[Target volume segmentation of PET images by an iterative method based on threshold value]. / Segmentación de volúmenes tumorales en imágenes PET mediante un método iterativo basado en valor umbral.

OBJECTIVES: An automatic segmentation method is presented for PET images based on an iterative approximation by threshold value that includes the influence of both lesion size and background present during the acquisition. MATERIAL AND METHODS: Optimal threshold values that represent a correct segmentation of volumes were determined based on a PET phantom study that contained different sizes spheres and different known radiation environments. These optimal values were normalized to background and adjusted by regression techniques to a two-variable function: lesion volume and signal-to-background ratio (SBR). This adjustment function was used to build an iterative segmentation method and then, based in this mention, a procedure of automatic delineation was proposed. This procedure was validated on phantom images and its viability was confirmed by retrospectively applying it on two oncology patients. RESULTS: The resulting adjustment function obtained had a linear dependence with the SBR and was inversely proportional and negative with the volume. During the validation of the proposed method, it was found that the volume deviations respect to its real value and CT volume were below 10% and 9%, respectively, except for lesions with a volume below 0.6 ml. CONCLUSIONS: The automatic segmentation method proposed can be applied in clinical practice to tumor radiotherapy treatment planning in a simple and reliable way with a precision close to the resolution of PET images.

A Limulus antilipopolysaccharide factor-derived peptide exhibits a new immunological activity with potential applicability in infectious diseases.

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-gamma) and IFN-alpha. 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-alpha 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.

Heparin and low molecular weight heparin decrease nitric oxide production by human polymorphonuclear cells.

BACKGROUND: Heparin and heparin derivatives with low anticoagulant activity exhibit a wide spectrum of biological functions affecting adhesion, activation and trafficking of leukocytes. METHODS: We investigated the in vitro effect of heparin and a low molecular weight heparin derivative (LMWH) on nitric oxide (NO) production by human polymorphonuclear leukocytes (PMN). RESULTS: N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated NO production was significantly decreased by heparin at doses of 0.5 and 5 micrograms/mL, while LMWH was only effective at doses of 50 and 200 micrograms/mL by means of a mechanism not related to NO synthase (NOS) activity. CONCLUSIONS: These results support the hypothesis that heparin and LMWH derivatives may offer therapeutic benefit for inflammatory diseases where NO plays a protagonic role.

Ca(2+)-independent nitric oxide synthase activity in human lung after cardiopulmonary bypass.

BACKGROUND: Because surgery involving cardiopulmonary bypass induces a systemic inflammatory response, the effect of cardiopulmonary bypass on nitric oxide (NO) generation was investigated in human lung tissue. METHODS: Nitric oxide synthase (NOS) activity was measured by the conversion of 14C-L-arginine to 14C-L-citrulline in tissue biopsy samples obtained before and after cardiopulmonary bypass. RESULTS: The Ca(2+)-independent production of NO found before cardiopulmonary bypass was extremely low (1.5 (0.5) pmol citrulline/mg/min), but was increased after the bypass operation (23.6 (11) pmol/mg/min). CONCLUSIONS: Ca(2+)-independent NOS activity was detected in human lung after cardiopulmonary bypass. This finding may provide an important insight into the pathogenesis of the tissue damage and acute phase response observed after such surgery.