ABSTRACT
Patients undergoing cardiac surgery represent a challenge in terms of pain management due to multiple factors relating to the patients and to the procedure itself. Our aim was to identify the influence of levels of preoperative anxiety on postoperative pain in patients undergoing cardiac surgery and explore associations between preoperative anxiety, postoperative pain, analgesic requirements, and sex. We present a prospective cohort study of 116 patients undergoing cardiac surgery between January and April 2020. Preoperative anxiety was evaluated using the State-Trait Anxiety Inventory and the amount of morphine needed to keep pain intensity below 4 on the verbal numerical rating scale was recorded for 48 h post-surgery. Given the extracorporeal circulation time, type of surgery and body surface, it was observed that every percentile increase in preoperative state anxiety led to an extra 0.068 mg of morphine being administered. For each extra year of age, the amount of morphine needed decreased by 0.26 mg, no difference was observed between men and women in terms of preoperative anxiety or postoperative analgesics requirements. It may be concluded that in cardiac surgery, postoperative analgesic requirements increased with higher levels of preoperative state anxiety and decreased for every extra year of age.
Subject(s)
Cardiac Surgical Procedures , Pain, Postoperative , Analgesics , Anxiety , Cardiac Surgical Procedures/adverse effects , Female , Humans , Male , Morphine/therapeutic use , Pain, Postoperative/drug therapy , Prospective StudiesABSTRACT
Several biological activities depend on iron-sulfur clusters ([Fe-S]). Even though they are well-known in several organisms their function and metabolic pathway were poorly understood in the majority of the organisms. We propose to use the amoeba Dictyostelium discoideum, as a biological model to study the biosynthesis of [Fe-S] at the molecular, cellular and organism levels. First, we have explored the D. discoideum genome looking for genes corresponding to the subunits that constitute the molecular machinery for Fe-S cluster assembly and, based on the structure of the mammalian supercomplex and amino acid conservation profiles, we inferred the full functionality of the amoeba machinery. After that, we expressed the recombinant mature form of D. discoideum frataxin protein (DdFXN), the kinetic activator of this pathway. We characterized the protein and its conformational stability. DdFXN is monomeric and compact. The analysis of the secondary structure content, calculated using the far-UV CD spectra, was compatible with the data expected for the FXN fold, and near-UV CD spectra were compatible with the data corresponding to a folded protein. In addition, Tryptophan fluorescence indicated that the emission occurs from an apolar environment. However, the conformation of DdFXN is significantly less stable than that of the human FXN, (4.0 vs. 9.0 kcal mol-1, respectively). Based on a sequence analysis and structural models of DdFXN, we investigated key residues involved in the interaction of DdFXN with the supercomplex and the effect of point mutations on the energetics of the DdFXN tertiary structure. More than 10 residues involved in Friedreich's Ataxia are conserved between the human and DdFXN forms, and a good correlation between mutational effect on the energetics of both proteins were found, suggesting the existence of similar sequence/function/stability relationships. Finally, we integrated this information in an evolutionary context which highlights particular variation patterns between amoeba and humans that may reflect a functional importance of specific protein positions. Moreover, the complete pathway obtained forms a piece of evidence in favor of the hypothesis of a shared and highly conserved [Fe-S] assembly machinery between Human and D. discoideum.
Subject(s)
Dictyostelium/metabolism , Friedreich Ataxia/genetics , Iron-Binding Proteins/chemistry , Iron-Binding Proteins/metabolism , Iron-Sulfur Proteins/metabolism , Amino Acid Sequence/genetics , Chromatography, High Pressure Liquid , Circular Dichroism , Computational Biology , Crystallography , Dictyostelium/genetics , Humans , Iron-Binding Proteins/genetics , Iron-Sulfur Proteins/biosynthesis , Iron-Sulfur Proteins/chemistry , Iron-Sulfur Proteins/genetics , Kinetics , Molecular Dynamics Simulation , Phylogeny , Protein Binding , Protein Structure, Tertiary , Recombinant Proteins , Sequence Alignment , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet , FrataxinABSTRACT
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