Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Type of Medium
Language
Year
  • 1
    In: Transplantation, 2000, Vol.69(9), pp.1977-1981
    Description: BACKGROUND.: Prostaglandin E2 (PGE2) is a powerful endogenous immune suppressant and interferes with various T-cell functions. However, it is not known in detail whether immunosuppressive drugs influence the PGE2-driven immune response in transplant patients. Therefore, we investigated the effect of several immunosuppressive compounds, in particular the novel drug mycophenolate mofetil (MMF), on endothelial PGE2 release. METHODS.: Endothelial cells (HUVEC) were activated by either allogeneic CD4 or CD8 T cells, or by the cytokines interleukin-1 or γ-interferon. Using an enzyme-linked immunosorbent assay, we analyzed PGE2 release of the activated HUVEC in the presence of MMF, cyclosporine, or tacrolimus. As verapamil and mibefradil also possess immunosuppressive properties, they were included in the study as well. RESULTS.: Activation of HUVEC with interleukin-1 or T cells resulted in a drastic accumulation of PGE2 in the supernatant. Cyclosporine or tacrolimus had no effect on PGE2 release. However, Ca channel blockers, when applied at higher dosages, caused a significant increase in PGE2. Interestingly, MMF strongly diminished the PGE2 level in the cell culture supernatant in a concentration-dependent manner. CONCLUSION.: The results demonstrate an inhibitory effect of MMF on PGE2 production, which may lower the benefits of the PGE2-triggered immune response after organ transplantation.
    Keywords: Endothelium ; Cytokines ; Lymphocytes T ; Immunosuppression ; Transplantation ; Interleukin 1 ; ^G-Interferon ; Prostaglandin E2 ; Mycophenolate Mofetil ; Clinical ; Man ; Immunology ; Gamma -Interferon ; Immunology ; Man ; Mycophenolate Mofetil ; Prostaglandin E2;
    ISSN: 0041-1337
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: LaboratoriumsMedizin / Journal of Laboratory Medicine, Sept 1, 2011, Vol.35(5), p.309(2)
    ISSN: 0342-3026
    E-ISSN: 14390477
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Clinica Chimica Acta, 08 September 2012, Vol.413(17-18), pp.1338-1349
    Description: The individualization of immunosuppression is an approach for preventing rejection in the early phase after transplantation and for avoiding the long-term side effects of over immunosuppression. Pharmacodynamic markers, either specific or nonspecific, have been proposed as complementary tools to drug monitoring of immunosuppressive drugs. A key event in graft rejection is the activation and proliferation of the recipient's lymphocytes, particularly T cells. Activated T cells express surface receptors, such as CD25 (the IL-2 receptor) and CD71 (the transferrin receptor), or co-stimulatory molecules (CD26, CD27, CD28, CD30, CD154 or CD40L, and CD134). Both surface marker expression and cell proliferation are predominately assessed by flow cytometry. Protocols have been established and utilized for both and investigations with either isolated lymphocytes or whole blood. This article reviews the current body of research regarding the use of lymphocyte proliferation and surface activation markers with an emphasis on T cells. Experimental and clinical results related to these markers, as well as methodological issues and open questions, are addressed. ► T cell activation leads to cell surface marker expression and cell proliferation. ► The innate immune system enhances the adaptive alloimmune response. ► Surface marker expression and cell proliferation can be assessed by flow cytometry. ► Immunosuppression affects cell surface marker expression and cell proliferation. ► Surface markers and cell proliferation have a potential to guide immunosuppression.
