The liposome-protein corona in mice and humans and its implications for in vivo delivery.

As soon as nanomaterials, such as nanoparticles (NPs), are injected into a physiological environment a rich coating of biomolecules known as the "protein corona" rapidly covers them. This protein dress is the main factor, which affects the interaction of NPs with living systems. While the relationship between NP features and the biomolecule corona has been extensively investigated, whether and how changes in the physiological environment affect the NP-protein corona remains under-investigated. This is one of the most important steps in translating results in animal models to the clinic. Here we investigated thoroughly the biological identity of lipid NPs (size, charge, aggregation state and composition of the corona) after incubation with human plasma (HP) and mouse plasma (MP) by dynamic light scattering, micro-electrophoresis and nano-liquid chromatography tandem mass spectrometry (nanoLC/MS-MS). Specifically, we used two different liposomal formulations: the first one was made of polyethyleneglycol (PEG)-coated 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), while the second one was made of 30% of DOTAP, 50% of neutral saturated 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 20% cholesterol. The temporal evolution and complexity of the NP-protein corona was found to be strongly dependent on the biological environment. In MP, liposomes were more negatively charged, less enriched in opsonins and appreciably more enriched in apolipoproteins than their counterparts in HP. Collectively, our results suggest that the biological identities of NPs in mice and humans can be markedly different from each other. Relevance of results to in vivo applications is discussed.

Kinking, coiling, and tortuosity of extracranial internal carotid artery: is it the effect of a metaplasia?

INTRODUCTION: Morphological anomalies of the extracranial internal carotid artery (ICA) cause symptomatic cerebrovascular insufficiency in 4-16% of the cases. The aim of the present study is to evaluate macroscopic and microscopic features of a group of extracranial ICA anomalies, specifically kinking, coiling, and tortuosity, eventually affecting the surgical approach. MATERIALS AND METHODS: From January 2003 to December 2005, 10 out of 169 (6%) revascularized patients (pts) were operated upon because of an ICA anomaly. They were all but two symptomatics. Seven pts were treated by ICA transection and end-to-side reimplantation of the ICA at the level of the carotid bulb; three pts were treated by ICA resection and end-to-end anastomosis. In all the cases a segment of ICA was resected; in three cases one more segment was also obtained from a common carotid artery (CCA) and these specimens were histologically examined. Patients were followed-up through a 3-year period. RESULTS: No pts died and none suffered of neurologic events. Duplex scan and arteriographic postoperative control showed the correct surgical reconstruction. Matching preoperative clinical findings with presence or absence of significant atherosclerotic stenotic lesion, we found out a positive cerebral CT in one pt (20%) in both groups; fluent neurological deficit was preeminent in pts with pure ICA anomalies (40% vs. 0%) (P = 0.2); pts with pure ICA anomalies were significantly younger than 65 years old (80% vs. 0%) (P = 0.03) and males were more involved by pure ICA anomalies (60% vs. 40%) (P = 0.1). The histological examination of ICA specimens showed a reduction of elastic fibers and muscular cells with a compensative increase of connective fibers. CONCLUSIONS: At our knowledge this is the first study focused on ICA anomalies like kinking, coiling, and tortuosity, comparing histologic features of CCA and ICA specimens coming from the same affected carotid axis. Our results, although preliminary, show elastic and muscular tissue substituted by loose connective tissue, configuring a metaplasia of tunica media limited to the ICA. Our hypothesis is that extracranial ICA, being a segment of transition between an elastic vessel (CCA) and a muscular vessel (intracranial ICA), is particularly subject to metaplastic transformation, analogously to other transition zones in human body. Our purpose is now to confirm by ultrastructural and molecular biology techniques, in a wider series, the presence of this metaplasia, since this could condition also the revascularization techniques.

Denatured venous homograft as an arterial substitute in civilian vascular injuries. Thirty months' experience.

OBJECTIVES: Autologous saphenous vein (ASV) for arterial reconstruction, in vascular limb injuries is the graft material of choice. Denatured saphenous vein homograft (DSVH), thanks to its characteristics of readily available autologous biological prosthesis, has been proposed as alternative. We report our prospective experience with DSVH employed for arterial reconstruction in civilian limb vascular injuries. MATERIALS: From January 1994 to June 1996, DSVH was implanted in 16 male patients (pts.) treated for arterial civilian injuries of eight upper limbs and eight lower limbs. METHODS: In 14 cases it was performed as an interposition graft and in two cases a bypass. We performed a 30-month follow-up and a 20-month mean follow-up. RESULTS: Four patients had graft thrombosis at the first postoperative week and were submitted to the replacement of the graft with reappearance of distal arterial pulse; one of them had graft failure at the fifth postoperative week and because the necrosis due to extensive soft tissue damage, he was submitted to limb amputation. After 30-months' follow-up we obtained 75% primary patency rate and 93% secondary patency rate. CONCLUSIONS: In the absence of suitable ASV, DSVH appears to be an interesting alternative for arterial repair in limbs in civilian vascular injuries.

Healing of aortic prosthetic grafts: a study by magnetic resonance imaging.

Thirty-six patients with aortoiliac reconstruction were studied by magnetic resonance imaging (MRI) to determine the diameter, baseline signal, and subsequent magnetic signal characteristics of postoperative periprosthetic collection (PPC). Our study confirmed the presence of PCC in most cases (32/36). The diameter was significantly (p < 0.05) correlated with the type of disease being treated, the type of proximal anastomosis created, and whether or not drainage and postoperative transfusion were used. PPC usually disappeared within 3 to 6 months postoperatively. Modifications of magnetic signals T1 and T2 require approximately the same amount of time to diminish. During follow-up investigations in this series, there was one case of prosthetic infection characterized by the persistence of PPC and a strong T2 signal 6 months after surgery, the latter corresponding to incomplete or delayed healing. The MRI aspects of normal healing of aortic grafts were analyzed to correctly interpret the MRI aspects of complications in surgery of the aorta.

Detection of internal carotid artery stenosis. Comparison of 2D-MR angiography, duplex scanning, and arteriography.

The purpose of this study was to compare digital subtraction angiography (DSA) and duplex scanning with 2D-Magnetic Resonance Angiography (MRA) to evaluate the accuracy of MRA in determining carotid stenosis. All three methods were applied to 101 carotid arteries in 51 patients. Diameter stenosis of the internal carotid artery was categorized as follows: 0 to 39%, 40% to 59%, 60% to 94%, 95% to 99%, and occlusion (100%). All images were read in blind fashion by different physicians. DSA is still considered the "gold standard" investigation. In 78 arteries the degree of stenosis according to MRA correlated exactly with that of conventional angiography. In the remaining 23, carotid arteries MRA upgraded the stenosis in 13 and downgraded it in 8. The principal problem is the overestimation of the lesion, which was particularly revealing in lesions of more than 60%. Furthermore to date MRA is not able to evaluate the presence of ulceration. For this reason 2D-MRA alone is not a reliable method for evaluating the presence of carotid artery stenosis.