5-HT obesity medication efficacy via POMC activation is maintained during aging

Peer reviewedPublisher PD

The effects of a sleeve knee brace during stair negotiation in patients with symptomatic patellofemoral osteoarthritis

Background: The patellofemoral joint is an important source of pain in knee osteoarthritis. Most biomechanical research in knee osteoarthritis has focused on the tibiofemoral joint during level walking. It is unknown what happens during stair negotiation in patients with patellofemoral joint osteoarthritis, a task commonly increasing pain. Conservative therapy for patellofemoral joint osteoarthritis includes the use of a sleeve knee brace. We aimed to examine the effect of a sleeve knee brace on knee biomechanics during stair negotiation in patellofemoral joint osteoarthritis patients. Methods: 30 patellofemoral joint osteoarthritis patients (40–70 years) ascended and descended an instrumented staircase with force plates under two conditions – wearing a Lycra flexible knee support (Bioskin Patellar Tracking Q Brace) and no brace (control condition). Knee joint kinematics (VICON) and kinetics were recorded. Findings: During stair ascent, at the knee, the brace significantly reduced the maximal flexion angle (2.70, P = 0.002), maximal adduction angle (2.00, P = 0.044), total sagittal range of motion (2.00, P = 0.008), total frontal range of motion (1.70, P = 0.023) and sagittal peak extension moment (0.05 Nm/kg, P = 0.043) compared to control. During stair descent, at the knee, the brace significantly reduced the maximal flexion angle (1.80, P = 0.039) and total sagittal range of motion (1.50, P = 0.045) compared to control. Interpretation: The small changes in knee joint biomechanics during stair negotiation observed in our study need to be investigated further to help explain mechanisms behind the potential benefits of a sleeve knee brace for painful patellofemoral joint osteoarthritis

5-HT2C receptor agonist anorectic efficacy potentiated by 5-HT1B receptor agonist coapplication:an effect mediated via increased proportion of pro-opiomelanocortin neurons activated

An essential component of the neural network regulating ingestive behavior is the brain 5-hydroxytryptamine2C receptor (5-HT2CR), agonists of which suppress food intake and were recently approved for obesity treatment by the US Food and Drug Administration. 5-HT2CR-regulated appetite is mediated primarily through activation of hypothalamic arcuate nucleus (ARC) pro-opiomelanocortin (POMC) neurons, which are also disinhibited through a 5-HT1BR-mediated suppression of local inhibitory inputs. Here we investigated whether 5-HT2CR agonist anorectic potency could be significantly enhanced by coadministration of a 5-HT1BR agonist and whether this was associated with augmented POMC neuron activation on the population and/or single-cell level. The combined administration of subanorectic concentrations of 5-HT2CR and 5-HT1BR agonists produced a 45% reduction in food intake and significantly greater in vivo ARC neuron activation in mice. The chemical phenotype of activated ARC neurons was assessed by monitoring agonist-induced cellular activity via calcium imaging in mouse POMC-EGFP brain slices, which revealed that combined agonists activated significantly more POMC neurons (46%) compared with either drug alone (∼25% each). Single-cell electrophysiological analysis demonstrated that 5-HT2CR/5-HT1BR agonist coadministration did not significantly potentiate the firing frequency of individual ARC POMC-EGFP cells compared with agonists alone. These data indicate a functional heterogeneity of ARC POMC neurons by revealing distinct subpopulations of POMC cells activated by 5-HT2CRs and disinhibited by 5-HT1BRs. Therefore, coadministration of a 5-HT1BR agonist potentiates the anorectic efficacy of 5-HT2CR compounds by increasing the number, but not the magnitude, of activated ARC POMC neurons and is of therapeutic relevance to obesity treatment

Neurochemical characterization of brainstem Pro-opiomelanocortin cells

Financial Support: Work was supported by the Wellcome Trust (WT081713, WT098012 and 204815/Z/16/Z to LKH; 093566/Z/10/A to LKH/LKB), the Biotechnology and Biological Sciences Research Council (BB/K001418/1, BB/NO17838/1 to LKH), and the Medical Research Council (MRC; MC/PC/15077 to LKH). The Genomics and Transcriptomics Core facility utilized was supported by the MRC (MRC_MC_UU_12012/5) and Wellcome Trust (100574/Z/12/Z).Peer reviewedPublisher PD

Knee Joint Biomechanics During Stair Descent in Patients with Knee Osteoarthritis vs. Controls

