Investigation on target normal sheath acceleration through measurements of ions energy distribution.

An experimental campaign aiming at investigating the ion acceleration mechanisms through laser-matter interaction in femtosecond domain has been carried out at the Intense Laser Irradiation Laboratory facility with a laser intensity of up to 2 × 10(19) W/cm(2). A Thomson parabola spectrometer was used to obtain the spectra of the ions of the different species accelerated. Here, we show the energy spectra of light-ions and we discuss their dependence on structural characteristics of the target and the role of surface and target bulk in the acceleration process.

Lisuride, a dopamine receptor agonist with 5-HT2B receptor antagonist properties: absence of cardiac valvulopathy adverse drug reaction reports supports the concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular fibrosis.

OBJECTIVES: The high incidence of fibrotic cardiac valvulopathies reported in association with the 8beta-ergoline dopamine (DA) agonist, pergolide, and also case reports for cabergoline and bromocriptine have made it necessary to review the theoretical basis and actual findings in the case of another DA agonist, the 8alpha-ergoline lisuride (used since the 1970s for migraine prophylaxis as well as since the 1980s for its prolactin-lowering and anti-Parkinson activity). METHODS: We have reviewed the pharmacology of lisuride in relation to other DA agonists, and we have performed a throughout literature search as well as a search of our own and other adverse drug reaction databases for a possible relationship of lisuride with cardiac valvulopathy or for any reports of fibrosis in other locations. RESULTS: Our review of the pharmacology and the literature strongly suggests that drug-induced cardiac valvulopathies are always related to a stimulatory drug effect on trophic 5-HT(2B) receptors. As lisuride is devoid of such an effect, but on the contrary is an extremely potent 5-HT(2B) antagonist, an association of lisuride therapy with cardiac valvulopathies seems to be highly unlikely. In agreement with this hypothesis, not a single report of a cardiac valvulopathy associated with lisuride therapy has been identified in any database so far.Furthermore, against a background of an estimated 360,000 patient years, we have found only a very small number of cases of any other form of fibrosis (1x retroperitoneal, 2x pleural, 2x pulmonary, 1x interstitial pulmonary changes), in part combined with other risk factors and confounding variables. This closely matches 4 reports available from WHO (1x retroperitoneal, 3x pleural fibrosis). In addition, only 5 other possibly related conditions (3x pleural effusion, 1x pleuritis, 1x pericarditis) were identified in the lisuride adverse drug reaction database of Schering, Berlin. CONCLUSIONS: No link has been found between lisuride use and fibrotic cardiac valvulopathy, in agreement with the 5-HT(2B) receptor antagonist effect of this drug. The very low incidence of spontaneous reports of any other fibrosis could be even compatible with an association by chance in the population exposed to lisuride. Although close monitoring for this kind of side effects is still to be recommended in the therapy with lisuride, our data do not support the concept of a class effect suggesting that all ergot-derived drugs and especially DA receptor agonists with some chemical similarity to the ergot structure will cause or facilitate cardiac valvulopathies as observed with pergolide.

Immunization of cancer patients with autologous cancer-derived heat shock protein gp96 preparations: a pilot study.

Heat shock protein (HSP)-peptide complexes isolated from murine cancers elicit protective immunity and T lymphocytes specific for the cancer from which the HSPs are isolated. A pilot study was designed to test the feasibility, immunogenicity and toxicity of such treatment in cancer patients. Sixteen patients with assorted advanced malignancies, which had become refractory to established therapies, were recruited. The gp96 vaccine was prepared for each patient from tumor obtained from that patient. Anti-tumor immune responses were evaluated using Elispot assays of T cells in peripheral blood after minimal in vitro stimulation. No unacceptable vaccine-related toxicities or auto-immune reactions were observed. Immunization with autologous gp96 elicited MHC I-restricted, tumor-specific CD8(+) T lymphocytes in 6/12 patients immunized. In addition, expansion of the NK cell population was seen in 8/13 of patients immunized. These observations are entirely consistent with the murine experience and form a firm basis for future trials with clinical end points, using autologous, patient-specific HSP-peptide vaccines.