praised them, even after controlling for peer-nominated chronic rejection and peer-nominated aggression. Thus, alienated youth are more aggressive than others when they experience acute peer rejection.

  9. Spinal Cord Vascular Disease

    Directory of Open Access Journals (Sweden)

    Abdoreza Ghoreishi

    2017-02-01

    Full Text Available The spinal cord is subject to many of the same vascular diseases that involve the brain, but its anatomy and embryology render it susceptible to some syndromes that do not have intracranial counterparts.The embryonic arterial supply to the spinal cord derives from intradural vessels that enter at each spinal level and divide to follow the dorsal and ventral roots. SPINAL CORD ISCHEMIA: The midthoracic levels of the spinal cord are traditionally considered to be the most vulnerable to compromise from hypoperfusion, but more recent evidence suggests that the lower thoracic cord is at greater risk . The actual prevalence of spinal cord infarction is unknown, but is generally cited as representing 1% to 2% of all central neurovascular events and 5% to 8% of all acute myelopathies. Weakness (100%, sensory loss (89%, back pain at onset (82%, and urinary complaints requiring catheterization (75% were the most common symptoms of cord ischemia at the time of presentation . Weakness most commonly affects both legs. Examination typically reveals flaccid paresis accompanied by diminished superficial and tendon reflexes below the level of the lesion. Preservation of strength and reflexes suggests the rare syndrome of posterior spinal artery territory infarction. Weakness most commonly affects both legs. Examination typically reveals flaccid paresis accompanied by diminished superficial and tendon reflexes below the level of the lesion. Preservation of strength and reflexes suggests the rare syndrome of posterior spinal artery territory infarction.   Aortic pathologies with regional hemodynamic compromise are the most common cause of spinal cord infarction, accounting for 30% to 40% of cases.                                                                                 The medical management of spinal cord ischemia is generally supportive and focused on reducing risk for

  10. Microsporidial infection masquerading as graft rejection post-Descemet's stripping automated endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Lumbini Devi

    2017-01-01

    Full Text Available A 51-year-old immunocompetent male with a history of Fuchs' endothelial dystrophy and immature cataract who underwent Descemet's stripping automated endothelial keratoplasty with intraocular lens implantation in both eyes presented with redness and defective vision of 1-day duration in his left eye. Slit lamp examination revealed coarse superficial punctate lesions with graft edema. He was diagnosed with acute graft rejection and treated with topical steroids. Two days later, symptoms worsened in his left eye with the involvement of his right eye showing a similar clinical picture. An infectious etiology was suspected and in vivo confocal microscopy ordered, which revealed hyperreflective dots, highly suggestive of microsporidial spores. The patient was prescribed topical fluconazole 0.3% in both eyes. This unique presentation of bilateral graft edema following microsporidial keratoconjunctivitis in postgraft patients requires a high index of suspicion as it can be easily be mistaken for and mismanaged as acute graft rejection.

  11. Ciclosporin metabolite pattern in blood and urine of liver graft recipients. II. Influence of cholestasis and rejection.

    Science.gov (United States)

    Christians, U; Kohlhaw, K; Budniak, J; Bleck, J S; Schottmann, R; Schlitt, H J; Almeida, V M; Deters, M; Wonigeit, K; Pichlmayr, R

    1991-01-01

    The pattern of metabolites of ciclosporin in blood and 24 h-urine of 58 liver graft recipients was routinely monitored by HPLC from transplantation until discharge from hospital. Liver function and ciclosporin metabolite pattern in patients with an uncomplicated clinical course and in those with cholestasis or acute rejection were compared. During cholestasis M19 and M1A, and during acute rejection M19, in blood were significantly elevated compared to the control group. Blood M19 was significantly correlated with bilirubin concentration and gamma-glutamyl transferase activity in serum, and M1A with the serum bilirubin concentration. Analysis of the metabolite pattern over the observation period showed higher concentrations of M19 and M1A in blood from patients with cholestasis and acute rejection than in the control group; concentrations were lower in the rejection group than in the cholestasis group. The metabolite pattern in 24 h-urine showed similar alterations in ciclosporin metabolite pattern to those in blood. Cholestasis and rejection shift the ciclosporin metabolite pattern in blood and urine to higher concentrations of M19 and M1A, whereas the concentrations of other metabolites and ciclosporin were not significantly affected.

  12. Vascular gastric anomalies as a cause of relapsing bleeding

    Directory of Open Access Journals (Sweden)

    Golubović Gradimir

    2008-01-01

    Full Text Available Background. Although relatively rare, gastric vascular anomalies can be recognized as a source of both chronic and acute blood loss, most often presenting as long term iron deficiency anemia, rarely as severe acute gastrointestinal bleeding. Case report. We present five patients with various gastric vascular anomalies, diagnosed during the year of 2003. in the Clinical Hospital Center Zemun. The diagnosis was based on endoscopic appearances, clinical history and characteristic histological findings. Gastric vascular anomalies presented in our review were: portal hypertensive gastropathy, gastric antral vascular ectasia, angiodysplasia, hereditary hemorrhagic telangiectasia and Dieulafoy lesion. The used treatment modalities included surgery and various endoscopic techniques (schlerotherapy, argon plasma coagulation. Conclusion. Patients presented with chronic iron deficiency anemia or acute and recurrent gastrointestinal hemorrhage should be considered as having one of gastric vascular anomalies.

  13. Batting 300 is good: perspectives of faculty researchers and their mentors on rejection, resilience, and persistence in academic medical careers.

    Science.gov (United States)

    DeCastro, Rochelle; Sambuco, Dana; Ubel, Peter A; Stewart, Abigail; Jagsi, Reshma

    2013-04-01

    Professional rejection is a frequent experience in an academic medical career. The authors sought to understand how rejection affects those pursuing such careers and why some individuals may be more resilient than others in a population of individuals with demonstrated ability and interest in research careers. Between February 2010 and August 2011, the authors conducted semistructured, in-depth telephone interviews with 100 former recipients of National Institutes of Health mentored career development awards and 28 of their mentors. Purposive sampling ensured a diverse range of viewpoints. Multiple analysts thematically coded verbatim transcripts using qualitative data analysis software. Participants described a variety of experiences with criticism and rejection in their careers, as well as an acute need for persistence and resilience in the face of such challenges. Through their narratives, participants also vividly described a range of emotional and behavioral responses to their experiences of professional rejection. Their responses illuminated the important roles that various factors, including mentoring and gender, have played in shaping the ultimate influence of rejection on their own careers and on the careers of those they have mentored. Responses to rejection vary considerably, and negative responses can lead promising individuals to abandon careers in academic medicine. Resilience does not, however, seem to be immutable-It can be learned. Given the frequency of experiences with rejection in academic medicine, strategies such as training mentors to foster resilience may be particularly helpful in improving faculty retention in academic medicine.

  14. History of abuse and risky sex among substance users: The role of rejection sensitivity and the need to belong.

    Science.gov (United States)

    Woerner, Jacqueline; Kopetz, Catalina; Lechner, William V; Lejuez, Carl

    2016-11-01

    This study investigates abuse and rejection sensitivity as important correlates of risky sexual behavior in the context of substance use. Victims of abuse may experience heightened sensitivity to acute social rejection and consequently engage in risky sexual behavior in an attempt to restore belonging. Data were collected from 258 patients at a substance use treatment facility in Washington, D.C. Participants' history of abuse and risky sexual behavior were assessed via self-report. To test the mediating role of rejection sensitivity, participants completed a social rejection task (Cyberball) and responded to a questionnaire assessing their reaction to the rejection experience. General risk-taking propensity was assessed using a computerized lab measure. Abuse was associated with increased rejection sensitivity (B=0.124, SE=0.040, p=0.002), which was in turn associated with increased risky sex (B=0.06, SE=0.028, p=0.03) (indirect effect=0.0075, SE=0.0043; 95% CI [0.0006, 0.0178]), but not with other indices of risk-taking. These findings suggest that rejection sensitivity may be an important mechanism underlying the relationship between abuse and risky sexual behavior among substance users. These effects do not extend to other risk behaviors, supporting the notion that risky sex associated with abuse represents a means to interpersonal connection rather than a general tendency toward self-defeating behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. DISTURBANCE OF THE CARDIOMYOCYTE’S MACROMOLECULAR STRUCTURE IN HEART ALLOGRAFTS AS A SIGN OF CHRONIC REJECTION

    Directory of Open Access Journals (Sweden)

    A. G. Kupriyanova

    2012-01-01

    Full Text Available Chronic rejection, especially cardiac allograft vasculopathy, is a major limiting factor for long-term transplant survival. This process affects not only the blood vessels, but also cardiomyocytes. However, there are extremely few reports on the evaluation of their macromolecular structure state. The aim of the study was to evaluate the structural proteins of cardiomyocytes (actin, myosin, troponin I, titin, desmin, vinculin of heart allografts in different periods after the operation (from 6 days to 15 years. Major changes of macromolecular structure were revealed in late period after transplantation (6 months – 15 years. The contribution of humoral immune response in the process of chronic cardiac allograft rejection was observed: in eight of twelve recipients episodes of acute humoral rejection had been repeatedly registered; disorders of the expression of 5 proteins out of 6 characterized were found in recipients with recurrent and persistent antibody-mediated rejection

  16. To Accept or Reject? The Impact of Adolescent Rejection Sensitivity on Early Adult Romantic Relationships

    Science.gov (United States)

    Hafen, Christopher A.; Spilker, Ann; Chango, Joanna; Marston, Emily S.; Allen, Joseph P.

    2013-01-01

    Successfully navigating entry into romantic relationships is a key task in adolescence, which sensitivity to rejection can make difficult to accomplish. This study uses multi-informant data from a community sample of 180 adolescents assessed repeatedly from age 16 to 22. Individuals with elevated levels of rejection sensitivity at age 16 were less likely to have a romantic partner at age 22, reported more anxiety and avoidance when they did have relationships, and were observed to be more negative in their interactions with romantic partners. In addition, females whose rejection sensitivity increased during late adolescence were more likely to adopt a submissive pattern within adult romantic relationships, further suggesting a pattern in which rejection sensitivity forecasts difficulties. PMID:24729668

  17. SUCCESSFUL APPLICATION OF PERIPHERAL VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION FOR CARDIAC ALLOGRAFT ANTIBODY-MEDIATED REJECTION WITH SEVERE HEMODYNAMIC COMPROMISE

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2015-01-01

    Full Text Available Introduction. Acute antibody-mediated rejection (AMR is one of the severe complications of early and late period after heart transplantation (HT. Only few case reports and studies presented of mechanical circulatory support (MCS application for refractory acute rejection causing hemodynamic compromise. Aim. We report the case of a woman with cardiogenic shock caused by severe AMR that was successfully treatment by peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO. Material and methods. In december 2014, a 60-year-old woman with dilated cardiomyopathy was operated for HT. The patient had a good initial cardiac allograft function and no and was discharged from ICU on the 4th day after HT. 1st endomyocardial biopsy (EMB (the 7th day after HT showed absence of acute cellular and antibody-mediated rejection. On the 11th day after HT patient aggravated and presented clinical signs of life-threatening acute cardiac allograft dysfunction: arterial blood pressure 78/49/38 mm Hg, HR 111 in min, CVP 20 mm Hg, PAP 47/34/25 mm Hg, PCWP 25 mm Hg, CI 1.5 l/min/m2, adrenalin 110 ng/kg/min, dopamine 15 mcg/kg/min. ECG showed impairment of systolic left (LVEF 25% and right (RVEF 15% ventricle function, left and right ventricle diffuse hypokinesis, thickness of IVS, LV and RV wall 1.7, 1.4 and 0.8 cm, tricuspid and mitral valve regurgitation 2–3 degrees. EMB presented AMR. In conscience peripheral VA ECMO was installed. We used peripheral transcutaneous cannulation technique via femoral vessels – arterial cannula 15 F, venous cannula – 23 F, vascular catheter 14 G for anterograde leg’s perfusion. ACT 130–150 sec. AMR therapy included: methylprednisolon pulse-therapy (10 mg/kg for 5 day, IgG, plasmapheresis (No 7, rituximab. Results. Under MCS by VA ECMO we noted quick improvement of hemodynamic, metabolic homeostasis and organ functions. On the 6th day of VA ECMO (blood flow 1.8 l/min: arterial blood pressure 133/81/54 mm Hg, CVP 5 mm

  18. Modeling the rejection probability in plant imports.

    Science.gov (United States)

    Surkov, I V; van der Werf, W; van Kooten, O; Lansink, A G J M Oude

    2008-06-01

    Phytosanitary inspection of imported plants and flowers is a major means for preventing pest invasions through international trade, but in a majority of countries availability of resources prevents inspection of all imports. Prediction of the likelihood of pest infestation in imported shipments could help maximize the efficiency of inspection by targeting inspection on shipments with the highest likelihood of infestation. This paper applies a multinomial logistic (MNL) regression model to data on import inspections of ornamental plant commodities in the Netherlands from 1998 to 2001 to investigate whether it is possible to predict the probability that a shipment will be (i) accepted for import, (ii) rejected for import because of detected pests, or (iii) rejected due to other reasons. Four models were estimated: (i) an all-species model, including all plant imports (136,251 shipments) in the data set, (ii) a four-species model, including records on the four ornamental commodities that accounted for 28.9% of inspected and 49.5% of rejected shipments, and two models for single commodities with large import volumes and percentages of rejections, (iii) Dianthus (16.9% of inspected and 46.3% of rejected shipments), and (iv) Chrysanthemum (6.9 and 8.6%, respectively). All models were highly significant (P < 0.001). The models for Dianthus and Chrysanthemum and for the set of four ornamental commodities showed a better fit to data than the model for all ornamental commodities. Variables that characterized the imported shipment's region of origin, the shipment's size, the company that imported the shipment, and season and year of import, were significant in most of the estimated models. The combined results of this study suggest that the MNL model can be a useful tool for modeling the probability of rejecting imported commodities even with a small set of explanatory variables. The MNL model can be helpful in better targeting of resources for import inspection. The

  19. Pharmacodynamics of cyclosporine in heart and heart-lung transplant recipients. I: Blood cyclosporine concentrations and other risk factors for cardiac allograft rejection.

    Science.gov (United States)

    Best, N G; Trull, A K; Tan, K K; Spiegelhalter, D J; Cary, N; Wallwork, J

    1996-11-27

    We have attempted to determine the optimal clinical use of cyclosporine during the first 3 months after heart transplantation. We used multiple logistic regression to quantify how blood cyclosporine concentrations and other potential risk factors influence the risk of histologically confirmed acute rejection in 111 heart transplant recipients. A 50% increase in cyclosporine concentration was associated with a 15% reduction in risk of rejection in the subsequent 5 days (P=0.002). Increasing oral corticosteroid dose also protected against rejection (P=0.01). Rejection was over 2.5 times more likely during the first 20 postoperative days, and patients with 2 HLA-DR mismatches who were transplanted for cardiomyopathy or who had multiple previous rejection episodes were predisposed to further rejection (Pcyclosporine concentrations was weakly associated with risk of rejection (P=0.1). Investigation of threshold levels for the cyclosporine concentration-effect relationship suggested that concentrations above 375 microgram L(-1) provide optimal protection against acute cardiac allograft rejection. This result yields an objectively defined therapeutic threshold for targeting early cyclosporine concentrations following heart transplantation, although the upper end of the range will depend on the individual's susceptibility to nephrotoxicity and infection.

  20. Plant Vascular Biology 2013: vascular trafficking.

    Science.gov (United States)

    Ursache, Robertas; Heo, Jung-Ok; Helariutta, Ykä

    2014-04-01

    About 200 researchers from around the world attended the Third International Conference on Plant Vascular Biology (PVB 2013) held in July 2013 at the Rantapuisto Conference Center, in Helsinki, Finland (http://www.pvb2013.org). The plant vascular system, which connects every organ in the mature plant, continues to attract the interest of researchers representing a wide range of disciplines, including development, physiology, systems biology, and computational biology. At the meeting, participants discussed the latest research advances in vascular development, long- and short-distance vascular transport and long-distance signalling in plant defence, in addition to providing a context for how these studies intersect with each other. The meeting provided an opportunity for researchers working across a broad range of fields to share ideas and to discuss future directions in the expanding field of vascular biology. In this report, the latest advances in understanding the mechanism of vascular trafficking presented at the meeting have been summarized.

