Previous studies have shown that cyclic peptides corresponding to residues 35 to 52 of the Limulus antilipopolysaccharide (anti-LPS) factor (LALF) bind and neutralize LPS-mediated in vitro and in vivo activities. Therapeutic approaches based on agents which bind and neutralize LPS activities are particularly attractive because these substances directly block the primary stimulus for the entire proinflammatory cytokine cascade. Here we describe new activities of the LALF 31-52 peptide, other than its LPS binding ability. Surprisingly, supernatants from human mononuclear cells stimulated with the LALF peptide are able to induce in vitro antiviral effects on the Hep-2 cell line mediated by gamma interferon (IFN-␥) and IFN-␣. Analysis of the effect of LALF 31-52 on tumor necrosis factor (TNF) and nitric oxide (NO) production by LPS-stimulated peritoneal macrophages revealed that a pretreatment with the peptide decreased LPS-induced TNF production but did not affect NO generation. This indicates that the LALF peptide modifies the LPS-induced response. In a model in mice with peritoneal fulminating sepsis, LALF 31-52 protected the mice when administered prophylactically, and this effect is related to reduced systemic TNF-␣ levels. This study demonstrates, for the first time, the anti-inflammatory properties of the LALF-derived peptide. These properties widen the spectrum of the therapeutic potential for this LALF-derived peptide and the molecules derived from it. These agents may be useful in the prophylaxis and therapy of viral and bacterial infectious diseases, as well as for septic shock.Lipopolysaccharide (LPS) is believed to be the initiator of the systemic inflammatory cascade that culminates in the organ damage and multiorgan failure found in septic patients (17,47). In recent years, attention has been focused on the release by macrophages of cytokines, particularly interleukin 1␤ (IL-1␤), IL-6, and tumor necrosis factor alpha (TNF-␣), that are important mediators of septic shock pathology (9, 39). Recent data have substantially advanced our knowledge on the complex timing and interactions among events like LPS exposure, cytokine release (32), and the development of septic shock. These data strongly involve LPS and macrophage cytokine release as primary effectors in the etiology of septic shock. They also suggest that LPS blockade, cytokine blockade, or specific cytokine modulation may be of therapeutic benefit in septic patients.Therapeutic approaches based on molecules that bind and neutralize LPS are particularly attractive, because they directly block the primary stimulus for the proinflammatory cytokine cascade. Recent studies have mainly involved rBPI (recombinant bactericidal permeability-increasing protein) (1) and peptides derived from it (13, 36). The Limulus anti-LPS factor (LALF) is a small, basic protein found in hemocytes from both Tachypleus tridentatus and Limulus polyphemus, which inhibits the endotoxin-mediated activation of the coagulation cascade (30), apparently by binding to LPS. This prot...

No abstract

Background: Breast cancers are becoming more frequently diagnosed at early stages with improved long term outcomes. Late normal tissue complications induced by radiotherapy must be avoided with new breast radiotherapy techniques being developed. The aim of the study was to compare dosimetric parameters of planning target volume (PTV) and organs at risk between conformal (CRT) and intensity-modulated radiation therapy (IMRT) after breast-conserving surgery. Materials and Methods: A total of 20 patients with early stage left breast cancer received adjuvant radiotherapy after conservative surgery, 10 by 3D-CRT and 10 by IMRT, with a dose of 50 Gy in 25 sessions. Plans were compared according to dose-volume histogram analyses in terms of PTV homogeneity and conformity indices as well as organs at risk dose and volume parameters. Results: The HI and CI of PTV showed no difference between 3D-CRT and IMRT, V95 gave 9.8% coverage for 3D-CRT versus 99% for IMRT, V107 volumes were recorded 11% and 1.3%, respectively. Tangential beam IMRT increased volume of ipsilateral lung V5 average of 90%, ipsilateral V20 lung volume was 13%, 19% with IMRT and 3D-CRT respectively. Patients treated with IMRT, heart volume encompassed by 60% isodose (30 Gy) reduced by average 42% (4% versus 7% with 3D-CRT), mean heart dose by average 35% (495cGy versus 1400 cGy with 3D-CRT). In IMRT minimal heart dose average is 356 cGy versus 90cGy in 3D-CRT. Conclusions: IMRT reduces irradiated volumes of heart and ipsilateral lung in high-dose areas but increases irradiated volumes in low-dose areas in breast cancer patients treated on the left side.

Our data represent a step further in the knowledge of Candida species present in Spanish patients with head and neck tumors under radiation therapy. This is an essential step to manage the prophylaxis and treatment of OPC, since it might lead to severe clinical complications causing treatment interruption and, thus, representing a reduction in anti-tumor efficacy.

No abstract

No abstract

No abstract

No abstract