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Sample records for mediate cardiovascular transplantation

  1. Screening for cardiovascular disease before kidney transplantation

    PubMed Central

    Palepu, Sneha; Prasad, G V Ramesh

    2015-01-01

    Pre-kidney transplant cardiac screening has garnered particular attention from guideline committees as an approach to improving post-transplant success. Screening serves two major purposes: To more accurately inform transplant candidates of their risk for a cardiac event before and after the transplant, thereby informing decisions about proceeding with transplantation, and to guide pre-transplant management so that post-transplant success can be maximized. Transplant candidates on dialysis are more likely to be screened for coronary artery disease than those not being considered for transplantation. Thorough history and physical examination taking, resting electrocardiography and echocardiography, exercise stress testing, myocardial perfusion scintigraphy, dobutamine stress echocardiography, cardiac computed tomography, cardiac biomarker measurement, and cardiac magnetic resonance imaging all play contributory roles towards screening for cardiovascular disease before kidney transplantation. In this review, the importance of each of these screening procedures for both coronary artery disease and other forms of cardiac disease are discussed. PMID:26722655

  2. Cardiovascular risk assessment of the liver transplant candidate.

    PubMed

    Raval, Zankhana; Harinstein, Matthew E; Skaro, Anton I; Erdogan, Ata; DeWolf, Andre M; Shah, Sanjiv J; Fix, Oren K; Kay, Nina; Abecassis, Michael I; Gheorghiade, Mihai; Flaherty, James D

    2011-07-12

    Liver transplantation (LT) candidates today are increasingly older, have greater medical acuity, and have more cardiovascular comorbidities than ever before. Steadily rising model for end-stage liver disease (MELD) scores at the time of transplant, resulting from high organ demand, reflect the escalating risk profiles of LT candidates. In addition to advanced age and the presence of comorbidities, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually demonstrate increased cardiac output and a compromised ventricular response to stress, a condition termed cirrhotic cardiomyopathy. These cardiac disturbances are likely mediated by decreased beta-agonist transduction, increased circulating inflammatory mediators with cardiodepressant properties, and repolarization changes. Low systemic vascular resistance and bradycardia are also commonly seen in cirrhosis and can be aggravated by beta-blocker use. These physiologic changes all contribute to the potential for cardiovascular complications, particularly with the altered hemodynamic stresses that LT patients face in the immediate post-operative period. Post-transplant reperfusion may result in cardiac death due to a multitude of causes, including arrhythmia, acute heart failure, and myocardial infarction. Recognizing the hemodynamic challenges encountered by LT patients in the perioperative period and how these responses can be exacerbated by underlying cardiac pathology is critical in developing recommendations for the pre-operative risk assessment and management of these patients. The following provides a review of the cardiovascular challenges in LT candidates, as well as evidence-based recommendations for their evaluation and management.

  3. Cardiovascular risk factors following renal transplant

    PubMed Central

    Neale, Jill; Smith, Alice C

    2015-01-01

    Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population. PMID:26722646

  4. Metabolic and cardiovascular complications in the liver transplant recipient

    PubMed Central

    Luca, Laura De; Westbrook, Rachel; Tsochatzis, Emmanuel A.

    2015-01-01

    Metabolic syndrome (MS) is an established risk factor for atherosclerosis and cardiovascular disease that affects 20-30% of the adult population in the western world, correlating with increased incidence of cardiovascular disease. Survival following liver transplantation (LT) has been steadily improving over the last 2 decades, with graft loss becoming a relatively rare cause of morbidity and mortality post LT. The improvement in short-term survival following LT has resulted in an increased incidence of metabolic and cardiovascular complications, which affect the mid- and long term survival. Patients following LT typically gain weight and might develop diabetes, hypertension and dyslipidemia as a consequence of their immunosuppressive therapy and their lifestyle. In this paper we review the prevalence of metabolic and cardiovascular complications following LT, their impact on post-transplant morbidity and mortality and their optimal management. PMID:25830307

  5. Validation of cardiovascular risk scores in a liver transplant population.

    PubMed

    Guckelberger, Olaf; Mutzke, Florian; Glanemann, Matthias; Neumann, Ulf P; Jonas, Sven; Neuhaus, Ruth; Neuhaus, Peter; Langrehr, Jan M

    2006-03-01

    Increased prevalence of cardiovascular risk factors has been acknowledged in liver transplant recipients, and an increased incidence of cardiovascular events has been suspected. Individual risk determination, however, has not yet been established. Outpatient charts of 438 primary liver transplants have been reviewed, and suspected cardiovascular risk factors were correlated with cardiovascular events observed during a follow-up period of 10 yr. Receiver operation characteristics curve (ROC) analysis was performed to validate established cardiovascular risk scores. For calibration, the Hosmer-Lemeshow test was performed. A total of 303 of 438 patients were available for risk factor analysis at 6 months and demonstrated complete follow-up data (175 male, 128 female). A total of 40 of those 303 patients experienced fatal or nonfatal cardiovascular events (13.2%). In univariate analysis, age (P < 0.001), gender (P = 0.002), body mass index (P = 0.018), cholesterol (P = 0.044), creatinine (P = 0.006), diabetes mellitus (P = 0.017), glucose (0.006), and systolic blood pressure (P = 0.043), but not cyclosporine A (P = 0.743), tacrolimus (P = 0.870), or steroid medication (P = 0.991), were significantly associated with cardiovascular events. Multivariate analysis, however, identified only age, gender, and cholesterol as independent predictors. In ROC analysis, corresponding areas under the curve for Systematic Coronary Risk Evaluation Project (SCORE), Prospective Cardiovascular Münster Study (PROCAM), and Framingham risk scores (FRSs) were calculated with 0.800, 0.778, and 0.707, respectively. Calibration demonstrated an improved goodness of fit for PROCAM compared to SCORE risk calculations. In conclusion, SCORE and PROCAM proved to be valuable in discriminating our liver transplant recipients for their individual risk of cardiovascular events. Furthermore, calibrated PROCAM risk estimates are required to calculate the number of patients needed to treat in the setup of

  6. Role of cardiovascular intervention as a bridge to liver transplantation.

    PubMed

    Raval, Zankhana; Harinstein, Matthew E; Flaherty, James D

    2014-08-21

    End stage liver disease (ESLD) is associated with many specific derangements in cardiovascular physiology, which influence perioperative outcomes and may profoundly influence diagnostic and management strategies in the preoperative period. This review focuses on evidence-based diagnosis and management of coronary, hemodynamic and pulmonary vascular disease in this population with an emphasis on specific strategies that may provide a bridge to transplantation. Specifically, we address the underlying prevalence of cardiovascular disease states in the ESLD population, and relevant diagnostic criteria thereof. We highlight traditional and non-traditional predictors of cardiovascular outcomes following liver transplant, as well as data to guide risk-factor based diagnostic strategies. We go on to discuss the alterations in cardiovascular physiology which influence positive- and negative-predictive values of standard noninvasive testing modalities in the ESLD population, and review the data regarding the safety and efficacy of invasive testing in the face of ESLD and its co-morbidities. Finally, based upon the totality of available data, we outline an evidence-based approach for the management of ischemia, heart failure and pulmonary vascular disease in this population. It is our hope that such evidence-driven strategies can be employed to more safely bridge appropriate candidates to liver transplant, and to improve their cardiovascular health and outcomes in the peri-operative period. PMID:25152569

  7. Cardiovascular Risk Assessment and Management in Prerenal Transplantation Candidates.

    PubMed

    Lindley, Eric M; Hall, Amanda K; Hess, Jordan; Abraham, Jo; Smith, Brigham; Hopkins, Paul N; Shihab, Fuad; Welt, Frederick; Owan, Theophilus; Fang, James C

    2016-01-01

    Cardiovascular (CV) assessment in prerenal transplant patients varies by center. Current guidelines recommend stress testing for candidates if ≥ 3 CV risk factors exist. We evaluated the CV assessment and management in 685 patients referred for kidney transplant over a 7-year period. All patients had CV risk factors, and the most common cause of end-stage renal disease was diabetes. Thirty-three percent (n = 229) underwent coronary angiography. The sensitivity of stress testing to detect obstructive coronary artery disease (CAD) was poor (0.26). Patients who had no CAD, nonobstructive CAD, or CAD with intervention had significantly higher event-free survival compared with patients with obstructive CAD without intervention. There were no adverse clinical events (death, myocardial infarction, stroke, revascularization, and graft failure) within 30 days post-transplant in patients who had preoperative angiography (n = 77). Of the transplanted patients who did not have an angiogram (n = 289), there were 8 clinical events (6 myocardial infarctions) in the first 30 days. In conclusion, our results indicate that stress testing and usual risk factors were poor predictors of obstructive CAD and that revascularization may prove beneficial in these patients.

  8. Aspirin resistance as cardiovascular risk after kidney transplantation

    NASA Astrophysics Data System (ADS)

    Sandor, Barbara; Varga, Adam; Rabai, Miklos; Toth, Andras; Papp, Judit; Toth, Kalman; Szakaly, Peter

    2014-05-01

    International surveys have shown that the leading cause of death after kidney transplantation has cardiovascular origin with a prevalence of 35-40%. As a preventive strategy these patients receive aspirin (ASA) therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurements were performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin (100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effective in case of low ( i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirin resistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years) were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11 years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared to the positive control group (PC) (35.9% vs. 25.6%, p < 0.002). Morbidity analysis demonstrated significantly higher incidence of myocardial infarction, hypertension and diabetes mellitus in the RT group (p < 0.05). The subgroup analysis revealed significantly higher incidence of infarction and stroke in the ASA resistant RT group compared to the RT patients without ASA resistance (p < 0.05). Furthermore, the incidence of myocardial infarction and hypertension was significantly higher in the non-resistant RT group than in the group of PC patients without ASA resistance (p < 0.05). These results may suggest that the elevated rate of aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

  9. The risk of cardiovascular disease associated with proteinuria in renal transplant patients.

    PubMed

    Fernández-Fresnedo, Gema; Escallada, Rafael; Rodrigo, Emilio; De Francisco, Angel L M; Cotorruelo, Julio G; Sanz De Castro, Saturnino; Zubimendi, Jose A; Ruiz, J C; Arias, Manuel

    2002-04-27

    Proteinuria in the general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplantation. We investigated the effect of proteinuria on cardiovascular disease after renal transplantation in 532 renal transplant patients with functioning grafts for more than 1 year. Patients were classified into two groups depending on the presence of persistent proteinuria. We analyzed graft and patient survival, posttransplantation cardiovascular disease, and main causes of graft loss and death. Five- and 10-year graft and patient survival rates were lower in the group with proteinuria. The main cause of death was vascular disease in both groups. The presence of posttransplantation cardiovascular disease was higher in the group with proteinuria. Persistent proteinuria was associated with graft loss (RR=4.18), patient death (RR=1.92), and cardiovascular disease (RR=2.45). In conclusion, persistent proteinuria was an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.

  10. Immune-Mediated Vascular Injury and Dysfunction in Transplant Arteriosclerosis

    PubMed Central

    von Rossum, Anna; Laher, Ismail; Choy, Jonathan C.

    2015-01-01

    Solid organ transplantation is the only treatment for end-stage organ failure but this life-saving procedure is limited by immune-mediated rejection of most grafts. Blood vessels within transplanted organs are targeted by the immune system and the resultant vascular damage is a main contributor to acute and chronic graft failure. The vasculature is a unique tissue with specific immunological properties. This review discusses the interactions of the immune system with blood vessels in transplanted organs and how these interactions lead to the development of transplant arteriosclerosis, a leading cause of heart transplant failure. PMID:25628623

  11. Cardiovascular risk factors and events in pancreas-kidney transplants.

    PubMed

    Martins, L; Fonseca, I; Dias, L; Malheiro, J; Rocha, A; Azevedo, P; Silva, H; Almeida, R; Henriques, A C; Davide, J; Cabrita, A

    2013-04-01

    Cardiovascular and cerebrovascular disease (CCVD) are major causes of morbidity and mortality among patients with diabetes. Strict control of treatable risk factors that contribute to atherosclerosis is important to reduce the risk of stroke, myocardial infarction, and peripheral arterial disease. Simultaneous pancreas-kidney transplantation (SPKT) may significantly improve these risk factors in patients with type 1 diabetes. We studied 103 SPKT from our center with both organs functioning for metabolic and hypertensive control; body mass index (BMI); immunosuppression; and CCVD events. The 53 females/50 males showed a mean age of 35 ± 6 years, diabetes for 24 ± 6 years, and on dialysis for 31 ± 23 months. The follow-up ranged from 6-142 months. Mean value of last creatinine clearance was 76 ± 24 mL/min, all 103 SPKT were insulin-independent with mean glycemia = 81 ± 10 mg/dL and hemoglobin A1c (HbA1c) = 5.3% ± 0.4%. All of them were under tacrolimus treatment; 9.7% also with sirolimus but 67% steroid-free. According to the National Cholesterol Education Program Adult Treatment Panel 3 criteria, 4 patients showed a fasting glucose > 100 mg/dL; only one, HbA1c > 5.6%. Hypertension was recorded in 38.5%; low high-density lipoprotein cholesterol in 19.4%; hypertriglyceridemia in 7.8%; BMI > 30% in only 2 patients; 21.4% were prescribed statins. We registered cardiovascular events in 7 patients (6.8%). Patients with steroid treatment showed higher triglycerides (122 ± 53 vs 90 ± 36 mg/dL; P = .001) and more often tended to be hypertensive (41.2% vs 37.7%, P = .073) compared with those free of these drugs. Hypertension was associated with an higher BMI (24.1 ± 2.8 vs 22.3 ± 2.9 kg/m(2), P = .002). BMI > 25% was associated with higher total cholesterol (195 ± 47 vs 169 ± 28 mg/dL, P = .015) and low-density lipoprotein cholesterol (116 ± 40 vs 96 ± 27 mg/dL, P = .003). Among our SPKT the prevalences of CCVD and metabolic syndrome were low. Hypertension was

  12. Inflammation, Coronary Artery Calcification and Cardiovascular Events in Incident Renal Transplant Recipients

    PubMed Central

    Roe, Peter; Wolfe, Megan; Joffe, Marshall; Rosas, Sylvia E

    2010-01-01

    Objective Coronary artery calcification (CAC) predicts cardiovascular events in the general population. We conducted a prospective study to determine if inflammatory markers were predictive of CAC and if CAC predicted cardiovascular events and mortality in incident renal transplant recipients. Methods A prospective cohort of 112 asymptomatic incident renal transplant recipients who had no prior history of coronary artery revascularization or myocardial infarction had coronary calcifications measured early post-transplant and at least 18 months later by Agatston score and volume method. Results The mean CAC score was 367.7 (682.3). Inflammatory markers such as WBC and CRP were predictive of CAC severity. Recipients with cardiovascular events (n=11) or death (n=12) during the follow-up period had higher mean [675.1 (669.3) vs. 296.8(669.0), p=0.02] and median [434.8 vs. 28.9, p=0.01] CAC score compared to those without them. Recipients with CAC score less than 100 had a better cumulative survival rate compared to the recipients with CAC score greater than 100 [95.1 vs. 82.3%, p=0.03]. We found a significant unadjusted and adjusted association between CAC score and cardiovascular events and mortality. A quarter (25.9%) of recipients had CAC progression. Coronary calcification progression also predicted cardiovascular events and mortality after adjustment for diabetes, age, dialysis vintage and presence of CAC at time of transplant. Conclusion CAC is prevalent in renal recipients and is predictive of cardiovascular events and mortality. Changes in coronary calcification are common and predict clinical outcomes. Inflammatory markers are predictive of CAC severity at time of transplant, but are not predictive of future cardiovascular event or mortality. PMID:20934074

  13. Pulse pressure is an independent risk factor of cardiovascular disease in renal transplant patients.

    PubMed

    Fernández-Fresnedo, G; Escallada, R; Rodrigo, E; de Francisco, A L M; Sanz de Castro, S; Ruiz, J C; Piñera, C; Cotorruelo, J G; Arias, M

    2003-08-01

    Elevated pulse pressure in the general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplant patients. We investigated the effects that a wide pulse pressure has on cardiovascular disease after renal transplantation in a cohort of 532 transplant patients with functioning grafts for more than one year. Patients were classified into two groups depending on whether the one-year pulse pressure was less than or greater than 65 mm Hg. We analyzed patient survival, posttransplant cardiovascular disease and principle causes of death. Five- and ten-year patient survival were lower among the group with higher pulse pressures. The main cause of death was vascular disease in both groups. The presence of posttransplant cardiovascular disease was higher among the group with higher pulse pressures (RR=1.73). In addition, the incidence of an elevated pulse pressure was directly associated with recipient age and posttransplant diabetes mellitus. In conclusion, pulse pressure represents an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.

  14. The Complement System and Antibody-Mediated Transplant Rejection.

    PubMed

    Stites, Erik; Le Quintrec, Moglie; Thurman, Joshua M

    2015-12-15

    Complement activation is an important cause of tissue injury in patients with Ab-mediated rejection (AMR) of transplanted organs. Complement activation triggers a strong inflammatory response, and it also generates tissue-bound and soluble fragments that are clinically useful markers of inflammation. The detection of complement proteins deposited within transplanted tissues has become an indispensible biomarker of AMR, and several assays have recently been developed to measure complement activation by Abs reactive to specific donor HLA expressed within the transplant. Complement inhibitors have entered clinical use and have shown efficacy for the treatment of AMR. New methods of detecting complement activation within transplanted organs will improve our ability to diagnose and monitor AMR, and they will also help guide the use of complement inhibitory drugs.

  15. The Complement System and Antibody-Mediated Transplant Rejection.

    PubMed

    Stites, Erik; Le Quintrec, Moglie; Thurman, Joshua M

    2015-12-15

    Complement activation is an important cause of tissue injury in patients with Ab-mediated rejection (AMR) of transplanted organs. Complement activation triggers a strong inflammatory response, and it also generates tissue-bound and soluble fragments that are clinically useful markers of inflammation. The detection of complement proteins deposited within transplanted tissues has become an indispensible biomarker of AMR, and several assays have recently been developed to measure complement activation by Abs reactive to specific donor HLA expressed within the transplant. Complement inhibitors have entered clinical use and have shown efficacy for the treatment of AMR. New methods of detecting complement activation within transplanted organs will improve our ability to diagnose and monitor AMR, and they will also help guide the use of complement inhibitory drugs. PMID:26637661

  16. The impact of cardiovascular disease and risk factor treatment on ethnic disparities in kidney transplant.

    PubMed

    Taber, David J; Pilch, Nicole A; Meadows, Holly B; McGillicuddy, John W; Bratton, Charles F; Chavin, Kenneth D; Baliga, Prabhakar K; Egede, Leonard E

    2013-05-01

    There is limited data on the use of cardiovascular disease (CVD) risk factor medications following renal transplant, especially when comparing use across ethnicities. The aim of this study was to compare the incidence, treatment, and impact of CVD between ethnicities in kidney transplant recipients. This was a retrospective cohort study of adults who underwent transplant between 2000 and 2008 within our academic medical transplant center. Pediatrics, multiorgan transplants, and those lost to follow-up were excluded. Data collection included all transplant and sociodemographic characteristics, medication use, CVD risk factor management, and follow-up events, including acute rejection, graft loss, and death. A total of 987 patients were included and followed for a mean of 6.7 ± 3.0 years. The baseline demographics revealed black patients were equally likely to have preexisting CVD (24% vs 25%, P = .651), but more likely to have preexisting diabetes (35% vs 23%, P < .001) or hypertension (97% vs 94%, P = .029). Black patients had poorer treatment of CVD risk factors, with lower rates of control of diabetes (35% vs 51%, P < .05) and dyslipidemia (37% vs 42%, P < .05). Black renal transplant recipients who had preexisting CVD had reduced graft survival rates compared to white patients (10-year rate 50% vs 60%, P = .033), but similar rates of graft survival were found in those without CVD (10-year rate 70% vs 71% in white patients, P = .483). CVD is common in transplant recipients, with black patients having higher rates and poorer control of diabetes and dyslipidemia.

  17. Adipokines and the cardiovascular system: mechanisms mediating health and disease.

    PubMed

    Northcott, Josette M; Yeganeh, Azadeh; Taylor, Carla G; Zahradka, Peter; Wigle, Jeffrey T

    2012-08-01

    This review focuses on the role of adipokines in the maintenance of a healthy cardiovascular system, and the mechanisms by which these factors mediate the development of cardiovascular disease in obesity. Adipocytes are the major cell type comprising the adipose tissue. These cells secrete numerous factors, termed adipokines, into the blood, including adiponectin, leptin, resistin, chemerin, omentin, vaspin, and visfatin. Adipose tissue is a highly vascularised endocrine organ, and different adipose depots have distinct adipokine secretion profiles, which are altered with obesity. The ability of many adipokines to stimulate angiogenesis is crucial for adipose tissue expansion; however, excessive blood vessel growth is deleterious. As well, some adipokines induce inflammation, which promotes cardiovascular disease progression. We discuss how these 7 aforementioned adipokines act upon the various cardiovascular cell types (endothelial progenitor cells, endothelial cells, vascular smooth muscle cells, pericytes, cardiomyocytes, and cardiac fibroblasts), the direct effects of these actions, and their overall impact on the cardiovascular system. These were chosen, as these adipokines are secreted predominantly from adipocytes and have known effects on cardiovascular cells.

  18. Updates on antibody-mediated rejection in intestinal transplantation

    PubMed Central

    Wu, Guo-Sheng

    2016-01-01

    Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation. PMID:27683635

  19. Updates on antibody-mediated rejection in intestinal transplantation.

    PubMed

    Wu, Guo-Sheng

    2016-09-24

    Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation. PMID:27683635

  20. Updates on antibody-mediated rejection in intestinal transplantation

    PubMed Central

    Wu, Guo-Sheng

    2016-01-01

    Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation.

  1. Gene therapy for cardiovascular disease mediated by ultrasound and microbubbles

    PubMed Central

    2013-01-01

    Gene therapy provides an efficient approach for treatment of cardiovascular disease. To realize the therapeutic effect, both efficient delivery to the target cells and sustained expression of transgenes are required. Ultrasound targeted microbubble destruction (UTMD) technique has become a potential strategy for target-specific gene and drug delivery. When gene-loaded microbubble is injected, the ultrasound-mediated microbubble destruction may spew the transported gene to the targeted cells or organ. Meanwhile, high amplitude oscillations of microbubbles increase the permeability of capillary and cell membrane, facilitating uptake of the released gene into tissue and cell. Therefore, efficiency of gene therapy can be significantly improved. To date, UTMD has been successfully investigated in many diseases, and it has achieved outstanding progress in the last two decades. Herein, we discuss the current status of gene therapy of cardiovascular diseases, and reviewed the progress of the delivery of genes to cardiovascular system by UTMD. PMID:23594865

  2. Central autonomic network mediates cardiovascular responses to acute inflammation: Relevance to increased cardiovascular risk in depression?

    PubMed Central

    Harrison, Neil A.; Cooper, Ella; Voon, Valerie; Miles, Ken; Critchley, Hugo D.

    2013-01-01

    Inflammation is a risk factor for both depression and cardiovascular disease. Depressed mood is also a cardiovascular risk factor. To date, research into mechanisms through which inflammation impacts cardiovascular health rarely takes into account central effects on autonomic cardiovascular control, instead emphasizing direct effects of peripheral inflammatory responses on endothelial reactivity and myocardial function. However, brain responses to inflammation engage neural systems for motivational and homeostatic control and are expressed through depressed mood state and changes in autonomic cardiovascular regulation. Here we combined an inflammatory challenge, known to evoke an acute reduction in mood, with neuroimaging to identify the functional brain substrates underlying potentially detrimental changes in autonomic cardiovascular control. We first demonstrated that alterations in the balance of low to high frequency (LF/HF) changes in heart rate variability (a measure of baroreflex sensitivity) could account for some of the inflammation-evoked changes in diastolic blood pressure, indicating a central (rather than solely local endothelial) origin. Accompanying alterations in regional brain metabolism (measured using 18FDG-PET) were analysed to localise central mechanisms of inflammation-induced changes in cardiovascular state: three discrete regions previously implicated in stressor-evoked blood pressure reactivity, the dorsal anterior and posterior cingulate and pons, strongly mediated the relationship between inflammation and blood pressure. Moreover, activity changes within each region predicted the inflammation-induced shift in LF/HF balance. These data are consistent with a centrally-driven component originating within brain areas supporting stressor evoked blood pressure reactivity. Together our findings highlight mechanisms binding psychological and physiological well-being and their perturbation by peripheral inflammation. PMID:23416033

  3. Aspirin and lipid mediators in the cardiovascular system.

    PubMed

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

    Aspirin is an unique compound because it bears two active moieties within one and the same molecule: a reactive acetyl group and the salicylate metabolite. Salicylate has some effects similar to aspirin, however only at higher concentrations, usually in the millimolar range, which are not obtained at conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological actions of aspirin in the cardiovascular system at these doses are largely if not entirely due to target structure acetylation. Several classes of lipid mediators become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with subsequent inhibition of thromboxane and, possibly, thrombin formation. By this action, aspirin also inhibits paracrine thromboxane functions on other lipid mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates eNOS with subsequent upregulation of NO formation and enhanced expression of the antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated. Many more acetylation targets have been identified in live cells by quantitative acid-cleavable activity-based protein profiling and might result in discovery of even more aspirin targets in the near future. PMID:26201059

  4. Aspirin and lipid mediators in the cardiovascular system.

    PubMed

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

    Aspirin is an unique compound because it bears two active moieties within one and the same molecule: a reactive acetyl group and the salicylate metabolite. Salicylate has some effects similar to aspirin, however only at higher concentrations, usually in the millimolar range, which are not obtained at conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological actions of aspirin in the cardiovascular system at these doses are largely if not entirely due to target structure acetylation. Several classes of lipid mediators become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with subsequent inhibition of thromboxane and, possibly, thrombin formation. By this action, aspirin also inhibits paracrine thromboxane functions on other lipid mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates eNOS with subsequent upregulation of NO formation and enhanced expression of the antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated. Many more acetylation targets have been identified in live cells by quantitative acid-cleavable activity-based protein profiling and might result in discovery of even more aspirin targets in the near future.

  5. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease

    PubMed Central

    Allison, Beth J.; Kaandorp, Joepe J.; Kane, Andrew D.; Camm, Emily J.; Lusby, Ciara; Cross, Christine M.; Nevin-Dolan, Rhianon; Thakor, Avnesh S.; Derks, Jan B.; Tarry-Adkins, Jane L.; Ozanne, Susan E.; Giussani, Dino A.

    2016-01-01

    Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2–1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.—Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease. PMID:26932929

  6. Kinase-SUMO networks in diabetes-mediated cardiovascular disease.

    PubMed

    Chang, Eugene; Abe, Jun-Ichi

    2016-05-01

    Type II diabetes mellitus (DM) is a common comorbidity in patients with cardiovascular disease (CVD). Epidemiological studies including the Framingham, UKPDS, and MRFIT studies have shown diabetes to be an independent risk factor for cardiovascular disease associated with increased incidence of morbidity and mortality. However, major randomized controlled clinical trials including ADVANCE, VAD, and ACCORD have failed to demonstrate a significant reduction in CVD complications from longstanding DM with strict glycemic control. This suggests that despite the strong clinical correlation between DM and CVD, the precise mechanisms of DM-mediated CVD pathogenesis remain unclear. Signal transduction investigations have shed some light on this question with numerous studies demonstrating the role of kinase pathways in facilitating DM and CVD pathology. Abnormalities in endothelial, vascular smooth muscle, and myocardial function from the pathological insults of hyperglycemia and oxidative stress in diabetes are thought to accelerate the development of cardiovascular disease. Extensive interplay between kinase pathways that regulate the complex pathology of DM-mediated CVD is heavily regulated by a number of post-translational modifications (PTMs). In this review, we focus on the role of a dynamic PTM known as SUMOylation and its role in regulating these kinase networks to provide a mechanistic link between DM and CVD. PMID:27085771

  7. Management of cardiovascular disease in the renal transplant recipient.

    PubMed

    Rigatto, Claudio

    2005-08-01

    RTRs are at high risk for ischemic heart disease and heart failure. Although some differences pertain, most of the major risk factors are similar to those in the general population. It is highly probable that interventions of proven benefit in the general population will also be of benefit in RTRs. A combination of lifestyle modifications (smoking cessation, maintenance of ideal bodyweight, healthy diet), aggressive blood pressure control (<130/80 mm Hg), use of ACE inhibitors or ARBs, lipid lowering with statins, antiplatelet therapy for diabetics and those with established coronary disease, and beta blockers for CHF or after myocardial infarction is likely to have a major benefit on patient survival and cardiac morbidity among transplant recipients. Coronary revascularization should be considered for the same indications as in the general population.

  8. Inadequacy of Cardiovascular Risk Factor Management in Chronic Kidney Transplantation -- Evidence from the FAVORIT Study

    PubMed Central

    Carpenter, Myra A.; Weir, Matthew R.; Adey, Deborah B.; House, Andrew A.; Bostom, Andrew G.; Kusek, John W.

    2015-01-01

    Background Kidney transplant recipients (KTRs) have increased risk for cardiovascular disease (CVD). Our objective is to describe the prevalence of CVD risk factors applying standard criteria and use of CVD risk factor lowering medications in contemporary KTRs. Methods The Folic Acid for Vascular Outcome Reduction in Transplantation study enrolled and collected medication data on 4,107 KTRs with elevated homocysteine and stable graft function an average of 5 years post-transplant. Results CVD risk factors were common (hypertension or use of blood pressure lowering medication in 92%, borderline or elevated LDL or use of lipid-lowering agent in 66%, history of diabetes mellitus in 41%, and obesity in 38%); prevalent CVD was reported in 20% of study participants. National Kidney Foundation blood pressure (BP) guidelines (BP < 130/80 mm Hg) were not met by 69% of participants. Uncontrolled hypertension (BP of 140/90 mm Hg or higher) was present in 44% of those taking anti-hypertension medication; 18% of participants had borderline or elevated LDL, of which 60% were untreated, and 31% of the participants with prevalent CVD were not using an anti-platelet agent. Conclusion There is opportunity to improve treatment and control of traditional CVD risk factors in kidney transplant recipients. PMID:22775763

  9. Chronic renal disease in renal transplant patients: management of cardiovascular risk factors.

    PubMed

    Fernández-Fresnedo, G; Gómez-Alamillo, C; Ruiz, J C; de Francisco, A L M; Arias, M

    2009-06-01

    Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Despite improvements in short-term patient and graft outcomes, there has been no major improvement in long-term outcomes. The aim of this study was to determine the prevalence of cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes, chronic kidney disease, and obesity, and the impact of their control among 526 stable renal transplant recipients according to the guidelines in the general population. Mean blood pressure was 133 +/- 16/81 +/- 9 mm Hg. The proportion of patients on antihypertensive therapy was 75%, and on ACE inhibitors or angiotensin II receptor blockers, 26%. The mean cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides were 195 +/- 41, 115 +/- 32, 51 +/- 17, and 137 +/- 75 mg/dL, respectively. The proportion of patients on statin treatment was 49.7%, and those with body mass indices between 25 and 30, 30 and 35, and >35 kg/m(2) were 35%, 15%, and 4%. We observed a high prevalence of chronic kidney disease, hypertension, dyslipidemia, and obesity among renal transplant patients. Suboptimal control was frequent and control of some of these complications was far below targets established for nontransplant patients despite progressive intensification of therapy with functional graft decline. The findings of this study may have an impact on the management of renal transplant recipients.

  10. Metabolic syndrome definitions and components in predicting major adverse cardiovascular events after kidney transplantation.

    PubMed

    Prasad, G V Ramesh; Huang, Michael; Silver, Samuel A; Al-Lawati, Ali I; Rapi, Lindita; Nash, Michelle M; Zaltzman, Jeffrey S

    2015-01-01

    Metabolic syndrome (MetS) associates with cardiovascular risk post-kidney transplantation, but its ambiguity impairs understanding of its diagnostic utility relative to components. We compared five MetS definitions and the predictive value of constituent components of significant definitions for major adverse cardiovascular events (MACE) in a cohort of 1182 kidney transplant recipients. MetS definitions were adjusted for noncomponent traditional Framingham risk factors and relevant transplant-related variables. Kaplan-Meier, logistic regression, and Cox proportional hazards analysis were utilized. There were 143 MACE over 7447 patient-years of follow-up. Only the World Health Organization (WHO) 1998 definition predicted MACE (25.3 vs 15.5 events/1000 patient-years, P = 0.019). Time-to-MACE was 5.5 ± 3.5 years with MetS and 6.8 ± 3.9 years without MetS (P < 0.0001). MetS was independent of pertinent MACE risk factors except age and previous cardiac disease. Among MetS components, dysglycemia provided greatest hazard ratio (HR) for MACE (1.814 [95% confidence interval 1.26-2.60]), increased successively by microalbuminuria (HR 1.946 [1.37-2.75]), dyslipidemia (3.284 [1.72-6.26]), hypertension (4.127 [2.16-7.86]), and central obesity (4.282 [2.09-8.76]). MetS did not affect graft survival. In summary, although the WHO 1998 definition provides greatest predictive value for post-transplant MACE, most of this is conferred by dysglycemia and is overshadowed by age and previous cardiac disease. PMID:25207680

  11. Impact of Cardiovascular Risk Factors on Graft Outcome Disparities in Black Kidney Transplant Recipients.

    PubMed

    Taber, David J; Hunt, Kelly J; Fominaya, Cory E; Payne, Elizabeth H; Gebregziabher, Mulugeta; Srinivas, Titte R; Baliga, Prabhakar K; Egede, Leonard E

    2016-09-01

    Although outcome inequalities for non-Hispanic black (NHB) kidney transplant recipients are well documented, there is paucity in data assessing the impact of cardiovascular disease (CVD) risk factors on this disparity in kidney transplantation. This was a longitudinal study of a national cohort of veteran kidney recipients transplanted between January 2001 and December 2007. Data included baseline characteristics acquired through the United States Renal Data System linked to detailed clinical follow-up information acquired through the Veterans Affairs electronic health records. Analyses were conducted using sequential multivariable modeling (Cox regression), incorporating blocks of variables into iterative nested models; 3139 patients were included (2095 non-Hispanic whites [66.7%] and 1044 NHBs [33.3%]). NHBs had a higher prevalence of hypertension (100% versus 99%; P<0.01) and post-transplant diabetes mellitus (59% versus 53%; P<0.01) with reduced control of hypertension (blood pressure <140/90 60% versus 69%; P<0.01), diabetes mellitus (A1c <7%, 35% versus 47%; P<0.01), and low-density lipoprotein (<100 mg/dL, 55% versus 61%; P<0.01). Adherence to medications used to manage CVD risk was significantly lower in NHBs. In the fully adjusted models, the independent risk of graft loss in NHBs was substantially reduced (unadjusted hazard ratio, 2.00 versus adjusted hazard ratio, 1.49). CVD risk factors and control reduced the influence of NHB race by 9% to 18%. Similar trends were noted for mortality, and estimates were robust across in sensitivity analyses. These results demonstrate that NHB kidney transplant recipients have significantly higher rates of CVD risk factors and reduced CVD risk control. These issues are likely partly related to medication nonadherence and meaningfully contribute to racial disparities for graft outcomes. PMID:27402921

  12. BP, Cardiovascular Disease, and Death in the Folic Acid for Vascular Outcome Reduction in Transplantation Trial

    PubMed Central

    John, Alin; Weir, Matthew R.; Smith, Stephen R.; Hunsicker, Lawrence; Kasiske, Bertram L.; Kusek, John W.; Bostom, Andrew; Ivanova, Anastasia; Levey, Andrew S.; Solomon, Scott; Pesavento, Todd; Weiner, Daniel E.

    2014-01-01

    The optimal BP level in kidney transplant recipients remains uncertain. This post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial cohort assessed associations of BP with a pooled cardiovascular disease (CVD) outcome and with all-cause mortality. In 3474 prevalent kidney transplant patients, mean age was 52±9 years, 63% were men, 76% were white, 20% had a history of CVD, 40% had a history of diabetes mellitus, and the median time since transplant was 4.1 years (25th to 75th percentiles, 1.7–7.4); mean systolic BP was 136±20 mmHg and mean diastolic BP was 79±12 mmHg. There were 497 CVD events and 406 deaths. After adjustment for demographic and transplant characteristics and CVD risk factors, each 20-mmHg increase in baseline systolic BP associated with a 32% increase in subsequent CVD risk (hazard ratio [HR], 1.32; 95% confidence interval [95% CI], 1.19 to 1.46) and a 13% increase in mortality risk (HR, 1.13; 95% CI, 1.01 to 1.27). Similarly, after adjustment, at diastolic BP levels<70 mmHg, each 10-mmHg decrease in diastolic BP level associated with a 31% increase in CVD risk (HR, 1.31; 95% CI, 1.06 to 1.62) and a 31% increase in mortality risk (HR, 1.31; 95% CI, 1.03 to 1.66). However, at diastolic BP levels>70 mmHg, there was no significant relationship between diastolic BP and outcomes. Higher systolic BP strongly and independently associated with increased risk of CVD and all-cause mortality, without evidence of a J shape, whereas only lower levels of diastolic BP associated with increased risk of CVD and death in this trial. PMID:24627349

  13. Metabolic syndrome in liver transplant recipients: prevalence, risk factors, and association with cardiovascular events.

    PubMed

    Laish, Ido; Braun, Marius; Mor, Eytan; Sulkes, Jaqueline; Harif, Yael; Ben Ari, Ziv

    2011-01-01

    Features of metabolic syndrome are not uncommon in patients after liver transplantation. To examine the prevalence and risk factors of posttransplantation metabolic syndrome (PTMS), the files of 252 transplant recipients (mean age, 54.5 ± 2.8 years, 57.9% male) were reviewed for pretransplant and posttransplant clinical and laboratory parameters (mean follow-up, 6.2 ± 4.4 years). Rates of obesity (body mass index >30 kg/m(2) ), hypertriglyceridemia (>150 mg/dL), high-density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women), hypertension, and diabetes were significantly higher after transplantation than before. Metabolic syndrome was diagnosed in 5.4% of patients before transplantation and 51.9% after. Besides significantly higher rates of the typical metabolic derangements (P < 0.0001), the patients with PTMS were older and heavier than those without PTMS, and they had a higher rate of pretransplant hepatitis C virus infection (P < 0.03) and more posttransplant major vascular and cardiac events (20 events in 15.2% of patients with PTMS versus 6 events in 4.9% of patients without PTMS; P < 0.007). There was no between-group difference in mortality or causes of death (mainly related to recurrent disease, graft failure, and sepsis). Significant independent predictors of PTMS on logistic regression analysis were age (odds ratio [OR] = 1.04), pretransplant nonalcoholic fatty liver disease (OR = 3.4), body mass index (OR = 1.13), diabetes (OR = 5.95), and triglycerides (OR = 1.01). The rate of metabolic syndrome in liver transplant recipients is more than twice that reported for the general population. PTMS is associated with cardiovascular morbidity but not mortality, and it may be predicted by pretransplantation conditions. Prospective studies are required to determine the significance and management of PTMS. PMID:21254340

  14. Pressure-Mediated Oligonucleotide Transfection of Rat and Human Cardiovascular Tissues

    NASA Astrophysics Data System (ADS)

    Mann, Michael J.; Gibbons, Gary H.; Hutchinson, Howard; Poston, Robert S.; Hoyt, E. Grant; Robbins, Robert C.; Dzau, Victor J.

    1999-05-01

    The application of gene therapy to human disease is currently restricted by the relatively low efficiency and potential hazards of methods of oligonucleotide or gene delivery. Antisense or transcription factor decoy oligonucleotides have been shown to be effective at altering gene expression in cell culture expreriments, but their in vivo application is limited by the efficiency of cellular delivery, the intracellular stability of the compounds, and their duration of activity. We report herein the development of a highly efficient method for naked oligodeoxynucleotide (ODN) transfection into cardiovascular tissues by using controlled, nondistending pressure without the use of viral vectors, lipid formulations, or exposure to other adjunctive, potentially hazardous substances. In this study, we have documented the ability of ex vivo, pressure-mediated transfection to achieve nuclear localization of fluorescent (FITC)-labeled ODN in approximately 90% and 50% of cells in intact human saphenous vein and rat myocardium, respectively. We have further documented that pressure-mediated delivery of antisense ODN can functionally inhibited target gene expression in both of these tissues in a sequence-specific manner at the mRNA and protein levels. This oligonucleotide transfection system may represent a safe means of achieving the intraoperative genetic engineering of failure-resistant human bypass grafts and may provide an avenue for the genetic manipulation of cardiac allograft rejection, allograft vasculopathy, or other transplant diseases.

  15. Diagnostic criteria of antibody-mediated rejection in kidney transplants.

    PubMed

    Mosquera Reboredo, J M; Vázquez Martul, E

    2011-01-01

    The diagnosis and treatment of anti-donor antibody-mediated rejection or humoral rejection (ABMR) is one of the main discussions at the moment in kidney transplantation. The search for histopathological markers that help us to diagnose ABMR has been more problematic, in contrast to the histological expression of cellular or tubulointerstitial rejection. Although the relationship between post-transplant anti-donor antibodies and the allograft's prognosis has been a topic of discussion for a long time, led in the main by P.Terasaki, it was not until the beginning of 1990s when P. Halloran studied the humoral mechanisms of rejection in greater depth. Feutch described the importance of C4d deposits as a marker that shows a humoral mechanism of allograft rejection in 1993. As a result of many studies carried out, the Banff consensus group established some diagnostic histopathological criteria of acute (ABMR) in 2003. These have been modified slightly in later meetings of the group. Furthermore, in 2005 this same working group looked at the physiopathological mechanisms causing chronic allograft failure in more detail and established the criteria defining chronic humoral rejection. In this review, we are trying to update any useful histopathological criteria for diagnosing acute and chronic ABMR.

  16. Acute Antibody-Mediated Rejection in Renal Transplantation: Current Clinical Management

    PubMed Central

    Schinstock, Carrie; Stegall, Mark D.

    2014-01-01

    Acute antibody mediated rejection (AMR) is recognized as a major cause of graft loss in renal transplant recipients. Early acute AMR in the first few days after transplantation occurs primarily in sensitized renal transplant recipients with donor-specific alloantibody at the time of transplant and is a relatively “pure” form of acute AMR. Late acute AMR occurs months to years after transplantation and is commonly a mixed cellular and humoral rejection. While there is no consensus regarding optimum treatment, we contend that rational therapeutic approaches are emerging and the acute episode can be managed in most instances. However, new therapies are needed to prevent ongoing chronic injury in these patients.

  17. Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT.

    PubMed

    DeFilipp, Zachariah; Duarte, Rafael F; Snowden, John A; Majhail, Navneet S; Greenfield, Diana M; Miranda, José López; Arat, Mutlu; Baker, K Scott; Burns, Linda J; Duncan, Christine N; Gilleece, Maria; Hale, Gregory A; Hamadani, Mehdi; Hamilton, Betty K; Hogan, William J; Hsu, Jack W; Inamoto, Yoshihiro; Kamble, Rammurti T; Lupo-Stanghellini, Maria Teresa; Malone, Adriana K; McCarthy, Philip; Mohty, Mohamad; Norkin, Maxim; Paplham, Pamela; Ramanathan, Muthalagu; Richart, John M; Salooja, Nina; Schouten, Harry C; Schoemans, Helene; Seber, Adriana; Steinberg, Amir; Wirk, Baldeep M; Wood, William A; Battiwalla, Minoo; Flowers, Mary E D; Savani, Bipin N; Shaw, Bronwen E

    2016-08-01

    Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.

  18. Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT.

    PubMed

    DeFilipp, Zachariah; Duarte, Rafael F; Snowden, John A; Majhail, Navneet S; Greenfield, Diana M; Miranda, José López; Arat, Mutlu; Baker, K Scott; Burns, Linda J; Duncan, Christine N; Gilleece, Maria; Hale, Gregory A; Hamadani, Mehdi; Hamilton, Betty K; Hogan, William J; Hsu, Jack W; Inamoto, Yoshihiro; Kamble, Rammurti T; Lupo-Stanghellini, Maria Teresa; Malone, Adriana K; McCarthy, Philip; Mohty, Mohamad; Norkin, Maxim; Paplham, Pamela; Ramanathan, Muthalagu; Richart, John M; Salooja, Nina; Schouten, Harry C; Schoemans, Helene; Seber, Adriana; Steinberg, Amir; Wirk, Baldeep M; Wood, William A; Battiwalla, Minoo; Flowers, Mary E D; Savani, Bipin N; Shaw, Bronwen E

    2016-08-01

    Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors. PMID:27184625

  19. Computational Chemical Imaging for Cardiovascular Pathology: Chemical Microscopic Imaging Accurately Determines Cardiac Transplant Rejection

    PubMed Central

    Tiwari, Saumya; Reddy, Vijaya B.; Bhargava, Rohit; Raman, Jaishankar

    2015-01-01

    Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a stain-less approach using an emerging technology, Fourier transform infrared (FT-IR) spectroscopic imaging to identify different components of cardiac tissue by their chemical and molecular basis aided by computer recognition, rather than by visual examination using optical microscopy. We studied this technique in assessment of cardiac transplant rejection to evaluate efficacy in an example of complex cardiovascular pathology. We recorded data from human cardiac transplant patients’ biopsies, used a Bayesian classification protocol and developed a visualization scheme to observe chemical differences without the need of stains or human supervision. Using receiver operating characteristic curves, we observed probabilities of detection greater than 95% for four out of five histological classes at 10% probability of false alarm at the cellular level while correctly identifying samples with the hallmarks of the immune response in all cases. The efficacy of manual examination can be significantly increased by observing the inherent biochemical changes in tissues, which enables us to achieve greater diagnostic confidence in an automated, label-free manner. We developed a computational pathology system that gives high contrast images and seems superior to traditional staining procedures. This study is a prelude to the development of real time in situ imaging systems, which can assist interventionists and surgeons actively during procedures. PMID:25932912

  20. Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study

    PubMed Central

    Scott Baker, K.; Ness, Kirsten K.; Steinberger, Julia; Carter, Andrea; Francisco, Liton; Burns, Linda J.; Sklar, Charles; Forman, Stephen; Weisdorf, Daniel; Gurney, James G.; Bhatia, Smita

    2007-01-01

    We ascertained the prevalence of self-reported late occurrence of diabetes, hypertension, and cardiovascular (CV) disease in 1089 hematopoietic cell transplantation (HCT) survivors who underwent HCT between 1974 and 1998, survived at least 2 years, and were not currently taking immunosuppressant agents and compared them with 383 sibling controls. All subjects completed a 255-item health questionnaire. The mean age at survey completion was 39.3 years for survivors and 38.6 years for siblings; mean follow-up was 8.6 years. Adjusting for age, sex, race, and body mass index (BMI), survivors of allogeneic HCT were 3.65 times (95% confidence interval [CI], 1.82-7.32) more likely to report diabetes than siblings and 2.06 times (95% CI, 1.39-3.04) more likely to report hypertension compared with siblings but did not report other CV outcomes with any greater frequency. Recipients of autologous HCTs were no more likely than siblings to report any of the outcomes studied. Allogeneic HCT survivors were also more likely to develop hypertension (odds ratio [OR] = 2.31; 95% CI, 1.45-3.67) than autologous recipients. Total body irradiation (TBI) exposure was associated with an increased risk of diabetes (OR = 3.42; 95% CI, 1.55-7.52). Thus, HCT survivors have a higher age- and BMI-adjusted risk of diabetes and hypertension, potentially leading to a higher than expected risk of CV events with age. PMID:17047152

  1. Oxidative stress as a mediator of cardiovascular disease

    PubMed Central

    Elahi, Maqsood M; Kong, Yu Xiang

    2009-01-01

    During physiological processes molecules undergo chemical changes involving reducing and oxidizing reactions. A molecule with an unpaired electron can combine with a molecule capable of donating an electron. The donation of an electron is termed as oxidation whereas the gaining of an electron is called reduction. Reduction and oxidation can render the reduced molecule unstable and make it free to react with other molecules to cause damage to cellular and sub-cellular components such as membranes, proteins and DNA. In this paper, we have discussed the formation of reactive oxidant species originating from a variety of sources such as nitric oxide (NO) synthase (NOS), xanthine oxidases (XO), the cyclooxygenases, nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase isoforms and metal-catalyzed reactions. In addition, we present a treatise on the physiological defences such as specialized enzymes and antioxidants that maintain reduction-oxidation (redox) balance. We have also given an account of how enzymes and antioxidants can be exhausted by the excessive production of reactive oxidant species (ROS) resulting in oxidative stress/nitrosative stress, a process that is an important mediator of cell damage. Important aspects of redox imbalance that triggers the activity of a number of signaling pathways including transcription factors activity, a process that is ubiquitous in cardiovascular disease related to ischemia/reperfusion injury have also been presented. PMID:20716913

  2. Elevated Circulating Interleukin 33 Levels in Stable Renal Transplant Recipients at High Risk for Cardiovascular Events

    PubMed Central

    Mansell, Holly; Soliman, Mahmoud; Elmoselhi, Hamdi; Shoker, Ahmed

    2015-01-01

    Background The Major Adverse Cardiovascular Events calculator (CRCRTR-MACE) estimates the burden of cardiovascular risk in renal transplant recipients (RTR). Our recent study of 95 RTR reported the 7-year median risk of cardiovascular events (CVE) to be 9.97%, ranging from 1.93 to 84.27%. Nearly a third (28.4%) of the cohort was above 20% risk for a CVE. Since interleukins (ILs) as part of the inflammatory response may play a role in the pathogenesis of cardiovascular disease (CVD), we extended this study to identify which ILs are associated with high cardiovascular risk in this population. Methods Twenty-two ILs were measured by multiplexed fluorescent bead-based immunoassay in 95 RTR and 56 normal controls. Stepwise analysis after multivariate determination of significant demographic and inflammatory variables was performed between the high and low-CVD risk groups (which were arbitrarily set at scores <10% and ≥20%, respectively). Normalized data was presented as mean ± SD and non-normalized data as median (minimum–maximum). Significance was measured at <0.05. Results 27.5% of the low-risk and 31.3% of the high-risk groups had mean IL levels above the 95 percentile of the normal control levels. In the non-parametric analysis IL-6, 9, 16, 17 and 33 were significantly higher in the high-risk group compared to the control. Univariate analysis (UVA) of the high-risk group identified IL-33 as the only IL that remained significantly higher than the control and low-risk groups (p = 0.000). The percentage of patients with IL-33 levels above the 90 percentile of control value in the low and high-risk groups were 15.6% and 52.0%, respectively (p<0.002). UVA of factors significant to high IL-33 levels included estimated glomerular filtration rate (eGFR), while diabetes mellitus, serum phosphorus, microalbuminuria and age also remained significant in the multivariate analysis. Conclusion Circulating IL-33 level is positively associated with high CRCRTR-MACE score

  3. Cardiorespiratory fitness is a marker of cardiovascular health in renal transplanted children.

    PubMed

    Tangeraas, Trine; Midtvedt, Karsten; Fredriksen, Per Morten; Cvancarova, Milada; Mørkrid, Lars; Bjerre, Anna

    2010-11-01

    Children with renal transplants (TX) are at increased risk of cardiovascular (CV) disease. Study objectives were to assess the level of cardiorespiratory fitness (CR fitness) and daily physical activity (PA) in renal TX children and adolescents in relation to traditional cardiovascular risk factors. Laboratory testing included assessment of CR fitness by treadmill exercise testing (VO(2peak)), 24-h ambulatory blood-pressure (ABPM) measurement, oral glucose tolerance test (OGTT), anthropometrics and measurement of lipid levels. PA was self-reported by questionnaire. Twenty-two TX patients with a median (range) age 14.5 (9-18) years were tested. Median V0(2peak) was 66% (36-97) of the expected values compared with controls. Nineteen (86%) children reported <60 min of daily moderate to vigorous physical activity (MVPA). Sixteen (73%) were hypertensive and 8 (34%) were overweight or obese. Four children fulfilled the criteria for a metabolic syndrome. Children with at least 2 of the 3 metabolic risk factors (hypertension, overweight, and glucose intolerance, n=7) achieved significantly lower VO(2peak) compared with those with one or none of these factors (median V0(2peak) 45% and 73% of the expected values respectively, p=0.003). Renal TX children and adolescents have severely impaired CR fitness and PA. Reduced CR fitness was associated with the clustering of CV risk factors. Routine counseling for increased PA is strongly recommended.

  4. Pre-Transplant Cardiovascular Risk Factors Affect Kidney Allograft Survival: A Multi-Center Study in Korea

    PubMed Central

    Lee, Jung Pyo; Bae, Eunjin; Kang, Eunjeong; Kim, Hack-Lyoung; Kim, Yong-Jin; Oh, Yun Kyu; Kim, Yon Su; Kim, Young Hoon; Lim, Chun Soo

    2016-01-01

    Background Pre-transplant cardiovascular (CV) risk factors affect the development of CV events even after successful kidney transplantation (KT). However, the impact of pre-transplant CV risk factors on allograft failure (GF) has not been reported. Methods and Findings We analyzed the graft outcomes of 2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012. We calculated the pre-transplant CV risk scores based on the Framingham risk model using age, gender, total cholesterol level, smoking status, and history of hypertension. Vascular disease (a composite of ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients. During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF. In the multivariable-adjusted Cox proportional hazard model, pre-transplant vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI 1.66–3.80). The HR for GF (comparing the highest with the lowest tertile regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22–2.23). In the competing risk model, both pre-transplant vascular disease and CV risk score were independent risk factors for GF. Moreover, the addition of the CV risk score, the pre-transplant vascular disease, or both had a better predictability for GF compared to the traditional GF risk factors. Conclusions In conclusion, both vascular disease and pre-transplant CV risk score were independently associated with GF in this multi-center study. Pre-transplant CV risk assessments could be useful in predicting GF in KT recipients. PMID:27501048

  5. Impact of tacrolimus and mycophenolate mofetil regimen vs. a conventional therapy with steroids on cardiovascular risk in liver transplant patients.

    PubMed

    Cuervas-Mons, Valentín; Herrero, J Ignacio; Gomez, Miguel A; González-Pinto, Ignacio; Serrano, Trinidad; de la Mata, Manuel; Fabregat, Joan; Gastaca, Mikel; Bilbao, Itxarone; Varo, Evaristo; Sánchez-Antolín, Gloria; Rodrigo, Juan; Espinosa, María Dolores

    2015-08-01

    The aim of this study was to evaluate the impact of a steroid-free regimen with tacrolimus and mycophenolate mofetil (modified therapy) vs. a standard regimen of tacrolimus and steroids on the cardiovascular risk score of liver transplant recipients. Patients who received a liver transplant were randomized to a modified therapy (n = 58) or a standard regimen (n = 59). Both groups were balanced at baseline, except for a higher prevalence of diabetes mellitus (DM) (p < 0.01) and a higher serum creatinine concentration (p < 0.05) in the modified therapy group. After 12 months, the prevalence of new-onset DM, arterial hypertension, hypercholesterolemia, hypertriglyceridemia, and changes in cardiovascular risk factors was similar in both groups. The increase in serum creatinine (mg/dL) compared to baseline at one yr post-transplantation was numerically lower in the modified therapy group (0.22 ± 0.42) than in the standard regimen group (0.41 ± 0.67) (p = 0.068). Although estimated cardiovascular risk score did not vary significantly compared to baseline in either group, there was a slight reduction in the modified regimen (-0.27 ± 2.87) vs. a mild increase (0.17 ± 2.94) in the standard regimen (p = 0.566). In conclusion, a steroid-free regimen with tacrolimus and mycophenolate mofetil was associated with a trend toward better preservation of kidney function and reduction of cardiovascular risk score.

  6. Effects of Liver Transplantation on Lipids and Cardiovascular Disease in Children With Homozygous Familial Hypercholesterolemia.

    PubMed

    Martinez, Mercedes; Brodlie, Susan; Griesemer, Adam; Kato, Tomoaki; Harren, Patricia; Gordon, Bruce; Parker, Thomas; Levine, Daniel; Tyberg, Theodore; Starc, Thomas; Cho, Iksung; Min, James; Elmore, Kimberly; Lobritto, Steven; Hudgins, Lisa Cooper

    2016-08-15

    Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited, life-threatening, metabolic disorder of low-density lipoprotein (LDL) receptor function characterized by elevated serum LDL cholesterol (LDL-C) and rapidly progressive atherosclerotic cardiovascular disease (ACVD). Since LDL receptors are predominantly found on hepatocytes, orthotopic liver transplantation (OLT) has emerged as a viable intervention for HoFH because LDL receptor activity is restored. This study assessed the effects of OLT on ACVD and ACVD risk factors in pediatric patients with HoFH. We analyzed lipids, lipoproteins, body mass index, glucose, blood pressure, and cardiovascular imaging in 8 pediatric patients who underwent OLT for HoFH. Total serum cholesterol, LDL-C, lipoprotein (a), and apolipoprotein B/apolipoprotein A1 ratio decreased to normal values in all subjects (p values <0.001) at 1 month after OLT and were maintained for the length of follow-up (2 to 6 years). There were few complications related to surgery or immunosuppressive therapy. Two patients developed mild hypertension. In the first 4 subjects monitored for 4 to 6 years after OLT, coronary artery disease did not develop or progress except in 1 minor artery in 1 subject and actually regressed in 2 subjects with >50% stenosis. However, aortic valve stenosis progressed in 2 of 4 subjects. In conclusion, OLT is an effective therapeutic option for patients with HoFH with coronary artery disease and persistently elevated serum LDL-C despite maximum medical therapy. Aortic valvular disease may progress. Long-term data are needed to evaluate the true risk-benefit ratio of this surgical approach. PMID:27365335

  7. A Comparison of Different Algorithms for the Assessment of Cardiovascular Risk in Patients at Waiting List for Kidney Transplantation

    PubMed Central

    Malyar, Viola; Schütte-Nütgen, Katharina; Schmidt, Renè; Pavenstädt, Hermann; Reinecke, Holger; Suwelack, Barbara

    2016-01-01

    Background Cardiovascular disease (CVD) is the leading cause of death after renal transplantation with a high prevalence in dialysis patients. It is still a matter of debate how to assess the cardiovascular risk in kidney transplant candidates. Several approaches and scores exist and found their way into the guidelines. Methods and Results We herein assessed PROCAM, Framingham, ESC-SCORE and our own dedicated algorithm in patients applying for renal transplantation at our transplantation center between July 2006 and August 2009. Data of 347 consecutive patients were recorded at baseline and during a follow-up of 4.1 years regarding cardiovascular (CV) events and event-free and overall survival. During follow-up 31 (8.9%) patients died, 24 (6.9%) myocardial infarctions occurred and 19 (5.5%) patients received a new diagnosis of cerebrovascular disease. Predictors for event-free survival identified by univariable Cox regression analysis were age at start of dialysis, ESC-SCORE as well as our own score. Final multivariable model with a stepwise model building procedure revealed age at start of dialysis and smoking to be prognostic for event-free (hazard ratio 1.07/year and 2.15) and overall survival (1.10/year and 3.72). Conclusion Comparison of CV risk assessment scores showed that ESC-SCORE most robustly predicted event-free and overall survival in our cohort. We conclude that CV risk assessment by ESC-SCORE can be reasonably performed in kidney transplant candidates. PMID:27768693

  8. Homocysteine-Lowering and Cardiovascular Disease Outcomes in Kidney Transplant Recipients: Primary Results from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

    PubMed Central

    Bostom, Andrew G.; Carpenter, Myra A.; Kusek, John W.; Levey, Andrew S.; Hunsicker, Lawrence; Pfeffer, Marc A.; Selhub, Jacob; Jacques, Paul F.; Cole, Edward; Gravens-Mueller, Lisa; House, Andrew A.; Kew, Clifton; McKenney, Joyce L.; Pacheco-Silva, Alvaro; Pesavento, Todd; Pirsch, John; Smith, Stephen; Solomon, Scott; Weir, Matthew

    2015-01-01

    Background Kidney transplant recipients, like other patients with chronic kidney disease (CKD), experience excess risk of cardiovascular disease (CVD) and elevated total homocysteine (tHcy) concentrations. Observational studies of patients with CKD suggest increased homocysteine is a risk factor for CVD. The impact of lowering total homocysteine (tHcy) levels in kidney transplant recipients is unknown. Methods and Results In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing tHcy concentrations reduced the rate of the primary composite arteriosclerotic CVD outcome (myocardial infarction, stroke, CVD death, resuscitated sudden death, coronary artery or renal artery revascularization, lower extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n= 547 total events; hazards ratio [95% confidence interval] = 0.99 [0.84–1.17]), or secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86–1.26]) or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93–1.43]) compared to the low dose multivitamin. Conclusions Treatment with a high dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level. PMID:21482964

  9. Brain structures mediating cardiovascular arousal and interoceptive awareness.

    PubMed

    Pollatos, Olga; Schandry, Rainer; Auer, Dorothee P; Kaufmann, Christian

    2007-04-13

    Different emotions are accompanied by different bodily states and it is unclear which brain structures are involved in both, the cerebral representation of the bodily change and the representation of its perception. Structures connecting bodily signals and interoceptive awareness could trigger, in a feedforward manner, behavioral responses appropriate to maintain a desired state of the cardiovascular system. The present functional magnetic resonance imaging study aimed at identifying brain structures that are mutually activated during interoceptive awareness of heartbeats and during cardiovascular arousal. Additionally, we searched for brain regions connecting interoception with feelings. During the interoceptive task (directing attention towards heartbeats in relation to an exteroceptive task) the thalamus, the insula, the medial frontal/dorsal cingulate and the inferior frontal gyrus, as well as the somatomotor cortex were activated. The conjunction of the interoceptive awareness of heartbeats and cardiovascular arousal revealed structures presumably connecting both conditions, i.e. the right thalamus, insula, somatomotor cortex, and the dorsal cingulate as well as medial frontal gyrus. Furthermore, the degree of interoceptive awareness predicted the degree of activation of both the insula and the medial frontal/dorsal cingulate gyrus. Negative feelings correlated with the BOLD response of the interoceptive awareness condition in the dorsal cingulate gyrus extending into the dorsomedial prefrontal cortex. We provide evidence that the insula, the dorsal cingulate gyrus, and the dorsomedial prefrontal cortex are specifically involved in processing cardiac sensations. The dorsal cingulate gyrus and the dorsomedial prefrontal cortex presumably represent the neural substrates of experiencing negative emotions. PMID:17296169

  10. Role of arterial baroreceptors in mediating cardiovascular response to exercise

    NASA Technical Reports Server (NTRS)

    Mcritchie, R. J.; Vatner, S. F.; Patrick, T. A.; Braunwald, E.; Boettcher, D.; Heyndrickx, G. R.

    1976-01-01

    Experiments were conducted to define the role of the major arterial baroreceptors during moderately severe exercise by comparing the responses of untethered conscious dogs instrumented for the measurement of aortic pressure and cardiac output with those of dogs with total arterial baroreceptor denervation. The reflex heart rate responses to intravenous bolus doses of methoxamine were also examined in intact animals, both at rest and during exercise. Methoxamine is found to cause striking bradycardia at rest, but little bradycardia during exercise. Experimental findings suggest that the arterial baroreceptor reflex is normally inhibited during severe exercise and therefore plays little role in modulating the cardiovascular response to exercise.

  11. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation

    PubMed Central

    Xia, Yu; Zhu, Kai; Lai, Hao; Lang, Meidong; Xiao, Yan; Lian, Sheng

    2015-01-01

    Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation. PMID:25432986

  12. Cardiovascular metabolic syndrome: mediators involved in the pathophysiology from obesity to coronary heart disease.

    PubMed

    Roos, Cornelis J; Quax, Paul H A; Jukema, J Wouter

    2012-02-01

    Patients with obesity and diabetes mellitus are at increased risk for cardiovascular events and have a higher cardiovascular morbidity and mortality. This worse prognosis is partly explained by the late recognition of coronary heart disease in these patients, due to the absence of symptoms. Early identification of coronary heart disease is vital, to initiate preventive medical therapy and improve prognosis. At present, with the use of cardiovascular risk models, the identification of coronary heart disease in these patients remains inadequate. To this end, biomarkers should improve the early identification of patients at increased cardiovascular risk. The first part of this review describes the pathophysiologic pathway from obesity to coronary heart disease. The second part evaluates several mediators from this pathophysiologic pathway for their applicability as biomarkers for the identification of coronary heart disease.

  13. Cardiovascular

    NASA Video Gallery

    Overview of Cardiovascular research which addresses risks of space flight, including adaptive changes to the cephalad fluid shift (such as reduced circulating blood volume), potential for heart rhy...

  14. A role for the central histaminergic system in the leptin-mediated increase in cardiovascular dynamics.

    PubMed

    Rao, Sumangala P; Dunbar, Joseph C

    2005-01-15

    The central nervous system (CNS) histaminergic neurons have been shown to regulate feeding behavior and are a target of leptin in the brain. The present study aimed to examine the involvement of the histaminergic system in the leptin-mediated regulation of cardiovascular dynamics. We investigated the cardiovascular responses to the CNS administration of histamine, leptin and alpha-melanocyte stimulating hormone (alpha-MSH) both in the presence and absence of the histamine H1 antagonist, chlorpheniramine. The intracerebroventricular (i.c.v.) administration of histamine resulted in an immediate increase in both mean arterial pressure (MAP) and heart rate (HR) and vasoconstricted the iliac, renal and superior mesenteric vessels. The i.c.v. pretreatment with chlorpheniramine attenuated the histamine-induced increase in MAP, HR and decreased vascular conductance. The i.c.v. administration of leptin increased MAP and HR and decreased vascular conductance. The i.c.v. pretreatment with chlorpheniramine decreased the leptin-induced increase in MAP and the leptin-mediated iliac vasoconstriction. The i.c.v. administration of alpha-MSH also increased MAP, HR and decreased vascular conductance. However, pretreatment with chlorpheniramine did not influence the central alpha-MSH-mediated increase in MAP, HR and decreased vascular conductance. These results indicate that the central histaminergic system mediated by H1 receptors have a role in the central signaling pathway and is involved in leptin's regulation of cardiovascular dynamics. It appears that leptin directly or indirectly stimulates histaminergic neurons that lead to increased cardiovascular activity.

