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1.
Chem Senses ; 492024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38421250

RESUMO

Many common chemotherapeutics produce disruptions in the sense of taste which can lead to loss of appetite, nutritional imbalance, and reduced quality of life, especially if taste loss persists after treatment ends. Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, affects taste sensitivity through its cytotoxic effects on mature taste receptor cells (TRCs) and on taste progenitor cell populations, retarding the capacity to replace TRCs. Mechanistic studies have focused primarily on taste cells, however, taste signaling requires communication between TRCs and the gustatory nerve fibers that innervate them. Here, we evaluate cyclophosphamide's effects on the peripheral gustatory nerve fibers that innervate the taste buds. Following histological analysis of tongue tissues, we find that CYP reduces innervation within the fungiform and circumvallates taste buds within 4 days after administration. To better understand the dynamics of the denervation process, we used 2-photon intravital imaging to visualize the peripheral gustatory nerve fibers within individual fungiform taste buds up to 20 days after CYP treatment. We find that gustatory fibers retract from the taste bud properly but are maintained within the central papilla core. These data indicate that in addition to TRCs, gustatory nerve fibers are also affected by CYP treatment. Because the connectivity between TRCs and gustatory neurons must be re-established for proper function, gustatory fibers should continue to be included in future studies to understand the mechanisms leading to chemotherapy-induced persistent taste loss.


Assuntos
Ageusia , Papilas Gustativas , Animais , Camundongos , Papilas Gustativas/fisiologia , Qualidade de Vida , Língua , Ciclofosfamida/farmacologia , Paladar
2.
Exp Biol Med (Maywood) ; 247(12): 1055-1060, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35369776

RESUMO

Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS-CoV-2 positive plasma samples tested exhibited significant neutralization capacity using a surrogate virus neutralization assay. Of the IgG subclasses, IgG1 and IgG3 exhibited the highest viral neutralization capacity; whereas, IgG2 and IgG4 viral neutralization was not observed. Comparison of SARS-CoV-2 elicited total IgG binding to emerging variant (alpha, beta, and delta) RBDs indicated decreased binding. Furthermore, neutralization by SARS-CoV-2 convalescent plasma of delta and omicron variant RBDs was significantly decreased suggesting that neutralizing antibodies in convalescent plasma are less effective in inhibiting variants currently in circulation.


Assuntos
COVID-19 , Imunidade Humoral , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/terapia , Humanos , Imunização Passiva , Imunoglobulina A , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Soroterapia para COVID-19
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