Effects of Ferumoxides – Protamine Sulfate Labeling on Immunomodulatory Characteristics of Macrophage-like THP-1 Cells

Superparamagnetic Iron Oxide (SPIO) complexed with cationic transfection agent is used to label various mammalian cells. Labeled cells can then be utilized as an in vivo magnetic resonance imaging (MRI) probes. However, certain number of in vivo administered labeled cells may be cleared from tissues by the host's macrophages. For successful translation to routine clinical application of SPIO labeling method it is important that this mode of in vivo clearance of iron does not elicit any diverse immunological effects. The purpose of this study was to demonstrate that SPIO agent ferumoxides-protamine sulfate (FePro) incorporation into macrophages does not alter immunological properties of these cells with regard to differentiation, chemotaxis, and ability to respond to the activation stimuli and to modulate T cell response. We used THP-1 cell line as a model for studying macrophage cell type. THP-1 cells were magnetically labeled with FePro, differentiated with 100 nM of phorbol ester, 12-Myristate-13-acetate (TPA) and stimulated with 100 ng/ml of LPS. The results showed 1) FePro labeling had no effect on the changes in morphology and expression of cell surface proteins associated with TPA induced differentiation; 2) FePro labeled cells responded to LPS with slightly higher levels of NFκB pathway activation, as shown by immunobloting; TNF-α secretion and cell surface expression levels of CD54 and CD83 activation markers, under these conditions, were still comparable to the levels observed in non-labeled cells; 3) FePro labeling exhibited differential, chemokine dependent, effect on THP-1 chemotaxis with a decrease in cell directional migration to MCP-1; 4) FePro labeling did not affect the ability of THP-1 cells to down-regulate T cell expression of CD4 and CD8 and to induce T cell proliferation. Our study demonstrated that intracellular incorporation of FePro complexes does not alter overall immunological properties of THP-1 cells. The described experiments provide the model for studying the effects of in vivo clearance of iron particles via incorporation into the host's macrophages that may follow after in vivo application of any type of magnetically labeled mammalian cells. To better mimic the complex in vivo scenario, this model may be further exploited by introducing additional cellular and biological, immunologically relevant, components

Consequences of the Reduction of Interest Rates on Insurance

In this paper we try to assess the impact of various policy changes on the ability of the insurance industry to preserve or increase the shareholders' value. As a proxy of shareholders value, we measure the sensitivity of ROE (Return On Equities) to three main variables i.e.: (1) Different asset allocation strategies (low and high risk investment of segregated funds). (2) Cost cutting policy (fixed and distribution costs). (3) Different floor options (minimum guaranteed from 4 to 0 percent). The ROE sensitivity is estimated through a Monte Carlo simulation, where we assume that the portfolio is invested in three total return market indices. The typical portfolio in the simulations is structured as follows: 5-year treasury bonds, 5-year corporate bonds, equity; and we neglect foreign exchange risk. A 10-year single premium policy, with a reimbursement only at maturity is considered. We show that a high minimum guaranteed return and the actual prevailing financial market conditions, aggressive investment policies (stocks in excess of 10–15 percent of total assets) are likely to destroy shareholders' value. Our results indicate that reduction of minimum guaranteed rates and cost cutting are imperative, and an appropriate combination of the two appears to be the best solution. The Geneva Papers on Risk and Insurance (2000) 25, 63–77. doi:10.1111/1468-0440.00049

High noon back pain- severe pseudoradicular pain as a lead symptom of superficial siderosis: a case report

A superficial siderosis of the central nervous system following a traumatic cervical nerve root avulsion usually leads to gait difficulties and hearing loss, whereas back pain is described only rarely. Here we report on the first case with circadian occurrence of severe back pain as the only symptom of a superficial siderosis. We present a case with the most severe pseudoradicular lumbosacral pain occurring daily at noon for the past 5 weeks. The 48-year-old male white patient did not complain of pain in the morning. A traumatic root avulsion 26 years earlier led to a brachial plexus palsy and Horner’s syndrome in this patient. Superficial hemosiderosis in cranial MRI and examination of the cerebrospinal fluid revealing massive red blood cells as well as xanthochromia and elevated protein levels (742 mg/l) led to the diagnosis of a superficial siderosis. A pseudomeningocele caused by a cervical nerve root avulsion is described as a rare reason for superficial siderosis. Surgery on a pseudomeningocele, diagnosed by MRI, led to an immediate disappearance of complaints in our case. Regular neurological investigation and possibly repeated lumbar puncture to exclude superficial siderosis should be considered in cases with severe back pain and a history of traumatic root avulsion. Modern susceptibility weighted MR imaging (SWI) techniques, sensible to the detection of superficial hemosiderosis, might be helpful in the making of a diagnosis