    Keywords: T Cell Activation ; Cell Proliferation ; Immunosuppressants ; Pharmacodynamics ; Mitogen Stimulation ; Transplantation ; Medicine ; Chemistry
    ISSN: 0009-8981
    E-ISSN: 1873-3492
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Clinical chemistry, May 2011, Vol.57(5), pp.670-3
    Description: A 9-year-old girl was admitted to our hospital with juvenile metachromatic leukodystrophy (arylsulfatase A deficiency). Symptoms of this lysosomal storage disease, such as decreased school performance and compromised motor skills, had started 1 year earlier. She underwent bone marrow transplantation from a matched unrelated donor after receiving conditioning with fludarabine, treosulfan, and thiotepa, together with thymoglobulin, a rabbit antithymocyte globulin. Conditioning was well tolerated, and the posttransplantation period was uneventful except for 1 febrile episode. Graft-vs-host disease (GvHD)4 prophylaxis consisted of 3 methotrexate doses in combination with a starting daily cyclosporin A (CsA) dosage of 3 mg · kg−1 · day−1. Trough CsA concentrations were monitored with the antibody-conjugated magnetic immunoassay (ACMIA) for CsA (RxL Dimension; Siemens). CsA concentrations entered the therapeutic interval after 3 days, and the dosage was adjusted to achieve trough concentrations of 120–150 μg/L (Fig. 1). The patient received CsA for 16 weeks. During this period, the CsA concentration was measured 31 times, with results from 98 μg/L to 219 μg/L (mean, 156 μg/L). Four weeks after transplantation, the patient developed a mild GvHD of the skin, which disappeared immediately after commencement of prednisolone treatment. Because B lymphocytes were absent or low early after transplantation, the patient received immunoglobulins for 5 months (Fig. 1). Endogenous immunoglobulin production started only in the later phase of immune reconstitution. Six weeks after discontinuation of CsA therapy, a concentration of 147 μg/L was still detected in whole blood. Although the patient was not supposed to have received CsA and the parents had denied the administration of CsA or drugs other than those prescribed, CsA concentrations between 116 μg/L and 174 μg/L were obtained over the next 4 months. Fig. 1. Time courses of the whole-blood CsA concentration measured with the ACMIA CsA assay, the administered daily CsA dose, and the B-lymphocyte count. ### QUESTIONS TO CONSIDER 1. Has the CsA therapy really been discontinued? 2. Can delayed drug elimination explain the continued increased CsA concentrations? 3. What …
    Keywords: Antibodies, Heterophile -- Blood ; Cyclosporine -- Blood ; Immunosuppressive Agents -- Blood ; Leukodystrophy, Metachromatic -- Therapy
    ISSN: 00099147
    E-ISSN: 1530-8561
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Clinical Biochemistry, September 2016, Vol.49(13-14), pp.1009-1023
    Description: Therapeutic Drug monitoring (TDM) is a multidisciplinary endeavor encompassing skills of the laboratory, clinical pharmacologists and physicians aimed at providing the best possible patient care via the individualization of drug therapy. The expanding role of liquid chromatography - tandem mass spectrometry (LC–MS/MS) in TDM is based on dramatic improvements in analytical instrumentation, thereby enabling unique specificity, extreme sensitivity, high throughput, the simultaneous analysis of multiple drugs and metabolites in a drop of blood within several minutes and the use of multiplexed platforms for the rapid determination of single analytes. However, analysis by LC–MS/MS does not automatically ensure reliable results and superiority over other assays. The aim of this article is to provide an overview of the current use, advantages, and challenges of LC–MS/MS methods in TDM services, to summarize ongoing issues, and to provide an outlook on new perspectives.