  15. The Biological Effects of IL-21 Signaling on B-Cell-Mediated Responses in Organ Transplantation

    PubMed Central

    Wu, Yongkang; van Besouw, Nicole M.; Shi, Yunying; Hoogduijn, Martin J.; Wang, Lanlan; Baan, Carla C.

    2016-01-01

    Antibody-mediated rejection has emerged as one of the major issues limiting the success of organ transplantation. It exerts a highly negative impact on graft function and outcome, and effective treatment is lacking. The triggers for antibody development, and the mechanisms leading to graft dysfunction and failure, are incompletely understood. The production of antibodies is dependent on instructions from various immunocytes including CD4 T-helper cells that secrete interleukin (IL)-21 and interact with antigen-specific B-cells via costimulatory molecules. In this article, we discuss the role of IL-21 in the activation and differentiation of B-cells and consider the mechanisms of IL-21 and B-cell interaction. An improved understanding of the biological mechanisms involved in antibody-mediated complications after organ transplantation could lead to the development of novel therapeutic strategies, which control humoral alloreactivity, potentially preventing and treating graft-threatening antibody-mediated rejection.

  16. The Biological Effects of IL-21 Signaling on B-Cell-Mediated Responses in Organ Transplantation

    PubMed Central

    Wu, Yongkang; van Besouw, Nicole M.; Shi, Yunying; Hoogduijn, Martin J.; Wang, Lanlan; Baan, Carla C.

    2016-01-01

    Antibody-mediated rejection has emerged as one of the major issues limiting the success of organ transplantation. It exerts a highly negative impact on graft function and outcome, and effective treatment is lacking. The triggers for antibody development, and the mechanisms leading to graft dysfunction and failure, are incompletely understood. The production of antibodies is dependent on instructions from various immunocytes including CD4 T-helper cells that secrete interleukin (IL)-21 and interact with antigen-specific B-cells via costimulatory molecules. In this article, we discuss the role of IL-21 in the activation and differentiation of B-cells and consider the mechanisms of IL-21 and B-cell interaction. An improved understanding of the biological mechanisms involved in antibody-mediated complications after organ transplantation could lead to the development of novel therapeutic strategies, which control humoral alloreactivity, potentially preventing and treating graft-threatening antibody-mediated rejection. PMID:27602031

  17. The Biological Effects of IL-21 Signaling on B-Cell-Mediated Responses in Organ Transplantation.

    PubMed

    Wu, Yongkang; van Besouw, Nicole M; Shi, Yunying; Hoogduijn, Martin J; Wang, Lanlan; Baan, Carla C

    2016-01-01

    Antibody-mediated rejection has emerged as one of the major issues limiting the success of organ transplantation. It exerts a highly negative impact on graft function and outcome, and effective treatment is lacking. The triggers for antibody development, and the mechanisms leading to graft dysfunction and failure, are incompletely understood. The production of antibodies is dependent on instructions from various immunocytes including CD4 T-helper cells that secrete interleukin (IL)-21 and interact with antigen-specific B-cells via costimulatory molecules. In this article, we discuss the role of IL-21 in the activation and differentiation of B-cells and consider the mechanisms of IL-21 and B-cell interaction. An improved understanding of the biological mechanisms involved in antibody-mediated complications after organ transplantation could lead to the development of novel therapeutic strategies, which control humoral alloreactivity, potentially preventing and treating graft-threatening antibody-mediated rejection. PMID:27602031

  18. Apolipoprotein C-III and E polymorphisms and cardiovascular syndrome, hyperlipidemia, and insulin resistance in renal transplantation.

    PubMed

    Rodrigo, Emilio; González-Lamuño, Domingo; Ruiz, Juan Carlos; Fernández-Fresnedo, Gema; Isla, Débora; González-Cotorruelo, Julio; Zubimendi, José Antonio; De Francisco, Angel Luis Martín; García-Fuentes, Miguel; Arias, Manuel

    2002-04-01

    Hyperlipidemia and insulin resistance frequently develop after renal transplantation, contributing to cardiovascular disease. Individual differences in response based upon genetic variations in proteins regulating lipidic and glucose tolerance metabolism could be expected. In the general population, the S2 allelic variant of the apoprotein (apo) C-III gene has been associated with hypertriglyceridemia and an insulin resistant state, whereas the E4 allele of the apo E has been associated with hypercholesterolemia and atherosclerosis. Its influence in renal transplant patients remains to be seen. In order to assess the impact of apo E and C-III major polymorphisms on atherosclerotic vascular disease, lipid profile and impaired glucose tolerance in renal transplant patients, we studied 110 consecutively examined patients undergoing kidney transplantation (age range 24-73 years). Atherosclerotic complications were detected in 25% of patients, with age, male sex and hypercholesterolemia being significant atherosclerotic risk factors. Among the male patients with E4 allele, the odds ratio for coronary disease and global atherosclerosis were 10.2 (95% CI) and 6.4 (95% CI), respectively. There were no significant differences in the frequency of any of the polymorphisms among patients with dyslipidemia and impaired glucose tolerance. As the number of patients in our sample was small, larger studies are needed to verify these issues. While in the studied population C-III polymorphism appears to have little association with the prevalence of atherosclerotic complications, E4 allele should be considered as a genetic marker of coronary artery disease and global atherosclerosis in renal transplant patients.

  19. Instant Blood-Mediated Inflammatory Reaction in Hepatocyte Transplantation: Current Status and Future Perspectives.

    PubMed

    Lee, Charlotte A; Dhawan, Anil; Smith, Richard A; Mitry, Ragai R; Fitzpatrick, Emer

    2016-01-01

    Hepatocyte transplantation (HT) is emerging as a promising alternative to orthotopic liver transplantation (OLT) in patients with certain liver-based metabolic disease and acute liver failure. Hepatocytes are generally infused into the portal venous system, from which they migrate into the liver cell plates of the native organ. One of the major hurdles to the sustained success of this therapy is early cell loss, with up to 70% of hepatocytes lost immediately following infusion. This is largely thought to be due to the instant blood-mediated inflammatory reaction (IBMIR), resulting in the activation of complement and coagulation pathways. Transplanted hepatocytes produce and release tissue factor (TF), which activates the coagulation pathway, leading to the formation of thrombin and fibrin clots. Thrombin can further activate a number of complement proteins, leading to the activation of the membrane attack complex (MAC) and subsequent hepatocyte cell death. Inflammatory cells including granulocytes, monocytes, Kupffer cells, and natural killer (NK) cells have been shown to cluster around transplanted hepatocytes, leading to their rapid clearance shortly after transplantation. Current research aims to improve cell engraftment and prevent early cell loss. This has been proven successful in vitro using pharmacological interventions such as melagatran, low-molecular-weight dextran sulphate, and N-acetylcysteine (NAC). Effective inhibition of IBMIR would significantly improve hepatocyte engraftment, proliferation, and function, providing successful treatment for patients with liver-based metabolic diseases. PMID:26996786

  20. Endoplasmic Reticulum Stress is a Mediator of Post-Transplant Injury in Severely Steatotic Liver Allografts

    PubMed Central

    Anderson, Christopher D.; Upadhya, Gundumi; Conzen, Kendra D.; Jia, Jianlou; Brunt, Elizabeth M.; Tiriveedhi, Venkataswarup; Xie, Yan; Ramachandran, Sabarinathan; Mohanakumar, Thalachallour; Davidson, Nicholas O.; Chapman, William C.

    2010-01-01

    Hepatic steatosis continues to present a major challenge in liver transplantation. These organs have been shown to have an increased susceptibility to cold ischemia and reperfusion (CIR) injury compared to otherwise comparable lean livers; the mechanisms governing this increased susceptibility to CIR injury are not fully understood. Endoplasmic reticulum (ER) stress is an important link between hepatic steatosis, insulin resistance and the metabolic syndrome. In this study, we investigated ER stress signaling and blockade in the mediation of CIR injury in severely steatotic rodent allografts. Steatotic allografts from genetically leptin-resistant rodents had increased ER stress responses and increased markers of hepatocellular injury following liver transplantation into strain-matched lean recipients. ER stress response components were decreased by the chemical chaperone, TUDCA, resulting in improvement of the allograft injury. TUDCA treatment decreased NF-κB activation, and the pro-inflammatory cytokines IL-6 and IL-1β. However, the predominant response was decreased expression of the ER stress cell death mediator, CHOP. Further, activation of the inflammation-associated caspase 11 was decreased linking ER Stress/CHOP to pro-inflammatory cytokine production following steatotic liver transplantation. These data confirm ER stress in steatotic allografts, and implicate this as a mediating mechanism of inflammation and hepatocyte death in the steatotic liver allograft. PMID:21280192

  1. Transplantation.

    PubMed

    Faro, Albert; Weymann, Alexander

    2016-08-01

    Despite improvement in median life expectancy and overall health, some children with cystic fibrosis (CF) progress to end-stage lung or liver disease and become candidates for transplant. Transplants for children with CF hold the promise to extend and improve the quality of life, but barriers to successful long-term outcomes include shortage of suitable donor organs; potential complications from the surgical procedure and immunosuppressants; risk of rejection and infection; and the need for lifelong, strict adherence to a complex medical regimen. This article reviews the indications and complications of lung and liver transplantation in children with CF. PMID:27469184

  2. Role of the Sympathetic Nervous System in Stress-Mediated Cardiovascular Disease.

    PubMed

    Hering, Dagmara; Lachowska, Kamila; Schlaich, Markus

    2015-10-01

    A high incidence of acute cardiovascular events and sudden cardiac death following unexpected acute emotional stress or a natural catastrophic disaster has been well-documented over the past decades. Chronic psychosocial factors have been shown to be directly linked to the development of hypertension, cardiovascular disease and stroke. Activation of various neurogenic pathways is an important mediator of acute and chronic stress-induced hypertension and heart disease. Heightened sympathetic activation has been shown to be a critical contributor linking psychogenic effects on cardiovascular regulation to serious and often fatal CV outcomes. Accordingly, several therapeutic approaches that attenuate autonomic imbalance via modulation of increased sympathetic outflow by either non-pharmacological or interventional means have been shown to alleviate clinical symptoms. Likewise stress reduction per se achieved with transcendental medicine has been linked to improved patient outcomes. Therapies that oppose adrenergic activity and/or have the potential to attenuate negative emotions are likely to reduce cardiovascular risk and its adverse consequences attributable to chronic mental stress.

  3. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab.

    PubMed

    Khan, Saif A; Al-Riyami, Dawood; Al-Mula Abed, Yasser W; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M

    2016-08-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR. PMID:27606122

  4. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab

    PubMed Central

    Khan, Saif A.; Al-Riyami, Dawood; Al-Mula Abed, Yasser W.; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M.

    2016-01-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR.

  5. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab

    PubMed Central

    Khan, Saif A.; Al-Riyami, Dawood; Al-Mula Abed, Yasser W.; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M.

    2016-01-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR. PMID:27606122

  6. Microbial mediation of biogeochemical cycles revealed by simulation of global changes with soil transplant and cropping

    PubMed Central

    Zhao, Mengxin; Xue, Kai; Wang, Feng; Liu, Shanshan; Bai, Shijie; Sun, Bo; Zhou, Jizhong; Yang, Yunfeng

    2014-01-01

    Despite microbes' key roles in driving biogeochemical cycles, the mechanism of microbe-mediated feedbacks to global changes remains elusive. Recently, soil transplant has been successfully established as a proxy to simulate climate changes, as the current trend of global warming coherently causes range shifts toward higher latitudes. Four years after southward soil transplant over large transects in China, we found that microbial functional diversity was increased, in addition to concurrent changes in microbial biomass, soil nutrient content and functional processes involved in the nitrogen cycle. However, soil transplant effects could be overridden by maize cropping, which was attributed to a negative interaction. Strikingly, abundances of nitrogen and carbon cycle genes were increased by these field experiments simulating global change, coinciding with higher soil nitrification potential and carbon dioxide (CO2) efflux. Further investigation revealed strong correlations between carbon cycle genes and CO2 efflux in bare soil but not cropped soil, and between nitrogen cycle genes and nitrification. These findings suggest that changes of soil carbon and nitrogen cycles by soil transplant and cropping were predictable by measuring microbial functional potentials, contributing to a better mechanistic understanding of these soil functional processes and suggesting a potential to incorporate microbial communities in greenhouse gas emission modeling. PMID:24694714

  7. Microbial mediation of biogeochemical cycles revealed by simulation of global changes with soil transplant and cropping.

    PubMed

    Zhao, Mengxin; Xue, Kai; Wang, Feng; Liu, Shanshan; Bai, Shijie; Sun, Bo; Zhou, Jizhong; Yang, Yunfeng

    2014-10-01

    Despite microbes' key roles in driving biogeochemical cycles, the mechanism of microbe-mediated feedbacks to global changes remains elusive. Recently, soil transplant has been successfully established as a proxy to simulate climate changes, as the current trend of global warming coherently causes range shifts toward higher latitudes. Four years after southward soil transplant over large transects in China, we found that microbial functional diversity was increased, in addition to concurrent changes in microbial biomass, soil nutrient content and functional processes involved in the nitrogen cycle. However, soil transplant effects could be overridden by maize cropping, which was attributed to a negative interaction. Strikingly, abundances of nitrogen and carbon cycle genes were increased by these field experiments simulating global change, coinciding with higher soil nitrification potential and carbon dioxide (CO2) efflux. Further investigation revealed strong correlations between carbon cycle genes and CO2 efflux in bare soil but not cropped soil, and between nitrogen cycle genes and nitrification. These findings suggest that changes of soil carbon and nitrogen cycles by soil transplant and cropping were predictable by measuring microbial functional potentials, contributing to a better mechanistic understanding of these soil functional processes and suggesting a potential to incorporate microbial communities in greenhouse gas emission modeling.

  8. Predictive Value of Echocardiographic Abnormalities and the Impact of Diastolic Dysfunction on In-hospital Major Cardiovascular Complications after Living Donor Kidney Transplantation

    PubMed Central

    Kim, Eun Jung; Chang, Suyon; Kim, So Yeon; Huh, Kyu Ha; Kang, Soojeong; Choi, Yong Seon

    2016-01-01

    Patients with end-stage renal disease (ESRD) show characteristic abnormalities in cardiac structure and function. We evaluated the influence of these abnormalities on adverse cardiopulmonary outcomes after living donor kidney transplantation in patients with valid preoperative transthoracic echocardiographic evaluation. We then observed any development of major postoperative cardiovascular complications and pulmonary edema until hospital discharge. In-hospital major cardiovascular complications were defined as acute myocardial infarction, ventricular fibrillation/tachycardia, cardiogenic shock, newly-onset atrial fibrillation, clinical pulmonary edema requiring endotracheal intubation or dialysis. Among the 242 ESRD study patients, 9 patients (4%) developed major cardiovascular complications, and 39 patients (16%) developed pulmonary edema. Diabetes, ischemia-reperfusion time, left ventricular end-diastolic diameter (LVEDd), left ventricular mass index (LVMI), right ventricular systolic pressure (RVSP), left atrium volume index (LAVI), and high E/E' ratios were risk factors of major cardiovascular complications, while age, LVEDd, LVMI, LAVI, and high E/E' ratios were risk factors of pulmonary edema. The optimal E/E' cut-off value for predicting major cardiovascular complications was 13.0, showing 77.8% sensitivity and 78.5% specificity. Thus, the patient's E/E' ratio is useful for predicting in-hospital major cardiovascular complications after kidney transplantation. We recommend that goal-directed therapy employing E/E' ratio be enacted in kidney recipients with baseline diastolic dysfunction to avert postoperative morbidity. (http://Clinical Trials.gov number: NCT02322567) PMID:27499694

  9. Predictive Value of Echocardiographic Abnormalities and the Impact of Diastolic Dysfunction on In-hospital Major Cardiovascular Complications after Living Donor Kidney Transplantation.

    PubMed

    Kim, Eun Jung; Chang, Suyon; Kim, So Yeon; Huh, Kyu Ha; Kang, Soojeong; Choi, Yong Seon

    2016-01-01

    Patients with end-stage renal disease (ESRD) show characteristic abnormalities in cardiac structure and function. We evaluated the influence of these abnormalities on adverse cardiopulmonary outcomes after living donor kidney transplantation in patients with valid preoperative transthoracic echocardiographic evaluation. We then observed any development of major postoperative cardiovascular complications and pulmonary edema until hospital discharge. In-hospital major cardiovascular complications were defined as acute myocardial infarction, ventricular fibrillation/tachycardia, cardiogenic shock, newly-onset atrial fibrillation, clinical pulmonary edema requiring endotracheal intubation or dialysis. Among the 242 ESRD study patients, 9 patients (4%) developed major cardiovascular complications, and 39 patients (16%) developed pulmonary edema. Diabetes, ischemia-reperfusion time, left ventricular end-diastolic diameter (LVEDd), left ventricular mass index (LVMI), right ventricular systolic pressure (RVSP), left atrium volume index (LAVI), and high E/E' ratios were risk factors of major cardiovascular complications, while age, LVEDd, LVMI, LAVI, and high E/E' ratios were risk factors of pulmonary edema. The optimal E/E' cut-off value for predicting major cardiovascular complications was 13.0, showing 77.8% sensitivity and 78.5% specificity. Thus, the patient's E/E' ratio is useful for predicting in-hospital major cardiovascular complications after kidney transplantation. We recommend that goal-directed therapy employing E/E' ratio be enacted in kidney recipients with baseline diastolic dysfunction to avert postoperative morbidity. (http://Clinical Trials.gov number: NCT02322567). PMID:27499694

  10. Nitric oxide-mediated protein modification in cardiovascular physiology and pathology.

    PubMed

    Gödecke, Axel; Schrader, Jürgen; Reinartz, Michael

    2008-06-01

    Nitric oxide (NO) is a key regulator of cardiovascular functions including the control of vascular tone, anti-inflammatory properties of the endothelium, cardiac contractility, and thrombocyte activation and aggregation. Numerous experimental data support the view that NO not only acts via cyclic guanosine monophosphate (cGMP)-dependent mechanisms but also modulates protein function by nitrosation, nitrosylation, glutathiolation, and nitration, respectively. To understand how NO regulates all of these diverse biological processes on the molecular level a comprehensive assessment of NO-mediated cGMP-dependent and independent targets is required. Novel proteomic approaches allow the simultaneous identification of large quantities of proteins modified in an NO-dependent manner and thereby will considerably deepen our understanding of the role NO plays in cardiovascular physiology and pathophysiology.

  11. Coronary Interventions before Liver Transplantation Might Not Avert Postoperative Cardiovascular Events.

    PubMed

    Snipelisky, David F; McRee, Chad; Seeger, Kristina; Levy, Michael; Shapiro, Brian P

    2015-10-01

    Percutaneous coronary intervention and coronary artery bypass grafting may be performed before orthotopic liver transplantation (OLT) to try to improve the condition of patients who have severe ischemic heart disease. However, data supporting improved outcomes are lacking. We reviewed the medical records of 2,010 patients who underwent OLT at our hospital from 2000 through 2010. The 51 patients who underwent coronary artery angiography within 6 months of transplantation were included in this study: 28 had mild coronary artery disease, 10 had moderate disease, and 13 had severe disease. We compared all-cause and cardiac-cause mortality rates. We found a significant difference in cardiac deaths between the groups (P <0.001), but none in all-cause death (P=0.624). Of the 10 patients who had moderate coronary artery disease, one underwent pre-transplant coronary artery bypass grafting. Of 13 patients with severe disease, 3 underwent percutaneous coronary intervention, and 6 underwent coronary artery bypass grafting. Overall, 50% of patients who underwent either intervention died of cardiac-related causes, whereas no patient died of a cardiac-related cause after undergoing neither intervention (P <0.0001). We conclude that, despite coronary intervention, mortality rates remain high in OLT patients who have severe coronary artery disease. PMID:26504436

  12. Immune-Mediated Inflammation May Contribute to the Pathogenesis of Cardiovascular Disease in Mucopolysaccharidosis Type I

    PubMed Central

    Gordts, Philip L.; Ellinwood, N. Matthew; Schwartz, Philip H.; Dickson, Patricia I.; Esko, Jeffrey D.; Wang, Raymond Y.

    2016-01-01

    Background Cardiovascular disease, a progressive manifestation of α-L-iduronidase deficiency or mucopolysaccharidosis type I, continues in patients both untreated and treated with hematopoietic stem cell transplantation or intravenous enzyme replacement. Few studies have examined the effects of α-L-iduronidase deficiency and subsequent glycosaminoglycan storage upon arterial gene expression to understand the pathogenesis of cardiovascular disease. Methods Gene expression in carotid artery, ascending, and descending aortas from four non-tolerized, non-enzyme treated 19 month-old mucopolysaccharidosis type I dogs was compared with expression in corresponding vascular segments from three normal, age-matched dogs. Data were analyzed using R and whole genome network correlation analysis, a bias-free method of categorizing expression level and significance into discrete modules. Genes were further categorized based on module-trait relationships. Expression of clusterin, a protein implicated in other etiologies of cardiovascular disease, was assessed in canine and murine mucopolysaccharidosis type I aortas via Western blot and in situ immunohistochemistry. Results Gene families with more than two-fold, significant increased expression involved lysosomal function, proteasome function, and immune regulation. Significantly downregulated genes were related to cellular adhesion, cytoskeletal elements, and calcium regulation. Clusterin gene overexpression (9-fold) and protein overexpression (1.3 to 1.62-fold) was confirmed and located specifically in arterial plaques of mucopolysaccharidosis-affected dogs and mice. Conclusions Overexpression of lysosomal and proteasomal-related genes are expected responses to cellular stress induced by lysosomal storage in mucopolysaccharidosis type I. Upregulation of immunity-related genes implicates the potential involvement of glycosaminoglycan-induced inflammation in the pathogenesis of mucopolysaccharidosis-related arterial disease, for

  13. IL-34 is a Treg-specific cytokine and mediates transplant tolerance

    PubMed Central

    Bézie, Séverine; Picarda, Elodie; Ossart, Jason; Tesson, Laurent; Usal, Claire; Renaudin, Karine; Anegon, Ignacio; Guillonneau, Carole

    2015-01-01

    Cytokines and metabolic pathway–controlling enzymes regulate immune responses and have potential as powerful tools to mediate immune tolerance. Blockade of the interaction between CD40 and CD40L induces long-term cardiac allograft survival in rats through a CD8+CD45RClo Treg potentiation. Here, we have shown that the cytokine IL-34, the immunoregulatory properties of which have not been previously studied in transplantation or T cell biology, is expressed by rodent CD8+CD45RClo Tregs and human FOXP3+CD45RCloCD8+ and CD4+ Tregs. IL-34 was involved in the suppressive function of both CD8+ and CD4+ Tregs and markedly inhibited alloreactive immune responses. Additionally, in a rat cardiac allograft model, IL-34 potently induced transplant tolerance that was associated with a total inhibition of alloantibody production. Treatment of rats with IL-34 promoted allograft tolerance that was mediated by induction of CD8+ and CD4+ Tregs. Moreover, these Tregs were capable of serial tolerance induction through modulation of macrophages that migrate early to the graft. Finally, we demonstrated that human macrophages cultured in the presence of IL-34 greatly expanded CD8+ and CD4+ FOXP3+ Tregs, with a superior suppressive potential of antidonor immune responses compared with non–IL-34–expanded Tregs. In conclusion, we reveal that IL-34 serves as a suppressive Treg–specific cytokine and as a tolerogenic cytokine that efficiently inhibits alloreactive immune responses and mediates transplant tolerance. PMID:26389674

  14. Molecular Mechanisms Mediating Retinal Reactive Gliosis Following Bone Marrow Mesenchymal Stem Cell Transplantation

    PubMed Central

    Tassoni, Alessia; Gutteridge, Alex; Barber, Amanda C.; Osborne, Andrew

    2015-01-01

    abstract A variety of diseases lead to degeneration of retinal ganglion cells (RGCs) and their axons within the optic nerve resulting in loss of visual function. Although current therapies may delay RGC loss, they do not restore visual function or completely halt disease progression. Regenerative medicine has recently focused on stem cell therapy for both neuroprotective and regenerative purposes. However, significant problems remain to be addressed, such as the long‐term impact of reactive gliosis occurring in the host retina in response to transplanted stem cells. The aim of this work was to investigate retinal glial responses to intravitreally transplanted bone marrow mesenchymal stem cells (BM‐MSCs) to help identify factors able to modulate graft‐induced reactive gliosis. We found in vivo that intravitreal BM‐MSC transplantation is associated with gliosis‐mediated retinal folding, upregulation of intermediate filaments, and recruitment of macrophages. These responses were accompanied by significant JAK/STAT3 and MAPK (ERK1/2 and JNK) cascade activation in retinal Muller glia. Lipocalin‐2 (Lcn‐2) was identified as a potential new indicator of graft‐induced reactive gliosis. Pharmacological inhibition of STAT3 in BM‐MSC cocultured retinal explants successfully reduced glial fibrillary acidic protein expression in retinal Muller glia and increased BM‐MSC retinal engraftment. Inhibition of stem cell‐induced reactive gliosis is critical for successful transplantation‐based strategies for neuroprotection, replacement, and regeneration of the optic nerve. Stem Cells 2015;33:3006–3016 PMID:26175331

  15. Late acute antibody mediated rejection after nine years of renal transplantation.

    PubMed

    Halim, Medhat Abdel; Al-Otaibi, Torki; Al-Waheeb, Salah; Tawab, Khaled Abdel; El Kholy, Osama; Nair, Prasad; Said, Tarek; Narayanan Nampoory, M R

    2010-11-01

    Acute antibody mediated rejection (AMR) is rarely reported as a long-term com-plication of renal transplantation, and it can present on top of another chronic pathology affecting the graft. A 45-year-old gentleman with chronic kidney disease due to unknown etiology received renal transplantation from his sister with 4 HLA mismatches. He received antithymocte globulin induction therapy and was maintained on steroids, azathioprine (AZA) and cyclosporine A (CsA). Up to eight years post-transplantation he was clinically and biochemically stable. He lost follow-up for about one year, and then presented with nephritic nephrotic syndrome and rise of serum creatinine (SCr.) to 210 μmol/L. Graft biopsy revealed picture suggestive of acute AMR on top of de novo membranoprolipherative glomerulonephritis (MPGN) with focal crescent formation, diffuse immune complex deposition and peritubular capillaries C4d positivity. Anti-HLA donor specific antibodies were highly positive for B and T cells class I and class II. The patient was treated with intravenous immunoglobulin, plasma exchange and anti-CD20 (rituximab). AZA was changed to mycophenolate mofetil and CsA to tacrolimus. He had partial response, but SCr. continued at 220 μmol/L.

  16. Dual Islet Transplantation Modeling of the Instant Blood-Mediated Inflammatory Reaction

    PubMed Central

    Martin, BM; Samy, KP; Lowe, MC; Thompson, PW; Cano, J; Farris, AB; Song, M; Dove, CR; Leopardi, FV; Strobert, EA; Jenkins, JB; Collins, BH; Larsen, CP; Kirk, AD

    2015-01-01

    Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood mediated inflammatory reaction (IBMIR). This syndrome of islet destruction has been incompletely defined and characterization in pig-to-primate models has been hampered by logistical and statistical limitations of large animal studies. To further investigate IBMIR, we developed a novel in vivo dual islet transplant model to precisely characterize IBMIR as proof-of-concept that this model can serve to properly control experiments comparing modified xenoislet preparations. Wild-type (WT) and α1,3-galactosyltransferase knockout (GTKO) neonatal porcine islets (NPIs) were studied in non-immunosuppressed rhesus macaques. Inert polyethylene microspheres served as a control for the effects of portal embolization. Digital analysis of immunohistochemistry targeting IBMIR mediators was performed at one and 24 hours after intraportal islet infusion. Early findings observed in transplanted islets include complement and antibody deposition, and infiltration by neutrophils, macrophages, and platelets. Insulin, complement, antibody, neutrophils, macrophages, and platelets were similar between GTKO and WT islets, with increasing macrophage infiltration at 24 hours in both phenotypes. This model provides an objective and internally controlled study of distinct islet preparations and documents the temporal histology of IBMIR. PMID:25702898

  17. Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events

    PubMed Central

    Liu, Jun-Yan; Li, Ning; Yang, Jun; Li, Nan; Qiu, Hong; Ai, Ding; Chiamvimonvat, Nipavan; Zhu, Yi; Hammock, Bruce D.

    2010-01-01

    Chronic administration of high levels of selective COX-2 inhibitors (coxibs), particularly rofecoxib, valdecoxib, and parecoxib, increases risk for cardiovascular disease. Understanding the possibly multiple mechanisms underlying these adverse cardiovascular events is critical for evaluating the risks and benefits of coxibs and for development of safer coxibs. The current understanding of these mechanisms is likely incomplete. Using a metabolomics approach, we demonstrate that oral administration of rofecoxib for 3 mo results in a greater than 120-fold higher blood level of 20-hydroxyeicosatetraenoic acid (20-HETE), which correlates with a significantly shorter tail bleeding time in a murine model. We tested the hypothesis that this dramatic increase in 20-HETE is attributable to inhibition of its metabolism and that the shortened bleeding time following rofecoxib administration is attributable, in part, to this increase. The s.c. infusion of 20-HETE shortened the tail bleeding time dramatically. Neither 20-HETE biosynthesis nor cytochrome P4A-like immune reactivity was increased by rofecoxib administration, but 20-HETE production increased in vitro with the addition of coxib. 20-HETE is significantly more potent than its COX-mediated metabolites in shortening clotting time in vitro. Furthermore, 20-HETE but not rofecoxib significantly increases rat platelet aggregation in vitro in a dose-dependent manner. These data suggest 20-HETE as a marker of rofecoxib exposure and that inhibition of 20-HETE's degradation by rofecoxib is a partial explanation for its dramatic increase, the shortened bleeding time, and, possibly, the adverse cardiovascular events associated with rofecoxib. PMID:20837537

  18. Alpha adrenergic receptor mediation of cardiovascular and metabolic responses to alcohol

    SciTech Connect

    Brackett, D.J.; Gauvin, D.V.; Lerner, M.R.; Holloway, F.H.; Wilson, M.F. Veterans Affairs Medical Center, Oklahoma City, OK )

    1992-02-26

    The role of alpha adrenergic receptors in acute cardiovascular and metabolic responses to alcohol (ETOH) have not been clearly defined. In this study two groups of male Sprague-Dawley rats were given intravenous phentolamine mesylate or saline prior to intragastric alcohol to blockade of alpha receptors during alcohol intoxication in conscious rats. ETOH alone evoked an increase in systemic vascular resistance (SVR), heart rate (HR), and blood glucose concentrations (G) and a decrease in mean arterial pressure (MAP), cardiac output (CO), central venous pressure (CVP), respiration rate (RR) and cardiac stroke volume (SV). Blood alcohol concentration (BAC) peaked at 30 min and remained elevated for the four hrs of monitoring. Phentolamine pretreatment produced a decrease in MAP and SV and an increase in HR. However, antagonism of the alpha receptor blocked the decrease in CO and the increase in SVR and G. The decrease in CVP was unaffected. Surprisingly, the early rise and peak in BAC in the phentolamine treated group was attenuated, but was the same as the untreated group during the final 3 hrs. These data suggest that alpha receptors are significant mediators of cardiovascular and glucoregulatory responses elicited by alcohol. Furthermore, alpha receptor blockade appears to effect the absorption and/or distribution of intragastrically administered alcohol.

  19. [Hydrogen sulfide as a biologically active mediator in the cardiovascular system].

    PubMed

    Bełtowski, Jerzy

    2004-07-19

    Recent studies suggest that apart from nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is another inorganic gaseous mediator in the cardiovascular system. H2S is synthesized from L-cysteine by either cystathionine beta-synthase (CBS) or cystathionin gamma--lyase (CSE), both using pyridoxal 5'-phosphate (vitamin B6) as a cofactor. CBS is the main H2S-producing enzyme in the brain and CSE is involved in H2S formation in the cardiovascular system. H2S induces hypotension in vivo and vasodilation vitro by opening KATP channels in vascular smooth muscle cells. Chronic administration of CSE inhibitor induces arterial hypertension in the rat. In addition, decreased H2S generation has been demonstrated in the vasculature of spontaneously hypertensive rat, in experimental hypertension induced by NO synthase blockade, and in hypoxia-induced pulmonary hypertension, and administration of exogenous H2S donor has significant therapeutic effects in these models. Deficiency of H2S may contribute to atherogenesis in some patients with hyperhomocysteinemia, in whom the metabolism of homocysteine to cysteine and H2S is compromised by vitamin B6 deficiency. Reduced H2S production in the brain was observed in patients with Alzheimer's disease. On the other hand, excess of H2S may lead to mental retardation in patients with Down's syndrome and may be involved in the pathogenesis of hypotension associated with septic shock.

  20. Influence of recipient gender on intrasplenic fetal liver tissue transplants in rats: cytochrome P450-mediated monooxygenase functions.

    PubMed

    Lupp, Amelie; Hugenschmidt, Sabine; Rost, Michael; Müller, Dieter

    2004-05-01

    Rat livers display a sex-specific cytochrome P450 (P450) isoforms expression pattern with consecutive differences in P450-mediated monooxygenase activities, which have been shown to be due to a differential profile of growth hormone (GH) secretion. Parallel to previous investigations on P450 isoforms expression, the aim of the present study was to elucidate the influence of recipient gender on P450-mediated monooxygenase activities in intrasplenic liver tissue transplants in comparison to orthotopic liver. Fetal liver tissue suspensions of mixed gender were transplanted into the spleen of adult male or female syngenic recipients. Four months after grafting transplant-recipients and age-matched controls were treated with beta-naphthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX) or the vehicles and sacrificed 24 or 48 h thereafter. P450-dependent monooxygenase activities were assessed by a series of model reactions for different P450 subtypes in liver and spleen 9000 g supernatants. In spleens of male and female control rats only very low monooxygenase activities were detectable, whereas with most model reactions distinct activities were observed in transplant-containing organs. Livers and transplant-containing spleens from male rats displayed higher basal ethoxycoumarin O-deethylase and testosterone 2alpha-, 2beta-, 6beta-, 14alpha-, 15alpha-, 15beta-, 16alpha-, 16beta- and 17-hydroxylase activities than those from females. On the other hand, like the respective livers, spleens from female transplant-recipients demonstrated more pronounced p-nitrophenol- and testosterone 6alpha- and 7alpha-hydroxylase activities than those from male hosts. With nearly all model reactions gender-specific differences in inducibility by BNF, PB or DEX could be demonstrated in livers as well as in transplant-containing spleens. These results further confirm that the P450 system of intrasplenic liver tissue transplants and the respective orthotopic livers is similarly influenced

  1. A type I interferon signature characterizes chronic antibody-mediated rejection in kidney transplantation.

    PubMed

    Rascio, Federica; Pontrelli, Paola; Accetturo, Matteo; Oranger, Annarita; Gigante, Margherita; Castellano, Giuseppe; Gigante, Maddalena; Zito, Anna; Zaza, Gianluigi; Lupo, Antonio; Ranieri, Elena; Stallone, Giovanni; Gesualdo, Loreto; Grandaliano, Giuseppe

    2015-09-01

    Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss. To uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of peripheral blood mononuclear cells (PBMCs) and, separately, of CD4(+) T lymphocytes isolated from CAMR patients, compared to kidney transplant recipients with normal graft function and histology. We enrolled 29 patients with biopsy-proven CAMR, 29 stable transplant recipients (controls), and 8 transplant recipients with clinical and histological evidence of interstitial fibrosis/tubular atrophy. Messenger RNA and microRNA profiling of PBMCs and CD4(+) T lymphocytes was performed using Agilent microarrays in eight randomly selected patients per group from CAMR and control subjects. Results were evaluated statistically and by functional pathway analysis (Ingenuity Pathway Analysis) and validated in the remaining subjects. In PBMCs, 45 genes were differentially expressed between the two groups, most of which were up-regulated in CAMR and were involved in type I interferon signalling. In the same patients, 16 microRNAs were down-regulated in CAMR subjects compared to controls: four were predicted modulators of six mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signalling. To further confirm this result, we investigated the transcriptomic profiles of CD4(+) T lymphocytes in an independent group of patients, observing that the activation of type I interferon signalling was a specific hallmark of CAMR. In addition, in CAMR patients, we detected a reduction of circulating BDCA2(+) dendritic cells, the natural type I interferon-producing cells, and their recruitment into the graft along with increased expression of MXA, a type I interferon-induced protein, at the tubulointerstitial and vascular level. Finally, interferon alpha mRNA expression was significantly increased in CAMR compared to control

  2. Rejection Triggers Liver Transplant Tolerance: Involvements of Mesenchyme-Mediated Immune Control Mechanisms

    PubMed Central

    Morita, Miwa; Joyce, Daniel; Miller, Charles; Fung, John J.; Lu, Lina; Qian, Shiguang

    2015-01-01

    Liver tolerance was initially recognized by the spontaneous acceptance of liver allograft in many species. The underlying mechanisms are not completely understood. We have been inspired by an unexpected phenomenon that the liver transplant tolerance absolutely requires interferon (IFN)-γ, a rejection-associated inflammatory cytokine. In this study, we investigate the rejection of liver allografts deficient in IFN-γ receptor and reveal that the liver graft is equipped with machineries capable of counterattacking the host immune response through a mesenchyme-mediated immune control (MMIC) mechanism. MMIC is triggered by T effectors (Tef) cell-derived IFN-γ to drive the expression of B7-H1 on graft mesenchymal cells leading to Tef cell apoptosis. We describe the negative feedback loop between graft mesenchymal and Tef cells that ultimately results in liver transplant tolerance. Comparable elevations of T regulatory cells and myeloid-derived suppressor cells are seen in both rejection and tolerance groups, and are not dependent on IFN-γ stimulation, suggesting a critical role of Tef cell elimination in tolerance induction. We identify potent MMIC activity in hepatic stellate cells and liver sinusoidal endothelial cells. MMIC is unlikely exclusive to the liver, as spontaneous acceptance of kidney allografts has been reported, although less commonly, probably reflecting variance in MMIC activity. MMCI may represent an important homeostatic mechanism that supports peripheral tolerance, and could be a target for the prevention and treatment of transplant rejection. This study highlights that the graft is actively participant in the equipoise between tolerance and rejection and warrants more attention in the search for tolerance biomarkers. PMID:25998530

  3. Optimising plasticity: environmental and training associated factors in transplant-mediated brain repair.

    PubMed

    Döbrössy, Màtè Daniel; Dunnett, Stephen B

    2005-01-01

    With progressively ageing populations, degeneration of nerve cells of the brain, due to accident or disease, represents one of the major problems for health and welfare in the developed world. The molecular environment in the adult brain promotes stability limiting its ability to regenerate or to repair itself following injury. Cell transplantation aims to repair the nervous system by introducing new cells that can replace the function of the compromised or lost cells. Alternatives to primary embryonic tissue are actively being sought but this is at present the only source that has been shown reliably to survive grafting into the adult brain and spinal cord, connect with the host nervous system, and influence behaviour. Based on animal studies, several clinical trials have now shown that embryonic tissue grafts can partially alleviate symptoms in Parkinson's disease, and related strategies are under evaluation for Huntington's disease, spinal cord injury, stroke and other CNS disorders. The adult brain is at its most plastic in the period following injury, offering a window of opportunity for therapeutic intervention. Enriched environment, behavioural experience and grafting can each separately influence neuronal plasticity and recovery of function after brain damage, but the extent to which these factors interact is at present unknown. To improve the outcome following brain damage, transplantation must make use of the endogenous potential for plasticity of both the host and the graft and optimise the external circumstances associated with graft-mediated recovery. Our understanding of mechanisms of brain plasticity subsequent to brain damage needs to be associated with what we know about enhancing intrinsic recovery processes in order to improve neurobiological and surgical strategies for repair at the clinical level. With the proof of principle beginning to emerge from clinical trials, a rich area for innovative research with profound therapeutic application, even

  4. Associations between the prenatal environment and cardiovascular risk factors in adolescent girls: Internalizing and externalizing behavior symptoms as mediators

    PubMed Central

    Beal, Sarah J.; Hillman, Jennifer; Dorn, Lorah D.; Out, Dorothée; Pabst, Stephanie

    2014-01-01

    This longitudinal study examines links among adolescent internalizing and externalizing symptoms, the prenatal environment (e.g., nicotine exposure) and pre/perinatal maternal health, and cardiovascular risk factors. Girls (N=262) ages 11–17 reported internalizing and externalizing behaviors and mothers reported about the prenatal environment and maternal health during and 3 months post-pregnancy. Adolescent cardiovascular risk included adiposity, smoking, blood pressure, and salivary C-reactive protein. Internalizing symptoms mediated relations between prenatal exposures/maternal health and adiposity; externalizing symptoms mediated relations between prenatal exposures and adolescent smoking. Healthcare providers who attend to internalizing and externalizing symptoms in girls may ultimately influence cardiovascular health, especially among those with pre/perinatal risk factors. PMID:25750471

  5. Adiponectin Fractions Influence the Development of Posttransplant Diabetes Mellitus and Cardiovascular Disease in Japanese Renal Transplant Recipients

    PubMed Central

    Adachi, Hiroki; Nakayama, Kanae; Hayashi, Norifumi; Matsui, Yuki; Fujimoto, Keiji; Yamaya, Hideki; Tonami, Hisao; Yokoyama, Hitoshi

    2016-01-01

    Background A few studies have investigated the role of adiponectin fraction for cardiovascular disease (CVD) in RTx recipients. Subjects and Methods We studied 57 adult subjects (39 males, 18 females; 10 cadaveric donors) with at least three years of allograft survival (median 251 months). We examined clinical backgrounds such as treated drugs, blood pressure (BP, mmHg), body mass index (BMI), and blood chemistry including cholesterol (total, LDL-C, HDL-C), glucose, glycated hemoglobin (HbA1c), and serum high and low-molecular-weight (HMW/LMW) ADPN fractions with regard to the associations of the visceral and subcutaneous fat areas on CT scan. We also analyzed the associations of CVD and post-transplant diabetes (PTDM) with ADPN fractions and the fat areas. Results The visceral fat area was inversely correlated with serum HMW and LMW ADPN levels and HMW ADPN ratio (r = -0.400, p = 0.002 and r = -0.296, p = 0.025 and r = -0.444, p<0.001, respectively). Furthermore, the visceral fat area was positively with the LMW ADPN ratio (r = 0.467, p<0.001), but no significant correlation was noted between the subcutaneous fat area and the ADPN ratio. On multiple regression analysis, eGFR and the visceral fat area were significant reducing factors of HMW ADPN levels, and the alteration of eGFR was identified as an increasing factor of HMW ADPN levels. Patients with CVD had larger visceral fat area (p = 0.004), lower HMW ADPN ratio (p = 0.022) and higher LMW ADPN ratio (p = 0.049). In addition, the higher HMW ADPN ratio and statin treatment were identified as reducing factors of the development of CVD, but the LDL-C level was an aggravating factor. Moreover, the higher LMW ADPN ratio and the visceral fat area were aggravating factors of PTDM. Conclusion Even in Japanese renal transplant recipients, visceral fat area and ADPN fractions were significant factors for the development of both CVD and PTDM. PMID:27706207

  6. Aged spontaneously hypertensive rats (SHRs) are predisposed to ultrafine carbon particle (UfCP) mediated cardiovascular impairment.

    EPA Science Inventory

    Background: Elderly individuals are considered to be more susceptible to particulate matter (PM) related cardiovascular (CV) health effects. In this study we investigated UfCP mediated CV effects on aged SHRs and compared the findings to that of adult SHRs to identify age related...

  7. High prevalence of cardiovascular and respiratory abnormalities in advanced, intensively treated (transplanted) myeloma: The case for ‘late effects’ screening and preventive strategies

    PubMed Central

    Samuelson, Clare; O'Toole, Laurence; Boland, Elaine; Greenfield, Diana; Ezaydi, Yousef; Ahmedzai, Sam H.; Snowden, John A.

    2016-01-01

    Objectives: Modern management of myeloma has significantly improved survival, with increasing numbers of patients living beyond a decade. However, little is known about the long-term cardiovascular and respiratory status of intensively treated and multiply relapsed survivors. Methods: We performed detailed cardiovascular and respiratory evaluations in patients with intensively treated, advanced but stable myeloma. All patients had received at least two lines of treatment, including at least one haematopoietic stem cell transplantation procedure, but had stable, controlled disease and were off active treatment at the time of evaluation. Results: Thirty-two patients with a median duration of 6 years (range 2–12) from original diagnosis of myeloma and three lines (range 2–6) of treatment were evaluated. Despite normal physical examination in the majority, there was a high prevalence of sub-clinical cardiac and respiratory dysfunction, reflected by abnormalities of electrocardiography (45%), echocardiography (50%), serum N-terminal pro-B-type natriuretic peptide level (NT-pro-BNP, 50%), and pulmonary function testing (45%). NT-pro-BNP level correlated negatively with quality of life (P = 0.012) and positively with serum ferritin (P = 0.027). Dyspnoea score correlated with BMI (P = 0.001). Risk factors for cardiovascular disease (obesity, hypertension, hyperlipidaemia, and hyperinsulinaemia) were common. Discussion: Even in the absence of overt clinical features, the majority of intensively treated long-term survivors of myeloma have established cardiovascular and/or respiratory dysfunction, above levels expected in the general population of a similar age. Conclusion: This study supports routine screening and lifestyle modification combined with primary and secondary preventive strategies to reduce cardiovascular and respiratory disease and to preserve quality of life in transplanted myeloma patients. PMID:27077780

  8. Acrolein inhalation alters arterial blood gases and triggers carotid body-mediated cardiovascular responses in hypertensive rats

    PubMed Central

    Perez, Christina M.; Hazari, Mehdi S.; Ledbetter, Allen D.; Haykal-Coates, Najwa; Carll, Alex P.; Cascio, Wayne E.; Winsett, Darrell W.; Costa, Daniel L.; Farraj, Aimen K.

    2016-01-01

    Context Air pollution exposure affects autonomic function, heart rate, blood pressure and left ventricular function. While the mechanism for these effects is uncertain, several studies have reported that air pollution exposure modifies activity of the carotid body, the major organ that senses changes in arterial oxygen and carbon dioxide levels, and elicits downstream changes in autonomic control and cardiac function. Objective We hypothesized that exposure to acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke and diesel exhaust, would activate the carotid body chemoreceptor response and lead to secondary cardiovascular responses in rats. Materials and methods Spontaneously hypertensive (SH) rats were exposed once for 3 h to 3 ppm acrolein gas or filtered air in whole body plethysmograph chambers. To determine if the carotid body mediated acrolein-induced cardiovascular responses, rats were pretreated with an inhibitor of cystathionine γ-lyase (CSE), an enzyme essential for carotid body signal transduction. Results Acrolein exposure induced several cardiovascular effects. Systolic, diastolic and mean arterial blood pressure increased during exposure, while cardiac contractility decreased 1 day after exposure. The cardiovascular effects were associated with decreases in pO2, breathing frequency and expiratory time, and increases in sympathetic tone during exposure followed by parasympathetic dominance after exposure. The CSE inhibitor prevented the cardiovascular effects of acrolein exposure. Discussion and conclusion Pretreatment with the CSE inhibitor prevented the cardiovascular effects of acrolein, suggesting that the cardiovascular responses with acrolein may be mediated by carotid body-triggered changes in autonomic tone. (This abstract does not reflect EPA policy.) PMID:25600140

  9. Television Viewing and Incident Cardiovascular Disease: Prospective Associations and Mediation Analysis in the EPIC Norfolk Study

    PubMed Central

    Wijndaele, Katrien; Brage, Søren; Besson, Hervé; Khaw, Kay-Tee; Sharp, Stephen J.; Luben, Robert; Bhaniani, Amit; Wareham, Nicholas J.; Ekelund, Ulf

    2011-01-01

    Background Although television viewing time is detrimentally associated with intermediate cardiovascular risk factors, the relationship with incident total (i.e. combined fatal and non-fatal) cardiovascular disease (CVD), non-fatal CVD and coronary heart disease is largely unknown. This study examined whether television viewing time is associated with these three outcomes, independently of physical activity energy expenditure and other confounding variables. Methodology/Principal Findings A population-based cohort of 12,608 men and women (aged 61.4±9.0), free from stroke, myocardial infarction and cancer at baseline in 1998–2000 were followed up until 2007 (6.9±1.9 years). Participants self-reported education, smoking, alcohol use, antihypertensive, lipid lowering and antidepressant medication, disease history, total energy intake, sleep duration, physical activity and television viewing. BMI, waist circumference, blood pressure, triglycerides, HDL cholesterol and glycated haemoglobin (HbA1c) were measured by standardized procedures; a clustered metabolic risk score was constructed. Every one hour/day increase in television viewing was associated with an increased hazard for total (HR = 1.06, 95%CI = 1.03–1.08; 2,620 cases), non-fatal CVD (HR = 1.06, 95%CI = 1.03–1.09; 2,134 cases), and coronary heart disease (HR = 1.08, 95%CI = 1.03–1.13; 940 cases), independent of gender, age, education, smoking, alcohol, medication, diabetes status, CVD family history, sleep duration and physical activity energy expenditure. Energy intake, BMI, waist circumference, blood pressure, triglycerides, HDL cholesterol, HbA1c and the clustered metabolic risk score only partially mediated these associations. Conclusions These results indicate that the most prevalent leisure time (sedentary) behaviour, television viewing, independently contributes to increased CVD risk. Recommendations on reducing television viewing time should be considered. PMID

  10. IGF-1-mediated osteoblastic niche expansion enhances long-term hematopoietic stem cell engraftment after murine bone marrow transplantation.

    PubMed

    Caselli, Anna; Olson, Timothy S; Otsuru, Satoru; Chen, Xiaohua; Hofmann, Ted J; Nah, Hyun-Duck; Grisendi, Giulia; Paolucci, Paolo; Dominici, Massimo; Horwitz, Edwin M

    2013-10-01

    The efficiency of hematopoietic stem cell (HSC) engraftment after bone marrow (BM) transplantation depends largely on the capacity of the marrow microenvironment to accept the transplanted cells. While radioablation of BM damages osteoblastic stem cell niches, little is known about their restoration and mechanisms governing their receptivity to engraft transplanted HSCs. We previously reported rapid restoration and profound expansion of the marrow endosteal microenvironment in response to marrow radioablation. Here, we show that this reorganization represents proliferation of mature endosteal osteoblasts which seem to arise from a small subset of high-proliferative, relatively radio-resistant endosteal cells. Multiple layers of osteoblasts form along the endosteal surface within 48 hours after total body irradiation, concomitant with a peak in marrow cytokine expression. This niche reorganization fosters homing of the transplanted hematopoietic cells to the host marrow space and engraftment of long-term-HSC. Inhibition of insulin-like growth factor (IGF)-1-receptor tyrosine kinase signaling abrogates endosteal osteoblast proliferation and donor HSC engraftment, suggesting that the cytokine IGF-1 is a crucial mediator of endosteal niche reorganization and consequently donor HSC engraftment. Further understanding of this novel mechanism of IGF-1-dependent osteoblastic niche expansion and HSC engraftment may yield clinical applications for improving engraftment efficiency after clinical HSC transplantation.

  11. Diagnosis of early pancreas graft failure via antibody-mediated rejection: single-center experience with 256 pancreas transplantations.

    PubMed

    de Kort, H; Mallat, M J K; van Kooten, C; de Heer, E; Brand-Schaaf, S H; van der Wal, A M; Roufosse, C; Roelen, D L; Bruijn, J A; Claas, F H; de Fijter, J W; Bajema, I M

    2014-04-01

    Early pancreas graft loss is usually attributed to technical failure while the possibility of antibody-mediated rejection (AMR) is generally overlooked. To investigate the role of AMR in early pancreas graft loss, we retrospectively assessed 256 patients with simultaneous pancreas-kidney transplantation (SPK) between 1985 and 2010 at our institute. We included 33 SPK patients who lost their pancreas graft <1 year after transplantation. AMR was diagnosed based on donor-specific antibodies, C4d and histology in 7 cases, 8 cases were suspicious for AMR and 18 pancreas graft losses were not due to AMR. Acute AMR occurred >1 month after transplantation in 6/7 cases, whereas all other causes typically led to loss <1 month after transplantation. Thrombotic lesions occurred equally among the 33 cases. In 12/18 concurrent kidney specimens, the diagnostic results paralleled those of the pancreas graft. All patients with acute AMR of the pancreas graft lost their renal grafts <1 year after transplantation. In the setting of a thrombotic event, histopathological analysis of early pancreas graft loss is advisable to rule out the possibility of AMR, particularly because a diagnosis of acute AMR has important consequences for renal graft outcomes.

  12. DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor.

    PubMed

    Aldrin-Kirk, Patrick; Heuer, Andreas; Wang, Gang; Mattsson, Bengt; Lundblad, Martin; Parmar, Malin; Björklund, Tomas

    2016-06-01

    Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson's disease (PD). Pioneering clinical trials using transplants of fetal DA neuroblasts have given promising results, although a number of patients have developed graft-induced dyskinesias (GIDs), and the mechanism underlying this troublesome side effect is still unknown. Here we have used a new model where the activity of the transplanted DA neurons can be selectively modulated using a bimodal chemogenetic (DREADD) approach, allowing either enhancement or reduction of the therapeutic effect. We show that exclusive activation of a cAMP-linked (Gs-coupled) DREADD or serotonin 5-HT6 receptor, located on the grafted DA neurons, is sufficient to induce GIDs. These findings establish a mechanistic link between the 5-HT6 receptor, intracellular cAMP, and GIDs in transplanted PD patients. This effect is thought to be mediated through counteraction of the D2 autoreceptor feedback inhibition, resulting in a dysplastic DA release from the transplant.

  13. Mindfulness may both moderate and mediate the effect of physical fitness on cardiovascular responses to stress: a speculative hypothesis

    PubMed Central

    Demarzo, Marcelo M. P.; Montero-Marin, Jesús; Stein, Phyllis K.; Cebolla, Ausiàs; Provinciale, Jaime G.; García-Campayo, Javier

    2014-01-01

    The psychological construct of mindfulness refers to an awareness that emerges by intentionally paying attention to the present experience in a non-judgmental or evaluative way. This particular quality of awareness has been associated to several indicators of physical and psychological health, and can be developed using mindfulness-based interventions (MBIs), and therefore MBIs have been successfully applied as preventive and complementary interventions and therapies in medicine and psychology. Together with quiet sitting and lying meditation practices, mindful physical exercises such as “mindful walking” and “mindful movement” are key elements in MBIs and couple muscular activity with an internally directed focus, improving interoceptive attention to bodily sensations. In addition, MBIs seem to share similar mechanisms with physical fitness (PF) by which they may influence cardiovascular responses to stress. Based on these facts, it is feasible to raise the question of whether physical training itself may induce the development of that particular quality of awareness associated with mindfulness, or if one's dispositional mindfulness (DM) (the tendency to be more mindful in daily life) could moderate the effects of exercise on cardiovascular response to stress. The role of mindfulness as a mediator or moderator of the effect of exercise training on cardiovascular responses to stress has barely been studied. In this study, we have hypothesized pathways (moderation and mediation) by which mindfulness could significantly influence the effects of PF on cardiovascular responses to stress and discussed potential practical ways to test these hypotheses. PMID:24723891

  14. Mindfulness may both moderate and mediate the effect of physical fitness on cardiovascular responses to stress: a speculative hypothesis.

    PubMed

    Demarzo, Marcelo M P; Montero-Marin, Jesús; Stein, Phyllis K; Cebolla, Ausiàs; Provinciale, Jaime G; García-Campayo, Javier

    2014-01-01

    The psychological construct of mindfulness refers to an awareness that emerges by intentionally paying attention to the present experience in a non-judgmental or evaluative way. This particular quality of awareness has been associated to several indicators of physical and psychological health, and can be developed using mindfulness-based interventions (MBIs), and therefore MBIs have been successfully applied as preventive and complementary interventions and therapies in medicine and psychology. Together with quiet sitting and lying meditation practices, mindful physical exercises such as "mindful walking" and "mindful movement" are key elements in MBIs and couple muscular activity with an internally directed focus, improving interoceptive attention to bodily sensations. In addition, MBIs seem to share similar mechanisms with physical fitness (PF) by which they may influence cardiovascular responses to stress. Based on these facts, it is feasible to raise the question of whether physical training itself may induce the development of that particular quality of awareness associated with mindfulness, or if one's dispositional mindfulness (DM) (the tendency to be more mindful in daily life) could moderate the effects of exercise on cardiovascular response to stress. The role of mindfulness as a mediator or moderator of the effect of exercise training on cardiovascular responses to stress has barely been studied. In this study, we have hypothesized pathways (moderation and mediation) by which mindfulness could significantly influence the effects of PF on cardiovascular responses to stress and discussed potential practical ways to test these hypotheses. PMID:24723891

  15. Cannabidiol Limits T Cell–Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

    PubMed Central

    Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Hask’, György; ’iháková, Daniela; Mechoulam, Raphael; Pacher, Pal

    2016-01-01

    Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a nonpsychoactive constituent of marijuana that exerts antiinflammatory effects independent of classical cannabinoid receptors. Recently, 80 clinical trials have investigated the effects of CBD in various diseases from inflammatory bowel disease to graft versus host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received U.S. Food and Drug Administration approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell–mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T-cell infiltration, profound inflammatory response and fibrosis (measured by quantitative real-time polymerase chain reaction, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with a pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ T cell–mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation. PMID:26772776

  16. Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II.

    PubMed

    Takayanagi, Takehiko; Forrester, Steven J; Kawai, Tatsuo; Obama, Takashi; Tsuji, Toshiyuki; Elliott, Katherine J; Nuti, Elisa; Rossello, Armando; Kwok, Hang Fai; Scalia, Rosario; Rizzo, Victor; Eguchi, Satoru

    2016-10-01

    Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which AngII elevates blood pressure and enhances cardiovascular remodeling and damage may be distinct. However, the signal transduction cascade by which AngII specifically initiates cardiovascular remodeling, such as hypertrophy and fibrosis, remains insufficiently understood. In vascular smooth muscle cells, a metalloproteinase ADAM17 mediates epidermal growth factor receptor transactivation, which may be responsible for cardiovascular remodeling but not hypertension induced by AngII. Thus, the objective of this study was to test the hypothesis that activation of vascular ADAM17 is indispensable for vascular remodeling but not for hypertension induced by AngII. Vascular ADAM17-deficient mice and control mice were infused with AngII for 2 weeks. Control mice infused with AngII showed cardiac hypertrophy, vascular medial hypertrophy, and perivascular fibrosis. These phenotypes were prevented in vascular ADAM17-deficient mice independent of blood pressure alteration. AngII infusion enhanced ADAM17 expression, epidermal growth factor receptor activation, and endoplasmic reticulum stress in the vasculature, which were diminished in ADAM17-deficient mice. Treatment with a human cross-reactive ADAM17 inhibitory antibody also prevented cardiovascular remodeling and endoplasmic reticulum stress but not hypertension in C57Bl/6 mice infused with AngII. In vitro data further supported these findings. In conclusion, vascular ADAM17 mediates AngII-induced cardiovascular remodeling via epidermal growth factor receptor activation independent of blood pressure regulation. ADAM17 seems to be a unique therapeutic target for the prevention of hypertensive complications.

  17. Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II.

    PubMed

    Takayanagi, Takehiko; Forrester, Steven J; Kawai, Tatsuo; Obama, Takashi; Tsuji, Toshiyuki; Elliott, Katherine J; Nuti, Elisa; Rossello, Armando; Kwok, Hang Fai; Scalia, Rosario; Rizzo, Victor; Eguchi, Satoru

    2016-10-01

    Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which AngII elevates blood pressure and enhances cardiovascular remodeling and damage may be distinct. However, the signal transduction cascade by which AngII specifically initiates cardiovascular remodeling, such as hypertrophy and fibrosis, remains insufficiently understood. In vascular smooth muscle cells, a metalloproteinase ADAM17 mediates epidermal growth factor receptor transactivation, which may be responsible for cardiovascular remodeling but not hypertension induced by AngII. Thus, the objective of this study was to test the hypothesis that activation of vascular ADAM17 is indispensable for vascular remodeling but not for hypertension induced by AngII. Vascular ADAM17-deficient mice and control mice were infused with AngII for 2 weeks. Control mice infused with AngII showed cardiac hypertrophy, vascular medial hypertrophy, and perivascular fibrosis. These phenotypes were prevented in vascular ADAM17-deficient mice independent of blood pressure alteration. AngII infusion enhanced ADAM17 expression, epidermal growth factor receptor activation, and endoplasmic reticulum stress in the vasculature, which were diminished in ADAM17-deficient mice. Treatment with a human cross-reactive ADAM17 inhibitory antibody also prevented cardiovascular remodeling and endoplasmic reticulum stress but not hypertension in C57Bl/6 mice infused with AngII. In vitro data further supported these findings. In conclusion, vascular ADAM17 mediates AngII-induced cardiovascular remodeling via epidermal growth factor receptor activation independent of blood pressure regulation. ADAM17 seems to be a unique therapeutic target for the prevention of hypertensive complications. PMID:27480833

  18. Magnetic nanoparticle-mediated gene transfer to oligodendrocyte precursor cell transplant populations is enhanced by magnetofection strategies.

    PubMed

    Jenkins, Stuart I; Pickard, Mark R; Granger, Nicolas; Chari, Divya M

    2011-08-23

    This study has tested the feasibility of using physical delivery methods, employing static and oscillating field "magnetofection" techniques, to enhance magnetic nanoparticle-mediated gene transfer to rat oligodendrocyte precursor cells derived for transplantation therapies. These cells are a major transplant population to mediate repair of damage as occurs in spinal cord injury and neurological diseases such as multiple sclerosis. We show for the first time that magnetic nanoparticles mediate effective transfer of reporter and therapeutic genes to oligodendrocyte precursors; transfection efficacy was significantly enhanced by applied static or oscillating magnetic fields, the latter using an oscillating array employing high-gradient NdFeB magnets. The effects of oscillating fields were frequency-dependent, with 4 Hz yielding optimal results. Transfection efficacies obtained using magnetofection methods were highly competitive with or better than current widely used nonviral transfection methods (e.g., electroporation and lipofection) with the additional critical advantage of high cell viability. No adverse effects were found on the cells' ability to divide or give rise to their daughter cells, the oligodendrocytes-key properties that underpin their regeneration-promoting effects. The transplantation potential of transfected cells was tested in three-dimensional tissue engineering models utilizing brain slices as the host tissue; modified transplanted cells were found to migrate, divide, give rise to daughter cells, and integrate within host tissue, further evidencing the safety of the protocols used. Our findings strongly support the concept that magnetic nanoparticle vectors in conjunction with state-of-the-art magnetofection strategies provide a technically simple and effective alternative to current methods for gene transfer to oligodendrocyte precursor cells.

  19. European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

    PubMed

    Badano, Luigi P; Miglioranza, Marcelo H; Edvardsen, Thor; Colafranceschi, Alexandre Siciliano; Muraru, Denisa; Bacal, Fernando; Nieman, Koen; Zoppellaro, Giacomo; Marcondes Braga, Fabiana G; Binder, Thomas; Habib, Gilbert; Lancellotti, Patrizio

    2015-09-01

    The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two-dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent

  20. European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

    PubMed

    Badano, Luigi P; Miglioranza, Marcelo H; Edvardsen, Thor; Colafranceschi, Alexandre Siciliano; Muraru, Denisa; Bacal, Fernando; Nieman, Koen; Zoppellaro, Giacomo; Marcondes Braga, Fabiana G; Binder, Thomas; Habib, Gilbert; Lancellotti, Patrizio

    2015-09-01

    The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two-dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent

  1. Postoperative rebound of antiblood type antibodies and antibody-mediated rejection after ABO-incompatible living-related kidney transplantation.

    PubMed

    Ishida, Hideki; Kondo, Tsunenori; Shimizu, Tomokazu; Nozaki, Taiji; Tanabe, Kazunari

    2015-03-01

    The purpose of this study is to examine whether postoperative antiblood type antibody rebound is attributed to kidney allograft rejection in ABO blood type-incompatible (ABO-I) living-related kidney transplantation (KTx). A total of 191 ABO-I recipients who received ABO-I living-related KTx between 2001 and 2013 were divided into two groups: Group 1 consisted of low rebound [(≦1:32), N = 170] and Group 2 consisted of high rebound [(≧1:64), N = 21], according to the levels of the rebounded antiblood type antibodies within 1 year after transplantation. No prophylactic treatment for rejection was administered for elevated antiblood type antibodies, regardless of the levels of the rebounded antibodies. Within 1 year after transplantation, T-cell-mediated rejection was observed in 13 of 170 recipients (13/170, 8%) in Group 1 and in 2 of 21 recipients (2/21, 10%) in Group 2 (Groups 1 vs. 2, P = 0.432). Antibody-mediated rejection was observed in 15 of 170 recipients (15/170, 9%) and 2 of 21 recipients (2/21, 10%) in Groups 1 and 2, respectively (P = 0.898). In this study, we found no correlation between the postoperative antiblood type antibody rebound and the incidence of acute rejection. We concluded that no treatment is necessary for rebounded antiblood type antibodies.

  2. Acrolein Inhalation Alters Arterial Blood Gases and Triggers Carotid Body Mediated Cardiovascular Responses in Hypertensive Rats

    EPA Science Inventory

    Exposure to air pollution increases risk of cardiovascular morbidity and mortality, especially in individuals with underlying cardiopulmonary disease. While the mechanisms accounting for these effects are unclear, several epidemiological studies have reported decreases in oxygen ...

  3. Ultrafine carbon particle mediated cardiovascular impairment of aged spontaneously hypertensive rats

    EPA Science Inventory

    Background: Previous studies provided compelling evidences for particulate matter (PM) associated cardiovascular health effects. Elderly individuals, particularly those with preexisting conditions like hypertension are regarded to be vulnerable. Experimental data are warranted to...

