Resveratrol loaded in cationic glucosylated liposomes to treat Staphylococcus epidermidis infections.

Glucosylated liposomes composed of the natural saturated phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol (Chol) and a cationic amphiphile featuring a glucosyl moiety (GL4), have been developed for delivering the antimicrobial trans-Resveratrol (RSV) to S. epidermidis, characterized by carbohydrate-specific adhesins able to recognize glucose. The cationic derivative of cholesterol, DC-Chol, was also included in liposome formulations, alone or in combination with GL4, in order to explore the role of both cationic charge and sugar moiety in the interaction of liposomes with bacterial cells. RSV was included inside glucosylated cationic liposomes by the thin film method, coupled with either extrusion or sonication; liposome mean diameter, polydispersity index, surface charge, RSV entrapment efficiency and concentration have been measured by DLS, electrophoretic mobility, and HPLC. The antimicrobial activity of RSV-loaded liposomes was evaluated by monitoring the bacterial growth curves of two cell lines of Staphylococcus epidermidis, a slime positive strain (i.e. a strain able to form a biofilm) and a slime negative one. Results point out that, when the glucosylamphiphile GL4 is included in the formulation, only the extrusion protocol allows obtaining monodisperse liposomes with high RSV entrapment efficiency. The mean diameters of empty and resveratrol-loaded liposomes are all around 120-140 nm and size distribution are narrow, except for samples including GL4 at 5 molar percentage. Here the higher polydispersity index may be the indication of the occurrence of a restructuring phenomenon. The microbiological tests put in evidence a different response of the two bacterial cell lines to liposome treatments, in fact, the slime negative bacterial cells, that are not able to produce the extracellular polymeric substances, are more susceptible to the cationic charge of the liposomes and to the detergent effect of GL4. The most interesting results concern DPPC/Chol/GL4 liposomes on the slime positive strain: this formulation, non-toxic in itself, displays an enhanced antibacterial efficacy with respect to free RSV, killing bacteria even at concentration tenfold under the MIC.

Inflammatory abdominal aortic aneurysm endovascular repair into the long-term follow-up.

BACKGROUND: To investigate long-term outcomes for inflammatory abdominal aortic aneurysms (IAAA) after endovascular treatment (EVAR). METHODS: Between May 1997 and January 2009, 9 male patients (Mean 67 years, range 54-75 years) with IAAA were treated with EVAR using commercially available endografts. Results were assessed using contrast-enhanced computed tomography (CT) at 3 months, 12 months, and biannually thereafter. Echo-color duplex scanning was also recommended at 3, 6, and 12 months after discharge, and annually thereafter. Primary endpoints were aneurysm-related mortality, aneurysm sac evolution, perianeurysmal fibrosis (PAF) thickness, and hydronephrosis progression. RESULTS: No aneurysm-related deaths were observed during the long-term follow-up of eight patients (one patient death unknown). Maximum aneurysm sac diameter progressively reduced in eight patients (89%) and remained unchanged in one (11%). The absolute mean reduction of the aneurysm size was 26.2%. PAF regressed in two patients (22%), reduced in five (56%), and remained unchanged in two (22%). The absolute median reduction of the PAF thickness was 55.1%. No endoleak was observed during the follow-up period. Hydronephrosis persisted in all three patients who were preoperatively diagnosed with this pathology. Survival rates were 89%, 66.7%, and 66.7% at 12, 36, and 60 months, respectively. CONCLUSIONS: This series suggests that EVAR for IAAA into the long-term is associated with a positive trend for both PAF and aneurysm diameter reduction. EVAR does not seem to offer any benefits for hydronephrosis, but seems to effectively exclude the aneurysm sac in anatomically suitable patients.

Thromboelastographic changes in liver and pancreatic cancer surgery: hypercoagulability, hypocoagulability or normocoagulability?

BACKGROUND AND OBJECTIVE: Despite clinical and laboratory evidence of perioperative hypercoagulability, alterations in haemostasis after potentially haemorrhagic oncologic surgery are difficult to predict. This study aims to evaluate the entity, the extent and the duration of perioperative coagulative alterations following pancreas and liver oncologic surgery, by the use of both routine tests and thromboelastogram (TEG). METHODS: Fifty-six patients undergoing liver (n = 38) and pancreatic (n = 18) surgery were studied. The coagulation profile was evaluated by platelet count, prothrombin time-international normalized ratio, activated partial thromboplastin time, antithrombin III and TEG at the beginning, at the end of the operation and on postoperative days 1, 3, 5 and 10. RESULTS: All preoperative coagulative screening and TEG traces were normal before incision. In the postoperative period of the liver and pancreas groups, despite an increase in prothrombin time-international normalized ratio, a reduction in antithrombin III and platelet count and normal activated partial thromboplastin time and fibrinogen, TEG evidenced a normocoagulability in the liver group, with a major tendency towards hypocoagulability in the pancreas group, as evidenced by a transient increase in R-time and K-time between postoperative days 1 and 3. During the study period, four cases of pulmonary embolism, resolved with heparin infusion, were recorded, in the absence of laboratory and thromboelastographic evidence of hypercoagulability. CONCLUSION: Despite laboratory tests evidencing hypocoagulability in both groups, TEG traces showed a normocoagulability in liver resections, whereas a transient thromboelastographic hypocoagulability was evident in patients undergoing pancreas surgery. The discrepancy between laboratory values and thromboelastographic variables was even more evident in patients undergoing major liver resections compared with minor ones. Our study supports the role of thromboelastography, despite its limitations, as a valuable tool for the evaluation of the perioperative whole coagulation process and hypercoagulability changes and to increase patient safety through better management of antithrombotic therapy.