Pregnancy-specific glycoprotein 1 (PSG1) activates TGF-ß and prevents dextran sodium sulfate (DSS)-induced colitis in mice.

Transforming growth factor-ßs (TGF-ßs) are secreted from cells as latent complexes and the activity of TGF-ßs is controlled predominantly through activation of these complexes. Tolerance to the fetal allograft is essential for pregnancy success; TGF-ß1 and TGF-ß2 play important roles in regulating these processes. Pregnancy-specific ß-glycoproteins (PSGs) are present in the maternal circulation at a high concentration throughout pregnancy and have been proposed to have anti-inflammatory functions. We found that recombinant and native PSG1 activate TGF-ß1 and TGF-ß2 in vitro. Consistent with these findings, administration of PSG1 protected mice from dextran sodium sulfate (DSS)-induced colitis, reduced the secretion of pro-inflammatory cytokines, and increased the number of T regulatory cells. The PSG1-mediated protection was greatly inhibited by the coadministration of neutralizing anti-TGF-ß antibody. Our results indicate that proteins secreted by the placenta directly contribute to the generation of active TGF-ß and identify PSG1 as one of the few known biological activators of TGF-ß2.

Elección del tratamiento antitrombótico en pacientes con síndrome coronario agudo sin elevación del segmento ST de alto riesgo / Choosing antithrombotic treatment for high-risk patients with non-ST-elevation acute coronary syndrome

Las guías de práctica clínica del síndrome coronario agudo sin elevación del segmento ST recomiendan la utilización de aspirina, heparina, clopidogrel e inhibidores de la glucoproteína IIb/IIIa asociados con una estrategia invasiva precoz en los pacientes de alto riesgo. Sin embargo, no hay evidencias directas que demuestren la eficacia, la seguridad y la relación coste-efectividad de esta actitud. En pacientes con alto riesgo de desarrollar eventos coronarios y bajo riesgo de sangrado, ésta es una actitud razonable. Sin embargo, una proporción importante de estos pacientes no cumple estos criterios. En estos casos, parece sensato restringir el tratamiento antitrombótico. Para ello, se revisan los aspectos que pueden ayudar a tomar este tipo de decisiones. Éstos pueden ser clínicos, como la edad, el sexo y los antecedentes de insuficiencia renal y diabetes, o logísticos, como la factibilidad de realizar una coronariografía en 48 h o una revascularización quirúrgica en menos de 5 días, al margen de las situaciones urgentes (AU)

Clinical practice guidelines on non-ST-elevation acute coronary syndrome recommend the use of aspirin, heparin, clopidogrel and glycoprotein IIb/IIIa inhibitors in addition to early invasive treatment for high-risk patients. However, no direct evidence is available showing the efficacy, safety, and cost-effectiveness of this strategy. In patients who are at a high risk of experiencing a coronary event and at a low risk of bleeding, it is a reasonable approach. However, a significant percentage of patients do not fulfill both criteria. In these patients, it seems wise to use antithrombotic therapy more cautiously. Here, we review the factors that may influence decision-making in this setting. These may be clinical, such as advanced age, female sex, or a history of diabetes or chronic renal failure, or logistic, such as the practicality of carrying out coronary angiography within 48 hours or of performing surgical coronary revascularization within five days in the absence of an urgent indication (AU)