Immunoscintigraphy for therapy decision making and follow-up of biological therapies

With the availability of new biological therapies there is the need of more accurate diagnostic tools to noninvasively assess the presence of their targets. In this scenario nuclear medicine offers many radiopharmaceuticals for SPECT or PET imaging of many pathological conditions. The availability of monoclonal antibodies provides tools to target specific antigens involved in angiogenesis, cell cycle or modulation of the immune systems. The radiolabelling of such therapeutic mAbs is a promising method to evaluate the antigenic status of each cancer lesion or inflamed sites before starting the therapy. It may also allow to perform follow-up of such biological therapies. In the present review we provide an overview of the most studied radiolabelled antibodies for therapy decision making and follow-up of patients affected by cancer and other pathological conditions

Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

The Problem of Inertia in Friedmann Universes

In this paper we study the origin of inertia in a curved spacetime, particularly the spatially flat, open and closed Friedmann universes. This is done using Sciama's law of inertial induction, which is based on Mach's principle, and expresses the analogy between the retarded far fields of electrodynamics and those of gravitation. After obtaining covariant expressions for electromagnetic fields due to an accelerating point charge in Friedmann models, we adopt Sciama's law to obtain the inertial force on an accelerating mass $m$ by integrating over the contributions from all the matter in the universe. The resulting inertial force has the form $F = -kma$, where $k < 1$ depends on the choice of the cosmological parameters such as $\Omega_{M}$, $\Omega_{\Lambda}$, and $\Omega_{R}$ and is also red-shift dependent.Comment: 10 page

Electron Positron Annihilation Radiation from SgrA East at the Galactic Center

Maps of the Galactic electron-positron annihilation radiation show evidence for three distinct and significant features: (1) a central bulge source, (2) emission in the Galactic plane, and (3) an enhancement of emission at positive latitudes above the Galactic Center. In this paper, we explore the possibility that Sgr A East, a very prominent radio structure surrounding the Galactic nucleus, may be a significant contributer to the central bulge feature. The motivation for doing so stems from a recently proposed link between this radio object and the EGRET gamma-ray source 2EG J1746-2852. If this association is correct, then Sgr A East is also expected to be a source of copious positron production. The results presented here show that indeed Sgr A East must have produced a numerically significant population of positrons, but also that most of them have not yet had sufficient time to thermalize and annihilate. As such, Sgr A East by itself does not appear to be the dominant current source of annihilation radiation, but it will be when the positrons have cooled sufficiently and they have become thermalized. This raises the interesting possibility that the bulge component may be due to the relics of earlier explosive events like the one that produced Sgr A East.Comment: This manuscript was prepared with the AAS Latex macros v4.0 It is 37 pages long and has 16 figure

Gravitational waveforms from the evaporating ACO cosmic string loop

The linearly polarized gravitational waveforms from a certain type of rotating, evaporating cosmic string - the Allen-Casper-Ottewill loop - are constructed and plotted over the lifetime of the loop. The formulas for the waveforms are simple and exact, and describe waves which attenuate self-similarly, with the amplitude and period of the waves falling off linearly with time.Comment: 30 pages, 16 figure

CULTURAL IDENTITY AND CONSERVATION OF INDIGENOUS AND NATIVE DIVERSITY

The economic development of rural areas has rarely followed that of urban centres, with greater evidence of this in developing countries where the outlying communities have remained considerably more remote from the systems of cultural and economic growth. Even if this has had negative repercussions in terms of social equilibrium within the various countries, from a strictly agronomic point of view it has often resulted in the natural conservation of indigenous and native biodiversity. This has been affected by the natural and daily use of local plant extracts both for nutritional purposes and for a variety of other reasons. The exchange of genetic material between one community and another, often a sign of respect and friendship, has helped to increase plant diversity and to enhance its role in the everyday diet of rural populations. Any activity aimed at conserving biodiversity cannot disregard the fact that native plant species (and even more indigenous species) now play a vital role in the cultural identity of rural communities, and that making such communities aware of this precious asset can also play a strategic part in the idea of promoting biological diversity as a way of developing local economies. Such evidence clearly emerged through the various activities conducted in the context of the project, FAO GTF/RAF/426/ITA Promoting Origin-linked Quality Products in Four Countries in West Africa, financed by the Slow Food Foundation for Biodiversity Onlus. This project, conducted in 4 West African countries (Sierra Leone, Guinea Bissau, Senegal and Mali), aimed to carry out a study of these 4 states and draw up an inventory of the traditional plant and animal species, to examine the link between these and the diet of rural populations, and to assess the risks of genetic erosion by actions to safeguard the native biodiversity

