BACKGROUND Coronavirus disease 19 (COVID-19) has not only been shown to affect the respiratory system, but has also demonstrated variable clinical presentations including gastrointestinal tract disorders. In addition, abnormalities in liver enzymes have been reported indicating hepatic injury. It is known that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might infect cells via the viral receptor angiotensin-converting enzyme 2 (ACE2) which is expressed in several organs including the liver. The viral Spike glycoprotein binds to ACE2 and must be cleaved by Furin and Type 2 Serine Protease to enter the cells. After that, the Akt/mTOR signaling pathway is activated and several COVID-19 changes are triggered. AIM To analyze liver and gastrointestinal symptoms and cell signaling pathways triggered by SARS-CoV-2 infection due to virus-liver interactions in silico . METHODS In this in silico study, the three-dimensional structures of the Akt, mTORC1 and Furin (receptors) were selected from the Protein Data Bank (PDB) and the structures of inhibitors (ligands) MK-2206, CC-223 and Naphthofluorescein were selected from PubChem and ZINC databases. Ligand files were downloaded as 2D structures and converted to optimized 3D structures using ViewerLite 4.2 software. Marvin Sketch ® software was used to calculate prediction of the protonated form of inhibitors in a physiological environment (pH 7.4). AutoDock Tools (ADT) software was used to calculate and delimit the Grid box used in the molecular docking of each structure selected in the PDB. In addition, protonated ligands were prepared for molecular docking using ADT software. Molecular docking was performed using ADT software tools connected to Vina software. Analysis of the amino acid residues involved in ligand interactions, as well as ligand twists, the atoms involved in interactions, bond type and strength of interactions were performed using PyMol ® and Discovery Studio ® (BIOVIA) software. RESULTS Molecular docking analysis showed that the mTORC1/CC-223 complex had affinity energy between the receptor and ligand of -7.7 kcal/moL with interactions ranging from 2.7 to 4.99 Å. There were four significant chemical bonds which involved two of five polypeptide chains that formed the FKBP12–Rapamycin-Binding (FRB) domain. The strongest was a hydrogen bond, the only polar interaction, and Van der Waals interactions shown to be present in 12 residues of mTORC1’s FRB domain. With regard to the Akt/MK-2206 complex there were three Van der Waals interactions and 12 chemical bonds in which seven residues of Akt were involved with all five rings of the MK-2206 structure. In this way, both ASP 388 and GLN 391 bind to the same MK-2206 ring, the smaller one. However, LYS 386 had four chemical bonds with the...
Objetivo: Contextualizar a cefaleia cervicogênica descrevendo sua etiologia, fisiopatologia, quadro clínico, critérios diagnósticos e tratamentos, para nortear a sociedade médica diante da patologia que está em crescente aumento de sua incidência. Métodos: O presente estudo realizou buscas nas bases de dados PubMed, Nature, Scielo e Wiley, utilizando os descritores cefaleia cervicogênica, e foram analisados trabalhos publicados entre os anos de 1980 e 2022, em todos os idiomas, além das respectivas traduções em inglês. Como fator de inclusão foi considerado: “trabalhos publicados dentro do escopo do estudo dentro do intervalo de tempo citado e relacionados a cefaleia cervicogênica e como fator de exclusão foi considerado: “trabalhos não relacionados ao tema de estudo e com relatos já ultrapassados de acordo com a literatura atual”. Resultados: Foram encontrados 1.319 artigos, após leitura e análise dos artigos foram selecionados 27 artigos, e de acordo com a relevância no assunto fazem parte do escopo do trabalho. Em relação a cefaleia cervicogênica é possível classifica-la como uma cefaleia secundária, atribuída a transtornos cervicais, com sintomatologia heterogênea, geralmente apresentando-se como uma cefaleia unilateral, não latenjante e não excruciante, podendo ser desencadeada por pontos gatilhos em região cervical podendo ainda se apresentar com pródomos autonômicos. Sua etiologia e fisiopatologia tem ligação direta com transtornos cervicais e irritação das fibras aferentes de C1-C2-C3, além da convergência para o núcleo trigêmeo-cervical aumentando a variabilidade de sintomas. Seu diagnóstico é baseado em critérios diagnósticos e existem uma grande variedade de tratamentos com eficácia limitada. Conclusão: A cefaleia cervicogênica pode se apresentar de formas heterogêneas dificultado seu diagnóstico e sendo subdiagnosticada e tratada erroneamente em até 50% dos casos, seu aumento em decorrência da pandemia alerta para a melhoria no diagnóstico e tratamento da cefaleia cervicogênica e os distúrbios osteomusculares associados.
The aim was to report the case of a patient with REM sleep behavior disorder, unresponsive to standard treatment and with complete control of the condition after association of amantadine. Female patient, 45 years old, with systemic arterial hypertension and hypothyroidism, referred to neurological care, reporting frequent episodes of nocturnal agitation in the first hours of sleep, with walking and vocalization, waking up easily if called. She complains of drowsiness and anxiety, secondary to the impact of the RBD on her personal life. She mentions previous attempts at drug treatment with benzodiazepines (Bromazepam and Clonazepam), Zolpidem and Trazodone, all without clinical improvement, with Quetiapine being introduced at a low dose (not yet tried) 25mg, with a therapeutic target of 50mg with partial improvement only with 25mg. When trying 50mg, presenting a worsening of the picture. In a new follow-up, therapy with Amantadine 50 mg/day associated with Quetiapine 25 mg/day was started. The patient returned reporting a significant improvement in the condition, less frequent episodes associated with reduced nocturnal movement. After adaptation of the combined therapy, with adjustments in the dose of Amantadine, an increase of 50mg every 14 days up to 200 mg/day, with the possibility of using quetiapine 50mg (balance between the drugs), the patient evolved stable, with a great improvement in the quality of life and absence of new episodes of the sleep disorder.
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