  4. Intestinal injury following liver transplantation was mediated by TLR4/NF-κB activation-induced cell apoptosis

    PubMed Central

    YUAN, DONG-DONG; CHI, XIN-JIN; JIN, YI; LI, XI; GE, MIAN; GAO, WAN-LING; GUAN, JIAN-QIANG; ZHANG, AI-LAN; HEI, ZI-QING

    2016-01-01

    Intestinal motility and barriers are often impaired due to intestinal congestion during liver transplantation. Intestinal bacteria and enterogenous endotoxins enter into the blood stream or lymphatic system and translocate to other organs, which can result in postoperative multi-organ dysfunction (MODF) and systemic inflammatory reaction syndrome (SIRS) severely affecting patient survival. However, the mechanisms underlying liver transplantation-induced intestinal injury remain unclear and effective therapies are lacking. Thus, the present study investigated whether these effects were associated with endotoxin-mediated apoptosis. Rat autologous orthotopic liver transplantation (AOLT) models were established to observe dynamic intestinal injuries at different time-points following reperfusion. Changes in the levels of endotoxins and the primary receptor, toll-like receptor 4 (TLR4), as well as its downstream signaling molecule, nuclear factor-κB (NF-κB) were all determined. Finally, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were conducted to detect caspase-3 expression and intestinal cell apoptosis, respectively. AOLT resulted in significant pathological intestinal injury, with the most serious intestine damage apparent four or eight hours following reperfusion. Furthermore, the levels of endotoxins and inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, peaked during this time period and gradually decreased to the normal level. Notably, TLR4 and downstream NF-κB expression, as well as NF-κB-mediated caspase-3 activation and intestinal cell aapoptosis coincided with the intestinal pathological damage. Thus, the possible mechanism of post-liver transplantation intestinal injury was demonstrated to be associated with NF-κB activation-induced cell apoptosis. PMID:26707779

  5. MicroRNAs as mediators of cardiovascular disease: Targets to be manipulated.

    PubMed

    Lee, Seahyoung; Choi, Eunhyun; Kim, Sung-Man; Hwang, Ki-Chul

    2015-05-26

    Cardiovascular disease has been the leading cause of death worldwide for the last few decades. Even with the rapid progression of the biomedical field, conquering/managing cardiovascular disease is not an easy task because it is multifactorial disease. One of the key players of the development and progression of numerous diseases is microRNA (miRNA). These small, non-coding RNAs bind to target mRNAs to inhibit translations of and/or degrade the target mRNAs, thus acting as negative regulators of gene expressions. Accumulating evidence indicates that non-physiological expressions of miRNAs contribute to both development and progression of cardiovascular diseases. Since even a single miRNA can have multiple targets, dysregulation of miRNAs can lead to catastrophic changes of proteins that may be important for maintaining physiologic conditions of cells, tissues, and organs. Current knowledge on the role of miRNAs in cardiovascular disease is mostly based on the observational data such as microarray of miRNAs in animal disease models, thus relatively lacking insight of how such dysregulation of miRNAs is initiated and regulated. Consequently, future research should aim to elucidate the more comprehensive mechanisms of miRNA dysregulation during pathogenesis of the cardiovascular system so that appropriate counter-measures to prevent/manage cardiovascular disease can be developed.

  6. European Transplant Registry of Senior Renal Transplant Recipients on Advagraf

    ClinicalTrials.gov

    2016-08-11

    Graft Failure; Death; Acute Rejection of Renal Transplant; Infections; Bone Disease; Post Transplant Diabetes Mellitus; Quality of Life; HLA Antibody Production; Cardiovascular Risk Factors; Non-HLA Antibody Production

  7. Coincidence of cellular and antibody mediated rejection in heart transplant recipients - preliminary report.

    PubMed

    Zakliczyński, Michał; Nożyński, Jerzy; Konecka-Mrówka, Dominika; Babińska, Agnieszka; Flak, Bożena; Hrapkowicz, Tomasz; Zembala, Marian

    2014-03-01

    Antibody mediated rejection (AMR) can significantly influence the results of orthotopic heart transplantation (OHT). However, AMR and cellular rejection (CR) coexistence is poorly described. Therefore we performed a prospective pilot study to assess AMR/CR concomitance in endomyocardial biopsies (EMBs) obtained electively in 27 OHT recipients (21 M/6 F, 45.4 ± 14.4 y/o). Biopsy samples were paraffin embedded and processed typically with hematoxylin/eosin staining to assess CR, and, if a sufficient amount of material remained, treated with immunohistochemical methods to localize particles C3d and C4d as markers of antibody dependent complement activation. With this approach 80 EMBs, including 41 (51%) harvested within the first month after OHT, were qualified for the study. Among them 14 (18%) were C3d+, 37 (46%) were C4d+, and 12 (15%) were both C3d and C4d positive. At least one C3d+, C4d+, and C3d/C4d+ EMB was found in 10 (37%), 17 (63%), and 8 (30%) patients, respectively. Among 37 CR0 EMBs C3d was observed in 4 (11%), C4d in 17 (46%), and both C3d/C4d in 3 (8%) cases. Among 28 CR1 EMBs C3d was observed in 3 (11%), C4d in 11 (39%), and C3d/C4d in 3 (11%) cases. Among 15 CR2 EMBs C3d was observed in 7 (47%), C4d in 9 (60%), and C3d/C4d in 6 (40%) cases. Differences in C3d and C3d/C4d occurrence between grouped CR0-1 EMBs and CR2 EMBs (7/65 - 11% vs. 7/15 - 47%; 6/65 - 9% vs. 6/15 - 40%) were significant (p = 0.0035 and p = 0.0091, respectively, χ(2) test). In conclusion, apparently frequent CR and AMR coexistence demonstrated in this preliminary study warrants further investigation in this field. PMID:26336395

  8. Coincidence of cellular and antibody mediated rejection in heart transplant recipients – preliminary report

    PubMed Central

    Nożyński, Jerzy; Konecka-Mrówka, Dominika; Babińska, Agnieszka; Flak, Bożena; Hrapkowicz, Tomasz; Zembala, Marian

    2014-01-01

    Antibody mediated rejection (AMR) can significantly influence the results of orthotopic heart transplantation (OHT). However, AMR and cellular rejection (CR) coexistence is poorly described. Therefore we performed a prospective pilot study to assess AMR/CR concomitance in endomyocardial biopsies (EMBs) obtained electively in 27 OHT recipients (21 M/6 F, 45.4 ± 14.4 y/o). Biopsy samples were paraffin embedded and processed typically with hematoxylin/eosin staining to assess CR, and, if a sufficient amount of material remained, treated with immunohistochemical methods to localize particles C3d and C4d as markers of antibody dependent complement activation. With this approach 80 EMBs, including 41 (51%) harvested within the first month after OHT, were qualified for the study. Among them 14 (18%) were C3d+, 37 (46%) were C4d+, and 12 (15%) were both C3d and C4d positive. At least one C3d+, C4d+, and C3d/C4d+ EMB was found in 10 (37%), 17 (63%), and 8 (30%) patients, respectively. Among 37 CR0 EMBs C3d was observed in 4 (11%), C4d in 17 (46%), and both C3d/C4d in 3 (8%) cases. Among 28 CR1 EMBs C3d was observed in 3 (11%), C4d in 11 (39%), and C3d/C4d in 3 (11%) cases. Among 15 CR2 EMBs C3d was observed in 7 (47%), C4d in 9 (60%), and C3d/C4d in 6 (40%) cases. Differences in C3d and C3d/C4d occurrence between grouped CR0-1 EMBs and CR2 EMBs (7/65 – 11% vs. 7/15 – 47%; 6/65 – 9% vs. 6/15 – 40%) were significant (p = 0.0035 and p = 0.0091, respectively, χ2 test). In conclusion, apparently frequent CR and AMR coexistence demonstrated in this preliminary study warrants further investigation in this field. PMID:26336395

  9. Do behavioral responses mediate or moderate the relation between cardiovascular reactivity to stress and parental history of hypertension?

    PubMed

    Frazer, Nicole L; Larkin, Kevin T; Goodie, Jeffrey L

    2002-05-01

    To examine whether differences in behavioral responses to stress mediated or moderated the relation between cardiovascular response to stress and parental history of hypertension, 64 healthy undergraduates-16 men with hypertensive parents (PH+), 16 men without hypertensive parents (PH-), 16 PH+ women, and 16 PH- women-participated in a mental arithmetic task, mirror tracing task, and 2 interpersonal role plays. PH+ participants exhibited higher resting heart rates than PH- participants and higher resting systolic blood pressures (SBPs) than PH- women. PH+ participants exhibited greater SBP responses to tasks and engaged in more negative verbal and nonverbal behavior across tasks than PH- counterparts. Differences in behavioral responding neither mediated nor moderated the observed relation between parental history status and SBP response to stress.

  10. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    PubMed Central

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units. PMID:27800206

  11. Potent inhibition of peroxynitrite-induced DNA strand breakage by ethanol: possible implications for ethanol-mediated cardiovascular protection.

    PubMed

    Cao, Zhuoxiao; Li, Yunbo

    2004-07-01

    Epidemiological studies have conclusively demonstrated that moderate consumption of ethanol is causally associated with a significant reduction in cardiovascular events. However, the exact mechanisms underlying the ethanol-mediated cardiovascular protection remain to be elucidated. Because peroxynitrite has been extensively implicated in the pathogenesis of various forms of cardiovascular disorders via its cytotoxic effects, this study was undertaken to investigate if ethanol could inhibit peroxynitrite-induced DNA strand breaks, a critical event leading to peroxynitrite-elicited cytotoxicity. Toward this goal, phiX-174 RF I plasmid DNA was used as an in vitro model to determine the protective effects of ethanol on peroxynitrite-induced DNA strand breaks. Incubation of phiX-174 plasmid DNA with the peroxynitrite generator, 3-morpholinosydnonimine (SIN-1) led to the formation of both single- and double-stranded DNA breaks in a concentration- and time-dependent fashion. The presence of ethanol at concentrations ranging from 0.01 to 1% (w/v) resulted in a significant inhibition of SIN-1-induced DNA strand breaks. Ethanol also showed inhibitory effects on SIN-1-induced DNA strand breakage in the presence of bicarbonate. The inhibition of SIN-1-induced DNA strand breaks by ethanol exhibited a concentration-dependent manner. Notably, a marked inhibition of SIN-1-elicited DNA strand breaks was observed with 0.01% ethanol. Ethanol at 0.01-1% was unable to affect SIN-1-mediated oxygen consumption, indicating that ethanol did not affect the auto-oxidation of SIN-1 to form peroxynitrite. Furthermore, incubation of the plasmid DNA with authentic peroxynitrite resulted in a significant formation of DNA strand breaks, which could be dramatically inhibited by the presence of 0.02-0.1% ethanol. Taken together, this study demonstrates for the first time that ethanol at physiologically relevant concentrations can potently inhibit peroxynitrite-induced DNA strand breakage. In view of

  12. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence.

    PubMed

    Sellarés, J; de Freitas, D G; Mengel, M; Reeve, J; Einecke, G; Sis, B; Hidalgo, L G; Famulski, K; Matas, A; Halloran, P F

    2012-02-01

    We prospectively studied kidney transplants that progressed to failure after a biopsy for clinical indications, aiming to assign a cause to every failure. We followed 315 allograft recipients who underwent indication biopsies at 6 days to 32 years posttransplant. Sixty kidneys progressed to failure in the follow-up period (median 31.4 months). Failure was rare after T-cell-mediated rejection and acute kidney injury and common after antibody-mediated rejection or glomerulonephritis. We developed rules for using biopsy diagnoses, HLA antibody and clinical data to explain each failure. Excluding four with missing information, 56 failures were attributed to four causes: rejection 36 (64%), glomerulonephritis 10 (18%), polyoma virus nephropathy 4 (7%) and intercurrent events 6 (11%). Every rejection loss had evidence of antibody-mediated rejection by the time of failure. Among rejection losses, 17 of 36 (47%) had been independently identified as nonadherent by attending clinicians. Nonadherence was more frequent in patients who progressed to failure (32%) versus those who survived (3%). Pure T-cell-mediated rejection, acute kidney injury, drug toxicity and unexplained progressive fibrosis were not causes of loss. This prospective cohort indicates that many actual failures after indication biopsies manifest phenotypic features of antibody-mediated or mixed rejection and also underscores the major role of nonadherence.

  13. Dietary potassium: a key mediator of the cardiovascular response to dietary sodium chloride.

    PubMed

    Kanbay, Mehmet; Bayram, Yeter; Solak, Yalcin; Sanders, Paul W

    2013-01-01

    Potassium and sodium share a yin/yang relationship in the regulation of blood pressure (BP). BP is directly associated with the total body sodium and negatively correlated with the total body potassium. Epidemiologic, experimental, and clinical studies have shown that potassium is a significant regulator of BP and further improves cardiovascular outcomes. Hypertensive cardiovascular damage, stroke, and stroke-related death are accelerated by salt intake but might be curbed by increasing dietary potassium intake. The antihypertensive effect of potassium supplementation appears to occur through several mechanisms that include regulation of vascular sensitivity to catecholamines, promotion of natriuresis, limiting plasma renin activity, and improving endothelial function. In the absence of chronic kidney disease, the combined evidence suggests that a diet rich in potassium content serves a vasculoprotective function, particularly in the setting of salt-sensitive hypertension and prehypertension.

  14. Activation of the central histaminergic system mediates arachidonic-acid-induced cardiovascular effects.

    PubMed

    Altinbas, Burcin; Topuz, Bora Burak; İlhan, Tuncay; Yilmaz, Mustafa Sertac; Erdost, Hatice; Yalcin, Murat

    2014-08-01

    The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague-Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3-H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions.

  15. Transplantation tolerance.

    PubMed

    Salisbury, Emma M; Game, David S; Lechler, Robert I

    2014-12-01

    Although transplantation has been a standard medical practice for decades, marked morbidity from the use of immunosuppressive drugs and poor long-term graft survival remain important limitations in the field. Since the first solid organ transplant between the Herrick twins in 1954, transplantation immunology has sought to move away from harmful, broad-spectrum immunosuppressive regimens that carry with them the long-term risk of potentially life-threatening opportunistic infections, cardiovascular disease, and malignancy, as well as graft toxicity and loss, towards tolerogenic strategies that promote long-term graft survival. Reports of "transplant tolerance" in kidney and liver allograft recipients whose immunosuppressive drugs were discontinued for medical or non-compliant reasons, together with results from experimental models of transplantation, provide the proof-of-principle that achieving tolerance in organ transplantation is fundamentally possible. However, translating the reconstitution of immune tolerance into the clinical setting is a daunting challenge fraught with the complexities of multiple interacting mechanisms overlaid on a background of variation in disease. In this article, we explore the basic science underlying mechanisms of tolerance and review the latest clinical advances in the quest for transplantation tolerance. PMID:24213880

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

    PubMed

    Ming, Yingzi; Hu, Juan; Luo, Qizhi; Ding, Xiang; Luo, Weiguang; Zhuang, Quan; Zou, Yizhou

    2015-01-01

    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.

  17. Amygdalar neuronal activity mediates the cardiovascular responses evoked from the dorsolateral periaqueductal gray in conscious rats.

    PubMed

    de Abreu, A R; Abreu, A R; Santos, L T; de Souza, A A; da Silva, L G; Chianca, D A; de Menezes, R C

    2015-01-22

    There is ample evidence that both lateral/dorsolateral periaqueductal gray (l/dlPAG) and basolateral amygdala (BLA) are essential for the regulation of the autonomic responses evoked during innate reactions to threatening stimuli. However, it is not well established to what extent the BLA regulates the upstream functional connection from the l/dlPAG. Here we evaluated the role of the BLA and its glutamatergic receptors in the cardiovascular responses induced by l/dlPAG stimulation in rats. We examined the influence of acute inhibition of the BLA, unilaterally, by injecting muscimol on the cardiovascular responses evoked by the injection of N-methyl D-aspartate (NMDA) into the l/dlPAG. We also evaluated the role of BLA ionotropic glutamate receptors in these responses by injecting antagonists of NMDA and AMPA/kainate receptor subtypes into the BLA. Our results show that the microinjection of NMDA in the BLA increased the mean arterial pressure (MAP) and heart rate (HR). Injection of NMDA into the l/dlPAG caused similar increases in these variables, which was prevented by the prior injection of muscimol, a GABAA agonist, into the BLA. Moreover, injection of glutamatergic antagonists (2-amino-5-phosphonopentanoate (AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) into the BLA reduced the increase in MAP and HR induced by l/dlPAG activation. Finally, the inhibition of the central amygdala neurons failed to reduce the cardiovascular changes induced by l/dlPAG activation. These results indicate that physiological responses elicited by l/dlPAG activation require the neuronal activity in the BLA. This ascending excitatory pathway from the l/dlPAG to the BLA might ensure the expression of the autonomic component of the defense reaction. PMID:25451289

  18. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation

    NASA Astrophysics Data System (ADS)

    Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T.; Darnell, Max C.; Desai, Rajiv M.; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N.; Mooney, David J.

    2015-12-01

    The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel’s elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel’s elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.

  19. Immunosuppressive Therapy in Immune-Mediated Liver Disease in the Non-Transplanted Patient

    PubMed Central

    Abhyankar, Anita; Tapper, Elliot; Bonder, Alan

    2013-01-01

    Autoimmune liver disease management goals are primarily slowing disease progression and symptomatic treatment. There are few options for curative medical management other than transplant for a spectrum of autoimmune liver disease that encompasses autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis as well as their overlap syndromes. These diseases are managed primarily with immunosuppressive therapy. Herein, we review the current literature, detailing the promise and pitfalls of the recommended immunosuppressive therapy for these challenging diseases. PMID:24380894

  20. Immunosuppressive therapy in immune-mediated liver disease in the non-transplanted patient.

    PubMed

    Abhyankar, Anita; Tapper, Elliot; Bonder, Alan

    2013-01-01

    Autoimmune liver disease management goals are primarily slowing disease progression and symptomatic treatment. There are few options for curative medical management other than transplant for a spectrum of autoimmune liver disease that encompasses autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis as well as their overlap syndromes. These diseases are managed primarily with immunosuppressive therapy. Herein, we review the current literature, detailing the promise and pitfalls of the recommended immunosuppressive therapy for these challenging diseases. PMID:24380894

  1. Human amniotic epithelial cells induce localized cell-mediated immune privilege in vitro: implications for pancreatic islet transplantation.

    PubMed

    Qureshi, Khalid M; Oliver, Robert J; Paget, Michelle B; Murray, Hilary E; Bailey, Clifford J; Downing, Richard

    2011-01-01

    Chronic systemic immunosuppression in cell replacement therapy restricts its clinical application. This study sought to explore the potential of cell-based immune modulation as an alternative to immunosuppressive drug therapy in the context of pancreatic islet transplantation. Human amniotic epithelial cells (AEC) possess innate anti-inflammatory and immunosuppressive properties that were utilized to create localized immune privilege in an in vitro islet cell culture system. Cellular constructs composed of human islets and AEC (islet/AEC) were bioengineered under defined rotational cell culture conditions. Insulin secretory capacity was validated by glucose challenge and immunomodulatory potential characterized using a peripheral blood lymphocyte (PBL) proliferation assay. Results were compared to control constructs composed of islets or AEC cultured alone. Studies employing AEC-conditioned medium examined the role of soluble factors, and fluorescence immunocytochemistry was used to identify putative mediators of the immunosuppressive response in isolated AEC monocultures. Sustained, physiologically appropriate insulin secretion was observed in both islets and islet/AEC constructs. Activation of resting PBL proliferation occurred on exposure to human islets alone but this response was significantly (p < 0.05) attenuated by the presence of AEC and AEC-conditioned medium. Mitogen (phytohaemagglutinin, 5 μg/ml)-induced PBL proliferation was sustained on contact with isolated islets but abrogated by AEC, conditioned medium, and the islet/AEC constructs. Immunocytochemical analysis of AEC monocultures identified a subpopulation of cells that expressed the proapoptosis protein Fas ligand. This study demonstrates that human islet/AEC constructs exhibit localized immunosuppressive properties with no impairment of β-cell function. The data suggest that transplanted islets may benefit from the immune privilege status conferred on them as a consequence of their close

  2. Toll-like receptor 4 in experimental kidney transplantation: early mediator of endogenous danger signals.

    PubMed

    Bergler, Tobias; Hoffmann, Ute; Bergler, Elisabeth; Jung, Bettina; Banas, Miriam C; Reinhold, Stephan W; Krämer, Bernhard K; Banas, Bernhard

    2012-01-01

    The role of toll-like receptors (TLRs) has been described in the pathogenesis of renal ischemia/reperfusion injury, but data on the expression and function of TLR4 during renal allograft damage are still scarce. We analyzed the expression of TLR4 in an experimental rat model 6 and 28 days after allogeneic kidney transplantation in comparison to control rats and rats after syngeneic transplantation. On day 6, a significant induction in TLR4 expression--restricted to the glomerular compartment--was found in acute rejecting allografts only. TLR4 expression strongly correlated with renal function, and TLR4 induction was accompanied by a significant increase in CC chemokine expression within the graft as well as in urinary CC chemokine excretion. TLR4 induction may be caused by an influx of macrophages as well as TLR4-expressing intrinsic renal cells. Fibrinogen deposition in renal allografts correlated with renal TLR4 expression and may act as a potent stimulator of chemokine release via TLR4 activation. This study provides, for the first time, data about the precise intrarenal localization and TLR4 induction after experimental kidney transplantation. It supports the hypothesis that local TLR4 activation by endogenous ligands may be one pathological link from unspecific primary allograft damage to subsequent chemokine release, infiltration and activation of immune cells leading to deterioration of renal function and induction of renal fibrosis. PMID:23171961

  3. Modulation of HCV reinfection after orthotopic liver transplantation by fibroblast growth factor-2 and other non-interferon mediators

    PubMed Central

    Van, Nguyen Dinh; Falk, Christine S; Sandmann, Lisa; Vondran, Florian W R; Helfritz, Fabian; Wedemeyer, Heiner; Manns, Michael P; Ciesek, Sandra; von Hahn, Thomas

    2016-01-01

    Objective In HCV infected individuals graft infection occurs shortly after orthotopic liver transplantation (OLT). We aimed to describe the composition of the inflammatory response at this time, how it affects the HCV replication cycle and identify novel proviral and antiviral factors. Design We used a Luminex assay to quantify 50 inflammatory mediators in sera before and shortly after OLT. In vitro grown HCV based on the JFH-1 isolate were used to characterise the effects of patient sera and individual mediators on HCV. Results Although the mediator composition is highly variable between individuals, sera drawn immediately post-OLT significantly enhance HCV infectivity compared with control sera from before OLT in about half of the cases. Among 27 non-interferon inflammatory mediators fibroblast growth factor (FGF)-2 stood out as it enhanced HCV RNA replication and release of infectious particles. The effect was concentration-dependent and detectable in dividing and non-dividing cells. Moreover, pharmacological inhibition of FGF-2 receptor signalling abrogated the enhancing effect of FGF-2 and inhibited HCV replication in the absence of serum FGF-2 suggesting that HCV replication is dependent on basal activation of the FGF-2 triggered signalling pathway. Finally, in individuals with chronic HCV infection with high viral load, serum FGF-2 was significantly higher compared with those with low viral load. Conclusions Although no single mediator may account for this effect, serum shortly post-OLT enhances HCV infection. FGF-2 is a novel endogenous driver of HCV replication and a potential therapeutic target. PMID:25800783

  4. Molecular mechanisms mediating mitochondrial dynamics and mitophagy and their functional roles in the cardiovascular system.

    PubMed

    Ikeda, Yoshiyuki; Shirakabe, Akihiro; Brady, Christopher; Zablocki, Daniela; Ohishi, Mitsuru; Sadoshima, Junichi

    2015-01-01

    Mitochondria are essential organelles that produce the cellular energy source, ATP. Dysfunctional mitochondria are involved in the pathophysiology of heart disease, which is associated with reduced levels of ATP and excessive production of reactive oxygen species. Mitochondria are dynamic organelles that change their morphology through fission and fusion in order to maintain their function. Fusion connects neighboring depolarized mitochondria and mixes their contents to maintain membrane potential. In contrast, fission segregates damaged mitochondria from intact ones, where the damaged part of mitochondria is subjected to mitophagy whereas the intact part to fusion. It is generally believed that mitochondrial fusion is beneficial for the heart, especially under stress conditions, because it consolidates the mitochondria's ability to supply energy. However, both excessive fusion and insufficient fission disrupt the mitochondrial quality control mechanism and potentiate cell death. In this review, we discuss the role of mitochondrial dynamics and mitophagy in the heart and the cardiomyocytes therein, with a focus on their roles in cardiovascular disease. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".

  5. Granulocyte-macrophage colony-stimulating factor dependent monocyte-mediated cytotoxicity post-autologous bone marrow transplantation.

    PubMed

    Nagler, A; Shur, I; Barak, V; Fabian, I

    1996-08-01

    We investigated the in vitro antitumor activity of monocytes derived from autologous bone marrow transplanted (ABMT) patients treated in vivo with granulocyte-macrophage colony-stimulating factor (GM-CSF). Thirty-four patients (17 female, 17 male), median age 42 (range 3-57) years, were enrolled in the study. Fourteen patients were diagnosed with non-Hodgkin's lymphoma (NHL), eight with Hodgkin's disease (HD), nine with breast cancer and three with neuroblastoma. Six patients who did not receive GM-CSF post-ABMT served as controls. We assessed cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), expression of the activation antigen CD16, and cytokine production by an enriched population of monocytes (> 90% CD+14) pre-, during and post-GM-CSF administration. Within the group of patients receiving treatment, ADCC was significantly higher during in vivo GM-CSF administration than post-therapy (P < 0.05) and in 50% of these patients, ADCC increased during in vivo GM-CSF administration over pretreatment values. In addition, in vivo GM-CSF administration caused the monocytes to secrete elevated levels of tumor necrosis factor-alpha (TNF-alpha) and GM-CSF (P < 0.05). We conclude that GM-CSF augments monocyte-mediated cytotoxicity post-ABMT, and therefore may have a role in controlling minimal residual disease post-transplant.

  6. PCL-PDMS-PCL copolymer-based microspheres mediate cardiovascular differentiation from embryonic stem cells

    NASA Astrophysics Data System (ADS)

    Song, Liqing

    Poly-epsilon-caprolactone (PCL) based copolymers have received much attention as drug or growth factor delivery carriers and tissue engineering scaffolds due to their biocompatibility, biodegradability, and tunable biophysical properties. Copolymers of PCL and polydimethylsiloxane (PDMS) also have shape memory behaviors and can be made into thermoresponsive shape memory polymers for various biomedical applications such as smart sutures and vascular stents. However, the influence of biophysical properties of PCL-PDMS-PCL copolymers on stem cell lineage commitment is not well understood. In this study, PDMS was used as soft segments of varying length to tailor the biophysical properties of PCL-based co-polymers. While low elastic modulus (<10 kPa) of the tri-block copolymer PCL-PDMS-PCL affected cardiovascular differentiation of embryonic stem cells, the range of 60-100 MPa PCL-PDMS-PCL showed little influence on the differentiation. Then different size (30-140 mum) of microspheres were fabricated from PCL-PDMS-PCL copolymers and incorporated within embryoid bodies (EBs). Mesoderm differentiation was induced using bone morphogenetic protein (BMP)-4 for cardiovascular differentiation. Differential expressions of mesoderm progenitor marker KDR and vascular markers CD31 and VE-cadherin were observed for the cells differentiated from EBs incorporated with microspheres of different size, while little difference was observed for cardiac marker alpha-actinin expression. Small size of microspheres (30 mum) resulted in higher expression of KDR while medium size of microspheres (94 mum) resulted in higher CD31 and VE-cadherin expression. This study indicated that the biophysical properties of PCL-based copolymers impacted stem cell lineage commitment, which should be considered for drug delivery and tissue engineering applications.

  7. Matrix Elasticity of Void-Forming Hydrogels Controls Transplanted Stem Cell-Mediated Bone Formation

    PubMed Central

    Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T; Darnell, Max C; Desai, Rajiv; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N; Mooney, David J.

    2015-01-01

    The effectiveness of stem-cell therapies has been hampered by cell death and limited control over fate1. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype2–4. Stem cell behavior can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials5–7, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem-cell behaviors in situ. PMID:26366848

  8. Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study.

    PubMed

    Bachelet, Thomas; Nodimar, Celine; Taupin, Jean-Luc; Lepreux, Sebastien; Moreau, Karine; Morel, Delphine; Guidicelli, Gwendaline; Couzi, Lionel; Merville, Pierre

    2015-05-01

    Outcome of patients with transplant glomerulopathy (TG) is poor. Using B-cell targeting molecules represent a rational strategy to treat TG during chronic antibody-mediated rejection. In this pilot study, 21 patients with this diagnosis received four doses of intravenous immunoglobulins and two doses of rituximab (IVIG/RTX group). They were retrospectively compared with a untreated control group of 10 patients. At 24 months post-biopsy, graft survival was similar and poor between the treated and the untreated group, 47% vs. 40%, respectively, p = 0.69. This absence of response of IVIG/RTX treatment was observed, regardless the phenotype of TG. Baseline estimated glomerular filtration rate (eGFR) and decline in eGFR during the first six months after the treatment were risk factors associated with 24-month graft survival. The IVIG/RTX therapy had a modest effect on the kinetics of donor-specific alloantibodies at M24, compared to the untreated group, not associated with an improvement in graft survival. The mean number of adverse events per patient was higher in the IVIG/RTX group than in the control group (p = 0.03). Taken together, IVIG/RTX treatment for severe TG during chronic antibody-mediated rejection does not seem to change the natural history of TG and is associated with a high incidence of adverse events.

  9. Characterizing the Mechanistic Pathways of the Instant Blood-Mediated Inflammatory Reaction in Xenogeneic Neonatal Islet Cell Transplantation

    PubMed Central

    Liuwantara, David; Chew, Yi Vee; Favaloro, Emmanuel J.; Hawkes, Joanne M.; Burns, Heather L.; O'Connell, Philip J.; Hawthorne, Wayne J.

    2016-01-01

    Introduction The instant blood-mediated inflammatory reaction (IBMIR) causes major loss of islets after transplantation and consequently represents the initial barrier to survival of porcine neonatal islet cell clusters (NICC) after xenotransplantation. Methods This study used novel assays designed to characterize the various immunologic components responsible for xenogeneic IBMIR to identify initiators and investigate processes of IBMIR-associated coagulation, complement activation and neutrophil infiltration. The IBMIR was induced in vitro by exposing NICC to platelet-poor or platelet-rich human plasma or isolated neutrophils. Results We found that xenogeneic IBMIR was characterized by rapid, platelet-independent thrombin generation, with addition of platelets both accelerating and exacerbating this response. Platelet-independent complement activation was observed as early as 30 minutes after NICC exposure to plasma. However, membrane attack complex formation was not observed in NICC histopathology sections until after 60 minutes. We demonstrated for the first time that NICC-mediated complement activation was necessary for neutrophil activation in the xenogeneic IBMIR setting. Finally, using the Seahorse extracellular flux analyzer, we identified substantial loss of islet function (up to 40%) after IBMIR with surviving NICC showing evidence of mitochondrial damage. Conclusions This study used novel assays to describe multiple key pathways by which xenogeneic IBMIR causes islet destruction, allowing further refinement of future interventions aimed at resolving the issue of IBMIR in xenotransplantation. PMID:27500267

  10. Cardiovascular actions of DOPA mediated by the gene product of ocular albinism 1.

    PubMed

    Goshima, Yoshio; Nakamura, Fumio; Masukawa, Daiki; Chen, Sandy; Koga, Motokazu

    2014-01-01

    l-3,4-Dihydroxyphenylalanine (DOPA) is the metabolic precursor of dopamine, and the single most effective agent in the treatment of Parkinson's disease. One problem with DOPA therapy for Parkinson's disease is its cardiovascular side effects including hypotension and syncope, the underlying mechanisms of which are largely unknown. We proposed that DOPA is a neurotransmitter in the central nervous system, but specific receptors for DOPA had not been identified. Recently, the gene product of ocular albinism 1 (OA1) was shown to possess DOPA-binding activity. It was unknown, however, whether or not OA1 is responsible for the actions of DOPA itself. Immunohistochemical examination revealed that OA1 was expressed in the nucleus tractus solitarii (NTS). OA1-positive cells adjacent to tyrosine hydroxylase-positive cell bodies and nerve fibers were detected in the depressor sites of the NTS. OA1 knockdown using oa1-specific shRNA-adenovirus vectors in the NTS reduced the expression levels of OA1 in the NTS. The prior injection of the shRNA against OA1 suppressed the depressor and bradycardic responses to DOPA but not to glutamate in the NTS of anesthetized rats. Thus OA-1 is a functional receptor of DOPA in the NTS, which warrants reexamination of the mechanisms for the therapeutic and untoward actions of DOPA. PMID:25185585

  11. Production of transgenic Xenopus laevis by restriction enzyme mediated integration and nuclear transplantation.

    PubMed

    Amaya, Enrique; Kroll, Kristen

    2010-01-01

    Stable integration of cloned gene products into the Xenopus genome is necessary to control the time and place of expression, to express genes at later stages of embryonic development, and to define how enhancers and promoters regulate gene expression within the embryo. The protocol demonstrated here can be used to efficiently produce transgenic Xenopus laevis embryos. This transgenesis approach involves three parts: 1. Sperm nuclei are isolated from adult X. laevis testis by treatment with lysolecithin, which permeabilizes the sperm plasma membrane. 2. Egg extract is prepared by low speed centrifugation, addition of calcium to cause the extract to progress to interphase of the cell cycle, and a high-speed centrifugation to isolate interphase cytosol. 3. Nuclear transplantation: the nuclei and extract are combined with the linearized plasmid DNA to be introduced as the transgene and a small amount of restriction enzyme. During a short reaction, egg extract partially decondenses the sperm chromatin and the restriction enzyme generates chromosomal breaks that promote recombination of the transgene into the genome. The treated sperm nuclei are then transplanted into unfertilized eggs. Integration of the transgene usually occurs prior to the first embryonic cleavage such that the resulting embryos are not chimeric. These embryos can be analyzed without any need to breed to the next generation, allowing for efficient and rapid generation of transgenic embryos for analyses of promoter and gene function. Adult X. laevis resulting from this procedure also propagate the transgene through the germline and can be used to generate lines of transgenic animals for multiple purposes. PMID:20811326

  12. Outcome of subclinical antibody-mediated rejection in kidney transplant recipients with preformed donor-specific antibodies.

    PubMed

    Loupy, A; Suberbielle-Boissel, C; Hill, G S; Lefaucheur, C; Anglicheau, D; Zuber, J; Martinez, F; Thervet, E; Méjean, A; Charron, D; Duong van Huyen, J P; Bruneval, P; Legendre, C; Nochy, D

    2009-11-01

    This study describes clinical relevance of subclinical antibody-mediated rejection (SAMR) in a cohort of 54 DSA-positive kidney transplant recipients receiving a deceased donor. In 3 months screening biopsies, 31.1% of patients met the criteria of SAMR. A total of 48.9% had an incomplete form of SAMR (g+/ptc+/C4d-negative) whereas 20% had no humoral lesions. Patients with SAMR at 3 months had at 1 year: a higher C4d score, ptc score, and arteriosclerosis score, higher rate of IFTA (100% vs. 33.3%, p < 0.01) and a higher rate of transplant glomerulopathy (43% vs. 0%, p = 0.02) compared to patients without 3-month SAMR. Patients with SAMR at 3 months exhibited at 1 year a higher class II MFImax-DSA and a lower mGFR compared to patients without SAMR (39.2 +/- 13.9 vs. 61.9 +/- 19.2 mL/min/1.73 m(2) respectively, p < 0.01). The group of patients with C4d-negative SAMR at 3 months developed more ptc and IFTA lesions, and lower GFR at 1 year in comparison to biopsies without humoral lesions. SAMR is a frequent entity in KTR with preexisting DSAs and promotes subsequent GFR impairment and development of chronic AMR. C4d-negative SAMR patients displayed an intermediate course between the no-SAMR group and the C4d+ SAMR group. Screening biopsies may be useful to recognize patients more likely to develop SAMR. PMID:19775320

  13. Post-transplant dyslipidemia: Mechanisms, diagnosis and management

    PubMed Central

    Agarwal, Arnav; Prasad, G V Ramesh

    2016-01-01

    Post-transplant dyslipidemia is highly prevalent and presents unique management challenges to the clinician. The two major outcomes to consider with post-transplant therapies for dyslipidemia are preserving or improving allograft function, and reducing cardiovascular risk. Although there are other cardiovascular risk factors such as graft dysfunction, hypertension, and diabetes, attention to dyslipidemia is warranted because interventions for dyslipidemia have an impact on reducing cardiac events in clinical trials specific to the transplant population. Dyslipidemia is not synonymous with hyperlipidemia. Numerous mechanisms exist for the occurrence of post-transplant dyslipidemia, including those mediated by immunosuppressive drug therapy. Statin therapy has received the most attention in all solid organ transplant recipient populations, although the effect of proper dietary advice and adjuvant pharmacological and non-pharmacological agents should not be dismissed. At all stages of treatment appropriate monitoring strategies for side effects should be implemented so that the benefits from these therapies can be achieved. Clinicians have a choice when there is a conflict between various transplant society and lipid society guidelines for therapy and targets. PMID:27011910

  14. Beta-adrenergic receptor mediated inflammation control by monocytes is associated with blood pressure and risk factors for cardiovascular disease.

    PubMed

    Hong, Suzi; Dimitrov, Stoyan; Cheng, Tiefu; Redwine, Laura; Pruitt, Christopher; Mills, Paul J; Ziegler, Michael G; Green, J Michael; Shaikh, Farah; Wilson, Kathleen

    2015-11-01

    Overwhelming data indicate that individuals with even mildly elevated blood pressure (BP) are at great risk for developing clinical hypertension and future cardiovascular disease (CVD). There remains a lack of consensus regarding treatment strategies for mildly elevated BP, termed prehypertension, and the knowledge of pathophysiology and mechanisms of its clinical outcomes remains limited. Our primary aim was to investigate βAR-mediated inflammation control (BARIC) responses of blood monocytes to isoproterenol (Iso) in relation to BP and CVD risk factors, including obesity, depressive mood, fasting glucose, triglycerides, and cholesterol levels in the 64 prehypertensive compared to 84 individuals with normal BP. BARIC was determined by measuring the degree of inhibition in lipopolysaccharides-stimulated monocytic intracellular TNF production by ex vivo Iso treatment (10(-8)M). Depressive mood was assessed by Beck Depression Inventory (BDI). Fasting metabolic and lipid panels were assessed, and plasma levels of inflammatory cytokines TNF, IL-1β, IL-6 were measured in a subset to confirm proinflammatory state of prehypertensive participants. Prehypertensive participants were older, heavier, included more men, and presented higher levels of fasting glucose, triglycerides, cholesterol, and plasma TNF compared to normotensive participants (p's<.05). BARIC was significantly attenuated in the prehypertensive compared to normotensive group (p<.05). BARIC was negatively associated with systolic BP, diastolic BP, age, BMI, fasting glucose, triglycerides, total and low density cholesterol levels, and somatic depressive symptoms in all participants (p's<.0001 to .05). However, among the prehypertensive individuals BARIC was positively associated with SBP even after controlling for the covariates (age, gender, race, BMI, glucose and lipid panel, somatic BDI scores) (p<.05). This differing nature of the BARIC-SBP relationship between the two BP groups may be attributed to

  15. Vasopressin and sympathetic system mediate the cardiovascular effects of the angiotensin II in the bed nucleus of the stria terminalis in rat.

    PubMed

    Nasimi, Ali; Kafami, Marzieh

    2016-07-01

    The bed nucleus of the stria terminalis (BST) is involved in cardiovascular regulation. The angiotensin II (Ang II) receptor (AT1), and angiotensinogen were found in the BST. In our previous study we found that microinjection of Ang II into the BST produced a pressor response. This study was performed to find the mechanisms mediating this response in anesthetized rats. Ang II was microinjected into the BST and the cardiovascular responses were re-tested after systemic injection of a blocker of autonomic or vasopressin V1 receptor. The ganglionic nicotinic receptor blocker, hexamethonium dichloride, attenuated the pressor response to Ang II, indicating that the cardiovascular sympathetic system is involved in the pressor effect of Ang II. A selective vasopressin V1 receptor antagonist greatly attenuated the pressor effect of Ang II, indicating that the Ang II increases the arterial pressure via stimulation of vasopressin release as well. In conclusion, in the BST, Ang II as a neurotransmitter increases blood pressure by exciting cardiovascular sympathetic system and directly or indirectly causing vasopressin to release into bloodstream by VPN. This is an interesting new finding that not only circulating Ang II but also brain Ang II makes vasopressin release.

  16. Suicide Gene-Mediated Sequencing Ablation Revealed the Potential Therapeutic Mechanism of Induced Pluripotent Stem Cell-Derived Cardiovascular Cell Patch Post-Myocardial Infarction

    PubMed Central

    Wang, Yuhua; Huang, Wei; Liang, Jialiang; Wen, Zhili; Chang, Dehua; Kang, Kai; Wang, Jiapeng; Xu, Meifeng; Millard, Ronald W.

    2014-01-01

    Abstract Aims: This study is designed to assess the protective cardiac effects after myocardial infarction (MI) of (i) cardiovascular progenitor cells (PC) differentiated directly into cardiomyocytes (CM) and endothelial cells (ECs) at the injury site, as separable from the effects of (ii) paracrine factors released from PC. Results: In vivo: bi-cell patch containing induced pluripotent stem cell (iPSC)-derived CM and EC (BIC) was transplanted onto the infarcted heart. BIC were transduced with herpes simplex virus thymidine kinase “suicide” gene driven by cardiac NCX1 or endothelial vascular endothelium-cadherin promoter. IGF-1α and VEGF levels released from ischemic tissues were significantly enhanced in the BIC patch treatment group. Heart function, infarction size, and vessel density were significantly improved after BIC patch treatment. These effects were completely abolished in the group given ganciclovir (GCV) at week 1 as a suicide gene activator, and partially abolished in the group given GCV at week 3 as compared with the untreated cell patch group. Innovation: This study was designed to distinguish between cell-based and noncell-based therapeutic effects of PC lineages after MI. PCs derived from iPSC were genetically modified to express “suicide” gene. iPSC-derived CM and EC were then ablated in situ at week 1 and 3 by intraperitoneal administration of GCV. This enabled direct assessment of the effects of iPSC transplantation on myocardial function and tissue regeneration potential. Conclusions: Data support a mechanism in which iPSC-derived cardiovascular lineages contribute directly to improved cardiac performance and attenuated remodeling. Paracrine factors provide additional support to the restoration of heart function. Antioxid. Redox Signal. 21, 2177–2191. PMID:24787391

  17. Transplant-mediated enhancement of spinal cord GABAergic inhibition reverses paclitaxel-induced mechanical and heat hypersensitivity.

    PubMed

    Bráz, João M; Wang, Xidao; Guan, Zhonghui; Rubenstein, John L; Basbaum, Allan I

    2015-06-01

    Decreased spinal cord GABAergic inhibition is a major contributor to the persistent neuropathic pain that can follow peripheral nerve injury. Recently, we reported that restoring spinal cord GABAergic signaling by intraspinal transplantation of cortical precursors of GABAergic interneurons from the embryonic medial ganglionic eminence (MGE) can reverse the mechanical hypersensitivity (allodynia) that characterizes a neuropathic pain model in the mouse. We show that MGE cell transplants are also effective against both the mechanical allodynia and the heat hyperalgesia produced in a paclitaxel-induced chemotherapy model of neuropathic pain. To test the necessity of GABA release by the transplants, we also studied the utility of transplanting MGE cells from mice with a deletion of VGAT, the vesicular GABA transporter. Transplants from these mice, in which GABA is synthesized but cannot be stored or released, had no effect on mechanical hypersensitivity or heat hyperalgesia in the paclitaxel model. Taken together, these results demonstrate the therapeutic potential of GABAergic precursor cell transplantation in diverse neuropathic pain models and support our contention that restoration of inhibitory controls through release of GABA from the transplants is their mode of action. PMID:25760475

  18. Suppression of lentivirus-mediated transgenic dendritic cells in graft-versus-host disease after allogeneic bone marrow transplantation in mice.

    PubMed

    Xu, Y J; Chen, W R; Li, D P; Song, L X; Wu, J Q; Zhang, P; Li, Z Y; Huang, Y H

    2015-01-01

    We determined whether genetically engineered immature dendritic cells (imDCs) mediated by lentiviral vectors alleviate acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) in mice. We introduced the mouse chemokine receptor 7 (Ccr7) gene into the bone marrow-derived imDCs of C57BL/6 mice to construct genetically engineered imDCs. A 1:1 mixture of bone marrow and spleen cells from the donors was injected into the recipients, which were divided into four groups: radiation, transplantation, empty vector, and transgenic imDC groups. Symptoms, clinical scores, GVHD pathological changes, and survival times and rates of recipients were recorded; secretion of IFN-γ and IL-4, and allogeneic chimerism rates were detected. The survival time of the transgenic imDC group (27.5 ± 7.55 days) was significantly longer than in the other three groups (P < 0.01). The GVHD score of the imDC group mice was significantly lower than in the transplantation and empty vector groups (P < 0.05), which meant that mice in the transgenic imDC group had the lightest pathology damage in the target organs. In the transplantation group, IFN-γ increased while IL-4 decreased. In contrast, IFN-γ decreased and IL-4 increased in both empty vector and trans-imDC groups, and the difference was significant in the latter (P < 0.01). Thirty days or more following transplantation, the allogeneic chimerism rate was still 95-100%, suggesting complete donor type implantation. Ccr7 transfection into imDCs suppressed occurrence and severity of acute GVHD after allo-BMT in mice; the mechanism might be associated with IFN-γ decrease and IL-4 increase. PMID:26436385

  19. Analysis of Host-Mediated Repair Mechanisms after Human CNS-Stem Cell Transplantation for Spinal Cord Injury: Correlation of Engraftment with Recovery

    PubMed Central

    Hooshmand, Mitra J.; Sontag, Christopher J.; Uchida, Nobuko; Tamaki, Stan

    2009-01-01

    Background Human central nervous system-stem cells grown as neurospheres (hCNS-SCns) self-renew, are multipotent, and have potential therapeutic applications following trauma to the spinal cord. We have previously shown locomotor recovery in immunodeficient mice that received a moderate contusion spinal cord injury (SCI) and hCNS-SCns transplantation 9 days post-injury (dpi). Engrafted hCNS-SCns exhibited terminal differentiation to myelinating oligodendrocytes and synapse-forming neurons. Further, selective ablation of human cells using Diphtheria toxin (DT) abolished locomotor recovery in this paradigm, suggesting integration of human cells within the mouse host as a possible mechanism for the locomotor improvement. However, the hypothesis that hCNS-SCns could alter the host microenvironment as an additional or alternative mechanism of recovery remained unexplored; we tested that hypothesis in the present study. Methods and Findings Stereological quantification of human cells using a human-specific cytoplasmic marker demonstrated successful cell engraftment, survival, migration and limited proliferation in all hCNS-SCns transplanted animals. DT administration at 16 weeks post-transplant ablated 80.5% of hCNS-SCns. Stereological quantification for lesion volume, tissue sparing, descending serotonergic host fiber sprouting, chondroitin sulfate proteoglycan deposition, glial scarring, and angiogenesis demonstrated no evidence of host modification within the mouse spinal cord as a result of hCNS-SCns transplantation. Biochemical analyses supplemented stereological data supporting the absence of neural stem-cell mediated host repair. However, linear regression analysis of the number of engrafted hCNS-SCns vs. the number of errors on a horizontal ladder beam task revealed a strong correlation between these variables (r = −0.78, p<0.05), suggesting that survival and engraftment were directly related to a quantitative measure of recovery. Conclusions Altogether

  20. Bone marrow transplant

    MedlinePlus

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

  1. Blunted GABA-mediated inhibition within the dorsomedial hypothalamus potentiates the cardiovascular response to emotional stress in rats fed a high-fat diet.

    PubMed

    Abreu, A R; de Abreu, A R; Santos, L T; de Souza, A A; da Silva, L G; Chianca, D A; de Menezes, R C

    2014-03-14

    Rats fed a high-fat diet (HFD) present an exaggerated endocrine response to stress conditions, which, like obesity, show a high correlation with cardiovascular diseases. Meanwhile the GABAergic neurotransmission within the dorsomedial hypothalamus (DMH) is involved in the regulation of the physiological responses during emotional stress. Here we evaluated the influence of obesity, induced by a HFD, on the cardiovascular responses induced by air jet stress in rats, and the role of the GABAergic tonus within the DMH in these changes. Our results showed that consumption of a HFD (45% w/w fat) for 9 weeks induced obesity and increases in baseline mean arterial pressure (MAP) and heart rate (HR). Moreover, obesity potentiated stress responsiveness, evidenced by the greater changes in MAP and HR induced by stress in obese rats. The injection of muscimol into the DMH reduced the maximal increases in HR and MAP induced by stress in both groups; however, the reduction in the maximal increases in MAP in the HFD group was less pronounced. Moreover, the injection of muscimol into the DMH of obese rats was less effective in reducing the stress-induced tachycardia, since the HR attained the same levels at the end of the stress paradigm as after the vehicle injection. Injection of bicuculline into DMH induced increases in MAP and HR in both groups. Nevertheless, obesity shortened the tachycardic response to bicuculline injection. These data show that obesity potentiates the cardiovascular response to stress in rats due to an inefficient GABAA-mediated inhibition within the DMH.

  2. Cardiovascular health outcomes of Latinos in the Affordable Housing as an Obesity Mediating Environment (AHOME) study: a study of rental assistance use.

    PubMed

    Chambers, Earle C; Rosenbaum, Emily

    2014-06-01

    Studies have shown that households subsidized with vouchers live in higher quality units and exhibit fewer physical, mental, and social problems than do their peers living in public housing. However, none of these studies have included cardiovascular outcomes. The objective of this study was to assess if use/type of rental assistance is independently associated with poor cardiovascular health among Latino adults (ages ≥ 18) who are eligible for federal low-income rental assistance and living in the Bronx, NY. Data from the cross-sectional, Affordable Housing as an Obesity Mediating Environment study, collected over 18 months (January 2011 to August 2012) were used. The prevalence of cardiovascular disease (CVD) outcomes was determined by measured high blood pressure and self-reported heart attack and/or stroke. Type of housing status was defined as: public housing units, units subsidized by section 8 vouchers, and units unassisted by either federal program. Statistical techniques used were analysis of variance and multivariate logistic regression. The prevalence of CVD was significantly higher among public housing residents than unassisted participants even in the presence of all individual level covariates. Public housing residents also have higher levels of CVD than do section 8 participants. The prevalence of CVD was similar for unassisted and section 8 participants. These findings point to the potential for health benefits arising from housing voucher use even within a fairly delimited geographic area. PMID:24190105

  3. Protective effect of thymoquinone improves cardiovascular function, and attenuates oxidative stress, inflammation and apoptosis by mediating the PI3K/Akt pathway in diabetic rats.

    PubMed

    Liu, Hui; Liu, Hong-Yang; Jiang, Yi-Nong; Li, Nan

    2016-03-01

    Thymoquinone is the main active monomer extracted from black cumin and has anti‑inflammatory, antioxidant and anti‑apoptotic functions. However, the protective effects of thymoquinone on cardiovascular function in diabetes remain to be fully elucidated. The present study aimed to investigate the molecular mechanisms underling the beneficial effects of thymoquinone on the cardiovascular function in streptozotocin‑induced diabetes mellitus (DM) rats. Supplement thymoquinone may recover the insulin levels and body weight, inhibit blood glucose levels and reduce the heart rate in DM‑induced rats. The results indicated that the heart, liver and lung to body weight ratios, in addition to the blood pressure levels, were similar for each experimental group. Treatment with thymoquinone significantly reduced oxidative stress damage, inhibited the increased endothelial nitric oxide synthase protein expression and suppressed the elevation of cyclooxygenase‑2 levels in DM‑induced rats. In addition, thymoquinone significantly suppressed the promotion of tumor necrosis factor‑α and interleukin‑6 levels in the DM‑induced rats. Furthermore, administration of thymoquinone significantly reduced caspase‑3 activity and the promotion of phosphorylated‑protein kinase B (Akt) protein expression levels in DM‑induced rats. These results suggest that the protective effect of thymoquinone improves cardiovascular function and attenuates oxidative stress, inflammation and apoptosis by mediating the phosphatidylinositol 3‑kinase/Akt pathway in DM‑induced rats. PMID:26820252

  4. Cardiovascular health outcomes of Latinos in the Affordable Housing as an Obesity Mediating Environment (AHOME) study: a study of rental assistance use.

    PubMed

    Chambers, Earle C; Rosenbaum, Emily

    2014-06-01

    Studies have shown that households subsidized with vouchers live in higher quality units and exhibit fewer physical, mental, and social problems than do their peers living in public housing. However, none of these studies have included cardiovascular outcomes. The objective of this study was to assess if use/type of rental assistance is independently associated with poor cardiovascular health among Latino adults (ages ≥ 18) who are eligible for federal low-income rental assistance and living in the Bronx, NY. Data from the cross-sectional, Affordable Housing as an Obesity Mediating Environment study, collected over 18 months (January 2011 to August 2012) were used. The prevalence of cardiovascular disease (CVD) outcomes was determined by measured high blood pressure and self-reported heart attack and/or stroke. Type of housing status was defined as: public housing units, units subsidized by section 8 vouchers, and units unassisted by either federal program. Statistical techniques used were analysis of variance and multivariate logistic regression. The prevalence of CVD was significantly higher among public housing residents than unassisted participants even in the presence of all individual level covariates. Public housing residents also have higher levels of CVD than do section 8 participants. The prevalence of CVD was similar for unassisted and section 8 participants. These findings point to the potential for health benefits arising from housing voucher use even within a fairly delimited geographic area.

  5. The role of GαO-mediated signaling in the rostral ventrolateral medulla oblongata in cardiovascular reflexes and control of cardiac ventricular excitability.

    PubMed

    Ang, Richard; Abramowitz, Joel; Birnbaumer, Lutz; Gourine, Alexander V; Tinker, Andrew

    2016-08-01

    The heart is controlled by the sympathetic and parasympathetic limbs of the autonomic nervous system with inhibitory signaling mechanisms recruited in both limbs. The aim of this study was to determine the role of inhibitory heterotrimeric G proteins in the central nervous mechanisms underlying autonomic control of the heart and its potential role in arrhythmogenesis. Mice with conditional deletion of the inhibitory heterotrimeric G protein GαO in the presympathetic area of the rostral ventral lateral medulla (RVLM) were generated to determine the role of GαO-mediated signalling in autonomic control and electrophysiological properties of the heart. GαO deletion within the RVLM was not associated with changes in heart rate (HR) or the arterial blood pressure at rest (home cage, normal behavior). However, exposure to stressful conditions (novel environment, hypoxia, or hypercapnia) in these mice was associated with abnormal HR responses and an increased baroreflex gain when assessed under urethane anesthesia. This was associated with shortening of the ventricular effective refractory period. This phenotype was reversed by systemic beta-adrenoceptor blockade, suggesting that GαO depletion in the RVLM increases central sympathetic drive. The data obtained support the hypothesis that GαO-mediated signaling within the presympathetic circuits of the RVLM contributes to the autonomic control of the heart. GαO deficiency in the RVLM has a significant impact on cardiovascular responses to stress, cardiovascular reflexes and electrical properties of the heart. PMID:27528004

  6. Protective actions of progesterone in the cardiovascular system: potential role of membrane progesterone receptors (mPRs) in mediating rapid effects.

    PubMed

    Thomas, Peter; Pang, Yefei

    2013-06-01

    The protective functions of progesterone in the cardiovascular system have received little attention even though evidence has accumulated that progesterone lowers blood pressure, inhibits coronary hyperactivity and has powerful vasodilatory and natriuretic effects. One possible reason why potential beneficial actions of progesterone on cardiovascular functions have not been extensively studied is that divergent effects to those of progesterone have been observed in many clinical trials with synthetic progestins such as medroxyprogesterone acetate which are associated with increased risk of coronary disease. Evidence that progesterone exerts protective effects on cardiovascular functions is briefly reviewed. The finding that progesterone administration decreases blood vessel vasoconstriction in several animal models within a few minutes suggests that rapid, nongenomic progesterone mechanisms are of physiological importance in regulating vascular tone. Rapid activation of second messenger pathways by progesterone has been observed in vascular endothelial and smooth muscle cells, resulting in alterations in endothelial nitric oxide synthase (eNOS) activity and calcium influx, respectively. Both nuclear progesterone receptors (PRs) and novel membrane progesterone receptors (mPRs) are candidates for the intermediaries in these rapid, cell-surface initiated progesterone actions in endothelial and smooth muscle vascular cells. PRs have been detected in both cell types. New data are presented showing mPRα, mPRβ and mPRγ are also present in human endothelial and smooth muscle vascular cells. Preliminary evidence suggests mPRs mediate rapid progestin signaling in these endothelial cells, resulting in down-regulation of cAMP production and increased nitric oxide synthesis. The role of mPRs in progesterone regulation of cardiovascular functions warrants further investigation.

  7. Protective actions of progesterone in the cardiovascular system: potential role of membrane progesterone receptors (mPRs) in mediating rapid effects.

    PubMed

    Thomas, Peter; Pang, Yefei

    2013-06-01

    The protective functions of progesterone in the cardiovascular system have received little attention even though evidence has accumulated that progesterone lowers blood pressure, inhibits coronary hyperactivity and has powerful vasodilatory and natriuretic effects. One possible reason why potential beneficial actions of progesterone on cardiovascular functions have not been extensively studied is that divergent effects to those of progesterone have been observed in many clinical trials with synthetic progestins such as medroxyprogesterone acetate which are associated with increased risk of coronary disease. Evidence that progesterone exerts protective effects on cardiovascular functions is briefly reviewed. The finding that progesterone administration decreases blood vessel vasoconstriction in several animal models within a few minutes suggests that rapid, nongenomic progesterone mechanisms are of physiological importance in regulating vascular tone. Rapid activation of second messenger pathways by progesterone has been observed in vascular endothelial and smooth muscle cells, resulting in alterations in endothelial nitric oxide synthase (eNOS) activity and calcium influx, respectively. Both nuclear progesterone receptors (PRs) and novel membrane progesterone receptors (mPRs) are candidates for the intermediaries in these rapid, cell-surface initiated progesterone actions in endothelial and smooth muscle vascular cells. PRs have been detected in both cell types. New data are presented showing mPRα, mPRβ and mPRγ are also present in human endothelial and smooth muscle vascular cells. Preliminary evidence suggests mPRs mediate rapid progestin signaling in these endothelial cells, resulting in down-regulation of cAMP production and increased nitric oxide synthesis. The role of mPRs in progesterone regulation of cardiovascular functions warrants further investigation. PMID:23357432

  8. Hair Transplants

    MedlinePlus

    ... How to Choose the Best Skin Care Products Hair Transplants What are hair transplants? In punch transplanting, a plug containing hair ... What should first be done before considering a hair transplant? Before the procedure, an ASDS doctor will ...

  9. Myeloid-Derived Suppressor Cells (MDSC) Protect Islet Transplants via B7-H1 Mediated Enhancement of T Regulatory Cells

    PubMed Central

    Chou, Hong-Shiue; Hsieh, Ching-Chuan; Charles, Ronald; Wang, Lianfu; Wagner, Timothy; Fung, John J.; Qian, Shiguang; L, Lina Lu

    2011-01-01

    Background Side effects of lifetime immunosuppression for cell transplants often outweigh the benefits, therefore, induction of transplant tolerance is needed. We have shown that cotransplantation with myeoid-derived suppressor cells (MDSC) effectively protect islet allografts from rejection without requirement of immunosuppression. This study was to investigate the underlying mechanisms. Methods MDSC were generated by addition of hepatic stellate cells (HpSC) from various stain mice into dendritic cell (DC) culture. The quality of MDSC was monitored by phenotype and function analyses. MDSC mixed with islet allografts were transplanted into diabetic recipients. T cell response was analyzed following transplant by flow and histochemical analyses, and compared to islet alone and islet/DC transplant groups. B7-H1 knockout mice were used to determine the role of B7-H1 on MDSC in regulation of T cell response. Results Cotransplantation with MDSC (not DC) effectively protected islet allografts without requirement of immunosuppression. This is associated with attenuation of CD8 T cells in the grafts and marked expansion of T regulatory (Treg) cells, which contributed to MDSC-induced T cell hyporesponsiveness. Antigen-specific Treg cells were prone to accumulate in lymphoid organs close to the grafts. Both in vitro and in vivo data demonstrated that B7-H1 was absolutely required for MDSC to exert immune regulatory activity and induction of Treg cells. Conclusion The described approach holds great clinical application potential, and may overcome the limitation of requiring chronic administration of immunosuppression in cell transplants. Understanding the underlying mechanisms will facilitate the development of this novel therapeutic strategy. PMID:22179405

  10. Cancer in the Transplant Recipient

    PubMed Central

    Chapman, Jeremy R.; Webster, Angela C.; Wong, Germaine

    2013-01-01

    Malignancy has become one of the three major causes of death after transplantation in the past decade and is thus increasingly important in all organ transplant programs. Death from cardiovascular disease and infection are both decreasing in frequency from a combination of screening, prophylaxis, aggressive risk factor management, and interventional therapies. Cancer, on the other hand, is poorly and expensively screened for; risk factors are mostly elusive and/or hard to impact on except for the use of immunosuppression itself; and finally therapeutic approaches to the transplant recipient with cancer are often nihilistic. This article provides a review of each of the issues as they come to affect transplantation: cancer before wait-listing, cancer transmission from the donor, cancer after transplantation, outcomes of transplant recipients after a diagnosis of cancer, and the role of screening and therapy in reducing the impact of cancer in transplant recipients. PMID:23818517

  11. Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane-mediated thromboxane A2 receptor activation.

    PubMed

    Bauer, Jochen; Ripperger, Anne; Frantz, Stefan; Ergün, Süleyman; Schwedhelm, Edzard; Benndorf, Ralf A

    2014-07-01

    Isoprostanes are free radical-catalysed PG-like products of unsaturated fatty acids, such as arachidonic acid, which are widely recognized as reliable markers of systemic lipid peroxidation and oxidative stress in vivo. Moreover, activation of enzymes, such as COX-2, may contribute to isoprostane formation. Indeed, formation of isoprostanes is considerably increased in various diseases which have been linked to oxidative stress, such as cardiovascular disease (CVD), and may predict the atherosclerotic burden and the risk of cardiovascular complications in the latter patients. In addition, several isoprostanes may directly contribute to the functional consequences of oxidant stress via activation of the TxA2 prostanoid receptor (TP), for example, by affecting endothelial cell function and regeneration, vascular tone, haemostasis and ischaemia/reperfusion injury. In this context, experimental and clinical data suggest that selected isoprostanes may represent important alternative activators of the TP receptor when endogenous TxA2 levels are low, for example, in aspirin-treated individuals with CVD. In this review, we will summarize the current understanding of isoprostane formation, biochemistry and (patho) physiology in the cardiovascular context.

  12. Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane-mediated thromboxane A2 receptor activation

    PubMed Central

    Bauer, Jochen; Ripperger, Anne; Frantz, Stefan; Ergün, Süleyman; Schwedhelm, Edzard; Benndorf, Ralf A

    2014-01-01

    Isoprostanes are free radical-catalysed PG-like products of unsaturated fatty acids, such as arachidonic acid, which are widely recognized as reliable markers of systemic lipid peroxidation and oxidative stress in vivo. Moreover, activation of enzymes, such as COX-2, may contribute to isoprostane formation. Indeed, formation of isoprostanes is considerably increased in various diseases which have been linked to oxidative stress, such as cardiovascular disease (CVD), and may predict the atherosclerotic burden and the risk of cardiovascular complications in the latter patients. In addition, several isoprostanes may directly contribute to the functional consequences of oxidant stress via activation of the TxA2 prostanoid receptor (TP), for example, by affecting endothelial cell function and regeneration, vascular tone, haemostasis and ischaemia/reperfusion injury. In this context, experimental and clinical data suggest that selected isoprostanes may represent important alternative activators of the TP receptor when endogenous TxA2 levels are low, for example, in aspirin-treated individuals with CVD. In this review, we will summarize the current understanding of isoprostane formation, biochemistry and (patho) physiology in the cardiovascular context. PMID:24646155

  13. Bone marrow transplant - discharge

    MedlinePlus

    Transplant - bone marrow - discharge; Stem cell transplant - discharge; Hematopoietic stem cell transplant - discharge; Reduced intensity; Non-myeloablative transplant - discharge; Mini transplant - discharge; Allogenic bone marrow transplant - ...

  14. Role of dendritic cells in cardiovascular diseases

    PubMed Central

    Zhang, Yi; Zhang, Cuihua

    2010-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells that bridge innate and adaptive immune responses. Recent work has elucidated the DC life cycle, including several important stages such as maturation, migration and homeostasis, as well as DC classification and subsets/locations, which provided etiological insights on the role of DCs in disease processes. DCs have a close relationship to endothelial cells and they interact with each other to maintain immunity. DCs are deposited in the atherosclerotic plaque and contribute to the pathogenesis of atherosclerosis. In addition, the necrotic cardiac cells induced by ischemia activate DCs by Toll-like receptors, which initiate innate and adaptive immune responses to renal, hepatic and cardiac ischemia reperfusion injury (IRI). Furthermore, DCs are involved in the acute/chronic rejection of solid organ transplantation and mediate transplant tolerance as well. Advancing our knowledge of the biology of DCs will aid development of new approaches to treat many cardiovascular diseases, including atherosclerosis, cardiac IRI and transplantation. PMID:21179302

  15. The PI3K signaling-mediated nitric oxide contributes to cardiovascular effects of angiotensin-(1-7) in the nucleus tractus solitarii of rats.