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake

The authors wish to thank members of staff of the Medical Research Facility, University of Aberdeen, Ms. Raffaella Chianese and Dr. Susan Jalicy, for technical assistance. PX330 and PX552 plasmids were a gift from Prof. Feng Zhang (Massachusetts Institute of Technology, Massachusetts, USA). DREADD vectors were a gift from Prof. Bryan Roth (University of North Carolina at Chapel Hill, North Carolina, USA). PomcDsRED and PomcNEO mice were a gift from Prof. Malcolm Low (University of Michigan, Michigan, USA). Codes to analyze operant-responding for food were a gift from Dr. Vladimir Orduña Trujillo (National Autonomous University of Mexico, Mexico). This work was supported by the Wellcome Trust (L.K.H.; WT098012), Wellcome Trust and the University of Aberdeen (G.D.; 105625/Z/14/Z), Biotechnology and Biological Sciences Research Council (L.K.H., BB/K001418/1, BB/N017838/1; and J.J.R., BB/K017772/1), Medical Research Council (J.J.R., MR/L002620/1; G.D., MR/P009824/1; L.K.H., J.J.R., G.D., MC/PC/15077), British Society of Neuroendocrinology (G.D.), NIH and the Marilyn H. Vincent Foundation (M.G.M.; DK056731, DK034933).Peer reviewedPublisher PD

The effects of a sleeve knee brace during stair negotiation in patients with symptomatic patellofemoral osteoarthritis

Background: The patellofemoral joint is an important source of pain in knee osteoarthritis. Most biomechanical research in knee osteoarthritis has focused on the tibiofemoral joint during level walking. It is unknown what happens during stair negotiation in patients with patellofemoral joint osteoarthritis, a task commonly increasing pain. Conservative therapy for patellofemoral joint osteoarthritis includes the use of a sleeve knee brace. We aimed to examine the effect of a sleeve knee brace on knee biomechanics during stair negotiation in patellofemoral joint osteoarthritis patients. Methods: 30 patellofemoral joint osteoarthritis patients (40–70 years) ascended and descended an instrumented staircase with force plates under two conditions – wearing a Lycra flexible knee support (Bioskin Patellar Tracking Q Brace) and no brace (control condition). Knee joint kinematics (VICON) and kinetics were recorded. Findings: During stair ascent, at the knee, the brace significantly reduced the maximal flexion angle (2.70, P = 0.002), maximal adduction angle (2.00, P = 0.044), total sagittal range of motion (2.00, P = 0.008), total frontal range of motion (1.70, P = 0.023) and sagittal peak extension moment (0.05 Nm/kg, P = 0.043) compared to control. During stair descent, at the knee, the brace significantly reduced the maximal flexion angle (1.80, P 0.039) and total sagittal range of motion (1.50, P = 0.045) compared to control. Interpretation: The small changes in knee joint biomechanics during stair negotiation observed in our study need to be investigated further to help explain mechanisms behind the potential benefits of a sleeve knee brace for painful patellofemoral joint osteoarthritis

The effects of a sleeve knee brace during stair negotiation in patients with symptomatic patellofemoral osteoarthritis.

The patellofemoral joint is an important source of pain in knee osteoarthritis. Most biomechanical research in knee osteoarthritis has focused on the tibiofemoral joint during level walking. It is unknown what happens during stair negotiation in patients with patellofemoral joint osteoarthritis, a task commonly increasing pain. Conservative therapy for patellofemoral joint osteoarthritis includes the use of a sleeve knee brace. We aimed to examine the effect of a sleeve knee brace on knee biomechanics during stair negotiation in patellofemoral joint osteoarthritis patients. 30 patellofemoral joint osteoarthritis patients (40-70 years) ascended and descended an instrumented staircase with force plates under two conditions - wearing a Lycra flexible knee support (Bioskin Patellar Tracking Q Brace) and no brace (control condition). Knee joint kinematics (VICON) and kinetics were recorded. During stair ascent, at the knee, the brace significantly reduced the maximal flexion angle (2.7 , P = 0.002), maximal adduction angle (2.0 , P = 0.044), total sagittal range of motion (2.0 , P = 0.008), total frontal range of motion (1.7 , P = 0.023) and sagittal peak extension moment (0.05 Nm/kg, P = 0.043) compared to control. During stair descent, at the knee, the brace significantly reduced the maximal flexion angle (1.8 , P = 0.039) and total sagittal range of motion (1.5 , P = 0.045) compared to control. The small changes in knee joint biomechanics during stair negotiation observed in our study need to be investigated further to help explain mechanisms behind the potential benefits of a sleeve knee brace for painful patellofemoral joint osteoarthritis. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD