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1.
Int J Mol Sci ; 23(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35955536

RESUMO

Viral pneumonia caused by highly infectious SARS-CoV-2 poses a higher risk to older people and those who have underlying health conditions, including Alzheimer's disease. In this work we present newly designed tacrine-based radioconjugates with physicochemical and biological properties that are crucial for the potential application as diagnostic radiopharmaceuticals. A set of ten tacrine derivatives was synthesized, labelled with gallium-68 and fully characterized in the context of their physicochemical properties. Based on these results, the final two most promising radioconjugates, [68Ga]Ga-NODAGA-Bn-NH(CH2)9Tac and [68Ga]Ga-THP-NH(CH2)9Tac, were selected for biodistribution studies. The latter compound was proven to be a good inhibitor of cholinesterases with significant affinity toward the lungs, according to the biodistribution studies. On the basis of molecular modelling combined with in vitro studies, we unraveled which structural properties of the developed tacrine derivatives are crucial for high affinity toward acetylcholinesterase, whose increased levels in lung tissues in the course of coronavirus disease indicate the onset of pneumonia. The radiopharmaceutical [68Ga]Ga-THP-NH(CH2)9Tac was ultimately selected due to its increased accuracy and improved sensitivity in PET imaging of lung tissue with high levels of acetylcholinesterase, and it may become a novel potential diagnostic modality for the determination of lung perfusion, including in inflammation after COVID-19.


Assuntos
Doença de Alzheimer , COVID-19 , Acetilcolinesterase , Idoso , Doença de Alzheimer/diagnóstico por imagem , COVID-19/diagnóstico por imagem , Radioisótopos de Gálio/química , Humanos , Compostos Radiofarmacêuticos/química , SARS-CoV-2 , Tacrina , Distribuição Tecidual
2.
Nutrients ; 13(6)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200310

RESUMO

Aspartame is a sweetener introduced to replace the commonly used sucrose. It was discovered by James M. Schlatter in 1965. Being 180-200 times sweeter than sucrose, its intake was expected to reduce obesity rates in developing countries and help those struggling with diabetes. It is mainly used as a sweetener for soft drinks, confectionery, and medicines. Despite its widespread use, its safety remains controversial. This narrative review investigates the existing literature on the use of aspartame and its possible effects on the human body to refine current knowledge. Taking to account that aspartame is a widely used artificial sweetener, it seems appropriate to continue research on safety. Studies mentioned in this article have produced very interesting results overall, the current review highlights the social problem of providing visible and detailed information about the presence of aspartame in products. The studies involving the impact of aspartame on obesity, diabetes mellitus, children and fetus, autism, neurodegeneration, phenylketonuria, allergies and skin problems, its cancer properties and its genotoxicity were analyzed. Further research should be conducted to ensure clear information about the impact of aspartame on health.


Assuntos
Aspartame/efeitos adversos , Aspartame/metabolismo , Alimentos , Humanos , Transtornos Mentais/induzido quimicamente , Mutagênicos/toxicidade , Degeneração Neural/induzido quimicamente , Preparações Farmacêuticas/análise
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