a-modified-surgical-model-hind-limb-ischemia-apoe-mice-using

A Modified Surgical Model of Hind Limb Ischemia in ApoE<sup>-/-</sup> Mice using a Miniature Incision

The purpose of this study is to introduce and evaluate a modified surgical approach to induce acute ischemia in mice that can be implemented in most ...

Heidelberg University

Conjugates of fatty acids with ethanolamine, amino acids or monoamine neurotransmitters occur widely in nature giving rise to so-called endocannabinoids. Anandamide and 2-arachidonoyl glycerol are the best characterized endocannabinoids activating both cannabinoid receptors (CB1 and CB2) and transient receptor potential vanilloid type 1 (TRPV1) channels (anandamide) or activating cannabinoid receptors only (2-arachidonoyl glycerol). TRPV1 is also activated by vanilloids, such as capsaicin, and endogenous neurolipins, e.g. N-arachidonoyl dopamine (NADA) and N-oleoyl dopamine (OLDA). Because donor dopamine treatment has shown to improve transplantation outcome in renal and heart recipients, this review will mainly focus on the biological activities of N-acyl dopamine derivates (NADD) as potential non-hemodynamic alternative for implementation in transplantation medicine. Hence the influence of NADD on transplantation relevant entities, i.e. cold inflicted injury, cytoprotection, I/R-injury, immune-modulation and inflammation will be summarized. The cytoprotective properties of endogenous endocannabinoids in this context will be briefly touched upon. 

N-acyl dopamine derivates as lead compound for implementation in transplantation medicine.

N-octanoyl dopamine (NOD) treatment improves renal function when applied to brain dead donors and in the setting of warm ischaemia-induced acute kidney injury (AKI). Because it also activates transient receptor potential vanilloid type 1 (TRPV1) channels, we first assessed if NOD conveys its renoprotective properties in warm ischaemia-induced AKI via TRPV1 and secondly, if renal transplant recipients also benefit from NOD treatment.

N-octanoyl dopamine treatment exerts renoprotective properties in acute kidney injury but not in renal allograft recipients.

Carcinosarcoma of the urinary bladder is a very rare and aggressive subtype of bladder cancer with poor prognosis. Characteristically carcinosarcomas exhibit biphasic nature with both epithelial and mesenchymal differentiation. Limited information is available regarding its clinical features and appropriate treatments due to its rarity. Development of tumour models can further our understanding of bladder carcinosarcoma. We report establishment and characterization of the first-ever bladder carcinosarcoma cell line MaS-3. It is established by the outgrow method from 86 year-old caucasian male who underwent a radical pelvic resection after neoadjuvant radiotherapy. MaS-3 showed carcinosarcoma profile with high conformity with to the original tumour in terms of immunocytochemistry. Proteome analysis also aligned the MaS-3 cell line with the carcinosarcoma specimen rather than corresponding non-malignant tissue. Chemotherapy sensitivity testing revealed a great sensitivity of MaS-3 growth to 5-Fluorouracil, Gemcitabine and Cisplatin, with almost no impact of Irinotecan. Additionally, the suitability of MaS-3 for 3D in vitro experiments was also demonstrated. The newly established cell line MaS-3 shows typical characteristics of the tumour and may thus be a useful in vitro model system for studying the tumour biology and developing future of treatments of this rare but very aggressive entity.

First report on establishment and characterization of a carcinosarcoma tumour cell line model of the bladder.

Methylglyoxal (MGO), a precursor of advanced glycation end products (AGEs), is regarded as a pivotal mediator of vascular damage in patients with diabetes. We have previously reported that MGO induces transcriptional changes compatible with p53 activation in cultured human endothelial cells. To further substantiate this finding and to explore the underlying mechanisms and possible consequences of p53 activation, we aimed (1) to provide direct evidence for p53 activation in MGO-treated human umbilical vein endothelial cells (HUVECs), (2) to assess putative mechanisms by which this occurs, (3) to analyze down-stream effects on mTOR and autophagy pathways, and (4) to assess the potential benefit of carnosine herein. Exposure of HUVECs to 800 µM of MGO for 5 h induced p53 phosphorylation. This was paralleled by an increase in TUNEL and γ-H2AX positive cells, indicative for DNA damage. Compatible with p53 activation, MGO treatment resulted in cell cycle arrest, inhibition of mTORC1 and induction of autophagy. Carnosine co-treatment did not counteract MGO-driven effects. In conclusion, our results demonstrate that MGO elicits DNA damage and p53 activation in HUVECs, resulting in modulation of downstream pathways, e.g. mTORC1.

Prama Pallavi

Department of Surgery,
Medical Faculty Manheim,
European Center of Angioscience ECAS,
Department of Surgery, Medical Faculty Manheim,
European Center of Angioscience ECAS, Medical Faculty Manheim

Heidelberg University

A Modified Surgical Model of Hind Limb Ischemia in ApoE^-/- Mice using a Miniature Incision

Prama Pallavi

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Surgery,Medical Faculty Manheim,European Center of Angioscience ECAS,Department of Surgery, Medical Faculty Manheim,European Center of Angioscience ECAS, Medical Faculty Manheim

Heidelberg University

A Modified Surgical Model of Hind Limb Ischemia in ApoE-/- Mice using a Miniature Incision

Department of Surgery,
Medical Faculty Manheim,
European Center of Angioscience ECAS,
Department of Surgery, Medical Faculty Manheim,
European Center of Angioscience ECAS, Medical Faculty Manheim

A Modified Surgical Model of Hind Limb Ischemia in ApoE^-/- Mice using a Miniature Incision