Vascularization of PEG-grafted macroporous hydrogel sponges: a three-dimensional in vitro angiogenesis model using human microvascular endothelial cells

The native extracellular matrix (ECM) of elastic tissues is strong and flexible and supports cell adhesion and enzymatic matrix remodeling. In an attempt to convey these ECM properties to a synthetic scaffold appropriate for soft tissue engineering applications, a biodegradable, elastomeric poly(ester urethane)urea (PEUU) was combined with type I collagen at various ratios (2.5, 5, 10, 20, 50, 60, 70, 80, and 90 wt% collagen) and electrospun to construct elastic matrices. Randomly orientated fibers in the electrospun matrices ranged in diameter from 100-900 nm, dependent on initial polymer concentration. Picrosirius red staining of matrices and CD spectroscopy of released collagen confirmed collagen incorporation and preservation of collagen structure at the higher collagen mass fractions. Matrices were strong and distensible possessing strengths of 2-13 MPa with breaking strains of 160-280% even with low PEUU content. Collagen incorporation significantly enhanced smooth muscle cell adhesion onto electrospun scaffolds. An approach has been demonstrated that mimics elastic extracellular matrices by using a synthetic component to provide mechanical function together with a biomacromolecule, collagen. Such matrices may find application in engineering soft tissue.     

Self-Help Devices: Communication and Vocations

While most nonviral causes of encephalitis are recognizable by ordinary means, the diagnosis of viral encephalitis is largely one of exclusion. Brain biopsy, the only reliable means of diagnosing herpes simplex encephalitis early, is justified only in certain critically ill patients. There is room for cautious optimism about idoxuridine therapy of encephalitis in man.     

Were all carbapenemases created equal? Treatment of NDM-producing extensively drug-resistant <Emphasis Type="Italic">Enterobacteriaceae</Emphasis>: a case report and literature review

Purpose

There is currently a paucity of published literature focused on the treatment of infections caused by NDM-producing organisms.

Methods

We describe a case of a bacteraemia caused by an extensively drug-resistant (XDR) New Delhi metallo-β-lactamase (NDM)-producing Serratia marcescens and review the treatment options for XDR NDM-producing Enterobacteriaceae.

Results

Infections caused by New Delhi beta-lactamase (NDM)-producing Enterobacteriaceae are becoming increasingly prevalent worldwide. The presence of the enzyme results in multidrug-resistant and extensively drug-resistant phenotypes which often pose a treatment challenge. Despite this challenge, case reports and series have demonstrated good clinical outcomes with numerous treatment options in comparison to infections due to KPC-producing Enterobacteriaceae.

Conclusions

Further good-quality research focused on the treatment of NDM-producing Enterobacteriaceae is warranted.

     

Assessing the transport of receptor-mediated drug-delivery devices across cellular monolayers

Receptor-mediated endocytosis (RME) has been extensively studied as a method for augmenting the transport of therapeutic devices across monolayers. These devices range from simple ligand-therapeutic conjugates to complex ligand-nanocarrier systems. However, characterizing the uptake of these carriers typically relies on their comparisons to the native therapeutic, which provides no understanding of the ligand or cellular performance. To better understand the potential of the RME pathway, a model for monolayer transport was designed based on the endocytosis cycle of transferrin, a ligand often used in RME drug-delivery devices. This model established the correlation between apical receptor concentration and transport capability. Experimental studies confirmed this relationship, demonstrating an upper transport limit independent of the applied dose. This contrasts with the dose-proportional pathways that native therapeutics rely on for transport. Thus, the direct comparison of these two transport mechanisms can produce misleading results that change with arbitrarily chosen doses. Furthermore, transport potential was hindered by repeated use of the RME cycle. Future studies should base the success of this technology not on the performance of the therapeutic itself, but on the capabilities of the cell. Using receptor-binding studies, we were able to demonstrate how these capabilities can be predicted and potentially adopted for high-throughput screening methods.     

