Vasostatin-I, a chromogranin A-derived peptide, in non-selected critically ill patients: distribution, kinetics, and prognostic significance.

PURPOSE: Chromogranin A (CGA) is released in the plasma during life-threatening illnesses. Its N-terminal 1-76 peptide, vasostatin-I (VS-I), has never been assessed in critically ill patients. Our aim was to examine whether the admission VS-I concentration has prognostic significance without having to specify a primary diagnosis. METHODS: VS-I concentrations were assessed with a new ELISA in 481 consecutive patients and 13 healthy controls. CGA and standard biological tests (including lactate) were performed; the simplified acute physiological score II (SAPS II) was calculated. Mortality was assessed at day 28. In a subgroup of 13 patients with shock, serial VS-I doses were given over 60 h. RESULTS: Critically ill patients had higher admission VS-I concentrations than controls [4.06 (2.78; 7.61) vs. 2.85 (2.47; 3.22) ng/ml, p < 0.001]. The plasma VS-I concentration was significantly lower in survivors than in non-survivors [3.70 (2.67; 6.12) vs. 5.75 (3.65; 11.20) ng/ml] and in the absence of shock [3.58 (2.59; 5.05) vs. 5.93 (3.30; 11.06) ng/ml, p < 0.001]. The survival rate was better in patients with VS-I concentrations under the median value of 3.97 ng/ml (p < 0.001). Admission VS-I and lactate values were independent predictors of mortality (p < 0.01). Moreover, taking them together, combined with age, provided a better indication for predicting mortality than taking each alone (p < 0.01). CONCLUSIONS: Significant amounts of VS-I are detected on admission in critically ill patients. A plasma VS-I concentration above 3.97 ng/ml is associated with poor outcome, and in routine practice simultaneous measurements of the three independent factors VS-I, lactate and age can affect the assessment of severity.

The N-terminal fragment of chromogranin A, vasostatin-1 protects mice from acute or chronic colitis upon oral administration.

BACKGROUND: Vasostatin-1 (VS-1), the N-terminal fragment of chromogranin A (CgA), decreases the permeability of endothelial cells in vitro and in vivo. AIMS: Here, we investigated whether a similar effect could be observed also on intestinal epithelial cells (IECs) in vitro and whether VS-1 could have favorable effects on animal models of acute or chronic colitis, which are characterized by increased permeability of the intestinal epithelium. METHODS: In vitro, VS-1 was tested on IEC monolayers showing increased permeability, on mechanically injured IEC monolayers, and on the production of the chemokine IL-8/KC by lipopolysaccharide (LPS)-stimulated IECs. In vivo, VS-1 was tested in animal models of dextran sodium salt (DSS)-induced acute or chronic colitis. RESULTS: In vitro, VS-1 inhibited increased permeability of IECs induced by interferon-γ and tumor necrosis factor-α. Moreover, VS-1 promoted healing of mechanically injured IEC monolayers, most likely through stimulation of cell migration, rather than cell proliferation. Eventually, VS-1 inhibited LPS-induced production of IL-8. In vivo, VS-1 exerted protective effects in animal models of acute or chronic colitis upon oral, but not systemic administration. CONCLUSIONS: VS-1 is therapeutically active in animal models of acute or chronic, DSS-induced colitis. The mechanisms underlying this effect are likely to be multiple, and may include inhibition of enhanced intestinal permeability, repair of injured intestinal mucosae, and inhibition of the production of IL-8/KC and possibly other inflammatory cytokines.

Tumor neuroendocrino de mama / No disponible

El tumor neuroendocrino de mama es poco frecuente, mástípico de mujeres con edad avanzada y asociado a un componentemucinoso. No se han publicado series acerca de tratamientoadyuvante en este grupo de pacientes, por lo que noexiste unanimidad en cuanto al empleo de quimioterapia o elesquema a utilizar. Se presenta un caso clínico en una mujerjoven con tumor neuroendocrino de mama que fue tratadacon cirugía, quimioterapia y hormonoterapia adyuvantes, y sehace una revisión de la literatura existente(AU)

Neuroendocrine breast tumor is an unusual breast cancerusually related to advanced age and a mucinous tumoral component.There are no series of adjuvant treatment of this kindof tumor, so that there is no a consensus about the best chemotherapyschedule to use in them. We present a case of ayoung woman with neuroendocrine breast cancer who wastreated with surgery, adjuvant chemoterapy and hormonetherapy.A literature review is made(AU)