PHOTODYNAMIC RELEASE OF PROTOPORPHYRIN FROM INTACT ERYTHROCYTES IN ERYTHROPOIETIC PROTOPORPHYRIA: THE EFFECT OF SMALL REPETITIVE LIGHT DOSES

Abstract— Erythrocytes from patients with erythropoietic protoporphyria contain large amounts of protoporphyrin bound to (hemo)globin. Irradiation of these cells causes a shift in fluorescence emission maximum and a decreased fluorescence intensity which is consistent with transfer of protoporphyrin from (hemo)globin to the cell membrane. When the erythrocytes were irradiated intermittently, nearly 70% of the protoporphyrin was released and the hemolysis was less than 3%. Giving the total light dose as a single pulse, resulted in 84% protoporphyrin release and 16% hemolysis.
In vivo the erythrocytes obtain small, repetitive light doses when circulating in the dermal capillaries. We suggest the possibility that in patients with erythropoietic protoporphyria these small light pulses could be sufficient to photodamage the binding place of protoporphyrin on (hemo)globin. In the dark, protoporphyrin can then move from (hemo)globin through the cell membrane and bind to albumin in the serum. Our findings indicate that if protoporphyrin is not present in the cell membrane during irradiation, no photohemolysis will occur. This may explain why patients with erythropoietic protoporphyria have no abnormal hemolysis. The effect of intermittent light pulses may also contribute to the understanding of the protoporphyrin release from erythrocytes in patients with erythropoietic protoporphyria.     

Authors reply to comments on "Line patterns in the mosaic electric properties of human skin--a cross correlation study."

We read with interest the comments of Lin et al. [ibid., vol. 49, p. 274, 2002] on our paper "Line patterns in the mosaic electric properties of human skin-A cross correlation study" [ibid., vol. 48, p. 731-4, 2001]. The authors point out that our measurements will only reveal meridian lines expressed in the epidermis. This is indeed true and the instrumentation was intentionally designed to focus on the epidermis since, to our knowledge, most publications regarding the electrical properties of acupuncture points or meridian lines deal with low-frequency or direct current and, hence, only the epidermis (dominated by the dead stratum corneum). The authors furthermore suggest identifying meridian lines indirectly by locating low-resistance points in the epidermis. The ohmic resistance of the epidermis is totally dominated by the dead stratum comeum and will greatly change locally where active sweat ducts form electrical shunt paths through the stratum corneum. Since the density of sweat orifices on most nonpalmar or nonplantar skin sites is roughly 100 pr /spl middot/ cm/sup 2/, these sweat ducts will be the most obvious reason for any low-resistance points found on skin, at least until otherwise is shown. Consequently, any detection method for acupuncture points will be inadequate if based on, or even influenced by, the direct current resistance (or conductance) of the skin, since it will also detect the large number of densely dispersed sweat ducts in the skin. This is the reason why also electrical susceptance was measured in our study, since this parameter is not influenced by the sweat ducts.     

Analytical Treatment of a Push–Pull “Echo” Test

A semi-analytical streamline-based model, employing stratification and macro physics only, is developed and utilized to simulate injection/production phases of single-well push–pull tests. Modeling results are compared with experimental field data, giving an excellent match, without resorting to parameter fitting, simply by putting in known test-site properties, such as stratification data, hydraulic head gradients, and test parameters.     

Time-reversal multiple signal classification in case of noise: a phase-coherent approach

The problem of locating point-like targets beyond the classical resolution limit is revisited. Although time-reversal MUltiple SIgnal Classification (MUSIC) is known for its super-resolution ability in localization of point scatterers, in the presence of noise this super-resolution property will easily break down. In this paper a phase-coherent version of time-reversal MUSIC is proposed, which can overcome this fundamental limit. The algorithm has been tested employing synthetic multiple scattering data based on the Foldy-Lax model, as well as experimental ultrasound data acquired in a water tank. Using a limited frequency band, it was demonstrated that the phase-coherent MUSIC algorithm has the potential of giving significantly better resolved scatterer locations than standard time-reversal MUSIC.     

Cluster states in the neutron excess nucleus 22Ne

High-spin states of the ²²Ne nucleus in the excitation energy range of 15–30 MeV have been studied. The angular correlation method has been used to determine the spins of excited states. A number of new states with high angular momenta—20.0 MeV (9^?), 20.7 MeV (11^?), 21.6 MeV (9^?), 22.2 MeV (12⁺), and 25.0 MeV (9^?)—have been revealed. They are intensely populated in the reaction ¹⁴C(¹²C, α₁)²²Ne* → α₂ + ¹⁸O and correspond to the rotational bands of various structures.     

On the Loss of Injectant and Apparent Dispersivity in Single-Well Push-Pull Tests Influenced by Natural Drift

In a previous article, a semi-analytical stream-line based model was developed for single-well push-pull tests in stratified reservoirs subject to natural drift. Based on that model, this article gives the theoretical maximum injection phase duration giving conservative injectant production, in a single-layer reservoir with natural drift. In addition, an analytical expression for the single-layer apparent dispersivity due to natural drift is given. Finally, it is shown how the large-scale apparent dispersivities observed in experimental data from a stratified aquifer may be predicted by constructing a production profile using the estimated single-layer apparent dispersivities.     

ERYTHROPOIETIC PROTOPORPHYRIA: PHOTODYNAMIC TRANSFER OF PROTOPORPHYRIN FROM INTACT ERYTHROCYTES TO OTHER CELLS

Erythrocytes in patients with erythropoietic protoporphyria (EPP) contain large amounts of protoporphyrin and are regarded as the main source of protoporphyrin in this disease. Cells in the skin of EPP patients accumulate protoporphyrin released from the erythrocytes and upon sun exposure endothelial cells are photodamaged. In the present study a light-induced transfer of protoporphyrin directly from EPP erythrocytes to cultured cells is demonstrated. Erythrocytes were layered upon cultured cells and irradiated. The nearness of erythrocyte and cultured cell membranes potentiated the transfer of protoporphyrin between these cells. This transfer was rapid and preceded the release of protoporphyrin to proteins in the medium. Further irradiation of the protoporphyrin-enriched cultured cells, after removal of the erythrocytes, caused severe photodamage to the cells and survival was dependent on both the amount of protoporphyrin transferred and on the light fluence. Clinical observations and the results of this study indicate that light energy may be involved in two steps in the pathophysiology of EPP: (A) light-induced release of protoporphyrin from erythrocytes to endothelial cells and (B) photodynamic damage to protoporphyrin-enriched endothelial cells.     

Productivity development of Norwegian institutions of higher education 2004–2013

Productivity growth of institutions of higher education is of interest for two main reasons: education is an important factor for productivity growth of the economy, and in countries where higher education is funded by the public sector, accountability of resource use is of key interest. Educational services consist of teaching, research and the “third mission” of dissemination of knowledge to the society at large. A bootstrapped Malmquist productivity change index is used to calculate productivity development for Norwegian institutions of higher education over the 10-year period 2004–2013. The confidence intervals from bootstrapping allow part of the uncertainty of point estimates stemming from sample variation to be revealed. The main result is that the majority of institutions have had a positive productivity growth over the total period. However, when comparing with growth in labour input, the impact on productivity varies a lot.