@phdthesis{Rikkala2015, author = {Rikkala, Prashanth Reddy}, title = {Regulation of the Na+-D-glucose cotransporter SGLT1 in the small intestine in response to bariatric surgery and peptides derived from protein RS1 (RSC1A1)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130608}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Bariatric surgery represents the first-line treatment for morbid obesity, resulting in weight loss and improved diabetes control. The positive effect of bariatric surgery on type-2 diabetes is unclear. Increased secretion of insulin regulating enterohormone glucagon-like-peptide 1 (GLP-1) has been observed in rats with experimental type 2-like diabetes following duodenal-jejunal bypass (DJB) and ileal transposition (IT). Sodium dependent glucose co-transporter (SGLT1) is involved in the secretion of GLP-1 that in turn regulates insulin secretion. In the present study, an attempt was made to elucidate the impact of DJB and IT on SGLT1 mediated glucose transport. Transport measurements using phlorizin inhibited uptake of SGLT1-specific glucose analogue [14C] α-Methyl-D-glucopyranoside (AMG) were performed to determine the changes in SGLT1 transport upon these surgical procedures. The data indicated that DJB decreased SGLT1-mediated glucose absorption in the small intestine which contributes to the body-weight independent improvement of type 2 diabetes. However, IT did not change the SGLT1-mediated glucose transport. Immunohistochemical analysis revealed that in IT, the transposed ileum showed increased diameter, increased villi length and increased number of GLP-1 secreting L-cells. The weight-independent improvement in glycemic control after IT is not related to SGLT1-mediated glucose absorption but may be linked to increased GLP-1 secretion. Along with this, the study also focused on the regulation of SGLT1 by several RS1 derived tripeptides in mouse and human intestinal tissues (ex vivo). Phlorizin inhibited uptake of AMG was measured without and with tripeptides. QEP and thiophosphorylated QSP down-regulated SGLT1 activity in small intestine in a concentration-dependent manner. Among the tested tripeptides, QEP showed higher activity and further analysis in various species demonstrated its universal role in SGLT1 regulation. The data thus indicates that RS1 derived tripeptides QEP and thiophosphorylated QSP may be employed for the treatment of type 2 diabetes.}, subject = {Glucosetransportproteine}, language = {en} } @article{WiegeringKorbThalheimeretal.2014, author = {Wiegering, Armin and Korb, Doreen and Thalheimer, Andreas and K{\"a}mmerer, Ulrike and Allmanritter, Jan and Matthes, Niels and Linnebacher, Michael and Schlegel, Nicolas and Klein, Ingo and Erg{\"u}n, S{\"u}leyman and Germer, Christoph-Thomas and Otto, Christoph}, title = {E7080 (Lenvatinib), a Multi-Targeted Tyrosine Kinase Inhibitor, Demonstrates Antitumor Activities Against Colorectal Cancer Xenografts}, doi = {10.1016/j.neo.2014.09.008}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111165}, year = {2014}, abstract = {Clinical prognosis of metastasized colorectal carcinoma (CRC) is still not at desired levels and novel drugs are needed. Here, we focused on the multi-tyrosine kinase inhibitor E7080 (Lenvatinib) and assessed its therapeutic efficacy against human CRC cell lines in vitro and human CRC xenografts in vivo. The effect of E7080 on cell viability was examined on 10 humanCRCcell lines and humanendothelial cells (HUVEC). The inhibitory effect of E7080 on VEGF-induced angiogenesis was studied in an ex vivo mouse aortic ring angiogenesis assay. In addition, the efficacy of E7080 against xenografts derived fromCRC cell lines and CRC patient resection specimenswithmutated KRASwas investigated in vivo. Arelatively low cytotoxic effect of E7080 on CRC cell viabilitywas observed in vitro. Endothelial cells (HUVEC)weremore susceptible to the incubation with E7080. This is in line with the observation that E7080 demonstrated an anti-angiogenic effect in a three-dimensional ex vivo mouse aortic ring angiogenesis assay. E7080 effectively disrupted CRC cell-mediated VEGF-stimulated growth of HUVEC in vitro. Daily in vivo treatment with E7080 (5 mg/kg) significantly delayed the growth of KRAS mutated CRC xenografts with decreased density of tumor-associated vessel formations and without tumor regression. This observation is in line with results that E7080 did not significantly reduce the number of Ki67-positive cells in CRC xenografts. The results suggest antiangiogenic activity of E7080 at a dosage thatwas well tolerated by nudemice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS.