Peripheral artery disease (PAD) is a systemic vascular disease of the legs that results in a blockage of blood flow from the heart to the lower extremities. Now one of the most common causes of mortality in the U.S., the first line of therapy for PAD is to mechanically open the blockages using balloon angioplasty. Coating the balloons with antiproliferative agents can potentially reduce vessel re-narrowing, or restenosis after surgical intervention, but current drug-coated balloons releasing chemotherapy agents like paclitaxel have in some cases shown increased mortality long-term. Our aim was to design a novel drug-coated balloon using a polymeric nanodelivery system for a sustained release of polyphenols that reduce restenosis but with reduced toxicity compared to chemotherapy agents. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles with entrapped quercetin, a dimethoxy quercetin (rhamnazin), as well as quercetin conjugated to PLGA, were developed. Balloon catheters were coated with polymeric nanoparticles using an ultrasonic method, and nanoparticle characteristics, drug loading, coating uniformity and drug release were determined. The adhesion of nanoparticles to vascular smooth muscle cells and the antiproliferative effect of nano-delivered polyphenols were also assessed. Of the nanoparticle systems tested, those with covalently attached quercetin provided the most sustained release over a 6-day period. Although these particles adhered to cells to a smaller extent compared to other nanoparticle formulations, their attachment was resistant to washing. These particles also exhibited the greatest anti-proliferative effect. In addition, their attachment was not altered when the cells were grown in calcifying conditions, and in PAD tissue calcification is typically a condition that impedes drug delivery. Moreover, the ultrasonic coating method generated a uniform balloon coating. The polymeric nanoparticle system with covalently attached quercetin developed herein is thus proposed as a promising platform to reduce restenosis post-angioplasty.
A 6-month-old female entire, mixed breed dog was presented for evaluation of a 3-week history of neck stiffness and pain on opening the mouth. Radiographs and subsequent CT were performed, as well as a further CT at a 3-month follow-up. The images revealed multiple osseous abnormalities characterised by severe periosteal reactions affecting the head, cervical vertebrae and the proximal thoracic limbs. Histopathological analysis was compatible with a severe case of extensive craniomandibular osteopathy (CMO). To the authors’ knowledge, a diffuse periosteal reaction effecting the cervical vertebrae, associated with CMO, has not been previously reported. Furthermore, it demonstrates that despite the novel distribution of the disease, clinical improvement is possible with conservative management, with partial resolution of excessive bone proliferation, improvement in the ability to flex and extend the neck, as well as a marked improvement in temporomandibular function.
Objectives The aim of this study was to describe how the addition of contrast-enhanced low-field magnetic resonance imaging sequences can confirm or change the initially planned surgical approach for canine intervertebral disc extrusions.
Study Design Magnetic resonance imagings of 20 dogs diagnosed with intervertebral disc extrusions were retrospectively reviewed by a board-certified neurologist for the location of extradural disc material, contrast enhancement, and whether enhancement reinforced or changed the initially planned surgical approach.
Results Extradural compressive material contrast-enhanced in 17/20 dogs. In 14/20 dogs, enhancement was considered to increase the confidence level of the location for surgery including two cases where the surgical approach was altered.
Conclusion Gadolinium-based contrast agents in low-field magnetic resonance imaging can aid the surgical planning of intervertebral disc extrusions in dogs by improving the confidence level of location and extent of extradural material and occasionally altering the surgical approach.
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