ABSTRACT
BACKGROUND: Patellofemoral pain syndrome (PFPS), characterized by retropatellar and peripatellar pain, is a common disorder affecting young women. Treatment has included exercise-based therapy and taping techniques for rapid reduction of symptoms and pain. Although Kinesio Taping® (KT) has been studied as adjunctive therapy, evidence on its effectiveness is limited and conflicting. OBJECTIVE: To determine the feasibility of performing a double-blind randomized controlled trial (RCT) using KT® for PFPS treatment and to determine an ideal sample size. DESIGN: Double-blind, randomized, controlled pilot study. METHOD: Forty-three women (aged 18-45 years) with at least a 3-month history of PFPS were randomized based on the mechanical correction techniques: using KT® for patellar medialization (KT-PM), using KT® for lateral rotation of the femur and tibia (KT-LRFT), and the control group (CG). All groups underwent the same muscle strengthening and motor control procedures for 12 weeks. Knee pain and function were evaluated at baseline, at 6 weeks, at treatment completion (12 weeks), and during the 12-week follow-up using the numerical pain rating scale (NPRS) at rest and during effort, Anterior Knee Pain Scale (AKPS), and single jump hop test. RESULTS: There were clinically significant differences between the KT-LRFT and the CG in terms of AKPS and NPRS scores during effort at the 6-week and 12-week follow-ups. All groups (within group) showed a significant improvement in pain and function. CONCLUSIONS: A complete RCT using KT® for the treatment of PFPS is feasible with some changes regarding outcome measures and treatment protocols.
Subject(s)
Athletic Tape , Exercise Therapy/methods , Muscle Strength/physiology , Patellofemoral Pain Syndrome/therapy , Adult , Double-Blind Method , Female , Humans , Middle Aged , Pain Measurement , Pilot Projects , Range of Motion, Articular/physiology , Treatment Outcome , Young AdultABSTRACT
Huntington's disease (HD) is a currently incurable neurodegenerative condition caused by an abnormally expanded polyglutamine tract in huntingtin (HTT). We identified new modifiers of mutant HTT toxicity by performing a large-scale 'druggable genome' siRNA screen in human cultured cells, followed by hit validation in Drosophila. We focused on glutaminyl cyclase (QPCT), which had one of the strongest effects on mutant HTT-induced toxicity and aggregation in the cell-based siRNA screen and also rescued these phenotypes in Drosophila. We found that QPCT inhibition induced the levels of the molecular chaperone αB-crystallin and reduced the aggregation of diverse proteins. We generated new QPCT inhibitors using in silico methods followed by in vitro screening, which rescued the HD-related phenotypes in cell, Drosophila and zebrafish HD models. Our data reveal a new HD druggable target affecting mutant HTT aggregation and provide proof of principle for a discovery pipeline from druggable genome screen to drug development.
Subject(s)
Aminoacyltransferases/drug effects , Aminoacyltransferases/genetics , Huntington Disease/drug therapy , Huntington Disease/genetics , RNA, Small Interfering , Aminoacyltransferases/antagonists & inhibitors , Animals , Cells, Cultured , Computational Biology , Drosophila , Drug Evaluation, Preclinical , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Green Fluorescent Proteins/metabolism , Humans , Huntingtin Protein , Mice , Mice, Inbred C57BL , Mutation/genetics , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurons/drug effects , Neurons/metabolism , Zebrafish , alpha-Crystallin B Chain/metabolismABSTRACT
Formation of SDS-insoluble protein aggregates in affected neurons is a cellular pathological feature of polyglutamine (polyQ) disease. We identified a multi-WD-domain protein, receptor for activated protein kinase C1 (RACK1), as a novel polyQ aggregate component from a Drosophila transgenic polyQ disease model. We showed that WD domains were crucial determinants for the recruitment of RACK1 to polyQ aggregates. Over-expression of the human RACK1 protein suppressed polyQ-induced neurodegeneration in vivo. This is the first report to demonstrate the involvement of WD-domain proteins in polyQ pathogenesis, and the proteomic approach described here can be applied to the investigation of other protein aggregation disorders including Alzheimer's and Parkinson's diseases.
Subject(s)
GTP-Binding Proteins/metabolism , Neoplasm Proteins/metabolism , Peptides/metabolism , Receptors, Cell Surface/metabolism , Animals , Animals, Genetically Modified , Disease Models, Animal , Drosophila melanogaster/genetics , Electrophoresis, Gel, Two-Dimensional , Formates/chemistry , GTP-Binding Proteins/genetics , GTP-Binding Proteins/isolation & purification , Heredodegenerative Disorders, Nervous System/enzymology , Heredodegenerative Disorders, Nervous System/genetics , Humans , Neoplasm Proteins/genetics , Neoplasm Proteins/isolation & purification , Peptides/chemistry , Peptides/toxicity , Protein Structure, Tertiary , Proteomics , Receptors for Activated C Kinase , Receptors, Cell Surface/genetics , Receptors, Cell Surface/isolation & purificationABSTRACT
The peroxisome proliferator-activated receptor alpha (PPARalpha) has been known to play a pivotal role in maintaining the energy balance during fasting; however, the battery of PPARalpha target genes involved in this metabolic response is still not fully characterized. Here, we report the identification and characterization of Ppsig (for PPARalpha-regulated and starvation-induced gene) with unknown biological function from mouse liver. Multiple Ppsig cDNAs which differed in the 3'-untranslated regions were identified. The open reading frame of Ppsig cDNA is 1830 bp which encodes a protein of 67.33 kDa. Ppsig contains 11 exons spanning at least 10 kb. Although the exact biological function of Ppsig is still not known, we found that Ppsig mRNA transcript was dramatically up-regulated during 72 h fasting and following treatment with a potent PPARalpha agonist, in a tissue-specific and PPARalpha-dependent manner. A functional peroxisome proliferator-response element was found in the intron 1 of Ppsig, thus confirming that Ppsig is a novel direct mouse PPARalpha target gene. This finding might help in elucidating the transcriptional regulatory mechanism of Ppsig in the cellular response to fasting.
