Bulletin et memoires de l'Academie royale de medecine de Belgique最新文献

The purpose of our research is to contribute to a better understanding of the residual brain function of patients who survive an acute brain damage but remain in a coma, vegetative state, minimally conscious state or locked-in syndrome. The diagnosis, prognosis, therapy and medical management of these patients remain difficult. These studies are also of interest scientifically, as they help to elucidate the neural correlates of human consciousness. We here review our studies on bedside behavioral evaluation scales, electrophysiology and functional neuroimaging in these disorders of consciousness and conclude by discussing methodological and ethical issues and current concepts of the standards for care and quality of life in these challenging conditions.

Understanding the molecular basis of the formation of blood vessels (angiogenesis) and nerves (neurogenesis) is of great medical relevance. It is well known that dysregulation of angiogenesis leads to tissue ischemia, cancer, inflammation and other disorders, while a dysfunction of the nerve system contributes to motorneuron disorders like amyotrophic lateral sclerosis (ALs) and other neurodegenerative diseases. The observations of Andreas Vesalius--Belgian anatomist of the 16th century--that patterning ofvessels and nerves show more than remarkable similarities, are currently revisited in exciting studies. Indeed, often, vessels and nerves even track alongside each other. Recent genetic studies revealed that vessels and nerves share many more common principles and signals for navigation, proliferation and survival than previously suspected. For instance, gene inactivation studies in mice and zebrafish showed that axon guidance signals regulate vessel navigation. Conversely, prototypic angiogenic factors such as VEGF control neurogenesis and regulate axon and neuron guidance, independently of their angiogenic activity. The next coming years promise to become an exciting journey to further unravel the molecular basis and explore the therapeutic potential of the neurovascular link.

Among the astonishing Einstein's papers from 1905, there is one which unexpectedly gave birth to a powerful method to explore the brain. Molecular diffusion was explained by Einstein on the basis of the random translational motion of molecules which results from their thermal energy. In the mid 1980s it was shown that water diffusion in the brain could be imaged using MRI. During their random displacements water molecules probe tissue structure at a microscopic scale, interacting with cell membranes and, thus, providing unique information on the functional architecture of tissues. A dramatic application of diffusion MRI has been brain ischemia, following the discovery that water diffusion drops immediately after the onset of an ischemic event, when brain cells undergo swelling through cytotoxic edema. On the other hand, water diffusion is anisotropic in white matter, because axon membranes limit molecular movement perpendicularly to the fibers. This feature can be exploited to map out the orientation in space of the white matter tracks and image brain connections. More recently, it has been shown that diffusion MRI could accurately detect cortical activation. As the diffusion response precedes by several seconds the hemodynamic response captured by BOLD fMRI, it has been suggested that water diffusion could reflect early neuronal events, such as the transient swelling of activated cortical cells. If confirmed, this discovery will represent a significant breakthrough, allowing non invasive access to a direct physiological marker of brain activation. This approach will bridge the gap between invasive optical imaging techniques in neuronal cell cultures, and current functional neuroimaging approaches in humans, which are based on indirect and remote blood flow changes.

Small-conductance ca2+ -activated potassium (SK) channels underlie one component of the afterhyperpolarization which follows one or several action potentials in neurons. Their blockade enhances neuronal excitability and, in some cases, produces a significant depolarization within dendrites. Three subtypes of SK subunits exist and are differentially expressed in the brain. We have developed SK channel blockers, we have characterized their potency and have used some of them as pharmacological tools. Moreover, we have shown that SK channel blockade increases dopaminergic and serotonergic, but not noradrenergic transmission. We believe that this is an original way of modulating brain function. Our next goal is to find subtype-selective blockers, using a variety of approaches, including molecular modelling.