MeV Right-handed Neutrinos and Dark Matter

We consider the possibility of having a MeV right-handed neutrino as a dark matter constituent. The initial reason for this study was the 511 keV spectral line observed by the satellite experiment INTEGRAL: could it be due to an interaction between dark matter and baryons? Independently of this, we find a number of constraints on the assumed right-handed interactions. They arise in particular from the measurements by solar neutrino experiments. We come to the conclusion that such particles interactions are possible, and could reproduce the peculiar angular distribution, but not the rate of the INTEGRAL signal. However, we stress that solar neutrino experiments are susceptible to provide further constraints in the future.Comment: 7 pages, figure 1 changed, added reference

Labelling and clinical performance of human leukocytes labelled with 99m Tc-HMPAO using leukokit® with gelofusine versus leukokit® with HES as sedimentation agent

The scintigraphy with radiolabelled autologous leukocytes (WBCs) is considered the gold-standard technique for imaging infections. Leukokit (R) is a commercially available, disposable, sterile kit for labelling WBCs ex vivo. In this kit, WBCs isolation from red blood cells (RBCs) was performed using poly(O-2-hydroxyethyl)starch (HES) as the RBCs sedimentation agent. Due to its poor availability, HES has been recently replaced by Gelofusine as the RBC sedimentation agent. The aim of this study was to compare the labelling efficiency and the diagnostic accuracy of WBCs labelled with Leukokit (R) with HES vs Leukokit (R) with Gelofusine. WBCs were isolated using HES or Gelofusine for 45minutes and then purified from platelets (PLTs) and labelled with 1.1 +/- 0.3 GBq of freshly prepared Tc-99m- HMPAO. The following parameters were evaluated: the number and type of recovered WBCs, RBCs contamination, PLTs contamination, vitality of neutrophils, and chemotactic properties of neutrophils. Clinical comparison was performed between 80 patients (33 males; age 67.5 +/- 14.2) injected with Tc-99m-HMPAO-WBCs, using HES as the sedimentation agent, and 92 patients (38 males; age 68.2 +/- 12.8) injected with Tc-99m-HMPAO-WBCs using Gelofusine as the sedimentation agent. Patients were affected by prosthetic joint infections, peripheral bone osteomyelitis, or vascular graft infection. We compared radiolabelling efficiency (LE), final recovery yield (RY), and diagnostic outcome based on microbiology or 2-year follow-up. Results showed that HES provides the lowest RBCs and PLTs contamination, but Gelofusine provides the highest WBC recovery. Both agents did not influence the chemotactic properties of WBCs, and no differences were found in terms of LE and RY. Sensitivity, specificity, and accuracy were also not significantly different for WBCs labelled with both agents (diagnostic accuracy 90.9%, CI = 74.9-96.1 vs 98.3%, CI = 90.8-100, for HES and Gelofusine, respectively). In conclusion, Gelofusine can be considered a suitable alternative of HES for WBCs separation and labelling

Triple Experiment Spectrum of the Sunyaev-Zeldovich Effect in the Coma Cluster: H_0

The Sunyaev-Zeldovich (SZ) effect was previously measured in the Coma cluster by the Owens Valley Radio Observatory and Millimeter and IR Testa Grigia Observatory experiments and recently also with the Wilkinson Microwave Anisotropy Probe satellite. We assess the consistency of these results and their implications on the feasibility of high-frequency SZ work with ground-based telescopes. The unique data set from the combined measurements at six frequency bands is jointly analyzed, resulting in a best-fit value for the Thomson optical depth at the cluster center, tau_{0}=(5.35 \pm 0.67) 10^{-3}. The combined X-ray and SZ determined properties of the gas are used to determine the Hubble constant. For isothermal gas with a \beta density profile we derive H_0 = 84 \pm 26 km/(s\cdot Mpc); the (1\sigma) error includes only observational SZ and X-ray uncertainties.Comment: 11 pages, 1 figur