    PubMed

    Wu, Zhao-Tang; Ren, Chang-Zhen; Yang, Ya-Hong; Zhang, Ru-Wen; Sun, Jia-Cen; Wang, Yang-Kai; Su, Ding-Feng; Wang, Wei-Zhong

    2016-01-30

    Angiotensin-1-7 [Ang-(1-7)], acting via the Mas receptor in the central nervous system, is involved in the regulation of cardiovascular activity. Nitric oxide (NO) is implicated as an important modulator in the nucleus tractus solitarii (NTS), a key region involved in control of cardiovascular activity. The aim of the present study was to determine the role of phosphatidylinositol 3-kinase (PI3K) signaling in mediating the effect of Ang-(1-7) on NO generation in the NTS. In Sprague-Dawley rats, acute injection of Ang-(1-7) into the NTS significantly increased NO generation and neuronal/endothelial NO synthase (n/eNOS) activity, which were abolished by the selective Mas receptor antagonist d-Alanine-[Ang-(1-7)] (A-779), the PI3K inhibitor LY294002, or the Akt inhibitor triciribine (TCN). Western blotting analysis further demonstrated that Ang-(1-7) significantly increased levels of Akt/NOS phosphorylation in the NTS, and Ang-(1-7)-induced e/nNOS phosphorylation was antagonized by LY294002 or TCN. Furthermore, gene knockdown of PI3K by lentivirus containing small hairpin RNA in the NTS prevented the Ang-(1-7)-induced increases in NOS/Akt phosphorylation and NO production. The physiological (in vivo) experiments showed that pretreatment with the NOS inhibitor l-NAME, LY294002, or TCN abolished the decreases in blood pressure, heart rate, and renal sympathetic nerve activity induced by Ang-(1-7) injected into the NTS. Our findings suggest that nitric oxide release meditated by the Mas-PI3K-NOS signaling pathway is involved in the cardiovascular effects of Ang-(1-7) in the NTS.

  16. Total Body Irradiation Is Permissive for Mesenchymal Stem Cell-Mediated New Bone Formation Following Local Transplantation

    PubMed Central

    Herberg, Samuel; Kondrikova, Galina; Hussein, Khaled A.; Periyasamy-Thandavan, Sudharsan; Johnson, Maribeth H.; Elsalanty, Mohammed E.; Shi, Xingming; Hamrick, Mark W.; Isales, Carlos M.

    2014-01-01

    Skeletal injury is a major clinical challenge accentuated by the decrease of bone marrow-derived mesenchymal stem/stromal cells (BMSCs) with age or disease. Numerous experimental and clinical studies have revealed that BMSCs hold great promise for regenerative therapies due to their direct osteogenic potential and indirect trophic/paracrine actions. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in modulating the host response to the injury. Common problems with BMSC therapy include poor cell engraftment, which can be addressed by total body irradiation (TBI) prior to transplantation. In this study, we tested the hypothesis that direct tibial transplantation of BMSCs drives endogenous bone formation in a dose-dependent manner, which is enhanced by TBI, and investigated the potential role of SDF-1 in facilitating these events. We found that TBI is permissive for transplanted BMSCs to engraft and contribute to new bone formation. Bone marrow (BM) interstitial fluid analysis revealed no differences of SDF-1 splice variants in irradiated animals compared to controls, despite the increased mRNA and protein levels expressed in whole BM cells. This correlated with increased dipeptidyl peptidase IV activity and the failure to induce chemotaxis of BMSCs in vitro. We found increased mRNA expression levels of the major SDF-1-cleaving proteases in whole BM cells from irradiated animals suggesting distinct spatial differences within the BM in which SDF-1 may play different autocrine and paracrine signaling roles beyond the immediate cell surface microenvironment. PMID:24914464

  17. Bioavailable dietary phosphate, a mediator of cardiovascular disease, may be decreased with plant-based diets, phosphate binders, niacin, and avoidance of phosphate additives.

    PubMed

    McCarty, Mark F; DiNicolantonio, James J

    2014-01-01

    Increased fasting serum phosphate within the normal physiological range has been linked to increased cardiovascular risk in prospective epidemiology; increased production of fibroblast growth factor 23, and direct vascular effects of phosphate, may mediate this risk. Although dietary phosphate intake does not clearly influence fasting serum phosphate in individuals with normal renal function, increased phosphate intake can provoke a rise in fibroblast growth factor 23, and in diurnal phosphate levels, and hence may adversely influence vascular health. Dietary phosphate absorption can be moderated by emphasizing plant-based dietary choices (which provide phosphate in less bioavailable forms); avoidance of processed foods containing inorganic phosphate food additives; and by ingestion of phosphate-binder drugs, magnesium supplements, or niacin, which precipitate phosphate or suppress its gastrointestinal absorption. The propensity of dietary phosphate to promote vascular calcification may be opposed by optimal intakes of magnesium, vitamin K, and vitamin D; the latter should also counter the tendency of phosphate to elevate parathyroid hormone.

  18. The Transplant Patient and Transplant Medicine in Family Practice

    PubMed Central

    Hughes, Lloyd D.

    2014-01-01

    Over the last two decades in particular there has been a remarkable increase in the number of solid organ transplants being performed worldwide alongside improvements in long-term survival rates. However, the infrastructure at transplant centres has been unable to keep pace with the current volume of the transplant patient work load. These pressures on transplant specialist centres has led to calls for an increased role of the general practitioner (GP) managing particular aspects of transplant patients’ medical care. Indeed, many aspects of follow-up care such as screening for malignancies, preventing infection through immunisation programmes, and managing cardiovascular risk factors are already important aspects of family practice medicine. This paper aims to review some of the aspects of transplant patient care that is important for healthcare workers in family practice to manage. PMID:25657941

  19. Adrenergic System Activation Mediates Changes in Cardiovascular and Psychomotoric Reactions in Young Individuals after Red Bull (©) Energy Drink Consumption.

    PubMed

    Cavka, Ana; Stupin, Marko; Panduric, Ana; Plazibat, Ana; Cosic, Anita; Rasic, Lidija; Debeljak, Zeljko; Martinovic, Goran; Drenjancevic, Ines

    2015-01-01

    Objectives. To assess the effect of Red Bull(©) on (1) blood glucose and catecholamine levels, (2) cardiovascular and respiratory function changes before, during, and after exercise, (3) reaction time, (4) cognitive functions, and (5) response to mental stress test and emotions in young healthy individuals (N=38). Methods. Heart rate (HR) and arterial blood pressure (ABP), blood glucose, adrenaline, and noradrenalin plasma levels were measured before and after Red Bull(©) intake. Participants were subjected to 4 different study protocols by randomized order, before and 30 minutes after consumption of 500 mL of Red Bull(©). Results. Mean ABP and HR were significantly increased at rest after Red Bull(©) intake. Blood glucose level and plasma catecholamine levels significantly increased after Red Bull(©) consumption. Heart rate, respiration rate, and respiratory flow rate were significantly increased during exercise after Red Bull(©) consumption compared to control condition. Intake of Red Bull(©) significantly improved reaction time, performance in immediate memory test, verbal fluency, and subject's attention as well as performance in mental stress test. Conclusion. This study demonstrated that Red Bull(©) has beneficial effect on some cognitive functions and effect on cardiovascular and respiratory system at rest and during exercise by increasing activity of the sympathetic nervous system.

  20. Oxidized lipids and lipid-mediators are involved in cardiovascular injury induced by diesel exhaust particles and ozone

    EPA Science Inventory

    The mechanisms by which air pollutants induce cardiac and vascular injuries are unknown. We hypothesized that these injuries involve alterations in'aortic membrane lipids and lipid-mediators. We exposed male Wistar Kyoto rats (12-15 wk old), nose-only to air, ozone (03; 0.5 ppm),...

  1. Brain mediators of cardiovascular responses to social threat, Part II: Prefrontal-subcortical pathways and relationship with anxiety

    PubMed Central

    Wager, Tor D.; van Ast, Vanessa A.; Hughes, Brent L.; Davidson, Matthew L.; Lindquist, Martin A.; Ochsner, Kevin N.

    2009-01-01

    Social evaluative threat (SET) is a potent stressor in humans linked to autonomic and endocrine responses, and multiple health problems. Neuroimaging has recently begun to elucidate the brain correlates of SET, but as yet little is known about the mediating cortical-brainstem pathways in humans. This paper replicates and extends findings in a companion paper (Wager et al., submitted) using an independent cohort of participants and different image acquisition parameters. Here, we focused specifically on relationships between the medial prefrontal cortex (MPFC), midbrain periaqueductal gray (PAG), and heart rate (HR). We applied multi-level path analysis to localize brain mediators of SET effects on HR and self-reported anxiety. HR responses were mediated by opposing signals in two distinct sub-regions of the MPFC—increases in rostral dorsal anterior cingulate cortex (rdACC) and deactivation in ventromedial prefrontal cortex (vmPFC). In addition, HR responses were mediated by PAG. Additional path analyses provided support for two cortical subcortical pathways: one linking vmPFC, PAG, and HR, and another linking rdACC, thalamus, and HR. PAG responses were linked with HR changes both before and during SET, whereas cortical regions showed stronger connectivity with HR during threat. Self-reported anxiety showed a partially overlapping, but weaker, pattern of mediators, including the vmPFC, dorsomedial PFC (dmPFC), and lateral frontal cortex, as well as substantial individual differences that were largely unexplained. Taken together, these data suggest pathways for the translation of social threats into both physiological and experiential responses, and provide targets for future research on the generation and regulation of emotion. PMID:19465135

  2. Kidney transplant

    MedlinePlus

    Renal transplant; Transplant - kidney ... Barry JM, Conlin MJ. In: Renal transplantation. Wein AJ, ed. Campbell-Walsh Urology . 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 44. Kidney Disease: Improving Global Outcomes ( ...

  3. Bi-directional CB1 receptor-mediated cardiovascular effects of cannabinoids in anaesthetized rats: role of the paraventricular nucleus.

    PubMed

    Grzeda, E; Schlicker, E; Luczaj, W; Harasim, E; Baranowska-Kuczko, M; Malinowska, B

    2015-06-01

    The activation of cannabinoid CB1 receptors decreases and increases blood pressure (BP) in anaesthetized and conscious rats, respectively. The aim of our study was to check the possible involvement of CB1 receptors in the paraventricular nucleus of the hypothalamus (PVN) in the cardiovascular effects of cannabinoids in rats. Methanandamide (metabolically stable analogue of the endocannabinoid anandamide) and the synthetic cannabinoid receptor agonist CP55940 were microinjected into the PVN of urethane-anaesthetized rats twice (S1 and S2, 20 min apart). Receptor antagonists were administered intravenously (i.v.) 5 min before S1. Methanandamide and CP55940 decreased blood pressure by 15 - 20%. The CB1 receptor antagonist AM251 reversed the depressor effect into a pressor response of 20 - 30%. The pressor effect of CP55940 observed in the presence of AM251 i.v. was reduced by AM251 given additionally into the PVN but not by the i.v. injection of the CB2 antagonist SR144528 or the vanilloid TRPV1 antagonist ruthenium red. In the presence of the peripherally restricted CB1 receptor antagonist AM6545, CP55940 given into the PVN increased BP by 40%. AM6545 reversed the decrease in BP induced by CP55940 i.v. into a marked increase. Bilateral chemical lesion of the PVN by kainic acid abolished all cardiovascular effects of CP55940 i.v. In conclusion, the cannabinoid CP55940 administered to the PVN of urethane-anaesthetized rats can induce depressor and pressor effects. The direction of the response probably depends on the sympathetic tone. The centrally induced hypertensive response of CP55940 can, in addition, be masked by peripheral CB1 receptors.

  4. Associations of Pre-Transplant Serum Albumin with Post-Transplant Outcomes in Kidney Transplant Recipients

    PubMed Central

    Molnar, Miklos Z; Kovesdy, Csaba P; Bunnapradist, Suphamai; Streja, Elani; Mehrotra, Rajnish; Krishnan, Mahesh; Nissenson, Allen R; Kalantar-Zadeh, Kamyar

    2011-01-01

    The association between pre-transplant serum albumin concentration and post-transplant outcomes in kidney transplant recipients is unclear. We hypothesized that in transplant-waitlisted hemodialysis patients, lower serum albumin concentrations are associated with worse post-transplant outcomes. Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 8961 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (Odds ratio [OR]), respectively. Patients were 48±13 years old and included 37% women and 27% diabetics. The higher pre-transplant serum albumin was associated with lower mortality, graft failure and DGF risk even after multivariate adjustment for case-mix, malnutrition-inflammation complex and transplant related variable. Every 0.2 g/dL higher pre-transplant serum albumin concentration was associated with 13% lower all-cause mortality (HR=0.87 [95% confidence interval: 0.82-0.93]), 17% lower cardiovascular mortality (HR=0.83[0.74-0.93]), 7% lower combined risk of death or graft failure (HR=0.93[0.89-0.97]), and 4% lower DGF risk (OR=0.96[0.93-0.99]). Hence, lower pre-transplant serum albumin level is associated with worse post-transplant outcomes. Clinical trials to examine interventions to improve nutritional status in transplant-wait-listed hemodialysis patients and their impacts on post-transplant outcomes are indicated. PMID:21449945

  5. Lipids in liver transplant recipients

    PubMed Central

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H

    2016-01-01

    Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation. PMID:27022213

  6. Lipids in liver transplant recipients.

    PubMed

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H

    2016-03-28

    Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation. PMID:27022213

  7. Excitatory Amino Acid Receptors Mediate Asymmetry and Lateralization in the Descending Cardiovascular Pathways from the Dorsomedial Hypothalamus

    PubMed Central

    Xavier, Carlos Henrique; Ianzer, Danielle; Lima, Augusto Martins; Marins, Fernanda Ribeiro; Pedrino, Gustavo Rodrigues; Vaz, Gisele; Menezes, Gustavo Batista; Nalivaiko, Eugene; Fontes, Marco Antônio Peliky

    2014-01-01

    The dorsomedial hypothalamus (DMH) and lateral/dorsolateral periaqueductal gray (PAG) are anatomically and functionally connected. Both the DMH and PAG depend on glutamatergic inputs for activation. We recently reported that removal of GABA-ergic tone in the unilateral DMH produces: asymmetry, that is, a right- (R-) sided predominance in cardiac chronotropism, and lateralization, that is, a greater increase in ipsilateral renal sympathetic activity (RSNA). In the current study, we investigated whether excitatory amino acid (EAA) receptors in the DMH–PAG pathway contribute to the functional interhemispheric difference. In urethane (1.2 to 1.4 g/kg, i.p.) anesthetized rats, we observed that: (i) nanoinjections of N-methyl D-aspartate (NMDA 100 pmol/100 nl) into the unilateral DMH produced the same right-sided predominance in the control of cardiac chronotropy, (ii) nanoinjections of NMDA into the ipsilateral DMH or PAG evoked lateralized RSNA responses, and (iii) blockade of EAA receptors in the unilateral DMH attenuated the cardiovascular responses evoked by injection of NMDA into either the R- or left- (L-) PAG. In awake rats, nanoinjection of kynurenic acid (1 nmol/100 nL) into the L-DMH or R- or L-PAG attenuated the tachycardia evoked by air stress. However, the magnitude of stress-evoked tachycardia was smallest when the EAA receptors of the R-DMH were blocked. We conclude that EAA receptors contribute to the right-sided predominance in cardiac chronotropism. This interhemispheric difference that involves EAA receptors was observed in the DMH but not in the PAG. PMID:25397884

  8. Activation of coagulation and fibrinolysis following OKT3 administration to renal transplant recipients: association with distinct mediators.

    PubMed

    Raasveld, M H; Hack, C E; ten Berge, I J

    1992-09-01

    Treatment with OKT3 induces cytokine release and activates the complement system. Since both phenomena may affect coagulation and fibrinolysis we studied these systems in 8 renal transplant recipients during OKT3 treatment. In 8 of 9 patients a similar pattern was observed: plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-alpha 2-antiplasmin-complex levels were increased as compared to pretreatment levels (p less than 0.05) at 15 min after the first OKT3 dose and reached peak values at 1 h. No significant changes were observed upon subsequent OKT3 administrations or in a control group of 8 patients. In one patient upon the first OKT3 administration only complement activation, and no cytokine release was observed, whereas plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-alpha 2-antiplasmin-complex levels increased only at 15 min. In conclusion, we demonstrate a biphasic activation of coagulation and fibrinolysis upon the first OKT3 dose; the initial phase seems to be associated with complement activation, the later phase with cytokine release.

  9. Hair transplantation.

    PubMed

    Avram, Marc R

    2012-12-01

    Hair transplantation is a purely dermatologic surgical procedure that dermatologists should be able to perform in appropriate candidates with hair loss. Hair transplantation techniques performed in the 1960s through the 1990s utilized large grafts that created an unfortunate public image of unnatural-appearing transplanted hair. Over the last 15 years, hair transplantation has been performed using follicular units to create consistently natural-looking transplanted hair in both men and women. This article provides an overview of candidate selection and state-of-the-art techniques for performing hair transplantation.

  10. Coronary artery calcification in renal transplant recipients.

    PubMed

    Rosas, Sylvia E; Mensah, Korlei; Weinstein, Rachel B; Bellamy, Scarlett L; Rader, Daniel J

    2005-08-01

    Cardiovascular disease is the leading cause of mortality in renal transplant recipients. Although renal transplant recipients frequently undergo cardiac functional tests prior to surgery, coronary atherosclerosis can remain undetected. Coronary artery calcification (CAC), an early marker of atherosclerosis can be quantified using EBCT. The purpose of this study was to determine the extent and characteristics of CAC at the time of renal transplantation. We evaluated 79 consecutive incident asymptomatic renal transplant recipients. Patients were mostly White (62%), male (54%) and had a deceased donor renal transplant (61%). The mean age was 47 (12.1) years. Sixty-five percentage of subjects had CAC. The mean CAC score was 331.5 (562.4) with a median of 43.3. Older age, presence of diabetes, not having a preemptive transplant, deceased donor transplantation and hypercholesterolemia were significantly associated with presence of CAC univariately. Median CAC scores were significantly increased in subjects with diabetes (127.8 vs. 28.9, p=0.05), exposed to dialysis (102.9 vs. 3.7, p<0.001) and deceased donor recipients (169.7 vs. 7.5, p=0.02). Using multiple logistic regression, age and time on dialysis were significantly associated with the presence of CAC at the time of transplant. In summary, CAC is prevalent in patients undergoing kidney transplant. CAC may be a method to identify renal transplant recipients at increased risk for future cardiovascular events. PMID:15996243

  11. Transplant services

    MedlinePlus

    ... diseased body part with a healthy one. SOLID ORGAN TRANSPLANTS Auto islet cell transplant is done after a ... selected experts, including: Surgeons who specialize in performing ... doctors Radiologists and medical imaging technologists Nurses ...

  12. Pancreas Transplantation

    MedlinePlus

    ... Text Size: A A A Listen En Español Pancreas Transplantation Some patients with type 1 diabetes have ... weigh the potential benefits and risks. Benefits of Pancreas Transplants You may be able to maintain a ...

  13. Clinical Significance of HLA-DQ Antibodies in the Development of Chronic Antibody-Mediated Rejection and Allograft Failure in Kidney Transplant Recipients.

    PubMed

    Lee, Hyeyoung; Min, Ji Won; Kim, Ji-Il; Moon, In-Sung; Park, Ki-Hyun; Yang, Chul Woo; Chung, Byung Ha; Oh, Eun-Jee

    2016-03-01

    With the development of the single antigen beads assay, the role of donor specific alloantibody (DSA) against human leukocyte antigens in kidney transplantation (KT) has been highlighted. This study aimed to investigate the clinical significance of DQ-DSA detected at renal allograft biopsy. We evaluated 263 KT recipients who underwent allograft biopsy and DSA detection at the same time. Among them, 155 patients who were nonsensitized before transplantation were selected to investigate the role of de-novo DQ-DSA. Both the total and nonsensitized subgroup was categorized into 4 groups each according to DSA results as: DQ only, DQ + non-DQ, non-DQ, and no DSA. In the total patient group, post-KT DSA was positive in 79 (30.0%) patients and DQ-DSA was most prevalent (64.6%). In the nonsensitized subgroup, de-novo DSAs were detected in 45 (29.0%) patients and DQ-DSA was also most prevalent (73.3%). The DQ only group showed a significantly longer post-KT duration compared to the other groups (P < 0.05). The overall incidence of antibody-mediated rejection (AMR) was 17.9%. B-DSA, DR-DSA, and DQ-DSA were associated with AMR (P < 0.05), but in the analysis for chronic AMR, only DQ-DSA showed significance in both the total and the nonsensitized subgroup (P < 0.05). On comparison of Banff scores among groups, those representing humoral immunity were significantly dominant in all DSA positive groups compared to the no DSA group (P < 0.05), and higher scores of markers representing chronic tissue injury were more frequently detected in the groups with DQ-DSA. The worst postbiopsy survival was seen in the DQ + non-DQ group of the total patient group, and patients with de-novo DQ-DSA showed poorer graft survival in the nonsensitized subgroup compared to the no DSA group (P < 0.05). In the multivariate analysis, de-novo DQ-DSA was the only significant risk factor associated with late allograft failure (P < 0.05). Our study is the first to demonstrate

  14. Oxidative Stress in Cardiovascular Disease

    PubMed Central

    Csányi, Gábor; Miller, Francis J.

    2014-01-01

    In the special issue “Oxidative Stress in Cardiovascular Disease” authors were invited to submit papers that investigate key questions in the field of cardiovascular free radical biology. The original research articles included in this issue provide important information regarding novel aspects of reactive oxygen species (ROS)-mediated signaling, which have important implications in physiological and pathophysiological cardiovascular processes. The issue also included a number of review articles that highlight areas of intense research in the fields of free radical biology and cardiovascular medicine. PMID:24722571

  15. Cardiac transplantation.

    PubMed

    Shanewise, Jack

    2004-12-01

    Cardiac transplantation is a proven, accepted mode of therapy for selected patients with end-stage heart failure, but the inadequate number of suitable donor hearts available ultimately limits its application. This chapter reviews adult cardiac transplantation, with an emphasis on the anesthetic considerations of the heart transplant operation itself.

  16. MicroRNA-Mediated Down-Regulation of Apoptosis Signal-Regulating Kinase 1 (ASK1) Attenuates the Apoptosis of Human Mesenchymal Stem Cells (MSCs) Transplanted into Infarcted Heart

    PubMed Central

    Lee, Chang Youn; Shin, Sunhye; Lee, Jiyun; Seo, Hyang-Hee; Lim, Kyu Hee; Kim, Hyemin; Choi, Jung-Won; Kim, Sang Woo; Lee, Seahyung; Lim, Soyeon; Hwang, Ki-Chul

    2016-01-01

    Stem cell therapy using adult stem cells, such as mesenchymal stem cells (MSCs) has produced some promising results in treating the damaged heart. However, the low survival rate of MSCs after transplantation is still one of the crucial factors that limit the therapeutic effect of stem cells. In the damaged heart, oxidative stress due to reactive oxygen species (ROS) production can cause the death of transplanted MSCs. Apoptosis signal-regulating kinase 1 (ASK1) has been implicated in the development of oxidative stress-related pathologic conditions. Thus, we hypothesized that down-regulation of ASK1 in human MSCs (hMSCs) might attenuate the post-transplantation death of MSCs. To test this hypothesis, we screened microRNAs (miRNAs) based on a miRNA-target prediction database and empirical data and investigated the anti-apoptotic effect of selected miRNAs on human adipose-derived stem cells (hASCs) and on rat myocardial infarction (MI) models. Our data indicated that miRNA-301a most significantly suppressed ASK1 expression in hASCs. Apoptosis-related genes were significantly down-regulated in miRNA-301a-enriched hASCs exposed to hypoxic conditions. Taken together, these data show that miRNA-mediated down-regulation of ASK1 protects MSCs during post-transplantation, leading to an increase in the efficacy of MSC-based cell therapy. PMID:27775615

  17. Antihypertensive agents and renal transplantation

    PubMed Central

    Vergoulas, G

    2007-01-01

    Advances in the field of kidney transplantation have led to a significant increase in the life of renal allograft with 1 - year graft survival rates of 93% to 99%.This increase in early graft survival has made it possible to observe the long-term morbidities that accompany renal transplantation. Studies correlating the reduction of arterial blood pressure with patient and graft survival as well as the risk of cardiovascular disease do not exist. The recommendations come from the general population and from comparative studies of hypertensive and normotensive kidney graft recipients. It is known that in the general population hypertension is a risk factor for chronic kidney disease but at the same time a risk factor for death, ischaemic heart disease, chronic heart failure and left ventricular hypertrophy. We must always have in mind that there are many similarities between a kidney graft recipient and a patient with chronic kidney disease. Renal transplant recipients represent a patient population with a very high risk for development of cardiovascular disease which has been identified as the leading cause of death in these patients1. Of 18,482 deaths among renal allograft recipients, 38% had functioning renal allografts 2, 3. Successful renal transplantation (Rt) can result in partial regression of left ventricular hypertrophy (LVH) if it is associated with hypertension (HTN) remission or if HTN is controlled by medications. Frequently post transplant HTN is associated with failure of LVH to regress. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit from renal allograft and cardiovascular perspective. The target must always be long term patient and graft survival and acceptable quality of life. The antihypertensive drugs usually used after kidney transplantation are diuretics, calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β – blockers. Most

  18. Hair transplantation.

    PubMed

    Al-Khair, Y M

    2000-09-01

    Hair transplantation is a technique in which hair follicles are harvested from the occipital area and re-transplanted in the frontal bald area. Hair transplantation is the most common cosmetic procedure in the United States nowadays despite the fact that it is expensive. Usually, patients need more than one session to receive a cosmetically acceptable result and patients need to be understanding and have realistic expectations. Although most of our patients are males, females represent about 10-15% of our new patients. This article reviews the basic principals of hair transplantation and describes new and improved techniques of hair transplantation. PMID:11376357

  19. Thoracic organ transplantation: laboratory methods.

    PubMed

    Patel, Jignesh K; Kobashigawa, Jon A

    2013-01-01

    Although great progress has been achieved in thoracic organ transplantation through the development of effective immunosuppression, there is still significant risk of rejection during the early post-transplant period, creating a need for routine monitoring for both acute antibody and cellular mediated rejection. The currently available multiplexed, microbead assays utilizing solubilized HLA antigens afford the capability of sensitive detection and identification of HLA and non-HLA specific antibodies. These assays are being used to assess the relative strength of donor specific antibodies; to permit performance of virtual crossmatches which can reduce the waiting time to transplantation; to monitor antibody levels during desensitization; and for heart transplants to monitor antibodies post-transplant. For cell mediated immune responses, the recent development of gene expression profiling has allowed noninvasive monitoring of heart transplant recipients yielding predictive values for acute cellular rejection. T cell immune monitoring in heart and lung transplant recipients has allowed individual tailoring of immunosuppression, particularly to minimize risk of infection. While the current antibody and cellular laboratory techniques have enhanced the ability to manage thoracic organ transplant recipients, future developments from improved understanding of microchimerism and graft tolerance may allow more refined allograft monitoring techniques. PMID:23775735

  20. Simultaneous transplantation.

    PubMed

    Sala, P

    1993-01-01

    1. Thoracic organ transplantation requires extensive preparation with little advance notice. 2. A single organ transplant requires a team of various staff members, and may include one or two circulating nurses, two scrub technologists or nurses, one perfusionist, one surgeon's assistant, two surgeons, and one anesthesiologist. 3. Timing is important in organ transplantation because thoracic organs ideally should be transplanted within four hours after cross-clamping the aorta of the donor. 4. The dedication, expertise, and thorough follow-up care provided by transplant surgeons, nurse transplant coordinators, organ procurement coordinators, and the CICU and coronary care nurses/departments directly relate to the success of a thoracic organ transplant program. PMID:8493710

  1. Undifferentiated Wharton's Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T-Cell-Mediated Autoimmunity in Nonobese Diabetic Mice.

    PubMed

    Tsai, Pei-Jiun; Wang, Hwai-Shi; Lin, Gu-Jiun; Chou, Shu-Cheng; Chu, Tzu-Hui; Chuan, Wen-Ting; Lu, Ying-Jui; Weng, Zen-Chung; Su, Cheng-Hsi; Hsieh, Po-Shiuan; Sytwu, Huey-Kang; Lin, Chi-Hung; Chen, Tien-Hua; Shyu, Jia-Fwu

    2015-01-01

    Type 1 diabetes mellitus is caused by T-cell-mediated autoimmune destruction of pancreatic β-cells. Systemic administration of mesenchymal stem cells (MSCs) brings about their incorporation into a variety of tissues with immunosuppressive effects, resulting in regeneration of pancreatic islets. We previously showed that human MSCs isolated from Wharton's jelly (WJ-MSCs) represent a potential cell source to treat diabetes. However, the underlying mechanisms are unclear. The purpose of this study was to discern whether undifferentiated WJ-MSCs can differentiate into pancreatic insulin-producing cells (IPCs) and modify immunological responses in nonobese diabetic (NOD) mice. Undifferentiated WJ-MSCs underwent lentiviral transduction to express green fluorescent protein (GFP) and then were injected into the retro-orbital venous sinus of NOD mice. Seven days after transplantation, fluorescent islet-like cell clusters in the pancreas were apparent. WJ-MSC-GFP-treated NOD mice had significantly lower blood glucose and higher survival rates than saline-treated mice. Systemic and local levels of autoaggressive T-cells, including T helper 1 cells and IL-17-producing T-cells, were reduced, and regulatory T-cell levels were increased. Furthermore, anti-inflammatory cytokine levels were increased, and dendritic cells were decreased. At 23 days, higher human C-peptide and serum insulin levels and improved glucose tolerance were found. Additionally, WJ-MSCs-GFP differentiated into IPCs as shown by colocalization of human C-peptide and GFP in the pancreas. Significantly more intact islets and less severe insulitis were observed. In conclusion, undifferentiated WJ-MSCs can differentiate into IPCs in vivo with immunomodulatory effects and repair the destroyed islets in NOD mice.

  2. Sex Related Differences in the Risk of Antibody-Mediated Rejection and Subsequent Allograft Vasculopathy Post-Heart Transplantation: A Single-Center Experience

    PubMed Central

    Grupper, Avishay; Nestorovic, Emilija M.; Daly, Richard C.; Milic, Natasa M.; Joyce, Lyle D.; Stulak, John M.; Joyce, David L.; Edwards, Brooks S.; Pereira, Naveen L.; Kushwaha, Sudhir S.

    2016-01-01

    Background Pregnancies may result in antibodies against HLA, a risk factor for antibody-mediated rejection (AMR) and subsequent cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). The aim of this study was to evaluate sex differences in the incidence of AMR events and subsequent risk of CAV among HTx recipients. Methods The study comprised 160 patients (51 [32%] women) who underwent HTx in 2008 to 2014. The cumulative effect of AMR events was calculated by AMR score (sum of myocardial biopsy grading divided by number of biopsies taken during 3 years post-HTx). Results Females had higher levels of anti-HLA I antibodies pre-HTx compared to males which was associated with a history of pregnancies, total number of children and with a higher AMR score at 6 months post-HTx (P < 0.05). Women demonstrated a significant increase in the total incidence of AMR events (27 vs. 7%, P = 0.001) and in AMR scores at 6, 12, 24 and 36 months post-HTx compared to men (P < 0.05). There were no differences in cellular rejection between the groups. A history of AMR events was associated with a significantly increased risk of severe CAV onset (hazard ratio, 7.0; 95% confidence interval, 1.5-31.5; P = 0.012). Conclusions Women are at higher risk for AMR post-HTx which subsequently increases their risk for CAV. Females recipients may benefit from closer surveillance to identify AMR at an earlier stage post-HTx, and targeted immunosuppressive therapy to attenuate the development of CAV.

  3. IFN-γ Receptor Deficient Donor T cells Mediate Protection from Graft-versus-Host Disease and Preserve Graft-versus-Tumor Responses After Allogeneic Bone Marrow Transplantation

    PubMed Central

    Sun, Kai; Hsiao, Hui-Hua; Li, Minghui; Ames, Erik; Bouchlaka, Myriam; Welniak, Lisbeth A.; Hagino, Takeshi; Jagdeo, Jared; Pai, Chien-Chun; Chen, Mingyi; Blazar, Bruce R.; Abedi, Mehrdad; Murphy, William J.

    2012-01-01

    Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT). It has been previously reported that lung GVHD severity directly correlates with the expansion of donor Th17 cells in the absence of IFN-γ. However, the consequence of Th17-associated lung GVHD in the presence of IFN-γ has not been well-characterized. In the current study, T cells from IFN-γ receptor knockout (IFN-γR-/-) mice, capable of producing IFN-γ but unable to signal in response to IFN-γ, have been used to further elucidate the role of IFN-γ in GVHD. We found the transfer of donor T cells from either IFN-γR-/- or IFN-γ knockout (IFN-γ-/-) mice resulted in significant increases in donor Th17 cells in the lung. Marked increases in IL4-producing Th2 cells infiltrating the lungs were also observed in the mice of donor IFN-γR-/- T cells. Interestingly, despite the presence of these cells, these mice did not show the severe immune mediated histopathological lung injury observed in mice receiving donor IFN-γ-/- T cells. Increases in lung GVHD did occur in mice with donor IFN-γR-/- T cells when treated in vivo with anti-IFN-γ demonstrating that the cytokine has a protective role on host tissues in GVHD. A survival benefit from acute GVHD was also observed using donor cells from IFN-γR-/-T cells compared with control donors. Importantly, tumor-bearing mice receiving IFN-γR-/- T cells, versus wild-type donor T cells, displayed similar graft-versus tumor (GVT) effects. These results demonstrate the critical role of the IFN-γ on host tissues and cell effector functions in GVHD/GVT. PMID:22778394

  4. Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality-Should Patients with Elevated Levels Be Supplemented with Citrulline?

    PubMed

    McCarty, Mark F

    2016-01-01

    The arginine metabolite asymmetric dimethylarginine (ADMA) is a competitive inhibitor and uncoupler of endothelial nitric oxide synthase (eNOS), an enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular arginine levels with supplemental citrulline. Although the long-term impact of supplemental citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with heart failure. Supplemental citrulline could be a practical option for primary or secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3-6 g daily) that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate citrulline's potential for aiding cardiovascular health. PMID:27417628

  5. Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality-Should Patients with Elevated Levels Be Supplemented with Citrulline?

    PubMed

    McCarty, Mark F

    2016-07-08

    The arginine metabolite asymmetric dimethylarginine (ADMA) is a competitive inhibitor and uncoupler of endothelial nitric oxide synthase (eNOS), an enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular arginine levels with supplemental citrulline. Although the long-term impact of supplemental citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with heart failure. Supplemental citrulline could be a practical option for primary or secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3-6 g daily) that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate citrulline's potential for aiding cardiovascular health.

  6. Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality—Should Patients with Elevated Levels Be Supplemented with Citrulline?

    PubMed Central

    McCarty, Mark F.

    2016-01-01

    The arginine metabolite asymmetric dimethylarginine (ADMA) is a competitive inhibitor and uncoupler of endothelial nitric oxide synthase (eNOS), an enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular arginine levels with supplemental citrulline. Although the long-term impact of supplemental citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with heart failure. Supplemental citrulline could be a practical option for primary or secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3–6 g daily) that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate citrulline’s potential for aiding cardiovascular health. PMID:27417628

  7. Cardiovascular Deconditioning

    NASA Technical Reports Server (NTRS)

    Charles, John B.; Fritsch-Yelle, Janice M.; Whitson, Peggy A.; Wood, Margie L.; Brown, Troy E.; Fortner, G. William

    1999-01-01

    Spaceflight causes adaptive changes in cardiovascular function that may deleteriously affect crew health and safety. Over the last three decades, symptoms of cardiovascular changes have ranged from postflight orthostatic tachycardia and decreased exercise capacity to serious cardiac rhythm disturbances during extravehicular activities (EVA). The most documented symptom of cardiovascular dysfunction, postflight orthostatic intolerance, has affected a significant percentage of U.S. Space Shuttle astronauts. Problems of cardiovascular dysfunction associated with spaceflight are a concern to NASA. This has been particularly true during Shuttle flights where the primary concern is the crew's physical health, including the pilot's ability to land the Orbiter, and the crew's ability to quickly egress and move to safety should a dangerous condition arise. The study of astronauts during Shuttle activities is inherently more difficult than most human research. Consequently, sample sizes have been small and results have lacked consistency. Before the Extended Duration Orbiter Medical Project (EDOMP), there was a lack of normative data on changes in cardiovascular parameters during and after spaceflight. The EDOMP for the first time allowed studies on a large enough number of subjects to overcome some of these problems. There were three primary goals of the Cardiovascular EDOMP studies. The first was to establish, through descriptive studies, a normative data base of cardiovascular changes attributable to spaceflight. The second goal was to determine mechanisms of cardiovascular changes resulting from spaceflight (particularly orthostatic hypotension and cardiac rhythm disturbances). The third was to evaluate possible countermeasures. The Cardiovascular EDOMP studies involved parallel descriptive, mechanistic, and countermeasure evaluations.

  8. Lung transplantation

    PubMed Central

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  9. Notch signaling-mediated neural lineage selection facilitates intrastriatal transplantation therapy for ischemic stroke by promoting endogenous regeneration in the hippocampus.

    PubMed

    Yang, Tao; Liu, Ling-yun; Ma, Yuan-yuan; Zhang, Wei

    2014-02-01

    Acquisition of highly efficient neural differentiation based on understanding of initial lineage commitment of human embryonic stem (hES) cells remains a challenge. This study describes a simple three-stage protocol to induce hES cells into neural lineage cells using a 2-week coculture with murine bone marrow stromal cell (BMSC) PA6 followed by a 2-week propagation culture in PA6-conditioned medium and an additional 2-week selection culture in chemically defined neurobasal medium. This protocol generated a relatively high yield of neural lineage cells without mesodermal and endodermal lineage cell contamination. Notably, we demonstrated that PA6 coculture can significantly enhance the expression level of Notch signaling components and promote neural lineage entry of hES cell derivatives. Manipulation of Notch signaling can boost or suppress neural differentiation of hES cell derivatives, suggesting that Notch signaling may underlie the PA6-mediated neural induction. In vivo studies demonstrated that derived neural cells could improve the cognitive function of ischemic stroke rats. Intrastriatal human neural cell grafts were noted to migrate to damaged cerebral regions, enhance basic fibroblast growth factor production in the hippocampus, and restore the pyramidal neuron density and morphology in the hippocampal CA1 region, although only a small number of human donor cells were present in the hippocampus, suggesting that donor cells can boost hippocampal reconstruction by promoting the endogenous regeneration process. These findings demonstrate a pivotal role for Notch in hES cell fate determination and that manipulation of Notch signaling is therefore likely to be a key factor in taking command of hES cell lineage choice. This study suggested the potential of utilizing PA6 coculture to imitate the embryonic niche for hES cell neural induction via Notch signaling and a high application potential of BMSC-involved protocol, which can yield a whole lineage of human

  10. Organ Transplantation

    MedlinePlus

    ... recipients to reduce the risk of transplant rejection. Rejection happens when your immune system attacks the new organ. If you have a transplant, you must take drugs the rest of your life to help keep your body from rejecting the new organ.

  11. Transplant rejection

    MedlinePlus

    ... Wood K, Shankar S, Mittal S. Concepts and challenges in organ transplantation. In: Rich RR, Fleisher TA, Shearer WT, et ... A.M. Editorial team. Related MedlinePlus Health Topics Organ Transplantation Browse the Encyclopedia A.D.A.M., Inc. ...

  12. Intestine Transplant

    MedlinePlus

    ... intestine segment, most intestine transplants involve a whole organ from a deceased donor. In addition, most intestine transplants are performed in ... blood before surgery. I am looking for ... allocation About UNOS Being a living donor Calculator - CPRA Calculator - KDPI Calculator - LAS Calculator - MELD ...

  13. Challenges of valve surgeries in post-renal transplant patients.

    PubMed

    Ahmad, Tanveer; Kishore, Kolkebaile Sadanand; Maheshwarappa, Nandakumar Neralakere; Pasarad, Ashwini Kumar

    2015-01-01

    Renal transplantation remains a mainstay of therapy for the end-stage renal disease. Cardiac disease has a high prevalence in this patient population. Cardiovascular disease remains the leading cause of death among kidney transplantation patients. The cardiac disease accounts for 43% of all-cause mortality among dialysis patients and for ≈38% of all-cause mortality after transplantation. In this article, we review the factors and outcomes associated with valve surgeries in renal transplant recipients and evaluate the strategy for open heart surgery after renal transplantation performed.

  14. Challenges of valve surgeries in post-renal transplant patients

    PubMed Central

    Ahmad, Tanveer; Kishore, Kolkebaile Sadanand; Maheshwarappa, Nandakumar Neralakere; Pasarad, Ashwini Kumar

    2015-01-01

    Renal transplantation remains a mainstay of therapy for the end-stage renal disease. Cardiac disease has a high prevalence in this patient population. Cardiovascular disease remains the leading cause of death among kidney transplantation patients. The cardiac disease accounts for 43% of all-cause mortality among dialysis patients and for ≈38% of all-cause mortality after transplantation. In this article, we review the factors and outcomes associated with valve surgeries in renal transplant recipients and evaluate the strategy for open heart surgery after renal transplantation performed. PMID:26440255

  15. Fear of Movement and Low Self-Efficacy Are Important Barriers in Physical Activity after Renal Transplantation

    PubMed Central

    Zelle, Dorien M.; Corpeleijn, Eva; Klaassen, Gerald; Schutte, Elise; Navis, Gerjan; Bakker, Stephan J. L.

    2016-01-01

    Background Physical activity (PA) and exercise are commonly used as preventive measures for cardiovascular disease in the general population, and could be effective in the management of post-transplantation cardiovascular risk. PA levels are low after renal transplantation and very few renal transplant recipients (RTR) meet the PA guidelines. Identification of barriers to regular PA is important to identify targets for intervention to improve PA levels after renal transplantation. We investigated fear of movement and physical self-efficacy as barriers to PA in RTR. Methods RTR were investigated between 2001–2003. The Tampa Score of Kinesiophobia–Dutch Version (TSK-11) was used to assess fear of movement. Physical self-efficacy was measured with the LIVAS-scale. PA was assessed using validated questionnaires (Tecumseh Occupational Activity Questionnaire and the Minnesota Leisure Time Physical Activity Questionnaire). Results A total of 487 RTR (age 51±12 years, 55% men) were studied. Median score [interquartile range] on TSK-11 was 22 [17–26]. Low physical self-efficacy (Exp B:0.41[0.31–0.54], p<0.001) and history of myocardial infarction, transient ischemic attack and cerebrovascular accident (Exp B:1.30[1.03–1.63],p = 0.03) were independent determinants for fear of movement. Fear of movement was associated with lower daily PA, occupational, sports and leisure time PA. Mediation-analysis showed that a large part (73%) of the effect of fear of movement on PA was explained by low physical self-efficacy. Conclusions This study was the first to examine fear of movement and self-efficacy in relation to PA in RTR. Fear of movement was associated with a low PA level, and the larger part of this relation was mediated by low physical self-efficacy. Both fear of movement and physical self-efficacy level are important targets for intervention during rehabilitation after renal transplantation. PMID:26844883

  16. Mesenchymal stromal cell-dependent reprogramming of Kupffer cells is mediated by TNF-α and PGE2 and is crucial for liver transplant tolerance.

    PubMed

    You, Yu; Zhang, Jiqin; Gong, Jianping; Chen, Yupei; Li, Yue; Yang, Kang; Liu, Zuojin

    2015-07-01

    The role of mesenchymal stromal cells (MSCs) in the modulation of liver transplant tolerance has attracted significant interest. However, the interaction between MSCs and Kupffer cells (KCs) has received little attention, and the effect of this interaction on liver transplant tolerance remains unclear. KCs were cultured in the presence and absence of MSCs. After 24 h, cells were treated with lipopolysaccharide (LPS), after which the production of cytokines and the expression of surface antigens were measured for cell function identification. Moreover, the effects of the KCs and the prostaglandin E2 (PGE2) levels produced by the MSCs were determined using an experimental rat liver transplantation model. Blood and liver samples were collected at three time points after transplantation for further analysis. After LPS treatment, when compared with the KC single cultures, the expression of pro-inflammatory cytokines (IL-1β, IL-6, MHC-II, CD40, CD80, and CD86) in the coculture system was down-regulated, whereas the expression of anti-inflammatory cytokines (TGF-β, IL-4, PGE2, and IL-10) was markedly increased. These data indicate that MSCs can reprogram the phenotype of KCs. However, KCs treated with miR/TNF-α (tumor necrosis factor) plasmid prior to coculture to inhibit the production of TNF-α resulted in an inhibition of the reprogramming effect of MSCs. Moreover, overexpression of PGE2 in MSCs increased the effect of MSCs on KC reprogramming. After rat liver transplantation, allograft recipients that received MSCs showed better allograft tolerance when compared with rats in which KC function was inhibited. Furthermore, rats treated with MSCs overexpressing PGE2 demonstrated the best liver tolerance of all of the groups tested. MSCs reprogram the phenotype of KCs through TNF-α and PGE2, and this process is crucial for the immunomodulatory function of MSCs in liver transplantation. PMID:25982496

  17. Mesenchymal stromal cell-dependent reprogramming of Kupffer cells is mediated by TNF-α and PGE2 and is crucial for liver transplant tolerance.

    PubMed

    You, Yu; Zhang, Jiqin; Gong, Jianping; Chen, Yupei; Li, Yue; Yang, Kang; Liu, Zuojin

    2015-07-01

    The role of mesenchymal stromal cells (MSCs) in the modulation of liver transplant tolerance has attracted significant interest. However, the interaction between MSCs and Kupffer cells (KCs) has received little attention, and the effect of this interaction on liver transplant tolerance remains unclear. KCs were cultured in the presence and absence of MSCs. After 24 h, cells were treated with lipopolysaccharide (LPS), after which the production of cytokines and the expression of surface antigens were measured for cell function identification. Moreover, the effects of the KCs and the prostaglandin E2 (PGE2) levels produced by the MSCs were determined using an experimental rat liver transplantation model. Blood and liver samples were collected at three time points after transplantation for further analysis. After LPS treatment, when compared with the KC single cultures, the expression of pro-inflammatory cytokines (IL-1β, IL-6, MHC-II, CD40, CD80, and CD86) in the coculture system was down-regulated, whereas the expression of anti-inflammatory cytokines (TGF-β, IL-4, PGE2, and IL-10) was markedly increased. These data indicate that MSCs can reprogram the phenotype of KCs. However, KCs treated with miR/TNF-α (tumor necrosis factor) plasmid prior to coculture to inhibit the production of TNF-α resulted in an inhibition of the reprogramming effect of MSCs. Moreover, overexpression of PGE2 in MSCs increased the effect of MSCs on KC reprogramming. After rat liver transplantation, allograft recipients that received MSCs showed better allograft tolerance when compared with rats in which KC function was inhibited. Furthermore, rats treated with MSCs overexpressing PGE2 demonstrated the best liver tolerance of all of the groups tested. MSCs reprogram the phenotype of KCs through TNF-α and PGE2, and this process is crucial for the immunomodulatory function of MSCs in liver transplantation.

  18. Ozone and cardiovascular injury.

    PubMed

    Srebot, Vera; Gianicolo, Emilio A L; Rainaldi, Giuseppe; Trivella, Maria Giovanna; Sicari, Rosa

    2009-06-24

    Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular diseases in urban communities. The potential detrimental effects are both acute and chronic having a strong impact on morbidity and mortality. The acute exposure to pollutants has been linked to adverse cardiovascular events such as myocardial infarction, heart failure and life-threatening arrhythmias. The long-terms effects are related to the lifetime risk of death from cardiac causes. The WHO estimates that air pollution is responsible for 3 million premature deaths each year. The evidence supporting these data is very strong nonetheless, epidemiologic and observational data have the main limitation of imprecise measurements. Moreover, the lack of clinical experimental models makes it difficult to demonstrate the individual risk. The other limitation is related to the lack of a clear mechanism explaining the effects of pollution on cardiovascular mortality. In the present review we will explore the epidemiological, clinical and experimental evidence of the effects of ozone on cardiovascular diseases. The pathophysiologic consequences of air pollutant exposures have been extensively investigated in pulmonary systems, and it is clear that some of the major components of air pollution (e.g. ozone and particulate matter) can initiate and exacerbate lung disease in humans 1. It is possible that pulmonary oxidant stress mediated by particulate matter and/or ozone (O3) exposure can result in downstream perturbations in the cardiovasculature, as the pulmonary and cardiovascular systems are intricately associated, and it is well documented that specific environmental toxins (such as tobacco smoke 2) introduced through the lungs can initiate and/or accelerate cardiovascular disease development. Indeed, several epidemiologic studies have proved that there is an association between PM and O3 and the increased incidence of cardiovascular morbidity and mortality 3. Most of the

  19. Anesthesia for parturient with renal transplantation

    PubMed Central

    Parikh, Beena K; Shah, Veena R; Bhosale, Guruprasad

    2012-01-01

    Management of successful pregnancy after renal transplantation is a unique challenge to nephrologist, obstetrician, and anesthesiologist, as these patients have altered physiology and are immune-compromised. We present the anesthetic management of three postrenal transplant patients scheduled for cesarean section. While conducting such cases, cardiovascular status, hematological status, and function of transplanted kidney should be assessed thoroughly. Side effects of immunosuppressant drugs and their interaction with anesthetic agents should be taken into consideration. Main goal of anesthetic management is to maintain optimum perfusion pressure of renal allograft to preserve its function. PMID:23225940

  20. Facial Transplantation.

    PubMed

    Russo, Jack E; Genden, Eric M

    2016-08-01

    Reconstruction of severe facial deformities poses a unique surgical challenge: restoring the aesthetic form and function of the face. Facial transplantation has emerged over the last decade as an option for reconstruction of these defects in carefully selected patients. As the world experience with facial transplantation grows, debate remains regarding whether such a highly technical, resource-intensive procedure is warranted, all to improve quality of life but not necessarily prolong it. This article reviews the current state of facial transplantation with focus on the current controversies and challenges, with particular attention to issues of technique, immunology, and ethics. PMID:27400850

  1. Adventitial transplantation of blood outgrowth endothelial cells in porcine haemodialysis grafts alleviates hypoxia and decreases neointimal proliferation through a matrix metalloproteinase-9-mediated pathway—a pilot study

    PubMed Central

    Hughes, Deborah; Fu, Alex A.; Puggioni, Alessandra; Glockner, James F.; Anwer, Bilal; McGuire, Antonio M.; Mukhopadhyay, Debabrata; Misra, Sanjay

    2009-01-01

    Purpose. We hypothesized that adventitial transplantation of blood outgrowth endothelial cells (BOEC) to the vein-to-graft anastomosis of polytetrafluoroethylene grafts will reduce neointimal hyperplasia by reducing hypoxia inducible factor-1α (HIF-1α), by increasing angiogenesis in a porcine model of chronic renal insufficiency with haemodialysis polytetrafluoroethylene grafts. Because matrix metalloproteinases (MMPs) have been shown to be involved with angiogenesis, the expression of MMPs and their inhibitors was determined. Methods. Chronic renal insufficiency was created by subtotal renal infarction and 28 days later, arteriovenous PTFE grafts were placed bilaterally from the carotid artery to the jugular vein. Autologous blood outgrowth endothelial cells labeled with Lac Z were transplanted to the adventitia of the vein-to-graft anastomosis using polyglycolic acid scaffolding and scaffolding only to other side (control). Animals were killed 14 days later and vessels were explanted from the vein-to-graft anastomosis of both sides and underwent immunohistochemical analysis, western blotting and zymography for HIF-1α, MMP-2, MMP-9, TIMP-1 and TIMP-2. BOEC were also made hypoxic and normoxic for 12, 24 and 48 h to determine protein expression for MMPs and TIMPs. Results. Under hypoxia, BOEC significantly increased the expression of pro MMP-2 by 12 h and TIMP-2 by 24 h when compared to normoxic cells (P < 0.05). Transplantation of BOEC resulted in a significant decrease in both HIF-1α and intima-to-media ratio with a significant increase in both pro and active MMP-9 when compared to control vessels (P < 0.05). MMP-9 activity was localized to the neointima of the transplanted vessels by immunohistochemistry. There was increased CD31 density with engraftment of BOEC cells into the neointima of both the transplanted vessels compared to controls (P = NS). Conclusion. Transplantation of BOEC resulted in a significant decrease in intimal hyperplasia and HIF-1α with

  2. Lung transplant

    MedlinePlus

    Solid organ transplant - lung ... the new lung Have severe disease of other organs Cannot reliably take their medicines Are unable to ... medicines Damage to your kidneys, liver, or other organs from anti-rejection medicines Future risk of certain ...

  3. Corneal transplant

    MedlinePlus

    ... transplant are: Bleeding Cataracts Infection of the eye Glaucoma (high pressure in the eye that can cause ... clot (blood thinners) for 10 days before the surgery. Some of these are aspirin, ibuprofen (Advil, Motrin), ...

  4. Pancreas Transplantation

    MedlinePlus

    The pancreas is a gland behind your stomach and in front of your spine. It produces the juices that ... hormones that help control blood sugar levels. A pancreas transplant is surgery to place a healthy pancreas ...

  5. Liver transplant

    MedlinePlus

    ... toxins in the blood Storing sugars, fats, iron, copper, and vitamins The most common reason for a ... cirrhosis or primary sclerosing cholangitis Metabolic disorders of copper or iron ( Wilson's disease and hemochromatosis ) Liver transplant ...

  6. Heart transplant

    MedlinePlus

    ... PA: Elsevier Saunders; 2014:chap 28. Bernstein D. Pediatric heart and heart-lung transplantation. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics . 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap ...

  7. State-of-the-art monitoring of cytomegalovirus-specific cell-mediated immunity after organ transplant: a primer for the clinician.

    PubMed

    Egli, Adrian; Humar, Atul; Kumar, Deepali

    2012-12-01

    Cytomegalovirus (CMV) is one of the most common infections after solid organ transplantation. Improved assays to predict viral replication and disease would help refine current preventive strategies. Monitoring of CMV-specific T-cell responses may help guide clinical decision making. Several techniques are now available to quantify CMV-specific T-cell responses, including flow cytometry, enzyme-linked immunosorbent spot assay, and enzyme-linked immunosorbent assay. Standardization and validation of these assays have the potential to significantly change the monitoring and treatment of CMV and further personalize CMV prevention strategies. In this review, we discuss the measurement of CMV-specific T-cell responses and their clinical impact on the management of CMV after organ transplantation.

  8. Transplant nephrectomy

    PubMed Central

    Akoh, Jacob A

    2011-01-01

    About 10% of all renal allografts fail during the first year of transplantation and thereafter approximately 3%-5% yearly. Given that approximately 69 400 renal transplants are performed worldwide annually, the number of patients returning to dialysis following allograft failure is increasing. A failed transplant kidney, whether maintained by low dose immunosuppression or not, elicits an inflammatory response and is associated with increased morbidity and mortality. The risk for transplant nephrectomy (TN) is increased in patients who experienced multiple acute rejections prior to graft failure, develop chronic graft intolerance, sepsis, vascular complications and early graft failure. TN for late graft failure is associated with greater morbidity and mortality, bleeding being the leading cause of morbidity and infection the main cause of mortality. TN appears to be beneficial for survival on dialysis but detrimental to the outcome of subsequent transplantation by virtue of increased level of antibodies to mismatched antigens, increased rate of primary non function and delayed graft function. Many of the studies are characterized by a retrospective and univariate analysis of small numbers of patients. The lack of randomization in many studies introduced a selection bias and conclusions drawn from such studies should be applied with caution. Pending a randomised controlled trial on the role of TN in the management of transplant failure patients, it is prudent to remove failed symptomatic allografts and all grafts failing within 3 mo of transplantation, monitor inflammatory markers in patients with retained failed allografts and remove the allograft in the event of a significant increase in levels. PMID:24175187

  9. Lung Transplantation for Hypersensitivity Pneumonitis

    PubMed Central

    Singer, Jonathan P.; Koth, Laura; Mooney, Joshua; Golden, Jeff; Hays, Steven; Greenland, John; Wolters, Paul; Ghio, Emily; Jones, Kirk D.; Leard, Lorriana; Kukreja, Jasleen; Blanc, Paul D.

    2015-01-01

    BACKGROUND: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). METHODS: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. RESULTS: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. CONCLUSIONS: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. PMID:25412059

  10. Diabetes Mellitus in the Transplanted Kidney

    PubMed Central

    Peev, Vasil; Reiser, Jochen; Alachkar, Nada

    2014-01-01

    Diabetes mellitus (DM) is the most common cause of chronic kidney disease and end stage renal disease. New onset diabetes mellitus after transplant (NODAT) has been described in approximately 30% of non-diabetic kidney-transplant recipients many years post transplantation. DM in patients with kidney transplantation constitutes a major comorbidity, and has significant impact on the patients and allografts’ outcome. In addition to the major comorbidity and mortality that result from cardiovascular and other DM complications, long standing DM after kidney-transplant has significant pathological injury to the allograft, which results in lowering the allografts and the patients’ survivals. In spite of the cumulative body of data on diabetic nephropathy (DN) in the native kidney, there has been very limited data on the DN in the transplanted kidney. In this review, we will shed the light on the risk factors that lead to the development of NODAT. We will also describe the impact of DM on the transplanted kidney, and the outcome of kidney-transplant recipients with NODAT. Additionally, we will present the most acceptable data on management of NODAT. PMID:25221544

  11. Adrenergic System Activation Mediates Changes in Cardiovascular and Psychomotoric Reactions in Young Individuals after Red Bull© Energy Drink Consumption

    PubMed Central

    Cavka, Ana; Stupin, Marko; Panduric, Ana; Plazibat, Ana; Cosic, Anita; Rasic, Lidija; Debeljak, Zeljko; Martinovic, Goran; Drenjancevic, Ines

    2015-01-01

    Objectives. To assess the effect of Red Bull© on (1) blood glucose and catecholamine levels, (2) cardiovascular and respiratory function changes before, during, and after exercise, (3) reaction time, (4) cognitive functions, and (5) response to mental stress test and emotions in young healthy individuals (N=38). Methods. Heart rate (HR) and arterial blood pressure (ABP), blood glucose, adrenaline, and noradrenalin plasma levels were measured before and after Red Bull© intake. Participants were subjected to 4 different study protocols by randomized order, before and 30 minutes after consumption of 500 mL of Red Bull©. Results. Mean ABP and HR were significantly increased at rest after Red Bull© intake. Blood glucose level and plasma catecholamine levels significantly increased after Red Bull© consumption. Heart rate, respiration rate, and respiratory flow rate were significantly increased during exercise after Red Bull© consumption compared to control condition. Intake of Red Bull© significantly improved reaction time, performance in immediate memory test, verbal fluency, and subject's attention as well as performance in mental stress test. Conclusion. This study demonstrated that Red Bull© has beneficial effect on some cognitive functions and effect on cardiovascular and respiratory system at rest and during exercise by increasing activity of the sympathetic nervous system. PMID:26124829

  12. Studies of nontarget-mediated distribution of human full-length IgG1 antibody and its FAb fragment in cardiovascular and metabolic-related tissues.

    PubMed

    Davidsson, Pia; Söderling, Ann-Sofi; Svensson, Lena; Ahnmark, Andrea; Flodin, Christine; Wanag, Ewa; Screpanti-Sundqvist, Valentina; Gennemark, Peter

    2015-05-01

    Tissue distribution and pharmacokinetics (PK) of full-length nontargeted antibody and its antigen-binding fragment (FAb) were evaluated for a range of tissues primarily of interest for cardiovascular and metabolic diseases. Mice were intravenously injected with a dose of 10 mg/kg of either human IgG1or its FAb fragment; perfused tissues were collected at a range of time points over 3 weeks for the human IgG1 antibody and 1 week for the human FAb antibody. Tissues were homogenized and antibody concentrations were measured by specific immunoassays on the Gyros system. Exposure in terms of maximum concentration (Cmax ) and area under the curve was assessed for all nine tissues. Tissue exposure of full-length antibody relative to plasma exposure was found to be between 1% and 10%, except for brain (0.2%). Relative concentrations of FAb antibody were the same, except for kidney tissue, where the antibody concentration was found to be ten times higher than in plasma. However, the absolute tissue uptake of full-length IgG was significantly higher than the absolute tissue uptake of the FAb antibody. This study provides a reference PK state for full-length whole and FAb antibodies in tissues related to cardiovascular and metabolic diseases that do not include antigen or antibody binding.

  13. [Fecal microbiota transplantation].

    PubMed

    Šturdík, Igor; Hlavatý, Tibor; Payer, Juraj

    2016-02-01

    Fecal microbiota transplantation (FMT) is a therapeutic method, in which the fecal microflora from healthy donors is transmitted to the patient to restore the healthy microbial composition of the gut. In the recent years, there is a growing interest in the therapeutic potential of FMT in various diseases. The standard FMT protocols do not exist. Procedures of FMT vary in several aspects such as donor selection, preparation of fecal material, preparation of the recipient and administration way. FMT appears to be the most successful in the treatment of recurrent Clostridium difficile infection (CDI), randomized controlled studies reported 90 % success rate. There is a limited evidence for FMT as a treatment of ulcerative colitis. FMT has been also studied as treatment of diseases with impaired gut microbiota, such as cardiovascular, autoimmune and metabolic diseases. Many unanswered questions with regard to FMT remain and further research is needed. PMID:27172442

  14. Transplant biopsy beyond light microscopy.

    PubMed

    Adam, Benjamin; Mengel, Michael

    2015-01-01

    Despite its long-standing status as the diagnostic "gold standard", the renal transplant biopsy is limited by a fundamental dependence on descriptive, empirically-derived consensus classification. The recent shift towards personalized medicine has resulted in an increased demand for precise, mechanism-based diagnoses, which is not fully met by the contemporary transplantation pathology standard of care. The expectation is that molecular techniques will provide novel pathogenetic insights that will allow for the identification of more accurate diagnostic, prognostic, and therapeutic targets. Here we review the current state of molecular renal transplantation pathology. Despite significant research activity and progress within the field, routine adoption of clinical molecular testing has not yet been achieved. The recent development of novel molecular platforms suitable for use with formalin-fixed paraffin-embedded tissue will offer potential solution for the major barriers to implementation. The recent incorporation of molecular diagnostic criteria into the 2013 Banff classification is a reflection of progress made and future directions in the area of molecular transplantation pathology. Transcripts related to endothelial injury and NK cell activation have consistently been shown to be associated with antibody-mediated rejection. Prospective multicenter validation and implementation of molecular diagnostics for major entities remains an unmet clinical need in transplantation. It is expected that an integrated system of transplantation pathology diagnosis comprising molecular, morphological, serological, and clinical variables will ultimately provide the greatest diagnostic precision. PMID:26249165

  15. Low rate of cardiovascular events in patients with acute myocarditis diagnosed by cardiovascular magnetic resonance

    PubMed Central

    De Stefano, Luciano; Yeyati, Ezequiel Levy; Pietrani, Marcelo; Kohan, Andres; Falconi, Mariano; Benger, Juan; Dragonetti, Laura; Garcia-Monaco, Ricardo; Cagide, Arturo

    2014-01-01

    Background Myocarditis is a relatively common inflammatory disease that affects the myocardium. Infectious disease accounts for most of the cases either because of a direct viral infection or post-viral immune-mediated reaction. Cardiovascular magnetic resonance (CMR) has become an established non-invasive diagnosis tool for acute myocarditis. A recent large single centre study with patients with biopsy-proven viral myocarditis undergoing CMR scans found a high rate of mortality. The aim of this study was to assess the rate of clinical events in our population of patients with diagnosed myocarditis by CMR scan. Methods Patients who consulted to the emergency department with diagnosis of myocarditis by CMR were retrospectively included in the study from January 2008 to May 2012. A CMR protocol was used in all patients, and were followed up to assess the rate of the composite endpoint of all-cause death, congestive heart failure, sudden cardiac death, hospitalization for cardiac cause, recurrent myocarditis or need of radiofrequency ablation or implantable cardiac defibrillator (ICD). A descriptive statistical analysis was performed. Results Thirty-two patients with myocarditis were included in the study. The mean age was 42.6±21.2 years and 81.2% were male. In a mean follow up of 30.4±17.8 months, the rate of the composite endpoint of all-cause death, congestive heart failure, sudden cardiac death, hospitalization for cardiac cause, recurrent myocarditis or need of radiofrequency ablation or ICD was 15.6% (n=5). Two patients had heart failure (one of them underwent heart transplant), one patient needed ICD because of ventricular tachycardia and two other patients were re-hospitalized, for recurrent chest pain and for recurrent myocarditis respectively. Conclusions In our series of acute myocarditis diagnosed by CMR we found a low rate of cardiovascular events without mortality. These findings might oppose data from recently published myocarditis trials. PMID

  16. Cell Therapy for Cardiovascular Regeneration

    PubMed Central

    2013-01-01

    A great numbers of cardiovascular disease patients all over the world are suffering in the poor outcomes. Under this situation, cardiac regeneration therapy to reorganize the postnatal heart that is defined as a terminal differentiated-organ is a very important theme and mission for human beings. However, the temporary success of several clinical trials using usual cell types with uncertain cell numbers has provided the transient effect of cell therapy to these patients. We therefore should redevelop the evidence of cell-based cardiovascular regeneration therapy, focusing on targets (disease, patient’s status, cardiac function), materials (cells, cytokines, genes), and methodology (transplantation route, implantation technology, tissue engineering). Meanwhile, establishment of the induced pluripotent stem (iPS) cells is an extremely innovative technology which should be proposed as embryonic stem (ES) cellularization of post natal somatic cells, and this application have also showed the milestones of the direct conversion to reconstruct cardiomyocyte from the various somatic cells, which does not need the acquisition of the re-pluripotency. This review discusses the new advance in cardiovascular regeneration therapy from cardiac regeneration to cardiac re-organization, which is involved in recent progress of on-going clinical trials, basic research in cardiovascular regeneration, and the possibility of tissue engineering technology. PMID:23825492

  17. Transplant production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    For field pepper (Capsicum spp.) production, plants can be established from direct seed or transplants depending on the location and cultural practices for the specific pepper type grown. Direct seeding can result in slow, variable, and reduced plant stands due to variations in soil temperature, wat...