  1. Background Rejection in the ARA Experiment

    Directory of Open Access Journals (Sweden)

    Pfendner Carl

    2017-01-01

    Full Text Available The Askaryan Radio Array (ARA is a radio frequency observatory under construction at the South Pole that is searching for ultrahigh energy neutrinos via the Askaryan effect. Thermal fluctuations currently dominate the trigger-level background for the observatory and anthropogenic sources also introduce a significant source of noise. By taking advantage of the observatory’s regular geometry and the expected coincident nature of the RF signals arriving from neutrino-induced events, this background can be filtered efficiently. This contribution will discuss techniques developed for the ARA analyses to reject these thermal signals, to reject anthropogenic backgrounds, and to search for neutrino-induced particle showers in the Antarctic ice. The results of a search for neutrinos from GRBs using the prototype station using some of these techniques will be presented.

  2. Differential intragraft cytokine messenger RNA profiles during rejection and repair of clinical heart transplants. A longitudinal study

    NARCIS (Netherlands)

    de Groot-Kruseman, Hester A; Mol, Wendy M; Niesters, Hubert G M; Maat, Alex P W; van Gelder, Teun; Balk, Aggie H M M; Weimar, Willem; Baan, Carla C

    After clinical heart transplantation, ischemia, acute rejection, and repair mechanisms can trigger the up-regulation of cytokines. To investigate the cytokine profile early after transplantation, we monitored messenger RNA (mRNA) expression levels of tumor necrosis factor-alpha (TNF-alpha), monocyte

  3. Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants

    NARCIS (Netherlands)

    van der Heide, J. J.; Bilo, H. J.; Donker, J. M.; Wilmink, J. M.; Tegzess, A. M.

    1993-01-01

    Dietary fish oil exerts effects on renal hemodynamics and the immune response that may benefit renal-transplant recipients treated with cyclosporine. To evaluate this possibility, we studied the effect of fish oil on renal function, blood pressure, and the incidence of acute rejection episodes in

  4. Peer acceptance/rejection and academic achievement

    Directory of Open Access Journals (Sweden)

    Spasenović Vera Z.

    2003-01-01

    Full Text Available Considerations of the nature and role of peer relations in child development indicate that peer interaction is an important factor in developing social and cognitive competences. Peer relations not only influence current but also subsequent academic, behavioral and emotional development. Accepted students more often display better academic achievement, whereas the status of rejection is coupled with academic difficulties and lower academic achievement. Peer rejection is a relatively stable characteristic that can be used to predict difficulties in the years to come, such as repeat of a grade, early drop out, unjustified absences, adaptability problems etc. It is considered that correlation between academic achievement and peer group status is mediated by student social behavior at school. The quality of peer relations and academic achievement are mutually influential i.e. peer acceptance serves as a social resource that facilitates academic achievement, but academic achievement has effects on student acceptance. To help students who display difficulties in social relations, various intervention programs have been well thought of so as to contribute to interpersonal efficiency promotion. Concerning interdependence of social behavior, peer status and academic achievement, it is reasonable to expect that positive changes in behavior, frequently leading to the change of rejection status, will produce, directly or indirectly, positive effects on academic achievement too.

  5. Mesenchymal stem cells avoid allogeneic rejection

    Directory of Open Access Journals (Sweden)

    Murphy J Mary

    2005-07-01

    Full Text Available Abstract Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.

  6. Active disturbance rejection controller for chemical reactor

    Energy Technology Data Exchange (ETDEWEB)

    Both, Roxana; Dulf, Eva H.; Muresan, Cristina I., E-mail: roxana.both@aut.utcluj.ro [Technical University of Cluj-Napoca, 400114 Cluj-Napoca (Romania)

    2015-03-10

    In the petrochemical industry, the synthesis of 2 ethyl-hexanol-oxo-alcohols (plasticizers alcohol) is of high importance, being achieved through hydrogenation of 2 ethyl-hexenal inside catalytic trickle bed three-phase reactors. For this type of processes the use of advanced control strategies is suitable due to their nonlinear behavior and extreme sensitivity to load changes and other disturbances. Due to the complexity of the mathematical model an approach was to use a simple linear model of the process in combination with an advanced control algorithm which takes into account the model uncertainties, the disturbances and command signal limitations like robust control. However the resulting controller is complex, involving cost effective hardware. This paper proposes a simple integer-order control scheme using a linear model of the process, based on active disturbance rejection method. By treating the model dynamics as a common disturbance and actively rejecting it, active disturbance rejection control (ADRC) can achieve the desired response. Simulation results are provided to demonstrate the effectiveness of the proposed method.

  7. Bioprinting for vascular and vascularized tissue biofabrication.

    Science.gov (United States)

    Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

    2017-03-15

    Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

  8. When is peer rejection justifiable?: Children's understanding across two cultures.

    Science.gov (United States)

    Park, Yoonjung; Killen, Melanie

    2010-07-01

    This study investigated how Korean (N = 397) and U.S. (N = 333) children and adolescents (10 and 13 years of age) evaluated personality (aggression, shyness) and group (gender, nationality) characteristics as a basis for peer rejection in three contexts (friendship rejection, group exclusion, victimization). Overall, peer rejection based on group membership was viewed as more unfair than peer rejection based on personality traits. Children viewed friendship rejection as more legitimate than group exclusion or victimization and used more personal choice reasoning for friendship rejection than for rejection in any other context. Although there were a few cultural differences, overall, the findings provided support for the cultural generalizability of social reasoning about peer rejection.

  9. Heterosexual Rejection and Mate Choice: A Sociometer Perspective.

    Science.gov (United States)

    Zhang, Lin; Liu, Shen; Li, Yue; Ruan, Lu-Jun

    2015-01-01

    Previous studies about the effects of social rejection on individuals' social behaviors have produced mixed results and tend to study mating behaviors from a static point of view. However, mate selection in essence is a dynamic process, and therefore sociometer theory opens up a new perspective for studying mating and its underlying practices. Based on this theory and using self-perceived mate value in the relationship between heterosexual rejection and mate choice as a mediating role, this current study examined the effects of heterosexual rejection on mate choice in two experiments. Results showed that heterosexual rejection significantly reduced self-perceived mate value, expectation, and behavioral tendencies, while heterosexual acceptance indistinctively increased these measures. Self-perceived mate value did not serve as a mediator in the relationship between heterosexual rejection and mate expectation, but it mediated the relationship between heterosexual rejection and mating behavior tendencies toward potential objects. Moreover, individuals evaded both rejection and irrelevant people when suffering from rejection.

  10. Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation.

    Directory of Open Access Journals (Sweden)

    Tobias Bergler

    Full Text Available Despite substantial progress in recent years, graft survival beyond the first year still requires improvement. Since modern immunosuppression addresses mainly T-cell activation and proliferation, we studied macrophage infiltration into the allografts of 103 kidney transplant recipients during acute antibody and T-cell mediated rejection. Macrophage infiltration was correlated with both graft function and graft survival until month 36 after transplantation.Macrophage infiltration was significantly elevated in antibody-mediated and T-cell mediated rejection, but not in kidneys with established IFTA. Treatment of rejection with steroids was less successful in patients with more prominent macrophage infiltration into the allografts. Macrophage infiltration was accompanied by increased cell proliferation as well as antigen presentation. With regard to the compartmental distribution severity of T-cell-mediated rejection was correlated to the amount of CD68+ cells especially in the peritubular and perivascular compartment, whereas biopsies with ABMR showed mainly peritubular CD68 infiltration. Furthermore, severity of macrophage infiltration was a valid predictor of resulting creatinine values two weeks as well as two and three years after renal transplantation as illustrated by multivariate analysis. Additionally performed ROC curve analysis showed that magnitude of macrophage infiltration (below vs. above the median was a valid predictor for the necessity to restart dialysis. Having additionally stratified biopsies in accordance to the magnitude of macrophage infiltration, differential CD68+ cell infiltration was reflected by striking differences in overall graft survival.The differences in acute allograft rejection have not only been reflected by different magnitudes of macrophage infiltration, but also by compartment-specific infiltration pattern and subsequent impact on resulting allograft function as well as need for dialysis initiation. There is

  11. Graft rejection in pediatric penetrating keratoplasty: Clinical features and outcomes

    Directory of Open Access Journals (Sweden)

    Rakhi Kusumesh

    2015-01-01

    Conclusion: This study showed irreversible graft rejection was the leading cause of graft failure of pediatric PK. Though, the incidence (12.1% of graft rejection in current study was not high, but the percentage of reversal (25% was one of the lowest in literature because of delayed presentation and longer interval between corneal graft rejection and treatment. In addition, categorization of the type of graft rejection was very difficult and cumbersome in pediatric patients.

  12. Rejection Sensitivity in Late Adolescence: Social and Emotional Sequelae

    OpenAIRE

    Marston, Emily G.; Hare, Amanda; Allen, Joseph P.

    2010-01-01

    This study used longitudinal, multi-reporter data, in a community sample, to examine the role of rejection sensitivity in late adolescents’ social and emotional development. Rejection sensitivity was linked to a relative increase in adolescent depressive and anxiety symptoms over a three-year period, even after accounting for teens’ baseline level of social competence. Additionally, reciprocal relationships emerged between rejection sensitivity and internalizing symptoms. Rejection sensitivit...

  13. Prevention of chronic renal allograft rejection by soluble CD83.

    Science.gov (United States)

    Lan, Zhu; Lian, Dameng; Liu, Weihua; Arp, Jacqueline; Charlton, Brayden; Ge, Wei; Brand, Stephen; Healey, Don; DeBenedette, Mark; Nicolette, Charles; Garcia, Bertha; Wang, Hao

    2010-12-27

    Recombinant human soluble CD83 had previously exhibited significant immunosuppressive properties that involved interference with dendritic cell maturation in both mouse and humans, inhibition of autoimmunity in mice, and induction of antigen-specific mouse cardiac allograft tolerance when used in combination with other immunosuppressive drugs. Our current research focus turned to examining the effects of peritransplant soluble CD83 (sCD83) administration on prevention of chronic renal allograft rejection. Fisher344-to-Lewis orthotopic rat renal transplants were performed with sequential recipient killing on postoperative days (PODs) 2, 14, and 140 to examine both the acute and chronic effects of peritransplant sCD83 treatment in rat recipients. Recipients treated with sCD83 exhibited a marked decrease in IgM and IgG deposition in the graft and antidonor antibody levels in the circulation, as early as POD14 and persisting until POD140. sCD83 treatment also reduced the infiltration of T cells and monocytes into the graft tissue and inhibited intragraft expression of MyD88 and inflammatory cytokine levels during the observation period. sCD83-treated grafts demonstrated normal histology beyond POD140, including dramatic reductions in tubular atrophy and interstitial fibrosis compared with untreated recipients. We have demonstrated that peritransplant treatment with recombinant sCD83 attenuates both innate and adaptive immune responses and leads to prevention of chronic rejection in a rat renal transplant model. Because sCD83 is of human origin, the therapeutic approach used in our rodent transplant model holds significant promise for clinical transplantation.

  14. When Is Peer Rejection Justifiable? Children's Understanding across Two Cultures

    Science.gov (United States)

    Park, Yoonjung; Killen, Melanie

    2010-01-01

    This study investigated how Korean (N = 397) and U.S. (N = 333) children and adolescents (10 and 13 years of age) evaluated personality (aggression, shyness) and group (gender, nationality) characteristics as a basis for peer rejection in three contexts (friendship rejection, group exclusion, victimization). Overall, peer rejection based on…

  15. Children's Coping with "In Vivo" Peer Rejection: An Experimental Investigation

    Science.gov (United States)

    Reijntjes, Albert; Stegge, Hedy; Terwogt, Mark Meerum; Kamphuis, Jan Henk; Telch, Michael J.

    2006-01-01

    We examined children's behavioral coping in response to an "in vivo" peer rejection manipulation. Participants (N = 186) ranging between 10 and 13 years of age, played a computer game based on the television show "Survivor" and were randomized to either peer rejection (i.e., being voted out of the game) or non-rejection control. During a five-min.…

  16. Paying to belong: when does rejection trigger ingratiation?

    Science.gov (United States)

    Romero-Canyas, Rainer; Downey, Geraldine; Reddy, Kavita S; Rodriguez, Sylvia; Cavanaugh, Timothy J; Pelayo, Rosemary

    2010-11-01

    Societies and social scientists have long held the belief that exclusion induces ingratiation and conformity, an idea in contradiction to robust empirical evidence linking rejection with hostility and aggression. The classic literatures on ingratiation and conformity help resolve this contradiction by identifying circumstances under which rejection may trigger efforts to ingratiate. Jointly, findings from these literatures suggest that when people are given an opportunity to impress their rejecters, ingratiation is likely after rejection experiences that are harsh and that occur in important situations that threaten the individual's self-definition. Four studies tested the hypothesis that people high in rejection sensitivity and therefore dispositionally concerned about rejection will utilize opportunities to ingratiate after harsh rejection in situations that are self-defining. In 3 studies of situations that are particularly self-defining for men, rejection predicted ingratiation among men (but not women) who were high in rejection sensitivity. In a 4th study, harsh rejection in a situation particularly self-defining for women predicted ingratiation among highly rejection-sensitive women (but not men). These findings help identify the specific circumstances under which people are willing to act in socially desirable ways toward those who have rejected them harshly.

  17. Cultural Rejection and Re-identification in Minority Group Members.

    Science.gov (United States)

    Diller, Jerry V.

    There is little consistent research available on cultural rejection and re-identification in minority group members, but this report uses case study material to extrapolate three general factors precipitating rejection: self-hatred and negative chauvinism, quality of ethnic experience and rejection of religious experience. A four-step model for…

  18. Analysis of Sera of Recipients with Allograft Rejection Indicates That Keratin 1 Is the Target of Anti-Endothelial Antibodies

    Directory of Open Access Journals (Sweden)

    Xuli Guo

    2017-01-01

    Full Text Available Anti-endothelial cell antibodies (AECAs are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera of kidney transplant recipients who were experiencing antibody-mediated rejection. Keratin 1 (KRT1 was identified as a novel antigenic target expressed on endothelial cells. To validate our finding, we produced recombinant proteins representing the three most common alleles of KRT1. The serum used for immunoprecipitation showed a strong reaction to KRT1 recombinants in western blot and ELISA. In the kidney transplant cohort, more AECA-positive recipients than AECA-negative recipients had KRT1 antibodies (32.2% versus 11.9%, p=0.002. Sera from 255 renal recipients were tested by ELISA. Of the 77 recipients with deteriorating graft function (serum creatinine > 120 μmol/L, 23 had anti-KRT1 antibodies. KRT1-IgG positivity was, therefore, associated with a higher risk of kidney transplant rejection (29.9% (23/77 versus 16.9% (30/178, p=0.0187. A better understanding of this antigenic target will improve long-term allograft survival.

  19. Analysis of Sera of Recipients with Allograft Rejection Indicates That Keratin 1 Is the Target of Anti-Endothelial Antibodies.

    Science.gov (United States)

    Guo, Xuli; Hu, Juan; Luo, Weiguang; Luo, Qizhi; Guo, Jing; Tian, Fang; Ming, Yingzi; Zou, Yizhou

    2017-01-01

    Anti-endothelial cell antibodies (AECAs) are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera of kidney transplant recipients who were experiencing antibody-mediated rejection. Keratin 1 (KRT1) was identified as a novel antigenic target expressed on endothelial cells. To validate our finding, we produced recombinant proteins representing the three most common alleles of KRT1. The serum used for immunoprecipitation showed a strong reaction to KRT1 recombinants in western blot and ELISA. In the kidney transplant cohort, more AECA-positive recipients than AECA-negative recipients had KRT1 antibodies (32.2% versus 11.9%, p = 0.002). Sera from 255 renal recipients were tested by ELISA. Of the 77 recipients with deteriorating graft function (serum creatinine > 120 μmol/L), 23 had anti-KRT1 antibodies. KRT1-IgG positivity was, therefore, associated with a higher risk of kidney transplant rejection (29.9% (23/77) versus 16.9% (30/178), p = 0.0187). A better understanding of this antigenic target will improve long-term allograft survival.

  20. The heartbrake of social rejection: heart rate deceleration in response to unexpected peer rejection.

    Science.gov (United States)

    Gunther Moor, Bregtje; Crone, Eveline A; van der Molen, Maurits W

    2010-09-01

    Social relationships are vitally important in human life. Social rejection in particular has been conceptualized as a potent social cue resulting in feelings of hurt. Our study investigated the psychophysiological manifestation of hurt feelings by examining the beat-by-beat heart rate response associated with the processing of social rejection. Study participants were presented with a series of unfamiliar faces and were asked to predict whether they would be liked by the other person. Following each judgment, participants were provided with feedback indicating that the person they had viewed had either accepted or rejected them. Feedback was associated with transient heart rate slowing and a return to baseline that was considerably delayed in response to unexpected social rejection. Our results reveal that the processing of unexpected social rejection is associated with a sizable response of the parasympathetic nervous system. These findings are interpreted in terms of a cardiovagal manifestation of a neural mechanism implicated in the central control of autonomic function during cognitive processes and affective regulation.

