Preliminary clinical outcome and imaging criterion for endovascular prosthesis development in high-risk patients who have aortoiliac and traumatic arterial lesions

PURPOSE: This report reviews our preliminary experience of prospective treatment of arterial lesions with endoluminal grafts in a Food and Drug Administration (FDA)-approved, investigator-sponsored Investigation Device Exemptions study. The utility and accuracy of various imaging methods, including angiography, cinefluoroscopy, computed tomography (CT), intravascular ultrasonography (IVUS), and duplex scanning, in performing the procedures was also assessed. METHODS: Thirty-one patients were evaluated; 17 patients were treated, including 11 with abdominal aortic aneurysms, one with an aortic occlusive lesion, two with iliac artery aneurysms, and three with traumatic arteriovenous fistulas. Twelve of the 14 patients who had aorta and iliac artery lesions were high-risk. The mean follow-up of patients treated was 9 months (range, 6 to 15 months). RESULTS: Aortoaortic endoluminal interposition procedures were not successful for treating abdominal aortic aneurysms early in the study (n = 3). Aortoiliac endoluminal bypass, contralateral iliac artery occlusion, and femorofemoral bypass procedures were successful in seven of eight subsequent cases (88%), with no incidence of endoleaks at either the proximal or distal fixation sites using the deployment methods described in this report. The 30-day operative mortality rate on follow-up evaluations for patients who underwent aortoiliac procedures was 14% (two of 14). Other major complications included transient renal failure in three patients that required short-term (two to eight times) dialysis, one arterial perforation and one dissection, and one prolonged intubation. No myocardial infarctions or strokes occurred. After major complications or identification of limitations in the study, the protocol was modified with the approval of the FDA to help avoid the recurrence of the same problems. There were no deaths or complications in the trauma cases. CONCLUSIONS: Contrast-enhanced CT (axial images and spiral reconstructions) was the most accurate method to determine candidacy for aortoiliac procedures and to choose the site for deployment of the devices. Angiographic scans were misleading in several patients regarding the critical determinants of patient candidacy and device deployment, particularly regarding the presence of a distal aortic neck. Cinefluoroscopy was used in all patient and was particularly useful for determining the continuity of vascular structures and the anatomy of branch arteries and for enabling precise positioning of stent devices. Determination of fixation sites and assessing dimensional information by cinefluoroscopy and angiography were limited by inaccuracies produced by image magnification, parallax, and uniplanar views. IVUS was used to determine the morphologic features of vascular structures (i.e., calcium, thrombus), to perform real-time observation of the expansion of devices, and to assure firm fixation of balloon-expanded stents before the procedures were completed. Duplex scanning was very helpful in assessing and identifying precisely the location of arteriovenous fistulas before intervention and provided assessment at follow-up intervals. Three-dimensional reconstruction imaging technologies such as spiral CT were particularly helpful for assessing the morphologic features of vascular anatomy before the intervention and at follow-up intervals, whereas 3-D IVUS provided a similar real-time perspective during the procedure.     

In Vivo toxicity assessment of gold nanoparticles in Drosophila melanogaster

The growing use of nanomaterials in commercial goods and novel technologies is generating increasing questions about possible risks for human health and environment, due to the lack of an in-depth assessment of their potential toxicity. In this context, we investigated the effects of citrate-capped gold nanoparticles (AuNPs) on the model system Drosophila melanogaster upon ingestion. We observed a significant in vivo toxicity of AuNPs, which elicited clear adverse effects in treated organisms, such as a strong reduction of their life span and fertility, presence of DNA fragmentation, as well as a significant overexpression of the stress proteins. Transmission electron microscopy demonstrated the localization of the nanoparticles in tissues of Drosophila. The experimental evidence of high in vivo toxicity of a nanoscale material, which is widely considered to be safe and biocompatible in its bulk form, opens up important questions in many fields, including nanomedicine, material science, health, drug delivery and risk assessment.      

Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine

The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release.     

The P2X7 Receptor: A Promising Pharmacological Target in Diabetic Retinopathy

Diabetes is a worldwide emergency. Its chronic complications impose a heavy burden on patients, health systems, and on society as a whole. Diabetic retinopathy is one of the most common and serious complications of diabetes, and an established risk factor for blindness in adults. Over 15 years of investigation led to the identification of vascular endothelial growth factor (VEGF) as a main pathogenic factor in diabetic retinopathy and to the introduction of highly effective anti-VEGF-based therapies, such as the monoclonal antibody bevacizumab or its fragment ranibizumab, which helped to prevent diabetes-related blindness in millions of patients. Recently, a pathogenic role for uncontrolled increases in the extracellular ATP concentration (eATP) and for overactivation of the purinergic receptor P2X7 (P2X7R) has been suggested. The P2X7R is an eATP-gated plasma membrane channel expressed in multiple tissues and organs, with a pleiotropic function in inflammation, immunity, cancer, and hormone and growth factor release. P2X7R stimulation or overexpression positively regulate the secretion and buildup of VEGF, thus promoting neo-angiogenesis in a wide variety of disease processes. In this review, we explore current evidence that supports the role of P2X7R receptor signaling in the pathogenesis of diabetic retinopathy, as well as the most appealing current therapeutical options for P2X7R targeting.     

Orientational imaging of subwavelength Au particles with higher order laser modes

We present a new method for the imaging of single metallic nanoparticles that provides information about their shape and orientation. Using confocal microscopy in combination with higher order laser modes, scattering images of individual particles are recorded. Gold nanospheres and nonorods render characteristic patterns reflecting the different particle geometries. In the case of nanorods, the scattering patterns also reveal the orientation of the particles. This novel technique provides a promising tool for the visualization of nonbleaching labels in the biosciences.     

Plasma Phytosterol Half‐Life and Levels Are Increased in Very Low Birth Weight Preterm Infants with Parenteral Nutrition‐Associated Cholestasis

Parenteral nutrition‐associated cholestasis (PNAC) has been linked to plasma accumulation of phytosterols in infants receiving vegetable‐oil‐based lipid emulsions (LE). To date, information on the ability of infants with PNAC to metabolize intravenous (IV) phytosterols has been very limited. We characterized plasma phytosterol half‐life in very low birth weight (VLBW) preterm infants with PNAC. As part of a prospective cohort study, VLBW infants with PNAC underwent serial blood sample measurements of sitosterol (Sito), campesterol (Camp), and stigmasterol (Stigma). Infants without PNAC served as controls (CTRL, control infants). Thirty‐seven PNAC infants and 14 CTRL were studied. On PN day 7 and PN day 14, PNAC infants had higher plasma phytosterol concentrations compared to those of CTRL (p < 0.05). A significant and positive correlation was found between plasma Camp, Stigma, Sito concentrations, and IV phytosterol intake from birth to PN day 7 (p = 0.001, p = 0.001, and p = 0.005, respectively). Stigma concentration was positively correlated with conjugated bilirubin on PN day 7 (p = 0.012). After stopping IV LE, half‐lives of Camp, Stigma, and Sito became significantly longer in PNAC infants than in CTRL (Camp: 18.8 ±6.2 vs 11.8 ±3.0 days, p = 0.001; Stigma: 13.8 ±5.8 vs 9.4 ±3.4 days, p = 0.023; Sito: 15.3 ±5.0 vs 9.8 ±3.0 days, p = 0.002). In conclusion, phytosterols increased earlier during PN and were eliminated slowly after stopping IV LE in PNAC infants than in CTRL. The Stigma concentration on PN day 7 could represent an early marker of cholestasis. Our results provide additional evidence on the relationship between IV phytosterols and PNAC.