  18. Transplantation tolerance

    PubMed Central

    Muller, Yannick D; Seebach, Jörg D; Bühler, Leo H; Pascual, Manuel

    2011-01-01

    The major challenge in transplantation medicine remains long-term allograft acceptance, with preserved allograft function under minimal chronic immunosuppression. To safely achieve the goal of sustained donor-specific T and B cell non-responsiveness, research efforts are now focusing on therapies based on cell subsets with regulatory properties. In particular the transfusion of human regulatory T cells (Treg) is currently being evaluated in phase I/II clinical trials for the treatment of graft versus host disease following hematopoietic stem cell transplantation, and is also under consideration for solid organ transplantation. The purpose of this review is to recapitulate current knowledge on naturally occurring as well as induced human Treg, with emphasis on their specific phenotype, suppressive function and how these cells can be manipulated in vitro and/or in vivo for therapeutic purposes in transplantation medicine. We highlight the potential but also possible limitations of Treg-based strategies to promote long-term allograft survival. It is evident that the bench-to-beside translation of these protocols still requires further understanding of Treg biology. Nevertheless, current data already suggest that Treg therapy alone will not be sufficient and needs to be combined with other immunomodulatory approaches in order to induce allograft tolerance. PMID:21776332

  19. Heart Transplantation

    MedlinePlus

    A heart transplant removes a damaged or diseased heart and replaces it with a healthy one. The healthy heart comes from a donor who has died. It is the last resort for people with heart failure when all other treatments have failed. The ...

  20. Pancreas transplant

    MedlinePlus

    ... evidence that the complications of diabetes, such as diabetic retinopathy, may not get worse and may even improve after a pancreas-kidney transplant. More than 95% of people survive ... of the donated pancreas and kidney for the rest of your life.

  1. Angiotensin-I- and -III-mediated cardiovascular responses in the freshwater North American eel, Anguilla rostrata: effect of Phe8 deletion.

    PubMed

    Butler, D G; Oudit, G Y

    1995-02-01

    Cardiovascular responses to synthetic eel [Asn1, Val5, Gly9]-ANG-I, ANG-III (2-8), and ANG-I (1-7) were measured in conscious and resting freshwater North American eels. Indwelling Doppler flow probes were placed on the ventral and dorsal aortas, a pressure catheter in the lienomesenteric artery, and a peptide delivery catheter in the caudal vein. Twenty-five and 150 ng.kg-1 ANG-III increased baseline cardiac output (CO) (15.23 +/- 0.31 ml.min-1.kg-1; n = 5) by 23 and 47%, respectively, by increasing stroke volume (SV) but not heart rate (HR). ANG-I (150 ng.kg-1) also elevated CO (62%) by increasing both SV (44%) and HR (14%). Estimated branchial shunting (BS) was increased by 150 ng.kg-1 ANG-I and -III suggesting that more blood perfused the arteriovenous pathway in the gills. Dorsal aortic blood pressure (PDA) (3.08 +/- 0.12 kPa) was elevated by 150 ng.kg-1 ANG-I (67%) and -III (52%). Pressor responses temporally preceded the blood flow increases and there was a significant increase in systemic vascular resistance (RSYS) at the peak pressor responses. At the peak flow responses, increased CO was solely responsible for the increase in PDA; RSYS had returned to baseline values. Pressor responses to ANG-III decayed more rapidly (18.6 min) compared with those of ANG-I and -II (36 min). ANG-I (1-7) had no measurable effect on cardiovascular function indicating that the carboxyl-terminal 8-phenylalanine is an absolute requirement for the hormonal activity of angiotensin in fishes.

  2. Gut Bacteria Drive Kupffer Cell Expansion via MAMP-Mediated ICAM-1 Induction on Sinusoidal Endothelium and Influence Preservation-Reperfusion Injury after Orthotopic Liver Transplantation

    PubMed Central

    Corbitt, Natasha; Kimura, Shoko; Isse, Kumiko; Specht, Susan; Chedwick, Lisa; Rosborough, Brian R.; Lunz, John G.; Murase, Noriko; Yokota, Shinichiro; Demetris, Anthony J.

    2014-01-01

    Bacteria in the gut microbiome shed microbial-associated molecule patterns (MAMPs) into the portal venous circulation, where they augment various aspects of systemic immunity via low-level stimulation. Because the liver is immediately downstream of the intestines, we proposed that gut-derived MAMPs shape liver immunity and affect Kupffer cell (KC) phenotype. Germ-free (GF), antibiotic-treated (AVMN), and conventional (CL) mice were used to study KC development, function, and response to the significant stress of cold storage, reperfusion, and orthotopic transplantation. We found that a cocktail of physiologically active MAMPs translocate into the portal circulation, with flagellin (Toll-like receptor 5 ligand) being the most plentiful and capable of promoting hepatic monocyte influx in GF mice. In MAMP-deficient GF or AVMN livers, KCs are lower in numbers, have higher phagocytic activity, and have lower major histocompatibility complex II expression. MAMP-containing CL livers harbor significantly increased KC numbers via induction of intercellular adhesion molecule 1 on liver sinusoidal endothelium. These CL KCs have a primed yet expected phenotype, with increased major histocompatibility complex class II and lower phagocytic activity that increases susceptibility to liver preservation/reperfusion injury after orthotopic transplantation. The KC number, functional activity, and maturational status are directly related to the concentration of gut-derived MAMPs and can be significantly reduced by broad-spectrum antibiotics, thereby affecting susceptibility to injury. PMID:23159949

  3. ASICs and cardiovascular homeostasis.

    PubMed

    Abboud, François M; Benson, Christopher J

    2015-07-01

    In this review we address primarily the role of ASICs in determining sensory signals from arterial baroreceptors, peripheral chemoreceptors, and cardiopulmonary and somatic afferents. Alterations in these sensory signals during acute cardiovascular stresses result in changes in sympathetic and parasympathetic activities that restore cardiovascular homeostasis. In pathological states, however, chronic dysfunctions of these afferents result in serious sympatho-vagal imbalances with significant increases in mortality and morbidity. We identified a role for ASIC2 in the mechano-sensitivity of aortic baroreceptors and of ASIC3 in the pH sensitivity of carotid bodies. In spontaneously hypertensive rats, we reported decreased expression of ASIC2 in nodose ganglia neurons and overexpression of ASIC3 in carotid bodies. This reciprocal expression of ASIC2 and ASIC3 results in reciprocal changes in sensory sensitivity of baro- and chemoreceptors and a consequential synergistic exaggeration sympathetic nerve activity. A similar reciprocal sensory dysautonomia prevails in heart failure and increases the risk of mortality. There is also evidence that ASIC heteromers in skeletal muscle afferents contribute significantly to the exercise pressor reflex. In cardiac muscle afferents of the dorsal root ganglia, they contribute to nociception and to the detrimental sympathetic activation during ischemia. Finally, we report that an inhibitory influence of ASIC2-mediated baroreceptor activity suppresses the sympatho-excitatory reflexes of the chemoreceptors and skeletal muscle afferents, as well as the ASIC1a-mediated excitation of central neurons during fear, threat, or panic. The translational potential of activation of ASIC2 in cardiovascular disease states may be a beneficial sympatho-inhibition and parasympathetic activation. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'.

  4. Cardiovascular effects of basal insulins.

    PubMed

    Mannucci, Edoardo; Giannini, Stefano; Dicembrini, Ilaria

    2015-01-01

    Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane) and basal insulin analogs (glargine, detemir, and the more recent degludec) differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with regard to cardiovascular safety will provide definitive evidence. PMID:26203281

  5. Cardiovascular effects of basal insulins

    PubMed Central

    Mannucci, Edoardo; Giannini, Stefano; Dicembrini, Ilaria

    2015-01-01

    Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane) and basal insulin analogs (glargine, detemir, and the more recent degludec) differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with regard to cardiovascular safety will provide definitive evidence. PMID:26203281

  6. Long-term outcomes of children after solid organ transplantation

    PubMed Central

    Kim, Jon Jin; Marks, Stephen D.

    2014-01-01

    Solid organ transplantation has transformed the lives of many children and adults by providing treatment for patients with organ failure who would have otherwise succumbed to their disease. The first successful transplant in 1954 was a kidney transplant between identical twins, which circumvented the problem of rejection from MHC incompatibility. Further progress in solid organ transplantation was enabled by the discovery of immunosuppressive agents such as corticosteroids and azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ transplantation is a conventional treatment with improved patient and allograft survival rates. However, the challenge that lies ahead is to extend allograft survival time while simultaneously reducing the side effects of immunosuppression. This is particularly important for children who have irreversible organ failure and may require multiple transplants. Pediatric transplant teams also need to improve patient quality of life at a time of physical, emotional and psychosocial development. This review will elaborate on the long-term outcomes of children after kidney, liver, heart, lung and intestinal transplantation. As mortality rates after transplantation have declined, there has emerged an increased focus on reducing longer-term morbidity with improved outcomes in optimizing cardiovascular risk, renal impairment, growth and quality of life. Data were obtained from a review of the literature and particularly from national registries and databases such as the North American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT for liver, International Society for Heart and Lung Transplantation and UNOS for intestinal transplantation. PMID:24860856

  7. Long-term outcomes of children after solid organ transplantation.

    PubMed

    Kim, Jon Jin; Marks, Stephen D

    2014-01-01

    Solid organ transplantation has transformed the lives of many children and adults by providing treatment for patients with organ failure who would have otherwise succumbed to their disease. The first successful transplant in 1954 was a kidney transplant between identical twins, which circumvented the problem of rejection from MHC incompatibility. Further progress in solid organ transplantation was enabled by the discovery of immunosuppressive agents such as corticosteroids and azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ transplantation is a conventional treatment with improved patient and allograft survival rates. However, the challenge that lies ahead is to extend allograft survival time while simultaneously reducing the side effects of immunosuppression. This is particularly important for children who have irreversible organ failure and may require multiple transplants. Pediatric transplant teams also need to improve patient quality of life at a time of physical, emotional and psychosocial development. This review will elaborate on the long-term outcomes of children after kidney, liver, heart, lung and intestinal transplantation. As mortality rates after transplantation have declined, there has emerged an increased focus on reducing longer-term morbidity with improved outcomes in optimizing cardiovascular risk, renal impairment, growth and quality of life. Data were obtained from a review of the literature and particularly from national registries and databases such as the North American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT for liver, International Society for Heart and Lung Transplantation and UNOS for intestinal transplantation. PMID:24860856

  8. Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients

    PubMed Central

    Min, Ji Won; Kim, Kyoung Woon; Kim, Bo-Mi; Doh, Kyoung Chan; Choi, Min Seok; Choi, Bum Soon; Park, Cheol Whee; Yang, Chul Woo; Kim, Yong-Soo

    2016-01-01

    It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; P<0.05). Post-transplant BAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes. PMID:27631619

  9. Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients.

    PubMed

    Min, Ji Won; Kim, Kyoung Woon; Kim, Bo-Mi; Doh, Kyoung Chan; Choi, Min Seok; Choi, Bum Soon; Park, Cheol Whee; Yang, Chul Woo; Kim, Yong-Soo; Oh, Eun-Jee; Chung, Byung Ha

    2016-01-01

    It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; P<0.05). Post-transplant BAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes. PMID:27631619

  10. Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis

    PubMed Central

    Zhang, Hongyu; Siegel, Christopher T.; Shuai, Ling; Lai, Jiejuan; Zeng, Linli; Zhang, Yujun; Lai, Xiangdong; Bie, Ping; Bai, Lianhua

    2016-01-01

    NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2+ cells) that were isolated from healthy adult mouse liver by using a “Percoll-Plate-Wait” procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 106 cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2+ cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2+ cells may be novel adult liver progenitors that participate in liver regeneration. PMID:26905303

  11. IFN-gamma-receptor signaling ameliorates transplant vasculopathy through attenuation of CD8+ T-cell-mediated injury of vascular endothelial cells.

    PubMed

    Bolinger, Beatrice; Engeler, Daniel; Krebs, Philippe; Miller, Simone; Firner, Sonja; Hoffmann, Matthias; Palmer, Douglas C; Restifo, Nicholas P; Tian, Yinghua; Clavien, Pierre-Alain; Ludewig, Burkhard

    2010-03-01

    Occlusive transplant vasculopathy (TV) is the major cause for chronic graft rejection. Since endothelial cells (EC) are the first graft cells encountered by activated host lymphocytes, it is important to delineate the molecular mechanisms that coordinate the interaction of EC with activated T cells. Here, the interaction of CD8(+) T cells with Ag-presenting EC in vivo was examined using a transgenic heart transplantation model with beta-galactosidase (beta-gal) expression exclusively in EC (Tie2-LacZ hearts). We found that priming with beta-gal peptide-loaded DC failed to generate a strong systemic IFN-gamma response, but elicited pronounced TV in both IFN-gamma receptor (IFNGR)-competent, and ifngr(-/-) Tie2-LacZ hearts. In contrast, stimulation of EC-specific CD8(+) T cells with beta-gal-recombinant mouse cytomegalovirus (MCMV-LacZ) in recipients of ifngr(+/+) Tie2-LacZ hearts did not precipitate significant TV. However, MCMV-LacZ infection of recipients of ifngr(-/-) Tie2-LacZ hearts led to massive activation of beta-gal-specific CD8 T cells, and led to development of fulminant TV. Further analyses revealed that the strong systemic IFN-gamma "storm" associated with MCMV infection induced upregulation of programmed death-1 ligand 1 (PD-L1) on EC, and subsequent attenuation of programmed death-1 (PD-1)-expressing EC-specific CD8(+) T cells. Thus, IFNGR signaling in ECs activates a potent peripheral negative feedback circuit that protects vascularized grafts from occlusive TV. PMID:20049875

  12. The cardiovascular action of hexarelin

    PubMed Central

    Mao, Yuanjie; Tokudome, Takeshi; Kishimoto, Ichiro

    2014-01-01

    Hexarelin, a synthetic growth hormone-releasing peptide, can bind to and activate the growth hormone secretagogue receptor (GHSR) in the brain similar to its natural analog ghrelin. However, the peripheral distribution of GHSR in the heart and blood vessels suggests that hexarelin might have direct cardiovascular actions beyond growth hormone release and neuroendocrine effects. Furthermore, the non-GHSR CD36 had been demonstrated to be a specific cardiac receptor for hexarelin and to mediate its cardioprotective effects. When compared with ghrelin, hexarelin is chemically more stable and functionally more potent. Therefore, it may be a promising therapeutic agent for some cardiovascular conditions. In this concise review, we discuss the current evidence for the cardiovascular action of hexarelin. PMID:25278975

  13. The Use of Statins in Hematopoietic Stem Cell Transplantation and Solid Organ Transplantation.

    PubMed

    Shimabukuro-Vornhagen, Alexander; Schlösser, Hans; Kisner, Tulay; Stippel, Dirk L; von Bergwelt-Baildon, Michael

    2013-01-14

    Allogeneic hematopoietic stem cell transplantation and solid organ transplantation have become established treatments offered to patients for whom there are otherwise no curative treatment options. Unfortunately, these therapeutic modalities are associated with severe complications that limit its applicability. Alloimmunity is an important cause of morbidity and mortality after both organ transplantation and allogeneic hematopoietic stem cell transplantation and represents a major barrier to the more wide-spread use of these treatment modalities. Statins are a class of lipid-lowering drugs, which also posses immunomodulatory effects. Results from preclinial research and early-stage clinical studies indicate that treatment with statins could be beneficial for the prevention and treatment of graft-versus-host disease and transplant rejection. In addition to preventing graft-versus-host disease or graft rejection statins possess several other effects that might prove beneficial in the setting of transplantation, such as cardiovascular protection and antineoplastic activity. Here we summarize the current knowledge about the immunomodulatory effects of statins and discuss the clinical implications for their use in patients undergoing stem cell transplantation or solid organ transplantation.

  14. Meniscal allograft transplantation

    MedlinePlus

    Meniscus transplant; Surgery - knee - meniscus transplant; Surgery - knee - cartilage; Arthroscopy - knee - meniscus transplant ... the lab for any diseases and infection. Other surgeries, such as ligament or cartilage repairs, may be ...

  15. Pancreatic Islet Transplantation

    MedlinePlus

    ... allo-transplantation?" For each pancreatic islet allo-transplant infusion, researchers use specialized enzymes to remove islets from ... in a lab. Transplant patients typically receive two infusions with an average of 400,000 to 500, ...

  16. Current Issues in Liver Transplantation

    PubMed Central

    2016-01-01

    The state of liver transplantation continues to evolve. This article focuses on 3 separate yet important issues within this field. First, there is a proposal to change the allocation of donor livers in the United States. The fundamental premise of this proposal is to equalize access to donor livers across the country. To accomplish this goal, the proposal is to increase the geographic area of liver allocation. As might be expected, there is a great deal of controversy surrounding the possibility of a major change in liver allocation and distribution. A second area of interest, and perhaps the most important therapeutic breakthrough in the field of hepatology, is the introduction of direct-acting antiviral agents against hepatitis C virus (HCV) infection. With cure rates up to 100%, an increasing proportion of liver transplant candidates and recipients are being cured of HCV infection with therapies that have minimal side effects. Consequently, the impact of HCV infection on patient and graft survival will likely improve substantially over the next few years. Finally, this article reviews the role of donor-specific antibodies (DSAs) in antibody-mediated rejection. Long recognized as an important factor in graft survival in renal transplantation, DSAs have recently been shown to be a strong predictor of graft and patient survival in liver transplantation. However, the importance of DSAs in liver transplantation is uncertain, in large part due to the absence of proven therapies. PMID:27231452

  17. Objectively measured second hand smoke exposure and risk of cardiovascular disease: what is the mediating role of inflammatory and haemostatic factors?

    PubMed Central

    Hamer, Mark; Stamatakis, Emmanuel; Kivimaki, Mika; Lowe, Gordon D; Batty, G. David

    2011-01-01

    Objectives To examine the association between objectively measured second–hand-smoke (SHS) exposure and incident CVD death, and assess the extent to which this association can be explained through novel circulating markers of inflammation and haemostasis. Background Existing evidence suggests there is an association between SHS and cardiovascular disease (CVD) risk, although the mechanisms remain poorly understood. Methods In a prospective study of 13,443 participants living in England and Scotland [aged 53.5, (SD 12.6 yrs), 52.3% women] we measured salivary cotinine (an objective marker of SHS exposure) and novel CVD biomarkers (C-reactive protein, fibrinogen) at baseline. Results 20.8% of the sample had high SHS exposure based on elevated levels of salivary cotinine (0.71 – 14.99 ng/mL). During a mean follow-up of 8 years, there were 1221 all-cause deaths and 364 CVD deaths. High SHS was associated with all-cause (age adjusted HR= 1.25, 95% CI, 1.02 – 1.53) and CVD death (age adjusted HR= 1.21, 95% CI, 0.85 – 1.73). High SHS was also associated with elevated CRP, which explained 48% of the association between SHS and CVD death. The excess risk of CVD associated with active smoking was exaggerated in relation to self report (age adjusted HR= 3.27, 95% CI, 2.48 – 4.31) compared with objective assessment (age adjusted HR= 2.44, 95% CI, 1.75 – 3.40). Conclusion Among a large representative sample of British adults we observed elevated levels of low grade inflammation in otherwise healthy participants exposed to high SHS, and this partly explained their elevated risk of CVD death. PMID:20620712

  18. Cardiovascular group

    NASA Technical Reports Server (NTRS)

    Blomqvist, Gunnar

    1989-01-01

    As a starting point, the group defined a primary goal of maintaining in flight a level of systemic oxygen transport capacity comparable to each individual's preflight upright baseline. The goal of maintaining capacity at preflight levels would seem to be a reasonable objective for several different reasons, including the maintenance of good health in general and the preservation of sufficient cardiovascular reserve capacity to meet operational demands. It is also important not to introduce confounding variables in whatever other physiological studies are being performed. A change in the level of fitness is likely to be a significant confounding variable in the study of many organ systems. The principal component of the in-flight cardiovascular exercise program should be large-muscle activity such as treadmill exercise. It is desirable that at least one session per week be monitored to assure maintenance of proper functional levels and to provide guidance for any adjustments of the exercise prescription. Appropriate measurements include evaluation of the heart-rate/workload or the heart-rate/oxygen-uptake relationship. Respiratory gas analysis is helpful by providing better opportunities to document relative workload levels from analysis of the interrelationships among VO2, VCO2, and ventilation. The committee felt that there is no clear evidence that any particular in-flight exercise regimen is protective against orthostatic hypotension during the early readaptation phase. Some group members suggested that maintenance of the lower body muscle mass and muscle tone may be helpful. There is also evidence that late in-flight interventions to reexpand blood volume to preflight levels are helpful in preventing or minimizing postflight orthostatic hypotension.

  19. Cardiovascular Disease

    PubMed Central

    Grace, Sherry L; Fry, Rick; Cheung, Angela; Stewart, Donna E

    2004-01-01

    Health Issue Cardiovascular disease (CVD) is the leading cause of death in Canadian women and men. In general, women present with a wider range of symptoms, are more likely to delay seeking medial care and are less likely to be investigated and treated with evidence-based medications, angioplasty or coronary artery bypass graft than men. Key Findings In 1998, 78,964 Canadians died from CVD, almost half (39,197) were women. Acute myocardial infarction, which increases significantly after menopause, was the leading cause of death among women. Cardiovascular disease accounted for 21% of all hospital admissions for Canadian women over age 50 in 1999. Admissions to hospital for ischemic heart disease were more frequent for men, but the mean length of hospital stay was longer for women. Mean blood pressure increases with age in both men and women. After age 65, however, high blood pressure is more common among Canadian women. More than one-third of postmenopausal Canadian women have hypertension. Diabetes increases the mortality and morbidity associated with CVD in women more than it does in men. Depression also contributes to the incidence and recovery from CVD, particularly for women who experience twice the rate of depression as men. Data Gaps and Recommendations CVD needs to be recognized as a woman's health issue given Canadian mortality projections (particularly heart failure). Health professionals should be trained to screen, track, and address CVD risk factors among women, including hypertension, elevated lipid levels, smoking, physical inactivity, depression, diabetes and low socio-economic status. PMID:15345078

  20. Air pollution and cardiovascular disease.

    PubMed

    Franklin, Barry A; Brook, Robert; Arden Pope, C

    2015-05-01

    An escalating body of epidemiologic and clinical research provides compelling evidence that exposure to fine particulate matter air pollution contributes to the development of cardiovascular disease and the triggering of acute cardiac events. There are 3 potential mediating pathways that have been implicated, including "systemic spillover," autonomic imbalance, and circulating particulate matter constituents. Further support that the increased morbidity and mortality attributed to air pollution comes from studies demonstrating the adverse cardiovascular effects of even brief periods of exposure to secondhand smoke. Accordingly, persons with known or suspected cardiovascular disease, the elderly, diabetic patients, pregnant women, and those with pulmonary disease should be counseled to limit leisure-time outdoor activities when air pollution is high. Recognizing the insidious and pervasive nature of air pollution, and the associated odds ratios and population attributable fractions for this widely underappreciated chemical trigger of acute cardiovascular events, may serve to maximize the potential for cardiovascular risk reduction by addressing at least a portion of the 10%-25% incidence of coronary disease that is unexplained by traditional risk factors.

  1. PPARs and the Cardiovascular System

    PubMed Central

    Hamblin, Milton; Chang, Lin; Fan, Yanbo; Zhang, Jifeng

    2009-01-01

    Abstract Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone-receptor superfamily. Originally cloned in 1990, PPARs were found to be mediators of pharmacologic agents that induce hepatocyte peroxisome proliferation. PPARs also are expressed in cells of the cardiovascular system. PPARγ appears to be highly expressed during atherosclerotic lesion formation, suggesting that increased PPARγ expression may be a vascular compensatory response. Also, ligand-activated PPARγ decreases the inflammatory response in cardiovascular cells, particularly in endothelial cells. PPARα, similar to PPARγ, also has pleiotropic effects in the cardiovascular system, including antiinflammatory and antiatherosclerotic properties. PPARα activation inhibits vascular smooth muscle proinflammatory responses, attenuating the development of atherosclerosis. However, PPARδ overexpression may lead to elevated macrophage inflammation and atherosclerosis. Conversely, PPARδ ligands are shown to attenuate the pathogenesis of atherosclerosis by improving endothelial cell proliferation and survival while decreasing endothelial cell inflammation and vascular smooth muscle cell proliferation. Furthermore, the administration of PPAR ligands in the form of TZDs and fibrates has been disappointing in terms of markedly reducing cardiovascular events in the clinical setting. Therefore, a better understanding of PPAR-dependent and -independent signaling will provide the foundation for future research on the role of PPARs in human cardiovascular biology. Antioxid. Redox Signal. 11, 1415–1452. PMID:19061437

  2. PPARs and the cardiovascular system.

    PubMed

    Hamblin, Milton; Chang, Lin; Fan, Yanbo; Zhang, Jifeng; Chen, Y Eugene

    2009-06-01

    Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone-receptor superfamily. Originally cloned in 1990, PPARs were found to be mediators of pharmacologic agents that induce hepatocyte peroxisome proliferation. PPARs also are expressed in cells of the cardiovascular system. PPAR gamma appears to be highly expressed during atherosclerotic lesion formation, suggesting that increased PPAR gamma expression may be a vascular compensatory response. Also, ligand-activated PPAR gamma decreases the inflammatory response in cardiovascular cells, particularly in endothelial cells. PPAR alpha, similar to PPAR gamma, also has pleiotropic effects in the cardiovascular system, including antiinflammatory and antiatherosclerotic properties. PPAR alpha activation inhibits vascular smooth muscle proinflammatory responses, attenuating the development of atherosclerosis. However, PPAR delta overexpression may lead to elevated macrophage inflammation and atherosclerosis. Conversely, PPAR delta ligands are shown to attenuate the pathogenesis of atherosclerosis by improving endothelial cell proliferation and survival while decreasing endothelial cell inflammation and vascular smooth muscle cell proliferation. Furthermore, the administration of PPAR ligands in the form of TZDs and fibrates has been disappointing in terms of markedly reducing cardiovascular events in the clinical setting. Therefore, a better understanding of PPAR-dependent and -independent signaling will provide the foundation for future research on the role of PPARs in human cardiovascular biology.

  3. Development of T cell-mediated immunity after autologous stem cell transplantation: prolonged impairment of antigen-stimulated production of gamma-interferon.

    PubMed

    van der Velden, A M T; Claessen, A M E; van Velzen-Blad, H; Biesma, D H; Rijkers, G T

    2007-08-01

    The conditioning regimens for autologous SCT (auto-SCT) lead to impairment of the immune system and concomitant increase in susceptibility to infections. We studied the recovery of cellular immunity by in vitro analysis of T-cell proliferation and cytokine production profiles during the first 15 months after auto-SCT in patients with multiple myeloma and non-Hodgkin's lymphoma. PBMC were collected at 6, 9 and 15 months after transplantation and stimulated with a combination of CD2 and CD28 monoclonal antibodies, with PHA or with tetanus toxoid as recall antigen. A multiplex enzyme linked immunoassay was used to determine levels of Th1 cytokines IL-2, IFN-gamma and tumour-necrosis factor-alpha (TNF-alpha), Th2 cytokines IL-4, IL-5 and IL-13, the regulatory cytokine IL-10 and the proinflammatory cytokines IL-1alpha, IL-1beta, IL-6 and the chemokine IL-8. T-cell proliferation progressively increased from 6 to 15 months after auto-SCT. Overall, cytokine production increased after auto-SCT. Production of Th2 cytokines IL-5 and IL-13 was superior to production of Th1 cytokines IFN-gamma and TNF-alpha. We hypothesize that prolonged impairment of IFN-gamma production might contribute to the relatively high incidence of viral infections after auto-SCT.

  4. Post-transplantation diabetes-state of the art.

    PubMed

    Sharif, Adnan; Cohney, Solomon

    2016-04-01

    With increasing success in overcoming the immunological and infectious challenges accompanying solid organ transplantation, susceptibility to post-transplant diabetes and cardiovascular disease has assumed increasing importance. Although some guidance is available from diabetes-related literature pertaining to the general population, some aspects are unique to solid organ allograft recipients. Both insulin resistance and β-cell dysfunction are generally agreed to contribute to development and manifestation of post-transplant diabetes, but controversy continues about which is most important and to what extent post-transplant diabetes is a distinct entity or simply a variant of type 2 diabetes with transplant-specific components. The optimum method and timing for detection and diagnosis of post-transplant diabetes remains an area of uncertainty. However, the greatest needs are to: address the absence of contemporary data for incidence and clinical outcomes associated with post-transplant diabetes; establish the role of glycaemic control; and assess the role of new diabetic therapies in prevention and management of post-transplant diabetes. We place the present knowledge base in the context of other advances in transplantation, challenge some existing ideas, and examine the potential role of emerging diabetes therapies. In highlighting existing deficiencies, we hope to provide direction for future research that will ultimately reduce incidence and improve management of post-transplant diabetes. PMID:26632096

  5. Perioperative monitoring in liver transplant patients.

    PubMed

    Singh, Shweta; Nasa, Vaibhav; Tandon, Manish

    2012-09-01

    Liver transplant (LT) is a major surgical undertaking involving major fluid shifts, hemodynamic instability and metabolic derangements in a patient with preexisting liver failure and multisystemic derangements. Monitoring and organ support initiated in the preoperative phase is continued intraoperatively and into the postoperative phase to ensure an optimal outcome. As cardiovascular events are the leading cause of non-graft related death among LT recipients, major emphasis is placed on cardiovascular monitoring. The other essential monitoring are the continuous assessment of coagulapathy, extent of metabolic derangements, dyselectrolytemis and intracranial pressure monitoring in patients with fulminant hepatic failure. The type and extent of monitoring differs with need according to preexisting child status of the patient and the extent of systemic derangements. It also varies among transplant centers and is mainly determined by individual or institutional practices.

  6. Perioperative monitoring in liver transplant patients.

    PubMed

    Singh, Shweta; Nasa, Vaibhav; Tandon, Manish

    2012-09-01

    Liver transplant (LT) is a major surgical undertaking involving major fluid shifts, hemodynamic instability and metabolic derangements in a patient with preexisting liver failure and multisystemic derangements. Monitoring and organ support initiated in the preoperative phase is continued intraoperatively and into the postoperative phase to ensure an optimal outcome. As cardiovascular events are the leading cause of non-graft related death among LT recipients, major emphasis is placed on cardiovascular monitoring. The other essential monitoring are the continuous assessment of coagulapathy, extent of metabolic derangements, dyselectrolytemis and intracranial pressure monitoring in patients with fulminant hepatic failure. The type and extent of monitoring differs with need according to preexisting child status of the patient and the extent of systemic derangements. It also varies among transplant centers and is mainly determined by individual or institutional practices. PMID:25755443

  7. Heart transplantation.

    PubMed

    Nakatani, Takeshi

    2009-06-01

    A total of 59 heart transplantations (HTx) have been performed in Japan as of September, 2008, since the Organ Transplantation Law was settled in October 1997. The majority of recipients were suffered from dilated cardiomyopathy and waiting condition of all recipients were status 1. The mean waiting time was 777 day; 50 patients (85%) were supported by several types of left ventricular assist systems (LVAS) and the mean duration of support was 780 days. The majority of patients underwent operation by modified bicaval method with Celsior solution for cardiac preservation, and 64% of recipients were administered triple therapy with cyclosporine, mycophenolate mofetil, and steroid as the initial immunosuppressive regimen. The 9-year survival rate was 94%, which was superior to that of the international registry. HTx in Japan has been very limited by a severe shortage of donors, but the results have been excellent even though the majority of recipients were waiting for long-term with a LVAS as a bridge to HTx.

  8. Endocannabinoids and the cardiovascular response to stress.

    PubMed

    O'Sullivan, Saoirse E; Kendall, Patrick J; Kendall, David A

    2012-01-01

    Stress activates the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS), resulting in cardiovascular responses. The endocannabinoid system (ECS), a ubiquitously expressed lipid signalling system, modulates both HPA and SNS activity. The purpose of this review is to explore the possible involvement/role of the ECS in the cardiovascular response to stress. The ECS has numerous cardiovascular effects including modulation of blood pressure, heart rate, the baroreflex, and direct vascular actions. It is also involved in a protective manner in response to stressors in cardiac preconditioning, and various stressors (for example, pain, orthostasis and social stress) increase plasma levels of endocannabinoids. Given the multitude of vascular effects of endocannabinoids, this is bound to have consequences. Beneficial effects of ECS upregulation could include cardioprotection, vasodilatation, CB(2)-mediated anti-inflammatory effects and activation of peroxisome proliferator-activated receptors. Negative effects of endocannabinoids could include mediation of the effects of glucocorticoids, CB(1)-mediated metabolic changes, and metabolism to vasoconstrictor products. It is also likely that there is a central role for the ECS in modulating cardiovascular activity via the HPA and SNS. However, much more work is required to fully integrate the role of the ECS in mediating many of the physiological responses to stress, including cardiovascular responses.

  9. Haemodynamic modeling of the cardiovascular system using mock circulation loops to test cardiovascular devices.

    PubMed

    Timms, Daniel L; Gregory, Shaun D; Stevens, Michael C; Fraser, John F

    2011-01-01

    Comprehensive testing and evaluation of cardiovascular device function and performance is required prior to clinical implementation. Initial proof of concept investigations are conducted within in-vitro mock circulation loops, before proof of principle is demonstrated via in-vivo animal testing. To facilitate the rapid transition of cardiovascular devices through this development period, a testing apparatus was developed that closely models the natural human cardiovascular system haemodynamics. This mock circulation system accurately replicates cardiac function, coupled to systemic and pulmonary circulations. The physiological response produced by a number of clinical cardiovascular conditions can be actively controlled by variable parameters such as vascular resistance, arterial/venous compliance, ventricle contractility, heart rate, and heart /vascular volumes, while anatomical variations such as valve regurgitation and septal defects can be included. Auto-regulation of these parameters was attempted to reproduce the Frank-Starling mechanism, baroreceptor reflex, skeletal muscle pump, and postural changes. Steady state validation of loop performance was achieved by replicating the progression of a patient's clinical haemodynamics from heart failure, through VAD support, to heart transplantation. The system has been used to evaluate pulsatile and non-pulsatile ventricular assist devices, counter pulsation devices, non-invasive cardiac output monitors and cardiovascular stents. The interaction of these devices with the cardiovascular system was also investigated with regards to physiological control strategies and cannula placement. The system is a valuable tool for the accelerated progression of cardiovascular device development.

  10. [Transplantation of autologous skeletal myoblasts in ischemic cardiac insufficiency].

    PubMed

    Pouzet, B; Hagège, A A; Vilquin, J T; Desnos, M; Duboc, D; Marolleau, J P; Menashé, P

    2001-01-01

    Despite medical therapeutic advances, congestive heart failure (CHF), which is the common ultimate consequence of many primary cardiovascular diseases, remains a major and growing public health problem. Although orthotopic heart transplantation is the gold standard, there is now growing evidence that one therapeutic option could be cellular cardiomyoplasty. Autologous adult skeletal myoblast transplantation seems to be the most clinically relevant, compared with other cell types, in that it avoids immunosuppression therapy, availability and ethical issues. Previous experimental studies have documented the efficacy of myoblast transplantation in improving function of infarcted myocardium. Although the mechanisms involved in this improvement are not elucidated, it has been demonstrated convincingly enough to consider ripping to clinical trials.

  11. Immunosuppressive protocols and immunological challenges related to hand transplantation.

    PubMed

    Ravindra, Kadiyala V; Ildstad, Suzanne T

    2011-11-01

    There are many immunological challenges related to hand transplantation. Curbing the immune system's ability to effectively mount an immune response against the graft is the goal. As the various components of the immune response are defined and their mechanisms of action delineated, more specific immunosuppressive agents and protocols have been developed. Complications related to immunosuppression in hand transplant recipients are similar to incidences among solid organ recipients. With longer follow-up, the increased cardiovascular risk factors or the development of a neoplasm will likely cause mortality. Standardizing immunosuppression in hand transplantation with the long-term goal of minimization is critically needed.

  12. [Long-term-management of organ transplant recipients].

    PubMed

    Bürger, Christin; Schmidt, Martina; Maschmeier, Miriam; Stella, Jaqueline; Hüsing, Anna; Wilms, Christian; Schmidt, Hartmut Hans-Jürgen; Kabar, Iyad

    2016-07-01

    Due to advances in immunosuppressive therapy and surgical techniques, survival rates after solid organ transplantation have constantly improved over the last decades. In long-term care after transplantation, physicians need to focus as much on diagnosis and treatment of allograft-related complications as they should consider comorbidities and evaluate risk-factors and adverse events of immunosuppressive agents to prevent secondary diseases. In particular, cardiovascular and metabolic diseases, malignancy and infection play a major role in long-term survival. Therefore, screening of organ transplant recipients in regard to these complications and adverse events is a crucial part of follow up in these patients. PMID:27359310

  13. Antibodies in Transplantation

    PubMed Central

    Platt, Jeffrey L.

    2011-01-01

    Transplantation of cells, tissues, and organs from one individual to another can incite the production of antibodies specific for foreign antigens, especially major histocompatibility antigens, in the graft. Antibodies specific for a graft provide an index of immunity and a potential trigger for injury and rejection. However, the index of immunity can sometimes miss antibody-mediated rejection and besides causing injury the antibodies against a graft can also protect a graft from injury by blocking immune recognition, called enhancement, regulating activation of complement, and inducing changes in the graft that resist damage. Reviewed here are potential limitations in the use of antibodies as an index of immunity and the ways antibodies cause and/or prevent injury. PMID:20807473

  14. Risk assessment and management of post-transplant diabetes mellitus.

    PubMed

    Han, Eugene; Kim, Myoung Soo; Kim, Yu Seun; Kang, Eun Seok

    2016-10-01

    The success rate of organ transplantation has been increasing with advances in surgical and pharmacological techniques. However, the number of solid organ transplant recipients who require metabolic disease management is also growing. Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation and is associated with risks of graft loss, cardiovascular morbidity, and mortality. Other risk factors for PTDM include older age, genetic background, obesity, hepatitis C virus infection, hypomagnesemia, and use of immunosuppressant agents (corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitor). Management of PTDM should be started before the transplantation plan to properly screen high-risk patients. Even though PTDM management is similar to that of general type 2 diabetes, therapeutic approaches must be made with consideration of drug interactions between immunosuppressive agents, glucose-lowering medications, and graft rejection and function.

  15. Risk assessment and management of post-transplant diabetes mellitus.

    PubMed

    Han, Eugene; Kim, Myoung Soo; Kim, Yu Seun; Kang, Eun Seok

    2016-10-01

    The success rate of organ transplantation has been increasing with advances in surgical and pharmacological techniques. However, the number of solid organ transplant recipients who require metabolic disease management is also growing. Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation and is associated with risks of graft loss, cardiovascular morbidity, and mortality. Other risk factors for PTDM include older age, genetic background, obesity, hepatitis C virus infection, hypomagnesemia, and use of immunosuppressant agents (corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitor). Management of PTDM should be started before the transplantation plan to properly screen high-risk patients. Even though PTDM management is similar to that of general type 2 diabetes, therapeutic approaches must be made with consideration of drug interactions between immunosuppressive agents, glucose-lowering medications, and graft rejection and function. PMID:27621191

  16. Non-alcoholic fatty liver disease and liver transplantation.

    PubMed

    Khan, Reenam S; Newsome, Philip N

    2016-08-01

    Cirrhosis secondary to non-alcoholic steatohepatitis (NASH) is a common indication for liver transplant. In comparison to other cirrhotic patients, patients with NASH cirrhosis are more likely to be older and have the metabolic syndrome. Pre-transplant, patients require careful evaluation of cardiovascular risk. As the incidence of non-alcoholic fatty liver disease (NAFLD) is rising, a greater proportion of donor grafts have steatosis greater than 30%, which is associated with poor outcomes. Grafts with steatosis greater than 60% are unsuitable for transplant. Overall, post-transplant survival outcomes for patients with NASH cirrhosis are similar to those with cirrhosis without NASH. However, NASH cirrhosis is associated with a higher 30-day mortality, predominantly from an increase in cardiovascular events and infections. Following liver transplant, there is a significant risk of NASH recurrence, although this seldom results in allograft loss. Furthermore, a significant number of patients who had a liver transplant for other reasons develop NASH de novo. When patients with NASH cirrhosis are considered for transplant, one of the major challenges lies in identifying which patients are too high risk for surgery. This review aims to provide information to aid this decision making process, and to provide guidance on the peri-operative care strategies that can modify risk. PMID:26997540

  17. Associations of Pre-transplant Prescription Narcotic Use with Clinical Complications after Kidney Transplantation

    PubMed Central

    Lentine, Krista L.; Lam, Ngan N.; Xiao, Huiling; Tuttle-Newhall, Janet E.; Axelrod, David; Brennan, Daniel C.; Dharnidharka, Vikas R.; Yuan, Hui; Nazzal, Mustafa; Zheng, Jie; Schnitzler, Mark A.

    2015-01-01

    Background Associations of narcotic use before kidney transplantation with post-transplant clinical outcomes are not well described. Methods We examined integrated national transplant registry, pharmacy records, and Medicare billing claims to follow 16,322 kidney transplant recipients, of whom 28.3% filled a narcotic prescription in the year before transplantation. Opioid analgesic fills were normalized to morphine equivalents (ME) and expressed as mg/kg exposures (approximate quartiles: 0.1– 1.7, 1.8–5.4, 5.5–23.7, and ≥23.8 mg/kg, respectively). Post-transplant cardiovascular, respiratory, neurological, accidents, substance abuse, and non-compliance events were identified using diagnosis codes on Medicare billing claims. Adjusted associations of ME level with post-transplant complications were quantified by multivariate Cox regression. Results The incidence of complications at 3 years post-transplant among those with the highest pre-transplant ME exposure compared to no use included: ventricular arrhythmias, 1.1% vs. 0.2% (p<0.001); cardiac arrest, 4.7% vs. 2.7% (p<0.05); hypotension, 14% vs. 8% (p<0.0001); hypercapnia, 1.6% vs. 0.9% (p<0.05); mental status changes, 5.3% vs. 2.7% (p<0.001); drug abuse/dependence, 7.0% vs. 1.7% (p<0.0001); alcohol abuse, 1.8% vs. 0.6% (p=0.0001); accidents, 0.9% vs. 0.3% (p<0.05); and non-compliance, 3.5% vs. 2.3% (p<0.05). In multivariate analyses, transplant recipients with the highest level of pre-transplant narcotic use had approximately 2-to-4-times the risks of post-transplant ventricular arrhythmias, mental status changes, drug abuse, alcohol abuse, and accidents compared with non-users, and 35% to 45% higher risks of cardiac arrest and hypotension. Conclusion Although associations may reflect underlying conditions or behaviors, high-level prescription narcotic use before kidney transplantation predicts increased risk of clinical complications after transplantation. PMID:25832723

  18. New options for the management of hyperparathyroidism after renal transplantation

    PubMed Central

    Douthat, Walter Guillermo; Chiurchiu, Carlos Raul; Massari, Pablo Ulises

    2012-01-01

    The persistence and severity of hyperparathyroidism (HPT) post-renal transplantation is relatively frequent and primarily associated with the timing and its magnitude in the pre-transplant period and with the presence of parathyroid adenomas. HPT after renal transplantation is clinically manifested with hypercalcemia, hypophosphatemia, bone pain, fractures, and in more serious cases with cardiovascular calcifications that affect the survival. The primary clinical objective for patients with secondary HPT after renal transplantation is to obtain a level of parathyroid hormone (PTH) adequate to the renal transplanted function and to normalize levels of calcium, phosphorus and vitamin D. In many cases during this period, the development of hypercalcemia and/or hypophosphatemia makes it necessary to take different therapeutic measures. The use of vitamin D or its analogues has been extrapolated from the management of pre-transplant HPT obtaining variable outcomes, although its use is limited by its capacity to produce hypercalcemia. Calcimimetics are drugs that have proven be effective in reducing PTH levels in patients with HPT on dialysis and has been effective in reducing up to 50% PTH levels in moderate to severe HPT in post-renal transplantation.When HPT persists after renal transplantation and does not respond to medical treatment, invasive management by percutaneous ethanol injection therapy of parathyroid glands or parathyroidectomy should be considered. The emergence of new methods for the management of HPT expands the availability of therapeutic tools for transplant patients. PMID:24175195

  19. Liposomes for cardiovascular targeting.

    PubMed

    Levchenko, Tatyana S; Hartner, William C; Torchilin, Vladimir P

    2012-04-01

    Liposome-based pharmaceuticals used within the cardiovascular system are reviewed in this article. The delivery of diagnostic and therapeutic agents by plain liposomes and liposomes with surface-attached targeting antibodies or polyethylene glycol to prolong their circulation time and accumulation at vascular injuries, ischemic zones or sites of thrombi are also discussed. An overview of the advantages and disadvantages of liposome-mediated in vitro, ex vivo and in vivo targeting is presented, including discussion of the targeting of liposomes to pathological sites on the blood vessel wall and a description of liposomes that can be internalized by endothelial cells. Diagnostic liposomes used to target myocardial infarction and the relative importance of liposome size, targetability of immunoliposomes and prolonged circulation time on the efficiency of sealing hypoxia-induced plasma membrane damage to cardiocytes are discussed as a promising approach for therapy. The progress in the use of targeted liposomal plasmids for the transfection of hypoxic cardiomyocytes and myocardium is presented. Stent-mediated liposomal-based drug delivery is also reviewed briefly. PMID:22834079

  20. Restoration of vision after transplantation of photoreceptors.

    PubMed

    Pearson, R A; Barber, A C; Rizzi, M; Hippert, C; Xue, T; West, E L; Duran, Y; Smith, A J; Chuang, J Z; Azam, S A; Luhmann, U F O; Benucci, A; Sung, C H; Bainbridge, J W; Carandini, M; Yau, K-W; Sowden, J C; Ali, R R

    2012-05-01

    Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1−/− mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.

  1. Ghrelin and the cardiovascular system.

    PubMed

    Tokudome, Takeshi; Kishimoto, Ichiro; Miyazato, Mikiya; Kangawa, Kenj

    2014-01-01

    Ghrelin is a peptide that was originally isolated from the stomach. It exerts potent growth hormone (GH)-releasing and orexigenic activities. Several studies have highlighted the therapeutic benefits of ghrelin for the treatment of cardiovascular disease. In animal models of chronic heart failure, the administration of ghrelin improved cardiac function and remodeling; these findings were replicated in human patients with heart failure. Moreover, in an animal study, ghrelin administration effectively reduced pulmonary hypertension induced by chronic hypoxia. In addition, repeated administration of ghrelin to cachectic patients with chronic obstructive pulmonary disease had positive effects on overall body function, including muscle wasting, functional capacity and sympathetic activity. The administration of ghrelin early after myocardial infarction (MI) reduced fatal arrhythmia and related mortality. In ghrelin-deficient mice, both exogenous and endogenous ghrelin were protective against fatal arrhythmia and promoted remodeling after MI. Although the mechanisms underlying the effects of ghrelin on the cardiovascular system remain unclear, there are indications that its beneficial effects are mediated through both direct physiological actions, including increased GH levels, improved energy balance and direct actions on cardiovascular cells, and regulation of autonomic nervous system activity. Therefore, ghrelin is a promising novel therapeutic agent for cardiovascular disease.

  2. [Liver transplants from living donors].

    PubMed

    Rogiers, X; Danninger, F; Malagó, M; Knoefel, W T; Gundlach, M; Bassas, A; Burdelski, M; Broelsch, C E

    1996-03-01

    In this article the authors discuss the advantages of Living Related Liver Transplantation (LRLT), criteria for the selection of donors and the standard operation technique. Among a total of 241 liver transplantation (LTx), 42 LRLT were performed at the University of Hamburg between October 1, 1991 and December 19, 1994. The body weight of recipients for LRLT ranged from 4,6 to 39 kg, with 64,2% having less than 10 kg. The volume of the donor left lateral liver lobe ranged from 100 cc to 350 cc. The average one year survival rate among electively operated patients-status 3-4 (UNOS 1995 classification) was 86.7%, two year survival rate 83.3%. The main advantages of LRLT are consired the following: 1. Absence of mortality on the waiting list, 2. Optimal timing of the transplantation (elective procedure, patient in a good condition), 3. Excellent organ (no primary non function), 4. A possible immunologic advantage, 5. Relief of the waiting list for cadaveric organs, 6. Psychological benefit for the family, 7. Cost effectiveness. Potential candidates for living donation with more than one cardiovascular risk factors were excluded. Social and psychological reasons leading to rejection of candidates were as follows: unstable family structure, expected professional or financial difficulties after living donation or withdrawal from consent. LRLT gives parents of a child with TLD a chance to avoid the risk of death on the waiting list or primary non function of the graft. LRLT has therefore established an important place in pediatric liver transplantation. PMID:8768973

  3. Organ transplantation in Tunisia.

    PubMed

    El Matri, Aziz; Ben Abdallah, Taieb

    2015-04-01

    Kidney transplants were first performed in Tunisia in 1986, and transplants soon extended to other organs including the heart, liver, and pancreas. Live-related donor and deceased-donor kidney transplants were both began in the summer of 1986. An organ procurement and transplant law was passed in March 1991, and the National Centre for Advancement of Organ Transplantation was created in 1995. The number of transplantation units has increased to 7 throughout the country, and the yearly transplant number has progressively increased to 139 in 2010, including 20% from deceased kidney donors. Despite these gains, the need continues to grow. Heart transplants began in January 1993, and Tunisia and Jordan are currently the only Arab countries where it is practiced. However, only 16 patients have received a heart transplant as of 2004, and the number of recipients has decreased in the past 10 years. Liver transplants are rare in other Arab countries, but began in Tunisia in January 1998. Over 10 years, 38 patients benefited from this procedure. After a few years of stagnation, the number of liver transplants is increasing. While all types of transplantation are needed, kidney transplantation is a priority in Tunisia. The target is to perform 400 transplants annually, which would require a long-term strategy to provide full financial coverage using the National Health Insurance Funds in both the public and private sectors.

  4. Prevalence of pre-transplant electrocardiographic abnormalities and post-transplant cardiac events in patients with liver cirrhosis

    PubMed Central

    2014-01-01

    Background Although cardiovascular disease is thouht to be common in cirrhosis, there are no systematic investigations on the prevalence of electrocardiographic (ECG) abnormalities in these patients and data on the occurrence of post-transplant cardiac events in comparison with the general population are lacking. We aimed to study the prevalence and predictors of ECG abnormalities in patients with cirrhosis undergoing liver transplantation and to define the risk of cardiac events post-transplant compared to the general population. Methods Cirrhotic patients undergoing first-time liver transplantation between 1999–2007 were retrospectively enrolled. ECGs at pre-transplant evaluation were reviewed using the Minnesota classification and compared to healthy controls. Standardized incidence ratios for post-transplant cardiac events were calculated. Results 234 patients with cirrhosis were included, 186 with an available ECG (36% with alcoholic and 24% with viral cirrhosis; mean follow-up 4 years). Cirrhotics had a prolonged QTc interval, a Q wave, abnormal QRS axis deviation, ST segment depression and a pathologic T wave more frequently compared to controls (p < 0.05 for all). Arterial hypertension, older age, cirrhosis severity and etiology were related to ECG abnormalities. Compared to the general Swedish population, patients were 14 times more likely to suffer a cardiac event post-transplant (p < 0.001). A prolonged QTc interval and Q wave were related to post-transplant cardiac events (p < 0.05 for all). Conclusions Pre-transplant ECG abnormalities are common in cirrhosis and are associated with cardiovascular risk factors and cirrhosis severity and etiology. Post-transplant cardiac events are more common than in the general population. PMID:24708568

  5. Who Needs a Lung Transplant?

    MedlinePlus

    ... from the NHLBI on Twitter. Who Needs a Lung Transplant? Your doctor may recommend a lung transplant ... lungs to pick up oxygen. Applying to a Lung Transplant Program Lung transplants are done in medical ...

  6. Transplantation: a brief history.

    PubMed

    Dangoor, Joseph Yoav; Hakim, David N; Singh, Rajinder Pal; Hakim, Nadey S

    2015-02-01

    Developments in transplantation have progressed dramatically over the past century. Current research is underway to optimize immune modulation, genetically engineering animals for xenografting, and breakthroughs are occurring in regenerative medicine. However, pioneering live-donor transplantation has transformed transplantation in the organ shortage, and these contribute an increased proportion of transplanted organs. Live-donor transplantation is associated with better long-term outcomes, and techniques to recover organs have become less invasive. We set out to examine the evolution of transplantation from its historic beginnings to the developments that make it successful today.

  7. Flagellin, a novel mediator of Salmonella-induced epithelial activation and systemic inflammation: I kappa B alpha degradation, induction of nitric oxide synthase, induction of proinflammatory mediators, and cardiovascular dysfunction.

    PubMed

    Eaves-Pyles, T; Murthy, K; Liaudet, L; Virág, L; Ross, G; Soriano, F G; Szabó, C; Salzman, A L

    2001-01-15

    Gram-negative sepsis is mediated by the actions of proinflammatory genes induced in response to microbes and their products. We report that flagellin, the monomeric subunit of flagella, is a potent proinflammatory species released by Salmonella. Flagellin (1 microgram/ml) induces IkappaBalpha degradation, NF-kappaB nuclear translocation, and inducible NO synthase expression in cultured intestinal epithelial cells (IEC). Aflagellic Salmonella mutants do not induce NF-kappaB activation or NO production by cultured IEC. Antiserum to flagellin blocks NO production in IEC induced by medium conditioned by a variety of motile Gram-negative enteric pathogens (Escherichia coli, Salmonella muenchen, Serratia marcescens, Proteus mirabilis, and Proteus vulgaris). Flagellin, when injected systemically (approximately 10 microgram/mouse), induces systemic inflammation characterized by the systemic expression of a range of proinflammatory cytokines and chemokines and of inducible NO synthase. At higher doses (approximately 300 microgram/mouse), flagellin induces shock, characterized by hypotension, reduced vascular contractility in mice, and death. The effects of flagellin do not diminish in C3H/HeJ LPS-resistant mice, indicating that the Toll-like receptor-4 receptor is not involved in flagellin's actions. In LPS-resistant mice, i.p. injection of S. dublin flagellin or medium conditioned by wild-type S. dublin induces serum IFN-gamma and TNF-alpha, whereas medium conditioned by aflagellic mutants has no effect. Flagellin can be detected in the blood of rats with septic shock induced by live bacteria at approximately 1 microg/ml. We propose that flagellin released by Gram-negative pathogens may contribute to the inflammatory response by an LPS- and Toll-like receptor-4-independent pathway.

  8. Gene therapy in corneal transplantation.

    PubMed

    Qazi, Yureeda; Hamrah, Pedram

    2013-01-01

    Corneal transplantation is the most commonly performed organ transplantation. Immune privilege of the cornea is widely recognized, partly because of the relatively favorable outcome of corneal grafts. The first-time recipient of corneal allografts in an avascular, low-risk setting can expect a 90% success rate without systemic immunosuppressive agents and histocompatibility matching. However, immunologic rejection remains the major cause of graft failure, particularly in patients with a high risk for rejection. Corticosteroids remain the first-line therapy for the prevention and treatment of immune rejection. However, current pharmacological measures are limited in their side-effect profiles, repeated application, lack of targeted response, and short duration of action. Experimental ocular gene therapy may thus present new horizons in immunomodulation. From efficient viral vectors to sustainable alternative splicing, we discuss the progress of gene therapy in promoting graft survival and postulate further avenues for gene-mediated prevention of allogeneic graft rejection.

  9. The Human Umbilical Cord Tissue-Derived MSC Population UCX(®) Promotes Early Motogenic Effects on Keratinocytes and Fibroblasts and G-CSF-Mediated Mobilization of BM-MSCs When Transplanted In Vivo.

    PubMed

    Miranda, Joana P; Filipe, Elysse; Fernandes, Ana Sofia; Almeida, Joana M; Martins, José P; De la Fuente, Alexandre; Abal, Miguel; Barcia, Rita N; Cruz, Pedro; Cruz, Helder; Castro, Matilde; Santos, Jorge M

    2015-01-01

    Mesenchymal stromal cells (MSCs) play an important role in tissue regeneration mainly through the secretion of trophic factors that enhance the repair of damaged tissues. The main goal of this work was to study the paracrine mechanisms by which an umbilical cord tissue-derived MSC population (UCX(®)) promotes the migration capacity of human dermal fibroblasts and keratinocytes, which is highly relevant for skin regeneration. Furthermore, the differences between paracrine activities of MSCs from the umbilical cord tissue and the bone marrow (BM-MSCs) were also evaluated. In vitro scratch assays revealed that conditioned media (CM) obtained from both growing and stationary-phase UCX(®) cultures induced human dermal fibroblast (HDF) and keratinocyte (HaCaT) migration. These assays showed that the motogenic activity of UCX(®) CM to HaCaTs was significantly higher than to HDFs, in opposition to the effect seen with CM produced by BM-MSCs that preferentially induced HDF migration. Accordingly, a comparative quantification of key factors with vital importance in the consecutive stages of wound healing revealed very different secretome profiles between UCX(®) and BM-MSCs. The relatively higher UCX(®) expression of EGF, FGF-2, and KGF strongly supports early induction of keratinocyte migration and function, whereas the UCX(®)-specific expression of G-CSF suggested additional roles in mobilization of healing-related cells including CD34(-)/CD45(-) precursors (MSCs) known to be involved in tissue regeneration. Accordingly, in vitro chemotaxis assays and an in vivo transplantation model for chemoattraction confirmed that UCX(®) are chemotactic to CD34(-)/CD45(-) BM-MSCs via a cell-specific mobilization mechanism mediated by G-CSF. Overall, the results strongly suggest different paracrine activities between MSCs derived from different tissue sources, revealing the potential of UCX(®) to extend the regenerative capacity of the organism by complementing the role of

  10. Ambulatory blood pressure monitoring in solid organ transplantation.

    PubMed

    Ramesh Prasad, G V

    2012-01-01

    Solid organ transplant recipients are at an increased risk for hypertension and cardiovascular disease. To assist in their management, 24-h ambulatory blood pressure monitoring (ABPM) has become increasingly used in both clinical research settings and practice. ABPM has been used to better define post-transplant hypertension incidence and prevalence in different solid organ transplantation populations. ABPM provides additional information on cardiovascular risk beyond that obtained by clinic-based readings, based on its ability to assess 24-h blood pressure (BP) load, detect nocturnal non-dipping, and predict target organ damage. It has provided some assurance about the safety of living kidney donation. Information from ABPM can be used to guide living kidney donor selection, and because ABPM-related data has been correlated with clinically important kidney and heart transplant recipient outcomes, it may be a valuable adjunct in their management. Despite these advantages, barriers to wider use of ABPM include expense, clinical inertia in hypertension management, lack of prospective clinical trial data, and clinical problems that compete with hypertension for attention such as acute or chronic allograft dysfunction. The increasing amount of research and clinical use for ABPM may allow for closer assessment and intervention to help address the increased cardiovascular risk faced by many solid organ transplant recipients. PMID:22220828

  11. Pancreas transplantation: review.

    PubMed

    Meirelles Júnior, Roberto Ferreira; Salvalaggio, Paolo; Pacheco-Silva, Alvaro

    2015-01-01

    Vascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone.

  12. Pancreas transplantation: review

    PubMed Central

    Meirelles, Roberto Ferreira; Salvalaggio, Paolo; Pacheco-Silva, Alvaro

    2015-01-01

    ABSTRACT Vascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone. PMID:26154551

  13. Notch signaling in the developing cardiovascular system.

    PubMed

    Niessen, Kyle; Karsan, Aly

    2007-07-01

    The Notch proteins encompass a family of transmembrane receptors that have been highly conserved through evolution as mediators of cell fate. Recent findings have demonstrated a critical role of Notch in the developing cardiovascular system. Notch signaling has been implicated in the endothelial-to-mesenchymal transition during development of the heart valves, in arterial-venous differentiation, and in remodeling of the primitive vascular plexus. Mutations of Notch pathway components in humans are associated with congenital defects of the cardiovascular system such as Alagille syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and bicuspid aortic valves. This article focuses on the role of the Notch pathway in the developing cardiovascular system and congenital human cardiovascular diseases.

  14. Potassium in hypertension and cardiovascular disease.

    PubMed

    Castro, Hector; Raij, Leopoldo

    2013-05-01

    The increased prevalence of hypertension and cardiovascular disease in industrialized societies undoubtedly is associated with the modern high-sodium/low-potassium diet. Extensive experimental and clinical data strongly link potassium intake to cardiovascular outcome. Most studies suggest that the sodium-to-potassium intake ratio is a better predictor of cardiovascular outcome than either nutrient individually. A high-sodium/low-potassium environment results in significant abnormalities in central hemodynamics, leading to potential target organ damage. Altered renal sodium handling, impaired endothelium-dependent vasodilatation, and increased oxidative stress are important mediators of this effect. It remains of paramount importance to reinforce consumption of a low-sodium/high-potassium diet as a critical strategy for prevention and treatment of hypertension and cardiovascular disease.

  15. Cardiovascular Disease and Diabetes

    MedlinePlus

    ... Blood Pressure Tools & Resources Stroke More Cardiovascular Disease & Diabetes Updated:Mar 23,2016 The following statistics speak ... disease. This content was last reviewed August 2015. Diabetes • Home • About Diabetes • Why Diabetes Matters Introduction Cardiovascular ...

  16. Iron deficiency and cardiovascular disease.

    PubMed

    von Haehling, Stephan; Jankowska, Ewa A; van Veldhuisen, Dirk J; Ponikowski, Piotr; Anker, Stefan D

    2015-11-01

    Iron deficiency affects up to one-third of the world's population, and is particularly common in elderly individuals and those with certain chronic diseases. Iron excess can be detrimental in cardiovascular illness, and research has now also brought anaemia and iron deficiency into the focus of cardiovascular medicine. Data indicate that iron deficiency has detrimental effects in patients with coronary artery disease, heart failure (HF), and pulmonary hypertension, and possibly in patients undergoing cardiac surgery. Around one-third of all patients with HF, and more than one-half of patients with pulmonary hypertension, are affected by iron deficiency. Patients with HF and iron deficiency have shown symptomatic improvements from intravenous iron administration, and some evidence suggests that these improvements occur irrespective of the presence of anaemia. Improved exercise capacity has been demonstrated after iron administration in patients with pulmonary hypertension. However, to avoid iron overload and T-cell activation, it seems that recipients of cardiac transplantations should not be treated with intravenous iron preparations.

  17. Infection and Cardiovascular Disease

    ClinicalTrials.gov

    2016-02-17

    Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Myocardial Infarction; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Atherosclerosis

  18. Islet Cell Transplantation

    MedlinePlus

    ... the body use glucose for energy. Islet cell transplantation transfers cells from an organ donor into the ... to make and release insulin. Researchers hope islet transplantation will help people with type 1 diabetes live ...

  19. Vascular calcification, bone and mineral metabolism after kidney transplantation

    PubMed Central

    D’Marco, Luis; Bellasi, Antonio; Mazzaferro, Sandro; Raggi, Paolo

    2015-01-01

    The development of end stage renal failure can be seen as a catastrophic health event and patients with this condition are considered at the highest risk of cardiovascular disease among any other patient groups and risk categories. Although kidney transplantation was hailed as an optimal solution to such devastating disease, many issues related to immune-suppressive drugs soon emerged and it became evident that cardiovascular disease would remain a vexing problem. Progression of chronic kidney disease is accompanied by profound alterations of mineral and bone metabolism that are believed to have an impact on the cardiovascular health of patients with advanced degrees of renal failure. Cardiovascular risk factors remain highly prevalent after kidney transplantation, some immune-suppression drugs worsen the risk profile of graft recipients and the alterations of mineral and bone metabolism seen in end stage renal failure are not completely resolved. Whether this complex situation promotes progression of vascular calcification, a hall-mark of advanced chronic kidney disease, and whether vascular calcifications contribute to the poor cardiovascular outcome of post-transplant patients is reviewed in this article. PMID:26722649

  20. Primary Care of the Renal Transplant Patient

    PubMed Central

    Unruh, Mark L.; Nolin, Thomas D.; Hasley, Peggy B.

    2010-01-01

    There has been a remarkable rise in the number of kidney transplant recipients (KTR) in the US over the last decade. Increasing use of potent immunosuppressants, which are also potentially diabetogenic and atherogenic, can result in worsening of pre-existing medical conditions as well as development of post-transplant disease. This, coupled with improving long-term survival, is putting tremendous pressure on transplant centers that were not designed to deliver primary care to KTR. Thus, increasing numbers of KTR will present to their primary care physicians (PCP) post-transplant for routine medical care. Similar to native chronic kidney disease patients, KTRs are vulnerable to cardiovascular disease as well as a host of other problems including bone disease, infections and malignancies. Deaths related to complications of cardiovascular disease and malignancies account for 60–65% of long-term mortality among KTRs. Guidelines from the National Kidney Foundation and the European Best Practice Guidelines Expert Group on the management of hypertension, dyslipidemia, smoking, diabetes and bone disease should be incorporated into the long-term care plan of the KTR to improve outcomes. A number of transplant centers do not supply PCPs with protocols and guidelines, making the task of the PCP more difficult. Despite this, PCPs are expected to continue to provide general preventive medicine, vaccinations and management of chronic medical problems. In this narrative review, we examine the common medical problems seen in KTR from the PCP’s perspective. Medical management issues related to immunosuppressive medications are also briefly discussed. PMID:20422302

  1. Buyer beware transplantation.

    PubMed

    Chapman, Jeremy R; Delmonico, Francis L

    2016-05-01

    Poor long-term outcomes of commercial transplantation of transplant tourists reinforce the need to prevent this form of human trafficking. The development of an International Convention by the Council of Europe is highlighted and the implications for physicians of the criminalizing of organ trafficking are considered. The causes of poor outcomes from transplant tourism are considered, with the actions needed to provide both equity and sufficiency of access to transplantation as critical deterrent measures. PMID:27083275

  2. Hp: an inflammatory indicator in cardiovascular disease.

    PubMed

    Graves, Karen L; Vigerust, David J

    2016-07-01

    Over the past decade significant advancement has occurred in the biological and pathological role that Hp has in cardiovascular disease. Hp is an acute-phase protein with a role in the neutralization and clearance of free heme. Iron has tremendous potential for initiating vascular oxidation, inflammation and exacerbating coronary atherosclerosis. Hp genotype has been linked as a prognostic biomarker of acute myocardial infarction, heart failure, restenosis and cardiac transplant rejection. The increased understanding of Hp as a biomarker has provided new insights into the mechanisms of inflammation after cardiac injury and support the concept that Hp is not only an important antioxidant in vascular inflammation and atherosclerosis, but also an enhancer of inflammation in cardiac transplant. PMID:27203711

  3. Organ Transplants in Kazakhstan.

    PubMed

    Baigenzhin, Abay; Doskaliyev, Zhaksylyk; Tuganbekova, Saltanat; Zharikov, Serik; Altynova, Sholpan; Gaipov, Abduzhappar

    2015-11-01

    The Republic of Kazakhstan is one of the fastest developing countries in the world and has a health care system that is unique in Central Asia. Its organ transplant services are also developing rapidly. We aimed to analyze and briefly report on the current status of organ transplant in the Republic of Kazakhstan. We analyzed organ transplant activities in that country for the period 2012 to 2014. All data were collected from the official database of the National Transplant Coordinating Center of the Republic of Kazakhstan. At the end of 2014, the number of transplant centers had increased to 10, three of which could perform multiorgan transplants; during the same period, the number of deceased-donor organ-donating hospitals increased up to 37. By 2013, the transplant activity rate for all centers had reached 9.22 per million population. During the previous 3 years (2012-2014), there was a 3-fold increase in the number of living donors and an 18-fold increase in the number of kidney transplants. Between 2012 and 2014, the number of living-donor liver transplants increased from 17 to 25, and the number of deceased-donor transplants increased from 3 to 7. During the last 3 years (2012-2014), the number of heart transplants increased to 7 cases. During the last 3 years (2012-2014), Kazakhstan achieved a significant improvement in the organization of its transplant services, and a noticeable upward trend in the system continues.

