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Andreas Boldt

Publications and source records attributed to Andreas Boldt.

7 recordsLinked to original sources
PubMed2006

Pharmacodynamic monitoring of the immunosuppressive therapy in patients after heart transplantation: whole blood flow cytometric analysis of lymphocyte function.

Despite therapeutic monitoring and daily measurements of blood concentrations (pharmacokinetics) of immunosuppressive medications, immunosuppressive therapy remains still a challenge after heart transplantation (HTx) due to drug interactions, toxicities and individual responses to drug effects. We established whole blood flow cytometric assays of lymphocyte function to assess the pharmacodynamics of immunosuppressive therapy and investigated both pharmacokinetic and pharmacodynamic approaches after HTx. Our results showed that pharmacodynamic measurements provide a more direct assessment of the functional activity of immunosuppressants on immune cells compared to drug level monitoring alone. The information from both pharmacokinetic and pharmacodynamic monitoring has the potential to increase the efficacy and safety of individual immunosuppressive therapy after HTx.

Aged↗
PubMed2006

The influence of immunosuppressive drugs on T- and B-cell apoptosis via p53-mediated pathway in vitro and in vivo.

BACKGROUND: This study was designed to assess the effects of calcineurin and inosine-5-monophosphate-dehydrogenase inhibitors on p53-mediated-apoptosis in T- and B-cells in vitro and in human heart-transplanted recipients (HTx-R). METHODS: For in vitro experiments, peripheral blood from healthy volunteers was collected and treated either with 1 microM cyclosporin A (CsA; n = 6), 10 microM mycophenolic acid (MPA; n = 6) or 100 nM tacrolimus (TRL; n = 6). For the second part, peripheral blood was collected from HTx-R undergoing CsA-MPA (n = 11) or TRL-MPA (n = 11) therapy before (0 hr) and after (2 hr) acute drug application and from healthy volunteers (n = 11) without drug therapy. Whole blood (part 1+2) was stimulated (24 hr) with eight different concentrations of actinomycin-D (0-800 nM), an apoptosis inductor acting via p53-pathway. Apoptotic lymphocytes were measured by TUNEL and expression of Annexin-V using FACS. Drug effects were calculated by taking the effects of actinomycin-D as baseline values. RESULTS: In vitro drug treatment with CsA, MPA, and TRL significantly (P < 0.05) decreased the apoptotic effect of actinomycin-D in T-cells in a noncompetitive manner. In HTx-R undergoing drug therapy, there was a similar antiapoptotic effect observed in both T- and B-cells (P < 0.05). Differences between 0 hr and 2 hr after acute drug application did not exist. Apoptosis induced by actinomycin-D can be completely blocked by caspase-inhibitor zVAD-FMK. CONCLUSION: Our results suggest that, in vitro and in HTx-R, an inhibition of calcineurin and inosine-5-monophosphate-dehydrogenase by CsA, TRL, or MPA lead to an inhibition of T-and B-cell apoptosis via p53-pathway. This assay may be helpful to provide insights into mechanisms of immunosuppressive drugs in regulation of apoptosis in lymphocytes.

Apoptosis↗
PubMed2006

Cytokine analysis to predict immunosuppression.

BACKGROUND: Recently, it has been realized that TH1/TH2 cytokine production offer the unique possibility to predict drug efficacy. However, there is still an incessant need to explore assay conditions and techniques of analyzing cytokines, which are specific and reliable for monitoring drug efficacy. METHODS: In this study we used the multiplex bead array technique to detect cytokines of TH1/TH2 cells in whole blood of heart transplanted (HTx) recipients. RESULTS: We found significantly different levels of cytokine expression in HTx recipients compared with cytokine levels in patients prior to HTx. Furthermore, particular cytokine levels were significantly decreased 2 h after drug dosing, compared with cytokine levels before dosing in mitogen-stimulated whole blood. CONCLUSIONS: Cytokine analysis with the multiplex array technique in mitogen-stimulated whole blood provides the possibility to predict immunosuppression.

Cyclosporine↗
PubMed2006

Novel apoptosis assay to analyze immunosuppression.

BACKGROUND: We developed a novel whole blood assay to assess the effects of immunosuppressants on lymphocyte apoptosis. METHODS: Peripheral blood for six experiments for each drug was treated either with cyclosporin A (CsA), mycophenolate acid (MPA), tacrolimus (TRL) or rapamycin (RAPA). Whole blood was stimulated with different concentrations of staurosporine (0-5 microM) for 24 h. Using FACS, apoptosis were measured by Annexin V expression (%cells +/- SEM). RESULTS: MPA, RAPA, TRL, but not CsA, increased (P < 0.05) apoptotic cells (MPA:20.9 +/- 3.7; RAPA:17.5 +/- 3.3; TRL:16.4 +/- 2.9 vs. control:15.2 +/- 2.8). CONCLUSION: This new whole blood assay exhibited that MPA has a stronger effect on apoptosis than RAPA and TRL, whereas CsA had no effect.

Annexin A5↗
PubMed2003

Expression of angiotensin II receptors in human left and right atrial tissue in atrial fibrillation with and without underlying mitral valve disease.

UNLABELLED: TIVES: We postulated a change of angiotensin II receptor subtype expression in patients with lone atrial fibrillation (AF) and AF with underlying mitral valve disease (MVD) both compared with sinus rhythm (SR). BACKGROUND: Atrial fibrillation is a progressive disease associated with electrical and structural remodeling. Angiotensin II (ANGII) is involved in the process of myocardial remodeling. Actions of ANGII are mediated by ANGII receptor subtypes 1 and 2 (AT(1) and AT(2)). METHODS: Left atrial (LA) and right atrial (RA) tissue samples were obtained from patients with AF or SR with or without underlying MVD. The AT(1) and AT(2) protein levels were measured by quantitative Western blotting techniques. RESULTS: The AT(1) protein level in the LA was significantly increased in patients with AF (all forms) compared with SR (p < 0.05), whereas AT(2) expression was not significantly altered. Comparison of the subgroups revealed a similar increase of AT(1) in both paroxysmal AF and chronic AF with or without MVD. Additionally, investigations of ANGII receptor subtypes in the RA did not exhibit any significant changes either in AT(1) or in AT(2) in patients with AF versus SR. Underlying MVD did not significantly affect AT(2) receptor subtype expression in LA. CONCLUSIONS: Atrial fibrillation is associated with an up-regulation of AT(1) in LA, but not in RA, and did not appear to influence the AT(2) expression in the atrium. Because we found an enhanced expression of AT(1)in the LA, we conclude that AT(1) might be involved in the pathogenesis of AF in the LA.

Adult↗