Antipsoriatic treatment extends beyond the skin: recovering of high-density lipoprotein function.

Epidemiological and clinical studies have shown a consistent association of psoriasis with systemic metabolic disorders including an increased prevalence of diabetes, obesity and cardiovascular disease. Psoriasis is accompanied by systemic inflammation and low levels of high-density lipoprotein (HDL) cholesterol. Recent studies provided clear evidence that psoriasis affects HDL composition and function. HDL isolated from patients with psoriasis showed a significantly impaired capability to mobilize cholesterol from macrophages, a crucial step in reverse cholesterol transport and markedly lower paraoxonase activity, a protein that co-transports with HDL in serum with well-known anti-atherogenic properties. Of particular interest, successful antipsoriatic therapy significantly improved HDL composition and function independently of serum HDL cholesterol levels. These novel findings suggest that the conventional approaches of evaluating cardiovascular risk in psoriasis may be in need of refinement. As these data argue for a loss of beneficial activities of HDL in patients with psoriasis, altered HDL functionality should be considered when evaluating the lipid status of patients.

Anti-psoriatic therapy recovers high-density lipoprotein composition and function.

Psoriasis is a chronic inflammatory disorder associated with increased cardiovascular mortality. Psoriasis affects high-density lipoprotein (HDL) composition, generating dysfunctional HDL particles. However, data regarding the impact of anti-psoriatic therapy on HDL composition and function are not available. HDL was isolated from 15 psoriatic patients at baseline and after effective topical and/or systemic anti-psoriatic therapy and from 15 age- and sex-matched healthy controls. HDL from psoriatic patients showed a significantly impaired capability to mobilize cholesterol from macrophages (6.4 vs. 8.0% [(3)H]cholesterol efflux, P<0.001), low paraoxonase (217 vs. 350 µM(-1) minute(-1) mg(-1) protein, P=0.011) and increased Lp-PLA2 activities (19.9 vs. 12.1 nM(-1) minute(-1) mg(-1) protein, P=0.028). Of particular interest, the anti-psoriatic therapy significantly improved serum lecithin-cholesterol acyltransferase activity and decreased total serum lipolytic activity but did not affect serum levels of HDL-cholesterol. Most importantly, these changes were associated with a significantly improved HDL-cholesterol efflux capability. Our results provide evidence that effective anti-psoriatic therapy recovers HDL composition and function, independent of serum HDL-cholesterol levels, and support to the emerging concept that HDL function may be a better marker of cardiovascular risk than HDL-cholesterol levels.

Limits of conventional therapies after prolonged normovolemic cardiac arrest in swine.

AIM: Patients' outcomes after prolonged cardiac arrest are often grim. The aim of this study was to find the longest period of normovolemic, normothermic, cardiac arrest no-flow after which good neurologic outcome can be achieved with conventional therapies. METHODS: Swine (28-37 kg) were subjected to ventricular fibrillation cardiac arrest, after which they were randomized into groups with 13 min (n=6), 15 min (n=6), or 17 min (n=6) of untreated cardiac arrest followed by advanced life support (ALS) for 20 min (epinephrine 0.04 mg/kg every 3 min and vasopressin 0.4 IE/kg every 6 min, no defibrillation attempts), followed by cardiopulmonary bypass (CPB). To mimic an unresuscitable situation after prolonged cardiac arrest, CPB was initiated 20 min after the start of resuscitation, followed by defibrillation attempts. Therapeutic mild hypothermia was applied for 20 h and a final neurologic evaluation (neurologic deficit score, NDS; overall performance category, OPC) was done after 9 days. RESULTS: In the 13-min group, restoration of spontaneous circulation (ROSC) was achieved in five of six swine, four of which survived to day 9, and all had favorable neurologic outcomes [one swine OPC 1, three swine OPC 2, NDS 15% (IQR 6-21)]. In the 15- and 17-min groups, ROSC was achieved in three of six and two of six swine, respectively, one survived to day 9 with OPC 3 in each group, and NDS values were 45 and 58%, respectively (Kruskal-Wallis test for OPC, p=0.048). CONCLUSIONS: In our model, the limit of normovolemic, normothermic, cardiac arrest no-flow time, followed by ACLS, CPB, and prolonged mild hypothermia, seems to be 13 min.