Cutaneous stimulation from patella tape causes a differential increase in vasti muscle activity in people with patellofemoral pain

Patella taping reduces pain ill individuals with patellofemoral pain (PFP), although the mechanism remains unclear. One possibility is that patella taping modifies vasti muscle activity via stimulation of cutaneous afferents. The aim of this study was to investigate the effect of stretching the skin over the patella on vasti Muscle activity in people with PFP. Electromyographic activity (EMG) of individual motor units in vastus medialis obliquus (VMO) was recorded via a needle electrode and from Surface electrodes placed over VMO and vastus lateralis (VL). A tape was applied to the skin directly over the patella and stretch was applied via the tape in three directions, while subjects maintained a gentle isometric knee extension effort at constant force. Recordings were made from five separate motor units in each direction. Stretch applied to the skin over the patella increased VMO surface EMG and was greatest with lateral stretch. There was no change in VL surface EMG activity. While there was no net increase in motor unit firing rate, it was increased in the majority of motor units during lateral stretch. Application of stretch to the skin over VMO via the tape can increase VMO activity, suggesting that cutaneous stimulation may be one mechanism by which patella taping produces a clinical effect. (c) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Designing supramolecular structures from models of cyclic peptide scaffolds with heterocyclic constraints

Cyclic peptides containing oxazole and thiazole heterocycles have been examined for their capacity to be used as scaffolds in larger, more complex, protein-like structures. Both the macrocyclic scaffolds and the supramolecular structures derived therefrom have been visualised by molecular modelling techniques. These molecules are too symmetrical to examine structurally by NMR spectroscopy. The cyclic hexapeptide ([Aaa-Thz](3), [Aaa-Oxz](3)) and cyclic octapeptide ([Aaa-Thz](4), [Aaa-Oxz](4)) analogues are composed of dipeptide surrogates (Aaa: amino acid, Thz: thiazole, Oxz: oxazole) derived from intramolecular condensation of cysteine or serine/threonine side chains in dipeptides like Aaa-Cys, Aaa-Ser and Aaa-Thr. The five-membered heterocyclic rings, like thiazole, oxazole and reduced analogues like thiazoline, thiazolidine and oxazoline have profound influences on the structures and bioactivities of cyclic peptides derived therefrom. This work suggests that such constrained cyclic peptides can be used as scaffolds to create a range of novel protein-like supramolecular structures (e.g. cylinders, troughs, cones, multi-loop structures, helix bundles) that are comparable in size, shape and composition to bioactive surfaces of proteins. They may therefore represent interesting starting points for the design of novel artificial proteins and artificial enzymes. (C) 2002 Elsevier Science Inc. All rights reserved.

Formation of mononuclear and chloro-bridged binuclear copper(II) complexes of patellamide D, a naturally occurring cyclic peptide: influence of anion and solvent

Patellamide D (patH(4)) is a cyclic octapeptide isolated from the ascidian Lissoclinum patella. The peptide possesses a 24-azacrown-8 macrocyclic structure containing two oxazoline and two thiazole rings, each separated by an amino acid. The present spectrophotometric, electron paramagnetic resonance (EPR) and mass spectral studies show that patellamide D reacts with CuCl, and triethylamine in acetonitrile to form mononuclear and binuclear copper(II) complexes containing chloride. Molecular modelling and EPR studies suggest that the chloride anion bridges the copper(II) ions in the binuclear complex [Cu-2(patH(2))(mu-Cl)](+). These results contrast with a previous study employing both base and methanol, the latter substituting for chloride in the copper(II) complexes en route to the stable mu-carbonato binuclear copper(II) complex [Cu-2 (patH(2))(mu-CO3)]. Solvent clearly plays an important role in both stabilising these metal ion complexes and influencing their chemical reactivities. (C) 2004 Elsevier Inc. All rights reserved.

The nature of anterior knee pain following injection of hypertonic saline into the infrapatellar fat pad

The infrapatellar fat pad has been implicated as a possible source of anterior knee pain. This study examined the nature, distribution and time-course of experimentally induced pain in the infrapatellar fat pad. Hypertonic saline (5%) was injected into the medial fat pad of 11 healthy individuals with no history of knee pain. Severity of pain was assessed at rest and during activity using an 11 point numerical rating scale (NRS) at regular intervals over 15-30 min following injection. Participants described the size of the pain region from a series of different sized circles while the area and type of pain was established from a body chart and the McGill pain questionnaire. The effect of pain on temperature-pain threshold and sensory thresholds of the anterior knee was assessed. Participants generally reported a deep aching pain that peaked in severity around 3 min and gradually declined over 15 min. Pain levels were not altered by clinical manoeuvres designed to impinge the fat pad. The size of the pain region was related to pain intensity. Pain was most commonly felt in the region of the fat pad medial to the patella, although some individuals reported proximal referred pain as far as the groin region. Thermal and sensory thresholds were not altered at a region close to the injection site during the experimental pain. These results suggest that nociceptive stimulation of the infrapatellar fat pad may cause anterior knee pain that is not necessarily confined locally particularly if pain is severe. This has implications for the investigation of pathological structures in patients presenting clinically with anterior knee pain and provides an experimental model of anterior knee pain. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Effect of knee joint angle on motor unit synchronization

