Different islet protein expression profiles during spontaneous diabetes development vs. allograft rejection in BB-DP rats

Type 1 diabetes (T1D) is characterized by selective autoimmune destruction of the insulin producing β-cells in the islets of Langerhans. When the β-cells are destroyed exogenous administration of insulin is necessary for maintenance of glucose homeostasis. Allogeneic islet transplantation has been used as a means to circumvent the need for insulin administration and has in some cases been able to restore endogenous insulin production for years. However, long life immunosuppression is needed to prevent the graft from being rejected and destroyed. Changes in protein expression pattern during spontaneous diabetes development in the diabetes prone BioBreeding rat (BB-DP) have previously been described. In the present study, we have investigated if any of the changes seen in the protein expression pattern during spontaneous diabetes development are also present during allograft rejection of BB-DP rat islets.

Two hundred neonatal islets were syngeneically transplanted under the kidney capsule of 30 day old BB-DP rats and removed prior to and at onset of diabetes. Allogeneically transplanted islets from BB-DP rats were removed before onset of allograft rejection and at maximal islet graft inflammation (rejection). The protein expression profiles of the transplants were visualised by two-dimensional gel (2-DG) electrophoresis, analysed and compared.

In total, 2590 protein spots were visualised and of these 310 changed expression (p < 0.01) in syngeneic islet transplants in the BB-DP rats from 7 days after transplantation until onset of diabetes. In BB-DP islets transplanted to WK rats 53 protein spots (p < 0.01) showed changes in expression when comparing islet grafts removed 7 days after transplantation with islet grafts removed 12 days after transplantation where mononuclear cell infiltration is at its maximum. Only four protein spots (1%) were significantly changed in both syngeneic (autoimmune) and allogeneic islet destruction. When comparing protein expression changes in syngeneic BB-DP islet transplants from 37 days after transplantation to onset of diabetes with protein expression changes in allografts from day 7 to 12 after transplantation only three spot were found to commonly change expression in both situations.

In conclusion, a large number of protein expression changes were detected in both autoimmune islet destruction and allogeneic islet rejection, only two overlaps were detected, suggesting that autoimmune islet destruction and allogeneic islet rejection may result from different target cell responses to signals induced by the cellular infiltrate. Whether this reflects activation of distinct signalling pathways in islet cells is currently unknown and need to be further investigated.     

Osteopontin gene expression determines spontaneous metastatic performance of orthotopic human breast cancer xenografts

A major problem in the therapeutic management of cancer is the growth of metastases in distant organs, but the genes orchestrating the process need to be identified for the rational design of new treatment. Here, we provide decisive experimental evidence demonstrating the causal involvement of a specific gene, osteopontin (OPN), in the pathogenesis of metastasis by human breast cancer cells and implicating some of its probable partners. Stable long-term depletion, or up-regulation, of OPN gene expression in a matched, isogenic pair of human breast cancer cell lines of differing metastatic proficiency reproducibly changed their ability to colonize distant organs. OPN down-regulation was achieved by transduction of the metastatic line with a DNA construct encoding a small hairpin RNA in a vector labeled with red fluorescent protein and resulted in a marked reduction of metastatic load (P < 0.01). Up-regulation of OPN in the negligibly metastatic line, with a green fluorescent protein-marked retroviral vector containing OPN cDNA driven by a strong promoter, resulted in heavy colonization of the lungs and lymph nodes (P < 0.005). The reciprocal changes in behavior of these matched cell lines cross-corroborate each other. Concomitant changes were seen in the expression of other metastasis-related genes in both modulated lines. The data indicate that therapeutic targeting of tumor OPN molecules could reset metastatically relevant gene networks, resulting in clinical benefit.     

Glucagon infusion alters the hyperpolarized 13C‐urea renal hemodynamic signature

Renal urea handling is central to the urine concentrating mechanism, and as such the ability to image urea transport in the kidney is an important potential imaging biomarker for renal functional assessment. Glucagon levels associated with changes in dietary protein intake have been shown to influence renal urea handling; however, the exact mechanism has still to be fully understood. Here we investigate renal function and osmolite distribution using [¹³C,¹⁵N] urea dynamics and ²³Na distribution before and 60 min after glucagon infusion in six female rats. Glucagon infusion increased the renal [¹³C,¹⁵N] urea mean transit time by 14%, while no change was seen in the sodium distribution, glomerular filtration rate or oxygen consumption. This change is related to the well‐known effect of increased urea excretion associated with glucagon infusion, independent of renal functional effects. This study demonstrates for the first time that hyperpolarized ¹³C‐urea enables monitoring of renal urinary excretion effects in vivo.     

