ABSTRACT
Resumen: Durante el embarazo se producen cambios a nivel de la concentración de los lípidos debido a cambios fisiológicos con el fin de favorecer una adecuada nutrición fetal, estos cambios rara vez tienen consecuencias clínicas. Se presenta el caso clínico de una gestante que a las 31 semanas de edad gestacional se le diagnostica un estado hipertensivo del embarazo, constatándose hipertrigliceridemia severa con alto riesgo de pancreatitis. Se realizó recambio plasmático terapéutico y gemfibrozilo, con buena respuesta clínica.
Abstract: During pregnancy, changes occur at the level of lipid concentration due to physiological changes in order to promote adequate fetal nutrition, these changes rarely have clinical consequences. The clinical case of a pregnant woman is presented who at 31 weeks of gestational age is diagnosed with a hypertensive state of pregnancy, confirming severe hypertriglyceridemia with a high risk of pancreatitis. Therapeutic plasma exchange and gemfibrozil were performed, with a good clinical response.
Resumo: Durante a gravidez ocorrem alterações ao nível da concentração de lípidos devido a alterações fisiológicas de forma a promover uma nutrição fetal adequada, estas alterações raramente têm consequências clínicas. Apresenta-se o caso clínico de uma grávida que às 31 semanas de idade gestacional é diagnosticada com estado hipertensivo da gravidez, confirmando hipertrigliceridemia grave com elevado risco de pancreatite. Foi realizada plasmaférese terapêutica e gemfibrozil, com boa resposta clínica.
ABSTRACT
The synthesis and pharmacological activity of a new series of bicyclic diazepinones with dual activity toward the α2δ-1 subunit of voltage-gated calcium channels (Cavα2δ-1) and the norepinephrine transporter (NET) are reported. Exploration of the positions amenable for substitution on a nonaminoacidic Cavα2δ-1 scaffold allowed the identification of favorable positions for the attachment of NET pharmacophores. Among the patterns explored, attachment of the 2-ethylamino-9-methyl-6-phenyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-e][1,4]diazepin-5-one framework to the meta-position of the phenyl ring of the 3-methylamino-1-phenylpropoxy and 3-methylamino-1-thiophenylpropoxy moieties provided dual compounds with excellent NET functionality. Alternative bicyclic frameworks were also explored, and some lead molecules were identified, which showed a balanced dual profile and exhibited good ADMET properties.
Subject(s)
Azepines/pharmacology , Calcium Channels/metabolism , Heterocyclic Compounds, 2-Ring/pharmacology , Norepinephrine Plasma Membrane Transport Proteins/metabolism , Animals , Azepines/chemical synthesis , Azepines/metabolism , CHO Cells , Cricetulus , HEK293 Cells , Heterocyclic Compounds, 2-Ring/chemical synthesis , Heterocyclic Compounds, 2-Ring/metabolism , Humans , Ligands , Molecular Docking Simulation , Molecular Structure , Protein Binding , Structure-Activity RelationshipABSTRACT
The Gemini analogs are the last significant contribution to the family of vitamin D derivatives in medicine, for the treatment of cancer. The first Gemini analog was characterized by two symmetric side chains at C-20. Following numerous modifications, the most active analog bears a C-23-triple bond, C-26, 27- hexafluoro substituents on one side chain and a terminal trideuteromethylhydroxy group on the other side chain. This progression was possible due to improvements in the synthetic methods for the preparation of these derivatives, which allowed for increasing molecular complexity and complete diastereoselective control at C-20 and the substituted sidechains.