    Keywords: Therapeutic Drug Monitoring ; Immunosuppresants ; Antiepileptics ; Antimicrobials ; Antifungals ; Antiviral Drugs ; Cardioactive Drugs ; Antipsychotics ; Anticancer Drugs ; Method Standardization ; Medicine ; Chemistry
    ISSN: 0009-9120
    E-ISSN: 1873-2933
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Clinical Biochemistry, March 2016, Vol.49(4-5), pp.317-319
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.clinbiochem.2016.01.005 Byline: Maria Shipkova, Eberhard Wieland Abstract: Solid organ transplantation is inevitably associated with the activation of the immune system of the graft recipient. An advanced knowledge of the immunological mechanisms leading to acute and chronic rejection, the advent of powerful immunosuppressive drugs, and refined surgical techniques have made solid organ transplantation a standard therapy to replace irretrievable loss of vital functions. The immune system is a complex network involving immune cells, cytokines, chemokines, antibodies, and the complement system. Monitoring and ideally influencing the allo-response of the organ recipient against the donor antigens may help to personalize the immunosuppressive therapy including the disclosure of those patients who are suitable for weaning or even discontinuation of immunosuppression. Immune monitoring comprises as plethora of candidate biomarkers capable of reflecting the donor specific and non-donor specific net activation state of the immune system in transplant recipients both before and after initiation of the immunosuppressive therapy. This special issue of Clinical Biochemistry on Immune Monitoring addresses the basic effects of immune activation in solid organ transplantation and critically reviews candidate biomarkers for immune monitoring and their analytical as well as clinical performance. Article History: Received 1 January 2016; Accepted 4 January 2016
    Keywords: Biomarker ; Immune Activation ; Immune Tolerance ; Pharmacodynamics ; Medicine ; Chemistry
    ISSN: 0009-9120
    E-ISSN: 1873-2933
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Trends in Analytical Chemistry, November 2016, Vol.84, pp.23-33
    Description: Currently therapeutic drug monitoring (TDM) of immunosuppressive drugs is one of the best established fields of application of TDM as a tool dedicated to therapy guidance and patient care improvement. LC-MS/MS techniques were introduced to this field about 20 years ago, and enabled a huge progress towards providing more adequate overall quality and turnaround time for TDM services. However, numerous LC-MS/MS difficulties have also been recognized and approaches to deal with them have been developed. Moreover, some further issues must be resolved to realize the full potential of this technique. This article aims to provide an update of the LC-MS/MS literature with a focus on new developments and applications that have been reported during the last five years. In addition, it summarizes important lessons and defines current needs in the context of TDM services, which must be addressed in the near future.
    Keywords: Immunosuppressants ; Therapeutic Drug Monitoring ; Transplantation ; Ciclosporin ; Tacrolimus ; Everolimus ; Sirolimus ; Mycophenolic Acid ; Thiopurines ; Pharmacokinetic ; Chemistry
    ISSN: 0165-9936
    E-ISSN: 1879-3142
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Clinical chemistry, February 2006, Vol.52(2), pp.240-7
    Description: Inosine triphosphate (ITP) pyrophosphohydrolase (ITPA) catalyzes the pyrophosphohydrolysis of ITP/dITP and xanthosine triphosphate to prevent incorporation of unusual nucleotides into RNA and DNA. Important mutations leading to enzyme deficiency are 94C〉A and IVS2 + 21A〉C. An association between ITPA 94C〉A and adverse reactions during azathioprine treatment has been shown. To investigate the ITPA phenotype, an HPLC procedure was developed and phenotype-genotype correlations were assessed. The enzymatic conversion of ITP to inosine monophosphate (IMP) was terminated by perchloric acid and saturated dipotassium hydrogen phosphate. We quantified the IMP at 262 nm after separation on an Aqua perfect C18 column using 20 mmol/L phosphate buffer, pH 2.5. We also genotyped samples for ITPA 94C〉A and IVS2 + 21A〉C by real-time fluorescence PCR. The assay was linear to 3 mmol/L IMP [approximately 500 micromol/(g Hb x h)] with a lower limit of quantification of 4 micromol/L [approximately 0.5 micromol/(g Hb x h)]. With IMP-enriched samples, within- and between-day imprecision was A) and 0.131 (IVS2 + 21A〉C). When we used a cutoff of 125 micromol IMP/(g Hb x h), phenotyping detected all 94C〉A mutant cases, all 94C〉A and IVS2 + 21A〉C compound heterozygotes, all IVS2 + 21A〉C homozygotes, and 6 of 24 IVS2 + 21A〉C heterozygote-only cases. A novel IVS2 + 68T〉C mutation was also found. The HPLC procedure provides an excellent ITPA phenotype-genotype correlation and led to the discovery of a novel IVS2 + 68T〉C mutation. The method could facilitate investigation of the role of ITPA activity for drug toxicity during thiopurine therapy.