Activity of the vasti has been argued to vary through knee range of movement due to changes in passive support of the patellofemoral joint and the relative contribution of these muscles to knee extension. Efficient function of the knee is dependent on optimal control of the patellofemoral joint, largely through coordinated activity of the medial and lateral quadriceps. Motor unit synchronization may provide a mechanism to coordinate the activity of vastus medialis (VMO) and vastus lateralis (VL), and may be more critical in positions of reduced passive support for the patellofemoral joint (i.e., full extension). Therefore, the aim of this study was to determine whether the degree of motor unit synchronization between the vasti muscles is dependent on joint angle. Electromyographic (EMG) recordings of single motor unit action potentials (MUAPs) were made from VMO and multiunit recordings from VL during isometric contractions of the quadriceps at 0 degrees, 30 degrees, and 60 degrees of knee flexion. The degree of synchronization between motor unit firing was evaluated by identification of peaks in the rectified EMG averages of VL, triggered from MUA-Ps in VMO. The proportion of cases in which there was a significant peak in the triggered averages was calculated. There was no significant difference in the degree of synchronization between the vasti at different knee angles (p = 0.57). These data suggest that this basic coordinative mechanism between the vasti muscles is controlled consistently throughout knee range of motion, and is not augmented at specific angles where the requirement for dynamic control of stability is increased. (D 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Spectroscopic characterization of copper(II) binding to the immunosuppressive drug mycophenolic acid

Mycophenolic acid (MPA) is a drug that has found widespread use as an immunosuppressive agent which limits rejection of transplanted organs. Optimal use of this drug is hampered by gastrointestinal side effects which can range in severity. One mechanism by which MPA causes gastropathy may involve a direct interaction between the drug and gastric phospholipids. To combat this interaction we have investigated the potential of MPA to coordinate Cu(II), a metal which has been used to inhibit gastropathy associated with use of the NSAID indomethacin. Using a range of spectroscopic techniques we show that Cu(II) is coordinated to two MPA molecules via carboxylates and, at low pH, water ligands. The copper complex formed is stable in solution as assessed by mass spectrometry and H-1 NMR diffusion experiments. Competition studies with glycine and albumin indicate that the copper-MPA complex will release Cu(II) to amino acids and proteins thereby allowing free MPA to be transported to its site of action. Transfer to serum albumin proceeds via a Cu(MPA)(albumin) ternary complex. These results raise the possibility that copper complexes of MPA may be useful in a therapeutic situation.

Automatic initialisation of 3D deformable models for cartilage segmentation

Deformable models are a highly accurate and flexible approach to segmenting structures in medical images. The primary drawback of deformable models is that they are sensitive to initialisation, with accurate and robust results often requiring initialisation close to the true object in the image. Automatically obtaining a good initialisation is problematic for many structures in the body. The cartilages of the knee are a thin elastic material that cover the ends of the bone, absorbing shock and allowing smooth movement. The degeneration of these cartilages characterize the progression of osteoarthritis. The state of the art in the segmentation of the cartilage are 2D semi-automated algorithms. These algorithms require significant time and supervison by a clinical expert, so the development of an automatic segmentation algorithm for the cartilages is an important clinical goal. In this paper we present an approach towards this goal that allows us to automatically providing a good initialisation for deformable models of the patella cartilage, by utilising the strong spatial relationship of the cartilage to the underlying bone.

3D statistical shape models to embed spatial relationship information

This paper presents the creation of 3D statistical shape models of the knee bones and their use to embed information into a segmentation system for MRIs of the knee. We propose utilising the strong spatial relationship between the cartilages and the bones in the knee by embedding this information into the created models. This information can then be used to automate the initialisation of segmentation algorithms for the cartilages. The approach used to automatically generate the 3D statistical shape models of the bones is based on the point distribution model optimisation framework of Davies. Our implementation of this scheme uses a parameterized surface extraction algorithm, which is used as the basis for the optimisation scheme that automatically creates the 3D statistical shape models. The current approach is illustrated by generating 3D statistical shape models of the patella, tibia and femoral bones from a segmented database of the knee. The use of these models to embed spatial relationship information to aid in the automation of segmentation algorithms for the cartilages is then illustrated.