Effects of Exercise on Nutritional Status in People with Cystic Fibrosis: A Systematic Review

Background: Physical exercise is an important part of regular care for people with cystic fibrosis (CF). It is unknown whether such exercise has beneficial or detrimental effects on nutritional status (body composition). Thus, the objective of this review was to evaluate the effect of exercise on measures of nutritional status in children and adults with CF. Methods: Standardized reporting guidelines for systematic reviews were followed and the protocol was prospectively registered. Multiple databases were utilized (e.g., PubMed, Scopus, and CINHAL). Two reviewers independently reviewed titles/abstracts and then the full text for selected studies. Results: In total, 924 articles were originally identified; data were extracted from 4 eligible studies. These four studies included only children; pulmonary function ranged from severe to normal, and the majority of participants were at or below their recommended weight. Exercise training did not worsen nutritional status in any study; two studies that included resistance exercise reported an increase in fat-free mass. Three of the four studies also reported increased aerobic capacity and/or muscle strength. Conclusions: Exercise training can produce positive physiologic changes in children with CF without impairing their nutritional status. In fact, resistance exercise can help improve body mass. Much less is known about how exercise may affect adults or those who are overweight.     

The correction of cerebrovascular insufficiency by transluminal dilatation: a preliminary report

Transluminal angioplasty is being extensively utilized to dilate arteriosclerotic lesions. However, this technique has not been widely used for the treatment of cerebrovascular insufficiency. This report describes the application of transluminal angioplasty to relieve cerebral ischemia secondary to extracranial arterial stenosis. A total of 10 patients presented with symptoms of vertebrobasilar insufficiency. Bilateral upper extremity pressures were measured prior to the performance of arteriography on all patients. Significant stenoses were found in the subclavian artery (9) and in the innominate artery (1). Dilating catheters were passed retrograde through surgically exposed brachial and common carotid arteries. Transluminal angioplasty under fluoroscopic control was attempted. Anatomic correction of all lesions was achieved without hemorrhagic or embolic complications. The mean increase in brachial systolic pressure was 38.2 mm Hg postdilatation. Initial symptomatic relief was total in seven patients, partial in two, and absent in one. It is believed that associated small vessel brain stem disease accounted for the less than total relief of symptoms of these three patients. Average follow-up for all patients was 13 months with one recurrent subclavian artery stenosis occurring at three months postangioplasty. Preliminary results suggest that some patients with cerebral ischemia secondary to extracranial arterial stenosis can be treated safely by transluminal angioplasty.     

Evaluation of porous networks of poly(2-hydroxyethyl methacrylate) as interfacial drug delivery devices

Long-term implantable drug delivery devices are desirable to achieve rapid and reliable delivery of bioactive substances to the body. The limitation of most implantable devices is the resulting chronic inflammatory response and fibrous encapsulation of the implant, which prevents effective drug delivery for prolonged periods. One method of overcoming this problem is the addition of an intermediary that could prevent capsule formation. Biocompatible materials with interconnected pore structures greater than 8-10 microm have been shown to support the ingrowth and maintenance of vascularized tissue. In this investigation, we evaluate the efficacy of using porous hydrogel sponges for the tissue interface in an implantable drug delivery device. Porous networks of poly(2-hydroxyethyl methacrylate) (PHEMA) were synthesized using a thermally initiated free-radical solution polymerization. To characterize the microstructure of the PHEMA networks, scanning electron microscopy and mercury porosimetry were used. By altering the solvent fraction in the reaction mixture, PHEMA sponges were synthesized with interconnected pores ranging in size from from 6 to 15 microm with porosities of 55% to 87%. Following the in vitro evaluation, sponges were attached to the distal end of a 20-gauge catheter tubing, and implanted subcutaneously and intraperitoneally. After 5 months implantation, insulin was infused into the devices from external pumps and rapid insulin absorption was observed in conjunction with dramatic lowering of blood glucose levels. From histological evaluation of explanted devices, we observed highly vascularized tissue surrounding the mesenteric implants. These results indicate that it may be possible to use PHEMA sponges for a tissue intermediary for long-term implantable drug delivery devices.