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1.
Orthopedics ; 46(6): e333-e340, 2023.
Article in English | MEDLINE | ID: mdl-37561100

ABSTRACT

Anterior cruciate ligament tears or ruptures are common orthopedic injuries. Anterior cruciate ligament reconstruction (ACLR) is an orthopedic procedure allowing for earlier return to sports, improved maintenance of lifestyle demands, and restored knee stability and kinematics. A perioperative rehabilitative adjunct recently gaining interest is blood flow restriction (BFR), a method in which temporary restriction of blood flow to a chosen extremity is introduced and can be used as early as a few days postoperative. There has been increasing investigation and recent literature regarding BFR. This review synthesizes current concepts of BFR use in the ACLR perioperative period. [Orthopedics. 2023;46(6):e333-e340.].


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Humans , Anterior Cruciate Ligament/surgery , Knee Joint/surgery , Anterior Cruciate Ligament Injuries/surgery , Postoperative Period , Anterior Cruciate Ligament Reconstruction/methods
2.
Int J Mol Sci ; 23(20)2022 Oct 11.
Article in English | MEDLINE | ID: mdl-36292948

ABSTRACT

The marine cone snail produces one of the fastest prey strikes in the animal kingdom. It injects highly efficacious venom, often causing prey paralysis and death within seconds. Each snail has hundreds of conotoxins, which serve as a source for discovering and utilizing novel analgesic peptide therapeutics. In this study, we discovered, isolated, and synthesized a novel α3/5-conotoxins derived from the milked venom of Conus obscurus (α-conotoxin OI) and identified the presence of α-conotoxin SI-like sequence previously found in the venom of Conus striatus. Five synthetic analogs of the native α-conotoxin OI were generated. These analogs incorporated single residue or double residue mutations. Three synthetic post-translational modifications (PTMs) were synthetically incorporated into these analogs: N-terminal truncation, proline hydroxylation, and tryptophan bromination. The native α-conotoxin OI demonstrated nanomolar potency in Poecilia reticulata and Homosapiens muscle-type nicotinic acetylcholine receptor (nAChR) isoforms. Moreover, the synthetic α-[P9K] conotoxin OI displayed enhanced potency in both bioassays, ranging from a 2.85 (LD50) to 18.4 (IC50) fold increase in comparative bioactivity. The successful incorporation of PTMs, with retention of both potency and nAChR isoform selectivity, ultimately pushes new boundaries of peptide bioengineering and the generation of novel α-conotoxin-like sequences.


Subject(s)
Conotoxins , Conus Snail , Receptors, Nicotinic , Animals , Conus Snail/chemistry , Venoms , Tryptophan/metabolism , Conotoxins/genetics , Conotoxins/chemistry , Receptors, Nicotinic/genetics , Receptors, Nicotinic/metabolism , Peptides/metabolism , Bioengineering , Proline/metabolism
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