  4. Immunomodulation during sepsis in organ transplanted children.

    PubMed

    Angele, M K; Loehe, F; Faist, E

    2005-10-01

    Newer immunosuppressive agents have dramatically reduced the rates of acute graft rejection over the last decade but may have exacerbated the problem of post-transplant infections. Causes of early mortality include graft dysfunction and sepsis. Late mortality occurs mainly due to sepsis. An excessive inflammatory response followed with a dramatic paralysis of cell-mediated immunity has been documented in septic patients. In transplanted individuals the pathophysiological changes of the immune response are further complicated by immunosuppressive agents. This article will focus on the effect of immunosuppressive agents and sepsis on cell-mediated immune responses. Moreover, potentially promising immunomodulatory approaches, i.e. human activated protein C, immunomodulatory diets containing L-arginine and fish oil, selective cytokine blockade, platelet-activating factor receptor antagonist, LPS receptor CD14 blockade and G-CSF, for the treatment of immunodysfunction in septic patients will be outlined in this review article. Most of them, however, have not been tested in the clinical arena in transplanted patients. Thus, the main part of the article, immunomodulation during sepsis in organ transplanted children is quite speculative and based on immunomodulatory strategies in other non-transplanted septic patients.

  5. Successful renal transplantation following prior bone marrow transplantation in pediatric patients.

    PubMed

    Thomas, Susan E; Hutchinson, Raymond J; DebRoy, Meelie; Magee, John C

    2004-10-01

    Improving survival rates following pediatric bone marrow transplantation (BMT) will likely result in greater numbers of children progressing to end-stage renal disease (ESRD) because of prior chemotherapy, irradiation, sepsis, and exposure to nephrotoxic agents. Renal transplantation remains the treatment of choice for ESRD; however, the safety of renal transplantation in this unique population is not well established. We report our experience with living related renal transplantation in three pediatric patients with ESRD following prior BMT. Two patients with neuroblastoma and ESRD because of BMT nephropathy, and one patient with Schimke immuno-osseous dysplasia and ESRD because of immune complex mediated glomerulonephritis and nephrotic syndrome. Age at time of BMT ranged from 2 to 7 yr. All patients had stable bone marrow function prior to renal transplantation. Age at renal transplant ranged from 8 to 14 yr. All three patients have been managed with conventional immunosuppression, as no patient received a kidney and BMT from the same donor source. These patients are currently 7 months to 6 yr status post-living related transplant. All have functioning bone marrow and kidney transplants, with serum creatinine levels ranging 0.6-1.2 mg/dL. There have been no episodes of rejection. One patient with a history of grade III skin and grade IV gastrointestinal-graft-vs.-host disease (GI-GVHD) prior to transplantation, had a mild flare of GI-GVHD (grade I) post-renal transplant and is currently asymptomatic. The incidence of opportunistic infection has been comparable with our pediatric renal transplant population without prior BMT. One patient was treated for basal cell carcinoma via wide local excision. Renal transplantation is an excellent option for the treatment of pediatric patients with ESRD following BMT. Short-term results in this small population show promising patient and graft survival, however long-term follow-up is needed. Pre-existing immune system

  6. Depression and cardiovascular disease.

    PubMed

    Elderon, Larkin; Whooley, Mary A

    2013-01-01

    Approximately one out of every five patients with cardiovascular disease (CVD) suffers from major depressive disorder (MDD). Both MDD and depressive symptoms are risk factors for CVD incidence, severity and outcomes. Great progress has been made in understanding potential mediators between MDD and CVD, particularly focusing on health behaviors. Investigators have also made considerable strides in the diagnosis and treatment of depression among patients with CVD. At the same time, many research questions remain. In what settings is depression screening most effective for patients with CVD? What is the optimal screening frequency? Which therapies are safe and effective? How can we better integrate the care of mental health conditions with that of CVD? How do we motivate depressed patients to change health behaviors? What technological tools can we use to improve care for depression? Gaining a more thorough understanding of the links between MDD and heart disease, and how best to diagnose and treat depression among these patients, has the potential to substantially reduce morbidity and mortality from CVD.

  7. [Transplantation and outcome quality].

    PubMed

    Bechstein, W O; Wullstein, C

    2002-06-01

    Organ transplants are procedures which require intensive personal and material resources. The results of organ transplants have continuously improved during recent decades. International data bases (registries) have documented the continuous evolution of organ transplantation. On the basis of the German Transplant Law guidelines for "Requirements regarding quality control for procedures related to organ procurement and transplantation" have been formulated by the German Medical Chamber. Thus, monitoring of outcome quality will become a requirement for all German transplant centers. In this paper, the guidelines for the different organ transplants (kidney, pancreas, liver, heart, lung) are discussed as well as quality control for living donor transplantation. Studies from the USA and Europe demonstrated volume-outcome relationships in organ transplantation. In addition, in kidney transplantation a centre-effect could be demonstrated which influences outcome more than the immunological match between donor and recipient. The introduction of required quality control may have far reaching consequences for the future structure of organ transplantation in Germany. PMID:12149941

  8. Cardiovascular complications of respiratory diseases.

    PubMed

    Chowdhuri, Susmita; Crook, Errol D; Taylor, Herman A; Badr, M Safwan

    2007-11-01

    A major burden of morbidity and mortality due to respiratory diseases can be directly related to the cardiovascular (CV) complications of these disorders. Evidence from cross-sectional and longitudinal studies link reduced lung function and cardiovascular diseases. However, the underlying pathogenic mechanisms are unclear. Hypoxia-induced increased sympathetic activity, blood viscosity, or inflammation, among other factors, may mediate the underlying pathogenesis. In addition, sleep-disordered breathing (SDB) has been implicated by association in multiple CV diseases including hypertension, ischemic heart disease, congestive heart failure, arrhythmias, and stroke. However, the exact contribution of SDB, including obstructive and central sleep apneas, to the development of cardiovascular diseases is not fully understood. In this context, the contribution of the new large, prospective, Jackson Heart Study could be significant in that it is designed to answer several of these questions, specifically in the African American population. This review examines the current evidence that links both reduced lung function and SDB to CV diseases. PMID:18004091

  9. Advances in pancreas transplantation.

    PubMed

    Dholakia, Shamik; Oskrochi, Youssof; Easton, Graham; Papalois, Vassilios

    2016-04-01

    The potential to reverse diabetes has to be balanced against the morbidity of long-term immunosuppression associated with transplantation. For a patient with renal failure, the treatment of choice is often a simultaneous transplant of the pancreas and kidney or pancreas after kidney. For a patient with glycaemic instability, choices between a solid organ or islet transplant have to be weighed against benefits and risks of remaining on insulin. Results of simultaneous transplant of the pancreas and kidney transplantation are comparable to other solid-organ transplants, and there is evidence of improved quality of life and life expectancy. There is some evidence of benefit with respect to the progression of secondary diabetic complications in patients with functioning transplants for several years.

  10. Infection Prevention in Transplantation.

    PubMed

    Pergam, Steven A

    2016-01-01

    The number of patients undergoing hematopoietic cell and solid organ transplantation are increasing every year, as are the number of centers both transplanting and caring for these patients. Improvements in transplant procedures, immunosuppressive regimens, and prevention of transplant-associated complications have led to marked improvements in survival in both populations. Infections remain one of the most important sources of excess morbidity and mortality in transplant, and therefore, infection prevention strategies are a critical element for avoiding these complications in centers caring for high-risk patients. This manuscript aims to provide an update of recent data on prevention of major healthcare-associated infections unique to transplantation, reviews the emergence of antimicrobial resistant infections, and discusses updated strategies to both identify and prevent transmission of these pathogens in transplant recipients.

  11. Neoplastic disease after liver transplantation: Focus on de novo neoplasms

    PubMed Central

    Burra, Patrizia; Rodriguez-Castro, Kryssia I

    2015-01-01

    De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma (HCC) recurrence have been reported with the use of mTOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs mTOR-inhibitor-free immunosuppression is more efficacious in reducing HCC recurrence. PMID:26269665

  12. Approach to kidney transplant in sensitized potential transplant recipients.

    PubMed

    Barbari, Antoine; Abbas, Souodod; Jaafar, Mahassen

    2012-10-01

    More than one-third of patients on waiting lists for kidney transplant are sensitized. Most have previously formed donor-specific and non-donor-specific serum antibodies and/or positive crossmatch by complement-dependent cytotoxity and/or flow cytometry. Two categories of alloantibodies include antibodies against major histocompatibility complex human leukocyte antigen class 1 and class 2 and antibodies against minor histocompatibility complex. A current positive crossmatch is an absolute contraindication for transplant. Positive historical panel reactive antibody and/or donor-specific antibodies (human leukocyte antigen and minor histocompatibility complex), even in the absence of a historical positive crossmatch, are associated with an increased risk for allosensitization, antibodymediated rejection, and accelerated graft failure. Desensitization protocols are numerous, complex, and expensive. It is recommended to perform a systematic determination of historical and current panel reactive antibody, donor-specific antibodies (human leukocyte antigen and minor histocompatibility complex), and crossmatch by the most sensitive assays. The risk of sensitization may be estimated from the combined results of the crossmatch with the donor and those of the recipient's panel reactive antibody and donor-specific antibodies at baseline. The adoption of a scoring system for risk stratification may facilitate the task of organ allocation for sensitized patients. Recipients with an estimated sensitization risk ≥ high may be referred preferably to the national waiting priority list and informed about the financial and the medical risks that may incur with future transplant. Sensitized patients at high risk for antibody-mediated rejection may benefit from a structured monitoring process involving systematic and regular immunologic, histologic, and functional assessments of the graft after transplant. We recommend the adoption and regular updating of these approaches to ensure

  13. Apelin and its receptor APJ in cardiovascular diseases.

    PubMed

    Yu, Xiao-Hua; Tang, Zhi-Bin; Liu, Li-Jing; Qian, Hong; Tang, Shi-Lin; Zhang, Da-Wei; Tian, Guo-Ping; Tang, Chao-Ke

    2014-01-20

    Apelin is an adipokine that has been identified as an endogenous ligand for the orphan receptor APJ. Apelin and APJ are expressed in a diverse range of tissues with particular preponderance for the heart and vasculature. Apelin has powerful positive inotropic actions and causes endothelium- and nitric oxide-dependent vasodilatation. Growing evidence shows that apelin/APJ system functions as a critical mediator of cardiovascular homeostasis and is involved in the pathophysiology of cardiovascular diseases. Targeting apelin/APJ axis produces protection against cardiovascular diseases. In the current review we have summarized recent data concerning the role and therapeutic potential of apelin/APJ in several major cardiovascular diseases. An increased understanding of the cardiovascular actions of apelin/APJ system will help to develop novel therapeutic interventions for cardiovascular diseases. PMID:24055369

  14. Obesity and cardiovascular disease.

    PubMed

    Jokinen, E

    2015-02-01

    Cardiovascular disease is the most common cause of mortality in rich countries and today it has the same meaning for health care as the epidemics of past centuries had for medicine in earlier times: 50% of the population in these countries die of cardiovascular disease. The amount of cardiovascular disease is also increasing in the developing countries together with economic growth. By 2015 one in three deaths will globally be due to cardiovascular diseases. Coronary heart disease is a chronic disease that starts in childhood, even if the symptoms first occur in the middle age. The risks for coronary heart disease are well-known: lipid disorders, especially high serum LDL-cholesterol concentration, high blood pressure, tobacco smoking, obesity, diabetes, male gender and physical inactivity. Obesity is both an independent risk factor for cardiovascular disease but is also closely connected with several other risk factors. This review focuses on the connection between overweight or obesity and cardiovascular disease. PMID:25387321

  15. [Hypertension in patients after heart transplantation].

    PubMed

    Matysek, J; Piwowarska, W

    1995-01-01

    Arterial hypertension is a serious and common complication of cyclosporine administration in humans. The prevalence of arterial hypertension in patients following orthotopic heart transplantation ranges from 38% to 92%. There are several characteristic features of this form of hypertension, including very early onset--usually within 4 to 6 weeks after transplantation and persistence with little alteration overtime. Diurnal profile shows the lack of normal nocturnal decline in blood pressure (BP) and appearance of the highest values of BP early in the morning. This phenomenon is caused by altered regulation of BP due to cardiac denervation. There was shown no correlation between the dose of cyclosporine and development of posttransplant arterial hypertension. It develops also independently of many investigated pretransplant and posttransplant cardiovascular risk factors. A great deal of attention has been focused on explantation of cyclosporine influence leading to hypertension occurrence. suggested mechanisms of this action are: elevation of systemic vascular resistance, prostaglandines and tromboxance production imbalance, hypomagnesemia, increased intravascular volume, modulation of sympathetic activity, nephrotoxicity. Reninangiotensin system seems to be not significantly associated with posttransplant hypertension, whereas the role of corticosteroides is still controversal. Hypertension remains the most common complication associated with cyclosporine administration in heart transplant recipients. Mechanisms of cyclosporine action leading to development of hypertension are still unknown. Further investigation is also needed into clinical significance of posttransplant hypertension and its influence on long-term survival after heart transplantation as they remain undefined.

  16. Metabolic complications in liver transplant recipients

    PubMed Central

    Jiménez-Pérez, Miguel; González-Grande, Rocío; Omonte Guzmán, Edith; Amo Trillo, Víctor; Rodrigo López, Juan Miguel

    2016-01-01

    The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS. PMID:27605877

  17. Metabolic complications in liver transplant recipients

    PubMed Central

    Jiménez-Pérez, Miguel; González-Grande, Rocío; Omonte Guzmán, Edith; Amo Trillo, Víctor; Rodrigo López, Juan Miguel

    2016-01-01

    The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS.

  18. Metabolic complications in liver transplant recipients.

    PubMed

    Jiménez-Pérez, Miguel; González-Grande, Rocío; Omonte Guzmán, Edith; Amo Trillo, Víctor; Rodrigo López, Juan Miguel

    2016-07-28

    The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS. PMID:27605877

  19. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  20. Genetic Modification of Stem Cells for Transplantation

    PubMed Central

    Phillips, M. Ian; Tang, Yao Liang

    2009-01-01

    Gene modification of cells for prior to their transplantation, especially stem cells, enhances their survival and increases their function in cell therapy. Like the Trojan horse, the gene modified cell has to gain entrance inside the host’s walls and survive and deliver its transgene products Using cellular, molecular and gene manipulation techniques the transplanted cell can be protected in a hostile environment from immune rejection, inflammation, hypoxia and apoptosis. Genetic engineering to modify cells involves constructing modules of functional gene sequences. They can be simple reporter genes or complex cassettes with gene switches, cell specific promoters and multiple transgenes. We discuss methods to deliver and construct gene cassettes with viral and non viral delivery, siRNA, and conditional Cre/Lox P. We review the current uses of gene modified stem cells in cardiovascular disease, diabetes, neurological diseases,( including Parkinson’s, Alzheimer’s and spinal cord injury repair), bone defects, hemophilia, and cancer. PMID:18031863

  1. Epigenomics in hematopoietic transplantation: novel treatment strategies.

    PubMed

    Engel, Nicole; Rank, Andreas

    2011-10-01

    Allogeneic hematopoietic stem cell transplantation is a high risk but curative treatment option for leukemia, myelodysplasia and other hematological malignancies. After high dose radio- or chemo-therapy, recipient's hematopoiesis is replaced by a new immunosystem and residual malignant cells are eliminated by the graft-versus-leukemia reaction. The benefit of this immunological effect is limited by the most frequent complication of hematopoietic stem cell transplantation: graft-versus-host disease. In addition to their well-known anti-tumor activity, epigenetic drugs mediate immunotolerance without reducing alloreactivity or even enhance graft-versus-leukemia effect without inducing graft-versus-host disease by regulating cytokine release, increasing the circulating number of regulatory T cells and interacting with natural killer cells. We focus on the use of epigenetic drugs in the allogeneic transplantation setting in relation to their anti-tumor and immunomodulatory potential.

  2. [Psoriasis and cardiovascular disease].

    PubMed

    Torres, Tiago; Sales, Rita; Vasconcelos, Carlos; Selores, Manuela

    2013-01-01

    Psoriasis is a common, chronic and systemic inflammatory disease associated with several comorbidities, such as obesity, hypertension, diabetes, dyslipidaemia and metabolic syndrome, but also with an increased risk of cardiovascular disease, like myocardial infarction or stroke. The chronic inflammatory nature of psoriasis has been suggested to be a contributing and potentially independent risk factor for the development of cardiovascular comorbidities and precocious atherosclerosis. Aiming at alerting clinicians to the need of screening and monitoring cardiovascular diseases and its risk factors in psoriatic patients, this review will focus on the range of cardiometabolic comorbidities and increased risk of cardiovascular disease associated with psoriasis.

  3. Mediastinal radiation and adverse outcomes after heart transplantation.

    PubMed

    Uriel, Nir; Vainrib, Alan; Jorde, Ulrich P; Cotarlan, Vlad; Farr, Maryjane; Cheema, Faisal H; Naka, Yoshifuma; Mancini, Donna; Colombo, Paolo C

    2010-03-01

    Orthotopic heart transplantation (OHT) may represent the only treatment option for patients with end-stage cardiovascular disease due to mediastinal radiation therapy (MRT). The primary aim of this study was to evaluate the safety and efficacy of OHT in this patient population. We conducted a retrospective, single-center cohort study of patients with MRT-associated cardiovascular disease who underwent OHT between January 1987 and September 2008. Nine patients (3 men), aged 46 +/- 11 years at the time of their OHT, were identified. Time from MRT to OHT was 26 +/- 11 years. Lymphoma was the indication for MRT in all patients. Five patients had non-ischemic dilated cardiomyopathy, 2 had ischemic cardiomyopathy and 2 had constrictive pericarditis. Three patients expired in the peri-operative period, whereas another patient died 3 years post-transplant from lung carcinoma. Two additional patients developed a secondary malignancy post-transplant. Five patients are still alive at a mean follow-up of 10 +/- 8 years. Early survival rate is poor in patients who undergo OHT for MRT-associated end-stage cardiovascular disease. In addition, long-term follow-up shows an elevated incidence of malignancies. Our results raise concern about the safety and efficacy of performing OHT in patients with MRT-associated cardiovascular disease.

  4. Transplantation psychoneuroimmunology: building hypotheses.

    PubMed

    Klapheke, M M

    2000-06-01

    The research findings of psychoneuroimmunology have not yet been fully applied to the field of transplantation psychiatry. Though much study has been devoted to the impact of psychiatric disease on the immunosuppressed state and disease progression in HIV-related illness, little has yet been written on the immunology implications of psychiatric disturbances in the immunosuppressed post-transplant patient. Utilizing Medline literature searches to review relevant research data in psychoneuroimmunology and transplantation immunology, the author formulates and examines four transplantation psychoneuroimmunology hypotheses involving the potential impact of depression on post-transplant organ rejection, cancer, coronary artery disease, and infections. The author concludes that though major questions remain, it appears reasonable to include the impact of depression, and possibly other psychological states, among factors that may affect the net state of immunosuppression in transplant patients.

  5. Lung transplantation at Duke

    PubMed Central

    Gray, Alice L.; Hartwig, Matthew G.

    2016-01-01

    Lung transplantation represents the gold-standard therapy for patients with end-stage lung disease. Utilization of this therapy continues to rise. The Lung Transplant Program at Duke University Medical Center was established in 1992, and since that time has grown to one of the highest volume centers in the world. The program to date has performed over 1,600 lung transplants. This report represents an up-to-date review of the practice and management strategies employed for safe and effective lung transplantation at our center. Specific attention is paid to the evaluation of candidacy for lung transplantation, donor selection, surgical approach, and postoperative management. These evidence-based strategies form the foundation of the clinical transplantation program at Duke. PMID:27076968

  6. Cuba's kidney transplantation program.

    PubMed

    Mármol, Alexander; Pérez, Alexis; Pérez de Prado, Juan C; Fernández-Vega, Silvia; Gutiérrez, Francisco; Arce, Sergio

    2010-10-01

    The first kidney transplant in Cuba was performed on 24 February 1970, using a cadaveric donor. In 1979, living donor kidney transplantation began between first-degree relatives. A total of 2775 patients are enrolled in renal replacement therapy in 47 hospitals across the country, 1440 of whom are awaiting kidney transplantation. Organs for the kidney program are procured in 63 accredited hospitals equipped for multidisciplinary management of brain death. Accordingly, over 90% of transplanted kidneys are from cadaveric donors. Identification of potential recipients is carried out through a national, computerized program that affords all patients the same opportunity regardless of distance from a transplant center, and selection of the most suitable candidate is based primarily on HLA compatibility. KEYWORDS Chronic renal failure, kidney transplantation.

  7. Future of transplantation medicine.

    PubMed

    Rowiński, Wojciech

    2007-01-01

    Organ transplantation has become very successful method of treatment of end stage organ disease. However the waiting lists of patients aiming such treatment are exponentially growing due to insufficient organ supply. Prognosis of the future for transplantation medicine is truly difficult. Prospects from past years, that "soon induction of tolerance will become possible"(1975), wide xenogenic transplant utilization (in 2000), fetal brain cell transplantation to treat some neurologic disease and transplantation of isolated cells instead of whole organs (1998) proved wrong. The research in the nearest future will be focused on tolerance induction, inhibition of alloreaction in blood-group discordant transplants (in immunized patients) and xenografts. In parallel, studies on hybrid and totally artificial, implantable devices (artificial pancreas and liver) will be carried on. 21st century will belong to regeneration medicine, with therapeutic applications of stem cells.

  8. Pre- and postmortem imaging of transplanted cells

    PubMed Central

    Andrzejewska, Anna; Nowakowski, Adam; Janowski, Miroslaw; Bulte, Jeff WM; Gilad, Assaf A; Walczak, Piotr; Lukomska, Barbara

    2015-01-01

    Therapeutic interventions based on the transplantation of stem and progenitor cells have garnered increasing interest. This interest is fueled by successful preclinical studies for indications in many diseases, including the cardiovascular, central nervous, and musculoskeletal system. Further progress in this field is contingent upon access to techniques that facilitate an unambiguous identification and characterization of grafted cells. Such methods are invaluable for optimization of cell delivery, improvement of cell survival, and assessment of the functional integration of grafted cells. Following is a focused overview of the currently available cell detection and tracking methodologies that covers the entire spectrum from pre- to postmortem cell identification. PMID:26366076

  9. Issues in solid-organ transplantation in children: translational research from bench to bedside

    PubMed Central

    Lipshultz, Steven E.; Chandar, Jayanthi J.; Rusconi, Paolo G.; Fornoni, Alessia; Abitbol, Carolyn L.; Burke III, George W.; Zilleruelo, Gaston E.; Pham, Si M.; Perez, Elena E.; Karnik, Ruchika; Hunter, Juanita A.; Dauphin, Danielle D.; Wilkinson, James D.

    2014-01-01

    In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children. PMID:24860861

  10. Endothelins and NADPH oxidases in the cardiovascular system.

    PubMed

    Dammanahalli, Karigowda J; Sun, Zhongjie

    2008-01-01

    1. The endothelin (ET) system and NADPH oxidase play important roles in the regulation of cardiovascular function, as well as in the pathogenesis of hypertension and other cardiovascular diseases. 2. Endothelins activate NADPH oxidases and thereby increase superoxide production, resulting in oxidative stress and cardiovascular dysfunction. Thus, NADPH oxidases may mediate the role of endothelins in some cardiovascular diseases. However, the role of reactive oxygen species (ROS) in mediating ET-induced vasoconstriction and cardiovascular disease remains under debate, as evidenced by conflicting reports from different research teams. Conversely, activation of NADPH oxidase can stimulate ET secretion via ROS generation, which further enhances the cardiovascular effects of NADPH oxidase. However, little is known about how ROS activate the endothelin system. It seems that the relationship between ET-1 and ROS may vary with cardiovascular disorders. 3. Endothelins activate NADPH oxidase via the ET receptor-proline-rich tyrosine kinase-2 (Pyk2)-Rac1 pathway. Rac1 is an important regulator of NADPH oxidase. There is ample evidence supporting direct stimulation by Rac1 of NADPH oxidase activity. In addition, Rac1-induced cardiomyocyte hypertrophy is mediated by the generation of ROS.

  11. PPAR-γ in the Cardiovascular System

    PubMed Central

    Duan, Sheng Zhong; Ivashchenko, Christine Y.; Usher, Michael G.; Mortensen, Richard M.

    2008-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ), an essential transcriptional mediator of adipogenesis, lipid metabolism, insulin sensitivity, and glucose homeostasis, is increasingly recognized as a key player in inflammatory cells and in cardiovascular diseases (CVD) such as hypertension, cardiac hypertrophy, congestive heart failure, and atherosclerosis. PPAR-γ agonists, the thiazolidinediones (TZDs), increase insulin sensitivity, lower blood glucose, decrease circulating free fatty acids and triglycerides, lower blood pressure, reduce inflammatory markers, and reduce atherosclerosis in insulin-resistant patients and animal models. Human genetic studies on PPAR-γ have revealed that functional changes in this nuclear receptor are associated with CVD. Recent controversial clinical studies raise the question of deleterious action of PPAR-γ agonists on the cardiovascular system. These complex interactions of metabolic responsive factors and cardiovascular disease promise to be important areas of focus for the future. PMID:18288291

  12. Cardiovascular Disease and Primary Ovarian Insufficiency

    PubMed Central

    Wellons, Melissa

    2012-01-01

    Cardiovascular disease (CVD) is the number-one killer of women. Women with primary ovarian insufficiency (POI) may be more burdened by cardiovascular disease, such as myocardial infarction and stroke, as compared with women with normal menopause. The increased burden may be mediated by a worsening of cardiovascular risk factors, such as lipids, corresponding with the loss of ovarian function. In contrast, the increased burden may be caused by factors that precede and potentially contribute to both CVD events and ovarian decline, such as X-chromosome abnormalities and smoking. Regardless of the cause, women with POI may serve as an important population to target for CVD screening and prevention strategies. These strategies should include the use of CVD risk stratification tools to identify women that may benefit from lifestyle modification and pharmacological therapy to prevent CVD. Sex steroid therapy for the sole purpose of CVD prevention in women with POI cannot be recommended, based on a lack of evidence. PMID:21969267

  13. Intestinal transplantation: a review.

    PubMed

    Desai, Chirag Sureshchandra; Khan, Khalid Mahmood; Girlanda, Raffaele; Fishbein, Thomas M

    2012-09-01

    Parenteral nutrition is a life-saving therapy for patients with intestinal failure. Intestinal transplantation is now recognized as a treatment for patients who develop complications of parenteral nutrition and in whom attempts at intestinal rehabilitation have failed. Patients with parenteral nutrition related liver disease will require a liver graft typically part of a multivisceral transplant. Isolated intestinal transplants are more commonly performed in adults while multivisceral transplants are most commonly performed in infants. Isolated intestinal transplants have the best short-term outcome, with over 80 % survival at 1 year. Patients requiring multivisceral transplants have a high rate of attrition with a 1 year survival less than 70 %. Prognostic factors for a poor outcome include patient hospitalization at the time of transplant and donor age greater than 40 years while systemic sepsis and acute rejection are the major determinant of early postoperative outcome. For patients surviving the first year the outcome of transplantation of the liver in addition to intestine affords some survival advantage though long-term outcome does not yet match other abdominal organs. Outcomes for intestinal retransplantation are poor as a result of immunology and patient debility. Overall intestinal transplantation continues to develop and is a clear indication with cost and quality of life advantages in patients with intestinal failure that do not remain stable on parenteral nutrition.

  14. [Infertility and kidney transplantation].

    PubMed

    Atallah, David; Salameh, Charbel; El Kassis, Nadine; Safi, Joelle; Lutfallah, Fouad; Bejjani, Lina; Ghaname, Wadih; Moukarzel, Maroun

    2015-01-01

    Renal failure impairs the endocrine system, especially in women, due to hyperprolactinemia, altering fertility, ovulatory cycles, libido and growth in adolescents. Renal transplantation is considered the best solution to the problems of renal failure and and of dialysis, as evidenced by comparing the rate of hyperprolactinemia (100% in chronic renal failure, 60% in patients on dialysis and 35% in post-transplantation). Kidney transplant is less efficient for restoring perfect function of the hypothalamic-pituitary-gonadal axis due in part to the immunosuppressant regimens prescribed. When these drugs are properly managed, transplantation will restore near normal sexual function.

  15. Split liver transplantation.

    PubMed

    Yersiz, H; Cameron, A M; Carmody, I; Zimmerman, M A; Kelly, B S; Ghobrial, R M; Farmer, D G; Busuttil, R W

    2006-03-01

    Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

  16. Ceruloplasmin and cardiovascular disease

    NASA Technical Reports Server (NTRS)

    Fox, P. L.; Mazumder, B.; Ehrenwald, E.; Mukhopadhyay, C. K.

    2000-01-01

    Transition metal ion-mediated oxidation is a commonly used model system for studies of the chemical, structural, and functional modifications of low-density lipoprotein (LDL). The physiological relevance of studies using free metal ions is unclear and has led to an exploration of free metal ion-independent mechanisms of oxidation. We and others have investigated the role of human ceruloplasmin (Cp) in oxidative processes because it the principal copper-containing protein in serum. There is an abundance of epidemiological data that suggests that serum Cp may be an important risk factor predicting myocardial infarction and cardiovascular disease. Biochemical studies have shown that Cp is a potent catalyst of LDL oxidation in vitro. The pro-oxidant activity of Cp requires an intact structure, and a single copper atom at the surface of the protein, near His(426), is required for LDL oxidation. Under conditions where inhibitory protein (such as albumin) is present, LDL oxidation by Cp is optimal in the presence of superoxide, which reduces the surface copper atom of Cp. Cultured vascular endothelial and smooth muscle cells also oxidize LDL in the presence of Cp. Superoxide release by these cells is a critical factor regulating the rate of oxidation. Cultured monocytic cells, when activated by zymosan, can oxidize LDL, but these cells are unique in their secretion of Cp. Inhibitor studies using Cp-specific antibodies and antisense oligonucleotides show that Cp is a major contributor to LDL oxidation by these cells. The role of Cp in lipoprotein oxidation and atherosclerotic lesion progression in vivo has not been directly assessed and is an important area for future studies.

  17. Role of the hypothalamic arcuate nucleus in cardiovascular regulation.

    PubMed

    Sapru, Hreday N

    2013-04-01

    Recently the hypothalamic arcuate nucleus (Arc) has been implicated in cardiovascular regulation. Both pressor and depressor responses can be elicited by the chemical stimulation of the Arc. The direction of cardiovascular responses (increase or decrease) elicited from the Arc depends on the baseline blood pressure. The pressor responses are mediated via increase in sympathetic nerve activity and involve activation of the spinal ionotropic glutamate receptors. Arc-stimulation elicits tachycardic responses which are mediated via inhibition of vagal input and excitation of sympathetic input to the heart. The pathways within the brain mediating the pressor and tachycardic responses elicited from the Arc have not been delineated. The depressor responses to the Arc-stimulation are mediated via the hypothalamic paraventricular nucleus (PVN). Gamma aminobutyric acid type A receptors, neuropeptide Y1 receptors, and opiate receptors in the PVN mediate the depressor responses elicited from the Arc. Some circulating hormones (e.g., leptin and insulin) may reach the Arc via the leaky blood-brain barrier and elicit their cardiovascular effects. Although the Arc is involved in mediating the cardiovascular responses to intravenously injected angiotensin II and angiotensin-(1-12), these effects may not be due to leakage of these peptides across the blood-brain barrier in the Arc; instead, circulating angiotensins may act on neurons in the SFO and mediate cardiovascular actions via the projections of SFO neurons to the Arc. Cardiovascular responses elicited by acupuncture have been reported to be mediated by direct and indirect projections of the Arc to the RVLM. PMID:23260431

  18. Basic and clinical research in the AMC Renal Transplant Unit.

    PubMed

    ten Berge, Ineke J M; Bemelman, Fréderike J

    2014-10-01

    Our research is aimed at characterization of the antiviral and allo-immune responses in kidney transplant recipients. In particular, we are interested in the differentiation, effector function and memory formation of T cells specific for the latent viruses cytomegalovirus (CMV) and BK virus (BKV) and in the impact of virus-specific immune responses on alloimmunity. Furthermore, we perform studies towards the most optimal, tailor-made immunosuppressive drug regimen and towards the impact of immunosuppression on infectious diseases; cognitive function and cardiovascular status of kidney transplant recipients.

  19. Cardiovascular disease among firefighters.

    PubMed

    Melius, J M

    1995-01-01

    The author reviews the literature of the past 20 years on heart disease among firefighters, covering the specific aspects of firefighting that may be related to potential cardiovascular disease. The author then outlines steps that can be taken to reduce the risks of developing cardiovascular disease.

  20. Desensitization for solid organ and hematopoietic stem cell transplantation.

    PubMed

    Zachary, Andrea A; Leffell, Mary S

    2014-03-01

    Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft.

  1. Desensitization for solid organ and hematopoietic stem cell transplantation

    PubMed Central

    Zachary, Andrea A; Leffell, Mary S

    2014-01-01

    Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft. PMID:24517434

  2. Bone marrow transplant – children - discharge

    MedlinePlus

    Transplant - bone marrow - children - discharge; Stem cell transplant - children - discharge; Hematopoietic stem cell transplant -children - discharge; Reduced intensity, non-myeloablative transplant - children - discharge; Mini transplant - children - discharge; Allogenic bone ...

  3. Restoration of sensory and motor function in earthworm escape reflex pathways following ventral nerve cord transplantation.

    PubMed

    Vining, E P; Drewes, C D

    1985-07-01

    Twelve segments of earthworm ventral nerve cord (VNC) were excised from either segments 10-22 (i.e., within the MGF sensory field) or segments 75-87 (i.e., within the LGF sensory field) in donor worms and heterotopically, or homotopically, transplanted into recipient animals. Morphological evidence indicated that by four days after transplantation, peripheral connections were formed between the transplanted VNC and the body wall of the recipient, many of these connections involving novel pathways projecting ventrally from the transplant. Restoration of giant fiber touch sensitivity in the transplant occurred from 4-14 days after transplantation. Regardless of the site of transplantation, the restored sensitivity (i.e., MGF versus LGF sensory field) always reflected the origin of the donor VNC. Restoration of MGF-mediated motor activity in the transplant occurred approximately 17-22 days after transplantation. In the case of heterotopic transplants (i.e., anterior VNC into posterior segments), the restored MGF-mediated muscle potentials were facilitating, indicating at least some tendency for persistence of this feature after transplantation. Behavioral observations suggested that reconnections involving other reflex pathways (e.g., those controlling setal movements and peristaltic locomotion) were made within the transplant region and that properties of the restored reflexes reflected those of the donor VNC. The rapid restoration of sensory and motor connections, despite heterotopic placement, indicates a significant capacity for peripheral regeneration by the transplanted VNC. On the other hand, the maintenance of various properties of reflex function, despite heterotopic transplantation, suggests a limited capacity for rearrangement of established central connections in the transplanted VNC. PMID:4031850

  4. Serum FGF23 and Risk of Cardiovascular Events in Relation to Mineral Metabolism and Cardiovascular Pathology

    PubMed Central

    Ärnlöv, Johan; Carlsson, Axel C.; Sundström, Johan; Ingelsson, Erik; Larsson, Anders; Lind, Lars

    2013-01-01

    Summary Background and objectives Circulating fibroblast growth factor-23 is associated with adverse cardiovascular outcomes in CKD and non-CKD individuals, but the underlying mechanism remains unclear. This study tested whether this association is independent of mineral metabolism and indices of subclinical cardiovascular pathology. Design, setting, participants, & measurements The prospective association between fibroblast growth factor-23 and major cardiovascular events (a composite of hospital-treated myocardial infarction, hospital-treated stroke, or all-cause mortality) was investigated in the community-based Prospective Investigation of the Vasculature in Uppsala Seniors (n=973; mean age=70 years, 50% women) using multivariate logistic regression. Subjects were recruited between January of 2001 and June of 2004. Results During follow-up (median=5.1 years), 112 participants suffered a major cardiovascular event. In logistic regression models adjusted for age, sex, and estimated GFR, higher fibroblast growth factor-23 was associated with increased risk for major cardiovascular events (odds ratio for tertiles 2 and 3 versus tertile 1=1.92, 95% confidence interval=1.19–3.09, P<0.01). After additional adjustments in the model, adding established cardiovascular risk factors, confounders of mineral metabolism (calcium, phosphate, parathyroid hormone, and 25(OH)-vitamin D), and indices of subclinical pathology (flow-mediated vasodilation, endothelial-dependent and -independent vasodilation, arterial stiffness, and atherosclerosis and left ventricular mass) attenuated this relationship, but it remained significant (odds ratio for tertiles 2 and 3 versus tertile 1=1.69, 95% confidence interval=1.01–2.82, P<0.05). Conclusions Fibroblast growth factor-23 is an independent predictor of cardiovascular events in the community, even after accounting for mineral metabolism abnormalities and subclinical cardiovascular damage. Circulating fibroblast growth factor-23 may

  5. Therapeutic Strategies for Oxidative Stress-Related Cardiovascular Diseases: Removal of Excess Reactive Oxygen Species in Adult Stem Cells

    PubMed Central

    Yun, Jisoo

    2016-01-01

    Accumulating evidence indicates that acute and chronic uncontrolled overproduction of oxidative stress-related factors including reactive oxygen species (ROS) causes cardiovascular diseases (CVDs), atherosclerosis, and diabetes. Moreover ROS mediate various signaling pathways underlying vascular inflammation in ischemic tissues. With respect to stem cell-based therapy, several studies clearly indicate that modulating antioxidant production at cellular levels enhances stem/progenitor cell functionalities, including proliferation, long-term survival in ischemic tissues, and complete differentiation of transplanted cells into mature vascular cells. Recently emerging therapeutic strategies involving adult stem cells, including endothelial progenitor cells (EPCs), for treating ischemic CVDs have highlighted the need to control intracellular ROS production, because it critically affects the replicative senescence of ex vivo expanded therapeutic cells. Better understanding of the complexity of cellular ROS in stem cell biology might improve cell survival in ischemic tissues and enhance the regenerative potentials of transplanted stem/progenitor cells. In this review, we will discuss the nature and sources of ROS, drug-based therapeutic strategies for scavenging ROS, and EPC based therapeutic strategies for treating oxidative stress-related CVDs. Furthermore, we will discuss whether primed EPCs pretreated with natural ROS-scavenging compounds are crucial and promising therapeutic strategies for vascular repair. PMID:27668035

  6. Therapeutic Strategies for Oxidative Stress-Related Cardiovascular Diseases: Removal of Excess Reactive Oxygen Species in Adult Stem Cells

    PubMed Central

    Yun, Jisoo

    2016-01-01

    Accumulating evidence indicates that acute and chronic uncontrolled overproduction of oxidative stress-related factors including reactive oxygen species (ROS) causes cardiovascular diseases (CVDs), atherosclerosis, and diabetes. Moreover ROS mediate various signaling pathways underlying vascular inflammation in ischemic tissues. With respect to stem cell-based therapy, several studies clearly indicate that modulating antioxidant production at cellular levels enhances stem/progenitor cell functionalities, including proliferation, long-term survival in ischemic tissues, and complete differentiation of transplanted cells into mature vascular cells. Recently emerging therapeutic strategies involving adult stem cells, including endothelial progenitor cells (EPCs), for treating ischemic CVDs have highlighted the need to control intracellular ROS production, because it critically affects the replicative senescence of ex vivo expanded therapeutic cells. Better understanding of the complexity of cellular ROS in stem cell biology might improve cell survival in ischemic tissues and enhance the regenerative potentials of transplanted stem/progenitor cells. In this review, we will discuss the nature and sources of ROS, drug-based therapeutic strategies for scavenging ROS, and EPC based therapeutic strategies for treating oxidative stress-related CVDs. Furthermore, we will discuss whether primed EPCs pretreated with natural ROS-scavenging compounds are crucial and promising therapeutic strategies for vascular repair.

  7. Cardiovascular histamine receptors in the domestic chicken.

    PubMed

    Chand, N; Eyre, P

    1975-08-01

    The effects of mepyramine (H1-antagonist) and burimamide (H2-antagonist) were studied on histamine, 2-methylhistamine (a selective H1-agonist), 4-methylhistamine (a selective H2-agonist) and acetylcholine-induced changes in systemic arterial and central venous pressure and respiration in anaesthetized chickens. The result of this study suggested a predominance of H1 and some H2 histamine receptors in the cardiovascular system of domestic fowl where both are mediating systemic hypotension. There also appears to be predominance of H1 receptors mediating venous hypertension and respiratory apnoea to large doses of histamine and 2-methylhistamine. In addition, a possible involvement of H2-receptors in the cardiovascular system of chicken is suggested by the finding that burimamide always blocked mepyramine potentiated secondary pressor response to histamine and its analogues.

  8. Transplantation activities in Iran.

    PubMed

    Broumand, Behrooz

    2005-06-01

    Iran is a tropical country with a land area of 1,648,000 square kilometers and a population of 68,100,000. Iran has a recorded history that dates back 2553 years. Its earliest medical school was Pasargad. Jondi Chapour University was founded 1753 years ago during the Sassanid dynasty as a center for higher education in medicine, philosophy, and pharmacology. Indeed, the idea of xenotransplantation dates back to days of Achaemenidae (Achaemenian dynasty), as evidenced by engravings of many mythologic chimeras still present in Persepolis. Avicenna (980-1037 AD), the great Iranian physician, performed the first nerve repair. Transplantation progress in Iran follows roughly the same pattern as that of the rest of the world, with some 10-20 years' delay. Modern organ transplantation dates back to 1935, when the first cornea transplant was performed at Farabi Hospital in Tehran, Iran. The first living-related kidney transplantation performed at Shiraz University Hospital dates back to 1968. The first bone marrow transplant was performed at Dr. Shariaati's Hospital in Tehran. The first heart transplant was performed 1993 in Tabriz, Iran. The first liver transplant was performed in 1993 in Shiraz. The first lung transplant was performed in 2001, and the first heart and lung transplants were performed in 2002, both at Tehran. In late 1985, the renal transplantation program was officially started in a major university hospital in Tehran and was poised to carry out 2 to 4 transplantations each week. Soon, another large center initiated a similar program. Both of these centers accepted surgical, medical, and nursing teams from other academic medical centers for training in kidney transplantation. Since 2002, Iran has grown to include 23 active renal, 68 cornea, 2 liver, 4 heart, 2 lung, and 2 bone marrow transplantation centers in different cities. In June 2000, the Organ Transplantation Brain Death Act was approved by the Parliament, followed by the establishment of the

  9. Arterial hypertension in liver transplant recipients.

    PubMed

    Hryniewiecka, E; Zegarska, J; Paczek, L

    2011-10-01

    Hypertension is an important cardiovascular risk factor that influences patient survival. This study sought to evaluate hypertension incidence and circadian rhythms of blood pressure (BP) among liver transplant recipients during the first posttransplant month. We also compared hypertension incidence according to clinical and automated blood pressure monitoring methods. BP was determined by clinical blood pressure monitoring (CBPM) methods and by automated blood pressure monitoring (ABPM) using the SpaceLabs device. We also assessed blood biochemistry, particularly kidney function parameters and immunosuppressive drug blood trough levels, among 32 white subjects (10 women and 22 men) of average age 47.58±14.19 years. The leading cause for transplantation was liver insufficiency due to viral hepatitis B and/or C infection (43.75%). The majority (93.75%) of patients was prescribed immunosuppressive treatment with tacrolimus. Although we observed hypertension in 28 patients (87.5%) by ABPM measurements and in 25 (78.12%) using CBPM method, the difference did not reach statistical significance. However, BP control was inadequate in 28 patients (87.5%) by ABPM assessment versus 3 (9.38%) according to CBPM readings (P=.025). The BP circadian rhythm was altered in 30 patients (93.75%) including 15 with higher nighttime BP readings. There was no correlation between tacrolimus blood levels and BP values or with kidney function as assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We concluded that prevalence of arterial hypertension among liver transplant recipients within 1 month after transplantation is high. The majority of the patients show disturbed circadian rhythms in the early period after liver transplantation with loss or even reversal of the normal nocturnal decrease in BP. Owing to the fact that ABPM enables more adequate daily assessment of BP values, it is an optimal method to adjust antihypertensive therapy to optimal levels

  10. Notch signaling in cardiovascular disease and calcification.

    PubMed

    Rusanescu, Gabriel; Weissleder, Ralph; Aikawa, Elena

    2008-08-01

    Recent increase in human lifespan has shifted the spectrum of aging-related disorders to an unprecedented upsurge in cardiovascular diseases, especially calcific aortic valve stenosis, which has an 80% risk of progression to heart failure and death. A current therapeutic option for calcified valves is surgical replacement, which provides only temporary relief. Recent progress in cardiovascular research has suggested that arterial and valve calcification are the result of an active process of osteogenic differentiation, induced by a pro-atherogenic inflammatory response. At molecular level, the calcification process is regulated by a network of signaling pathways, including Notch, Wnt and TGFbeta/BMP pathways, which control the master regulator of osteogenesis Cbfa1/Runx2. Genetic and in vitro studies have implicated Notch signaling in the regulation of macrophage activation and cardiovascular calcification. Individuals with inactivating Notch1 mutations have a high rate of cardiovascular disorders, including valve stenosis and calcification. This article reviews recent progress in the mechanism of cardiovascular calcification and discusses potential molecular mechanisms involved, focusing on Notch receptors. We propose a calcification model where extreme increases in vascular wall cell density due to inflammation-induced cell proliferation can trigger an osteogenic differentiation program mediated by Notch receptors. PMID:19936191

  11. Racism and cardiovascular disease in African Americans.

    PubMed

    Wyatt, Sharon B; Williams, David R; Calvin, Rosie; Henderson, Frances C; Walker, Evelyn R; Winters, Karen

    2003-06-01

    This article provides an overview of the evidence on the ways racism can affect the disproportionate rates of cardiovascular disease (CVD) in African Americans. It describes the significant health disparities in CVD for blacks and whites and suggests that racial disparities should be understood within the context of persistent inequities in societal institutions and relations. Evidence and potential pathways for exploring effects of 3 levels of racism on cardiovascular health risk factors and outcomes are reviewed. First, institutional racism can lead to limited opportunities for socioeconomic mobility, differential access to goods and resources, and poor living conditions that can adversely affect cardiovascular health. Second, perceived/personally mediated racism acts as a stressor and can induce psychophysiological reactions that negatively affect cardiovascular health. Third, in race-conscious societies, such as the United States, the negative self-evaluations of accepting negative cultural stereotypes as true (internalized racism) can have deleterious effects on cardiovascular health. Few population-based studies have examined the relationship between racism and CVD. The findings, though suggestive of a positive association, are neither consistent nor clear. The research agenda of the Jackson Heart Study in addressing the role of racism in CVD is presented.

  12. PPAR Agonists and Cardiovascular Disease in Diabetes.

    PubMed

    Calkin, Anna C; Thomas, Merlin C

    2008-01-01

    Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPARalpha agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPARgamma agonists, and more recently dual PPARalpha/gamma coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPARgamma receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease.

  13. PPAR Agonists and Cardiovascular Disease in Diabetes

    PubMed Central

    Calkin, Anna C.; Thomas, Merlin C.

    2008-01-01

    Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPARα agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPARγ agonists, and more recently dual PPARα/γ coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPARγ receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease. PMID:18288280

  14. Cardiovascular effects of selective cyclooxygenase-2 inhibitors.

    PubMed

    Krum, Henry; Liew, Danny; Aw, Juan; Haas, Steven

    2004-03-01

    Selective cyclooxygenase-2 inhibitors represent a significant advance in the management of inflammatory disorders. They have similar efficacy to nonselective 'conventional' nonsteroidal anti-inflammatory drugs, but a superior gastrointestinal safety profile. However, a significant caveat is the perceived potential of cyclooxygenase-2 inhibitors to cause adverse cardiovascular effects, an issue first raised by the Vioxx Gastrointestinal Outcomes Research (VIGOR) study of rofecoxib (Vioxx, Merck & Co. Inc.). Mechanisms by which cyclooxygenase-2 inhibitors may increase cardiovascular risk are selective inhibition of prostaglandin I2 over thromboxane A2 within the eicosanoid pathway, which promotes thrombosis, and inhibition of prostaglandins E2 and I2 within the kidney, which leads to sodium and water retention and blood pressure elevation. In spite of this, the cardiovascular findings from VIGOR are not firmly supported by observations from large cohort studies and other clinical trials of selective cyclooxygenase-2 inhibitors, including the Celecoxib Long-term Arthritis Safety Study. The two main theories that explain the VIGOR findings are that the comparator used (naproxen; Naprosyn, Roche) is cardioprotective and that very high doses of rofecoxib were used, but at present neither is backed by firm evidence. Indeed, there is now early evidence that selective cyclooxygenase-2 inhibition with celecoxib may even protect against the progression of cardiovascular disease, on the basis that cyclooxygenase-2 mediates key processes in atherothrombosis. Currently, it is not clear what the net cardiovascular effects of cyclooxygenase-2 inhibitors are. The data are inconsistent and at best, speculative. It may be also that celecoxib and rofecoxib differ in their cardiovascular effects. Clarification of these issues is of vital importance given the vast number of patients presently taking both types of cyclooxygenase-2 inhibitors. Therefore, what is clear in this situation is

  15. Findings of graft biopsy specimens within 90 days after ABO blood group incompatible living donor kidney transplantation compared with ABO-identical and non-identical transplantation.

    PubMed

    Ushigome, Hidetaka; Okamoto, Masahiko; Koshino, Katsuhiro; Nobori, Syuji; Okajima, Hideaki; Masuzawa, Naoko; Urasaki, Koji; Yoshimura, Norio

    2010-07-01

    As immunosuppressive therapy has advanced, we have markedly improved the outcome of ABO blood group incompatible living donor kidney transplantation. Consequently, graft survival at early phase after ABO-incompatible transplantation has been favorable than ABO-compatible transplantation in Japan. But in these days, it has been assumed that transplant glomerulopathy within one yr after ABO-incompatible kidney transplantation might be significantly precipitated. That may be because of chronic, active antibody-mediated rejection (AMR). We performed kidney graft biopsies at the early phase within 90 d after living donor kidney transplantation that involved the episode and protocol biopsies and studied findings of graft biopsy specimens when compared with ABO incompatible and compatible involving non-identical and identical transplantations. In ABO-incompatible transplant cases, the ratio occurring glomerulitis, especially severe injury of g 2-3, was significantly higher than that of identical and non-identical transplant cases (p < 0.01). There was no significant difference in t score, i score, ptc score and v score between three transplant groups. The cases occurring AMR were concordant with the cases recognized with severe glomerulitis. AMR was difficult to be diagnosed by C4d analysis in ABO-incompatible transplant cases. Glomerular injury score, g score, may be considered as more significant and the injury should be cured thoroughly.

  16. Hepatitis C: liver transplantation.

    PubMed

    Metts, Julius; Carmichael, Lesley; Kokor, Winfred; Scharffenberg, Robert

    2014-12-01

    Hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma account for approximately 40% of the 6,000 adult liver transplantations performed each year in the United States. Survival rates are 76% to 83% at 2 years and 69% to 72% at 5 years. If eligible for surgery and in the absence of contraindications, any patient with HCV infection who develops decompensated liver disease or hepatocellular carcinoma is a candidate for liver transplantation. Most transplantation programs require that a patient with a history of alcohol or drug abuse be abstinent for at least 6 months and active in a substance abuse rehabilitation program. Prioritization for transplantation is based primarily on a patient's model for end-stage liver disease score, though other factors are considered. Complications after liver transplantation include recurrence of HCV infection, rejection of the transplanted liver, and an increased rate of infection because of immunosuppression. Various drugs are used to prevent infection and organ rejection. Liver transplant recipients also develop diabetes, hypertension, hyperlipidemia, renal dysfunction, osteopenia, and cancers at high rates, likely because of the effects of immunosuppressive drugs, particularly steroids and calcineurin inhibitors. The family physician's role in caring for liver transplant recipients often involves detection and management of these conditions. PMID:25478647

  17. Organ transplantation and replacement

    SciTech Connect

    Cerilli, G.J.

    1988-01-01

    This book contains 49 chapters. Some of the titles are: Molecular, Genetic, and Clinical Aspects of the HLA System; The Normal Immune Response; Significance of the ABO Antigen System; The Role of Dialysis in the Management of End-Stage Renal Disease; Access for Dialysis; Patient Selection for Renal Transplantation; The Living Donor in Kidney Transplantation; and Kidney Preservation by Cold Storage.

  18. Islet cell transplantation.

    PubMed

    Srinivasan, P; Huang, G C; Amiel, S A; Heaton, N D

    2007-04-01

    People with type 1 diabetes have normal exocrine pancreatic function, making islet cell rather than whole organ transplantation an attractive option. Achieving insulin independence in type 1 diabetes was the perceived goal of islet cell transplantation. The success of the Edmonton group in achieving this in a selected group of type 1 patients has led to renewed optimism that this treatment could eventually replace whole organ pancreas transplantation. However the long-term results of this treatment indicate that insulin independence is lost with time in a significant proportion of patients, although they may retain glycaemic stability. In this context, the indications for islet cell transplantation, which have evolved over the last 5 years, indicate that the patients who benefit most are those who experience severe hypoglycaemic reactions despite optimal insulin therapy. This review will summarise the history of islet cell transplantation, islet isolation techniques, the transplant procedure, immunosuppressive therapy, indications for islet cell transplantation, current clinical trials, the early UK islet cell transplant experience using the Edmonton protocol, and some of the challenges that lie ahead. PMID:17403947

  19. Introduction: Cardiovascular physics

    NASA Astrophysics Data System (ADS)

    Wessel, Niels; Kurths, Jürgen; Ditto, William; Bauernschmitt, Robert

    2007-03-01

    The number of patients suffering from cardiovascular diseases increases unproportionally high with the increase of the human population and aging, leading to very high expenses in the public health system. Therefore, the challenge of cardiovascular physics is to develop high-sophisticated methods which are able to, on the one hand, supplement and replace expensive medical devices and, on the other hand, improve the medical diagnostics with decreasing the patient's risk. Cardiovascular physics-which interconnects medicine, physics, biology, engineering, and mathematics-is based on interdisciplinary collaboration of specialists from the above scientific fields and attempts to gain deeper insights into pathophysiology and treatment options. This paper summarizes advances in cardiovascular physics with emphasis on a workshop held in Bad Honnef, Germany, in May 2005. The meeting attracted an interdisciplinary audience and led to a number of papers covering the main research fields of cardiovascular physics, including data analysis, modeling, and medical application. The variety of problems addressed by this issue underlines the complexity of the cardiovascular system. It could be demonstrated in this Focus Issue, that data analyses and modeling methods from cardiovascular physics have the ability to lead to significant improvements in different medical fields. Consequently, this Focus Issue of Chaos is a status report that may invite all interested readers to join the community and find competent discussion and cooperation partners.

  20. Mannan-Binding Lectin in Cardiovascular Disease

    PubMed Central

    Cedzyński, Maciej

    2014-01-01

    Cardiovascular disease remains the leading cause of mortality and morbidity worldwide so research continues into underlying mechanisms. Since innate immunity and its potent component mannan-binding lectin have been proven to play an important role in the inflammatory response during infection and ischaemia-reperfusion injury, attention has been paid to its role in the development of cardiovascular complications as well. This review provides a general outline of the structure and genetic polymorphism of MBL and its role in inflammation/tissue injury with emphasis on associations with cardiovascular disease. MBL appears to be involved in the pathogenesis of atherosclerosis and, in consequence, coronary artery disease and also inflammation and tissue injury after myocardial infarction and heart transplantation. The relationship between MBL and disease is rather complex and depends on different genetic and environmental factors. That could be why the data obtained from animal and clinical studies are sometimes contradictory proving not for the first time that innate immunity is a “double-edge sword,” sometimes beneficial and, at other times disastrous for the host. PMID:24877121

  1. Heart transplantation: review

    PubMed Central

    Mangini, Sandrigo; Alves, Bárbara Rubim; Silvestre, Odílson Marcos; Pires, Philippe Vieira; Pires, Lucas José Tachotti; Curiati, Milena Novaes Cardoso; Bacal, Fernando

    2015-01-01

    ABSTRACT Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants. PMID:26154552

  2. Bioethics of Organ Transplantation

    PubMed Central

    Caplan, Arthur

    2014-01-01

    As the ability to transplant organs and tissues has grown, the demand for these procedures has increased as well—to the point at which it far exceeds the available supply creating the core ethical challenge for transplantation—rationing. The gap between supply and demand, although large, is worse than it appears to be. There are two key steps to gaining access to a transplant. First, one must gain access to a transplant center. Then, those waiting need to be selected for a transplant. Many potential recipients do not get admitted to a program. They are deemed too old, not of the right nationality, not appropriate for transplant as a result of severe mental impairment, criminal history, drug abuse, or simply because they do not have access to a competent primary care physician who can refer them to a transplant program. There are also financial obstacles to access to transplant waiting lists in the United States and other nations. In many poor nations, those needing transplants simply die because there is no capacity or a very limited capacity to perform transplants. Although the demand for organs now exceeds the supply, resulting in rationing, the size of waiting lists would quickly expand were there to suddenly be an equally large expansion in the number of organs available for transplantation. Still, even with the reality of unavoidable rationing, saving more lives by increasing organ supply is a moral good. Current public policies for obtaining organs from cadavers are not adequate in that they do not produce the number of organs that public polls of persons in the United States indicate people are willing to donate. PMID:24478386

  3. Estrogen and estrogen receptors in cardiovascular oxidative stress.

    PubMed

    Arias-Loza, Paula-Anahi; Muehlfelder, Melanie; Pelzer, Theo

    2013-05-01

    The cardiovascular system of a premenopausal woman is prepared to adapt to the challenges of increased cardiac output and work load that accompany pregnancy. Thus, it is tempting to speculate whether enhanced adaptability of the female cardiovascular system might be advantageous under conditions that promote cardiovascular disease. In support of this concept, 17β-estradiol as the major female sex hormone has been shown to confer protective cardiovascular effects in experimental studies. Mechanistically, these have been partially linked to the prevention and protection against oxidative stress. Current evidence indicates that estrogens attenuate oxidative stress at two levels: first, by preventing generation of reactive oxygen species (ROS) and, second, by scavenging ROS in the myocardium and in the vasculature. The purpose of this review is to give an overview on current concepts on conditions and mechanisms by which estrogens protect the cardiovascular system against ROS-mediated cellular injury.

  4. Testosterone and Cardiovascular Disease

    PubMed Central

    Tambo, Amos; Roshan, Mohsin H.K.; Pace, Nikolai P.

    2016-01-01

    Cardiovascular disease [CVD] is a leading cause of mortality accounting for a global incidence of over 31%. Atherosclerosis is the primary pathophysiology underpinning most types of CVD. Historically, modifiable and non-modifiable risk factors were suggested to precipitate CVD. Recently, epidemiological studies have identified emerging risk factors including hypotestosteronaemia, which have been associated with CVD. Previously considered in the realms of reproductive biology, testosterone is now believed to play a critical role in the cardiovascular system in health and disease. The actions of testosterone as they relate to the cardiac vasculature and its implication in cardiovascular pathology is reviewed. PMID:27014372

  5. Cardiovascular disease screening.

    PubMed

    Duffy, Jennifer Y; Hameed, Afshan B

    2015-06-01

    Cardiovascular disease is the leading cause of death amongst women worldwide. Cardiovascular risk assessment and primary prevention are important strategies to improve morbidity and mortality. In additional to the traditional risk factors, pregnancy complications such as pre-eclampsia and gestational diabetes increment future risk of developing cardiovascular complications. Additionally, several serum biomarkers are valuable measures for both risk assessment and predictors of clinical outcomes in women. The purpose of this review is to describe current risk stratification schemes as well as outline the role of obstetric history and serum biomarkers in adjusting risk stratification in women. PMID:26143091

  6. An update on liver transplantation: A critical review.

    PubMed

    Neuberger, James

    2016-01-01

    Liver transplantation, although now a routine procedure, with defined indications and usually excellent outcomes, still has challenges. Donor shortage remains a key issue. Transplanted organs are not free of risk and may transmit cancer, infection, metabolic or autoimmune disease. Approaches to the donor shortage include use of organs from donors after circulatory death, from living donors and from those previously infected with Hepatitis B and C and even HIV for selected recipients. Normothermic regional and/or machine perfusion, whether static or pulsatile, normo- or hypothermic, are being explored and will be likely to have a major place in improving donation rates and outcomes. The main indications for liver replacement are alcoholic liver disease, HCV, non-alcoholic liver disease and liver cancer. Recent studies have shown that selected patients with severe alcoholic hepatitis may also benefit from liver transplant. The advent of new and highly effective treatments for HCV, whether given before or after transplant will have a major impact on outcomes. The role of transplantation for those with liver cell cancer continues to evolve as other interventions become more effective. Immunosuppression is usually required life-long and adherence remains a challenge, especially in adolescents. Immunosuppression with calcineurin inhibitors (primarily tacrolimus), antimetabolites (azathioprine or mycophenolate) and corticosteroids remains standard. Outcomes after transplantation are good but not normal in quality or quantity. Premature death may be due to increased risk of cardiovascular disease, de novo cancer, recurrent disease or late technical problems.

  7. Polycaprolactone nanowire surfaces as interfaces for cardiovascular applications

    NASA Astrophysics Data System (ADS)

    Leszczak, Victoria

    Cardiovascular disease is the leading killer of people worldwide. Current treatments include organ transplants, surgery, metabolic products and mechanical/synthetic implants. Of these, mechanical and synthetic implants are the most promising. However, rejection of cardiovascular implants continues to be a problem, eliciting a need for understanding the mechanisms behind tissue-material interaction. Recently, bioartificial implants, consisting of synthetic tissue engineering scaffolds and cells, have shown great promise for cardiovascular repair. An ideal cardiovascular implant surface must be capable of adhering cells and providing appropriate physiological responses while the native tissue integrates with the scaffold. However, the success of these implants is not only dependent on tissue integration but also hemocompatibility (interaction of material with blood components), a property that depends on the surface of the material. A thorough understanding of the interaction of cardiovascular cells and whole blood and its components with the material surface is essential in order to have a successful application which promotes healing as well as native tissue integration and regeneration. The purpose of this research is to study polymeric nanowire surfaces as potential interfaces for cardiovascular applications by investigating cellular response as well as hemocompatibility.

  8. Prognostic Indicators of Cardiovascular Risk in Renal Disease

    PubMed Central

    Hildreth, Cara M.

    2011-01-01

    Although the annual mortality rate for end-stage renal disease (ESRD) is decreasing, likely due to an increase in kidney transplantation rate, the survival probability for ESRD patients from day one of dialysis has not changed, and is still poor with a 5-year survival rate of approximately 34%. This is contributed to by a high prevalence of cardiovascular disease, which is the leading cause of death in ESRD patients. In order to improve survival outcomes, patients at high risk of cardiovascular related mortality need to be identified. Heart rate variability (HRV), baroreceptor sensitivity, and baroreceptor reflex effectiveness index can be used to assess heart rate control and may predict cardiovascular mortality. This paper will discuss how HRV, baroreceptor sensitivity, and baroreceptor reflex effectiveness index are altered in renal disease and the utility of these indices as markers of cardiac risk in this patient population. PMID:22294981

  9. Clinical Application of Stem Cells in the Cardiovascular System

    NASA Astrophysics Data System (ADS)

    Stamm, Christof; Klose, Kristin; Choi, Yeong-Hoon

    Regenerative medicine encompasses "tissue engineering" - the in vitro fabrication of tissues and/or organs using scaffold material and viable cells - and "cell therapy" - the transplantation or manipulation of cells in diseased tissue in vivo. In the cardiovascular system, tissue engineering strategies are being pursued for the development of viable replacement blood vessels, heart valves, patch material, cardiac pacemakers and contractile myocardium. Anecdotal clinical applications of such vessels, valves and patches have been described, but information on systematic studies of the performance of such implants is not available, yet. Cell therapy for cardiovascular regeneration, however, has been performed in large series of patients, and numerous clinical studies have produced sometimes conflicting results. The purpose of this chapter is to summarize the clinical experience with cell therapy for diseases of the cardiovascular system, and to analyse possible factors that may influence its outcome.

  10. Small Bowel Transplant

    PubMed Central

    2003-01-01

    EXECUTIVE SUMMARY Objective The Medical Advisory Secretariat undertook a review of the evidence on the effectiveness and cost-effectiveness of small bowel transplant in the treatment of intestinal failure. Small Bowel Transplantation Intestinal failure is the loss of absorptive capacity of the small intestine that results in an inability to meet the nutrient and fluid requirements of the body via the enteral route. Patients with intestinal failure usually receive nutrients intravenously, a procedure known as parenteral nutrition. However, long-term parenteral nutrition is associated with complications including liver failure and loss of venous access due to recurrent infections. Small bowel transplant is the transplantation of a cadaveric intestinal allograft for the purpose of restoring intestinal function in patients with irreversible intestinal failure. The transplant may involve the small intestine alone (isolated small bowel ISB), the small intestine and the liver (SB-L) when there is irreversible liver failure, or multiple organs including the small bowel (multivisceral MV or cluster). Although living related donor transplant is being investigated at a limited number of centres, cadaveric donors have been used in most small bowel transplants. The actual transplant procedure takes approximately 12-18 hours. After intestinal transplant, the patient is generally placed on prophylactic antibiotic medication and immunosuppressive regimen that, in the majority of cases, would include tacrolimus, corticosteroids and an induction agent. Close monitoring for infection and rejection are essential for early treatment. Medical Advisory Secretariat Review The Medical Advisory Secretariat undertook a review of 35 reports from 9 case series and 1 international registry. Sample size of the individual studies ranged from 9 to 155. As of May 2001, 651 patients had received small bowel transplant procedures worldwide. According to information from the Canadian Organ Replacement

  11. Rodent Studies of Cardiovascular Deconditioning

    NASA Technical Reports Server (NTRS)

    Shoukas, Artin A.