  1. The activity of nintedanib in an animal model of allogenic left lung transplantation resembling aspects of allograft rejection.

    Science.gov (United States)

    von Suesskind-Schwendi, Marietta; Boxhammer, Elke; Hirt, Stephan W; Schreml, Stephan; Schmid, Christof; Wollin, Lutz; Lehle, Karla

    The prevention and treatment of chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx) remain unsatisfactory. Growth factors may play an important role in the development of CLAD. This study evaluated the effects of nintedanib, a receptor tyrosine kinase inhibitor, in the treatment of CLAD after experimental LTx. A rat model of left lung allo-transplantation (Fisher 344 to Wistar Kyoto) was used to evaluate the effect of nintedanib (50 mg/kg per day) on the development of CLAD. Therapy with nintedanib began 2 days before LTx and ended on postoperative day (POD) 20 (n = 6) or 60 (n = 6). Nontreated animals who underwent LTx (n = 12) were used as controls, whereas naïve lungs (n = 24) served as reference for physiological healthy organs without transplantation damage or medical effects. Acute and chronic rejection were evaluated on POD 20 and 60, respectively. Immunohistologic analysis showed a decrease in growth factors/receptors on POD 60 (nintedanib-treated vs. nontreated controls: platelet-derived growth factor (PDGF) A: [P ≤ 0.001]; PDGF receptor-α: [P ≤ 0.001]; vascular endothelial growth factor (VEGF) A: [P ≤ 0.001]; VEGF receptor-2: [P ≤ 0.001]). However, no reductions in fibrotic changes were observed in nintedanib-treated allografts compared with nontreated allografts. Although nintedanib treatment started before LTx none of the animals showed impaired wound healing. No dehiscence of the sutures of the bronchus, vessels or skin, or stenosis of the bronchus was found. In conclusion, while nintedanib reduced the expression of growth factors/receptors in a rat LTx model, a reduction in fibrotic alterations was not observed at POD 60.

  2. Collagen vascular disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on this page, ... previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many specific conditions ...

  3. Soluble CD30 for the prediction and detection of kidney transplant rejection.

    Science.gov (United States)

    Arjona, Alvaro

    2009-09-01

    Although safer and more effective immunosuppressants as well as enhanced immunosuppressive protocols are continuously being developed in order to increase graft survival, they come at the steep price of drug-related complications and important side effects. In addition, the value of panel reactive antibodies determination, which at present is the single most used indicator of an increased risk of transplant rejection, is now being reevaluated. Therefore, effective tailoring of immunosuppressive therapy minimizing the above-mentioned pitfalls requires the existence of dependable biomarkers that adequately monitor rejection risk both before and after transplantation. Here we review the data yielded by studies assessing the usefulness of measuring soluble CD30 levels (sCD30) in kidney transplant rejection. These data collectively show that sCD30 serum content has a considerable predictive/diagnostic value for acute rejection of renal grafts, particularly when measured a few days after transplantation. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

  4. [Extremity vascular traumas].

    Science.gov (United States)

    Angelini, Romeo; Rutolo, Ferdinando; Cozzolino, Giuseppe; D'Amario, Vanessa; Spigonardo, Francesca

    2005-01-01

    The Authors report on a series of 61 vascular traumas treated over a 7 years, separated in two groups. The first one includes 35 cases, that are street accidents, on the work and gunshot wounds. The second group includes 26 iatrogenic causes due to arterial catheterism. All patients underwent ecocolor Doppler directly in the operating theatre and, when this diagnostic procedure was not enough, pre-operating angiography was used (10 cases of complex traumas of the lower limb). One death was reported far each groups (3.27%). In 55 cases (90.1%), limb savage was achieved. In the others 4 (6.93%) of the first group, limb demolition was necessary for different causes. In the first group, severe neurological sequelaes were observed in 2 cases and motor deficits caused by tendon lesions in 1 case. The good results obtained are the result of the short ischemic interval between the acute event and treatment, thanks to a multidisciplinary approach of a specific equipe, that is rapid as possible.

  5. Partial interference subspace rejection in CDMA systems

    DEFF Research Database (Denmark)

    Hansen, Henrik; Affes, Sofiene; Mewelstein, Paul

    2001-01-01

    Previously presented interference subspace rejection (ISR) proposed a family of new efficient multiuser detectors for CDMA. We reconsider in this paper the modes of ISR using decision feedback (DF). DF modes share similarities with parallel interference cancellation (PIC) but attempt to cancel...... interference by nulling rather than subtraction. However like the PIC they are prone to wrong tentative decisions. We propose a modification to DF modes that performs partial ISR instead of complete interference cancellation. When tentative decisions are correct, interference is therefore not perfectly...

  6. Solar Rejection Filter for Large Telescopes

    Science.gov (United States)

    Hemmati, Hamid; Lesh, James

    2009-01-01

    To reject solar radiation photons at the front aperture for large telescopes, a mosaic of large transmission mode filters is placed in front of the telescope or at the aperture of the dome. Filtering options for effective rejection of sunlight include a smaller filter down-path near the focus of the telescope, and a large-diameter filter located in the front of the main aperture. Two types of large filters are viable: reflectance mode and transmittance mode. In the case of reflectance mode, a dielectric coating on a suitable substrate (e.g. a low-thermal-expansion glass) is arranged to reflect only a single, narrow wavelength and to efficiently transmit all other wavelengths. These coatings are commonly referred to as notch filter. In this case, the large mirror located in front of the telescope aperture reflects the received (signal and background) light into the telescope. In the case of transmittance mode, a dielectric coating on a suitable substrate (glass, sapphire, clear plastic, membrane, and the like) is arranged to transmit only a single wavelength and to reject all other wavelengths (visible and near IR) of light. The substrate of the large filter will determine its mass. At first glance, a large optical filter with a diameter of up to 10 m, located in front of the main aperture, would require a significant thickness to avoid sagging. However, a segmented filter supported by a structurally rugged grid can support smaller filters. The obscuration introduced by the grid is minimal because the total area can be made insignificant. This configuration can be detrimental to a diffraction- limited telescope due to diffraction effects at the edges of each sub-panel. However, no discernable degradation would result for a 20 diffraction-limit telescope (a photon bucket). Even the small amount of sagging in each subpanel should have minimal effect in the performance of a non-diffraction limited telescope because the part has no appreciable optical power. If the

  7. Legal nature of acceptance and rejection wand

    OpenAIRE

    DEHGHANI, Asieh; KHOEINI, Ghafoor

    2015-01-01

    Abstract. We must conclude from existing legal articles and research that bequest ownership is not resulting of inherit will (or determination) and ownership does not take place by his satisfaction. The ownership of bequest is enforcement and that is, take place by the law verdict, and inherit determination don’t have interference in it and death die is initialized of it. The major effect of bequest accepts and reject is, in charge of that debts are on the hereditary obligation and remained f...

  8. C4d-negative antibody-mediated rejection with high anti-angiotensin II type I receptor antibodies in absence of donor-specific antibodies.

    Science.gov (United States)

    Fuss, Alexander; Hope, Christopher M; Deayton, Susan; Bennett, Greg Donald; Holdsworth, Rhonda; Carroll, Robert P; Coates, P Toby H

    2015-07-01

    Acute antibody-mediated rejection can occur in absence of circulating donor-specific antibodies. Agonistic antibodies targeting the anti-angiotensin II type 1 receptor (anti-AT1 R) are emerging as important non-human leucocyte antigen (HLA) antibodies. Elevated levels of anti-angiotensin II receptor antibodies were first observed in kidney transplant recipients with malignant hypertension and allograft rejection. They have now been studied in three separate kidney transplant populations and associate to frequency of rejection, severity of rejection and graft failure. We report 11 cases of biopsy-proven, Complement 4 fragment d (C4d)-negative, acute rejection occurring without circulating donor-specific anti-HLA antibodies. In eight cases, anti-angiotensin receptor antibodies were retrospectively examined. The remaining three subjects were identified from our centre's newly instituted routine anti-angiotensin receptor antibody screening. All subjects fulfilled Banff 2013 criteria for antibody-mediated rejection and all responded to anti-rejection therapy, which included plasma exchange and angiotensin receptor blocker therapy. These cases support the routine assessment of anti-AT1 R antibodies in kidney transplant recipients to identify subjects at risk. Further studies will need to determine optimal assessment protocol and the effectiveness of pre-emptive treatment with angiotensin receptor blockers. © 2015 Asian Pacific Society of Nephrology.

  9. Rat Cytomegalovirus Vaccine Prevents Accelerated Chronic Rejection in CMV-Naïve Recipients of Infected Donor Allograft Hearts.

    Science.gov (United States)

    Streblow, D N; Hwee, Y K; Kreklywich, C N; Andoh, T; Denton, M; Smith, P; Hart, E; Broekel, R; Pallett, C; Rogers, K; Streblow, A D; Chuop, M; Perry, A; Slifka, M; Messaoudi, I; Orloff, S L

    2015-07-01

    Cytomegalovirus accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in solid organ transplants; however, the mechanisms involved are unclear. We determined the efficacy of a CMV vaccine in preventing CMV-accelerated rat cardiac allograft rejection in naïve recipients of CMV+ donor hearts. F344 donor rats were infected with RCMV 5 days prior to heterotopic cardiac transplantation into CMV-naïve or H2 O2 -inactivated RCMV-vaccinated Lewis recipients. Recipients of RCMV-infected donor hearts rejected at POD59, whereas vaccinated recipients exhibited a significantly prolonged time to rejection-POD97, similar to recipients of uninfected donor hearts (POD108). Although all of the donor hearts were preinfected, the vaccinated recipients had lower graft and PBMC viral loads at POD 7 compared to unvaccinated controls. Adoptive T cell and passive antibody transfers from vaccinated Lewis rats into naïve recipients demonstrate that both T-cell and B-cell arms of the adaptive immune response provide protection against CMV-accelerated rejection. Similar findings were obtained when testing three different adjuvants in passive transfer experiments. We have determined that the timing of the vaccine prior to transplantation and the specific adjuvant play critical roles in mediating anti-viral responses and promoting graft survival. CMV vaccination prior to transplantation may effectively increase graft survival. © Copyright 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals Inc.

  10. Social Rejection and Alcohol Use in Daily Life.

    Science.gov (United States)

    Laws, Holly B; Ellerbeck, Nicole E; Rodrigues, Alyne S; Simmons, Jessica A; Ansell, Emily B

    2017-04-01

    Prior studies have found that social rejection is associated with increases in negative affect, distress, and hostility. Fewer studies, however, have examined the impact of social rejection on alcohol use, and no known studies have tested whether the impact of social rejection by close others differs from social rejection by acquaintances in its association with subsequent drinking. Participants completed event-contingent reports of their social interactions and alcohol use for 14 consecutive days on smartphones. Multilevel negative binomial regression models tested whether experiencing more social rejection than usual was associated with increased drinking, and whether this association was stronger when participants were rejected by close others (e.g., friends, spouses, family members) versus strangers or acquaintances. Results showed a significant interaction between social rejection and relationship closeness. On days characterized by rejection by close others, the likelihood of drinking significantly increased. On days characterized by rejection by acquaintances, by contrast, there was no increase in the likelihood of drinking. There was no main effect of rejection on likelihood of drinking. These results suggest that relationship type is a key factor in whether social rejection translates to potentially harmful behaviors, such as increased alcohol use. This finding is in contrast to many laboratory paradigms of rejection, which emphasize rejection and ostracism by strangers rather than known others. In the more naturalistic setting of measuring social interactions on smartphone in daily life, our findings suggest that only social rejection delivered by close others, and not strangers, led to subsequent drinking. Copyright © 2017 by the Research Society on Alcoholism.

  11. Prevention of organ rejection in renal and liver transplantation with extended release tacrolimus

    Directory of Open Access Journals (Sweden)

    Reschen ME

    2014-09-01

    Full Text Available Michael E Reschen, Christopher A O’Callaghan Henry Wellcome Building, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom Abstract: Tacrolimus is the key immunosuppressant used to prevent allograft rejection in kidney and liver transplant recipients. Despite the efficacy of tacrolimus and adjunctive immunosuppressants, a substantial number of patients experience episodes of acute rejection and late graft loss. Nonadherence is an etiological factor in both acute rejection and graft loss. In 2007, a prolonged release version of tacrolimus became available that allows once daily administration, thus halving the pill burden compared to the standard twice-daily tacrolimus. An increasing number of studies in de novo transplantation and in treatment conversion have evaluated the pharmacokinetic profile, efficacy, and safety of prolonged-release tacrolimus. We have reviewed the literature on the use of prolonged-release tacrolimus and hope that this will be of value in the design of protocols for transplant immunosuppression.Keywords: immunosuppression, kidney, hepatic, allograft, adherence

  12. Imaging features of non-traumatic vascular liver emergencies.

    Science.gov (United States)

    Onur, Mehmet Ruhi; Karaosmanoglu, Ali Devrim; Akca, Onur; Ocal, Osman; Akpinar, Erhan; Karcaaltincaba, Musturay

    2017-05-01

    Acute non-traumatic liver disorders can originate from abnormalities of the hepatic artery, portal vein and hepatic veins. Ultrasonography and computed tomography can be used in non-traumatic acute vascular liver disorders according to patient status, indication and appropriateness of imaging modality. Awareness of the imaging findings, in the appropriate clinical context, is crucial for prompt and correct diagnosis, as delay may cause severe consequences with significant morbidity and mortality. This review article will discuss imaging algorithms, and multimodality imaging findings for suspected acute vascular disorders of the liver.

  13. The heartbrake of social rejection: heart rate deceleration in response to unexpected peer rejection

    NARCIS (Netherlands)

    Gunther Moor, B.; Crone, E.A.; van der Molen, M.W.

    2010-01-01

    Social relationships are vitally important in human life. Social rejection in particular has been conceptualized as a potent social cue resulting in feelings of hurt. Our study investigated the psychophysiological manifestation of hurt feelings by examining the beat-by-beat heart rate response

  14. The Role of the Endothelium during Antibody-Mediated Rejection: From Victim to Accomplice

    Directory of Open Access Journals (Sweden)

    Amy Rachael Cross

    2018-01-01

    Full Text Available Antibody-mediated rejection (AMR of solid organ transplants is characterized by the activation and injury of the allograft endothelium. Histological and transcriptomic studies have associated microvascular inflammation and endothelial lesions with the severity of rejection and poor graft outcomes. The allograft endothelium forms the physical barrier between the donor organ and the recipient; this position directly exposes the endothelium to alloimmune responses. However, endothelial cells are not just victims and can actively participate in the pathogenesis of rejection. In healthy tissues, the endothelium plays a major role in vascular and immune homeostasis. Organ transplantation, however, subjects the endothelium to an environment of inflammation, alloreactive lymphocytes, donor-specific antibodies, and potentially complement activation. As a result, endothelial cells become activated and have modified interactions with the cellular effectors of allograft damage: lymphocytes, natural killer, and myeloid cells. Activated endothelial cells participate in leukocyte adhesion and recruitment, lymphocyte activation and differentiation, as well as the secretion of cytokines and chemokines. Ultimately, highly activated endothelial cells promote pro-inflammatory alloresponses and become accomplices to AMR.

  15. The Role of the Endothelium during Antibody-Mediated Rejection: From Victim to Accomplice.

    Science.gov (United States)

    Cross, Amy Rachael; Glotz, Denis; Mooney, Nuala

    2018-01-01

    Antibody-mediated rejection (AMR) of solid organ transplants is characterized by the activation and injury of the allograft endothelium. Histological and transcriptomic studies have associated microvascular inflammation and endothelial lesions with the severity of rejection and poor graft outcomes. The allograft endothelium forms the physical barrier between the donor organ and the recipient; this position directly exposes the endothelium to alloimmune responses. However, endothelial cells are not just victims and can actively participate in the pathogenesis of rejection. In healthy tissues, the endothelium plays a major role in vascular and immune homeostasis. Organ transplantation, however, subjects the endothelium to an environment of inflammation, alloreactive lymphocytes, donor-specific antibodies, and potentially complement activation. As a result, endothelial cells become activated and have modified interactions with the cellular effectors of allograft damage: lymphocytes, natural killer, and myeloid cells. Activated endothelial cells participate in leukocyte adhesion and recruitment, lymphocyte activation and differentiation, as well as the secretion of cytokines and chemokines. Ultimately, highly activated endothelial cells promote pro-inflammatory alloresponses and become accomplices to AMR.