}, language = {en} } @article{KrzymanskiWaagaUlrichsetal.1991, author = {Krzymanski, Maciej and Waaga, Ana M. and Ulrichs, Karin and Deja, Aadam and Oko, Andrzej and Rommel, Thomas and M{\"u}ller-Ruchholtz, Wolfgang}, title = {The influence of MHC class II antigen blockade by perfusion with a monoclonal antibody on rat renal graft survival}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64431}, year = {1991}, abstract = {To decrease immunogenicity of the rat kidney, grafts were perfused with an anti-MHC class li monoclonal antibody (mAb ). How effectively this procedure blocked dass li-positive cells, which were mainly dendritic in appearance, was checked by immunostaining renal sections after perfusion and comparing them with in vitro stained sections. Optimum conditions were applied for graft pretreatment before transplantation. This procedure prolonged graft survival, though not satisfactorily from the biological point ofview (9.6 ± 0.8 versus 7.7 ± 0.5 days in the control group; P < 0.02). The dendritic cells were not killed but blocked. Several hours after transplantation, the mAb dissociated from these dass li-positive cells. It was also shown that donor cells migrate into the recipient's spieen early after transplantation. The number of these cells was smaller when the transplanted organ was perfused with the mAb. Further studies are suggested to deplete the graft of donor dendritic cells more adequately. They should also combine graft perfusion with antidass II mAb and recipient immunosuppression at reduced doses.}, subject = {Chirurgie}, language = {en} } @article{UlrichsWinotoMorbachHeringetal.1990, author = {Ulrichs, Karin and Winoto-Morbach, S. and Hering, B. and M{\"u}ller-Ruchholtz, W.}, title = {A Useful Biotechnological Approach to Solve the Problem of Graft Purity in Human Pancreatic Islet Transplantation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45619}, year = {1990}, abstract = {No abstract available}, subject = {Chirurgie}, language = {en} } @article{UlrichsMuellerRuchholtz1985, author = {Ulrichs, Karin and M{\"u}ller-Ruchholtz, W.}, title = {Further Analyses of Pancreas Islet Immunogenicity, a Major Barrier to Successful Islet Transplantation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45563}, year = {1985}, abstract = {No abstract available}, subject = {Chirurgie}, language = {en} } @article{UlrichsMuellerRuchholtz1988, author = {Ulrichs, Karin and M{\"u}ller-Ruchholtz, W.}, title = {Expression of MHC Structures on Immunologically Reactive and Non Reactive Cells in Islets of Langerhans and Other Tissues}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45557}, year = {1988}, abstract = {No abstract available}, subject = {Chirurgie}, language = {en} } @article{WaagaUlrichsKrzymanskietal.1990, author = {Waaga, AM and Ulrichs, Karin and Krzymanski, M. and Treumer, J. and Hansmann, ML and Rommel, T. and M{\"u}ller-Ruchholz, W.}, title = {The immunosuppressive agent 15-deoxyspergualin induces tolerance and modulates MHC-antigen expression and interleukin-1 production in the early phase of rat allograft responses}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45253}, year = {1990}, abstract = {No abstract available}, subject = {Chirurgie}, language = {en} } @article{UlrichsEcksteinMuellerBuchholtz1994, author = {Ulrichs, Karin and Eckstein, V. and M{\"u}ller-Buchholtz, W.}, title = {Xenogeneic T-cell-mediated immune reactivity in the model of pig-to-humans: first findings with native stimulator cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-44755}, year = {1994}, abstract = {No abstract available}, subject = {Chirurgie}, language = {en} } @article{UlrichsBosseWackeretal.1994, author = {Ulrichs, Karin and Bosse, M. and Wacker, HH and Heiser, A. and M{\"u}ller-Ruchholtz, W.}, title = {Histologic analysis of the porcine pancreas to improve islet yield and integrity after collagenase digestion}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45166}, year = {1994}, abstract = {No abstract available}, subject = {Chirurgie}, language = {en} } @article{HeiserUlrichsMuellerRuchholtz1994, author = {Heiser, A. and Ulrichs, Karin and M{\"u}ller-Ruchholtz, W.}, title = {Influence of porcine strain, age, and pH of the isolation medium on porcine pancreatic islet isolation success}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45171}, year = {1994}, abstract = {No abstract available}, subject = {Chirurgie}, language = {en} }