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1.
Artículo en Inglés | MEDLINE | ID: mdl-39074530

RESUMEN

BACKGROUND: Baseball is one of the most popular sports among youth athletes in the United States, and among these players, pitchers are at a particularly high risk of sustaining an injury. Overuse of the arm from repetitive pitching is a common mechanism for injury. Despite the attention that overuse injury has received, little is known regarding the mechanism that leads to elbow injury. This study aims to determine the effect of increasing pitch count on elbow flexion at ball release in a youth pitching cohort. The authors hypothesize that elbow flexion will increase as pitch count increases. METHODS: Study subjects included volunteers from youth baseball players from local teams and public advertisements. Retro-reflective markers attached to bony landmarks were placed on the players according to ISG recommendations. Pitchers threw an indoor simulated game. Three-dimensional marker trajectories were collected using a 12-camera optical motion capture system, and ball velocity was captured using a radar gun. Voluntary maximal isometric strength of the internal and external rotators was evaluated before and after pitching. Paired two-tailed t-tests were performed to determine if a significant change occurred between the fresh and fatigued sets. RESULTS: Twelve adolescent male pitchers were recruited. Eleven of 12 pitchers completed the prescribed 6 sets of 15 pitches, culminating in a 90-pitch simulated game. The ball speed in the second set was found to be the highest in all pitchers and was considered the "peak set" (p = .021) while ball speed was the slowest in the sixth set of pitches and was therefore considered the "fatigue set" (p = .001). There was a moderate but statistically significant inverse correlation between elbow flexion at ball release and maximum internal rotation velocity (p = .005). Elbow flexion at ball release was also significantly positively correlated with shoulder abduction at ball release (p = 0.004). Elbow flexion at ball release was not significantly correlated with ball velocity (p=.108). DISCUSSION: In a simulated game laboratory setting, increasing pitch count was associated with increasing elbow flexion angle at ball release in youth baseball pitchers. These findings demonstrate that pitching with fatigue may cause biomechanical changes that have been associated with increased rates of elbow injury in the adult throwing population. Further investigation on the association between elbow flexion angle and elbow injury in the youth baseball population is needed.

2.
Am J Pathol ; 189(5): 989-998, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30735627

RESUMEN

Light chain-associated amyloidosis is characterized by the extracellular deposition of amyloid fibrils in abdominothoracic organs, skin, soft tissue, and peripheral nerves. Phagocytic cells of the innate immune system appear to be ineffective at clearing the material; however, human light chain amyloid extract, injected subcutaneously into mice, is rapidly cleared in a process that requires neutrophil activity. To better elucidate the phagocytosis of light chain fibrils, a potential method of cell-mediated dissolution, amyloid-like fibrils were labeled with the pH-sensitive dye pHrodo red and a near infrared fluorophore. After injecting this material subcutaneously in mice, optical imaging was used to quantitatively monitor phagocytosis and dissolution of fibrils concurrently. Histologic evaluation of the residual fibril masses revealed the presence of CD68+, F4/80+, ionized calcium binding adaptor molecule 1- macrophages containing Congo red-stained fibrils as well as neutrophil-associated proteins with no evidence of intact neutrophils. These data suggest an early infiltration of neutrophils, followed by extensive phagocytosis of the light chain fibrils by macrophages, leading to dissolution of the mass. Optical imaging of this novel murine model, coupled with histologic evaluation, can be used to study the cellular mechanisms underlying dissolution of synthetic amyloid-like fibrils and human amyloid extracts. In addition, it may serve as a test bed to evaluate investigational opsonizing agents that might serve as therapeutic agents for light chain-associated amyloidosis.


Asunto(s)
Amiloide/fisiología , Amiloidosis/patología , Macrófagos/fisiología , Imagen Óptica/métodos , Fagocitosis , Animales , Femenino , Macrófagos/citología , Ratones
3.
Bioorg Med Chem Lett ; 22(21): 6587-90, 2012 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-23017882

RESUMEN

A series of bipolar biphenyl compounds was synthesized as proteomimetic analogs of the LXXLL penta-peptide motif responsible for the binding of coactivator proteins to the nuclear hormone receptor coactivator binding domain. These compounds were subjected to multiple in vitro assays to evaluate their effectiveness as competitive binding inhibitors. The results from this initial study indicate that these proteomimetics possess the ability to inhibit this protein-protein interaction.


Asunto(s)
Compuestos de Bifenilo/síntesis química , Compuestos de Bifenilo/farmacología , Coactivadores de Receptor Nuclear/antagonistas & inhibidores , Sitios de Unión , Unión Competitiva , Compuestos de Bifenilo/química , Línea Celular Tumoral , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Estructura Molecular , Coactivador 2 del Receptor Nuclear/metabolismo , Unión Proteica/efectos de los fármacos
4.
Org Lett ; 14(17): 4630-3, 2012 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-22928631

RESUMEN

The stannylation of indole derivatives proceeds in good yields under palladium catalysis (5 mol %) without protection of the indolic nitrogen. The general utility of both PdCl(2)(PhCN)(2)/PCy(3) and Pd(2)dba(3)/PCy(3) as catalytic systems for the stannylation of three indole derivatives, with varying degrees of electron density, is presented.


Asunto(s)
Química Orgánica/métodos , Indoles/química , Compuestos Orgánicos de Estaño/síntesis química , Paladio/química , Catálisis , Técnicas Químicas Combinatorias , Estructura Molecular , Compuestos Orgánicos de Estaño/química , Estereoisomerismo
5.
Org Lett ; 11(23): 5370-3, 2009 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-19902964

RESUMEN

A novel series of biphenyl proteomimetic compounds were designed as estrogen receptor-alpha (ER(alpha)) coactivator binding inhibitors. Synthesis was accomplished through a convergent approach, employing Suzuki coupling chemistry to ligate the individual modular units. Initial biological results support the ability of these compounds to compete for the ER(alpha) coactivator binding groove.


Asunto(s)
Compuestos de Bifenilo/síntesis química , Receptor alfa de Estrógeno/efectos de los fármacos , Imitación Molecular , Sitios de Unión , Compuestos de Bifenilo/química , Compuestos de Bifenilo/farmacología , Diseño de Fármacos , Humanos , Estructura Molecular
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