  16. Antibody-Mediated Rejection in Sensitized Nonhuman Primates: Modeling Human Biology.

    Science.gov (United States)

    Burghuber, C K; Kwun, J; Page, E J; Manook, M; Gibby, A C; Leopardi, F V; Song, M; Farris, A B; Hong, J J; Villinger, F; Adams, A B; Iwakoshi, N N; Knechtle, S J

    2016-06-01

    We have established a model of sensitization in nonhuman primates and tested two immunosuppressive regimens. Animals underwent fully mismatched skin transplantation, and donor-specific antibody (DSA) response was monitored by flow cross-match. Sensitized animals subsequently underwent kidney transplantation from their skin donor. Immunosuppression included tacrolimus, mycophenolate, and methylprednisolone. Three animals received basiliximab induction; compared with nonsensitized animals, they showed a shorter mean survival time (4.7 ± 3.1 vs. 187 ± 88 days). Six animals were treated with T cell depletion (anti-CD4/CD8 mAbs), which prolonged survival (mean survival time 21.6 ± 19.0 days). All presensitized animals showed antibody-mediated rejection (AMR). In two of three basiliximab-injected animals, cellular rejection (ACR) was prominent. After T cell depletion, three of six monkeys experienced early acute rejection within 8 days with histological evidence of thrombotic microangiopathy and AMR. The remaining three monkeys survived 27-44 days, with mixed AMR and ACR. Most T cell-depleted animals experienced a rebound of DSA that correlated with deteriorating kidney function. We also found an increase in proliferating memory B cells (CD20(+) CD27(+) IgD(-) Ki67(+) ), lymph node follicular helper T cells (ICOS(+) PD-1(hi) CXCR5(+) CD4(+) ), and germinal center (GC) response. Depletion controlled cell-mediated rejection in sensitized nonhuman primates better than basiliximab, yet grafts were rejected with concomitant DSA rise. This model provides an opportunity to test novel desensitization strategies. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. Vascular Adventitia Calcification and Its Underlying Mechanism.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available Previous research on vascular calcification has mainly focused on the vascular intima and media. However, we show here that vascular calcification may also occur in the adventitia. The purpose of this work is to help elucidate the pathogenic mechanisms underlying vascular calcification. The calcified lesions were examined by Von Kossa staining in ApoE-/- mice which were fed high fat diets (HFD for 48 weeks and human subjects aged 60 years and older that had died of coronary heart disease, heart failure or acute renal failure. Explant cultured fibroblasts and smooth muscle cells (SMCswere obtained from rat adventitia and media, respectively. After calcification induction, cells were collected for Alizarin Red S staining. Calcified lesions were observed in the aorta adventitia and coronary artery adventitia of ApoE-/-mice, as well as in the aorta adventitia of human subjects examined. Explant culture of fibroblasts, the primary cell type comprising the adventitia, was successfully induced for calcification after incubation with TGF-β1 (20 ng/ml + mineralization media for 4 days, and the phenotype conversion vascular adventitia fibroblasts into myofibroblasts was identified. Culture of SMCs, which comprise only a small percentage of all cells in the adventitia, in calcifying medium for 14 days resulted in significant calcification.Vascular calcification can occur in the adventitia. Adventitia calcification may arise from the fibroblasts which were transformed into myofibroblasts or smooth muscle cells.

  18. Pediatric Vascular Surgery Review with a 30-Year-Experience in a Tertiary Referral Center

    Science.gov (United States)

    Min, Seung-Kee; Cho, Sungsin; Kim, Hyun-Young; Kim, Sang Joon

    2017-01-01

    Pediatric vascular disease is rare, and remains a big challenge to vascular surgeons. In contrast to adults, surgery for pediatric vascular disease is complicated by issues related to small size, future growth, and availability of suitable vascular conduit. During the last 30 years, 131 major vascular operations were performed in a tertiary referral center, Seoul National University Hospital, including aortoiliac aneurysm, acute or chronic arterial occlusion, renovascular hypertension, portal venous hypertension, trauma, tumor invasion to major abdominal vessels, and others. Herein we review on the important pediatric vascular diseases and share our clinical experiences on these rare diseases. PMID:28690995

  19. The relations between secrecy, rejection sensitivity and autonomy-connectedness.

    Science.gov (United States)

    Wismeijer, Andreas A J; Van Assen, Marcel A L M; Bekker, Marrie H J

    2014-01-01

    The aim of this study was to examine the effects of two attachment-related variables on secrecy: rejection sensitivity and autonomy-connectedness. We hypothesized that rejection sensitivity is positively associated with secrecy, and autonomy-connectedness negatively with rejection sensitivity and secrecy. These hypotheses were generally corroborated in a sample of 303 university students. Moreover, we found that autonomy-connectedness at least partly explained the association between rejection sensitivity and secrecy. Self-awareness was negatively related to secrecy, suggesting that being aware of what one needs and thinks and being able to realize one's needs in social interactions reduce the tendency to keep secrets. In addition, interesting gender effects were found suggesting that men have a higher tendency to have secrets than women after controlling for the effects of autonomy-connectedness and rejection sensitivity. Our findings deepen the insight into possible reasons behind established associations between rejection sensitivity and secrecy, and may have clinical implications.

  20. The rejection-rage contingency in borderline personality disorder.

    Science.gov (United States)

    Berenson, Kathy R; Downey, Geraldine; Rafaeli, Eshkol; Coifman, Karin G; Paquin, Nina Leventhal

    2011-08-01

    Though long-standing clinical observation reflected in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) suggests that the rage characteristic of borderline personality disorder (BPD) often appears in response to perceived rejection, the role of perceived rejection in triggering rage in BPD has never been empirically tested. Extending basic personality research on rejection sensitivity to a clinical sample, a priming-pronunciation experiment and a 21-day experience-sampling diary examined the contingent relationship between perceived rejection and rage in participants diagnosed with BPD compared with healthy controls. Despite the differences in these 2 assessment methods, the indices of rejection-contingent rage that they both produced were elevated in the BPD group and were strongly interrelated. They provide corroborating evidence that reactions to perceived rejection significantly explain the rage seen in BPD. © 2011 American Psychological Association

  1. Rejection Sensitivity in Late Adolescence: Social and Emotional Sequelae

    Science.gov (United States)

    Marston, Emily G.; Hare, Amanda; Allen, Joseph P.

    2010-01-01

    This study used longitudinal, multi-reporter data, in a community sample, to examine the role of rejection sensitivity in late adolescents’ social and emotional development. Rejection sensitivity was linked to a relative increase in adolescent depressive and anxiety symptoms over a three-year period, even after accounting for teens’ baseline level of social competence. Additionally, reciprocal relationships emerged between rejection sensitivity and internalizing symptoms. Rejection sensitivity was also linked to relative decreases in peer-reports of teens’ social competence over a three-year period. Consistent with research on gendered socialization, males reported higher levels of rejection sensitivity than females at age 16 and 17. Results are interpreted as highlighting the importance of rejection sensitivity in understanding late adolescent social and emotional development. PMID:21113326

  2. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning

    DEFF Research Database (Denmark)

    Masmas, T.N.; Petersen, S.L.; Madsen, H.O.

    2008-01-01

    Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage therapy in eight patients in a retrospective analysis of 124 consecutive patients is reported. The patients were conditioned with low......-dose fludarabine and total body irradiation (TBI). The association of pretransplantation risk factors with rejection and the effect of chimerism and graft-versus-host disease on rejection were analyzed. Overall survival (OS) and progression free survival (PFS) were compared between patients with and without...... rejection. Retransplantation was performed with increased TBI conditioning for all patients, and with increased mycophenolate mofetil doses for recipients with HLA-identical sibling donors. No known pretransplantation risk factors were confirmed in this study. Rejection episodes were unevenly distributed...

  3. Challenging men to reject gender stereotypes.

    Science.gov (United States)

    Gokova, J K

    1998-01-01

    Creation of a society based on gender justice requires the involvement of men as well as women. Padare, an anti-sexist organization for men in Zimbabwe, encourages men to reject gender-based stereotypes and work to recognize women as equal partners. Patriarchy forces men to be collaborators in a system that oppresses women. Men's insistence on a doctrine of male superiority undermines their own psychological growth and forces them to deny their own humanity. The challenge is for men to devise new role models that complement those of women who are demanding respect and recognition as individuals. Padare encourages men to discuss the assumptions they have internalized that make them oppressive and prevent them from establishing equal relationships with women. It serves as a support group for men who are committed to social change. From these discussions, a new definition of African manhood is emerging.

  4. Rejection Sensitivity, Jealousy, and the Relationship to Interpersonal Aggression.

    Science.gov (United States)

    Murphy, Anna M; Russell, Gemma

    2016-01-21

    The development and maintenance of interpersonal relationships lead individuals to risk rejection in the pursuit of acceptance. Some individuals are predisposed to experience a hypersensitivity to rejection that is hypothesized to be related to jealous and aggressive reactions within interpersonal relationships. The current study used convenience sampling to recruit 247 young adults to evaluate the relationship between rejection sensitivity, jealousy, and aggression. A mediation model was used to test three hypotheses: Higher scores of rejection sensitivity would be positively correlated to higher scores of aggression (Hypothesis 1); higher scores of rejection sensitivity would be positively correlated to higher scores of jealousy (Hypothesis 2); jealousy would mediate the relationship between rejection sensitivity and aggression (Hypothesis 3). Study results suggest a tendency for individuals with high rejection sensitivity to experience higher levels of jealousy, and subsequently have a greater propensity for aggression, than individuals with low rejection sensitivity. Future research that substantiates a link between hypersensitivity to rejection, jealousy, and aggression may provide an avenue for prevention, education, or intervention in reducing aggression within interpersonal relationships. © The Author(s) 2016.

  5. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all...

  6. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension.

    Science.gov (United States)

    Ghobadi, G; Bartelds, B; van der Veen, S J; Dickinson, M G; Brandenburg, S; Berger, R M F; Langendijk, J A; Coppes, R P; van Luijk, P

    2012-04-01

    Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an important role in the development of radiation-induced pulmonary toxicity. Therefore, the authors investigated whether irradiation of the lung also induces pulmonary hypertension. Different sub-volumes of the rat lung were irradiated with protons known to induce different levels of pulmonary vascular damage. Early loss of endothelial cells and vascular oedema were observed in the irradiation field and in shielded parts of the lung, even before the onset of clinical symptoms. 8 weeks after irradiation, irradiated volume-dependent vascular remodelling was observed, correlating perfectly with pulmonary artery pressure, right ventricle hypertrophy and pulmonary dysfunction. The findings indicate that partial lung irradiation induces pulmonary vascular remodelling resulting from acute pulmonary endothelial cell loss and consequential pulmonary hypertension. Moreover, the close resemblance of the observed vascular remodelling with vascular lesions in PAH makes partial lung irradiation a promising new model for studying PAH.

  7. Uterine vascular lesions.

    Science.gov (United States)

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management.

  8. Vascular biology of preeclampsia.

    Science.gov (United States)

    Myatt, L; Webster, R P

    2009-03-01

    Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, resolves on delivery of the placenta. Normal pregnancy is itself characterized by systemic inflammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. This is exacerbated in preeclampsia with an associated breakdown of compensatory mechanisms, eventually leading to placental and vascular dysfunction. The underlying pathology of preeclampsia is thought to be a relatively hypoxic or ischemic placenta. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can interact to produce peroxynitrite a powerful prooxidant that covalently modifies proteins by nitration of tyrosine residues, to possibly alter vascular function in preeclampsia. The linkage between placental hypoxia and maternal vascular dysfunction has been proposed to be via placental syncytiotrophoblast basement membranes shed by the placenta or via angiogenic factors which include soluble flt1 and endoglin secreted by the placenta that bind vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) in the maternal circulation. There is also abundant evidence of altered reactivity of the maternal and placental vasculature and of the altered production of autocoids in preeclampsia. The occurrence of preeclampsia is increased in women with preexisting vascular disease and confers a long-term risk for development of cardiovascular disease. The vascular stress test of pregnancy thus identifies those women with a previously unrecognized at risk vascular system and promotes the development of preeclampsia. Preexisting maternal vascular dysfunction intensified by placental factors is possibly responsible for the individual pathologies of preeclampsia.

  9. Increased Expression of Peripheral Blood Leukocyte Genes Implicate CD14+ Tissue Macrophages in Cellular Intestine Allograft Rejection

    Science.gov (United States)

    Ashokkumar, Chethan; Ningappa, Mylarappa; Ranganathan, Sarangarajan; Higgs, Brandon W.; Sun, Qing; Schmitt, Lori; Snyder, Sara; Dobberstein, Jennifer; Branca, Maria; Jaffe, Ronald; Zeevi, Adriana; Squires, Robert; Alissa, Feras; Shneider, Benjamin; Soltys, Kyle; Bond, Geoffrey; Abu-Elmagd, Kareem; Humar, Abhinav; Mazariegos, George; Hakonarson, Hakon; Sindhi, Rakesh

    2011-01-01

    Recurrent rejection shortens graft survival after intestinal transplantation (ITx) in children, most of whom also experience early acute cellular rejection (rejectors). To elucidate mechanisms common to early and recurrent rejection, we used a test cohort of 20 recipients to test the hypothesis that candidate peripheral blood leukocyte genes that trigger rejection episodes would be evident late after ITx during quiescent periods in genome-wide gene expression analysis and would achieve quantitative real-time PCR replication pre-ITx (another quiescent period) and in the early post-ITx period during first rejection episodes. Eight genes were significantly up-regulated among rejectors in the late post-ITx and pre-ITx periods, compared with nonrejectors: TBX21, CCL5, GNLY, SLAMF7, TGFBR3, NKG7, SYNE1, and GK5. Only CCL5 was also up-regulated in the early post-ITx period. Among resting peripheral blood leukocyte subsets in randomly sampled nonrejectors, CD14+ monocytes expressed the CCL5 protein maximally. Compared with nonrejectors, rejectors demonstrated higher counts of both circulating CCL5+CD14+ monocytes and intragraft CD14+ monocyte-derived macrophages in immunohistochemistry of postperfusion and early post-ITx biopsies from the test and an independent replication cohort. Donor-specific alloreactivity measured with CD154+ T-cytotoxic memory cells correlated with the CCL5 gene and intragraft CD14+ monocyte-derived macrophages at graft reperfusion and early post-ITx. CCL5 gene up-regulation and CD14+ macrophages likely prime cellular ITx rejection. Infiltration of reperfused intestine allografts with CD14+ macrophages may predict rejection events. PMID:21854741

  10. Corneal allograft rejection: Risk factors, diagnosis, prevention, and treatment

    Directory of Open Access Journals (Sweden)

    Dua Harminder

    1999-01-01

    Full Text Available Recent advances in corneal graft technology, including donor tissue retrieval, storage and surgical techniques, have greatly improved the clinical outcome of corneal grafts. Despite these advances, immune mediated corneal graft rejection remains the single most important cause of corneal graft failure. Several host factors have been identified as conferring a "high risk" status to the host. These include: more than two quadrant vascularisation, with associated lymphatics, which augment the afferent and efferent arc of the immune response; herpes simplex keratitis; uveitis; silicone oil keratopathy; previous failed (rejected grafts; "hot eyes"; young recipient age; and multiple surgical procedures at the time of grafting. Large grafts, by virtue of being closer to the host limbus, with its complement of vessels and antigen-presenting Langerhans cells, also are more susceptible to rejection. The diagnosis of graft rejection is entirely clinical and in its early stages the clinical signs could be subtle. Graft rejection is largely mediated by the major histocompatibility antigens, minor antigens and perhaps blood group ABO antigens and some cornea-specific antigens. Just as rejection is mediated by active immune mediated events, the lack of rejection (tolerance is also sustained by active immune regulatory mechanisms. The anterior chamber associated immune deviation (ACAID and probably, conjunctiva associated lymphoid tissue (CALT induced mucosal tolerance, besides others, play an important role. Although graft rejection can lead to graft failure, most rejections can be readily controlled if appropriate management is commenced at the proper time. Topical steroids are the mainstay of graft rejection management. In the high-risk situations however, systemic steroids, and other immunosuppressive drugs such as cyclosporin and tacrolimus (FK506 are of proven benefit, both for treatment and prevention of rejection.

  11. Acute Toxicity of Vildagliptin.

    Science.gov (United States)

    Hoffmann, Peter; Martin, Lori; Keselica, Michael; Gunson, Diane; Skuba, Elizabeth; Lapadula, Dan; Hayes, Michael; Bentley, Phil; Busch, Steve

    2017-01-01

    This article describes acute toxicity data in cynomolgus monkeys following oral treatment with vildagliptin, a dipeptidyl peptidase-4 inhibitor. Acute toxicity symptoms in cynomolgus monkeys include edema formation of the extremities, tails, and face associated with skeletal muscle necrosis, and elevations of lactate dehydrogenase, creatine kinase, alanine transaminase, and aspartate aminotransferase activities in the serum; hypothermia; hypotension; tachycardia; moribundity; and death in a few isolated instances. In surviving animals, symptoms were reversible even if treatment was continued. Cynomolgus monkeys from Mauritius appear more sensitive than monkeys of Asian origin. The underlying mechanism(s) of these symptoms in cynomolgus monkeys is currently not well understood, although a vascular mechanism including initial vasoconstriction and subsequent vascular leakage in distal extremities may play a role. The monkey data are reviewed and discussed in the context of other preclinical and clinical data, and it is concluded that acute toxicity following vildagliptin treatment is a monkey-specific phenomenon without relevance for humans.

