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1.
Plast Reconstr Surg Glob Open ; 12(9): e6135, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39234413

RESUMEN

Atraumatic soft issue handling is essential for optimal wound healing. Simulation is a safe and effective way to improve surgical skills outside the operating room. Our primary aim was the development of a pressure-sensing forceps that measures the force applied to a given tissue and provides real-time biofeedback. Seventy-eight students and trainees performed four trials of a continuous subcuticular closure using our Tissue Handling Trainer System device on a silicone skin model. We recorded the occurrence of above-threshold pressure and duration of time over the threshold. A one-way analysis of variance with Tukey post hoc test was used to analyze duration above-threshold pressure. There were statistically significant differences in the duration above threshold from trials 1 to 3 (P < 0.001). A 36% reduction occurred between trials 1 and 2 after participants learned of the study purpose, but a 70% reduction between trials 2 and 3 with audible feedback. There was no statistically significant difference between trials 3 and 4 (P = 0.807). The Tissue Handling Trainer System may be an effective technique for improving tissue handling skills in the surgical simulation laboratory.

2.
J Surg Case Rep ; 2022(1): rjab546, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35035876

RESUMEN

A 58-year-old male with an insignificant past medical history presented with chronic myelogenous leukemia in blast crisis. He began induction chemotherapy complicated by neutropenic fever. The patient then developed a nontender 1.5 cm violaceous firm indurated papule above the left patella with satellite lesions on his wrist and chest. A biopsy of the left patella showed obliterated blood vessels in the deep reticular dermis and numerous hyphae with septation and acute angle branching in the vessel wall consistent with angioinvasive aspergillosis. He was started on liposomal amphotericin and empiric voriconazole. Urgent local surgical excision of the primary lesion was recommended for source control. There is no clear recommendation on surgical intervention for angioinvasive aspergillosis, and further direction is needed. We present a case that illustrates surgical debridement for angioinvasive aspergillosis to be an effective method of source control along with systemic antifungal therapy.

3.
Artículo en Inglés | MEDLINE | ID: mdl-32387315

RESUMEN

Cocaine use disorders include short-term and acute pathologies (e.g. overdose) and long-term and chronic disorders (e.g. intractable addiction and post-abstinence relapse). There is currently no available treatment that can effectively reduce morbidity and mortality associated with cocaine overdose or that can effectively prevent relapse in recovering addicts. One recently developed approach to treat these problems is the use of enzymes that rapidly break down the active cocaine molecule into inactive metabolites. In particular, rational design and site-directed mutagenesis transformed human serum recombinant butyrylcholinesterase (BChE) into a highly efficient cocaine hydrolase with drastically improved catalytic efficiency toward (-)-cocaine. A current drawback preventing the clinical application of this promising enzyme-based therapy is the lack of a cost-effective production strategy that is also flexible enough to rapidly scale-up in response to continuous improvements in enzyme design. Plant-based expression systems provide a unique solution as this platform is designed for fast scalability, low cost and the advantage of performing eukaryotic protein modifications such as glycosylation. A Plant-derived form of the Cocaine Super Hydrolase (A199S/F227A/S287G/A328W/Y332G) we designate PCocSH protects mice from cocaine overdose, counters the lethal effects of acute cocaine overdose, and prevents reinstatement of extinguished drug-seeking behavior in mice that underwent place conditioning with cocaine. These results demonstrate that the novel PCocSH enzyme may well serve as an effective therapeutic for cocaine use disorders in a clinical setting.


Asunto(s)
Hidrolasas de Éster Carboxílico/uso terapéutico , Trastornos Relacionados con Cocaína/tratamiento farmacológico , Cocaína/envenenamiento , Sobredosis de Droga/tratamiento farmacológico , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Plantas/química , Proteínas Recombinantes/uso terapéutico , Animales , Butirilcolinesterasa/química , Butirilcolinesterasa/uso terapéutico , Condicionamiento Operante/efectos de los fármacos , Sobredosis de Droga/mortalidad , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Nicotiana/química , Nicotiana/metabolismo
4.
Sci Rep ; 8(1): 17223, 2018 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-30443038

RESUMEN

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

5.
Sci Rep ; 7(1): 10419, 2017 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-28874829

RESUMEN

Butyrylcholinesterase (BChE) is an enzyme with broad substrate and ligand specificities and may function as a generalized bioscavenger by binding and/or hydrolyzing various xenobiotic agents and toxicants, many of which target the central and peripheral nervous systems. Variants of BChE were rationally designed to increase the enzyme's ability to hydrolyze the psychoactive enantiomer of cocaine. These variants were cloned, and then expressed using the magnICON transient expression system in plants and their enzymatic properties were investigated. In particular, we explored the effects that these site-directed mutations have over the enzyme kinetics with various substrates of BChE. We further compared the affinity of various anticholinesterases including organophosphorous nerve agents and pesticides toward these BChE variants relative to the wild type enzyme. In addition to serving as a therapy for cocaine addiction-related diseases, enhanced bioscavenging against other harmful agents could add to the practicality and versatility of the plant-derived recombinant enzyme as a multivalent therapeutic.


Asunto(s)
Butirilcolinesterasa/química , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Cocaína/metabolismo , Proteínas de Plantas , Proteínas Recombinantes , Regulación Alostérica , Sitios de Unión , Butirilcolinesterasa/genética , Dominio Catalítico , Cocaína/química , Variación Genética , Hidrólisis , Mutación , Unión Proteica , Estereoisomerismo
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