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Stephan Neidhardt Jens Garbade Fabian Emrich Kristin Klaeske Michael A. Borger Sven Lehmann Khalil Jawad Maja-Theresa Dieterlen 《Journal of cardiac failure》2019,25(3):204-212
Background
Oxidative stress due to reactive oxygen species (ROS) production is a key factor in the development of heart failure (HF). This study investigated the thioredoxin (Trx) system, which plays a major role in antioxidant defense, in patients suffering from ischemic (ICM) or dilated (DCM) cardiomyopathy.Methods and Results
Myocardial tissue from ICM (n?=?13) and DCM (n?=?13) patients, as well as septal tissue of patients with aortic stenosis but without diagnosed hypertrophic cardiomyopathy or subaortic stenosis (control; n?=?12), was analyzed for Trx1, Trx-interacting protein (TXNIP) and E3 ligase ITCH (E3 ubiquitin-protein ligase Itchy homolog) expression. Trx-reductase 1 (TXNRD1) amount and activity, cytosolic cytochrome C content, and apoptosis markers were quantified by means of enzyme-linked immunosorbent assay and multiplexing. Compared with control samples, ITCH and Trx1 expression, TXNRD1 amount and activity were reduced and TXNIP expression was increased in ICM (ITCH: P?=?.013; Trx1: P?=?.028; TXNRD1 amount: P?=?.035; TXNRD1 activity: P?=?.005; TXNIP: P?=?.014) but not in DCM samples. A higher level of the downstream apoptosis marker caspase-9 (ICM: 582 ± 262 MFI [P?=?.995]; DCM: 1251 ± 548 MFI [P?=?.002], control: 561 ± 214 MFI) was detected in DCM tissue. A higher expression of Bcl-2 was found in DCM (P?=?.011).Conclusion
The Trx system was impaired in ICM but not in DCM. ITCH appeared to be responsible for the down-regulation of the Trx system. ROS-induced mitochondrial instability appeared to play a role in DCM. 相似文献2.
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M.‐T. Dieterlen H. B. Bittner A. Pierzchalski S. Dhein F. W. Mohr M. J. Barten 《Clinical and experimental immunology》2014,176(1):120-128
Extracorporeal photopheresis (ECP) has been used as a prophylactic and therapeutic option to avoid and treat rejection after heart transplantation (HTx). Tolerance‐inducing effects of ECP such as up‐regulation of regulatory T cells (Tregs) are known, but specific effects of ECP on regulatory T cell (Treg) subsets and dendritic cells (DCs) are lacking. We analysed different subsets of Tregs and DCs as well as the immune balance status during ECP treatment after HTx. Blood samples were collected from HTx patients treated with ECP for prophylaxis (n = 9) or from patients with histologically proven acute cellular rejection (ACR) of grade ≥ 1B (n = 9), as well as from control HTx patients without ECP (HTxC; n = 7). Subsets of Tregs and DCs as well as different cytokine levels were analysed. Almost 80% of the HTx patients showed an effect to ECP treatment with an increase of Tregs and plasmacytoid DCs (pDCs). The percentage of pDCs before ECP treatment was significantly higher in patients with no ECP effect (26·3% ± 5·6%) compared to patients who showed an effect to ECP (9·8% ± 10·2%; P = 0·011). Analysis of functional subsets of CD4+CD25highCD127low Tregs showed that CD62L‐, CD120b‐ and CD147‐positive Tregs did not differ between the groups. CD39‐positive Tregs increased during ECP treatment compared to HTxC. ECP‐treated patients showed higher levels for T helper type 1 (Th1), Th2 and Th17 cytokines. Cytokine levels were higher in HTx patients with rejection before ECP treatment compared to patients with prophylactic ECP treatment. We recommend a monitoring strategy that includes the quantification and analysis of Tregs, pDCs and the immune balance status before and up to 12 months after starting ECP. 相似文献
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P Dieterlen 《Annales de pédiatrie》1991,38(4):240-243
Ketoacidosis in pediatric diabetes mellitus remains an active problem. Although the authors have recorded no deaths among their own patients, fatal cases still occur in France and other countries, usually as a result of inappropriate therapy, sometimes based on mistaken immediate pathophysiologic interpretations of laboratory test results. A very simple protocol based on the author's extensive experience is proposed. Rehydration solutions (optimal sodium bicarbonate, isotonic saline for the first two hours, then 10% glucose solution with electrolytes infused at a fixed rate of 3 l/m2 body surface area) are given at the same time as insulin (22 units per liter in each infusion flask). This protocol is remarkably effective and gives rise to no complications. In extreme conditions, reagent strip assays of blood glucose levels and evaluation of acidosis by respiratory rate measurements would suffice to ensure appropriate monitoring. A simple method for treating hypoglycemia is also described. 相似文献
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Constantin Schreiber Maja-Theresa Dieterlen Jens Garbade Michael A. Borger Franz Sieg Ricardo Spampinato Monica Dobrovie Anna L. Meyer 《Artificial organs》2022,46(1):106-116
The resolution of functional mitral valve regurgitation (MR) in patients awaiting left ventricular assist device (LVAD) implantation is discussed controversially. The present study analyzed MR and echocardiographic parameters of the third-generation LVAD HeartMate 3 (HM3) over 3 years. Of 135 LVAD patients (with severe MR, n = 33; with none, mild, or moderate MR, n = 102), data of transthoracic echocardiography were included preoperatively to LVAD implantation, up to 1 month postoperatively, and at 1, 2, and 3 years after LVAD implantation. Demographic data and clinical characteristics were collected. Severe MR was reduced immediately after LVAD implantation in all patients. The echocardiographic parameters left ventricular end-diastolic diameter (P < .001), right ventricular end-diastolic diameter (P < .001), tricuspid annular plane systolic excursion (P < .001), and estimated pulmonary artery pressure (P < .001) decreased after HM3 implantation independently from the grade of MR prior to implantation and remained low during the 2 years follow-up period. Following LVAD implantation, right heart failure, ventricular arrhythmias, ischemic stroke as well as pump thrombosis and bleeding events were comparable between the groups. The incidences of death and cardiac death did not differ between the patient groups. Furthermore, the Kaplan-Meier analysis showed that survival was comparable between the groups (P = .073). HM3 implantation decreases preoperative severe MR immediately after LVAD implantation. This effect is long-lasting in most patients and reinforces the LVAD implantation without MR surgery. The complication rates and survival were comparable between patients with and without severe MR. 相似文献
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