  12. Composite filter steepens rejection slopes in microwave application

    Science.gov (United States)

    1966-01-01

    Composite filter is used to obtain sharp rejection slopes in microwave transmission by filtering techniques. It consists of a bandpass filter to shape the passband and a bandreject filter on each edge of the bandpass filter to steepen the rejection slopes.

  13. Cytokine mRNA expression during experimental corneal allograft rejection

    NARCIS (Netherlands)

    Torres, P. F.; de Vos, A. F.; van der Gaag, R.; Martins, B.; Kijlstra, A.

    1996-01-01

    Allograft rejection is the main cause of corneal graft failure. T lymphocytes and macrophages have been implied to be involved in corneal rejection, but little is known about the molecular mechanism in this process. In this study, cytokine mRNA expression in the cornea was analysed during

  14. Peer victimization and peer rejection during early childhood

    Science.gov (United States)

    Godleski, Stephanie A.; Kamper, Kimberly E.; Ostrov, Jamie M.; Hart, Emily J.; Blakely-McClure, Sarah J.

    2014-01-01

    Objective The development and course of the subtypes of peer victimization is a relatively understudied topic despite the association of victimization with important developmental and clinical outcomes. Moreover, understanding potential predictors, such as peer rejection and emotion regulation, in early childhood may be especially important to elucidate possible bi-directional pathways between relational and physical victimization and rejection. The current study (N = 97) was designed to explore several gaps and limitations in the peer victimization and peer rejection literature. In particular, the prospective associations between relational and physical victimization and peer rejection over the course of 3.5 months during early childhood (i.e., 3- to 5- years-old) were investigated in an integrated model. Method The study consisted of 97 (42 girls) preschool children recruited from four early childhood schools in the northeast of the US. Using observations, research assistant report and teacher report, relational and physical aggression, relational and physical victimization, peer rejection, and emotion regulation were measured in a short-term longitudinal study. Path analyses were conducted to test the overall hypothesized model. Results Peer rejection was found to predict increases in relational victimization. In addition, emotion regulation was found to predict decreases in peer rejection and physical victimization. Conclusions Implications for research and practice are discussed, including teaching coping strategies for peer rejection and emotional distress. PMID:25133659

  15. Rejection Sensitivity in Late Adolescence: Social and Emotional Sequelae

    Science.gov (United States)

    Marston, Emily G.; Hare, Amanda; Allen, Joseph P.

    2010-01-01

    This study used longitudinal, multireporter data, in a community sample, to examine the role of rejection sensitivity in late adolescents' social and emotional development. Rejection sensitivity was linked to a relative increase in adolescent depressive and anxiety symptoms over a 3-year period, even after accounting for teens' baseline level of…

  16. Peer victimization and peer rejection during early childhood.

    Science.gov (United States)

    Godleski, Stephanie A; Kamper, Kimberly E; Ostrov, Jamie M; Hart, Emily J; Blakely-McClure, Sarah J

    2015-01-01

    The development and course of the subtypes of peer victimization is a relatively understudied topic despite the association of victimization with important developmental and clinical outcomes. Moreover, understanding potential predictors, such as peer rejection and emotion regulation, in early childhood may be especially important to elucidate possible bidirectional pathways between relational and physical victimization and rejection. The current study (N = 97) was designed to explore several gaps and limitations in the peer victimization and peer rejection literature. In particular, the prospective associations between relational and physical victimization and peer rejection over the course of 3.5 months during early childhood (i.e., 3 to 5 years old) were investigated in an integrated model. The study consisted of 97 (42 girls) preschool children recruited from four early childhood schools in the northeast of the United States. Using observations, research assistant report, and teacher report, relational and physical aggression, relational and physical victimization, peer rejection, and emotion regulation were measured in a short-term longitudinal study. Path analyses were conducted to test the overall hypothesized model. Peer rejection was found to predict increases in relational victimization. In addition, emotion regulation was found to predict decreases in peer rejection and physical victimization. Implications for research and practice are discussed, including teaching coping strategies for peer rejection and emotional distress.

  17. Developmental Pathways from Child Maltreatment to Peer Rejection.

    Science.gov (United States)

    Bolger, Kerry E.; Patterson, Charlotte J.

    2001-01-01

    Used prospective longitudinal design to examine peer rejection, aggressive behavior, and social withdrawal among 107 maltreated and 107 nonmaltreated children. Found that chronic maltreatment was associated with heightened risk of peer rejection from childhood to early adolescence. Aggression accounted largely for the association between chronic…

  18. Peer Rejection in Preschool: Foregrounding Children’s Voices

    Science.gov (United States)

    Tay-Lim, Joanna; Gan, Linda

    2013-01-01

    Existing studies on peer rejection are predominantly quantitative in nature and do not adequately engage children’s voices and provide a comprehensive view of the peer rejection phenomenon. There are also limited studies at the preschool level, especially in the Singapore context. This study addresses these limitations by presenting insights into…

  19. Social Rejection and ADHD in Young Adults: An Analogue Experiment

    Science.gov (United States)

    Paulson, James F.; Buermeyer, Curt; Nelson-Gray, Rosemery O.

    2005-01-01

    Poor outcomes in ADHD may be related to problematic social functioning and consequences of social rejection. This study examines how ADHD symptom expression affects mood and social rejection. Working from findings in depression that describe maintenance through negative interpersonal interactions, the authors seek to examine this theory's…

  20. 32 CFR 274.8 - Bids-revocations-rejections-postponements.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Bids-revocations-rejections-postponements. 274.8... EXPORT LOAN AGREEMENTS § 274.8 Bids-revocations-rejections-postponements. The Secretary of Defense or his... these respects shall be final. In the event of a postponement, known bidders will be advised thereof and...

  1. Effects of composite mango ( Mangifera indica ) fruit reject meal on ...

    African Journals Online (AJOL)

    The experiment was conducted to determine the effect of mango fruit reject meal on growth performance, digestibility and economics of production of growing rabbits. Mango fruit rejects were sliced such that the peel and pulp were together and the seed discarded, sun dried until it attained about 10% moisture and milled to ...

  2. Heterosexual Rejection and Mate Choice: A Sociometer Perspective

    Directory of Open Access Journals (Sweden)

    Lin eZHANG

    2015-12-01

    Full Text Available Previous studies about the effects of social rejection on individuals’ social behaviors have produced mixed results and tend to study mating behaviors from a static point of view. However, mate selection in essence is a dynamic process, and therefore sociometer theory opens up a new perspective for studying mating and its underlying practices. Based on this theory and using self-perceived mate value in the relationship between heterosexual rejection and mate choice as a mediating role, this current study examined the effects of heterosexual rejection on mate choice in two experiments. Results showed that heterosexual rejection significantly reduced self-perceived mate value, expectation, and behavioral tendencies, while heterosexual acceptance indistinctively increased these measures. Self-perceived mate value did not serve as a mediator in the relationship between heterosexual rejection and mate expectation, but it mediated the relationship between heterosexual rejection and mating behavior tendencies towards potential objects. Moreover, individuals evaded both rejection and irrelevant people when suffering from rejection.

  3. Apoptosis of acinar cells in pancreas allograft rejection

    NARCIS (Netherlands)

    Boonstra, J. G.; Wever, P. C.; Laterveer, J. C.; Bruijn, J. A.; van der Woude, F. J.; ten Berge, I. J.; Daha, M. R.

    1997-01-01

    BACKGROUND: Recently it has been recognized that apoptosis of target cells may occur during liver and kidney allograft rejection and is probably induced by infiltrating cells. Pancreas rejection is also characterized by a cellular infiltrate, however, the occurrence of apoptosis has not been

  4. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...

  5. Quantum Communication Using Coherent Rejection Sampling

    Science.gov (United States)

    Anshu, Anurag; Devabathini, Vamsi Krishna; Jain, Rahul

    2017-09-01

    Compression of a message up to the information it carries is key to many tasks involved in classical and quantum information theory. Schumacher [B. Schumacher, Phys. Rev. A 51, 2738 (1995), 10.1103/PhysRevA.51.2738] provided one of the first quantum compression schemes and several more general schemes have been developed ever since [M. Horodecki, J. Oppenheim, and A. Winter, Commun. Math. Phys. 269, 107 (2007); , 10.1007/s00220-006-0118-xI. Devetak and J. Yard, Phys. Rev. Lett. 100, 230501 (2008); , 10.1103/PhysRevLett.100.230501A. Abeyesinghe, I. Devetak, P. Hayden, and A. Winter, Proc. R. Soc. A 465, 2537 (2009), 10.1098/rspa.2009.0202]. However, the one-shot characterization of these quantum tasks is still under development, and often lacks a direct connection with analogous classical tasks. Here we show a new technique for the compression of quantum messages with the aid of entanglement. We devise a new tool that we call the convex split lemma, which is a coherent quantum analogue of the widely used rejection sampling procedure in classical communication protocols. As a consequence, we exhibit new explicit protocols with tight communication cost for quantum state merging, quantum state splitting, and quantum state redistribution (up to a certain optimization in the latter case). We also present a port-based teleportation scheme which uses a fewer number of ports in the presence of information about input.

  6. Evaluation of sustainable concrete produced with desalinated reject brine

    Directory of Open Access Journals (Sweden)

    Kazi P. Fattah

    2017-06-01

    With the intent of reducing the carbon footprint of concrete production, a study was carried out to determine the effect of using reject brine as the source of water and the use of ground granulated blast furnace slag (GGBS as a replacement for cement. Concrete samples having three different cement contents were prepared with normal tap water and reject brine. Results showed that the use of GGBS and reject brine improved the strength of concrete produced by 16.5%. Replacing 50% of the cement with GGBS and using reject brine as the source of water has a potential for reducing 176 kg CO2 and 1.7–3.4 kg of CO2 equivalents per one cubic meter of concrete, respectively. The use of the waste reject brine can potentially save USD 170–340 per cubic meter of concrete produced.

  7. Group marginalization: extending research on interpersonal rejection to small groups.

    Science.gov (United States)

    Betts, Kevin R; Hinsz, Verlin B

    2013-11-01

    An extensive research literature has examined the reactions of individuals facing interpersonal rejection. Small groups can also be rejected, but current research tells us little about the experiences of groups and their members directly. We integrate findings from various literatures to gain insight into shared rejection experiences and their outcomes. Of most practical importance, we argue that groups can be expected to react with more hostility than individuals when rejected. Four existing models that account for how group processes might alter such reactions are examined: a need-threat model, a rejection-identification model, a multimotive model, and a dual attitudes model. Aspects of these models are then integrated into a unifying framework that is useful for understanding hostile reactions to group marginalization. Implications for natural groups such as terrorist cells, school cliques, racial and ethnic minorities, and gangs are discussed.

  8. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs.

    Science.gov (United States)

    Sánchez-Fueyo, Alberto; Strom, Terry B

    2011-01-01

    Transplantation of organs between genetically different individuals of the same species causes a T cell-mediated immune response that, if left unchecked, results in rejection and graft destruction. The potency of the alloimmune response is determined by the antigenic disparity that usually exists between donors and recipients and by intragraft expression of proinflammatory cytokines in the early period after transplantation. Studies in animal models have identified many molecules that, when targeted, inhibit T-cell activation. In addition, some of these studies have shown that certain immunologic interventions induce transplantation tolerance, a state in which the allograft is specifically accepted without the need for chronic immunosuppression. Tolerance is an important aspect of liver transplantation, because livers have a unique microenvironment that promotes tolerance rather than immunity. In contrast to the progress achieved in inducing tolerance in animal models, patients who receive transplanted organs still require nonspecific immunosuppressant drugs. The development of calcineurin inhibitors has reduced the acute rejection rate and improved short-term, but not long-term, graft survival. However, long-term use of immunosuppressive drugs leads to nephrotoxicity and metabolic disorders, as well as manifestations of overimmunosuppression such as opportunistic infections and cancers. The status of pharmacologic immunosuppression in the clinic is therefore not ideal. We review recently developed therapeutic strategies to promote tolerance to transplanted livers and other organs and diagnostic tools that might be used to identify patients most likely to accept or reject allografts. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Arterial healing following primary PCI using the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) versus the durable polymer everolimus-eluting metallic stent (XIENCE) in patients with acute ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Räber, Lorenz; Onuma, Yoshinobu; Brugaletta, Salvatore

    2015-01-01

    Aims: The Absorb bioresorbable vascular scaffold (Absorb BVS) provides similar clinical outcomes compared with a durable polymer-based everolimus-eluting metallic stent (EES) in stable coronary artery disease patients. ST-elevation myocardial infarction (STEMI) lesions have been associated with d...

  10. Vascular cognitive impairment and vascular dementia

    Directory of Open Access Journals (Sweden)

    Klavdija Ovčar

    2017-09-01

    Full Text Available In the developed world, five to ten percent of people older than 65 years have dementia. One fifth of dementia etiologies are due to vascular brain lesions (VaD – vascular dementia. A milder form is called vascular cognitive impairment (VCI. The main clinical criteria for VaD are: 1. cognitive decline verified with standardized cognitive test/scale, 2. evidence of the associated vascular brain lesion, 3. excluded reversible causes of cognitive decline. The main risk factors for VaD are age, atherosclerosis, diabetes and hypertension. They play a key role in pathogenesis of the cognitive impairment. Depending on the damaged brain region, different cognitive domains may be affected with or without other neurological signs. These diversities in the clinical picture challenge the correct diagnosis. Unique feature of VaD is its progression, which can be stopped, if patients receive an appropriate treatment.The treatment of VCI and VaD symptoms is similar to that in Alzheimer’s disease. More importantly, VCI may be slowed down or even stopped with proper secondary stroke prevention and good rehabilitation. The most efficient is primary stroke prevention with healthy lifestyle and treatment of acquired risk factors.

  11. MEDICAL AND SOCIAL ISSUES OF OCCUPATIONAL REHABILITATION IN ELDERLY PATIENTS WITH VASCULAR OPHTHALMOPATHY

    Directory of Open Access Journals (Sweden)

    A. M. Razumovskaya

    2015-01-01

    Full Text Available Aim: To assess medical and social issues of occupational rehabilitation in elderly patients with vascular eye diseases. Materials and methods: The results of examination of 572 patients and disabled persons after acute occlusion of central retinal artery, central retinal vein or optic nerve ischemia with sequelae were analyzed. Results: The majority of patients (> 70% with history of acute occlusion of central retinal artery, central retinal vein or optic nerve ischemia were elderly and had extensive professional background. Frequency of acute vascular eye diseases-related disability was as follows: 12.7% after occlusion of central retinal artery, 60.1% after acute occlusion of central retinal vein and 27.2% after acute optic nerve ischemia. Conclusion: Key determinants of occupational abilities in patients with vascular eye diseases are: visual function, positive motivation for work, compensation status of background vascular condition and adequate working environment.

  12. Rejection of micropollutants by clean and fouled forward osmosis membrane

    KAUST Repository

    Valladares Linares, Rodrigo

    2011-12-01

    As forward osmosis (FO) gains attention as an efficient technology to improve wastewater reclamation processes, it is fundamental to determine the influence of fouling in the rejection of emerging contaminants (micropollutants). This study focuses on the rejection of 13 selected micropollutants, spiked in a secondary wastewater effluent, by a FO membrane, using Red Sea water as draw solution (DS), differentiating the effects on the rejection caused by a clean and fouled membrane. The resulting effluent was then desalinated at low pressure with a reverse osmosis (RO) membrane, to produce a high quality permeate and determine the rejection with a coupled forward osmosis - low pressure reverse osmosis (FO-LPRO) system. When considering only FO with a clean membrane, the rejection of the hydrophilic neutral compounds was between 48.6% and 84.7%, for the hydrophobic neutrals the rejection ranged from 40.0% to 87.5%, and for the ionic compounds the rejections were between 92.9% and 96.5%. With a fouled membrane, the rejections were between 44.6% and 95.2%, 48.7%-91.5% and 96.9%-98.6%, respectively. These results suggest that, except for the hydrophilic neutral compounds, the rejection of the micropollutants is increased by the presence of a fouling layer, possibly due to the higher hydrophilicity of the FO fouled membrane compared to the clean one, the increased adsorption capacity of hydrophilic compounds and reduced mass transport capacity, membrane swelling, and the higher negative charge of the membrane surface, related to the foulants composition, mainly NOM acids (carboxylic radicals) and polysaccharides or polysaccharide-like substances. However, when coupled with RO, the rejections in both cases increased above 96%. The coupled FO-LPRO system was an effective double barrier against the selected micropollutants. © 2011 Elsevier Ltd.

