Suramin induces and enhances apoptosis in a model of hyperoxia-induced oligodendrocyte injury

Recent evidence suggests oxygen as a powerful trigger for cell death in the immature white matter, leading to periventricular leukomalacia (PVL) as a cause of adverse neurological outcome in survivors of preterm birth. This oligodendrocyte (OL) death is associated with oxidative stress, upregulation of apoptotic signaling factors (i.e., Fas, caspase-3) and decreased amounts of neurotrophins. In search of neuroprotective strategies we investigated whether the polysulfonated urea derivative suramin, recently identified as a potent inhibitor of Fas signaling, affords neuroprotection in an in vitro model of hyperoxia-induced injury to immature oligodendrocytes. Immature OLs (OLN-93) were subjected to 80% hyperoxia (48 h) in the presence or absence of suramin (0, 30, 60, 120 microM). Cell death was assessed by flow cytometry (Annexin V, caspase-3 activity assay) and immunohistochemistry for activated caspase-3. Immunoblotting for the death receptor Fas, cleaved caspase-8 and the phosphorylated isoform of the serine-threonin kinase Akt (pAkt) was performed. Suramin lead to OL apoptosis and potentiated hyperoxia-induced injury in a dose-dependent manner. Immunoblotting revealed increased Fas and caspase-8 expression by suramin treatment. This effect was significantly enhanced when suramin was combined with hyperoxia. Furthermore, pAkt levels decreased following suramin exposure, indicating interference with neurotrophin-dependent growth factor signaling. These data indicate that suramin causes apoptotic cell death and aggravates hyperoxia-induced cell death in immature OLs. Its mechanism of action includes an increase of previously described hyperoxia-induced expression of pro-apoptotic factors and deprivation of growth factor dependent signaling components.     

Innovative Power of Health Care Organisations Affects IT Adoption: A bi-National Health IT Benchmark Comparing Austria and Germany

Multinational health IT benchmarks foster cross-country learning and have been employed at various levels, e.g. OECD and Nordic countries. A bi-national benchmark study conducted in 2007 revealed a significantly higher adoption of health IT in Austria compared to Germany, two countries with comparable healthcare systems. We now investigated whether these differences still persisted. We further studied whether these differences were associated with hospital intrinsic factors, i.e. the innovative power of the organisation and hospital demographics. We thus performed a survey to measure the “perceived IT availability” and the “innovative power of the hospital” of 464 German and 70 Austrian hospitals. The survey was based on a questionnaire with 52 items and was given to the directors of nursing in 2013/2014. Our findings confirmed a significantly greater IT availability in Austria than in Germany. This was visible in the aggregated IT adoption composite score “IT function” as well as in the IT adoption for the individual functions “nursing documentation” (OR?=?5.98), “intensive care unit (ICU) documentation” (OR?=?2.49), “medication administration documentation” (OR?=?2.48), “electronic archive” (OR?=?2.27) and “medication” (OR?=?2.16). “Innovative power” was the strongest factor to explain the variance of the composite score “IT function”. It was effective in hospitals of both countries but significantly more effective in Austria than in Germany. “Hospital size” and “hospital system affiliation” were also significantly associated with the composite score “IT function”, but they did not differ between the countries. These findings can be partly associated with the national characteristics. Indicators point to a more favourable financial situation in Austrian hospitals; we thus argue that Austrian hospitals may possess a larger degree of financial freedom to be innovative and to act accordingly. This study is the first to empirically demonstrate the effect of “innovative power” in hospitals on health IT adoption in a bi-national health IT benchmark. We recommend directly including the financial situation into future regression models. On a political level, measures to stimulate the “innovative power” of hospitals should be considered to increase the digitalisation of healthcare.     

