Prolongation of Graft Survival in Allogeneic Pancreas and Liver Transplantation by (&amp;ndash;)15-Deoxyspergualin

Thies, Jochen; Walter, P; Zimmermann, Franz; Dickneite, Gerhard; Sedlacek, H.H.; Keller, H; Feifel, G.

doi:10.1159/000128691

Cited by 11 publications

(6 citation statements)

References 6 publications

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“…DSG is an agent with antibacterial, anti-tumor (34)(35)(36) and immunosuppressive properties (37)(38)(39)(40)(41). The compound specifically binds to Hsp70, a heat shock protein, and thus inhibits nuclear localization of NF-kappa b, which is induced by CD40 ligation in APCs, an important early step in T-cell costimulation.…”

Section: -Dsgmentioning

confidence: 99%

Novel immunosuppressants

Krieger

Emre

2004

Pediatric Transplantation

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Advances in maintenance immunosuppression over the past decade has resulted in dramatic improvements in short- and long-term outcomes in organ transplantation as well as a decreased incidence of acute rejection. However, immunosuppressive drugs need to be given long term, lack specificity, and are accompanied by adverse metabolic derangements, toxicities, the risk of infection and cancer, and a myriad of other side effects. Further, they fail to prevent and control chronic rejection. This review will outline a number of immunosuppressive agents that are currently being explored in experimental and clinical transplantation. These include biologic agents that have more specificity and selectivity, and are aimed at T-cell depletion, blockade of costimulation, adhesion markers, or at novel targets. Most of the studies have been limited to adults but should be applied to the pediatric population as well.

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Section: -Dsgmentioning

confidence: 99%

Novel immunosuppressants

Krieger

Emre

2004

Pediatric Transplantation

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“…(_+)-15-deoxyspergualin is a potent immunosuppressive drug to prolong allogeneic graft survival in kidney [30] as well as in pancreas, liver and heart transplantation [29]. In addition, DOS-treatment is known to improve graft survival after allogeneic intraportal islet transplantation [3•].…”

Section: Effect Of ( +_ )-15-deoxyspergualin On Islet Xenograft Rejecmentioning

confidence: 99%

Die Bedeutung der Mikrozirkulation bei der Absto�ung frei transplantierter Langerhans Inseln

Menger

Wolf

Höbel

et al. 1991

Langenbecks Arch Chir

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Transplantation of insulin secreting tissue as a free graft has the potential to become a safe and simple procedure to cure diabetes. However, clinical results, i.e. achievement of insulin independency, are poor, in spite of the use of immunosuppressive regimens, which are regularly successful in whole organ transplantation. In contrast to whole organ grafts, which are revascularized immediately after transplantation, free pancreatic islet grafts require the process of revascularization in order to establish a microvascular network, sufficient for the nutritional blood supply. We have demonstrated for the first time in vivo images of the process of revascularization of free islet xenografts including microvascular phenomena during graft rejection. Rat islet xenografts were isolated by collagenase digestion and transplanted into hamster dorsal skinfold chambers. After 6, 10 and 14 days the microvasculature of the islet grafts was analyzed by means of intravital fluorescence microscopy. Xenogeneic grafts were revascularized during the first 6 days similarly compared to syngeneic grafts; however, on day 10 after transplantation a reduction in size of the microvascular network as well as a decrease in functional capillary density and a reduction in capillary red blood cell velocity were observed, accompanied by microvascular rejection phenomena, such as an increase of microvascular permeability, edema formation, capillary widening and intravascular accumulation of white blood cells (WBCs) with concomitant WBC-endothelium interaction in post-capillary venules. Treatment with 2.5 mg/kg/d (+/-)-15-deoxyspergualin could not completely alleviate these microvascular rejection phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…It is known from animal experiments and human clinical trials that deoxyspergualin prevents rejection of organ allografts (3,6) and more particularly reverses acute rejection episodes (7); thus making this drug potentially very useful for more widespread clinical use in the broad field of transplantation. We examined the effects of deoxyspergualin on cellular cytotoxicity in an attempt to demonstrate the potential pathway inhibited by this powerful immunosuppressive drug.…”

Section: Introductionmentioning

confidence: 99%

Deoxyspergualin inhibits cytotoxic T lymphocytes but not NK or LAK cells

Kerr

Atkins

1991

Immunology & Cell Biology

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Summary Deoxyspergualin (DOSP) is a new immunosuppressive agent whieh probably inhibits various functions of monocytes, B eells and T eells. We examined the effects of deoxyspergualin on eellular cytotoxicity. including eytotoxic T lymphocyte (CTL) mediated killer, natural killer (NK) eell and lymphokineactivaied killer (LAK) cell killing. Deoxyspergualin inhibited eellular cytotoxicity generated by 7 days allo-antigenic challenge: it also inhibited cell killing ifadded on day 6 of this 7 day culture period. The drug did not significantly inhibit NKor LAK cell killing. The inhibitory effects of deoxyspergualin. however, were dependent on the serum used in the culture medium. Normal human serum (NHS) was associated with less inhibition than fetal calfserum (FCS). Finally, interleukin 2 (IL-2) was able to prevent the inhibitory effects of deoxyspergualin on antigen-specific cytotoxieity.

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Prolongation of Graft Survival in Allogeneic Pancreas and Liver Transplantation by (–)15-Deoxyspergualin

Cited by 11 publications

References 6 publications

Novel immunosuppressants

Novel immunosuppressants

Die Bedeutung der Mikrozirkulation bei der Absto�ung frei transplantierter Langerhans Inseln

Deoxyspergualin inhibits cytotoxic T lymphocytes but not NK or LAK cells

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