  13. Vascular disease burden in Indian subjects with vascular dementia.

    Science.gov (United States)

    Chandra, Mina; Anand, Kuljeet Singh

    2015-01-01

    Vascular disease factors like hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease contribute to the development of vascular dementia. As comorbidity of vascular disease factors in vascular dementia is common, we investigated the vascular disease burden in subjects with vascular dementia. To investigate the vascular disease burden due to four vascular disease factors: hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease in Indian subjects with vascular dementia. In this study, 159 subjects with probable vascular dementia (as per NINDS-AIREN criteria) attending the memory clinic at a tertiary care hospital were assessed for the presence of hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease using standardised operational definitions and for severity of dementia on the Clinical Dementia Rating (CDR) scale. The data obtained was subjected to appropriate statistical analysis. Dyslipidaemia (79.25 per cent) was the most common vascular disease factor followed by hypertension (73.58 per cent), ischaemic heart disease (58.49 per cent), and diabetes mellitus (40.80 per cent). Most subjects (81.1 per cent) had two or more vascular disease factors. Subjects with more severe dementia had more vascular disease factors (sig 0.001). People with moderate to severe dementia have a significantly higher vascular disease burden; therefore, higher vascular disease burden may be considered as a poor prognostic marker in vascular dementia. Subjects with vascular dementia and their caregivers must manage cognitive impairment and ADL alongside managing serious comorbid vascular diseases that may worsen the dementia.

  14. Vascular dementia: Facts and controversies

    Directory of Open Access Journals (Sweden)

    Pavlović Aleksandra

    2013-01-01

    Full Text Available Vascular dementia (VaD is the second most frequent dementia after Alzheimer’s disease, and is diagnosed during lifetime in 20% of demented patients. Five­year survival rate in VaD is 39%, while it is estimated to be 75% in healthy persons of the same age. It is therefore important to make correct diagnosis of VaD early in the course of the disease. Risk factors for VaD are identical to stroke risk factors, and there are significant possibilities for the prevention of vascular cognitive decline. Cognitive decline develops acutely or step­by­step within three months after stroke, but more gradual progression of intellectual decline is also possible. Neurological examination can reveal pyramidal and extrapyramidal signs, pseudobulbar palsy, gait disturbance and urinary incontinence. Neuropsychological profile comprises the loss of cognitive set shifting, decline in word fluency, verbal learning difficulties, perseverations, difficulties in complex figure copying, and in patients with cortically located lesions also problems with speech and praxia. The basis of the diagnosis is, besides history, neurological examination and neuropsychological assessment, computed tomography and/ or magnetic resonance brain imaging. Vascular risk factors control is the most important measure in VaD prevention. Modern guidelines for the treatment of cognitive decline in VaD emphasize that donepezil can be useful in the improvement of cognitive status at the level of Class IIa recommendation at the level of evidence A, while memantine may be useful in patients with mixed VaD and Alzheimer’s disease dementia. [Projekat Ministarstva nauke Republike Srbije, br. 175022 i br. 175033

  15. Trait rejection sensitivity is associated with vigilance and defensive response rather than detection of social rejection cues

    Directory of Open Access Journals (Sweden)

    Taishi eKawamoto

    2015-10-01

    Full Text Available Prior studies suggest that psychological difficulties arise from higher trait rejection sensitivity (RS—heightened vigilance and differential detection of social rejection cues and defensive response to. On the other hand, from an evolutionary perspective, rapid and efficient detection of social rejection cues can be considered beneficial. We conducted a survey and an electrophysiological experiment to reconcile this seeming contradiction. We compared the effects of RS and rejection detection capability (RDC on perceived interpersonal experiences (Study 1 and on neurocognitive processes in response to cues of social rejection (disgusted faces; Study 2. We found that RS and RDC were not significantly related, although RS was positively related to perceived social rejection experiences and RDC was positively related to perceived social inclusion experiences. Event-related brain potentials (ERPs revealed that higher RS was related to cognitive avoidance (i.e., P1 and heightened motivated attention (i.e., late positive potential: LPP, but not to facial expression encoding (i.e., N170 toward disgusted faces. On the other hand, higher RDC was related to heightened N170 amplitude, but not to P1 and LPP amplitudes. These findings imply that sensitivity to rejection is apparently distinct from the ability to detect social rejection cues and instead reflects intense vigilance and defensive response to those cues. We discussed an alternative explanation of the relationship between RS and RDC from a signal detection perspective.

  16. Rejected by Peers--Attracted to Antisocial Media Content: Rejection-Based Anger Impairs Moral Judgment among Adolescents

    Science.gov (United States)

    Plaisier, Xanthe S.; Konijn, Elly A.

    2013-01-01

    Adolescence is an important developmental stage during which both peers and the media have a strong influence. Both peer rejection and the use of morally adverse media are associated with negative developmental outcomes. This study examines processes by which peer rejection might drive adolescents to select antisocial media content by tying…

  17. Rejected by peers – Attracted to antisocial media content: Rejection-based anger impairs moral judgment among adolescents

    NARCIS (Netherlands)

    Plaisier, X.S.; Konijn, E.A.

    2013-01-01

    Adolescence is an important developmental stage during which both peers and the media have a strong influence. Both peer rejection and the use of morally adverse media are associated with negative developmental outcomes. This study examines processes by which peer rejection might drive adolescents

  18. Rejected by peers-attracted to antisocial media content: rejection-based anger impairs moral judgment among adolescents.

    Science.gov (United States)

    Plaisier, Xanthe S; Konijn, Elly A

    2013-06-01

    Adolescence is an important developmental stage during which both peers and the media have a strong influence. Both peer rejection and the use of morally adverse media are associated with negative developmental outcomes. This study examines processes by which peer rejection might drive adolescents to select antisocial media content by tying together developmental research on peer rejection and research on media effects. Assumed underlying mechanisms are rejection-based anger and frustration and the adolescent's moral judgment. A between-participants experimental design manipulated peer rejection versus acceptance in adolescents (Mage = 13.88 years; N = 74) and young adults (Mage = 21.37 years; N = 75), applying the Cyberball paradigm. Measures included the State Anger Inventory (STAXI) to assess feelings of rejection and the newly devised Media, Morals, and Youth Questionnaire (MMaYQue) to assess media preferences and moral judgment of media content. Using bootstrapping analyses, a double mediation was established: Higher levels of state anger in peer-rejected adolescents induced more tolerable moral judgments of antisocial media content, subsequently instigating a preference for antisocial media content. In contrast, the young adult sample showed no relations between peer rejection and antisocial media preference. Results are discussed within a downward spiral framework of combined peer and media influences. PsycINFO Database Record (c) 2013 APA, all rights reserved

  19. Immunosuppressive effects of ginsenoside-Rd on skin allograft rejection in rats.

    Science.gov (United States)

    Wang, Li; Zhang, Yunxin; Chen, Jiajia; Li, Sijia; Wang, Yanhong; Hu, Lamei; Wang, Lihua; Wu, Yongjie

    2012-07-01

    Organ transplantation is a life-saving procedure for patients with organ failure. However, the side effects of long-term application of classic immunosuppressant remain major obstacles for successful transplantation. Therefore, new and safe immunosuppressive drugs against acute and chronic rejection are eagerly awaited. In the present study, we detected the effect of ginsenoside-Rd on mitogen-induced mouse spleen lymphocytes proliferation in vitro and observed the effect of ginsenoside-Rd on allograft rejection in a rat skin transplantation model. Th1/Th2 type cytokines secretion and T-cell subsets were also detected. The results showed that ginsenoside-Rd could markedly inhibit Concanavalin A (ConA)-induced mouse spleen T lymphocytes proliferation. Also, ginsenoside-Rd could significantly prolong the mean survival time of skin allograft and improve the skin allograft pathological damage. Furthermore, ginsenoside-Rd could markedly suppress alloantigen-specific production of Th1 cytokines IL-2 and IFN-γ as well as proinflammatory cytokines TNFα and IL-12. In parallel, Th2 cytokine IL-10 production in serum of rat recipients was markedly up-regulated. Ginsenoside-Rd at a dose of 25 mg/kg could significantly reduce the percentages of CD4(+) T cells and CD8(+) T cells in peripheral blood of rat recipients. Our results suggest that ginsenoside-Rd can effectively antagonize transplant rejection, which might qualify ginsenoside-Rd as a putative, therapeutic drug for the treatment of Th1-driven diseases, including transplant rejection. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Quantum Communication Using Coherent Rejection Sampling.

    Science.gov (United States)

    Anshu, Anurag; Devabathini, Vamsi Krishna; Jain, Rahul

    2017-09-22

    Compression of a message up to the information it carries is key to many tasks involved in classical and quantum information theory. Schumacher [B. Schumacher, Phys. Rev. A 51, 2738 (1995)PLRAAN1050-294710.1103/PhysRevA.51.2738] provided one of the first quantum compression schemes and several more general schemes have been developed ever since [M. Horodecki, J. Oppenheim, and A. Winter, Commun. Math. Phys. 269, 107 (2007); CMPHAY0010-361610.1007/s00220-006-0118-xI. Devetak and J. Yard, Phys. Rev. Lett. 100, 230501 (2008); PRLTAO0031-900710.1103/PhysRevLett.100.230501A. Abeyesinghe, I. Devetak, P. Hayden, and A. Winter, Proc. R. Soc. A 465, 2537 (2009)PRLAAZ1364-502110.1098/rspa.2009.0202]. However, the one-shot characterization of these quantum tasks is still under development, and often lacks a direct connection with analogous classical tasks. Here we show a new technique for the compression of quantum messages with the aid of entanglement. We devise a new tool that we call the convex split lemma, which is a coherent quantum analogue of the widely used rejection sampling procedure in classical communication protocols. As a consequence, we exhibit new explicit protocols with tight communication cost for quantum state merging, quantum state splitting, and quantum state redistribution (up to a certain optimization in the latter case). We also present a port-based teleportation scheme which uses a fewer number of ports in the presence of information about input.

  1. Vascular remodelling in asthma.

    Science.gov (United States)

    Walters, Eugene Haydn; Soltani, Amir; Reid, David William; Ward, Chris

    2008-02-01

    We review the recent literature, focusing on 2006 and 2007, to produce an update on the patho-biology of angiogenesis and vascular endothelial growth factor in the asthmatic airway. In terms of conceptual development in asthma research, airway inflammation and remodelling have been regarded as separate processes or perhaps as sequential, with early inflammation leading later to remodelling. Recent insights identify a central role for vascular endothelial growth factor in stimulating both inflammation and vascular remodelling coincidentally, with the full panoply of vascular endothelial growth factor mediated events being complex and wide. Both nitric oxide and matrix metalloproteinase-9 induction may be important downstream pathogenic mechanisms. Virus-mediated exacerbations are a prime manifestation of the oscillating trajectory of clinical asthma. The early stimulation of vascular endothelial growth factor production is probably a central aetiological mechanism, with secondary inflammation and angiogenesis. The time scale of the latter, especially, fits with the time scale of clinico-physiological changes after exacerbation. These vascular endothelial growth factor induced changes are potentially modifiable with therapy. Insights into the importance of vascular endothelial growth factor and angiogenesis in asthma pathogenesis now lead to potential new therapeutic possibilities and elucidate why recent advances in asthma therapeutics have been so successful.

  2. Inflammatory Acute Response. Biochemical and Cellular Considerations

    National Research Council Canada - National Science Library

    Milagros Lisset León Regal; Ania Alvarado Borges; José Omar de Armas García; Luciano Miranda Alvarado; Javier Antonio Varens Cedeño; José Ángel Cuesta del Sol

    2015-01-01

    .... The present work aimed at argumenting on the mechanisms that explain the vascular changes, and the establishment of the signs of the acute inflammatory response with an in-depth molecular level...

  3. Systemic Multiple Aneurysms Caused by Vascular Ehlers-Danlos Syndrome.

    Science.gov (United States)

    Gui, Xinyu; Li, Fangda; Wu, Lingeer; Zheng, Yuehong

    2016-07-01

    Systemic multiple aneurysms are rare and usually associated with collagen tissue disease, such as Ehlers-Danlos syndrome (EDS) or Marfan syndrome. In the present case, we describe a 39-year-old male patient with systemic multiple aneurysms and acute intraperitoneal hemorrhage who was clinically diagnosed with vascular EDS. Coil embolization of the distal segment of the common hepatic artery was performed, which resolved the patient's symptoms. With this case presentation, we aim to increase the awareness of vascular EDS among clinicians and emphasize the extreme fragility of the arteries in patients with vascular EDS. © The Author(s) 2016.

  4. Hyperexpression of the granzyme B inhibitor PI-9 in human renal allografts: A potential mechanism for stable renal function in patients with subclinical rejection

    NARCIS (Netherlands)

    Rowshani, Ajda T.; Florquin, Sandrine; Bemelman, Frederike; Kummer, J. Alain; Hack, C. Erik; ten Berge, Ineke J. M.

    2004-01-01

    Background. Granzyme B-positive T lymphocytes infiltrate renal allografts during acute cellular rejection and cause graft injury by inducing apoptosis of tubular cells. Protease inhibitor 9 (PI-9), an intracellular serpin that inhibits granzyme B, is known to protect cells from the action of

  5. Effect of dietary fish-oil on renal-function and rejection in cyclosporine-treated recipients of renal-transplants

    NARCIS (Netherlands)

    van der Heide, Jaap J. Homan; Bilo, Henk J. G.; Donker, J. M.; Wilmink, J. M.; Tegzess, Adam M.

    1993-01-01

    Background. Dietary fish oil exerts effects on renal hemodynamics and the immune response that may benefit renal-transplant recipients treated with cyclosporine. To evaluate this possibility, we studied the effect of fish oil on renal function, blood pressure, and the incidence of acute rejection

  6. Reject mechanisms for massively parallel neural network character recognition systems

    Science.gov (United States)

    Garris, Michael D.; Wilson, Charles L.

    1992-12-01

    Two reject mechanisms are compared using a massively parallel character recognition system implemented at NIST. The recognition system was designed to study the feasibility of automatically recognizing hand-printed text in a loosely constrained environment. The first method is a simple scalar threshold on the output activation of the winning neurode from the character classifier network. The second method uses an additional neural network trained on all outputs from the character classifier network to accept or reject assigned classifications. The neural network rejection method was expected to perform with greater accuracy than the scalar threshold method, but this was not supported by the test results presented. The scalar threshold method, even though arbitrary, is shown to be a viable reject mechanism for use with neural network character classifiers. Upon studying the performance of the neural network rejection method, analyses show that the two neural networks, the character classifier network and the rejection network, perform very similarly. This can be explained by the strong non-linear function of the character classifier network which effectively removes most of the correlation between character accuracy and all activations other than the winning activation. This suggests that any effective rejection network must receive information from the system which has not been filtered through the non-linear classifier.

  7. Lunar Dust on Heat Rejection System Surfaces: Problems and Prospects

    Science.gov (United States)

    Gaier, James R.; Jaworske, Donald A.

    2007-01-01

    Heat rejection from power systems will be necessary for human and robotic activity on the lunar surface. Functional operation of such heat rejection systems is at risk of degradation as a consequence of dust accumulation. The Apollo astronauts encountered marked degradation of performance in heat rejection systems for the lunar roving vehicle, science packages, and other components. Although ground testing of dust mitigation concepts in support of the Apollo mission identified mitigation tools, the brush concept adopted by the Apollo astronauts proved essentially ineffective. A better understanding of the issues associated with the impact of lunar dust on the functional performance of heat rejection systems and its removal is needed as planning gets underway for human and robotic missions to the Moon. Renewed emphasis must also be placed on ground testing of pristine and dust-covered heat rejection system surfaces to quantify degradation and address mitigation concepts. This paper presents a review of the degradation in performance of heat rejection systems encountered on the lunar surface to-date, and will discuss current activities underway to evaluate the durability of candidate heat rejection system surfaces and current dust mitigation concepts.