Einfluß der adjuvanten radiotherapie auf das psychische befinden von patientinnen mit einem brusterhaltend operierten mammakarzinom

BACKGROUND: In literature there are only few informations about the influence of postoperative irradiation on the psychological health of breast cancer patients treated by breast-conserving surgery. However, psychological distress and anxiety related to irradiation are often observed. Purpose of our study was the evaluation of the influence of radiotherapy-induced distress in these patients. PATIENTS AND METHODS: Between October 1995 and June 1996 in 48 breast cancer patients (31 to 76 years old) treated by breast-conserving surgery adjuvant irradiation with or without systemic therapy was applied. On the first and the last day of radiotherapy they were given a questionnaire (Table 1) which was designed together with psychologists. Covering different situations related to radiotherapy the construction of items are determined by factors with possible influence on psychological distress and perception with regard to irradiation. RESULTS: Most of the women (92%) stated to be well informed about the irradiation and tried to obtain further information about this treatment (83%). 56% tried not to think about radiotherapy and/or to distract themselves (81%). 40% were anxious about the fact to undergo irradiation. In the end of treatment 77% reported to have been anxious only initially or never; only 19% were anxious almost or most of the time. 35% were worried about the expected cosmetic alterations of their breast; only 30% observed acute cosmetic changes. With regard to situation-related distress all patients (100%) stated that the communication with the medical staff made it easier to stand the irradiation treatment. CONCLUSIONS: In spite of theoretical considerations our results are explorative in character. However, following statements seem to be important: 1. A large requirement exists to get information about radiotherapy. 2. The patients experience irradiation treatment more positive than initially expected by themselves. 3. With regard to radiotherapy anxiety is reduced during the course of treatment. Here the psychosocial care of the medical staff is an important support for reduction of anxiety.     

Petrous carotid artery pseudoaneurysm in bilateral carotid fibromuscular dysplasia: treatment by means of self-expanding covered stent

BACKGROUND: Pseudoaneurysms of the petrous carotid artery may occur in the setting of trauma, dissection, invasive tumors, or as a complication of surgery. These aneurysms may grow and constitute a potential source of thromboembolic complications or rupture. CASE DESCRIPTION: We present a patient with bilateral carotid FMD presenting with a large petrous pseudoaneurysm. Because carotid occlusion was not appropriate, a self-expandable covered stent was implanted. This treatment allowed complete exclusion of the pseudoaneurysm and preservation of the parent artery. CONCLUSION: The accepted treatment of psuedoaneurysms located at petrous ICA is either sacrifice of the carotid artery or exclusion of the aneurysm from the preserved carotid artery. These procedures have specific limitations, and they are technically demanding and associated with a substantial morbidity rate. The endovascular treatment of these lesions is the preferred alternative. Among the various endovascular techniques that have been tested so far, we propose self-expandable covered stents as ideal for treating arterial aneurysms and pseudoaneurysms of the petrous and cavernous carotid segments.     

Modeling placental transport: Correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion

The placental passage of three compounds with different physicochemical properties was recently investigated in ex vivo human placental perfusion experiments (caffeine, benzoic acid, and glyphosate) [Mose, T., Kjaerstad, M.B., Mathiesen, L., Nielsen, J.B., Edelfors, S., Knudsen, L.E., 2008. Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J. Toxicol. Environ. Health, Part A 71, 984–991]. In this work, the transport of these same three compounds, plus the reference compound antipyrine, was investigated using BeWo (b30) cell monolayers. Transport across the BeWo cells was observed in the rank order of caffeine > antipyrine > benzoic acid > glyphosate in terms of both the apparent permeability coefficient and the initial slope, defined as the linear rate of substance transferred to the fetal compartment as percent per time, a parameter used to compare the two experimental models. The results from the in vitro studies were in excellent agreement with the ex vivo results (caffeine ≈ antipyrine > benzoic acid > glyphosate). However the transfer rate was much slower in the BeWo cells compared to the perfusion system. The advantages and limitations of each model are discussed in order to assist in the preparation, prediction, and performance of future studies of maternal–fetal transfer.