Reversal of asymptomatic cardiac dysfunction following renal transplantation.
Ontology highlight
ABSTRACT:
SUBMITTER: Chinnappa S
PROVIDER: S-EPMC8023313 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Monocyte dysfunction in filarial infection has been proposed as one mechanism underlying the diminished antigen-specific T-cell response seen in patent lymphatic filariasis. Cytokine/chemokine production and gene expression in monocytes from filaria-infected patients and uninfected healthy donors were assessed unstimulated and in response to stimulation with Staphylococcus aureus Cowan I bacteria plus gamma interferon both before and 8 months following treatment. Monocytes from filaria-infected individuals were studded with intracellular microfilarial antigens. Furthermore, monocytes from these individuals were less capable of producing interleukin-8 (IL-8), Exodus II, MIP-1alpha, MIP-1beta, and IL-1alpha and preferentially expressed genes involved in apoptosis and adhesion compared with monocytes from uninfected donors. Eight months following treatment with a single dose of ivermectin-albendazole, some of these defects were reversed, with monocyte production of IL-8, IL-1alpha, MIP-1alpha, and IL-10 being comparable to that seen in the uninfected controls. In addition, a marked increase in mRNA expression of genes associated with protein metabolism, particularly heat shock proteins, was seen compared with pretreatment expression. These data suggest that the function and gene expression of monocytes in filaria-infected patients are altered but that this dysfunction is partially reversible following antifilarial treatment.
| S-EPMC1539612 | biostudies-literature
Project description: Not available
| S-EPMC8575406 | biostudies-literature
Project description:To assess the function of peripheral blood derived monocytes in patently infected filaria patients (either Wuchereria bancrofti, Mansonella perstans, or both), we investigated the cytokine production and gene expression profile of these cells in filaria infected patients and compared them with those from uninfected normal blood bank donors. Monocytes from infected individuals were studded with intracellular microfilarial antigens. In addition, Staphylococcus aureus Cowan I bacteria (SAC)/IFN γ activated monocytes from the infected individuals produced less IL 8, Exodus II, MIP 1a, MIP 1b, eotaxin, RANTES, IL 1a, and MIP 3b compared with normal patients. Microarray analysis of ex vivo isolated monocytes demonstrated that multiple genes involved in signal transduction, apoptosis, and adhesion were expressed to a greater degree in filaria infected patient monocytes compared with those of uninfected normal individuals. Eight months following treatment with a single dose of ivermectin/albendazole, monocytes of W. bancrofti infected individuals were capable of producing more IL 8, IL 1a, MIP 1a, and IL 10 in response to SAC/IFN γ compared with their pretreatment levels. Further, when monocyte global expression was compared before and after treatment of the W. bancrofti, there was a marked increase in mRNA expression of genes associated with protein metabolism, and in HSP most particularly, compared with pretreatment expression. These data suggest that the function and gene expression of monocytes in filaria infected patients are altered; however, this dysfunction can be reveresed to a degree following treatment with a single dose of ivermection/albendazole. Keywords: other
2005-01-12 | GSE2135 | GEO
Project description:Recipients of donation after circulatory death (DCD) grafts are reportedly at higher risk of developing renal dysfunction after liver transplantation (LT). We compared the development of acute kidney injury (AKI) and chronic kidney disease (CKD) after LT in recipients of DCD versus donation after brain death (DBD) or living donor liver transplantation (LDLT) livers. Adult recipients of DBD, LDLT, and DCD between 2012 and 2016 at Toronto General Hospital were included. AKI was defined as a post-LT increase of serum creatinine (sCr) ?26.5 µmol/L within 48 hours or a ?50% increase from baseline, and CKD was defined as an estimated glomerular filtration rate <60 mL/minute for >3 months. A total of 681 patients (DCD, n = 57; DBD, n = 446; and LDLT, n = 178) with similar baseline comorbidities were included. Perioperative AKI (within the first 7 postoperative days) was observed more frequently in the DCD group (61%; DBD, 40%; and LDLT, 44%; P = 0.01) and was associated with significantly higher peak AST levels (P < 0.001). Additionally, patients in the DCD group had a significantly higher peak sCr (P < 0.001) and a trend toward higher rates of AKI stage 3 (DCD, 33%; DBD, 21%; LDLT, 21%; P = 0.11). The proportions of recovery from AKI (DCD, 77%; DBD, 72%; LDLT, 78%; P = 0.45) and patients developing CKD (DCD, 33%; DBD, 32%; LDLT, 32%; P = 0.99) were similar. Nevertheless, patients who received DCD or DBD LT and required perioperative renal replacement therapy showed significantly lower patient survival in multivariate analysis (hazard ratio, 7.90; 95% confidence interval, 4.51-13.83; P < 0.001). In conclusion, recipients of DCD liver grafts experience higher rates of short-term post-LT renal dysfunction compared with DBD or LDLT. Additional risk factors for the development of severe kidney injury, such as high Model for End-Stage Liver Disease score, massive transfusions, or donor age ?60 years should be avoided.