Radiotherapy using proton beams (proton therapy) is rapidly taking an important role among the techniques used in cancer therapy. At the end of 2007, 65.000 patients had been treated for cancer by proton beams in one of the 34 proton therapy facilities operating in the world. When compared to the now classical IMRT, and for a similar dose to the tumor, proton therapy provides a lower integral dose to the healthy organs surrounding the tumor. It is generally accepted that any reduction of the dose to healthy organs reduces the probability of radiation induced complications and of secondary malignancies. Proton therapy equipment can be obtained today from well established medical equipment companies such as Varian, Hitachi or Mitsubishi. But it is a Belgian company, Ion Beam Applications of Louvain-la-Neuve that is the undisputed leader in this market, with more than 55% of the world installed base. In addition to the now classical proton therapy equipments, using synchrotrons or cyclotrons as accelerators, new solutions have been proposed, claiming to be more compact and less expensive. A small startup company from Boston (Still Rivers) is proposing a very high magnetic field, gantry mounted superconducting synchrocyclotron. The us Company Tomotherapy is working to develop a new accelerator concept invented at Lawrence Livermore National Laboratory: the Dielectric Wall Accelerator. Besides proton beam therapy, which is progressively becoming an accepted part of radiation therapy, interest is growing for another form of radiotherapy using ions heavier than protons. Carbon ions have, even to a higher degree, the ballistic selectivity of protons. In addition, carbon ions stopping in the body exhibit a very high Linear Energy Transfer (LET). From this high LET results a very high Relative Biological Efficiency (RBE). This high RBE allows carbon ions to treat efficiently tumors who are radio-resistant and which are difficult to treat with photons or protons. The largest experience in carbon beam therapy comes from Japan, from the National Institute for Radiation Science (NIRS) in Chiba, where more than 4000 patients have been treated with carbon beams. In Europe, carbon beam therapy has been tested on a limited number of patients in GSI, a national laboratory for heavy ion research in Darmstadt. A clinical carbon therapy center has been developed by GSI and the prototype is located at the German National Cancer Research Center (DKFZ) in Heidelberg. This center (HICAT) is close to being completed, and should treat patients in 2009. Another national carbon therapy facility is under construction in Pavia (Italy), and is build by a group of Italian physics laboratories. Siemens has obtained the intellectual rights of the GSI design in Heidelberg, and has sold two other carbon therapy systems in Germany, one in Marburg and one in Kiel. All existing systems for carbon therapy use cyclotrons as accelerators. IBA has introduced the innovative concept of

By definition, radiobiology studies energy transferring from ionizing radiations to biological material. For a long time, radiobiologists have mainly focused in physical issues and its impact on biological cells and tissues. Moreover, DNA damage, specifically of single and double strands (correctly or not restored by enzymatic repair processes), was studied through diverse mathematical models but only one experimental method: cell death measurement. Today, radiobiology has become again a strictly biological science, focused on the future of energy deposit. Genomic instability is the first step, as it studies the amplification over time of a gene signal in a clonal population derived from a single surviving cell after radiation exposure, independently of initial radiation doses. Bystander effect demonstrates that damage signals may be transmitted from irradiated to non-irradiated cells in a population with the same long term radio-induced effect. Abscopal effect is a reaction produced following irradiation, but occurring outside the site of radiation absorption (for example, from irradiated right lung to DNA damage of the left lung). Clastogenic factors are chromosome damaging substances which are present in irradiated patients's plasma. These data could change the fundamentals of radioprotection, as declared UNSCEAR during the 54th session of may 2006.

We show that proliferation-related signals are omnipresent in the breast cancer transcriptome. As a result, many transcriptional signatures generated at random are valuable for the prognosis of disease-free survival: despite their biological rationale, 30-60% of published prognostic signatures are not significantly better. We propose a mathematical transformation, the super PCNA decovolution, which removes proliferation-related signals from tumours transcriptional profiles. Both random and published signatures loose nearly all their prognostic value after removal of these signals.

Treatment of human immunodeficiency virus (HIV) infection with highly active antiretroviral therapy (HAART) has become highly effective. However the persistence of a small population of infected cells containing transcriptionally silent but re-activatable HIV proviruses prevents complete elimination of the infection. Here, we review recent progress in our understanding of the molecular mechanisms underlying HIV proviral latency and highlight experimental therapies designed to eliminate the latent population.