3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus.

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study's objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.

Effect of the shoulder position on the biceps brachii emg in different dumbbell curls.

Incline Dumbbell Curl (IDC) and Dumbbell Preacher Curl (DPC) are two variations of the standard Dumbbell Biceps Curl (DBC), generally applied to optimize biceps brachii contribution for elbow flexion by fixing shoulder at a specific angle. The aim of this study is to identify changes in the neuromuscular activity of biceps brachii long head for IDC, DPC and DBC exercises, by taking into account the changes in load moment arm and muscle length elicited by each dumbbell curl protocol. A single cycle (concentric-eccentric) of DBC, IDC and DPC, was applied to 22 subjects using a submaximal load of 40% estimated from an isometric MVC test. The neuromuscular activity of biceps brachii long head was compared by further partitioning each contraction into three phases, according to individual elbow joint range of motion. Although all protocols elicited a considerable level of activation of the biceps brachii muscle (at least 50% of maximum RMS), the contribution of this muscle for elbow flexion/extension varied among exercises. The submaximal elbow flexion (concentric) elicited neuro muscular activity up to 95% of the maximum RMS value during the final phase of IDC and DBC and 80% for DPC at the beginning of the movement. All exercises showed significant less muscle activity for the elbow extension (eccentric). The Incline Dumbbell Curl and the classical Dumbbell Biceps Curl resulted in similar patterns of biceps brachii activation for the whole range of motion, whereas Dumbbell Preacher Curl elicited high muscle activation only for a short range of elbow joint angle. Key pointsThe Incline Dumbbell Curl and the Dumbbell Biceps Curl resulted in a considerable neuromuscular effort throughout the whole elbow range of motion.The Incline Dumbbell Curl and the Dumbbell Biceps Curl may be preferable for the improvement of biceps brachii force in training programs.