  8. Rejection of Organic Micropollutants by Clean and Fouled Nanofiltration Membranes

    Directory of Open Access Journals (Sweden)

    Lifang Zhu

    2015-01-01

    Full Text Available The rejection of organic micropollutants, including three polycyclic aromatic hydrocarbons (PAHs and three phthalic acid esters (PAEs, by clean and fouled nanofiltration membranes was investigated in the present study. The rejection of organic micropollutants by clean NF90 membranes varied from 87.9 to more than 99.9%, while that of NF270 membranes ranged from 32.1 to 92.3%. Clear time-dependence was observed for the rejection of hydrophobic micropollutants, which was attributed to the adsorption of micropollutants on the membrane. Fouling with humic acid had a negligible influence on the rejection of organic micropollutants by NF90 membranes, while considerable effects were observed with NF270 membranes, which are significantly looser than NF90 membranes. The observed enhancement in the rejection of organic micropollutants by fouled NF270 membranes was attributed to pore blocking, which was a dominating fouling mechanism for loose NF membranes. Changes in the ionic strength (from 10 to 20 mM reduced micropollutant rejection by both fouled NF membranes, especially for the rejection of dimethyl phthalate and diethyl phthalate by NF270 membranes (from 65.8 to 25.0% for dimethyl phthalate and 75.6 to 33.3% for diethyl phthalate.

  9. Effect of Donor and Recipient Factors on Corneal Graft Rejection

    Science.gov (United States)

    Stulting, R. Doyle; Sugar, Alan; Beck, Roy; Belin, Michael; Dontchev, Mariya; Feder, Robert S.; Gal, Robin L.; Holland, Edward J.; Kollman, Craig; Mannis, Mark J.; Price, Francis; Stark, Walter; Verdier, David D.

    2014-01-01

    Purpose To assess the relationship between donor and recipient factors and corneal allograft rejection in eyes that underwent penetrating keratoplasty (PK) in the Cornea Donor Study. Methods 1090 subjects undergoing corneal transplantation for a moderate risk condition (principally Fuchs’ dystrophy or pseudophakic corneal edema) were followed for up to 5 years. Associations of baseline recipient and donor factors with the occurrence of a probable or definite rejection event were assessed in univariate and multivariate proportional hazards models. Results Eyes with pseudophakic or aphakic corneal edema (N=369) were more likely to experience a rejection event than eyes with Fuchs’ dystrophy (N=676) (34% ± 6% versus 22% ± 4%; hazard ratio = 1.56; 95% confidence interval 1.21 to 2.03). Among eyes with Fuchs’dystrophy, a higher probability of a rejection event was observed in phakic post-transplant eyes compared with eyes that underwent cataract extraction with or without intraocular lens implantation during PK (29% vs. 19%; hazard ratio = 0.54; 95% confidence interval 0.36 to 0.82). Female recipients had a higher probability of a rejection event than males (29% vs. 21%; hazard ratio=1.42; 95% confidence interval 1.08 to 1.87), after controlling for the effect of preoperative diagnosis and lens status. Donor age and donor recipient ABO compatibility were not associated with rejection. Conclusions There was a substantially higher graft rejection rate in eyes with pseudophakic or aphakic corneal edema compared with eyes with Fuchs’ dystrophy. Female recipients were more likely to have a rejection event than males. Graft rejection was not associated with donor age. PMID:22488114

  10. Ozone Therapy Protects Against Rejection in a Lung Transplantation Model: A New Treatment?

    Science.gov (United States)

    Santana-Rodríguez, Norberto; Llontop, Pedro; Clavo, Bernardino; Fiuza-Pérez, María D; Zerecero, Keila; Ayub, Adil; Alshehri, Khalid; Yordi, Nagib A; Re, Lamberto; Raad, Wissam; Fernández-Pérez, Leandro; García-Herrera, Ricardo; Huang, Chyun-Yin J; Bhora, Faiz Y

    2017-08-01

    No satisfactory treatment exists for chronic rejection (CR) after lung transplantation (LT). Our objective was to assess whether ozone (O3) treatment could ameliorate CR. Male Sprague-Dawley inbred rats (n = 36) were randomly assigned into four groups: (1) control (n = 6), (2) sham (n = 6), (3) LT (n = 12), and (4) O3-LT (n = 12). Animals underwent left LT. O3 was rectally administered daily for 2 weeks before LT (from 20 to 50 μg) and 3 times/wk (50 μg/dose) up to 3 months. CR; acute rejection; and Hspb27, Prdx, Epas1, Gpx3, Vegfa, Sftpa1, Sftpb, Plvap, Klf2, Cldn5, Thbd, Dsip, Fmo2, and Sepp1 mRNA gene expression were determined. Severe CR was observed in all animals of LT group, but none of the O3-LT animals showed signs of CR, just a mild acute rejection was observed in 1 animal. A significant decrease of Hspb27, Prdx, Epas1, Gpx3, Vegfa, Sftpa1, Sftpb, Plvap, Klf2, Cldn5, Thbd, Dsip, and Fmo2 gene expression in the O3-LT group was observed CONCLUSIONS: O3 therapy significantly delayed the onset of CR regulating the expression of genes involved in its pathogenesis. No known immunosuppressive therapy has been capable of achieving similar results. From a translational point of view, O3 therapy could become a new adjuvant treatment for CR in patients undergoing LT. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  11. Effect of CD4+ memory T cells on rejection response of ectopic heart transplantation in mice.

    Science.gov (United States)

    Zhao, Y; Shan, Z; Li, Q; Zhou, Y; Zeng, X; Fan, Q; Liao, C; Zhu, Y; Zhao, Y; Lu, X; Liu, J

    2011-06-01

    CD4(+) memory T cells mediate resistance of the body to infection by exotic pathogens. This study investigated the effects of alloreactive CD4(+) memory T cells on acute graft rejection responses toward ectopic hearts in the abdominal cavities of mice. BALB/C mice were used as recipients and C57BL/6 mice as donors. The animals in the CD4(+) memory T-cell group were infused with CD4(+) memory T cells, those in the other group were infused with nonsensitized CD4(+) T cells, and those in the control group received no CD4(+) T cells. Heart transplantation was performed at 3 weeks after the cell infusion with cyclosporine administered beginning 1 day before transplantation via intraperitoneal injection. The survival among the CD4(+) memory T-cell group was significantly shorter than that of the nonsensitized CD4(+) T-cell group or the control group (P .05; n = 10). On the 5th day after the transplantation of heart, the histologic grades of the nonsensitized CD4(+) T-cell and the blank control group were lower than those of the CD4(+) memory T-cell group. There was no significant difference in the histologic grades between the nonsensitized CD4(+) T-cell and control groups. The CD4(+) memory T cells that mediate acute rejection of allografted hearts are insensitive to cyclosporine. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Suicide Screening for Prisoners: An Ethical Critique of Research Rejection.

    Science.gov (United States)

    Guinn, David; Burgermeister, Diane M

    2016-01-01

    A retrospective review of medical records was proposed to examine mental health staff compliance with documentation of a suicide assessment tool according to institutional policy on suicide screening within a U.S. correctional facility. A shift in focus was necessary when the proposed study was rejected by the institutional review board. Reasons for the rejection included low perceived benefit versus greater risk to the correctional facility and the need for prisoner informed consent, albeit the design was a retrospective medical record review. Because of this rejection, ethical issues in the prevention of suicide in prisons were examined with implications for the forensic nurse leading quality improvement initiatives.

  13. Understanding Vascular Endothelium

    OpenAIRE

    Gimbrone, Michael A.

    2014-01-01

    Understanding Vascular Endothelium : Nature’s Container for Blood The entire cardiovascular system, from the chambers of the heart to the smallest capillaries of peripheral tissues, is lined by a single-cell-thick continuous layer—the vascular endothelium. For many years, this gossamer membrane was thought to function largely as an inert barrier, passively separating the reactive components of the circulating blood from the cells and connective tissue matrix of the various organs of the body....

  14. Hypercholesterolaemia and vascular dementia

    OpenAIRE

    Appleton, Jason P.; Scutt, Polly; Sprigg, Nikola; Bath, Philip M.

    2017-01-01

    Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors–diabetes, hypercholesterolaemia, hypertension and smoking–are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet no...

  15. Transgenic expression of human heme oxygenase-1 in pigs confers resistance against xenograft rejection during ex vivo perfusion of porcine kidneys.

    Science.gov (United States)

    Petersen, Björn; Ramackers, Wolf; Lucas-Hahn, Andrea; Lemme, Erika; Hassel, Petra; Queisser, Anna-Lisa; Herrmann, Doris; Barg-Kues, Brigitte; Carnwath, Joseph W; Klose, Johannes; Tiede, Andreas; Friedrich, Lars; Baars, Wiebke; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

    2011-01-01

    The major immunological hurdle to successful porcine-to-human xenotransplantation is the acute vascular rejection (AVR), characterized by endothelial cell (EC) activation and perturbation of coagulation. Heme oxygenase-1 (HO-1) and its derivatives have anti-apoptotic, anti-inflammatory effects and protect against reactive oxygen species, rendering HO-1 a promising molecule to control AVR. Here, we report the production and characterization of pigs transgenic for human heme oxygenase-1 (hHO-1) and demonstrate significant protection in porcine kidneys against xenograft rejection in ex vivo perfusion with human blood and transgenic porcine aortic endothelial cells (PAEC) in a TNF-α-mediated apoptosis assay. Transgenic and non-transgenic PAEC were tested in a TNF-α-mediated apoptosis assay. Expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) was measured by real-time PCR. hHO-1 transgenic porcine kidneys were perfused with pooled and diluted human AB blood in an ex vivo perfusion circuit. MHC class-II up-regulation after induction with IFN-γ was compared between wild-type and hHO-1 transgenic PAEC. Cloned hHO-1 transgenic pigs expressed hHO-1 in heart, kidney, liver, and in cultured ECs and fibroblasts. hHO-1 transgenic PAEC were protected against TNF-α-mediated apoptosis. Real-time PCR revealed reduced expression of adhesion molecules like ICAM-1, VCAM-1, and E-selectin. These effects could be abrogated by the incubation of transgenic PAECs with the specific HO-1 inhibitor zinc protoporphorine IX (Zn(II)PPIX, 20 μm). IFN-γ induced up-regulation of MHC class-II molecules was significantly reduced in PAECs from hHO-1 transgenic pigs. hHO-1 transgenic porcine kidneys could successfully be perfused with diluted human AB-pooled blood for a maximum of 240 min (with and without C1 inh), while in wild-type kidneys, blood flow ceased after ∼60 min. Elevated levels of d-Dimer and TAT were detected, but no significant consumption of fibrinogen and

  16. Associations between rejection sensitivity and mental health outcomes : A meta-analytic review

    NARCIS (Netherlands)

    Gao, S.; Assink, M.; Cipriani, A.; Lin, K.

    2017-01-01

    Rejection sensitivity is a personality disposition characterized by oversensitivity to social rejection. Using a three-level meta-analytic model, 75 studies were reviewed that examined associations between rejection sensitivity and five mental health outcomes: depression, anxiety, loneliness,

  17. Children's coping with in vivo peer rejection: an experimental investigation.

    Science.gov (United States)

    Reijntjes, Albert; Stegge, Hedy; Terwogt, Mark Meerum; Kamphuis, Jan Henk; Telch, Michael J

    2006-12-01

    We examined children's behavioral coping in response to an in vivo peer rejection manipulation. Participants (N=186) ranging between 10 and 13 years of age, played a computer game based on the television show Survivor and were randomized to either peer rejection (i.e., being voted out of the game) or non-rejection control. During a five-min. post-feedback waiting period children's use of several behavioral coping strategies was assessed. Rejection elicited a marked shift toward more negative affect, but higher levels of perceived social competence attenuated the negative mood shift. Children higher in depressive symptoms were more likely to engage in passive and avoidant coping behavior. Types of coping were largely unaffected by gender and perceived social competence. Implications are discussed.

  18. Oxidative stress and vascular inflammation in aging.

    Science.gov (United States)

    El Assar, Mariam; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2013-12-01

    Vascular aging, a determinant factor for cardiovascular disease and health status in the elderly, is now viewed as a modifiable risk factor. Impaired endothelial vasodilation is a early hallmark of arterial aging that precedes the clinical manifestations of vascular dysfunction, the first step to cardiovascular disease and influencing vascular outcomes in the elderly. Accordingly, the preservation of endothelial function is thought to be an essential determinant of healthy aging. With special attention on the effects of aging on the endothelial function, this review is focused on the two main mechanisms of aging-related endothelial dysfunction: oxidative stress and inflammation. Aging vasculature generates an excess of the reactive oxygen species (ROS), superoxide and hydrogen peroxide, that compromise the vasodilatory activity of nitric oxide (NO) and facilitate the formation of the deleterious radical, peroxynitrite. Main sources of ROS are mitochondrial respiratory chain and NADPH oxidases, although NOS uncoupling could also account for ROS generation. In addition, reduced antioxidant response mediated by erythroid-2-related factor-2 (Nrf2) and downregulation of mitochondrial manganese superoxide dismutase (SOD2) contributes to the establishment of chronic oxidative stress in aged vessels. This is accompanied by a chronic low-grade inflammatory phenotype that participates in defective endothelial vasodilation. The redox-sensitive transcription factor, nuclear factor-κB (NF-κB), is upregulated in vascular cells from old subjects and drives a proinflammatory shift that feedbacks oxidative stress. This chronic NF-κB activation is contributed by increased angiotensin-II signaling and downregulated sirtuins and precludes adequate cellular response to acute ROS generation. Interventions targeted to recover endogenous antioxidant capacity and cellular stress response rather than exogenous antioxidants could reverse oxidative stress-inflammation vicious cycle in

  19. Paying To Belong: When Does Rejection Trigger Ingratiation?

    OpenAIRE

    Romero-Canyas, Rainer; Downey, Geraldine; Reddy, Kavita S; Rodriguez, Sylvia; Cavanaugh, Timothy J.; Pelayo, Rosemary

    2010-01-01

    Societies and social scientists have long held the belief that exclusion induces ingratiation and conformity, an idea in contradiction with robust empirical evidence linking rejection with hostility and aggression. The classic literatures on ingratiation and conformity help resolve this contradiction by identifying circumstances under which rejection may trigger efforts to ingratiate. Jointly, findings from these literatures suggest that when people are given an opportunity to impress their r...

  20. Effects of mir-21 on Cardiac Microvascular Endothelial Cells After Acute Myocardial Infarction in Rats: Role of Phosphatase and Tensin Homolog (PTEN)/Vascular Endothelial Growth Factor (VEGF) Signal Pathway

    OpenAIRE

    Yang, Feng; Liu, Wenwei; Yan, Xiaojuan; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Yu, Ming; Zhu, Xiaoshan; Ma, Kezhong

    2016-01-01

    Background This study investigated how miR-21 expression is reflected in acute myocardial infarction and explored the role of miR-21 and the PTEN/VEGF signaling pathway in cardiac microvascular endothelial cells. Material/Methods We used an in vivo LAD rat model to simulate acute myocardial infarction. MiR-21 mimics and miR-21 inhibitors were injected and transfected into model rats in order to alter miR-21 expression. Cardiac functions were evaluated using echocardiographic measurement, ELIS...

  1. Rejection or selection: influence of framing in investment decisions.

    Science.gov (United States)

    Cheng, Pi-Yueh; Chiou, Wen-Bin

    2010-02-01

    According to prospect theory, reflection effects result in preferences for risk-averse choices in gain situations and risk-seeking choices in loss situations. However, relevant literature in regard to decision making has suggested that positive information receives more weight in a selection task, whereas negative information receives more weight in a rejection task. The present study examined whether the nature of a decision task (selection vs rejection) would moderate the reflection effects. Undergraduates (47 men, 49 women; M age = 20.5 yr., SD = 1.1), selected according to specific screening criteria, participated in an experimental study. Typical reflection effects were observed in both selection and rejection task conditions. More importantly, negative information (i.e., the information about probable loss in risky choice of gain situations and the information about certain loss in cautious choice of loss situations) provided in the context of a rejection task received more weight and resulted in more frequent endorsements of the cautious choice in gain situations and of the risky choice in loss situations. Hence, the findings suggest that a decision context characterized by rejection may expand the reflection effects and thereby provide important information about situations in which investment decisions occur in a context characterized by rejection.

  2. Higher boron rejection with a new TFC forward osmosis membrane

    KAUST Repository

    Valladares Linares, Rodrigo

    2014-07-17

    Due to the stringent limits for boron in drinking and irrigation water, water treatment facilities have to incur additional treatment to remove boron down to a safe concentration. Forward osmosis (FO) is a membrane technology that may reduce the energy required to remove boron present in seawater. In direct FO desalination hybrid systems, fresh water is recovered from seawater using a recoverable draw solution, FO membranes are expected to show high boron rejection. This study focuses on determining the boron rejection capabilities of a new generation thin-film composite (TFC) FO membrane compared to a first generation cellulose triacetate (CTA) FO membrane. The effects of water permeate flux, membrane structure, draw solute charge, and reverse solute flux on boron rejection were determined. For TFC and CTA FO membranes, experiments showed that when similar operating conditions are applied (e.g. membrane type and draw solute type) boron rejection decreases with increase in permeate flux. Reverse draw solute flux and membrane fouling have no significant impact on boron rejection. Compared to the first generation CTA FO membrane operated at the same conditions, the TFC FO membrane showed a 40% higher boron rejection capability and a 20% higher water flux. This demonstrates the potential for boron removal for new generation TFC FO membranes. © 2014 © 2014 Balaban Desalination Publications. All rights reserved.