    Keywords: Erythrocytes -- Enzymology ; Pyrophosphatases -- Genetics
    ISSN: 0009-9147
    E-ISSN: 15308561
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Clinical chemistry, February 2004, Vol.50(2), pp.438-41
    Description: Determination of thiopurine S -methyltransferase (TPMT; EC 2.1.1.67) activity is intended to screen patients before therapy with thiopurine drugs (6-mercaptopurine, 6-thioguanine, and azathioprine) to rule out a deficiency in this enzyme. The enzyme catalyzes the S-methylation of these medicinal agents, a metabolic pathway that competes with the formation of pharmacologically active 6-thioguanine nucleotides (6-TGNs), thereby modulating their therapeutic and toxic effects (1)(2). Individuals with low TPMT activity are known to be at high risk for severe thiopurine-induced myelodepression. In addition to a genetic polymorphism of TPMT alleles, which is responsible for the wide interindividual differences in TPMT activity, cotherapy with various drugs, including aminosalicylates, has been shown to influence enzyme activity (1)(2). In vitro kinetic studies with recombinant human TPMT demonstrated that sulfasalazine, 5-aminosalicylic acid, balsalazide, and olsalazine (3)(4)(5) inhibit the enzyme activity in a noncompetitive manner. Therefore, simultaneous therapy with both thiopurines and aminosalicylates was postulated to create a “phenocopy” of individuals with a low TPMT activity genotype (1). In line with this hypothesis, Lewis et al. (3) described a case of a patient with Crohn disease and TPMT activity in the low normal range who had severe bone marrow dysfunction while receiving treatment with 6-mercaptopurine and olsalazine. The authors speculated that the TPMT activity determined ex vivo represented the patient’s baseline TPMT activity in vivo because the inhibitory effect of olsalazine would be removed by dilution in the assay. Subsequently, several groups (6)(7)(8) investigated this drug–drug interaction in clinical studies with more cases. As indicators of an inhibitory effect, ex vivo determination of erythrocyte TPMT activity and erythrocyte 6-TGNs were chosen. No changes in TPMT activity, but significantly increased 6-TGN concentrations, were observed under combined thiopurine/aminosalicylate therapy (6)(8). Whereas Lowry et al. (6) speculated …
    Keywords: Erythrocytes -- Enzymology ; Methyltransferases -- Antagonists & Inhibitors ; Sulfasalazine -- Adverse Effects
    ISSN: 0009-9147
    E-ISSN: 15308561
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Clinical chemistry, February 2003, Vol.49(2), pp.260-8
    Description: Measurement of 6-thioguanine nucleotide (6-TGN) concentrations in erythrocytes is widely accepted for use in optimization of thiopurine therapy. Various chromatographic methods have been developed for this purpose. In preliminary experiments we observed a considerable difference between 6-TGN concentrations... We analyzed 6-TGNs in erythrocyte preparations (n = 50) from patients on azathioprine therapy by both methods, using the original protocols. In one set of experiments, we replaced the 0.5 mol/L sulfuric acid in the Lennard method with the 1 mol/L perchloric acid used by Dervieux and Boulieu. In a second... Direct comparison of both methods showed that 6-TGN concentrations were, on average, 2.6-fold higher in the Dervieux-Boulieu method over the concentration range tested, although the correlation (r = 0.99; P 〈0.001) was good. Replacement of sulfuric acid by perchloric acid reduced this difference to approximately... The difference between 6-TGN concentrations measured by the two methods is attributable, at least in part, to differences in the extent of nucleotide hydrolysis. For optimization of thiopurine therapy, method-dependent therapeutic ranges are necessary, which precludes comparison of results from clinical...
    Keywords: Antimetabolites, Antineoplastic -- Blood ; Erythrocytes -- Chemistry ; Guanine Nucleotides -- Blood ; Immunosuppressive Agents -- Blood ; Thionucleotides -- Blood
    ISSN: 0009-9147
    E-ISSN: 15308561
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages