Functionality-type and chemical-composition separation of poly(lactide-co-glycolide) using gradient elution normal-phase liquid chromatography with basic and acidic additives

End groups of poly(Lactide-co-glycolide) (PLGA) play an important role in determining the properties of polymers for use in drug delivery systems. For instance, it has been reported that the encapsulation efficiency in PLGA microspheres varies significantly between ester-terminated and acid-terminated PLGA. More importantly, the in-vivo degradation time of such polymer excipients is influenced by the functional end-group of the copolymer used.The end group distribution in PLGA polymers has been studied using electrospray and matrix-assisted laser-desorption/ionization – high-resolution mass spectrometry. In both cases, the application of these methods is typically limited to PLGA having a molecular weight of up to 4 kDa. 13Carbon-nuclear-magnetic-resonance has also been reported as a method to differentiate and quantify PLGA end groups with a molecular weight up to 136 kDa. However, reported NMR methods take over 12 h per sample, limiting throughput.Cryoprobe NMR can reduce the time required for the process, however such NMR equipment is costly, which makes it unsuitable for the quality control of PLGA.Here, we present a normal-phase liquid chromatography method capable of resolving functionality type distribution (FTD) and, partially, chemical composition distribution (CCD) in commercial PLGA polymers obtained from ring opening polymerization. This method can separate PLGA polymers with a molecular weight of up to 183.0 kDa while also enabling the simultaneous separation of the difference of Lactic acid (LA)/Glycolic acid (GA) ratios.To achieve this, a cross-linked diol column was used with a ternary gradient from HEX to 0.1 % v/v TEA in EA to 0.1 % v/v FA in THF to allow first for the elution of mono-ester terminated PLGA, followed by the di-acid terminated. In addition, a separation of ester-terminated PLGA in the difference of the LA/GA ratio was achieved.This method is expected to aid in understanding the correlation between PLGA's FTD, CCD, and physical properties, facilitating product development and quality control

Cardiovascular and Interventional Radiological Society of Europe Commentary on the Treatment of Chronic Cerebrospinal Venous Insufficiency

Chronic cerebrospinal venous insufficiency (CCSVI) is a putative new theory that has been suggested by some to have a direct causative relation with the symptomatology associated with multiple sclerosis (MS) [1]. The core foundation of this theory is that there is abnormal venous drainage from the brain due to outflow obstruction in the draining jugular vein and/or azygos veins. This abnormal venous drainage, which is characterised by special ultrasound criteria, called the “venous hemodynamic insufficiency severity score” (VHISS), is said to cause intracerebral flow disturbance or outflow problems that lead to periventricular deposits [2]. In the CCSVI theory, these deposits have a great similarity to the iron deposits seen around the veins in the legs in patients with chronic deep vein thrombosis. Zamboni, who first described this new theory, has promoted balloon dilatation to treat the outflow problems, thereby curing CCSVI and by the same token alleviating MS complaints. However, this theory does not fit into the existing bulk of scientific data concerning the pathophysiology of MS. In contrast, there is increasing worldwide acceptance of CCSVI and the associated balloon dilatation treatment, even though there is no supporting scientific evidence. Furthermore, most of the information we have comes from one source only. The treatment is called “liberation treatment,” and the results of the treatment can be watched on YouTube. There are well-documented testimonies by MS patients who have gained improvement in their personal quality of life (QOL) after treatment. However, there are no data available from patients who underwent unsuccessful treatments with which to obtain a more balanced view. The current forum for the reporting of success in treating CCSVI and thus MS seems to be the Internet. At the CIRCE office and the MS Centre in Amsterdam, we receive approximately 10 to 20 inquiries a month about this treatment. In addition, many interventional radiologists, who are directly approached by MS patients, contact the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) for advice. Worldwide, several centres are actively promoting and performing balloon dilatation, with or without stenting, for CCSVI. Thus far, no trial data are available, and there is currently no randomized controlled trial (RCT) in progress Therefore, the basis for this new treatment rests on anecdotal evidence and successful testimonies by patients on the Internet. CIRSE believes that this is not a sound basis on which to offer a new treatment, which could have possible procedure-related complications, to an often desperate patient population

Persistent Organic Pollutant in the Venetian coastal environment

The Venetian coastal area is characterized by a strong anthropogenic impact and its quality is very important because of local economical activities, such as tourism or fishing. In the context of the Water Framework Directive (WFD, 2000/60/EC), the aim of the project Q-ALiVe (Qualità dell’Ambiente Litoraneo Veneto) is to check the environmental quality of the Venetian coastal area and whether rivers contamination could influence it. We studied an area going from the mouth of the Adige river to the Malamocco inlet of the Venice lagoon (including the mouth of the Brenta river and the Chioggia lagoon inlet), to distance from the coast of up to about a kilometer. In this work we presented the data relative to Persistent Organic Pollutants (POPs) as PCBs, PBDEs and PAHs, in samples of seawater. Samples were collected during four different sampling campaigns, in different seasons (June 2011, August 2011, September 2011, November 2011); in each sampling campaign we collected 10 samples of surface water. Analytical samples procedures for POPs include liquid-liquid continuous extraction, followed by an automated purification step, with neutral silica columns. Analysis were made by HRGC-HRMS (PCBs) or HRGC-LRMS (PAHs and PBDEs). Quantification was made by isotope dilution. Results suggest a negligible influence of rivers contamination to the quality of the sea facing the city of Chioggia and the Venice lagoon. Funds for this work were provided, in the framework of Q-ALiVe Project, by the Regione del Veneto - L.R. 15/07