Adrenal angiosarcoma: report of a case

Adrenal epithelioid angiosarcoma is an extremely rare tumor. Even if such tumors are very aggressive, a long survival may occasionally be observed after an adrenal ectomy. A 70-year-old woman suffering from persistent right flank pain showed a 5-cm right adrenal mass plus a 2-cm liver mass at the radiologic workup, and both were suspected of being malignant. No adrenal hypersecretion was demonstrated. During an explorative median laparotomy the right adrenal gland with the whole periadrenal tissue and locoregional lymph nodes was removed. A histological examination revealed an adrenal angiosarcoma. The resection margin was tumor-free with no lymph node infiltration. The liver mass turned out to be a cistobiliary adenoma. Since no distant metastases were observed, no adjuvant chemotherapy was performed. After an 18-month follow-up the patient is still well with no sign of a relapse. When this rare adrenal tumor is encountered and curative treatment is attempted initially extensive surgical procedures are essential. Received: April 16, 2001 / Accepted: November 20, 2001     

Improvement of the cold storage of blood vessels with a vascular preservation solution. Study in porcine aortic segments

BACKGROUND: Cold-induced injury to various cell types has been shown to be mediated predominantly by chelatable iron. For endothelial cells, this type of injury has so far only been shown in cultured cells. Hypothesizing that this iron-dependent cold-induced injury might also occur in the endothelium of intact vessels, we here set out to optimize the hypothermic storage of blood vessels. METHODS: Segments of porcine aorta were stored for 2 to 21 days in histidine-tryptophan-ketoglutarate (HTK) solution or in modified solutions with or without the iron chelators deferoxamine or LK 614 at 4 degrees C. Parts of the segments were assayed immediately after cold storage, the other parts after subsequent rewarming. The percentage of dead (propidium iodide-positive) endothelial cells was assessed by "intravital" fluorescence microscopy, mitochondrial membrane potential was assessed by laser scanning microscopy after staining with tetramethylrhodamine methyl ester (TMRM) and thrombocyte adhesion was studied using 5-(and -6)-carboxy SNARF-1-stained thrombocytes. RESULTS: The endothelium of porcine aortic segments sustained moderate injury during the cold incubation itself, but major injury during rewarming. The addition of the iron chelator deferoxamine (1 mmol/L) significantly inhibited cold-induced endothelial cell injury irrespective of the solution used for cold storage (eg, 14 days of cold storage + 3 hours rewarming: HTK 66 +/- 7%, HTK + 1 mmol/L deferoxamine 40 +/- 10% propidium iodide-positive endothelial cells). An amino acid (glycine, alanine, aspartate)-containing base solution with N-acetylhistidine as buffer was optimized. The optimized base solution with pH 7.0 and potassium and chloride as main ions yielded a further decrease of endothelial cell injury. Combination of deferoxamine (in lower concentration, ie, 0.1 mmol/L) with the new, more membrane-permeable iron chelator LK 614 (20 mumol/L) further improved preservation so that even after 3 weeks of cold storage plus 3 hours rewarming only 10 +/- 1% of endothelial cells were propidium iodide positive. In this optimized solution, both endothelial cell survival and mitochondrial membrane potential were significantly better preserved than in the clinically used solutions HTK, University of Wisconsin (UW) and Perfadex, or in physiological saline. Thrombocyte adhesion was also significantly reduced after cold storage in the optimized solution compared with HTK solution. CONCLUSION: Cold-induced injury to the endothelium of porcine aortic segments is, as the injury to cultured endothelial cells, mediated by chelatable iron. Thus, iron chelators, but also optimized base solutions, are options to improve the storage of vascular endothelium. The optimized solution should now be tested in in vivo animal experiments.     

Neuroendocrine tumor of the pancreas and bilateral adrenal pheochromocytomas. A rare manifestation of von Hippel-Lindau disease in childhood

Background

A 12-year-old girl presenting with intermittent epigastric pains and diarrhea was referred to our clinic. Diagnostic workup revealed nonfunctional bilateral adrenal pheochromocytomas as well as a neuroendocrine tumor of the pancreatic head. This is the first report on the combination of a neuroendocrine pancreatic tumor with adrenal pheochromocytoma in a pediatric patient with von Hippel-Lindau (VHL) disease.

Methods

von Hippel-Lindau disease was confirmed by molecular genetic analysis of peripheral blood lymphocytes, which revealed the mutation VHL c. 695 G > A. The family history showed also VHL disease in the mother who carried the same mutation.

Results and Conclusion

Open laparotomy, organ-sparing enucleation of pheochromocytoma, and pylorus-preserving resection of the pancreatic head tumor were successfully performed. After an uneventful postoperative course, the child fully recovered. She was free of further manifestations of VHL disease 30 months after surgery.