RESUMEN
Main pulmonary vascular diseases (PVD) with precapillary pulmonary hypertension (PH) are pulmonary arterial and chronic thromboembolic PH. Guidelines recommend supplemental oxygen therapy (SOT) for severely hypoxemic patients with PH, but evidence is scarce. The authors performed a systematic review and where possible meta-analyses on the effects of SOT on hemodynamics and exercise performance in patients with PVD. In PVD, short-term SOT significantly improved mean pulmonary artery pressure and exercise performance. There is growing evidence on the benefit of long-term SOT for selected patients with PVD regarding exercise capacity and maybe even survival.
Asunto(s)
Hipertensión Pulmonar , Enfermedades Vasculares , Humanos , Circulación Pulmonar , Arteria Pulmonar , Hemodinámica , Oxígeno/uso terapéuticoRESUMEN
Diphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we investigated the role of Hsp90 and its co-chaperones during the uptake of native diphtheria toxin into human cells and identified the components of the Hsp90 machinery including Hsp90, Hsp70, Cyp40 and the FK506 binding proteins FKBP51 and FKBP52 as DTA binding partners. Moreover, pharmacological inhibition of the chaperone activity of Hsp90 and Hsp70 and of the peptidyl-prolyl cis/trans isomerase (PPIase) activity of Cyps and FKBPs protected cells from intoxication with diphtheria toxin and inhibited the pH-dependent trans-membrane transport of DTA into the cytosol. In conclusion, these host cell factors facilitate toxin uptake into human cells, which might lead to development of novel therapeutic strategies against diphtheria.