Evaluation of a New Balloon Catheter for Difficult Calcified Lesions in Infrainguinal Arterial Disease: Outcome of a Multicenter Registry

The purpose of this study was to assess the technical performance and immediate procedure outcome of a new balloon catheter in the treatment of calcified lesions in infrainguinal arterial disease. Seventy-five patients with infrainguinal arterial disease were prospectively entered into the registry. The catheter (ReeKross Clearstream, Ireland) is a 5- to 6-Fr balloon catheter with a rigid shaft intended for enhanced pushability. Only technical procedural outcome was recorded. Treated calcified lesions (range: 5–30 cm), assessed angiographically, were located in the superficial femoral, popliteal, and crural arteries. In 67 patients the lesion was an occlusion. Guidewire passage occurred subintimally in 68 patients. In 24 patients a standard balloon catheter was chosen as first treatment catheter: 5 failed to cross the lesion, 8 balloons ruptured, and in 11 patients there was an inadequate dilatation result. In only one of the five patients did subsequent use of the ReeKross catheter also fail in lesion crossing. The ReeKross was successful as secondary catheter in the other 23 cases. In 50 patients the ReeKross was used as primary catheter. In total the ReeKross crossed the lesions in 74 patients. After passage and dilatation with this catheter in 73 patients (1 failed true-lumen reentry), 19 had >30% residual lesions, of which 11 were not treated and 8 were successfully stented. No ReeKross balloons ruptured. We conclude that in the treatment of difficult calcified lesions in arterial stenotic or occlusive disease, the choice of a high-pushability angioplasty catheter, with more calcification-resistant balloon characteristics, like the ReeKross, warrants consideration

Always Contact a Vascular Interventional Specialist Before Amputating a Patient with Critical Limb Ischemia

Patients with severe critical limb ischemia (CLI) due to long tibial artery occlusions are often poor candidates for surgical revascularization and frequently end up with a lower limb amputation. Subintimal angioplasty (SA) offers a minimally invasive alternative for limb salvage in this severely compromised patient population. The objective of this study was to evaluate the results of SA in patients with CLI caused by long tibial occlusions who have no surgical options for revascularization and are facing amputation. We retrospectively reviewed all consecutive patients with CLI due to long tibial occlusions who were scheduled for amputation because they had no surgical options for revascularization and who were treated by SA. A total of 26 procedures in 25 patients (14 males; mean age, 70 ± 15 [SD] years) were evaluated. Technical success rate was 88% (23/26). There were four complications, which were treated conservatively. Finally, in 10 of 26 limbs, no amputation was needed. A major amputation was needed in 10 limbs (7 below-knee amputations and 3 above-knee amputations). Half of the major amputations took place within 3 months after the procedure. Cumulative freedom of major amputation after 12 months was 59% (SE = 11%). In six limbs, amputation was limited to a minor amputation. Seven patients (28%) died during follow-up. In conclusion, SA of the tibial arteries seem to be a valuable treatment option to prevent major amputation in patients with CLI who are facing amputation due to lack of surgical options

Effectiveness of revascularisation of the ulcerated foot in patients with diabetes and peripheral artery disease: A systematic review

In patients with diabetes, foot ulceration and peripheral artery disease (PAD), it is often difficult to determine whether, when and how to revascularise the affected lower extremity. The presence of PAD is a major risk factor for non-healing and yet clinical outcomes of revascularisation are not necessarily related to technical success. The International Working Group of the Diabetic Foot updated systematic review on the effectiveness of revascularisation of the ulcerated foot in patients with diabetes and PAD is comprised of 64 studies describing >13000 patients. Amongst 60 case series and 4 non-randomised controlled studies, we summarised clinically relevant outcomes and found them to be broadly similar between patients treated with open vs endovascular therapy. Following endovascular revascularisation, the 1 year and 2 year limb salvage rates were 80% (IQR 78-82%) and 78% (IQR 75-83%), whereas open therapy was associated with rates of 85% (IQR 80-90%) at 1 year and 87% (IQR 85-88%) at 2years, however these results were based on a varying combination of studies and cannot therefore be interpreted as cumulative. Overall, wound healing was achieved in a median of 60% of patients (IQR 50-69%) at 1 year in those treated by endovascular or surgical therapy, and the major amputation rate of endovascular vs open therapy was 2% vs 5% at 30days, 10% vs 9% at 1 year and 13% vs 9% at 2years. For both strategies, overall mortality was found to be high, with 2% (1-6%) perioperative (or 30day) mortality, rising sharply to 13% (9-23%) at 1 year, 29% (19-48%) at 2years and 47% (39-71%) at 5years. Both the angiosome concept (revascularisation directly to the area of tissue loss via its main feeding artery) or indirect revascularisation through collaterals, appear to be equally effective strategies for restoring perfusion. Overall, the available data do not allow us to recommend one method of revascularisation over the other and more studies are required to determine the best revascularisation approach in diabetic foot ulceration.Peer reviewe