Revascularization of the superficial femoral artery with paclitaxel-coated balloon for claudication

Background: Percutaneous angioplasty of the superficial femoral artery (SFA) with paclitaxel-coated balloon, intended to reduce restenosis, has been proven safe and effective in recent randomized controlled trials.

Objective: To assess outcome results of angioplasty of the SFA with paclitaxel-coated balloon in claudicants in real-world practice of a single center.

Material &; Methods: A continuous prospective cohort study of 53 claudicants (62 lower limbs) from January 2015 to December 2016. Study end points include primary patency, freedom from clinically driven target-lesion revascularization and symptom relief.

Results: It concerns 17 women (32%) and 36 men (68%) with a mean age of 67.8 years, suffering life-style-limiting claudication. Only short to intermediate-length stenoses or occlusions (30.6%), with a mean length of 59.6?mm were selected for percutaneous angioplasty with a paclitaxel-coated balloon. Technical success was 100%. At 16 months, primary patency attained 92.0% (3 early occlusions, 2 restenoses). There were two re-interventions at 6 and 9 months, resulting in a clinically driven target lesion revascularization rate of 3.2%. At the end of the follow-up of 16 months, all but two patients (96.2%) remained symptom-free. Two patients died during follow-up (no procedure-related deaths).

Conclusion: Paclitaxel-coated balloon angioplasty of the SFA gives in routine clinical practice excellent midterm results, with a restenosis rate of 6.5% at 1 year. This procedure has authors’ preference as first-choice technique for correction of short- and intermediate-length symptomatic stenoses of the SFA.     

The kinase domain of mitochondrial PINK1 faces the cytoplasm

Mutations in PTEN-induced putative kinase 1 (PINK1) are a cause of autosomal recessive familial Parkinson's disease (PD). Efforts in deducing the PINK1 signaling pathway have been hindered by controversy around its subcellular and submitochondrial localization and the authenticity of its reported substrates. We show here that this mitochondrial protein exhibits a topology in which the kinase domain faces the cytoplasm and the N-terminal tail is inside the mitochondria. Although deletion of the transmembrane domain disrupts this topology, common PD-linked PINK1 mutations do not. These results are critical in rectifying the location and orientation of PINK1 in mitochondria, and they should help decipher its normal physiological function and potential pathogenic role in PD.     

Inhibition of TLR Ligand- and Interferon Gamma-Induced Murine Microglial Activation by Panax Notoginseng

Among the many products which influence microglial activation and resulting neuroinflammation, herbal medicine has recently drawn much attention due to its immunomodulatory and neuroprotective activities. The purpose of the current study was to investigate the effects of an extract of Panax notoginseng (NotoG?) on TLR ligand- and IFNγ-induced activation in N9 and EOC20 microglial cells lines. NotoG suppressed microglial activation as measured by reduced expression of accessory molecules (CD40 and CD86), decreased production of inflammatory mediators (IL-6 and TNFα), and diminished release of antibacterial products (nitric oxide). Furthermore, this immunosuppressive activity was neither dependent on the glucocorticoid receptor, nor the result of a single ginsenosides (Rb1, Rg1, or Re), which are the major active constituents of the whole extract. NotoG and select ginsenosides may therefore be of therapeutic benefit in treating or preventing neurodegenerative diseases such as multiple sclerosis and parkinson's disease.     

Safety and patient perception of an insulin pen with simple memory function for children and adolescents with type 1 diabetes - the REMIND study

Abstract Objectives: NovoPen Echo * is a durable pediatric insulin pen incorporating half-unit dosing starting at 0.5 units and a last-dose memory function. The REMIND ? (Rating the Effects of Memory function in pediatric INsulin Devices) study primarily examined the safety of this new device by collecting data on technical complaints (TCs) related to adverse reactions (ARs) during use in a clinical setting. *NovoPen Echo? Novo Nordisk A/S, Bagsv?rd, Denmark ?REMIND? Novo Nordisk A/S, Bagv?rd, Denmark Methods: REMIND was an observational, multicenter study involving patients with type 1 diabetes on injection therapy, aged 2-18 years, from Canada, Finland, Israel and Sweden. Questionnaires and case report forms were completed at baseline and after using NovoPen Echo for 12-18 weeks. Results: In total, 358 patients participated and 315 completed. No serious ARs were reported. Three ARs related to TCs were reported, equated to one every 29 patient-years. Most patients found it 'easy' or 'somewhat easy' to read amount (99%) and hours lapsed (95%) since last dose using the memory function. The proportion of children self-injecting was significantly higher (71%) compared with those on previous device (66%, p?=?0.006). 80% of physicians answers reported they could train users in ≤10 minutes. Conclusions: Only three device safety events were reported for NovoPen Echo. Physicians found it easy and quick to educate users. Patients/caregivers missed fewer injections and reported greater confidence in managing their insulin injections. As this was an observational study without controls or centralized laboratory testing, caution should be used in interpreting outcomes in glycemic control. Further studies are required to examine the effects of features such as memory function and half-unit dosing on HbA(1c) and hypoglycemia over a longer time period.     

Mouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production

Objective

Animal models of asthma mimic major features of human disease. Since the genetic background of experimental animals might affect hyperresponsiveness and inflammation, we studied its potential influence and the mechanisms leading to differences in strains.

Methods

We applied a mouse model of allergic asthma to BALB/c and C57BL/6 mice.

Results

BALB/c mice displayed greater levels of airway reactivity to methacholine than C57BL/6 mice. Moreover, BALB/c mice exhibited higher numbers of mast cells in lung tissue when compared to C57BL/6. On the contrary, eosinophil and neutrophil counts in bronchoalveolar lavage fluid (BALF) as well as peribronchial eosinophilia were greater in C57BL/6. IL (Interleukin)-4, IL-5, IL-13, and CCL11 levels measured in whole-lung extracts were higher in BALB/c, while, in sharp contrast, CCL11 and CCL5 levels were higher in BALF of C57BL/6 mice.

Conclusions

We observed phenotypic differences between C57BL/6 and BALB/c mice in an asthma model with different distributions of pro-inflammatory cytokines and inflammatory cells.     

IGL-1 solution in kidney transplantation: first multi-center study

Abstract:  IGL-1 solution is characterized by inversion of K+ and Na+ concentrations in the University Wisconsin (UW) solution and polyethylene glycol 35 (PEG 35) substitution for hydroxy ethyl starch. In this prospective study, 121 patients transplanted with kidneys preserved in IGL-1 solution were compared to 102 patients grafted with kidneys preserved in UW solution. Serum creatinine and creatinine clearance, delayed graft function (DGF) and rejection episodes, patient and graft survival were evaluated in the first post-transplant year. Groups were comparable regarding to donor and recipient characteristics. Median creatinine levels were significantly lower in IGL-1 group from day 6 to day 14 and it decreased more rapidly in the IGL-1 group (from day 4 to day 15: p < 0.05). Creatinine clearance values were usually higher in the IGL-1 group for the first 15 d. During the follow-up period serum creatinine concentrations were lower in IGL-1 group at one, three, six and 12 months after transplantation (p = 0.04; p = 0.06, p = 0.01 and p = 0.08, respectively) while creatinine clearance values were similar during the follow-up. No significant difference in DGF and rejection rates as well as in patient and graft survival was shown between the two groups. Kidneys preserved in IGL-1 solution showed to have the same function as kidneys preserved in UW solution.     

The effect of RGD density on osteoblast and endothelial cell behavior on RGD-grafted polyethylene terephthalate surfaces

Hybrid materials combining polyethylene terephthalate and different types of cells (endothelial and osteoblastic cells) have been developed thanks to the covalent grafting of different densities of RGD containing peptides onto the polymer surface. Biomimetic modifications were performed by means of a three-step reaction procedure: creation of COOH functions, coupling agent grafting and the immobilization of the RGDC peptides. High resolution μ-imager was used to evaluate RGD densities (varying between 0.6 and 2.4 pmol/mm²) and has exhibited the stability of the surface grafted peptides when treated in harsh conditions. The efficiency of this route for biomimetic modification of a PET surface was demonstrated by measuring the adhesion of MC3T3 and HSVEC cells and by focal adhesion observation. Results obtained prove that a minimal RGDC density of 1 pmol/mm² is required to improve MC3T3 and HSVEC cells responses. Indeed, cells seeded onto a RGDC-modified PET with a density higher than 1 pmol/mm² were able to establish focal adhesion as visualized by fluorescence microscope compared to cells immobilized onto unmodified PET and RGDC-modified PET with densities lower than 1 pmol/mm². Moreover, the number of focal contacts was enhanced by the increase of RGDC peptide densities grafted onto the material surface. With this study we proved that the density of peptides immobilized on the surface is a very important parameter influencing osteoblast or endothelial cell adhesion and focal contact formation.