We used the recombinant trimeric spike (S) glycoprotein in the prefusion conformation to immunize horses for the production of hyperimmune globulins against SARS-CoV-2. Serum antibody titers measured by ELISA were above 1:10
6
, and the neutralizing antibody titer against authentic virus (WT) was 1:14,604 (average PRNT
90
). Plasma from immunized animals was pepsin digested to remove the Fc portion and purified, yielding an F(ab’)
2
preparation with PRNT
90
titers 150-fold higher than the neutralizing titers in human convalescent plasma. Challenge studies were carried out in hamsters and showed the
in vivo
ability of equine F(ab’)
2
to reduce viral load in the pulmonary tissues and significant clinical improvement determined by weight gain. The neutralization curve by F(ab’)
2
was similar against WT and P.2 variant but displaced to higher concentrations by 0.39 log units against P.1 (Gamma) variant. These results support the possibility of using equine F(ab’)
2
preparation for the clinical treatment of COVID patients.
Resumo Introdução: a avaliação de uma exposição mensura sua intensidade, frequência e duração, podendo detectar danos precoces que, se ignorados, podem evoluir para um quadro nocivo. Nos campos da saúde ambiental e ocupacional, os biomarcadores de genotoxicidade tem sido largamente utilizados para essa avaliação. Objetivo: identificar, descrever e discutir os principais bioindicadores de genotoxicidade e seu uso conjunto com técnicas de avaliação de expressão gênica em estudos de exposição ocupacional ao benzeno em postos de revenda de combustíveis (PRC). Métodos: revisão bibliográfica de trabalhos publicados entre 1995 e 2015. Resultados: as técnicas identificadas foram: ensaio cometa, estresse oxidativo, micronúcleos, aberrações cromossômicas, polimorfismos, adutos de DNA e proteínas, fatores epigenéticos e expressão gênica. Foi observado que testes de danos genéticos e epigenéticos são utilizados em frentistas de PRC que participam de programas de saúde do trabalhador ou de pesquisas, embora um baixo número de publicações sobre o tema tenha sido identificado. Esse fato talvez possa ser explicado pelos poucos países onde a profissão persiste e pelas limitações para o desenvolvimento de pesquisas nesses países. Conclusão: os bioindicadores de genotoxicidade e as técnicas de expressão gênica são úteis na detecção de dano precoce desta exposição ocupacional e devem ser avaliados em conjunto.
Purpose: to investigate the toxicity effects of major hydrocarbons present in gasoline on the auditory system and the related mechanisms of action. Methods: a literature review between 2005 and 2015 was conducted using LILACS, MEDLINE and SciELO, by combining descriptors and their respective terms in Portuguese, English and Spanish. Results: studies performed in humans and animals with hearing impairment, confirmed by morphological tests in rats, the influence of factors such as dose, duration, species and type of stimulus in hearing loss, and ineffective protection of workers by the threshold levels of exposure in the mixture of the compounds, were chosen. Conclusion: toluene is regarded as an ototoxic compound that damages outer hair cells in the middle region of the cochlea, with evidence of interaction with noise. Ethylbenzene and xylenes can be considered potentially ototoxic based on the results of animal studies. No sufficient data were found on benzene to form a conclusion.
The immune response is crucial for coronavirus disease 19 (COVID‐19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is able to induce neutrophil activation by CLEC5A and Toll‐like receptor 2, leading to an aggressive inflammatory cascade, but little is known about the molecular interactions between CLEC5A and SARS‐CoV‐2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS‐CoV‐2 infection using immunological tools with in vitro, in vivo, and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID‐19 patients in comparison with mild COVID‐19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID‐19. In hamsters, we detected CLEC5A gene expression during 3–15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS‐CoV‐2, promoting inflammatory cytokine production, probably through an interaction with the receptor‐binding domain in the N‐acetylglucosamine binding site (NAG‐601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID‐19 progression; therapy with a monoclonal antibody could be a good strategy for COVID‐19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.
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