    1999-01-01

    Changes in blood pressure can occur for two reasons: 1) A decrease in cardiac output resulting from the altered contractility of the heart or through changes in venous filling pressure via the Frank Starling mechanism or; 2) A change in systemic vascular resistance. The observed changes in cardiac output and blood pressure after long term space flight cannot be entirely explained through changes in contractility or heart rate alone. Therefore, alterations in filling pressure mediated through changes in systemic venous capacitance and arterial resistance function may be important determinants of cardiac output and blood pressure after long term space flight. Our laboratory and previous studies have shown the importance of veno-constriction mediated by the carotid sinus baroreceptor reflex system on overall circulatory homeostasis and in the regulation of cardiac output. Our proposed experiments test the overall hypothesis that alterations in venous capacitance function and arterial resistance by the carotid sinus baroreceptor reflex system are an important determinant of the cardiac output and blood pressure response seen in astronauts after returning to earth from long term exposure to microgravity. This hypothesis is important to our overall understanding of circulatory adjustments made during long term space flight. It also provides a framework for investigating counter measures to reduce the incidence of orthostatic hypotension caused by an attenuation of cardiac output. We continue to use hind limb unweighted (HLU) rat model to simulate the patho physiological effects as they relate to cardiovascular deconditioning in microgravity. We have used this model to address the hypothesis that microgravity induced cardiovascular deconditioning results in impaired vascular responses and that these impaired vascular responses result from abnormal alpha-1 AR signaling. The impaired vascular reactivity results in attenuated blood pressure and cardiac output responses to an

  12. Testosterone and Cardiovascular Disease.

    PubMed

    Kloner, Robert A; Carson, Culley; Dobs, Adrian; Kopecky, Stephen; Mohler, Emile R

    2016-02-01

    Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety. PMID:26846952

  13. Autophagy in cardiovascular biology

    PubMed Central

    Lavandero, Sergio; Chiong, Mario; Rothermel, Beverly A.; Hill, Joseph A.

    2015-01-01

    Cardiovascular disease is the leading cause of death worldwide. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells, vascular smooth muscle cells, and macrophages. In all cases, a window of optimal autophagic activity appears to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. In this Review, we discuss the potential for targeting autophagy therapeutically and our vision for where this exciting biology may lead in the future. PMID:25654551

  14. Autophagy in cardiovascular biology.

    PubMed

    Lavandero, Sergio; Chiong, Mario; Rothermel, Beverly A; Hill, Joseph A

    2015-01-01

    Cardiovascular disease is the leading cause of death worldwide. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells, vascular smooth muscle cells, and macrophages. In all cases, a window of optimal autophagic activity appears to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. In this Review, we discuss the potential for targeting autophagy therapeutically and our vision for where this exciting biology may lead in the future.

  15. Cardiovascular modeling and diagnostics

    SciTech Connect

    Kangas, L.J.; Keller, P.E.; Hashem, S.; Kouzes, R.T.

    1995-12-31

    In this paper, a novel approach to modeling and diagnosing the cardiovascular system is introduced. A model exhibits a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. Potentially, a model will be incorporated into a cardiovascular diagnostic system. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and the variables of an individual at a given time are used for diagnosis. This approach also exploits sensor fusion to optimize the utilization of biomedical sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.

  16. [Cardiovascular prevention - 2016].

    PubMed

    Vértes, András; Szabados, Eszter

    2016-09-01

    Cardiovascular diseases are the main causes of premature death worldwide despite the fact that cardiovascular mortality decreased significantly in the last few decades in financially developed countries. This reduction is partly due to the modern medical and revascularisation treatments, and partly because of the effectiveness of prevention strategies such as lowering blood pressure and cholesterol level, as well as successful strategies against smoking. However, this positive trend is undermined by the striking growth in obesity and in type 2 diabetes mellitus, which could also be successfully controlled by lifestyle changes. This summary is based on an overview of the recent (2016) European Guideline for the Prevention of Cardiovascular Diseases. Here the authors describe preventive strategies and goals to be achieved, the most important lifestyle suggestions, and the secondary prevention medical treatment for patients with already established cardiovascular disease. Orv. Hetil., 2016, 157(38), 1526-1531. PMID:27640620

  17. [Cardiovascular risk among firefighters].

    PubMed

    Serra, A

    2012-01-01

    Firefighting is a high-hazard job for hearth disease, smoke exposure, physical exertion, psychological stressors and noise increase cardiovascular risk among fire fighters. In U.S.A. during the period 1984-2011 45% of on-duty fire fighter fatalities were due to sudden cardiac death. However numerous mortality studies have not shown consistent evidence of an increased risk of cardiovascular diseases. In Italy fire fighters, burdened with elevated cardiovascular risk and psycho-physical demand, have entry-level and periodic medical evaluations. For these workers wellness/fitness programs, strategies aimed to reduce cardiovascular risk factors and fitness evaluations to ensure that are physically capable of performing the essential job tasks of their profession should be encouraged. PMID:23405620

  18. Cocaine and Cardiovascular Events.

    ERIC Educational Resources Information Center

    Cantwell, John D.; Rose, Fred D.

    1986-01-01

    The case of a 21-year-old man who suffered a myocardial infarction after using cocaine and amphetamines is reported. A brief literature review provides evidence of cocaine's potential cardiovascular effects. (Author/MT)

  19. [Cardiovascular syphilis: diagnosis, treatment].

    PubMed

    Carrada-Bravo, Teodoro

    2006-01-01

    Cardiovascular tertiary syphilis may lead to aortitis, aortic aneurism, coronary stenosis, aortic insufficiency and, rarely, to myocarditis. The physician must be familiar with the clinical presentations of this process, including the asymptomatic variety and must be able to have an organized plan for the diagnosis and evaluation to establish or exclude the presence of cardiovascular pathology and the differential diagnosis with other entities. Once the etiologic and topographic diagnosis is established, the patient should be treated with penicillin, doxicycline and other antibiotics, and the consequences of the disorder, both actual and potential, should be considered before deciding weather to recommend surgical intervention. Although late syphilis can be prevented by appropriate therapy of early syphilis, this is a cardiovascular disease that most likely will continue to be diagnosed lately. Understanding of the pathology and pathophysiology of the disease, is most important for its prompt recognition and subsequent management. This paper reviews the natural history, diagnosis and therapy of cardiovascular syphilis. PMID:17469346

  20. Understanding cardiovascular disease

    MedlinePlus

    ... of plaque. Narrow arteries reduce or block blood flow. When blood and oxygen can't get to the legs, it can injure nerves and tissue. High blood pressure (hypertension) is a cardiovascular disease that ...

  1. Violence and Cardiovascular Health

    PubMed Central

    Suglia, Shakira F.; Sapra, Katherine J.; Koenen, Karestan C.

    2014-01-01

    Context Violence, experienced in either childhood or adulthood, has been associated with physical health outcomes including cardiovascular disease. However, the consistency of the existing literature has not been evaluated. Evidence acquisition In 2013, the authors conducted a PubMed and Web of Science review of peer reviewed articles published prior to August 2013 on the relation between violence exposure, experienced in either childhood or adulthood, and cardiovascular outcomes. To meet inclusion criteria, articles had to present estimates for the relation between violence exposure and cardiovascular outcomes (hypertension, blood pressure, stroke, coronary disease, or myocardial infarction) adjusted for demographic factors. Articles focusing on violence from TV, video games, natural disasters, terrorism, or war were excluded. Evidence synthesis The initial search yielded 2,273 articles; after removing duplicates and applying inclusion and exclusion criteria, 30 articles were selected for review. A consistent positive relation was noted on the association between violence experienced during childhood and cardiovascular outcomes in adulthood (i.e., hypertension, coronary heart disease, and myocardial infarction). Associations across genders with varying types of violence exposure were also noted. By contrast, findings were mixed on the relation between adult violence exposure and cardiovascular outcome. Conclusions Despite varying definitions of violence exposure and cardiovascular endpoints, a consistent relation exists between childhood violence exposure, largely assessed retrospectively, and cardiovascular endpoints. Findings are mixed for the adult violence–cardiovascular health relation. The cross-sectional nature of most adult studies and the reliance of self-reported outcomes can potentially be attributed to the lack of findings among adult violence exposure studies. PMID:25599905

  2. Variability and cardiovascular homeostasis.

    PubMed

    Hughson, R L; Gharib, C

    1995-01-01

    The inability to maintain the upright posture due to a failure in the arterial blood pressure regulatory mechanisms on return from space travel or after a period of head down tilt bed rest (HDBR) is the ultimate sign of cardiovascular deconditioning. Yet, the final response of syncope is potentially heralded by a series of precursor events that can be quantified and analyzed in new, more insightful ways to attempt to understand the integrative nature of autonomic control of the cardiovascular system.

  3. Cardiovascular information systems.

    PubMed

    Marion, Joe

    2012-01-01

    The ARRA/HITECH Act has made electronic medical records a front burner issue, and many believe that EMRs will make departmental systems redundant. Some cardiologists beg to differ, arguing that cardiovascular information systems are deeply clinical and essential to the cardiovascular workflow. Here's a look at the evolution of CVIS, EMR, and their roles as the healthcare landscape is being transformed by meaningful use.

  4. Cardiovascular Effects of Caffeine

    PubMed Central

    Myers, Martin G.

    1992-01-01

    A review of the literature on the cardiovascular effects of caffeine indicates that moderate caffeine consumption does not cause cardiac arrhythmias, hypertension, or an increased incidence of coronary heart disease. Caffeine use is often associated with atherogenic behavior, such as cigarette smoking. Failure to take into account covariables for cardiovascular disease could be responsible for commonly held misconceptions about caffeine and heart disease. PMID:21221403

  5. Pediatric heart transplantation

    PubMed Central

    Stiasny, Brian; Dave, Hitendu; Cavigelli-Brunner, Anna; Balmer, Christian; Kretschmar, Oliver; Bürki, Christoph; Klauwer, Dietrich; Hübler, Michael

    2015-01-01

    Pediatric heart transplantation (pHTx) represents a small (14%) but very important and particular part in the field of cardiac transplantation. This treatment has lifelong impact on children. To achieve the best short and especially long-term survival with adequate quality of life, which is of crucial importance for this young patient population, one has to realize and understand the differences with adult HTx. Indication for transplantation, waitlist management including ABO incompatible (ABOi) transplantation and immunosuppression differ. Although young transplant recipients are ultimately likely to be considered for re-transplantation. One has to distinguish between myopathy and complex congenital heart disease (CHD). The differences in anatomy and physiology make the surgical procedure much more complex and create unique challenges. These recipients need a well-organized and educated team with pediatric cardiologists and intensivists, including a high skilled surgeon, which is dedicated to pHTx. Therefore, these types of transplants are best concentrated in specialized centers to achieve promising outcome. PMID:25922739

  6. Pediatric heart transplantation.

    PubMed

    Schweiger, Martin; Stiasny, Brian; Dave, Hitendu; Cavigelli-Brunner, Anna; Balmer, Christian; Kretschmar, Oliver; Bürki, Christoph; Klauwer, Dietrich; Hübler, Michael

    2015-03-01

    Pediatric heart transplantation (pHTx) represents a small (14%) but very important and particular part in the field of cardiac transplantation. This treatment has lifelong impact on children. To achieve the best short and especially long-term survival with adequate quality of life, which is of crucial importance for this young patient population, one has to realize and understand the differences with adult HTx. Indication for transplantation, waitlist management including ABO incompatible (ABOi) transplantation and immunosuppression differ. Although young transplant recipients are ultimately likely to be considered for re-transplantation. One has to distinguish between myopathy and complex congenital heart disease (CHD). The differences in anatomy and physiology make the surgical procedure much more complex and create unique challenges. These recipients need a well-organized and educated team with pediatric cardiologists and intensivists, including a high skilled surgeon, which is dedicated to pHTx. Therefore, these types of transplants are best concentrated in specialized centers to achieve promising outcome.

  7. Intestinal and multivisceral transplantation

    PubMed Central

    Meira, Sérgio Paiva; Guardia, Bianca Della; Evangelista, Andréia Silva; Matielo, Celso Eduardo Lourenço; Neves, Douglas Bastos; Pandullo, Fernando Luis; Felga, Guilherme Eduardo Gonçalves; Alves, Jefferson André da Silva; Curvelo, Lilian Amorim; Diaz, Luiz Gustavo Guedes; Rusi, Marcela Balbo; Viveiros, Marcelo de Melo; de Almeida, Marcio Dias; Epstein, Marina Gabrielle; Pedroso, Pamella Tung; Salvalaggio, Paolo; Meirelles, Roberto Ferreira; Rocco, Rodrigo Andrey; de Almeida, Samira Scalso; de Rezende, Marcelo Bruno

    2015-01-01

    Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990’s, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run. PMID:25993080

  8. [Surgical techniques of organ transplants].

    PubMed

    Froněk, Jiří

    2015-01-01

    The list of surgical procedures of solid organ transplantations appears very interesting and colorful, even with overlap among techniques. Liver transplantation is a life-saving procedure in a majority of cases, the liver can be transplanted as a full or partial graft. The liver graft can be split for two recipients; it can also be reduced for a small recipient if splitting is not indicated. Kidney transplantation is the most common solid organ transplant procedure, the majority of kidney grafts come from brain-dead donors whereas the number of live donor transplants is increasing, also thanks to paired donation and blood group incompatible transplantation methods. The small bowel and multivisceral transplantation are rare procedures; they serve selected patients with short bowel syndrome, some patients with retroperitoneal tumors or with extensive visceral thrombosis. Solid organ transplants are well established treatment methods with good and proven outcomes. A majority of patients can return to a normal life after their transplants.

  9. Transplant tourism: understanding the risks.

    PubMed

    Babik, Jennifer M; Chin-Hong, Peter

    2015-04-01

    Transplant tourism is commonly defined as travel abroad for the purpose of transplantation, but the term evokes ethical and legal concerns about commercial transplantation. Due to the mismatch in supply and demand for organs, transplant tourism has increased over the last several decades and now accounts for 10 % of transplants worldwide. Patients from the USA who pursue transplantation abroad do so most commonly for renal transplantation, and travel mostly to China, the Philippines, and India. Transplant tourism puts the organ recipient at risk for surgical complications, poor graft outcome, increased mortality, and a variety of infectious complications. Bacterial, viral, fungal, and parasitic infections have all been described, and most concerning are the high rates of blood-borne viral infections and invasive, often fatal, fungal infections. Transplant and infectious diseases physicians should have a high degree of suspicion for infectious complications in patients returning from transplantation abroad.

  10. [Surgical techniques of organ transplants].

    PubMed

    Froněk, Jiří

    2015-01-01

    The list of surgical procedures of solid organ transplantations appears very interesting and colorful, even with overlap among techniques. Liver transplantation is a life-saving procedure in a majority of cases, the liver can be transplanted as a full or partial graft. The liver graft can be split for two recipients; it can also be reduced for a small recipient if splitting is not indicated. Kidney transplantation is the most common solid organ transplant procedure, the majority of kidney grafts come from brain-dead donors whereas the number of live donor transplants is increasing, also thanks to paired donation and blood group incompatible transplantation methods. The small bowel and multivisceral transplantation are rare procedures; they serve selected patients with short bowel syndrome, some patients with retroperitoneal tumors or with extensive visceral thrombosis. Solid organ transplants are well established treatment methods with good and proven outcomes. A majority of patients can return to a normal life after their transplants. PMID:26585110

  11. Cardiovascular function in acromegaly.

    PubMed

    Clayton, R N

    2003-06-01

    Even with modern treatment, acromegaly is associated with a 2- to 3-fold increase in mortality, mainly from vascular disease, which is probably a result of the long exposure of tissues to excess GH before diagnosis and treatment. There is accumulating evidence that effective treatment to lower serum GH levels to less than 1-2 ng/ml (glucose suppressed or random, respectively) and normalize IGF-I improves long-term outcome and survival. In addition to recognized cardiovascular risk factors of hypertension, type 2 diabetes mellitus, and dyslipidemia, there is accumulating evidence of specific structural and functional changes in the heart in acromegaly. Along with endothelial dysfunction, these changes may contribute to the increased mortality in this disease. There are specific structural changes in the myocardium with increased myocyte size and interstitial fibrosis of both ventricles. Left ventricular hypertrophy is common even in young patients with short duration of disease. Some of these structural changes can be reversed by effective treatment. Functionally, the main consequence of these changes is impaired left ventricular diastolic function, particularly when exercising, such that exercise tolerance is reduced. Diastolic function improves with treatment, but the effect on exercise tolerance is more variable, and more longitudinal data are required to assess the benefits. What scant data there are on rhythm changes suggest an increase in complex ventricular arrhythmias, possibly as a result of the disordered left ventricular architecture. The functional consequences of these changes are unclear, but they may provide a useful early marker for the ventricular remodeling that occurs in the acromegalic heart. Endothelial dysfunction, especially flow-mediated dilatation, is an early marker of atherosclerosis, and limited data imply that this is impaired in active acromegaly and can be improved with treatment. Similarly, early arterial structural changes, such as

  12. Living related liver transplantation.

    PubMed

    Makuuchi, M; Kawarazaki, H; Iwanaka, T; Kamada, N; Takayama, T; Kumon, M

    1992-01-01

    Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a living donor. After the first successful living related liver transplantation was performed by Strong in Brisbane, Australia, Japanese hepatic and transplant surgeons also began to perform such operations. As of February 1991, 16 living related liver transplantations had already been performed in Japan, mainly for children with biliary atresia. Five of these patients subsequently died, however, our patient has survived more than 1 year, and she is presently leading a normal school life. The most important issue regarding living related liver transplantation is to ensure the donor's safety. For this purpose, we conducted a preoperative banking of the donor's own blood and plasma. In addition, a selective vascular occlusion was carried out to reduce blood loss during the resection of the liver. Intraoperative color Doppler ultrasonography was introduced for evaluating the circulation of the graft. By using this modality, the following three points were able to be accurately estimated in order to obtain optimal graft perfusion: 1) The most suitable position for the graft to be fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed and 3) the indication for a ligation of the collateral veins to form a porto-systemic shunt. Thanks to these procedures, living related liver transplantations have now become an acceptable transplant method, however, a transplantation from a cadaver that is brain dead but still has a beating heart is still absolutely necessary for adult recipients. Therefore, in the future, both methods should be performed.

  13. Hypertension and arterial stiffness in heart transplantation patients

    PubMed Central

    de Souza-Neto, João David; de Oliveira, Ítalo Martins; Lima-Rocha, Hermano Alexandre; Oliveira-Lima, José Wellington; Bacal, Fernando

    2016-01-01

    OBJECTIVES: Post-transplantation hypertension is prevalent and is associated with increased cardiovascular morbidity and subsequent graft dysfunction. The present study aimed to identify the factors associated with arterial stiffness as measured by the ambulatory arterial stiffness index. METHODS: The current study used a prospective, observational, analytical design to evaluate a group of adult heart transplantation patients. Arterial stiffness was obtained by monitoring ambulatory blood pressure and using the ambulatory arterial stiffness index as the surrogate outcome. Multivariate logistic regression analyses were performed to control confounding. RESULTS: In a group of 85 adult heart transplantation patients, hypertension was independently associated with arterial stiffness (OR 4.98, CI 95% 1.06-23.4) as well as systolic and diastolic blood pressure averages and nighttime descent. CONCLUSIONS: Measurement of ambulatory arterial stiffness index is a new, non-invasive method that is easy to perform, may contribute to better defining arterial stiffness prognosis and is associated with hypertension.

  14. Hypertension and arterial stiffness in heart transplantation patients

    PubMed Central

    de Souza-Neto, João David; de Oliveira, Ítalo Martins; Lima-Rocha, Hermano Alexandre; Oliveira-Lima, José Wellington; Bacal, Fernando

    2016-01-01

    OBJECTIVES: Post-transplantation hypertension is prevalent and is associated with increased cardiovascular morbidity and subsequent graft dysfunction. The present study aimed to identify the factors associated with arterial stiffness as measured by the ambulatory arterial stiffness index. METHODS: The current study used a prospective, observational, analytical design to evaluate a group of adult heart transplantation patients. Arterial stiffness was obtained by monitoring ambulatory blood pressure and using the ambulatory arterial stiffness index as the surrogate outcome. Multivariate logistic regression analyses were performed to control confounding. RESULTS: In a group of 85 adult heart transplantation patients, hypertension was independently associated with arterial stiffness (OR 4.98, CI 95% 1.06-23.4) as well as systolic and diastolic blood pressure averages and nighttime descent. CONCLUSIONS: Measurement of ambulatory arterial stiffness index is a new, non-invasive method that is easy to perform, may contribute to better defining arterial stiffness prognosis and is associated with hypertension. PMID:27652829

  15. Sexual Health in Hematopoietic Stem Cell Transplant Recipients

    PubMed Central

    Li, Zhuoyan; Mewawalla, Prerna; Stratton, Pamela; Yong, Agnes S.M.; Shaw, Bronwen E.; Hashmi, Shahrukh; Jagasia, Madan; Mohty, Mohamad; Majhail, Navneet S.; Savani, Bipin N.; Rovó, Alicia

    2016-01-01

    Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT. PMID:26372459

  16. Aspergillus Mediastinitis after Orthotopic Heart Transplantation: A Case Report.

    PubMed

    El-Sayed Ahmed, Magdy M; Almanfi, Abdelkader; Aftab, Muhammad; Singh, Steve K; Mallidi, Hari R; Frazier, O H

    2015-10-01

    A 55-year-old woman was admitted for orthotopic heart transplantation. Her medical history was notable for multiple cardiovascular problems, including ischemic cardiomyopathy that necessitated circulatory support with a left ventricular assist device. Five weeks after undergoing orthotopic heart transplantation, she developed Aspergillus calidoustus mediastinitis, for which she underwent a prolonged course of antifungal treatment that comprised (in sequence) posaconazole for 11 days, voriconazole for 10 days, and amphotericin B for 42 days. During this period, she also underwent repeated mediastinal drainage and sternal débridement, followed by sternal wiring and coverage with bilateral pectoralis advancement flaps. Four months postoperatively, she was discharged from the hospital with a successfully controlled infection and a healed sternum. To our knowledge, only 3 previous cases of Aspergillus mediastinitis after orthotopic heart transplantation have been reported in the literature, none of which was Aspergillus calidoustus.

  17. Pediatric transplantation: preventing thrombosis.

    PubMed

    Robertson, J D

    2015-06-01

    Due to progressive advances in surgical techniques, immunosuppressive therapies, and supportive care, outcomes from both solid organ transplantation and hematopoietic stem cell transplantation continue to improve. Thrombosis remains a challenging management issue in this context, with implications for both graft survival and long-term quality of life. Unfortunately, there remains a general paucity of pediatric-specific data regarding thrombosis incidence, risk stratification, and the safety or efficacy of preventative strategies with which to guide treatment algorithms. This review summarizes the available evidence and rationale underlying the spectrum of current practices aimed at preventing thrombosis in the transplant recipient, with a particular focus on risk factors, pathophysiology, and described antithrombotic regimens.

  18. Liver transplantation: Current status and challenges

    PubMed Central

    Jadlowiec, Caroline C; Taner, Timucin

    2016-01-01

    Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death (DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function. PMID:27182155

  19. Successful kidney transplantation in highly sensitized patients.

    PubMed

    Zhang, Weijie; Chen, Dong; Chen, Zhishui; Zeng, Fanjun; Ming, Changsheng; Lin, Zhengbin; Zhou, Ping; Chen, Gang; Chen, Xiaoping

    2011-03-01

    Highly sensitized patients experience an increased number of rejection episodes and have poorer graft survival rates; hence, sensitization is a significant barrier to both access to and the success of organ transplantation. This study reports our experience in kidney transplantation in highly sensitized patients. Fourteen patients with sensitization or high levels of panelreactive antibodies (PRA) were studied. All patients were desensitized with pre-transplant intravenous immunoglobulin (IVIG)/plasmapheresis (PP) with or without rituximab and thymoglobulin induction therapy, combined with a Prograf/MMF/Pred immunosuppressive regimen. Of 14 patients, 10 showed good graft functions without acute rejection (AR) episodes. Acute cellular rejection in two patients was reversed by methylprednisolone. Two patients underwent antibody-mediated rejection; one was treated with PP/IVIG successfully, whereas the other lost graft functions due to the de novo production of donor-specific antibodies (DSA). Graft functions were stable, and there were no AR episodes in other patients. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful live-donor kidney transplantation in sensitized recipients. PMID:21681679

  20. Advances in the understanding of transplant glomerulopathy.

    PubMed

    Husain, Sufia; Sis, Banu

    2013-08-01

    Transplant glomerulopathy is a sign of chronic kidney allograft damage. It has poor survival and no effective therapies. This entity develops as a maladaptive repair/remodeling response to sustained endothelial injury and is characterized by duplication/multilamination of capillary basement membranes. This review provides up-to-date information for transplant glomerulopathy, including new insights into underlying causes and mechanisms, and highlights unmet needs in diagnostics. Transplant glomerulopathy is widely accepted as the principal manifestation of chronic antibody-mediated rejection, mostly with HLA antigen class II antibodies. However, recent data suggest that at least in some patients, there also is an association with hepatitis C virus infection, autoimmunity, and late thrombotic microangiopathy. Furthermore, intragraft molecular studies reveal nonresolving inflammation after sustained endothelial injury as a key mechanism and therapeutic target. Unfortunately, current international criteria rely heavily on light microscopy and miss patients at early stages, when they likely are treatable. Therefore, better tools, such as electron microscopy or molecular probes, are needed to detect patients when kidney injury is in an early active phase. Better understanding of causes and effector mechanisms coupled with early diagnosis can lead to the development of new therapeutics for transplant glomerulopathy and improved kidney outcomes.

  1. Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to Develop a Core Outcome Set for Trials in Kidney Transplantation

    PubMed Central

    Tong, Allison; Budde, Klemens; Gill, John; Josephson, Michelle A.; Marson, Lorna; Pruett, Timothy L.; Reese, Peter P.; Rosenbloom, David; Rostaing, Lionel; Warrens, Anthony N.; Wong, Germaine; Craig, Jonathan C.; Crowe, Sally; Harris, Tess; Hemmelgarn, Brenda; Manns, Braden; Tugwell, Peter; Van Biesen, Wim; Wheeler, David C.; Winkelmayer, Wolfgang C.; Evangelidis, Nicole; Sautenet, Benedicte; Howell, Martin; Chapman, Jeremy R.

    2016-01-01

    Background Although advances in treatment have dramatically improved short-term graft survival and acute rejection in kidney transplant recipients, long-term graft outcomes have not substantially improved. Transplant recipients also have a considerably increased risk of cancer, cardiovascular disease, diabetes, and infection, which all contribute to appreciable morbidity and premature mortality. Many trials in kidney transplantation are short-term, frequently use unvalidated surrogate endpoints, outcomes of uncertain relevance to patients and clinicians, and do not consistently measure and report key outcomes like death, graft loss, graft function, and adverse effects of therapy. This diminishes the value of trials in supporting treatment decisions that require individual-level multiple tradeoffs between graft survival and the risk of side effects, adverse events, and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative aims to develop a core outcome set for trials in kidney transplantation that is based on the shared priorities of all stakeholders. Methods This will include a systematic review to identify outcomes reported in randomized trials, a Delphi survey with an international multistakeholder panel (patients, caregivers, clinicians, researchers, policy makers, members from industry) to develop a consensus-based prioritized list of outcome domains and a consensus workshop to review and finalize the core outcome set for trials in kidney transplantation. Conclusions Developing and implementing a core outcome set to be reported, at a minimum, in all kidney transplantation trials will improve the transparency, quality, and relevance of research; to enable kidney transplant recipients and their clinicians to make better-informed treatment decisions for improved patient outcomes. PMID:27500269

  2. Bone Marrow Transplantation

    MedlinePlus

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a person's ...

  3. Liver transplant - series (image)

    MedlinePlus

    Liver failure causes many problems, including malnutrition, problems with blood clotting, bleeding form the gastrointestinal tract, and jaundice. Frequently, patients who undergo liver transplantation are quite ill, and require ...

  4. Textbooks, Transitions, and Transplants

    ERIC Educational Resources Information Center

    Callahan, Leroy G.; Passi, Sneh Lata

    1972-01-01

    Three popular textbooks were analyzed for level of cognitive processes used, and implications were drawn regarding supplementary activities if the English primary school model is to be transplanted" in America. (MM)

  5. Corneal transplant - series (image)

    MedlinePlus

    Corneal transplantation is recommended for: severe corneal infection, injury, damage, or scarring corneas that no longer allow light to pass through (opaque), often secondary to lens surgery (see cataract surgery), infections, and inherited diseases ...

  6. Kidney transplant - slideshow

    MedlinePlus

    ... M. Editorial team. Related MedlinePlus Health Topics Kidney Transplantation A.D.A.M., Inc. is accredited by ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  7. Talking about Kidney Transplants.

    ERIC Educational Resources Information Center

    Solomon, Joan; Swift, Julia

    1990-01-01

    Described is a project in which information about the moral issues surrounding tissue transplants was obtained and videotaped for classroom use. Moral positions and possible educational strategies are discussed. Examples of student statements are presented. (CW)

  8. Clinical potential of DNA methylation in organ transplantation.

    PubMed

    Peters, Fleur S; Manintveld, Olivier C; Betjes, Michiel G H; Baan, Carla C; Boer, Karin

    2016-07-01

    Identification of patients at risk for post-transplant complications is a major challenge, but it will improve clinical care and patient health after organ transplantation. The poor predictive value of the current biomarkers highlights the need to explore novel and innovative methods, such as epigenetics, for the discovery of new biomarkers. Cell differentiation and function of immune cells is dependent on epigenetic mechanisms, which regulate gene expression without altering the original DNA sequence. These epigenetic mechanisms are dynamic, potentially heritable, change with age, and can be regulated and influenced by environmental conditions. One of the most well-known epigenetic mechanisms is DNA methylation, which comprises the methylation of a cytosine (C) next to a guanine (G; CpG dinucleotides). Aberrant DNA methylation is increasingly associated with disease, including immune-mediated diseases, and these alterations precede the clinical phenotype. The impact of DNA methylation profiles on transplant acceptance and rejection as well as on other post-transplant complications is unknown. In this study we examine the current evidence of the functional role of recipient and donor DNA methylation on outcome after organ transplantation. Changes in DNA methylation may predict the risk of developing post-transplant complications, such as infections, malignancies and allograft rejection. We speculate that identification of these changes in DNA methylation contributes to earlier diagnosis and prevention of post-transplant complications, leading to improved patient care. PMID:27085975

  9. Microbial responses to southward and northward Cambisol soil transplant.

    PubMed

    Wang, Mengmeng; Liu, Shanshan; Wang, Feng; Sun, Bo; Zhou, Jizhong; Yang, Yunfeng

    2015-12-01

    Soil transplant serves as a proxy to simulate climate changes. Recently, we have shown that southward transplant of black soil and northward transplant of red soil altered soil microbial communities and biogeochemical variables. However, fundamental differences in soil types have prevented direct comparison between southward and northward transplants. To tackle it, herein we report an analysis of microbial communities of Cambisol soil in an agriculture field after 4 years of adaptation to southward and northward soil transplants over large transects. Analysis of bare fallow soils revealed concurrent increase in microbial functional diversity and coarse-scale taxonomic diversity at both transplanted sites, as detected by GeoChip 3.0 and DGGE, respectively. Furthermore, a correlation between microbial functional diversity and taxonomic diversity was detected, which was masked in maize cropped soils. Mean annual temperature, soil moisture, and nitrate (NO3 ¯-N) showed strong correlations with microbial communities. In addition, abundances of ammonium-oxidizing genes (amoA) and denitrification genes were correlated with nitrification capacity and NO3 ¯-N contents, suggesting that microbial responses to soil transplant could alter microbe-mediated biogeochemical cycle at the ecosystem level.

  10. Clinical potential of DNA methylation in organ transplantation.

    PubMed

    Peters, Fleur S; Manintveld, Olivier C; Betjes, Michiel G H; Baan, Carla C; Boer, Karin

    2016-07-01

    Identification of patients at risk for post-transplant complications is a major challenge, but it will improve clinical care and patient health after organ transplantation. The poor predictive value of the current biomarkers highlights the need to explore novel and innovative methods, such as epigenetics, for the discovery of new biomarkers. Cell differentiation and function of immune cells is dependent on epigenetic mechanisms, which regulate gene expression without altering the original DNA sequence. These epigenetic mechanisms are dynamic, potentially heritable, change with age, and can be regulated and influenced by environmental conditions. One of the most well-known epigenetic mechanisms is DNA methylation, which comprises the methylation of a cytosine (C) next to a guanine (G; CpG dinucleotides). Aberrant DNA methylation is increasingly associated with disease, including immune-mediated diseases, and these alterations precede the clinical phenotype. The impact of DNA methylation profiles on transplant acceptance and rejection as well as on other post-transplant complications is unknown. In this study we examine the current evidence of the functional role of recipient and donor DNA methylation on outcome after organ transplantation. Changes in DNA methylation may predict the risk of developing post-transplant complications, such as infections, malignancies and allograft rejection. We speculate that identification of these changes in DNA methylation contributes to earlier diagnosis and prevention of post-transplant complications, leading to improved patient care.

  11. The evolving roles of memory immune cells in transplantation

    PubMed Central

    Chen, Wenhao; Ghobrial, Rafik M.; Li, Xian C.

    2015-01-01

    Memory cells are the products of immune responses but also exert significant impact on subsequent immunity and immune tolerance, thus placing them in a unique position in transplant research. Memory cells are heterogeneous, including not only memory T cells but also memory B cells and innate memory cells. Memory cells are a critical component of protective immunity against invading pathogens, especially in immunosuppressed patients, but they also mediate graft loss and tolerance resistance. Recent studies suggest that some memory cells unexpectedly act as regulatory cells, promoting rather than hindering transplant survival. This functional diversity makes therapeutic targeting of memory cells a challenging task in transplantation. In this article we highlight recent advances in our understanding of memory cells, focusing on diversity of memory cells and mechanisms involved in their induction and functions. We also provide a broad overview on the challenges and opportunities in targeting memory cells in the induction of transplant tolerance. PMID:26102615

  12. Adipocytokines in renal transplant recipients

    PubMed Central

    Nagy, Kristof; Nagaraju, Shankar Prasad; Rhee, Connie M.; Mathe, Zoltan; Molnar, Miklos Z.

    2016-01-01

    In the last two decades, perceptions about the role of body fat have changed. Adipocytes modulate endocrine and immune homeostasis by synthesizing hundreds of hormones, known as adipocytokines. Many studies have been investigating the influences and effects of these adipocytokines and suggest that they are modulated by the nutritional and immunologic milieu. Kidney transplant recipients (KTRs) are a unique and relevant population in which the function of adipocytokines can be examined, given their altered nutritional and immune status and subsequent dysregulation of adipocytokine metabolism. In this review, we summarize the recent findings about four specific adipocytokines and their respective roles in KTRs. We decided to evaluate the most widely described adipocytokines, including leptin, adiponectin, visfatin and resistin. Increasing evidence suggests that these adipocytokines may lead to cardiovascular events and metabolic changes in the general population and may also increase mortality and graft loss rate in KTRs. In addition, we present findings on the interrelationship between serum adipocytokine levels and nutritional and immunologic status, and mechanisms by which adipocytokines modulate morbidity and outcomes in KTRs. PMID:27274819

  13. Allergy and the cardiovascular system.

    PubMed

    Triggiani, M; Patella, V; Staiano, R I; Granata, F; Marone, G

    2008-09-01

    The most dangerous and life-threatening manifestation of allergic diseases is anaphylaxis, a condition in which the cardiovascular system is responsible for the majority of clinical symptoms and for potentially fatal outcome. The heart is both a source and a target of chemical mediators released during allergic reactions. Mast cells are abundant in the human heart, where they are located predominantly around the adventitia of large coronary arteries and in close contact with the small intramural vessels. Cardiac mast cells can be activated by a variety of stimuli including allergens, complement factors, general anesthetics and muscle relaxants. Mediators released from immunologically activated human heart mast cells strongly influence ventricular function, cardiac rhythm and coronary artery tone. Histamine, cysteinyl leukotrienes and platelet-activating factor (PAF) exert negative inotropic effects and induce myocardial depression that contribute significantly to the pathogenesis of anaphylactic shock. Moreover, cardiac mast cells release chymase and renin that activates the angiotensin system locally, which further induces arteriolar vasoconstriction. The number and density of cardiac mast cells is increased in patients with ischaemic heart disease and dilated cardiomyopathies. This observation may help explain why these conditions are major risk factors for fatal anaphylaxis. A better understanding of the mechanisms involved in cardiac mast cell activation may lead to an improvement in prevention and treatment of systemic anaphylaxis.

  14. Dyslipidemia after allogeneic hematopoietic stem cell transplantation: evaluation and management.

    PubMed

    Griffith, Michelle L; Savani, Bipin N; Boord, Jeffrey B

    2010-08-26

    Currently, approximately 15,000 to 20,000 patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) annually throughout the world, with the number of long-term survivors increasing rapidly. In long-term follow-up after transplantation, the focus of care moves beyond cure of the original disease to the identification and treatment of late effects after HSCT. One of the more serious complications is therapy-related cardiovascular disease. Long-term survivors after HSCT probably have an increased risk of premature cardiovascular events. Cardiovascular complications related to dyslipidemia and other risk factors account for a significant proportion of late nonrelapse morbidity and mortality. This review addresses the risk and causes of dyslipidemia and impact on cardiovascular complications after HSCT. Immunosuppressive therapy, chronic graft-versus-host disease, and other long-term complications influence the management of dyslipidemia. There are currently no established guidelines for evaluation and management of dyslipidemia in HSCT patients; in this review, we have summarized our suggested approach in the HSCT population.

  15. Marathon run: cardiovascular adaptation and cardiovascular risk.

    PubMed

    Predel, Hans-Georg

    2014-11-21

    The first marathon run as an athletic event took place in the context of the Olympic Games in 1896 in Athens, Greece. Today, participation in a 'marathon run' has become a global phenomenon attracting young professional athletes as well as millions of mainly middle-aged amateur athletes worldwide each year. One of the main motives for these amateur marathon runners is the expectation that endurance exercise (EE) delivers profound beneficial health effects. However, with respect to the cardiovascular system, a controversial debate has emerged whether the marathon run itself is healthy or potentially harmful to the cardiovascular system, especially in middle-aged non-elite male amateur runners. In this cohort, exercise-induced increases in cardiac biomarkers-troponin and brain natriuretic peptide-and acute functional cardiac alterations have been observed and interpreted as potential cardiac damage. Furthermore, in the cohort of 40- to 65-year-old males engaged in intensive EE, a significant risk for the development of atrial fibrillation has been identified. Fortunately, recent studies demonstrated a normalization of the cardiac biomarkers and the functional alterations within a short time frame. Therefore, these alterations may be perceived as physiological myocardial reactions to the strenuous exercise and the term 'cardiac fatigue' has been coined. This interpretation is supported by a recent analysis of 10.9 million marathon runners demonstrating that there was no significantly increased overall risk of cardiac arrest during long-distance running races. In conclusion, intensive and long-lasting EE, e.g. running a full-distance Marathon, results in high cardiovascular strain whose clinical relevance especially for middle-aged and older athletes is unclear and remains a matter of controversy. Furthermore, there is a need for evidence-based recommendations with respect to medical screening and training strategies especially in male amateur runners over the age of

  16. Burnout in transplant nurses.

    PubMed

    Jesse, Michelle T; Abouljoud, Marwan S; Hogan, Kathy; Eshelman, Anne

    2015-09-01

    Context-Burnout is a response to chronic strain within the workplace and is common across nursing professions. Little has been published about burnout in organ transplant nurses. Objective-To report the prevalence of the 3 main components of burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) in organ transplant nurses and to examine factors that contribute to the development of burnout in transplant nurses. Design-Cross-sectional survey of transplant nurses (recruited via listservs) on professional and personal demographics, decisional authority, psychological job demands, supervisor and coworker support, frequency and comfort with difficult patient interactions, and burnout. Participants-369 transplant nurses. Results-About half reported high levels of emotional exhaustion, 15.7% reported high levels of depersonalization, and 51.8% reported low levels of personal accomplishment. Working more hours per week, lower decisional authority, greater psychological job demands, lower perceived supervisor support, and greater frequency and discomfort with difficult patient interactions were significant predictors of emotional exhaustion. Greater frequency and discomfort with difficult patient interactions were significant predictors of depersonalization. Younger age, lower decisional authority, and greater discomfort with difficult patient interactions were predictors of low personal accomplishment. Conclusions-The study provides strong evidence of the presence of burnout in transplant nurses and opportunities for focused and potentially very effective interventions aimed at reducing burnout. PMID:26308777

  17. Burnout in transplant nurses.

    PubMed

    Jesse, Michelle T; Abouljoud, Marwan S; Hogan, Kathy; Eshelman, Anne

    2015-09-01

    Context-Burnout is a response to chronic strain within the workplace and is common across nursing professions. Little has been published about burnout in organ transplant nurses. Objective-To report the prevalence of the 3 main components of burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) in organ transplant nurses and to examine factors that contribute to the development of burnout in transplant nurses. Design-Cross-sectional survey of transplant nurses (recruited via listservs) on professional and personal demographics, decisional authority, psychological job demands, supervisor and coworker support, frequency and comfort with difficult patient interactions, and burnout. Participants-369 transplant nurses. Results-About half reported high levels of emotional exhaustion, 15.7% reported high levels of depersonalization, and 51.8% reported low levels of personal accomplishment. Working more hours per week, lower decisional authority, greater psychological job demands, lower perceived supervisor support, and greater frequency and discomfort with difficult patient interactions were significant predictors of emotional exhaustion. Greater frequency and discomfort with difficult patient interactions were significant predictors of depersonalization. Younger age, lower decisional authority, and greater discomfort with difficult patient interactions were predictors of low personal accomplishment. Conclusions-The study provides strong evidence of the presence of burnout in transplant nurses and opportunities for focused and potentially very effective interventions aimed at reducing burnout.

  18. Emerging role of gasotransmitters in renal transplantation.

    PubMed

    Snijder, P M; van den Berg, E; Whiteman, M; Bakker, S J L; Leuvenink, H G D; van Goor, H

    2013-12-01

    Once patients with kidney disease progress to end-stage renal failure, transplantation is the preferred option of treatment resulting in improved quality of life and reduced mortality compared to dialysis. Although 1-year survival has improved considerably, graft and patient survival in the long term have not been concurrent, and therefore new tools to improve long-term graft and patient survival are warranted. Over the past decades, the gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have emerged as potent cytoprotective mediators in various diseases. All three gasotransmitters are endogenously produced messenger molecules that possess vasodilatory, anti-apoptotic, anti-inflammatory and anti-oxidant properties by influencing an array of intracellular signaling processes. Although many regulatory functions of gasotransmitters have overlapping actions, differences have also been reported. In addition, crosstalk between NO, CO and H2S results in synergistic regulatory effects. Endogenous and exogenous manipulation of gasotransmitter levels modulates several processes involved in renal transplantation. This review focuses on mechanisms of gas-mediated cytoprotection and complex interactions between gasotransmitters in renal transplantation.

  19. Acute renal failure and volume overload syndrome secondary to a femorofemoral arteriovenous fistula angioplasty in a kidney transplant recipient.

    PubMed

    Bertrand, Dominique; Desbuissons, Geoffroy; Pallet, Nicolas; Sartorius, Albane; Legendre, Christophe; Mamzer, Marie-France; Sberro Soussan, Rebecca

    2013-01-01

    Experimental and clinical studies analyzing the impact of AVF on cardiovascular and renal parameters, as well as outcomes, in kidney transplant recipients are lacking. On the other hand, it is not known whether AVF ligation after transplantation modifies hemodynamic parameters and kidney function. We report a case of a renal transplant recipient who developed an acute congestive heart failure accompanied by renal failure, which were triggered by femorofemoral AVF angioplasty. Prompt AVF ligation rapidly reversed clinical symptoms and normalized cardiac and renal functions. This paper illustrates the potential deleterious consequences of high-output AVF after kidney transplantation and raises considerations regarding the impact of the fistula on cardiac status and kidney function after kidney transplantation and, consequently, the management AVF after transplantation. PMID:23533921

  20. Nutrition and cardiovascular health.

    PubMed

    Berciano, Silvia; Ordovás, José M

    2014-09-01

    A multitude of studies have been published on the relationship between cardiovascular disease risk and a variety of nutrients, foods, and dietary patterns. Despite the well-accepted notion that diet has a significant influence on the development and prevention of cardiovascular disease, the foods considered healthy and harmful have varied over the years. This review aims to summarize the current scientific evidence on the cardioprotective effect of those foods and nutrients that have been considered healthy as well as those that have been deemed unhealthy at any given time in history. For this purpose, we reviewed the most recent literature using as keywords foods and nutrients (ie, meat, omega-3) and cardiovascular disease-related terms (ie, cardiovascular diseases, stroke). Emphasis has been placed on meta-analyses and Cochrane reviews. In general, there is a paucity of intervention studies with a high level of evidence supporting the benefits of healthy foods (ie, fruits and vegetables), whereas the evidence supporting the case against those foods considered less healthy (ie, saturated fat) seems to be weakened by most recent evidence. In summary, most of the evidence supporting the benefits and harms of specific foods and nutrients is based on observational epidemiological studies. The outcome of randomized clinical trials reveals a more confusing picture with most studies providing very small effects in one direction or another; the strongest evidence comes from dietary patterns. The current status of the relationship between diet and cardiovascular disease risk calls for more tailored recommendations based on genomic technologies.

  1. Cardiovascular disease mortality.

    PubMed

    Onwuanyi, Anekwe E; Clarke, Aubrey; Vanderbush, Eric

    2003-12-01

    Although mortality from cardiovascular diseases (CVDs) has been declining, it remains the leading cause of death among urban U.S. blacks. McCord and Freeman reported CVD as the major contributor to excess mortality in Central Harlem. However the disease-specific CVD mortality was not assessed. Thus, it was unclear what the distribution of specific CVDs was in Central Harlem and their contribution to excess mortality. We reviewed the vital statistics records of New York City (NYC) Department of Health for 1990 and identified all cases in which the cause of death was coded as cardiovascular (International Classification of Diseases-ICD, 9th Revision, codes 391, 393-398, 401-404, 410, 411, 414-417, 420-438 and 440-444). The total and disease-specific CVD mortality for NYC and Central Harlem were calculated using the appropriate 1990 census data as the denominator. Central Harlem residents aged between 25-64 years were at least twice as likely to die from cardiovascular causes, compared to NYC residents. Hypertension-related deaths, ICD codes 401 (essential hypertension), 402 (hypertensive heart disease), 403 (hypertensive renal disease), and 404 (hypertensive heart and renal disease), were the major cause of excess death for men and women in Central Harlem. These findings show the importance of hypertension as the main determinant of the excess cardiovascular mortality in urban blacks and suggest an increased risk of cardiovascular death in blacks residing in Central Harlem.

  2. Diabetes Drugs and Cardiovascular Safety

    PubMed Central

    2016-01-01

    Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration. PMID:27302713

  3. Caroli's disease and orthotopic liver transplantation.

    PubMed

    Habib, Shahid; Shakil, Obaid; Couto, Osvaldo F; Demetris, Anthony J; Fung, John J; Marcos, Amadeo; Chopra, Kapil

    2006-03-01

    Caroli's disease is a rare congenital hepatic disease, characterized by segmental dilatation of the biliary tree. Patients who have recurrent bouts of biliary infection, particularly those with complications related to portal hypertension, may require orthotopic liver transplantation (OLT). Few case reports have described the outcome of OLT in patients with Caroli's disease and to date there is no large series reported in the literature. We retrospectively analyzed the outcome of OLT in patients with Caroli's disease who underwent OLT between 1982 and 2002 at Starzl Transplantation Institute, University of Pittsburgh. Patients were identified and data was collected by computerized search of the electronic database system. All patients had confirmation of diagnosis by histopathology of explanted liver. A total of 33 patients with Caroli's disease were listed for liver transplantation, 3 of whom were excluded, as they were not transplanted. A total of 90% had signs of hepatic decompensation at the time of OLT. Median posttransplantation follow-up was 7.7 yr. Short-term graft and patient survival at 1 month was 83% and 86%, whereas overall long-term graft survival rates at 1, 5, and 10 yr were 73%, 62%, and 53%, respectively, and patient survival rates were 76%, 65%, and 56%, respectively. Long-term outcome in patients who survived the first year after transplantation was significantly better. Their survival rate at 5 and 10 yr was 90% and 78%. On univariable analysis, recipient age, donor male gender, coexistent congenital hepatic fibrosis, and re-OLT were associated with poor patient survival. Eight patients were retransplanted, 3 of whom had primary nonfunction. A total of 13 patients died; the most common cause of death being sepsis and cardiovascular complications. Patients who died of sepsis had cholangitis pre-OLT. In conclusion, OLT is a form of curative and life-saving therapy in patients with Caroli's disease, especially in those with decompensated liver

  4. Tea and Cardiovascular Disease

    PubMed Central

    Deka, Apranta; Vita, Joseph A.

    2011-01-01

    There is increasing evidence for a protective effect of tea consumption against cardiovascular disease. This review summarizes the available epidemiological data providing evidence for and against such an effect. We also review observational and intervention studies that investigated an effect of tea and tea extracts on cardiovascular risk factors, including blood pressure, serum lipids, diabetes mellitus, and obesity. Finally, we review potential mechanisms of benefit, including anti-inflammatory, anti-oxidant, and anti-proliferative effects, as well as favorable effects on endothelial function. Overall, the observational data suggest a benefit, but results are mixed and likely confounded by lifestyle and background dietary factors. The weight of evidence indicates favorable effects on risk factors and a number of plausible mechanisms have been elucidated in experimental and translational human studies. Despite the growing body evidence, it remains uncertain whether tea consumption should be recommended to the general population or to patients as a strategy to reduce cardiovascular risk. PMID:21477653

  5. Cardiovascular disease prevention.

    PubMed

    Van Camp, G

    2014-12-01

    Cardiovascular diseases remain the first killer in the Western countries. Equivalent contributions of prevention initiatives, pharmaceutical developments and technological improvements have led to an important success in the reduction of mortality related to cardiovascular diseases in some of the countries of the Western world. However, increase in life expectance, incomplete adherence to guidelines, difficulties in convincing governments and the population to support and adhere to prevention measures make that the burden of cardiovascular diseases is still extremely high. This review gives a restricted summary of the most important prevention guidelines supported by the European Society of Cardiology. It also illustrates the still very incomplete adherence to these guidelines in the different European countries as published in the EUROASPIRE surveys.

  6. Mitochondria and Cardiovascular Aging

    PubMed Central

    Dai, Dao-Fu; Ungvari, Zoltan

    2013-01-01

    Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (e.g. renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics and exercise training. PMID:22499901

  7. Transplant Outcomes (Bone Marrow and Cord Blood)

    MedlinePlus

    ... reports show patient survival and transplant data of bone marrow and umbilical cord blood transplants in the transplant ... Data by Center Report —View the number of bone marrow and cord blood transplants performed at a specific ...

  8. The global alliance for transplantation.

    PubMed

    Groth, C G; Chapman, J R

    2006-03-01

    In 2002, The Transplantation Society proposed the creation of a Global Alliance for Transplantation, with the purpose of reducing the existing disparity regarding transplantation activities across the globe. This alliance should include major international scientific societies, international governmental organizations, and pharmaceutical companies. Consultations with each of these parties have taken place during the past 18 months and three Strategic Programs have been initiated: (1) the collection of information on transplantation; (2) the expansion of education in transplantation; and (3) the development of professional guidelines for organ donation and transplantation. PMID:16549119

  9. Cardiovascular disease and dyslipidemia: beyond LDL.

    PubMed

    Pöss, Janine; Custodis, Florian; Werner, Christian; Weingärtner, Oliver; Böhm, Michael; Laufs, Ulrich

    2011-01-01

    Low-density lipoproteins (LDL) are atherogenic and represent a strong cardiovascular risk factor. Therefore, LDL-cholesterol (LDL-C) remains the primary target in lipid lowering therapy. However, since many cardiovascular events occur despite an optimal LDL-C, it is necessary to focus on the remaining cardiovascular risk. Treatment of low high-density lipoprotein-cholesterol (HDL-C) and high triglycerides (TG) are options to achieve cardiovascular risk reduction beyond LDL. HDL mediates reverse cholesterol transport and exerts several other athero-protective effects. Epidemiologic evidence has shown that low HDL-cholesterol (HDL-C) is a strong and independent cardiovascular risk marker. However, since the anti-atherogenic effects of HDL particles rather depend on their functionality rather than on their cholesterol content, an increase in HDL-C concentration does not always have to result in a clinical benefit. Besides established strategies to increase HDL-C, e.g. with fibrates and nicotinic acid, CETP (Cholesteryl ester transfer protein)-inhibition is a promising new therapeutic option. The failure of torcetrapib, the first CETP-inhibitor, seems to be attributed to "off-target" effects. Treatment with the newer CETP-inhibitors dalcetrapib and anacetrapib has been shown to be efficacious and safe - but their usefulness in clinical practice remains to be determined in ongoing clinical endpoint trials. TG concentrations have been shown to correlate with cardiovascular risk. However, interpretation of plasma TG concentrations remains difficult due to considerable intra-individual variability of plasma concentrations. Post-prandial triglyceride concentrations may be better predictors of cardiovascular risk than fasting TG. In patients with hypertriglyceridemia, achievement of the LDL-C goal remains the primary lipid target. The basis of therapy in patients with hypertriglyceridemia are life style modifications. In addition, non-HDL-C should be addressed. For selected

  10. Cardiovascular Disease and Menopause

    PubMed Central

    Dosi, Rupal; Bhatt, Nikita; Shah, Priyanki; Patell, Rushad

    2014-01-01

    Aim: The aim of the study was to study the abnormalities in the cardiovascular profile in postmenopausal Indian women and to compare the same with the cardiovascular profile of pre menopausal Indian women belonging to the same age group; taken as controls. The goal was to throw some light on the cardiovascular risk in postmenopausal women of the Indian population as this population is thought to be at higher risk than their western counterparts and significant studies of the same kind in this population have been few. Materials and Methods: A cross-sectional comparative study on 100 women who were either postmenopausal or premenopausal and were between the age group of 40 to 55 years was carried out over a period of ten months at our hospital. The variations in the cardiovascular profile between both groups were studied. All the women were subjected to a detailed history, thorough examination, investigations and imaging studies. Results: The evaluation revealed that Coronary Artery Disease (CAD), hypertension, abnormal Body Mass Index (BMI) and abnormal Waist Hip Ratio (WHR) were significantly higher in the postmenopausal group as compared to the premenopausal group. The post menopausal women had significantly higher prevalence of abnormal lipid profiles as compared to their premenopausal counterparts. The postmenopausal women with a normal lipid profile also had increased prevalence of CAD and SAHT, which emphasizes the non-lipid cardiovascular benefits of estrogen. Conclusion: Thus, we can conclude that cardiovascular disease was more common in postmenopausal women of age group 40-55 years as compared to those not yet achieved menopause in a population of western Indian women. And this risk was significantly associated with central obesity, an abnormal lipid profile and the postmenopausal state in itself. PMID:24701484

  11. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    PubMed Central

    Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft. PMID:27725836

  12. The Innate Immune System and Transplantation

    PubMed Central

    Farrar, Conrad A.; Kupiec-Weglinski, Jerzy W.; Sacks, Steven H.

    2013-01-01

    The sensitive and broadly reactive character of the innate immune system makes it liable to activation by stress factors other than infection. Thermal and metabolic stresses experienced during the transplantation procedure are sufficient to trigger the innate immune response and also augment adaptive immunity in the presence of foreign antigen on the donor organ. The resulting inflammatory and immune reactions combine to form a potent effector response that can lead to graft rejection. Here we examine the evidence that the complement and toll-like receptor systems are central to these pathways of injury and present a formidable barrier to transplantation. We review extensive information about the effector mechanisms that are mediated by these pathways, and bring together what is known about the damage-associated molecular patterns that initiate this sequence of events. Finally, we refer to two ongoing therapeutic trials that are evaluating the validity of these concepts in man. PMID:24086066

  13. Advancing cardiovascular tissue engineering

    PubMed Central

    Truskey, George A.

    2016-01-01

    Cardiovascular tissue engineering offers the promise of biologically based repair of injured and damaged blood vessels, valves, and cardiac tissue. Major advances in cardiovascular tissue engineering over the past few years involve improved methods to promote the establishment and differentiation of induced pluripotent stem cells (iPSCs), scaffolds from decellularized tissue that may produce more highly differentiated tissues and advance clinical translation, improved methods to promote vascularization, and novel in vitro microphysiological systems to model normal and diseased tissue function. iPSC technology holds great promise, but robust methods are needed to further promote differentiation. Differentiation can be further enhanced with chemical, electrical, or mechanical stimuli. PMID:27303643

  14. Clocks and cardiovascular function

    PubMed Central

    McLoughlin, Sarah C.; Haines, Philip; FitzGerald, Garret A.

    2016-01-01

    Circadian clocks in central and peripheral tissues enable the temporal synchronization and organization of molecular and physiological processes of rhythmic animals, allowing optimum functioning of cells and organisms at the most appropriate time of day. Disruption of circadian rhythms, from external or internal forces, leads to widespread biological disruption and is postulated to underlie many human conditions, such as the incidence and timing of cardiovascular disease. Here, we describe in vivo and in vitro methodology relevant to studying the role of circadian rhythms in cardiovascular function and dysfunction PMID:25707279

  15. Cardiovascular autonomic neuropathy

    PubMed Central

    McCarty, Niamh

    2016-01-01

    Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this disease, including weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which occurred 2 years after his type 1 diabetes diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic hypotension, which suggests sympathetic denervation. He did not have complete cardiovascular autonomic reflex testing, which would have been helpful, but improved with aggressive diabetes treatment and the increase of beta-blockade. It is important to identify these patients to understand their signs and symptoms and consider appropriate therapies. PMID:27034552

  16. Cardiovascular autonomic neuropathy.

    PubMed

    McCarty, Niamh; Silverman, Barry

    2016-04-01

    Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this disease, including weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which occurred 2 years after his type 1 diabetes diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic hypotension, which suggests sympathetic denervation. He did not have complete cardiovascular autonomic reflex testing, which would have been helpful, but improved with aggressive diabetes treatment and the increase of beta-blockade. It is important to identify these patients to understand their signs and symptoms and consider appropriate therapies. PMID:27034552

  17. Emerging role of neurotensin in regulation of the cardiovascular system.

    PubMed

    Osadchii, Oleg E

    2015-09-01

    There is increasing evidence in support of an important role played by neurotensin (NT), a tridecapeptide originally found in bovine hypothalamus, in regulation of cardiovascular system. Elevated systemic levels of NT may contribute to pathogenesis of acute circulatory disoders, and predict the risk for cardiovascular morbidity and mortality in population-based studies. Within cardiovascular system, NT-containing neural fibers are found in close contact with atrial and ventricular cardiac myocytes, cardiac conduction system, intracardiac ganglia, as well as coronary vessels in humans and various animal species. The density of NT-immunoreactive innervation is reduced in cardiac disease. NT produces a variety of cardiovascular actions including effects on heart rate, myocardial contractility, systemic blood pressure, coronary vascular tone, venous smooth muscle tone, and regional blood flow in gastrointestinal tract, cutaneous and adipose tissue. NT could trigger cardiovascular reflexes by stimulating primary visceral afferents synaptically connected with preganglionic sympathetic neurons at the spinal cord. Structural determinants of biological activity of NT reside primarily in the C-terminal portion of its molecule which is responsible for receptor activation. NT effects are mediated via activation of NT receptors, or produced indirectly via stimulation of release of various endogenous neuromodulators/neurotransmitters such as histamine, catecholamines and prostaglandins. Three subtypes of NT receptor (NTS1, NTS2 and NTS3) have been shown to be expressed in the myocardium. NTS1, a high-affinity NT binding site coupled to phospholipase C-inositoltrisphosphate transduction pathway, is thought to mediate NT-induced cardiovascular responses.

  18. Antidiabetic therapy in post kidney transplantation diabetes mellitus.

    PubMed

    Werzowa, Johannes; Säemann, Marcus; Haidinger, Michael; Krebs, Michael; Hecking, Manfred

    2015-07-01

    Post-transplantation diabetes mellitus (PTDM) is a common complication after kidney transplantation that affects up to 40% of kidney transplant recipients. By pathogenesis, PTDM is a diabetes form of its own, and may be characterised by a sudden, drug-induced deficiency in insulin secretion rather than worsening of insulin resistance over time. In the context of deteriorating allograft function leading to a re-occurrence of chronic kidney disease after transplantation, pharmacological interventions in PTDM patients deserve special attention. In the present review, we aim at presenting the current evidence regarding efficacy and safety of the modern antidiabetic armamentarium. Specifically, we focus on incretin-based therapies and insulin treatment, besides metformin and glitazones, and discuss their respective advantages and pitfalls. Although recent pilot trials are available in both prediabetes and PTDM, further studies are warranted to elucidate the ideal timing of various antidiabetics as well as its long-term impact on safety, glucose metabolism and cardiovascular outcomes in kidney transplant recipients.

  19. Liver transplantation in Germany.

    PubMed

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD.

  20. Liver transplantation in Germany.

    PubMed

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD. PMID:27082951

  1. Liver transplantation in Spain.

    PubMed

    de la Rosa, Gloria; Fondevila, Constantino; Navasa, Miquel

    2016-09-01

    Liver transplantation (LT) activity started in Spain in 1984 and has exceeded 23,700 interventions, with more than 1000 transplants performed yearly. Every hospital needs official authorization to perform a LT, which implies the obligation to register all patients on the national waiting list. The Spanish National Transplant Organization (ONT) provides essential support for organ procurement, allocation, and management of the waiting list at a national level. Liver allocation is center-oriented as all available organs are referred to the ONT for the whole country. The allocation rules for LT are made according to disease severity after consensus among professionals from every transplant center and ratified by representatives of the regional health authorities. Authorization and location/distribution of transplant centers are regulated by the country (Spain) and by the different regions according to the Real Decreto 1723/2012. For a total population of 47,850,795 inhabitants, there are 24 centers for LT for adults (1 team/2 million people) and 5 for LT for children (1 team/9.5 million people). Nonbiliary cirrhosis, particularly alcohol- and hepatitis C virus-related cirrhosis (60%), and tumors, mainly hepatocellular carcinoma (19%), are the most common indications for LT in Spain. Unusual causes of LT include metabolic diseases like Wilson's disease, familial amyloid polyneuropathy and hyperoxaluria type I, polycystic kidney and liver disease, and some tumors (epithelioid hemangioendothelioma and neuroendocrine tumors). Important efforts are now being undertaken to improve the quality and transplantability of extended criteria livers, in particular those arising from DCD, which represent the greatest opportunity to expand the donor pool. These efforts have to be addressed to adapt the organ preservation procedures, be it through the application of regional perfusion in situ or the use of machine perfusion preservation ex situ. Liver Transplantation 22 1259-1264 2016

  2. Microrefined microfollicular hair transplant: a new modification in hair transplant.

    PubMed

    Gupta, Amit

    2014-09-01

    : Hair transplant is the most common cosmetic surgery procedure in men; at our center, we perform nearly 40 transplants a month, with nearly 450 procedures in a year. Current techniques of hair transplant are well established and several authors have had remarkable results using the current techniques of microfollicular hair transplant. Orentreich described hair transplant, Shiell has reviewed current techniques in his paper, whereas Rose reviews the latest innovations in hair transplant including Neograft and robotic procedures. We present our modifications to the process based on our experience of more than 1000 cases in the last 3 years.Microrefined microfollicular hair transplant is a procedure with innovations at each step of the standard microfollicular hair transplant procedure to improve results.The steps of the procedure are as follows: PMID:24374401

  3. De Novo Glomerular Diseases after Renal Transplantation

    PubMed Central

    Moroni, Gabriella; Glassock, Richard J.

    2014-01-01

    Glomerular diseases developing in the kidney allograft are more often recurrences of the original disease affecting the native kidneys. However, in an undefined number of cases de novo, glomerular diseases unrelated to the original disease in the native kidneys can develop in the transplanted kidney. The clinical presentation and histologic features of de novo diseases are often similar to those features observed in patients with primary or secondary GN in the native kidneys. However, in transplanted kidneys, the glomerular, vascular, and tubulointerstitial changes are often intertwined with structural abnormalities already present at the time of transplant or caused by antibody- or cell-mediated allograft rejection, immunosuppressive drugs, or superimposed infection (most often of a viral nature). The pathophysiology of de novo glomerular diseases is quite variable. In rare cases of de novo minimal change disease, circulating factors increasing the glomerular permeability likely participate. Maladaptive hemodynamic changes and tissue fibrosis caused by calcineurin inhibitors or other factors may be involved in the pathogenesis of de novo FSGS. The exposure of cryptic podocyte antigens may favor the development of de novo membranous nephropathy. Many cases of de novo membranoproliferative GN are related to hepatitis C virus infection. Patients with Alport syndrome lacking antigenic epitopes in their glomerular basement membrane may develop antibodies against these glomerular basement membrane antigens expressed in the transplanted kidney. Infection may cause acute GN to have a heterogeneous clinical presentation and outcome. De novo pauci-immune GN in renal transplant is rare. Preexisting or acquired intolerance to glucose may, in the long term, cause diabetic nephropathy. The prognosis of de novo diseases depends on the type of GN, the severity of lesions caused by the alloimmune response, or the efficacy of immunosuppressive therapy. In most cases, the management

  4. Anaesthetic Management of Renal Transplant Surgery in Patients of Dilated Cardiomyopathy with Ejection Fraction Less Than 40%

    PubMed Central

    Tiwari, Tanmay; Sahu, Sandeep; Chandra, Abhilash; Dhiraaj, Sanjay

    2014-01-01

    Cardiovascular disease (CVD) is an important comorbidity of chronic kidney disease, and reducing cardiovascular events in this population is an important goal for the clinicians who care for chronic kidney disease patients. The high risk for CVD in transplant recipients is in part explained by the high prevalence of conventional CVD risk factors (e.g., diabetes, hypertension, and dyslipidemia) in this patient population. Current transplant success allows recipients with previous contraindications to transplant to have access to this procedure with more frequency and safety. Herein we provide a series of eight patients with dilated cardiomyopathy with poor ejection fraction posted for live donor renal transplantation which was successfully performed under regional anesthesia with sedation. PMID:25210514

  5. [Renal transplantation: ethical issues].