| S-EPMC7317208 | biostudies-literature
Project description:To assess the function of peripheral blood derived monocytes in patently infected filaria patients (either Wuchereria bancrofti, Mansonella perstans, or both), we investigated the cytokine production and gene expression profile of these cells in filaria infected patients and compared them with those from uninfected normal blood bank donors. Monocytes from infected individuals were studded with intracellular microfilarial antigens. In addition, Staphylococcus aureus Cowan I bacteria (SAC)/IFN γ activated monocytes from the infected individuals produced less IL 8, Exodus II, MIP 1a, MIP 1b, eotaxin, RANTES, IL 1a, and MIP 3b compared with normal patients. Microarray analysis of ex vivo isolated monocytes demonstrated that multiple genes involved in signal transduction, apoptosis, and adhesion were expressed to a greater degree in filaria infected patient monocytes compared with those of uninfected normal individuals. Eight months following treatment with a single dose of ivermectin/albendazole, monocytes of W. bancrofti infected individuals were capable of producing more IL 8, IL 1a, MIP 1a, and IL 10 in response to SAC/IFN γ compared with their pretreatment levels. Further, when monocyte global expression was compared before and after treatment of the W. bancrofti, there was a marked increase in mRNA expression of genes associated with protein metabolism, and in HSP most particularly, compared with pretreatment expression. These data suggest that the function and gene expression of monocytes in filaria infected patients are altered; however, this dysfunction can be reveresed to a degree following treatment with a single dose of ivermection/albendazole.
2008-06-12 | E-GEOD-2135 | biostudies-arrayexpress
Project description:IntroductionAllograft ureteral strictures after renal transplantation impact graft function and increase patient morbidity. They can be challenging to treat and may require complex surgical repair. Therefore, the objective of this study was to identify contemporary risk factors for the development of post-renal transplant ureteral strictures.MethodsA retrospective analysis was performed on all renal transplant patients at Vancouver General Hospital from 2008-2019. Demographics, clinical parameters, and outcomes were compared between patients who did and did not develop ureteral strictures. Putative risk factors for ureteral stricture were analyzed using logistic regression.ResultsA total of 1167 patients were included with a mean followup of 61.9±40.8 months. Ureteral strictures occurred in 25 patients (2.1%). Stricture patients had no demographic differences compared to non-stricture patients but had significantly higher rates of postoperative complications, longer hospital stays, and decreased renal function one year post-transplant (all p<0.05). On multivariable analysis, cold ischemia time >435 minutes (odds ratio [OR] 43.9, confidence interval [CI] 1.6-1238.8, p=0.027), acute rejection (OR 3.0, CI 1.1-7.4, p=0.027), and postoperative complications (OR 112.4, CI 2.4-5332.6, p=0.016) were risk factors for stricture.ConclusionsRenal transplant patients with ureteral stricture experience greater morbidity and reduced post-transplant renal function compared to non-stricture patients. Our findings support attempts to reduce cold ischemia time, acute rejection, and postoperative complications to mitigate this potential complication. Our study is limited by the low incidence of ureteral stricture resulting in a small sample of stricture patients. Future research in a larger, multicenter setting is warranted.
| S-EPMC9245959 | biostudies-literature
Project description:Cardiac progenitor cells are a potential source of cell therapy for heart failure. Although recent studies have shown that transplantation of cardiac stem/progenitor cells improves function of infarcted hearts, the precise mechanisms of the improvement in function remain poorly understood. The present study demonstrates that transplantation of sheets of clonally expanded stem cell antigen 1-positive (Sca-1-positive) cells (CPCs) ameliorates cardiac dysfunction after myocardial infarction in mice. CPC efficiently differentiated into cardiomyocytes and secreted various cytokines, including soluble VCAM-1 (sVCAM-1). Secreted sVCAM-1 induced migration of endothelial cells and CPCs and prevented cardiomyocyte death from oxidative stress through activation of Akt, ERK, and p38 MAPK. Treatment with antibodies specific for very late antigen-4 (VLA-4), a receptor of sVCAM-1, abolished the effects of CPC-derived conditioned medium on cardiomyocytes and CPCs in vitro and inhibited angiogenesis, CPC migration, and survival in vivo, which led to attenuation of improved cardiac function following transplantation of CPC sheets. These results suggest that CPC transplantation improves cardiac function after myocardial infarction through cardiomyocyte differentiation and paracrine mechanisms mediated via the sVCAM-1/VLA-4 signaling pathway.
