Somatic mutations in KCNJ5, ATP1A1, or CACNA1D genes are not limited to APAs but are also found in the more frequent multinodular adrenals. In multinodular glands, only one nodule harbors a mutation. This suggests that the occurrence of a mutation and nodule formation are independent processes. The implications for clinical management remain to be determined.
Nitric
oxide (NO) is a highly potent but short-lived endogenous radical with
a wide spectrum of physiological activities. In this work, we developed
an enzymatic approach to the site-specific synthesis of NO mediated
by biocatalytic surface coatings. Multilayered polyelectrolyte films
were optimized as host compartments for the immobilized β-galactosidase
(β-Gal) enzyme through a screen of eight polycations and eight
polyanions. The lead composition was used to achieve localized production
of NO through the addition of β-Gal–NONOate, a prodrug
that releases NO following enzymatic bioconversion. The resulting
coatings afforded physiologically relevant flux of NO matching that
of the healthy human endothelium. The antiproliferative effect due
to the synthesized NO in cell culture was site-specific: within a
multiwell dish with freely shared media and nutrients, a 10-fold inhibition
of cell growth was achieved on top of the biocatalytic coatings compared
to the immediately adjacent enzyme-free microwells. The physiological
effect of NO produced via the enzyme prodrug therapy was validated
ex vivo in isolated arteries through the measurement of vasodilation.
Biocatalytic coatings were deposited on wires produced using alloys
used in clinical practice and successfully mediated a NONOate concentration-dependent
vasodilation in the small arteries of rats. The results of this study
present an exciting opportunity to manufacture implantable biomaterials
with physiological responses controlled to the desired level for personalized
treatment.
Collagen has been extensively used as a biomaterial, yet for tubular organ repair, synthetic polymers or metals (e.g., stents) are typically used. In this study, we report a novel type of tubular implant solely consisting of type I collagen, suitable to self‐expand in case of minimal invasive implantation. Potential benefits of this collagen scaffold over conventional materials include improved endothelialization, biodegradation over time, and possibilities to add bioactive components to the scaffold, such as anticoagulants. Implants were prepared by compression of porous scaffolds consisting of fibrillar type I collagen (1.0–2.0% (w/v)). By applying carbodiimide cross‐linking to the compressed scaffolds in their opened position, entropy‐driven shape memory was induced. The scaffolds were subsequently crimped and dried around a guidewire. Upon exposure to water, crimped scaffolds deployed within 15–60 s (depending on the collagen concentration used), thereby returning to the original opened form. The scaffolds were cytocompatible as assessed by cell culture with human primary vascular endothelial and smooth muscle cells. Compression force required to compress the open scaffolds increased with collagen content from 16 to 32 mN for 1.0% to 2.0% (w/v) collagen scaffolds. In conclusion, we report the first self‐expandable tubular implant consisting of solely type I collagen that may have potential as a biological vascular implant.
The unexpected discovery presented herein is that industrialized metallic wires can perform conversion of the glucuronide prodrugs with ensuing antibacterial effects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.