    PubMed

    Mamzer-Bruneel, Marie-France; Laforêt, Emmanuelle Grand; Kreis, Henri; Thervet, Éric; Martinez, Frank; Snanoudj, Renaud; Hervé, Christian; Legendre, Christophe

    2012-12-01

    One of the most significant advances in medicine during the last 50 years is the development of organ transplantation. In the context of chronic kidney diseases, renal transplantation offers patients a better clinical outcome than other treatment options. However, the benefits of organ transplantation have not been maximized due to an inadequate supply of organs for transplantation. Despite the establishment of elaborate legal rules for organs procurement, both on deceased and living donors in numerous countries, ethical concerns remain. Most of them are consequences of the strategies implemented or proposed to address the so-called organ shortage. The involvement of society in these complex problems is crucial as numerous questions emerge: could actual state of organ procurement change? Is it possible and/or realistic to increase the number of organs, with respects to living donors or deceased persons? Is the shortage an indicator to limit the use of kidney transplantation? How do we maintain efficiency and justice, in this context. PMID:23168353

  6. Ultrasound biomicroscopy in mouse cardiovascular development

    NASA Astrophysics Data System (ADS)

    Turnbull, Daniel H.

    2001-05-01

    The mouse is the preferred animal model for studying mammalian cardiovascular development and many human congenital heart diseases. Ultrasound biomicroscopy (UBM), utilizing high-frequency (40-50-MHz) ultrasound, is uniquely capable of providing in vivo, real-time microimaging and Doppler blood velocity measurements in mouse embryos and neonates. UBM analyses of normal and abnormal mouse cardiovascular function will be described to illustrate the power of this microimaging approach. In particular, real-time UBM images have been used to analyze dimensional changes in the mouse heart from embryonic to neonatal stages. UBM-Doppler has been used recently to examine the precise timing of onset of a functional circulation in early-stage mouse embryos, from the first detectable cardiac contractions. In other experiments, blood velocity waveforms have been analyzed to characterize the functional phenotype of mutant mouse embryos having defects in cardiac valve formation. Finally, UBM has been developed for real-time, in utero image-guided injection of mouse embryos, enabling cell transplantation and genetic gain-of-function experiments with transfected cells and retroviruses. In summary, UBM provides a unique and powerful approach for in vivo analysis and image-guided manipulation in normal and genetically engineered mice, over a wide range of embryonic to neonatal developmental stages.

  7. Epigenetics and cardiovascular disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only...

  8. Cardiovascular effects of gliptins.

    PubMed

    Scheen, André J

    2013-02-01

    Dipeptidyl peptidase 4 (DPP-4) inhibitors (commonly referred to as gliptins) are a novel class of oral antihyperglycaemic agents with demonstrated efficacy in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data and mechanistic studies have indicated a possible beneficial action on blood vessels and the heart, via both glucagon-like peptide 1 (GLP-1)-dependent and GLP-1-independent effects. DPP-4 inhibition increases the concentration of many peptides with potential vasoactive and cardioprotective effects. Clinically, DPP-4 inhibitors improve several risk factors in patients with T2DM. They improve blood glucose control (mainly by reducing postprandial glycaemia), are weight neutral (or even induce modest weight loss), lower blood pressure, improve postprandial lipaemia, reduce inflammatory markers, diminish oxidative stress, and improve endothelial function. Some positive effects on the heart have also been described in patients with ischaemic heart disease or congestive heart failure, although their clinical relevance requires further investigation. Post-hoc analyses of phase II-III, controlled trials suggest a possible cardioprotective effect with a trend for a lower incidence of major cardiovascular events with gliptins than with placebo or active agents. However, the actual relationship between DPP-4 inhibition and cardiovascular outcomes remains to be proven. Major prospective clinical trials with predefined cardiovascular outcomes and involving various DPP-4 inhibitors are now underway in patients with T2DM and a high-risk cardiovascular profile.

  9. Cardiovascular Effects Of Weightlessness

    NASA Technical Reports Server (NTRS)

    Sandler, Harold

    1992-01-01

    NASA technical memorandum presents study of effects of weightlessness and simulations upon cardiovascular systems of humans and animals. Reviews research up to year 1987 in United States and Soviet space programs on such topics as physiological changes induced by weightlessness in outer space and by subsequent return to Earth gravity and also reviews deconditioning effects of prolonged bed rest on ground.

  10. Cardiovascular Health, Part 2

    PubMed Central

    Baman, Timir S.; Gupta, Sanjaya; Day, Sharlene M.

    2010-01-01

    Context: An athlete’s health may be endangered if he or she continues to compete after diagnosis of certain cardiovascular conditions. The most worrisome risk is sudden cardiac death; the annual rate in US athletes is 1 in 50 000 to 200 000. Evidence Acquisition: Part 2 of this review highlights the current guidelines and controversies surrounding compatibility of participation with a variety of cardiac conditions in competitive and recreational athletics. Data sources were limited to peer-reviewed publications from 1984 to the April 2009. Results: The guidelines published by the American College of Cardiology and the European Society of Cardiology provide a framework for safe competitive and recreational sports participation in athletes with a broad spectrum of inherited and acquired cardiovascular disorders. These guidelines are necessarily conservative because it is not currently possible to individualize risk prediction. Few data are available in many areas, particularly in the noncompetitive arena or in older athletes. Conclusions: Published national guidelines are currently the foundation governing return-to-play decisions in athletes with cardiovascular conditions. Further studies are needed to refine risk stratification algorithms to allow athletes with cardiovascular conditions to reap the health benefits of regular exercise and sports participation without undue risk. PMID:23015920

  11. Neuropeptides in cardiovascular control.

    PubMed

    Ganong, W F

    1984-12-01

    Neuropeptides can affect cardiovascular function in various ways. They can serve as cotransmitters in the autonomic nervous system; for example, vasoactive intestinal peptide (VIP) is released with acetylcholine and neuropeptide Y with norepinephrine from postganglionic neurons. Substance P and, presumably, other peptides can can affect cardiovascular function when released near blood vessels by antidromically conducted impulses in branches of stimulated sensory neurons. In the central nervous system, many different neuropeptides appear to function as transmitters or contransmittes in the neural pathways that regulate the cardiovascular system. In addition neuropeptides such as vasopressin and angiotensin II also circulate as hormones that are involved in cardiovascular control. Large doses of exogenous vasopressin are required to increase blood pressure in normal animals because the increase in total peripheral resistance produced by the hormones is accompanied by a decrease in cardiac output. However, studies with synthetic peptides that selectively antagonize the vasopressor action of vasopressin indicate that circulating vasopressin is important in maintaining blood pressure when animals are hypovolemic due to dehydration, haemorrhage or adrenocortical insufficiency. VIP dilates blood vessels and stimulates renin secretion by a direct action on the juxtaglomerular cells. Renin secretion is stimulated when the concentration of VIP in plasma exceeds 75 pmol/litre, and higher values are seen in a number of conditions. Neostigmine, a drug which increases the secretion of endogenous VIP, also increases renin secretion, and this increase is not blocked by renal denervation or propranolol. Thus, VIP may be a physiologically significant renin stimulating hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Epidemiology of Cardiovascular Diseases.

    ERIC Educational Resources Information Center

    Jenkins, C. David

    1988-01-01

    Reviews epidemiological studies of cardiovascular diseases especially coronary heart disease (CHD), to document their major public health importance, changes in mortality during this century, and international comparisons of trends. Finds major risk factors for CHD are determined in large part by psychosocial and behavioral mechanisms. Asserts…

  13. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  14. Intraocular retinal transplantation: a review.

    PubMed

    Hammer, R M; Yinon, U

    1991-01-01

    This review covers intraocular transplantation of retinal tissue. This has importance both for theoretical understanding of retinal and neural development and for possible future clinical application. Transplantation sites have ranged from the anterior chamber through the retina to the subretinal space. Transplanted tissue has ranged from whole retina to specific retinal layers or specific types of retinal cells. Both within-species and inter-species transplants have been performed, and donor age has ranged from embryonic to adult. The ability of transplanted tissue to be accepted and to differentiate in host eyes has been studied. The conditions under which successful transplants are obtained, host-graft interactions, and transplantation methodologies have been explored. Morphological, and to a small extent, also functional characteristics of the transplants have been studied. PMID:1747393

  15. About the Operation: Liver Transplant

    MedlinePlus

    ... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Transplant There are two very different surgical approaches to liver transplantation: the orthotopic and the heterotopic approach, both ...

  16. Transgenerational epigenetics: the role of maternal effects in cardiovascular development.

    PubMed

    Ho, Dao H

    2014-07-01

    Transgenerational epigenetics, the study of non-genetic transfer of information from one generation to the next, has gained much attention in the past few decades due to the fact that, in many instances, epigenetic processes outweigh direct genetic processes in the manifestation of aberrant phenotypes across several generations. Maternal effects, or the influences of maternal environment, phenotype, and/or genotype on offsprings' phenotypes, independently of the offsprings' genotypes, are a subcategory of transgenerational epigenetics. Due to the intimate role of the mother during early development in animals, there is much interest in investigating the means by which maternal effects can shape the individual. Maternal effects are responsible for cellular organization, determination of the body axis, initiation and maturation of organ systems, and physiological performance of a wide variety of species and biological systems. The cardiovascular system is the first to become functional and can significantly influence the development of other organ systems. Thus, it is important to elucidate the role of maternal effects in cardiovascular development, and to understand its impact on adult cardiovascular health. Topics to be addressed include: (1) how and when do maternal effects change the developmental trajectory of the cardiovascular system to permanently alter the adult's cardiovascular phenotype, (2) what molecular mechanisms have been associated with maternally induced cardiovascular phenotypes, and (3) what are the evolutionary implications of maternally mediated changes in cardiovascular phenotype?

  17. Arterial hypertension and cardiovascular risk in HIV-infected patients.

    PubMed

    Calò, Lorenzo A; Caielli, Paola; Maiolino, Giuseppe; Rossi, Gianpaolo

    2013-08-01

    The dramatic change of the natural history of HIV-infected patients by highly active antiretroviral therapy (HAART) has exposed these patients to cardiovascular risk, including cardiovascular disease and hypertension. In HIV-infected patients, the development of arterial hypertension, at least in the medium-long term is an established feature, although recognized predictors of its development have not been clearly identified. In addition, conflicting data regarding the influence of antiretroviral therapy (ART) are reported. The presence of a proinflammatory state and oxidative stress-mediated endothelial dysfunction seem, however, to play a pathophysiologic role. In this review, we examine and provide a comprehensive, literature based, consideration of the pathophysiologic aspects of hypertension in these patients. HIV-infected patients, independently of the presence of hypertension, remain at very high cardiovascular risk due to the presence of the same cardiovascular risk factors recognized for the general population with, in addition, the indirect influence of the ART, essentially via its effect on lipid metabolism. This review based on the evidence from the literature, concludes that the management of HIV-infected patients in terms of cardiovascular prevention emerges as a priority. The consideration of cardiovascular risk in these patients should receive the same emphasis given for the general population at high cardiovascular risk, including adequate blood pressure control according to international guidelines.

  18. In vivo prevention of transplant arteriosclerosis by ex vivo-expanded human regulatory T cells.

    PubMed

    Nadig, Satish N; Wieckiewicz, Joanna; Wu, Douglas C; Warnecke, Gregor; Zhang, Wei; Luo, Shiqiao; Schiopu, Alexandru; Taggart, David P; Wood, Kathryn J

    2010-07-01

    Transplant arteriosclerosis is the hallmark of chronic allograft dysfunction (CAD) affecting transplanted organs in the long term. These fibroproliferative lesions lead to neointimal thickening of arteries in all transplanted allografts. Luminal narrowing then leads to graft ischemia and organ demise. To date, there are no known tolerance induction strategies that prevent transplant arteriosclerosis. Therefore, we designed this study to test the hypothesis that human regulatory T cells (T(reg) cells) expanded ex vivo can prevent transplant arteriosclerosis. Here we show the comparative capacity of T(reg) cells, sorted via two separate strategies, to prevent transplant arteriosclerosis in a clinically relevant chimeric humanized mouse system. We found that the in vivo development of transplant arteriosclerosis in human arteries was prevented by treatment of ex vivo-expanded human T(reg) cells. Additionally, we show that T(reg) cells sorted on the basis of low expression of CD127 provide a more potent therapy to conventional T(reg) cells. Our results demonstrate that human T(reg) cells can inhibit transplant arteriosclerosis by impairing effector function and graft infiltration. We anticipate our findings to serve as a foundation for the clinical development of therapeutics targeting transplant arteriosclerosis in both allograft transplantation and other immune-mediated causes of vasculopathy.

  19. [Preventing cardiovascular risk in miners].

    PubMed

    Lipatova, L V; Izmailova, O A

    2016-01-01

    The article presents results concerning usage of intravenous laser radiation of blood in miners with cardiovascular diseases. After cardiovascular state assessment, the miners at high cardiovascular risk were subjected to prophylactic procedures with traditional medical treatment added by intravenous laser therapy. Findings are anti-arrhythmic, antihypertensive, antiatherogenic and anti-aggregation effects of complex treatment with intravenous laser radiation of blood in miners at high cardiovascular risk and its subsequent decrease due to treatment. PMID:27265943

  20. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    PubMed Central

    Gitto, Stefano; Villa, Erica

    2016-01-01

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis. PMID:27049380

  1. Transplanted fetal striatum in Huntington's disease: Phenotypic development and lack of pathology

    PubMed Central

    Freeman, Thomas B.; Cicchetti, Francesca; Hauser, Robert A.; Deacon, Terrence W.; Li, Xiao-Jiang; Hersch, Steven M.; Nauert, G. Michael; Sanberg, Paul R.; Kordower, Jeffrey H.; Saporta, Samuel; Isacson, Ole

    2000-01-01

    Neural and stem cell transplantation is emerging as a potential treatment for neurodegenerative diseases. Transplantation of specific committed neuroblasts (fetal neurons) to the adult brain provides such scientific exploration of these new potential therapies. Huntington's disease (HD) is a fatal, incurable autosomal dominant (CAG repeat expansion of huntingtin protein) neurodegenerative disorder with primary neuronal pathology within the caudate–putamen (striatum). In a clinical trial of human fetal striatal tissue transplantation, one patient died 18 months after transplantation from cardiovascular disease, and postmortem histological analysis demonstrated surviving transplanted cells with typical morphology of the developing striatum. Selective markers of both striatal projection and interneurons such as dopamine and c-AMP-related phosphoprotein, calretinin, acetylcholinesterase, choline acetyltransferase, tyrosine hydroxylase, calbindin, enkephalin, and substance P showed positive transplant regions clearly innervated by host tyrosine hydroxylase fibers. There was no histological evidence of immune rejection including microglia and macrophages. Notably, neuronal protein aggregates of mutated huntingtin, which is typical HD neuropathology, were not found within the transplanted fetal tissue. Thus, although there is a genetically predetermined process causing neuronal death within the HD striatum, implanted fetal neural cells lacking the mutant HD gene may be able to replace damaged host neurons and reconstitute damaged neuronal connections. This study demonstrates that grafts derived from human fetal striatal tissue can survive, develop, and are unaffected by the disease process, at least for 18 months, after transplantation into a patient with HD. PMID:11106399

  2. Epigenetics and cardiovascular disease.

    PubMed

    Webster, Andrew L H; Yan, Matthew Shu-Ching; Marsden, Philip A

    2013-01-01

    A commonly-assumed paradigm holds that the primary genetic determinant of cardiovascular disease resides within the DNA sequence of our genes. This paradigm can be challenged. For example, how do sequence changes in the non-coding region of the genome influence phenotype? Why are all diseases not shared between identical twins? Part of the answer lies in the fact that the environment or exogenous stimuli clearly influence disease susceptibility, but it was unclear in the past how these effects were signalled to the static DNA code. Epigenetics is providing a newer perspective on these issues. Epigenetics refers to chromatin-based mechanisms important in the regulation of gene expression that do not involve changes to the DNA sequence per se. The field can be broadly categorized into three areas: DNA base modifications (including cytosine methylation and cytosine hydroxymethylation), post-translational modifications of histone proteins, and RNA-based mechanisms that operate in the nucleus. Cardiovascular disease pathways are now being approached from the epigenetic perspective, including those associated with atherosclerosis, angiogenesis, ischemia-reperfusion damage, and the cardiovascular response to hypoxia and shear stress, among many others. With increasing interest and expanding partnerships in the field, we can expect new insights to emerge from epigenetic perspectives of cardiovascular health. This paper reviews the principles governing epigenetic regulation, discusses their presently-understood importance in cardiovascular disease, and considers the growing significance we are likely to attribute to epigenetic contributions in the future, as they provide new mechanistic insights and a host of novel clinical applications. PMID:23261320

  3. Gut microbiota and allogeneic transplantation.

    PubMed

    Wang, Weilin; Xu, Shaoyan; Ren, Zhigang; Jiang, Jianwen; Zheng, Shusen

    2015-08-23

    The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gut microbiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gut microbiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the

  4. Donor selection in heart transplantation

    PubMed Central

    Emani, Sitaramesh; Sai-Sudhakar, Chittoor B.; Higgins, Robert S. D.; Whitson, Bryan A.

    2014-01-01

    There is increased scrutiny on the quality in health care with particular emphasis on institutional heart transplant survival outcomes. An important aspect of successful transplantation is appropriate donor selection. We review the current guidelines as well as areas of controversy in the selection of appropriate hearts as donor organs to ensure optimal outcomes. This decision is paramount to the success of a transplant program as well as recipient survival and graft function post-transplant. PMID:25132976

  5. Neurological complications of transplantation.

    PubMed

    Pustavoitau, Aliaksei; Bhardwaj, Anish; Stevens, Robert

    2011-01-01

    Recipients of solid organ or hematopoietic cell transplants are at risk of life-threatening neurological disorders including encephalopathy, seizures, infections and tumors of the central nervous system, stroke, central pontine myelinolysis, and neuromuscular disorders-often requiring admission to, or occurring in, the intensive care unit (ICU). Many of these complications are linked directly or indirectly to immunosuppressive therapy. However, neurological disorders may also result from graft versus host disease, or be an expression of the underlying disease which prompted transplantation, as well as injury induced during radiation, chemotherapy, surgery, and ICU stay. In rare cases, neuroinfectious pathogens may be transmitted with the transplanted tissue or organ. Diagnosis may be a challenge because clinical symptoms and findings on neuroimaging lack specificity, and a biological specimen or tissue diagnosis is often needed for definitive diagnosis. Management is centered on preventing further neurological injury, etiology-targeted therapy, and balancing the benefits and toxicities of specific immunosuppressive agents. PMID:21764765

  6. Liver transplantation: current concepts.

    PubMed Central

    Wall, W J

    1988-01-01

    In this decade liver transplantation has been established as the preferred treatment for children and adults with irreversible end-stage liver disease. Biliary atresia in children and nonalcoholic cirrhosis in adults are the most common indications for the procedure. Transplantation currently plays only a minor role in the treatment of hepatic malignant disease. Blood group compatibility between donor and recipient is preferred, but histocompatibility matching (tissue typing) currently has no significant role in the selection of recipients. Approximately 70% of recipients survive for 1 year, and these patients have an excellent prospect of long-term survival. The emerging evidence indicates that the quality of life and rehabilitation of most liver recipients are good. The current success of liver transplantation can be attributed to critical selection of recipients, modern anesthetic and surgical techniques, improved perioperative care, accurate diagnosis of rejection and superior immunosuppression with cyclosporine. PMID:3289710

  7. Pediatric liver transplantation

    PubMed Central

    Spada, Marco; Riva, Silvia; Maggiore, Giuseppe; Cintorino, Davide; Gridelli, Bruno

    2009-01-01

    In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation. PMID:19222089

  8. History of Clinical Transplantation

    PubMed Central

    Starzl, Thomas E.

    2010-01-01

    The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations in surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipients had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts. PMID:10833242

  9. THEMES OF LIVER TRANSPLANTATION

    PubMed Central

    Starzl, Thomas E.; Fung, John J.

    2010-01-01

    Liver transplantation was the product of 5 interlocking themes. These began in 1958-59 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g. familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and ALG. With this regimen, the world’s longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979) which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as

  10. Immunosuppressive Therapy in Transplantation.

    PubMed

    Allison, Terri L

    2016-03-01

    This article discusses immunosuppressive medications used in organ and hematopoietic stem cell transplantation. Induction, maintenance, and rescue therapy are administered throughout different periods during and after transplantation to modulate the immune system response in the recipient to prevent or treat rejection or graft-versus-host disease. Indications, dosing strategies, required monitoring, complications, adverse events, and concomitant drug interactions associated with immunosuppressive medications are presented. Classes of medications discussed include polyclonal and monoclonal antibodies, calcineurin inhibitors, antiproliferative agents, mammalian target of rapamycin inhibitors, and corticosteroids. Medications having significant interactions with immunosuppression are also examined.

  11. Xenogeneic lung transplantation models

    PubMed Central

    Burdorf, Lars; Azimzadeh, Agnes M.; Pierson, Richard N.

    2014-01-01

    Summary Study of lung xenografts has proven useful to understand the remaining barriers to successful transplantation of other organ xenografts. In this chapter, the history and current status of lung xenotransplantation will be briefly reviewed and two different experimental models, the ex vivo porcine-to-human lung perfusion and the in vivo xenogeneic lung transplantation, will be presented. We will focus on the technical details of these lung xenograft models in sufficient detail, list the needed materials and mention analysis techniques to allow others to adopt them with minimal learning curve. PMID:22565996

  12. Obesity and liver transplantation

    PubMed Central

    Ayloo, Subhashini; Armstrong, John; Hurton, Scott; Molinari, Michele

    2015-01-01

    The percentage of overweight and obese patients (OPs) waiting for a liver transplant continues to increase. Despite the significant advances occurred in bariatric medicine, obesity is still considered a relative contraindication to liver transplantation (LT). The main aim of this review is to appraise the literature on the outcomes of OPs undergoing LT, treatments that might reduce their weight before, during or after surgery, and discuss some of the controversies and limitations of the current knowledge with the intent of highlighting areas where future research is needed. PMID:26421262

  13. Childhood obesity and cardiovascular disease

    PubMed Central

    Bridger, Tracey

    2009-01-01

    Childhood obesity has reached epidemic proportions. Many of these children have risk factors for later disease, including cardiovascular disease. For optimal cardiovascular health, health care professionals must be able to identify children and youth at risk and provide appropriate support as needed. The present article reviews the current medical literature on obesity and cardiovascular disease risk factors in the paediatric population, the long-term cardiovascular consequences of childhood obesity and the importance of early life. Recommendations promoting optimal cardiovascular health in all children and youth are discussed. PMID:20190900

  14. The implication of protein malnutrition on cardiovascular control systems in rats

    PubMed Central

    Silva, Fernanda C.; de Menezes, Rodrigo C.; Chianca, Deoclécio A.

    2015-01-01

    The malnutrition in early life is associated with metabolic changes and cardiovascular impairment in adulthood. Deficient protein intake-mediated hypertension has been observed in clinical and experimental studies. In rats, protein malnutrition also increases the blood pressure and enhances heart rate and sympathetic activity. In this review, we discuss the effects of post-weaning protein malnutrition on the resting mean arterial pressure and heart rate and their variabilities, cardiovascular reflexes sensitivity, cardiac autonomic balance, sympathetic and renin-angiotensin activities and neural plasticity during adult life. These insights reveal an interesting prospect on the autonomic modulation underlying the cardiovascular imbalance and provide relevant information on preventing cardiovascular diseases. PMID:26388783

  15. Changing Role of Heart Transplantation.

    PubMed

    Kittleson, Michelle M

    2016-07-01

    Heart transplantation has become standard of care for end-stage heart failure. Challenges include the limited supply of donor organs and the increased complexity of heart transplant candidates who are at higher risk for poor outcomes. Recent advances may address these challenges, including proposed changes in heart transplant allocation policy, a better understanding of the definition and management of primary graft dysfunction, and advances in the management of sensitized heart transplant candidates. Developments in these areas may result in more equitable distribution and expansion of the donor pool and improved quality of life and survival for heart transplant recipients. PMID:27371517

  16. [Running through the liver transplantation].

    PubMed

    Grecu, F

    2003-01-01

    An overview of the organization, timing and developing of the liver transplantation is difficult to be made in terms of multiple sequences and a great variety of activities during the developing of such activity. A well-trained transplant team must carry out the potential donor, the liver grafts manipulation and the graft receptor, in the condition of a competitive medical system. A summary presentation, showing the essentials of the proceedings in liver transplantation could be assimilated as a guide of multidisciplinary sequences that leads to the completion of the liver grafting. The common feature of all that means the liver transplantation and generally in organ transplantation is the performance and exactingness.

  17. The importance of non-HLA antibodies in transplantation.

    PubMed

    Zhang, Qiuheng; Reed, Elaine F

    2016-08-01

    The development of post-transplantation antibodies against non-HLA autoantigens is associated with rejection and decreased long-term graft survival. Although our knowledge of non-HLA antibodies is incomplete, compelling experimental and clinical findings demonstrate that antibodies directed against autoantigens such as angiotensin type 1 receptor, perlecan and collagen, contribute to the process of antibody-mediated acute and chronic rejection. The mechanisms that underlie the production of autoantibodies in the setting of organ transplantation is an important area of ongoing investigation. Ischaemia-reperfusion injury, surgical trauma and/or alloimmune responses can result in the release of organ-derived autoantigens (such as soluble antigens, extracellular vesicles or apoptotic bodies) that are presented to B cells in the context of the transplant recipient's antigen presenting cells and stimulate autoantibody production. Type 17 T helper cells orchestrate autoantibody production by supporting the proliferation and maturation of autoreactive B cells within ectopic tertiary lymphoid tissue. Conversely, autoantibody-mediated graft damage can trigger alloimmunity and the development of donor-specific HLA antibodies that can act in synergy to promote allograft rejection. Identification of the immunologic phenotypes of transplant recipients at risk of non-HLA antibody-mediated rejection, and the development of targeted therapies to treat such rejection, are sorely needed to improve both graft and patient survival. PMID:27345243

  18. Slow breathing and cardiovascular disease.

    PubMed

    Chaddha, Ashish

    2015-01-01

    Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine. PMID:26170595

  19. Slow breathing and cardiovascular disease

    PubMed Central

    Chaddha, Ashish

    2015-01-01

    Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine. PMID:26170595

  20. Cardiovascular Health Disparities

    PubMed Central

    Davis, Andrew M.; Vinci, Lisa M.; Okwuosa, Tochi M.; Chase, Ayana R.; Huang, Elbert S.

    2008-01-01

    Racial and ethnic disparities in cardiovascular health care are well documented. Promising approaches to disparity reduction are increasingly described in literature published since 1995, but reports are fragmented by risk, condition, population, and setting. The authors conducted a systematic review of clinically oriented studies in communities of color that addressed hypertension, hyperlipidemia, physical inactivity, tobacco, and two major cardiovascular conditions, coronary artery disease and heart failure. Virtually no literature specifically addressed disparity reduction. The greatest focus has been African American populations, with relatively little work in Hispanic, Asian, and Native American populations. The authors found 62 interventions, 27 addressing hypertension, 9 lipids, 18 tobacco use, 8 physical inactivity, and 7 heart failure. Only 1 study specifically addressed postmyocardial infarction care. Data supporting the value of registries, multidisciplinary teams, and community outreach were found across several conditions. Interventions addressing care transitions, using telephonic outreach, and promoting medication access and adherence merit further exploration. PMID:17881625

  1. Cardiovascular instrumentation for spaceflight

    NASA Technical Reports Server (NTRS)

    Schappell, R. T.; Polhemus, J. T.; Ganiaris, N. J.

    1976-01-01

    The observation mechanisms dealing with pressure, flow, morphology, temperature, etc. are discussed. The approach taken in the performance of this study was to (1) review ground and space-flight data on cardiovascular function, including earlier related ground-based and space-flight animal studies, Mercury, Gemini, Apollo, Skylab, and recent bed-rest studies, (2) review cardiovascular measurement parameters required to assess individual performance and physiological alternations during space flight, (3) perform an instrumentation survey including a literature search as well as personal contact with the applicable investigators, (4) assess instrumentation applicability with respect to the established criteria, and (5) recommend future research and development activity. It is concluded that, for the most part, the required instrumentation technology is available but that mission-peculiar criteria will require modifications to adapt the applicable instrumentation to a space-flight configuration.

  2. HRT and cardiovascular disease.

    PubMed

    Stevenson, John C

    2009-02-01

    Hormone replacement therapy (HRT) has profound effects on the cardiovascular system, with plausible biological mechanisms explaining both the benefits and harm. Benefits may result from oestrogen action on metabolic risk factors, such as lipids, glucose and insulin metabolism, as well as direct arterial effects, reducing atherogenesis. Harm may arise from inappropriately high starting doses causing transient increases in coagulation activation and adverse vascular remodelling. Observational studies of HRT suggest that there is a beneficial effect on the incidence of coronary heart disease (CHD). Any benefit of HRT seen in randomized clinical trials appears to be confined to those women within several years of their menopause, and it is clear from the randomized trials that age at initiation is a crucially important consideration. Women initiating HRT within 10 years of menopause onset may achieve cardiovascular benefit, particularly in terms of primary CHD prevention, whilst avoiding risks of stroke and venous thrombo-embolism.

  3. Cardiovascular adaptation to spaceflight

    NASA Technical Reports Server (NTRS)

    Hargens, A. R.; Watenpaugh, D. E.

    1996-01-01

    This article reviews recent flight and ground-based studies of cardiovascular adaptation to spaceflight. Prominent features of microgravity exposure include loss of gravitational pressures, relatively low venous pressures, headward fluid shifts, plasma volume loss, and postflight orthostatic intolerance and reduced exercise capacity. Many of these short-term responses to microgravity extend themselves during long-duration microgravity exposure and may be explained by altered pressures (blood and tissue) and fluid balance in local tissues nourished by the cardiovascular system. In this regard, it is particularly noteworthy that tissues of the lower body (e.g., foot) are well adapted to local hypertension on Earth, whereas tissues of the upper body (e.g., head) are not as well adapted to increase in local blood pressure. For these and other reasons, countermeasures for long-duration flight should include reestablishment of higher, Earth-like blood pressures in the lower body.

  4. Cardiovascular adaptation to spaceflight

    NASA Technical Reports Server (NTRS)

    Charles, John B.; Lathers, Claire M.

    1991-01-01

    Data are presented on the rate of adaptation of the human cardiovascular system to conditions of spaceflight, with particular attention given to data obtained during spaceflight in the U.S. Space Shuttle Program. It is pointed out that many of the cardiovascular changes that occurred during spaceflights that lasted from 2 to 11 days can be traced directly to changes in the body fluid volume. The beneficial effects of a fluid loading countermeasure (oral rehydration) and of the supine body position on the heart rate during the spaceflight are demonstrated. It is noted that, after hours or a few days of spaceflight, a state of adaptation is reached, in which the subject is well adapted and appropriately hydrated for the weightless environment. However, the return to the normal gravity of the earth leaves the individual especially sensitive to orthostatic stress.

  5. Cardiovascular responses to spaceflight

    NASA Technical Reports Server (NTRS)

    Nicogossian, A.; Pool, S. L.; Rambaut, P. C.

    1983-01-01

    The cardiovascular system's adaptive changes during and after spaceflight are discussed. Cephalic fluid shifts are demonstrated by photographs along with calf girth and leg volume changes. Inflight measurements show an increase in average resting heart rate and systolic blood pressure, and a sympathetic-parasympathetic neural imbalance. Postflight findings include a small but reversible decrease in the left ventricular muscle mass. Since 1980, NASA's research has emphasized cardiovascular deconditioning and countermeasures: hemodynamic changes, endocrine and neurohumoral aspects, etiologic factors, and lower body negative pressure devices. Though human beings acclimate to the space environment, questions concerning the immediate and long-term aspects of spaceflight need to be answered for adequate planning of extended space missions.

  6. Lycopene and cardiovascular disease.

    PubMed

    Arab, L; Steck, S

    2000-06-01

    Considerable evidence suggests that lycopene, a carotenoid without provitamin A activity found in high concentrations in a small set of plant foods, has significant antioxidant potential in vitro and may play a role in preventing prostate cancer and cardiovascular disease in humans. Tomato products, including ketchup, tomato juice, and pizza sauce, are the richest sources of lycopene in the US diet, accounting for >80% of the total lycopene intake of Americans. Unlike other carotenoids, lycopene is not consistently lower among smokers than among nonsmokers, suggesting that any possible preventive activity is not as an antioxidant. Instead, lycopene may have a cholesterol synthesis-inhibiting effect and may enhance LDL degradation. Available evidence suggests that intimal wall thickness and risk of myocardial infarction are reduced in persons with higher adipose tissue concentrations of lycopene. The question of whether lycopene helps to prevent cardiovascular disease can only be answered by a trial specifically evaluating its effectiveness in this area. PMID:10837319

  7. Stem Cell Transplantation for Pulpal Regeneration: A Systematic Review.

    PubMed

    Fawzy El-Sayed, Karim M; Jakusz, Kimberley; Jochens, Arne; Dörfer, Christof; Schwendicke, Falk

    2015-10-01

    For treating pulpal pathological conditions, pulpal regeneration through transplanted stem/progenitor cells might be an alternative to conventional root canal treatment. A number of animal studies demonstrated beneficial effects of stem/progenitor cell transplantation for pulp-dentin complex regeneration, that is, pulpal tissue, neural, vascular, and dentinal regeneration. We systematically reviewed animal studies investigating stem/progenitor cell-mediated pulp-dentin complex regeneration. Studies quantitatively comparing pulp-dentin complex regeneration after transplantation of stem/progenitor cells versus no stem/progenitor cell transplantation controls in intraoral in vivo teeth animal models were analyzed. The following outcomes were investigated: regenerated pulp area per root canal total area, capillaries per total surface, regenerated dentinal area per total defect area, and nerves per total surface. PubMed and EMBASE were screened for studies published until July 2014. Cross-referencing and hand searching were used to identify further articles. Standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects meta-analysis. To assess possible bias, SYRCLE's risk of bias tool for animal studies was used. From 1364 screened articles, five studies (representing 64 animals) were included in the quantitative analysis. Risk of bias of all studies was high. Stem/progenitor cell-transplanted pulps showed significantly larger regenerated pulp area per root canal total area (SMD [95% CI]: 2.28 [0.35-4.21]) and regenerated dentin area per root canal total area (SMD: 6.91 [5.39-8.43]) compared with no stem/progenitor cell transplantation controls. Only one study reported on capillaries per or nerves per total surface and found both significantly increased in stem/progenitor cell-transplanted pulps compared with controls. Stem/progenitor cell transplantation seems to enhance pulp-dentin complex regeneration in animal models

  8. Stem Cell Transplantation for Pulpal Regeneration: A Systematic Review

    PubMed Central

    Jakusz, Kimberley; Jochens, Arne; Dörfer, Christof; Schwendicke, Falk

    2015-01-01

    For treating pulpal pathological conditions, pulpal regeneration through transplanted stem/progenitor cells might be an alternative to conventional root canal treatment. A number of animal studies demonstrated beneficial effects of stem/progenitor cell transplantation for pulp–dentin complex regeneration, that is, pulpal tissue, neural, vascular, and dentinal regeneration. We systematically reviewed animal studies investigating stem/progenitor cell-mediated pulp–dentin complex regeneration. Studies quantitatively comparing pulp–dentin complex regeneration after transplantation of stem/progenitor cells versus no stem/progenitor cell transplantation controls in intraoral in vivo teeth animal models were analyzed. The following outcomes were investigated: regenerated pulp area per root canal total area, capillaries per total surface, regenerated dentinal area per total defect area, and nerves per total surface. PubMed and EMBASE were screened for studies published until July 2014. Cross-referencing and hand searching were used to identify further articles. Standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects meta-analysis. To assess possible bias, SYRCLE's risk of bias tool for animal studies was used. From 1364 screened articles, five studies (representing 64 animals) were included in the quantitative analysis. Risk of bias of all studies was high. Stem/progenitor cell-transplanted pulps showed significantly larger regenerated pulp area per root canal total area (SMD [95% CI]: 2.28 [0.35–4.21]) and regenerated dentin area per root canal total area (SMD: 6.91 [5.39–8.43]) compared with no stem/progenitor cell transplantation controls. Only one study reported on capillaries per or nerves per total surface and found both significantly increased in stem/progenitor cell-transplanted pulps compared with controls. Stem/progenitor cell transplantation seems to enhance pulp–dentin complex regeneration in

  9. Lung Transplantation for Cystic Fibrosis

    PubMed Central

    Adler, Frederick R.; Aurora, Paul; Barker, David H.; Barr, Mark L.; Blackwell, Laura S.; Bosma, Otto H.; Brown, Samuel; Cox, D. R.; Jensen, Judy L.; Kurland, Geoffrey; Nossent, George D.; Quittner, Alexandra L.; Robinson, Walter M.; Romero, Sandy L.; Spencer, Helen; Sweet, Stuart C.; van der Bij, Wim; Vermeulen, J.; Verschuuren, Erik A. M.; Vrijlandt, Elianne J. L. E.; Walsh, William; Woo, Marlyn S.; Liou, Theodore G.

    2009-01-01

    Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patient's quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions. PMID:20008865

  10. Facial transplantation: A concise update

    PubMed Central

    Barrera-Pulido, Fernando; Gomez-Cia, Tomas; Sicilia-Castro, Domingo; Garcia-Perla-Garcia, Alberto; Gacto-Sanchez, Purificacion; Hernandez-Guisado, Jose-Maria; Lagares-Borrego, Araceli; Narros-Gimenez, Rocio; Gonzalez-Padilla, Juan D.

    2013-01-01

    Objectives: Update on clinical results obtained by the first worldwide facial transplantation teams as well as review of the literature concerning the main surgical, immunological, ethical, and follow-up aspects described on facial transplanted patients. Study design: MEDLINE search of articles published on “face transplantation” until March 2012. Results: Eighteen clinical cases were studied. The mean patient age was 37.5 years, with a higher prevalence of men. Main surgical indication was gunshot injuries (6 patients). All patients had previously undergone multiple conventional surgical reconstructive procedures which had failed. Altogether 8 transplant teams belonging to 4 countries participated. Thirteen partial face transplantations and 5 full face transplantations have been performed. Allografts are varied according to face anatomical components and the amount of skin, muscle, bone, and other tissues included, though all were grafted successfully and remained viable without significant postoperative surgical complications. The patient with the longest follow-up was 5 years. Two patients died 2 and 27 months after transplantation. Conclusions: Clinical experience has demonstrated the feasibility of facial transplantation as a valuable reconstructive option, but it still remains considered as an experimental procedure with unresolved issues to settle down. Results show that from a clinical, technical, and immunological standpoint, facial transplantation has achieved functional, aesthetic, and social rehabilitation in severely facial disfigured patients. Key words:Face transplantation, composite tissue transplantation, face allograft, facial reconstruction, outcomes and complications of face transplantation. PMID:23229268

  11. Imaging in liver transplantation

    PubMed Central

    Caruso, Settimo; Miraglia, Roberto; Maruzzelli, Luigi; Gruttadauria, Salvatore; Luca, Angelo; Gridelli, Bruno

    2009-01-01

    The aim of this study was to illustrate the role of non-invasive imaging tools such as ultrasonography, multi-detector row computed tomography, and magnetic resonance imaging in the evaluation of pediatric and adult liver recipients and potential liver donors, and in the detection of potential complications arising from liver transplantation. PMID:19222090

  12. Organ Harvesting and Transplants

    ERIC Educational Resources Information Center

    Baskette, Kimberly G.; Ritz, John M.

    2010-01-01

    Humans and animals need healthy organs to live. Due to medical conditions and accidents, some organs fail to function properly. For these reasons, the medical community has experimented and can now perform successful organ transplants, allowing patients to continue to live their lives. Many countries have medical programs where individuals can…

  13. [Glaucoma and corneal transplantation].

    PubMed

    Geerling, G; Müller, M; Zierhut, M; Klink, T

    2010-05-01

    Glaucoma and corneal disorders are often associated and are of diagnostic, therapeutic and prognostic relevance for each other. Glaucoma is already present in approximately 15% of eyes prior to keratoplasty, whereas in addition approximately 15% of cases are diagnosed following corneal transplantation. Corneal opacities, surface irregularities and pachymetric deviations from the norm can have a negative impact on tonometry, perimetry and morphological glaucoma diagnosis. Digital and intracameral tonometry as well as flash VEP to determine the visual potential can be helpful in this setting. Increased intraocular pressure (IOP), long-term application of antiglaucomatous medication or the use of antimetabolites in glaucoma surgery can all induce keratopathy. Therefore, intraocular pressure should be regulated prior to corneal transplantation. Risk factors for the evolution of glaucoma following corneal transplantation are the specific indication and surgical technique (e. g. combined corneal and cataract/vitreoretinal surgery), as well as postoperative steroid application and chamber angle synechiae. Unpreserved glaucoma medication without pro-inflammatory effects should be preferred following keratoplasty. In the long term surgery to control IOP is required in approximately 25% of eyes. The wider use of lamellar techniques for corneal transplantation is likely to reduce the incidence of secondary glaucoma.

  14. After the Transplant

    MedlinePlus

    ... you from post-surgical pain for a short time. Follow your team's pain management instructions to make the overall experience as comfortable as possible. Transplant is major surgery. It may take time to get back to eating normally, moving around, ...

  15. Hair transplantation update.

    PubMed

    Rogers, Nicole E

    2015-06-01

    Contemporary hair transplant surgery offers results that are natural and undetectable. It is an excellent treatment option for male and female pattern hair loss. Patients are encouraged to also use medical therapy to help protect their surgical results and prevent ongoing thinning of the surrounding hairs. The two major techniques of donor elliptical harvesting and follicular unit extraction are discussed here. PMID:26176286

  16. Ovary and uterus transplantation.

    PubMed

    Gosden, Roger G

    2008-12-01

    Ovarian and uterine transplantation are procedures gaining more attention again because of potential applications in respectively fertility preservation for cancer and other patients and, more tentatively, women with uterine agenesis or hysterectomy. Cryopreservation of tissue slices, and possibly whole organs, is providing opportunities for banking ovaries for indefinite periods before transplanting them back to restore fertility. The natural plasticity of this organ facilitates grafting to different sites where they can be revascularized and rapidly restore the normal physiology of secretion and ovulation. Ischemic damage is a chief limitation because many follicles are lost, at least in avascular grafts, and functional longevity is reduced. Nevertheless, grafts of young ovarian tissue, even after cryopreservation, can be highly fertile in laboratory rodents and, in humans, autografts have functioned for up to 3 years before needing replacement. Transplantation by vascular anastomosis provides potentially longer function but it is technically much more demanding and riskier for the recipient. It is the only practicable method with the uterus, and has enabled successful pregnancies in several species, but not yet in humans. Contrary to claims made many years ago, neither organ is privileged immunologically, and allografts become rapidly rejected except in hosts whose immune system is deficient or suppressed pharmacologically. All in all, transplantation of these organs, especially the ovary, provides a broad platform of opportunities for research and new applications in reproductive medicine and conservation biology.

  17. Selenoproteins and cardiovascular stress.

    PubMed

    Rose, Aaron H; Hoffmann, Peter R

    2015-03-01

    Dietary selenium (Se) is an essential micronutrient that exerts its biological effects through its incorporation into selenoproteins. This family of proteins contains several antioxidant enzymes such as the glutathione peroxidases, redox-regulating enzymes such as thioredoxin reductases, a methionine sulfoxide reductase, and others. In this review, we summarise the current understanding of the roles these selenoproteins play in protecting the cardiovascular system from different types of stress including ischaemia-reperfusion, homocysteine dysregulation, myocardial hypertrophy, doxirubicin toxicity, Keshan disease, and others.

  18. Nanotechnology in cardiovascular medicine.

    PubMed

    Patel, Devang N; Bailey, Steven R

    2007-04-01

    Nanotechnology is a new field of science and technology that has already had significant impact in the development of novel products in industry. In medicine, application of nanotechnology has the potential to develop new imaging agents, pharmaceutical drugs and medical devices with unique physical and chemical properties. This article reviews the potential for various nanoparticles in cardiovascular imaging and therapeutics, nanoporous structures for sensing and implant based drug delivery, and self-assembled monolayers for surface modification and implant based drug delivery.

  19. Cardiovascular disease in systemic sclerosis

    PubMed Central

    Cannarile, Francesca; Valentini, Valentina; Mirabelli, Giulia; Alunno, Alessia; Terenzi, Riccardo; Luccioli, Filippo; Bartoloni, Elena

    2015-01-01

    Cardiovascular (CV) system involvement is a frequent complication of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It still remains unclear if a premature atherosclerosis (ATS) occurs even in systemic sclerosis (SSc). Although microvascular disease is a hallmark of SSc, in the last few years a number of studies highlighted a higher prevalence of macrovascular disease in SSc patients in comparison to healthy individuals and these data have been correlated with a poorer prognosis. The mechanisms promoting ATS in SSc are not fully understood, but it is believed to be secondary to multi-system organ inflammation, endothelial wall damage and vasculopathy. Both traditional risk factors and endothelial dysfunction have been proposed to participate to the onset and progression of ATS in such patients. In particular, endothelial cell injury induced by anti-endothelial antibodies, ischemia/reperfusion damage, immune-mediated cytotoxicity represent the main causes of vascular injury together with an impaired vascular repair mechanism that determine a defective vasculogenesis. Aim of this review is to analyse both causes and clinical manifestations of macrovascular involvement and ATS in SSc. PMID:25705640

  20. Immunity, atherosclerosis and cardiovascular disease

    PubMed Central

    2013-01-01

    Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition with immune competent cells in lesions producing mainly pro-inflammatory cytokines. Dead cells and oxidized forms of low density lipoproteins (oxLDL) are abundant. The major direct cause of CVD appears to be rupture of atherosclerotic plaques. oxLDL has proinflammatory and immune-stimulatory properties, causes cell death at higher concentrations and contains inflammatory phospholipids with phosphorylcholine (PC) as an interesting epitope. Antibodies against PC (anti-PC) may be atheroprotective, one mechanism being anti-inflammatory. Bacteria and virus have been discussed, but it has been difficult to find direct evidence, and antibiotic trials have not been successful. Heat shock proteins could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include pro-inflammatory cytokines, chemokines, and lipid mediators. To prove that inflammation is a cause of atherosclerosis and CVD, clinical studies with anti-inflammatory and/or immune-modulatory treatment are needed. The potential causes of immune reactions and inflammation in atherosclerosis and how inflammation can be targeted therapeutically to provide novel treatments for CVD are reviewed. PMID:23635324

  1. Hypercoagulability in Kidney Transplant Recipients.

    PubMed

    Parajuli, Sandesh; Lockridge, Joseph B; Langewisch, Eric D; Norman, Douglas J; Kujovich, Jody L

    2016-04-01

    Thrombosis remains an important complication after kidney transplantation. Outcomes for graft and deep vein thrombosis are not favorable. The majority of early kidney transplant failure in adults is due to allograft thrombosis. Risk stratification, early diagnosis, and appropriate intervention are critical to the management of thrombotic complications of transplant. In patients with end-stage renal disease, the prevalence of acquired risk factors for thrombosis is significantly high. Because of hereditary and acquired risk factors, renal transplant recipients manifest features of a chronic prothrombotic state. Identification of hereditary thrombotic risk factors before transplantation may be a useful tool for selecting appropriate candidates for thrombosis prophylaxis immediately after transplantation. Short-term anticoagulation may be appropriate for all patients after kidney transplantation.

  2. Transplant tourism: a growing phenomenon.

    PubMed

    Cohen, David J

    2009-03-01

    Medical tourism is increasing owing to high costs of care, lack of availability or long waits for procedures, and improvements in technology and standards of care in many countries. Transplant tourism is one example of medical tourism that has been attracting increasing attention because of concerns over poor treatment and outcomes of both donors and recipients. Most such cases involve vended kidneys obtained from vulnerable populations, and both donors and recipients receive inferior care by US standards. This commentary discusses a paper by Gill et al. that compared outcomes of 33 transplant tourists with those of patients transplanted at a US center. Fewer complications and better outcomes were seen in patients transplanted in the US center than among transplant tourists. Large transplant centers with long waiting times are increasingly likely to see patients return newly transplanted from overseas; such patients require urgent attention, with particular consideration to infectious complications.

  3. Will Regenerative Medicine Replace Transplantation?

    PubMed Central

    Orlando, Giuseppe; Soker, Shay; Stratta, Robert J.; Atala, Anthony

    2013-01-01

    Recent groundbreaking advances in organ bioengineering and regeneration have provided evidence that regenerative medicine holds promise to dramatically improve the approach to organ transplantation. The two fields, however, share a common heritage. Alexis Carrel can be considered the father of both regenerative medicine and organ transplantation, and it is now clear that his legacy is equally applicable for the present and future generations of transplant and regenerative medicine investigators. In this review, we will briefly illustrate the interplay that should be established between these two complementary disciplines of health sciences. Although regenerative medicine has shown to the transplant field its potential, transplantation is destined to align with regenerative medicine and foster further progress probably more than either discipline alone. Organ bioengineering and regeneration technologies hold the promise to meet at the same time the two most urgent needs in organ transplantation, namely, the identification of a new, potentially inexhaustible source of organs and immunosuppression-free transplantation of tissues and organs. PMID:23906883

  4. Will regenerative medicine replace transplantation?

    PubMed

    Orlando, Giuseppe; Soker, Shay; Stratta, Robert J; Atala, Anthony

    2013-08-01

    Recent groundbreaking advances in organ bioengineering and regeneration have provided evidence that regenerative medicine holds promise to dramatically improve the approach to organ transplantation. The two fields, however, share a common heritage. Alexis Carrel can be considered the father of both regenerative medicine and organ transplantation, and it is now clear that his legacy is equally applicable for the present and future generations of transplant and regenerative medicine investigators. In this review, we will briefly illustrate the interplay that should be established between these two complementary disciplines of health sciences. Although regenerative medicine has shown to the transplant field its potential, transplantation is destined to align with regenerative medicine and foster further progress probably more than either discipline alone. Organ bioengineering and regeneration technologies hold the promise to meet at the same time the two most urgent needs in organ transplantation, namely, the identification of a new, potentially inexhaustible source of organs and immunosuppression-free transplantation of tissues and organs.

  5. Kidney Transplantation in the Elderly

    PubMed Central

    Huang, Edmund; Segev, Dorry L.; Rabb, Hamid

    2010-01-01

    Summary There is an increase in the older incident end-stage renal disease population that is associated with an increasing prevalence of end-stage renal disease in the United States. This trend is paralleled by an increasing rate of kidney transplantation in the elderly. Although patient survival is lower in older versus younger kidney recipients, the elderly benefit from a reduction in mortality rate and improved quality of life with transplantation compared with dialysis. Immunologic, physiologic, and psychosocial factors influence transplant outcomes and should be recognized in the care of the elderly transplant patient. In this review, we discuss transplantation in the elderly patient, particularly the topics of access to transplantation, patient and graft survival, the impact of donor quality on transplant outcomes, immunology and immunosuppression of aging, and ethical considerations in the development of an equitable organ allocation scheme. PMID:20006794

  6. Will regenerative medicine replace transplantation?

    PubMed

    Orlando, Giuseppe; Soker, Shay; Stratta, Robert J; Atala, Anthony

    2013-08-01

    Recent groundbreaking advances in organ bioengineering and regeneration have provided evidence that regenerative medicine holds promise to dramatically improve the approach to organ transplantation. The two fields, however, share a common heritage. Alexis Carrel can be considered the father of both regenerative medicine and organ transplantation, and it is now clear that his legacy is equally applicable for the present and future generations of transplant and regenerative medicine investigators. In this review, we will briefly illustrate the interplay that should be established between these two complementary disciplines of health sciences. Although regenerative medicine has shown to the transplant field its potential, transplantation is destined to align with regenerative medicine and foster further progress probably more than either discipline alone. Organ bioengineering and regeneration technologies hold the promise to meet at the same time the two most urgent needs in organ transplantation, namely, the identification of a new, potentially inexhaustible source of organs and immunosuppression-free transplantation of tissues and organs. PMID:23906883

  7. Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host

    PubMed Central

    Léobon, Bertrand; Garcin, Isabelle; Menasché, Philippe; Vilquin, Jean-Thomas; Audinat, Etienne; Charpak, Serge

    2003-01-01

    Survival and differentiation of myogenic cells grafted into infarcted myocardium have raised the hope that cell transplantation becomes a new therapy for cardiovascular diseases. The approach was further supported by transplantation of skeletal myoblasts, which was shown to improve cardiac performance in several animal species. Despite the success of myoblast transplantation and its recent trial in human, the mechanism responsible for the functional improvement remains unclear. Here, we used intracellular recordings coupled to video and fluorescence microscopy to establish whether myoblasts, genetically labeled with enhanced GFP and transplanted into rat infarcted myocardium, retain excitable and contractile properties, and participate actively to cardiac function. Our results indicate that grafted myoblasts differentiate into peculiar hyperexcitable myotubes with a contractile activity fully independent of neighboring cardiomyocytes. We conclude that mechanisms other than electromechanical coupling between grafted and host cells are involved in the improvement of cardiac function. PMID:12805561

  8. Face Transplantation in a Highly Sensitized Recipient.

    PubMed

    Chandraker, Anil; Arscott, Ramon; Murphy, George; Lian, Christine; Bueno, Ericka; Marty, Francisco; Rennke, Helmut; Milford, Edgar; Tullius, Stefan; Pomahac, Bodhan

    2016-05-01

    Face transplantation was performed in a highly sensitized recipient with positive preoperative crossmatch and subsequent antibody-mediated rejection. The recipient was a 45-year-old female with extensive conventional reconstructions after chemical burns over the majority of the body. Residual quality of life and facial functions were poor. Levels of circulating anti-human leukocyte antigen (HLA) antibodies were high, and panel reactive antibody score was 98%. A potential donor was identified; however, with positive T and B cell flow crossmatches. The transplant team proceeded with face transplantation from this donor, under tailored immune suppression and with available salvage options. The operation was successful. Plasmapheresis and induction immune suppression (i.e., thymoglobulin followed by mycophenolate mofetil, tacrolimus, and steroids) were provided. Five days later, there was significant facial swelling, rising anti-HLA antibody titers, and unprecedented evidence of C4d deposits on skin. High doses of steroids and thymoglobulin were provided; however, rejection increased such that by day 19 it was diagnosed grade III in the BANFF scale. After stopping thymoglobulin because of serum sickness, combination therapy of plasmapheresis, eculizumab, bortezomib, and alemtuzumab was provided. HLA antibody levels decreased while swelling and redness improved. At 3 months, there were no longer signs of rejection on biopsy. PMID:27168576

  9. Functional hyposplenism following allogeneic bone marrow transplantation.

    PubMed Central

    Cuthbert, R J; Iqbal, A; Gates, A; Toghill, P J; Russell, N H

    1995-01-01

    AIMS--To investigate the incidence of functional hyposplenism in a group of patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS--Splenic function was assessed by counting the number of gluteraldehyde fixed red blood cells containing pits or indentations as examined by interference phase microscopy. Normal values are < 2% whereas splenectomy patients have values of 25 to 40%. RESULTS--Twenty eight BMT recipients (17 men, 11 women) were studied at varying periods post-transplant and the results compared with 20 healthy volunteers and 10 patients who had undergone splenectomy or had splenic atrophy because of haematological conditions. Of the 28 BMT recipients, one had undergone a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four patients, one had active extensive chronic graft versus host disease (GvHD) which has been previously reported to be associated with functional hyposplenism following transplantation. Only one of the four patients had peripheral blood red cell changes typical of hyposplenism. CONCLUSION--These results confirm that extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of functional hyposplenism may also occur following BMT in the absence of chronic GvHD and in the absence of haematological features of hyposplenism on routine blood films. This may be of significance in mediating the susceptibility to infection with encapsulating bacteria seen following allogeneic BMT. PMID:7730489

  10. Key issues in transplant tourism.

    PubMed

    Akoh, Jacob A

    2012-02-24

    Access to organ transplantation depends on national circumstances, and is partly determined by the cost of health care, availability of transplant services, the level of technical capacity and the availability of organs. Commercial transplantation is estimated to account for 5%-10% (3500-7000) of kidney transplants performed annually throughout the world. This review is to determine the state and outcome of renal transplantation associated with transplant tourism (TT) and the key challenges with such transplantation. The stakeholders of commercial transplantation include: patients on the waiting lists in developed countries or not on any list in developing countries; dialysis funding bodies; middlemen, hosting transplant centres; organ-exporting countries; and organ vendors. TT and commercial kidney transplants are associated with a high incidence of surgical complications, acute rejection and invasive infection which cause major morbidity and mortality. There are ethical and medical concerns regarding the management of recipients of organs from vendors. The growing demand for transplantation, the perceived failure of altruistic donation in providing enough organs has led to calls for a legalised market in organ procurement or regulated trial in incentives for donation. Developing transplant services worldwide has many benefits - improving results of transplantation as they would be performed legally, increasing the donor pool and making TT unnecessary. Meanwhile there is a need to re-examine intrinsic attitudes to TT bearing in mind the cultural and economic realities of globalisation. Perhaps the World Health Organization in conjunction with The Transplantation Society would set up a working party of stakeholders to study this matter in greater detail and make recommendations. PMID:24175191

  11. Key issues in transplant tourism.

    PubMed

    Akoh, Jacob A

    2012-02-24

    Access to organ transplantation depends on national circumstances, and is partly determined by the cost of health care, availability of transplant services, the level of technical capacity and the availability of organs. Commercial transplantation is estimated to account for 5%-10% (3500-7000) of kidney transplants performed annually throughout the world. This review is to determine the state and outcome of renal transplantation associated with transplant tourism (TT) and the key challenges with such transplantation. The stakeholders of commercial transplantation include: patients on the waiting lists in developed countries or not on any list in developing countries; dialysis funding bodies; middlemen, hosting transplant centres; organ-exporting countries; and organ vendors. TT and commercial kidney transplants are associated with a high incidence of surgical complications, acute rejection and invasive infection which cause major morbidity and mortality. There are ethical and medical concerns regarding the management of recipients of organs from vendors. The growing demand for transplantation, the perceived failure of altruistic donation in providing enough organs has led to calls for a legalised market in organ procurement or regulated trial in incentives for donation. Developing transplant services worldwide has many benefits - improving results of transplantation as they would be performed legally, increasing the donor pool and making TT unnecessary. Meanwhile there is a need to re-examine intrinsic attitudes to TT bearing in mind the cultural and economic realities of globalisation. Perhaps the World Health Organization in conjunction with The Transplantation Society would set up a working party of stakeholders to study this matter in greater detail and make recommendations.

  12. Key issues in transplant tourism

    PubMed Central

    Akoh, Jacob A

    2012-01-01

    Access to organ transplantation depends on national circumstances, and is partly determined by the cost of health care, availability of transplant services, the level of technical capacity and the availability of organs. Commercial transplantation is estimated to account for 5%-10% (3500-7000) of kidney transplants performed annually throughout the world. This review is to determine the state and outcome of renal transplantation associated with transplant tourism (TT) and the key challenges with such transplantation. The stakeholders of commercial transplantation include: patients on the waiting lists in developed countries or not on any list in developing countries; dialysis funding bodies; middlemen, hosting transplant centres; organ-exporting countries; and organ vendors. TT and commercial kidney transplants are associated with a high incidence of surgical complications, acute rejection and invasive infection which cause major morbidity and mortality. There are ethical and medical concerns regarding the management of recipients of organs from vendors. The growing demand for transplantation, the perceived failure of altruistic donation in providing enough organs has led to calls for a legalised market in organ procurement or regulated trial in incentives for donation. Developing transplant services worldwide has many benefits - improving results of transplantation as they would be performed legally, increasing the donor pool and making TT unnecessary. Meanwhile there is a need to re-examine intrinsic attitudes to TT bearing in mind the cultural and economic realities of globalisation. Perhaps the World Health Organization in conjunction with The Transplantation Society would set up a working party of stakeholders to study this matter in greater detail and make recommendations. PMID:24175191

  13. Altered phosphodiesterase 3-mediated cAMP hydrolysis contributes to a hypermotile phenotype in obese JCR:LA-cp rat aortic vascular smooth muscle cells: implications for diabetes-associated cardiovascular disease.

    PubMed

    Netherton, Stuart J; Jimmo, Sandra L; Palmer, Daniel; Tilley, Douglas G; Dunkerley, Heather A; Raymond, Daniel R; Russell, James C; Absher, P Marlene; Sage, E Helene; Vernon, Robert B; Maurice, Donald H

    2002-04-01

    Cardiovascular diseases represent a significant cause of morbidity and mortality in diabetes. Of the many animal models used in the study of non-insulin-dependent (type 2) diabetes, the JCR:LA-cp rat is unique in that it develops insulin resistance in the presence of obesity and manifests both peripheral and coronary vasculopathies. In this animal model, arterial vascular smooth muscle cells (VSMCs) from homozygous obese (cp/cp) rats, but not from age-matched healthy (+/+ or + /cp, collectively defined +/?) littermates, display an " activated" phenotype in vitro and in vivo and have an elevated level of cAMP phosphodiesterase (PDE) activity. In this report, we confirm that cp/cp rat aortic VSMCs have an elevated level of PDE3 activity and show that only particulate PDE3 (PDE3B) activity is elevated. In marked contrast to results obtained in + /? VSMCs, simultaneous activation of adenylyl cyclase and inhibition of PDE3 activity in cp/cp VSMCs synergistically increased cAMP. Although PDE3 inhibition did not potentiate the antimigratory effects of forskolin on +/? VSMCs, PDE3 inhibition did markedly potentiate the forskolin-induced inhibition of migration of cp/cp-derived VSMCs. Although PDE3 activity was elevated in cp/cp rat aortic VSMCs, levels of expression of cytosolic PDE3 (PDE3A) and PDE3B in +/? and cp/cp VSMCs, as well as activation of these enzymes following activation of the cAMP-protein kinase A signaling cascade, were not different. Our data are consistent with an increased role for PDE3 in regulating cAMP-dependent signaling in cp/cp VSMCs and identify PDE3 as a cellular activity potentially responsible for the phenotype of cp/cp VSMCs.

  14. The Role of Immunogenicity in Cardiovascular Disease

    PubMed Central

    Jan, Michael; Virtue, Anthony T.; Pansuria, Meghanaben; Liu, Jingshan; Xiong, Xinyu; Fang, Pu; Meng, Shu; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    Recently, many of the complexities associated with cardiovascular diseases (CVD) have been unlocked. However, despite these breakthroughs, CVD and its related complications are the leading contributors of morbidity and mortality worldwide, which indicates the shortcomings of current treatment regimens and the need for continued research. Published data within the field clearly indicates that CVD are built on inflammation and autoimmune platforms, though a strong, fundamental understanding of the mechanisms remains elusive. Areas such as the mechanisms underlying increased immunogenicity of self-proteins in the cardiovascular system, the roles of immunogenic auto-antigens in eliciting inflammatory autoimmune responses, and the immunosuppressive mechanisms involved in controlling inflammatory and autoimmune cardiovascular diseases remain to be well-understood. We will delve into these topics and the advancements made within the field in this review. Specifically, we will concentrate on the innate and adaptive immune responses mediating immunogenicity; the mechanisms of inflammation and autoimmunity in atherogenesis; the mechanisms of inflammation and autoimmunity in diabetic atherosclerosis; immunogenicity and stem cell therapy; as well as immunogenicity and immunosuppression. In depth examination and comprehension of these topics will provide insight into the recent progress of the field and bring to the forefront potentially novel therapeutic avenues. PMID:24511305

  15. Promethazine affects autonomic cardiovascular mechanisms minimally

    NASA Technical Reports Server (NTRS)

    Brown, T. E.; Eckberg, D. L.

    1997-01-01

    Promethazine hydrochloride, Phenergan, is a phenothiazine derivative with antihistaminic (H1), sedative, antiemetic, anticholinergic, and antimotion sickness properties. These properties have made promethazine a candidate for use in environments such as microgravity, which provoke emesis and motion sickness. Recently, we evaluated carotid baroreceptor-cardiac reflex responses during two Space Shuttle missions 18 to 20 hr after the 50 mg intramuscular administration of promethazine. Because the effects of promethazine on autonomic cardiovascular mechanisms in general and baroreflex function in particular were not known, we were unable to exclude a possible influence of promethazine on our results. Our purpose was to determine the ground-based effects of promethazine on autonomic cardiovascular control. Because of promethazine's antihistaminic and anticholinergic properties, we expected that a 50-mg intramuscular injection of promethazine would affect sympathetically and vagally mediated cardiovascular mechanisms. Eight healthy young subjects, five men and three women, were studied at rest in recumbency. All reported drowsiness as a result of the promethazine injection; most also reported nervous excitation, dry mouth, and fatigue. Three subjects had significant reactions: two reported excessive anxiety and one reported dizziness. Measurements were performed immediately prior to injection and 3.1 +/- 0.1 and 19.5 +/- 0.4 hr postinjection. We found no significant effect of promethazine on resting mean R-R interval, arterial pressure, R-R interval power spectra, carotid baroreflex function, and venous plasma catecholamine levels.

  16. De novo autoimmune hepatitis after liver transplantation.

    PubMed

    Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin

    2007-10-01

    The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development