| S-EPMC2719947 | biostudies-literature
Project description:To address the pathophysiological mechanisms underlying chronic kidney disease with comorbid cardiac dysfunction, we investigated renal and cardiac, functional and structural damage when myocardial infarction (MI) was applied in the setting of kidney injury (induced by 5/6 nephrectomy-STNx). STNx or Sham surgery was induced in male Sprague-Dawley rats with MI or Sham surgery performed 4 weeks later. Rats were maintained for a further 8 weeks. Rats (n = 36) were randomized into four groups: Sham+Sham, Sham+MI, STNx+Sham and STNx+MI. Increased renal tubulointerstitial fibrosis (P < 0.01) and kidney injury molecule-1 expression (P < 0.01) was observed in STNx+MI compared to STNx+Sham animals, while there were no further reductions in renal function. Heart weight was increased in STNx+MI compared to STNx+Sham or Sham+MI animals (P < 0.05), despite no difference in blood pressure. STNx+MI rats demonstrated greater cardiomyocyte cross-sectional area and increased cardiac interstitial fibrosis compared to either STNx+Sham (P < 0.01) or Sham+MI (P < 0.01) animals which was accompanied by an increase in diastolic dysfunction. These changes were associated with increases in ANP, cTGF and collagen I gene expression and phospho-p38 MAPK and phospho-p44/42 MAPK protein expression in the left ventricle. Addition of MI accelerated STNx-induced structural damage but failed to significantly exacerbate renal dysfunction. These findings highlight the bidirectional response in this model known to occur in cardiorenal syndrome (CRS) and provide a useful model for examining potential therapies for CRS.
| S-EPMC5742721 | biostudies-literature
Project description:Cardiac complications have been well-described in sickle cell disease; however, it has been rare to see improvements in cardiac abnormalities following any interventions. Previous work has shown no significant structural changes after treatment with hydroxyurea. The cardiac effects of red blood cell exchange transfusion (RBCx) and hematopoietic stem cell transplantation (HSCT) have not been well described. We studied 56 patients undergoing HSCT (41 HLA-matched, 15 haploidentical), of whom 32 had RBCx within 3 months before HSCT. Echocardiograms and laboratory parameters were obtained at baseline, and at 3, 6, and 12 months following HSCT. Although hemolytic parameters and anemia improved following RBCx, there was a small increase in left ventricular volume index. Following successful HSCT, however, there were significant improvements in cardiac size, function, and diastolic filling parameters at 3 months followed by continued smaller improvements up to 1 year. There was a significant improvement in N-terminal pro B-type natriuretic peptide levels and a trend toward improvement in 6-minute walk time 1 year after HSCT. The magnitude of cardiac improvement seen following HSCT was comparable to that observed following correction of a volume overload state as seen in pregnancy or after repair of chronic valvular regurgitation. Further studies in sickle cell disease patients will help delineate which cardiac complications and what level of severity should be considered indications for HSCT.
| S-EPMC6784516 | biostudies-literature
Project description:Study aimsCardiac arrest mortality is significantly affected by failure to obtain return of spontaneous circulation (ROSC) despite cardiopulmonary resuscitation (CPR). Severe myocardial dysfunction and cardiovascular collapse further affects mortality within hours of initial ROSC. Recent work suggests that enhancement of nitric oxide (NO) signaling within minutes of CPR can improve myocardial function and survival. We studied the role of NO signaling on cardiovascular outcomes following cardiac arrest and resuscitation using endothelial NO synthase knockout (NOS3(-/-)) mice.MethodsAdult female wild-type (WT) and NOS3(-/-) mice were anesthetized, intubated, and instrumented with left-ventricular pressure-volume catheters. Cardiac arrest was induced with intravenous potassium chloride. CPR was performed after 8min of untreated arrest. ROSC rate, cardiac function, whole-blood nitrosylhemoglobin (HbNO) concentrations, heart NOS3 content and phosphorylation (p-NOS3), cyclic guanosine monophosphate (cGMP), and phospho-troponin I (p-TnI) were measured.ResultsDespite equal quality CPR, NOS3(-/-) mice displayed lower rates of ROSC compared to WT (47.6% [10/21] vs. 82.4% [14/17], p<0.005). Among ROSC animals, NOS3(-/-) vs. WT mice exhibited increased left-ventricular dysfunction and 120min mortality. Prior to ROSC, myocardial effectors of NO signaling including cGMP and p-TnI were decreased in NOS3(-/-) vs. WT mice (p<0.05). Following ROSC in WT mice, significant NOS3-dependent increases in circulating HbNO were seen by 120min. Significant increases in cardiac p-NOS3 occurred between end-arrest and 15min post-ROSC, while total NOS3 content was increased by 120min post-ROSC (p<0.05).ConclusionsGenetic deletion of NOS3 decreases ROSC rate and worsens post-ROSC left-ventricular function. Poor cardiovascular outcomes are associated with differences in NOS3-dependent myocardial cGMP signaling and circulating NO metabolites.
| S-EPMC3018673 | biostudies-literature