Status of low-energy accelerator-based BNCT worldwide and in Argentina.

Existing and active low-energy Accelerator-Based BNCT programs worldwide will be reviewed and compared. In particular, the program in Argentina will be discussed which consists of the development of an Electro-Static-Quadrupole (ESQ) Accelerator-Based treatment facility. The facility is conceived to operate with the deuteron-induced reactions 9Be(d,n)10B and 13C(d,n)14N at 1.45 MeV deuteron energy, as neutron sources. Neutron production target development status is specified. The present status of the construction of the new accelerator development laboratory and future BNCT centre is shown.

Microtubule Destabilization Paves the Way to Parkinson's Disease.

Microtubules are dynamic structures normally associated to the cell division, during which they form the mitotic spindle, as well as to the initial phases of specification and polarization of various cell types, including neurons. Although microtubules could have a role in the death of many cells and tissues, the microtubule-based degenerative mechanisms have been poorly investigated; nevertheless, during the last two decades, many clues have been accumulated suggesting the importance of the microtubule system during neurodegeneration. Thus, the aim of this review is to analyse how the changes of the microtubule cytoskeleton, in terms of organization and dynamics, as well as the failure of the microtubule-dependent neuronal processes, as axonal transport, may play a pivotal role in the chain of events leading to Parkinson's disease. Last but not least, since disease-modifying or neuroprotective strategies are a clinical priority in Parkinson's disease, we will also present the hints about the concrete possibility of a microtubule-targeted therapy, which would have the potentiality to block the running degenerative events and to prompt the regeneration of the lost tissues.

Present status of accelerator-based BNCT: Focus on developments in Argentina.

In this work we provide some information on the present status of accelerator-based BNCT (AB-BNCT) worldwide and subsequently concentrate on the recent accelerator technology developments in Argentina.

Accelerator-based BNCT.

The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases.

Development of a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

We describe the present status of an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction. The machine currently being constructed is a folded TESQ with a high-voltage terminal at 0.6 MV. We report here on the progress achieved in a number of different areas.

Accelerator tube construction and characterization for a tandem-electrostatic-quadrupole for accelerator-based boron neutron capture therapy.

The accelerator tubes are essential components of the accelerator. Their function is to transport and accelerate a very intense proton or deuteron beam through the machine, from the ion source to the neutron production target, without significant losses. In this contribution, we discuss materials selected for the tube construction, the procedures used for their assembly and the testing performed to meet the stringent requirements to which it is subjected.

Electrostatic design and beam transport for a folded tandem electrostatic quadrupole accelerator facility for accelerator-based boron neutron capture therapy.

Within the frame of an ongoing project to develop a folded Tandem-Electrostatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT), we discuss here the electrostatic design of the machine, including the accelerator tubes with electrostatic quadrupoles and the simulations for the transport and acceleration of a high intensity beam.

Search for viruses in the CSF of patients with acute neurological disorders: possible involvement of beta-and gamma-herpesviruses.

In the years 1999-2001, 868 samples of cerebrospinal fluid (CSF) from as many patients with acute neurological manifestations of suspected viral origin were analysed for the presence of viruses at the Centre for the Diagnosis of Viral Diseases of the University of Modena and Reggio Emilia. Neurological patients included 788 immunocompetent subjects and 80 patients with impaired immunity due to human immunodeficiency virus (HIV) seropositivity. Of the CSF samples, 125 (15.8%) were positive for one or more viruses among the immunocompetent patients, whereas 33 (41.1%) were positive among the HIV cohort. DNA and RNA viruses were detected in the first group of CSF samples whereas only DNA viruses were found in the second group. In immunocompetent patients the frequency of enteroviruses prevailed over that of other RNA virus families (p = 0.001) and that of herpesviruses over the frequency of other DNA virus families (p = 0.001). Among herpesvirus members, the Epstein-Barr gamma-herpesvirus prevailed on alpha-herpesviruses in each of the two groups of patients (p = 0.05 in the immunocompetent group and p = 0.006 in HIV-positive patients). The clinical relevance both of this virus and of beta-herpesviruses as a cause of neurological disorders is discussed.

Lymphokine enhances oxygen-independent activity against intracellular pathogens.

To determine if mechanisms other than the generation of toxic oxygen intermediates are active against intracellular pathogens, oxidatively deficient mouse L cells and monocyte-derived macrophages from patients with chronic granulomatous disease were stimulated with soluble lymphocyte products. Despite no enhancement in oxidative activity, these cells displayed effective microbistatic activity against both T. gondii and C. psittaci. These results suggest a potential role for nonoxidative mechanisms in the mononuclear phagocyte's activity against intracellular pathogens, and indicate that lymphokines can regulate both oxygen-dependent and oxygen-independent antimicrobial responses.

Killing of intracellular Leishmania donovani by human mononuclear phagocytes. Evidence for oxygen-dependent and -independent leishmanicidal activity.

Human peripheral blood monocytes were cultivated for 1-30 d before assay for H2O2 release or challenge with Leishmania donovani promastigotes (LDP) or amastigotes (LDA). 1-d cells readily generated H2O2 in response to both phorbol myristate acetate triggering (1,013 +/- 58 nmol/mg protein . 90 min) and LDP ingestion, and killed 50% of LDP within 6 h, and 90% by 24 h. In contrast, the same cells released little H2O2 during LDA ingestion, killed no LDA at 6 h and less than 30% by 24 h, and supported intracellular LDA replication. Monocyte-derived macrophages (cells first cultivated for greater than or equal to 7 d) generated less than 125 nmol H2O2/mg . 90 min after phorbol myristate acetate triggering, killed neither LDP nor LDA, and permitted both forms to replicate. The addition of mitogen- or antigen-stimulated lymphokines, however, prevented the decline in monocyte oxidative capacity, enhanced macrophage H2O2 release by more than sixfold, and, in parallel, induced 1-d monocytes to kill LDA and cultivated macrophages to display both promastigocidal and amastigocidal activity. In comparison to 1-d monocytes and lymphokine-activated macrophages from normal donors, the same cells from patients with chronic granulomatous disease (CGD) or normal cells whose oxidative activity had been impaired by catalase pretreatment or glucose deprivation exerted considerably less or no antileishmanial activity during the early (6-24 h) postphagocytic period. By 48 h after infection, however, 1-d CGD monocytes and oxidatively impaired normal cells killed 40 and greater than 80% of LDP, respectively. Although a longer period of lymphokine stimulation was required and the resulting antileishmanial effects were not as rapid as with normal cells, activated CGD monocytes and macrophages also eventually achieved promastigocidal and amastigostatic activity. These results indicate that human mononuclear phagocytes utilize both oxygen-dependent and -independent mechanisms to achieve activity against ingested Leishmania, and also demonstrate (a) the differential susceptibilities of the two forms of L. donovani to intracellular killing, (b) the key role of oxygen intermediates in effective mononuclear phagocyte antimicrobial activity, (c) the capacity of lymphocyte products to enhance oxygen-dependent as well as -independent pathways, and (d) the vulnerability of the monocyte-derived macrophage to Leishmania infection in the absence of lymphokine stimulation.