  3. Macrophage migration inhibitory factor induces vascular leakage via autophagy

    Directory of Open Access Journals (Sweden)

    Hong-Ru Chen

    2015-01-01

    Full Text Available Vascular leakage is an important feature of acute inflammatory shock, which currently has no effective treatment. Macrophage migration inhibitory factor (MIF is a pro-inflammatory cytokine that can induce vascular leakage and plays an important role in the pathogenesis of shock. However, the mechanism of MIF-induced vascular leakage is still unclear. In this study, using recombinant MIF (rMIF, we demonstrated that MIF induced disorganization and degradation of junction proteins and increased the permeability of human endothelial cells in vitro. Western blotting analysis showed that rMIF treatment induced LC3 conversion and p62 degradation. Inhibition of autophagy with a PI3K inhibitor (3-MA, a ROS scavenger (NAC or autophagosomal-lysosomal fusion inhibitors (bafilomycin A1 and chloroquine rescued rMIF-induced vascular leakage, suggesting that autophagy mediates MIF-induced vascular leakage. The potential involvement of other signaling pathways was also studied using different inhibitors, and the results suggested that MIF-induced vascular leakage may occur through the ERK pathway. In conclusion, we showed that MIF triggered autophagic degradation of endothelial cells, resulting in vascular leakage. Inhibition of MIF-induced autophagy may provide therapeutic targets against vascular leakage in inflammatory shock.

  4. Antioxidants and vascular health.

    Science.gov (United States)

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  5. The role of indium-111 antimyosin (Fab) imaging as a noninvasive surveillance method of human heart transplant rejection

    Energy Technology Data Exchange (ETDEWEB)

    De Nardo, D.; Scibilia, G.; Macchiarelli, A.G.; Cassisi, A.; Tonelli, E.; Papalia, U.; Gallo, P.; Antolini, M.; Pitucco, G.; Reale, A. (Universita degli Studi di Roma I La Sapienza Policlinico Umberto I (Italy))

    1989-09-01

    The identification of rejection after heart transplantation in patients receiving cyclosporine immunosuppressive therapy requires the endomyocardial biopsy, an invasive method associated with a finite morbidity. To evaluate the role of indium-111 antimyosin (Fab) scintigraphy as a noninvasive surveillance method of heart transplant rejection, the Fab fragment of murine monoclonal antimyosin antibodies labeled with indium-111 was administered intravenously in 30 scintigraphic studies to 10 consecutive heart transplant recipients. Endomyocardial biopsy specimens were obtained 72 hours after each scintigraphic study. Nineteen scintigraphic studies had negative findings; no false negative finding was obtained. Eleven antimyosin scintigraphic studies had positive findings, and in these studies endomyocardial biopsy revealed mild rejection in two cases, moderate acute rejection with myocyte necrosis in two cases, myocyte necrosis as a consequence of ischemic injury in six cases, and possibly cytotoxic damage in one case. Antimyosin scintigraphy may represent a reliable screening method for the surveillance of heart transplant patients. In the presence of a negative finding from antimyosin scintigraphy, it may be possible to avoid endomyocardial biopsy. Conversely, in patients who have a positive finding from antimyosin scintigraphy, the endomyocardial biopsy is mandatory to establish the definitive diagnosis by histologic examination of the myocardium.

  6. Novel Non-Histocompatibility Antigen Mismatched Variants Improve the Ability to Predict Antibody-Mediated Rejection Risk in Kidney Transplant

    Directory of Open Access Journals (Sweden)

    Silvia Pineda

    2017-12-01

    Full Text Available Transplant rejection is the critical clinical end-point limiting indefinite survival after histocompatibility antigen (HLA mismatched organ transplantation. The predominant cause of late graft loss is antibody-mediated rejection (AMR, a process whereby injury to the organ is caused by donor-specific antibodies, which bind to HLA and non-HLA (nHLA antigens. AMR is incompletely diagnosed as donor/recipient (D/R matching is only limited to the HLA locus and critical nHLA immunogenic antigens remain to be identified. We have developed an integrative computational approach leveraging D/R exome sequencing and gene expression to predict clinical post-transplant outcome. We performed a rigorous statistical analysis of 28 highly annotated D/R kidney transplant pairs with biopsy-confirmed clinical outcomes of rejection [either AMR or T-cell-mediated rejection (CMR] and no-rejection (NoRej, identifying a significantly higher number of mismatched nHLA variants in AMR (ANOVA—p-value = 0.02. Using Fisher’s exact test, we identified 123 variants associated mainly with risk of AMR (p-value < 0.001. In addition, we applied a machine-learning technique to circumvent the issue of statistical power and we found a subset of 65 variants using random forest, that are predictive of post-tx AMR showing a very low error rate. These variants are functionally relevant to the rejection process in the kidney and AMR as they relate to genes and/or expression quantitative trait loci (eQTLs that are enriched in genes expressed in kidney and vascular endothelium and underlie the immunobiology of graft rejection. In addition to current D/R HLA mismatch evaluation, additional mismatch nHLA D/R variants will enhance the stratification of post-tx AMR risk even before engraftment of the organ. This innovative study design is applicable in all solid organ transplants, where the impact of mitigating AMR on graft survival may be greater, with considerable benefits on

  7. Selective cyclooxygenase-1 inhibition improves collateral vascular reactivity in biliary cirrhotic rats

    Directory of Open Access Journals (Sweden)

    Ching-Chih Chang

    2013-10-01

    Conclusion: There was no significant hemodynamic change and renal toxicity after acute administration of COX inhibitor in the FBDL-induced cirrhotic rats. Preincubation of selective COX-1, but not COX-2, inhibitor could enhance collateral vascular response to AVP, indicating that COX-1 plays a major role in the collateral vascular reactivity.

  8. Treatment of hemobilia by transcatheter vascular occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, R.; Roesch, J.; Keller, F.S.; Antonovic, R.

    1984-08-01

    Four cases of hemobilia treated by transcatheter arterial occlusion are presented and reviewed with 30 similar cases reported in the literature. Transcatheter vascular occlusion successfully controlled hemorrhage in all 34 patients. No obvious liver parenchymal damage appeared in 26 patients; transient elevation of liver enzymes occurred in 6 patients (18%) including one in our series; two of the patients reviewed died of acute hepatic insufficiency following nonselective hepatic artery embolization. Hemobilia should be considered when gastrointestinal hemorrhage occurs after abdominal trauma, liver biopsy or other manipulative liver procedures. Hepatic angiography establishes the diagnosis and selective vascular occlusion is the treatment of choice for control of intractable or recurrent hemorrhage. Techniques and precautions for the diagnosis and transcatheter therapy of hemobilia are discussed.

  9. [Vascular complications associated with lumbar spinal surgery].

    Science.gov (United States)

    Riedemann-Wistuba, M; Alonso-Pérez, M; Llaneza-Coto, J M

    2016-01-01

    Although there are currently less invasive techniques available for the treatment of spinal injuries, open surgery is still required in many cases. Vascular injuries occurring during lumbar spine surgery, although uncommon, are of great importance due to their potential gravity. Clinical manifestations vary from an acute hemorrhagic shock that needs urgent treatment to save the patient's life, to insidious injuries or an asymptomatic evolution, and should be studied to choose the best therapeutic alternative. Four cases are reported that represent this range of possibilities and emphasize the importance of a careful surgical technique during lumbar spine interventions, and the need for high clinical suspicion, essential for the early diagnosis of these vascular complications. The current therapeutic options are also discussed. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  10. Vascularized epiphyseal transplant.

    Science.gov (United States)

    Innocenti, Marco; Delcroix, Luca; Romano, G Federico; Capanna, Rodolfo

    2007-01-01

    In skeletally immature patients, the transfer of vascularized epiphysis along with a variable amount of adjoining diaphysis may provide the potential for growth of such a graft, preventing future limb length discrepancy. This article describes the authors' experience with the vascularized transfer of the proximal fibular epiphysis in the reconstruction of large bone defects including the epiphysis in a series of 27 patients ranging in age from 2 to 11 years. The follow-up, ranging from 2 to 14 years, has been long enough to allow some evaluation of the validity, indications, and limits of this reconstructive option.

  11. Effects of mir-21 on Cardiac Microvascular Endothelial Cells After Acute Myocardial Infarction in Rats: Role of Phosphatase and Tensin Homolog (PTEN)/Vascular Endothelial Growth Factor (VEGF) Signal Pathway

    Science.gov (United States)

    Yang, Feng; Liu, Wenwei; Yan, Xiaojuan; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Yu, Ming; Zhu, Xiaoshan; Ma, Kezhong

    2016-01-01

    Background This study investigated how miR-21 expression is reflected in acute myocardial infarction and explored the role of miR-21 and the PTEN/VEGF signaling pathway in cardiac microvascular endothelial cells. Material/Methods We used an in vivo LAD rat model to simulate acute myocardial infarction. MiR-21 mimics and miR-21 inhibitors were injected and transfected into model rats in order to alter miR-21 expression. Cardiac functions were evaluated using echocardiographic measurement, ELISA, and Masson staining. In addition, lenti-PTEN and VEGF siRNA were transfected into CMEC cells using standard procedures for assessing the effect of PTEN and VEGE on cell proliferation, apoptosis, and angiogenesis. MiR-21, PTEN, and VEGF expressions were examined by RT-PCR and Western blot. The relationship between miR-21 and PTEN was determined by the luciferase activity assay. Results We demonstrated that miR-21 bonded with the 3′-UTR of PTEN and suppressed PTEN expressions. Established models significantly induced cardiac infarct volume and endothelial injury marker expressions as well as miR-21 and PTEN expressions (Pcell proliferation, apoptosis, and angiogenesis (P<0.05). Conclusions MiR-21 exerts protective effects on endothelial injury through the PTEN/VEGF pathway after acute myocardial infarction. PMID:27708252

  12. Rejection mechanisms for contaminants in polymeric reverse osmosis membranes

    CERN Document Server

    Shen, Meng; Lueptow, Richard M

    2016-01-01

    Despite the success of reverse osmosis (RO) for water purification, the molecular-level physico-chemical processes of contaminant rejection are not well understood. Here we carry out NEMD simulations on a model polyamide RO membrane to understand the mechanisms of transport and rejection of both ionic and neutral contaminants in water. We observe that the rejection changes non-monotonously with ion sizes. In particular, the rejection of urea, 2.4 A radius, is higher than ethanol, 2.6 A radius, and the rejections for organic solutes, 2.2-2.8 A radius, are lower than Na+, 1.4 A radius, or Cl-, 2.3 A radius. We show that this can be explained in terms of the solute accessible intermolecular volume in the membrane and the solute-water pair interaction energy. If the smallest open spaces in the membrane's molecular structure are all larger than the hydrated solute, then the solute-water pair interaction energy does not matter. However, when the open spaces in the polymeric structure are such that solutes have to s...

  13. The composition of the microbiota modulates allograft rejection.

    Science.gov (United States)

    Lei, Yuk Man; Chen, Luqiu; Wang, Ying; Stefka, Andrew T; Molinero, Luciana L; Theriault, Betty; Aquino-Michaels, Keston; Sivan, Ayelet S; Nagler, Cathryn R; Gajewski, Thomas F; Chong, Anita S; Bartman, Caroline; Alegre, Maria-Luisa

    2016-07-01

    Transplantation is the only cure for end-stage organ failure, but without immunosuppression, T cells rapidly reject allografts. While genetic disparities between donor and recipient are major determinants of the kinetics of transplant rejection, little is known about the contribution of environmental factors. Because colonized organs have worse transplant outcome than sterile organs, we tested the influence of host and donor microbiota on skin transplant rejection. Compared with untreated conventional mice, pretreatment of donors and recipients with broad-spectrum antibiotics (Abx) or use of germ-free (GF) donors and recipients resulted in prolonged survival of minor antigen-mismatched skin grafts. Increased graft survival correlated with reduced type I IFN signaling in antigen-presenting cells (APCs) and decreased priming of alloreactive T cells. Colonization of GF mice with fecal material from untreated conventional mice, but not from Abx-pretreated mice, enhanced the ability of APCs to prime alloreactive T cells and accelerated graft rejection, suggesting that alloimmunity is modulated by the composition of microbiota rather than the quantity of bacteria. Abx pretreatment of conventional mice also delayed rejection of major antigen-mismatched skin and MHC class II-mismatched cardiac allografts. This study demonstrates that Abx pretreatment prolongs graft survival, suggesting that targeting microbial constituents is a potential therapeutic strategy for enhancing graft acceptance.

  14. The role of peer rejection in adolescent depression.

    Science.gov (United States)

    Platt, Belinda; Cohen Kadosh, Kathrin; Lau, Jennifer Y F

    2013-09-01

    Adolescence is a period of major risk for depression, which is associated with negative personal, social, and educational outcomes. Yet, in comparison to adult models of depression, very little is known about the specific psychosocial stressors that contribute to adolescent depression, and whether these can be targeted by interventions. In this review, we consider the role of peer rejection. First, we present a comprehensive review of studies using innovative experimental paradigms to understand the role of peer rejection in adolescent depression. We show how reciprocal relationships between peer rejection and depressive symptoms across adolescence powerfully shape and maintain maladaptive trajectories. Second, we consider how cognitive biases and their neurobiological substrates may explain why some adolescents are more vulnerable to the effects of, and perhaps exposure to, peer rejection compared to others. Finally, we draw attention to emerging cognitive and functional magnetic resonance imaging-based neurofeedback training, which by modifying aspects of information processing may promote more adaptive responses to peer rejection. A better understanding of the mechanisms underlying adolescent depression may not only alleviate symptoms during a period of substantial developmental challenges, but may also reduce the burden of the disorder across the lifespan. © 2013 Wiley Periodicals, Inc.

  15. Atrial fibrillation and vascular disease-a bad combination

    DEFF Research Database (Denmark)

    Bjerring Olesen, Jonas; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian

    2012-01-01

    This article provides an overview of (i) the risk of stroke associated with vascular disease (acute coronary syndromes and peripheral artery disease) in patients with atrial fibrillation, (ii) the frequent coexistence of vascular disease in patients with atrial fibrillation and, (iii......) the cardiovascular risk associated with the coexisting of the two diseases. The literature on this topic is relatively sparse, and we discuss results from both clinical trials and observational studies. There is a clear indication of an increased stroke risk associated with vascular disease in patients with atrial...... fibrillation. Indeed, patients with atrial fibrillation often had coexisting vascular disease (around 18%), and the combination of the two diseases substantially increases the risk of future cardiovascular events. The increased risk associated with peripheral artery disease in atrial fibrillation is even more...

  16. C-reactive protein (CRP) in cerebro-vascular events.

    Science.gov (United States)

    Canova, C R; Courtin, C; Reinhart, W H

    1999-11-01

    C-reactive protein (CRP) is a useful prognostic factor in coronary heart disease. It has not been previously studied in acute cerebro-vascular events, which was the topic of the present study. Patients admitted to the hospital for an acute cerebro-vascular event were prospectively investigated. C-reactive protein was determined nephelometrically. Infection or inflammation were excluded clinically and with an erythrocyte sedimentation rate brain was performed. According to initial brain imaging and the clinical course the 138 patients were divided into five groups: 20 with transient ischemic attack, 20 with reversible neurological deficit lasting less than 2 weeks, 61 with completed stroke and restitution, 16 with stroke without restitution and 21 with cerebral hemorrhage. Median CRP values (range) were 3.2 (2.4-13.5), 3.3 (2.4-39.4), 4.2 (2.4-73. 4), 3.4 (3.2-44.0) and 3.5 (2.4-104.0 mg/l), respectively with no significant differences between groups in a non-parametric test (Kruskal-Wallis). Risk factors for vascular disease in general and stroke in particular had no visible influence on CRP levels. No relationship was found between time interval since onset of symptoms and CRP measurement, suggesting that an acute cerebro-vascular event has little influence on CRP values. CRP is not a useful marker to predict the outcome of an acute cerebro-vascular event on hospital admission. This is in contrast to acute coronary events.

  17. [Gastric vascular lesions in cirrhosis: gastropathy and antral vascular ectasia].

    Science.gov (United State