Effects of Self-Myofascial Release on Shoulder Function and Perception in Adolescent Tennis Players.

CONTEXT: Tennis induces a decreased internal rotation range of motion at the dominant glenohumeral joint. The effects of self-myofascial release have not yet been investigated to restore glenohumeral range of motion. OBJECTIVE: This study aimed at investigating the effects of self-myofascial release on shoulder function and perception in adolescent tennis players. DESIGN: Test-retest design. SETTING: Tennis training sport facilities. PARTICIPANTS: Eleven male players participated in this study (age: 15 [3] y; height: 173.1 [11.1] cm; mass: 56.0 [15.1] kg; International Tennis Number: 3). INTERVENTION: During 5 weeks, the players performed their regular tennis training. During 5 additional weeks, self-myofascial release of the infraspinatus and pectoralis muscles was implemented 3 times per week after the warm-up of the regular training session. MAIN OUTCOME MEASURES: The primary outcome was glenohumeral internal rotation range of motion. The secondary outcomes were perceived shoulder instability and tennis serve accuracy and velocity. RESULTS: Adding self-myofascial release allowed an increase of 11° (2°) of internal rotation range of motion at the dominant glenohumeral joint (P < .001) and a decreased perception of shoulder instability (P = .03), while maintaining tennis serve velocity and accuracy. CONCLUSIONS: Implementing self-myofascial release on infraspinatus and pectoralis muscles 3 times per week during 5 weeks improved dominant glenohumeral internal rotation range of motion in tennis players. It can be used as a strategy to preserve the mobility of this joint.

Non-clinical safety and biodistribution of AS03-adjuvanted inactivated pandemic influenza vaccines.

Pandemic-influenza vaccines containing split-inactivated-virus antigen have been formulated with the immunostimulatory Adjuvant System AS03 to enhance the antigen immunogenicity and reduce antigen content per dose. AS03 is an oil-in-water emulsion containing α-tocopherol, squalene and polysorbate 80. To support the clinical development of AS03-adjuvanted pandemic-influenza vaccines, the local and systemic toxicity of test articles containing split-influenza A(H5N1) and/or AS03 were evaluated after 3-4 intramuscular (i.m.) injections in rabbits. Treatment-related effects were restricted to mild inflammatory responses and were induced primarily by the test articles containing AS03. The injection-site inflammation was mild at 3 days, and minimal at 4 weeks after the last injection; and was reflected by signs of activation in the draining lymph nodes and by systemic effects in the blood including a transient increase of neutrophils. In addition, a study in mice explored the biodistribution of A(H5N1) vaccines or AS03 through radiolabelling the antigen or constituents of AS03 prior to injection. In this evaluation, 57-73% of AS03's principal constituents had cleared from the injection site 3 days after injection, and their different clearance kinetics were suggestive of AS03's dissociation. All these AS03 constituents entered into the draining lymph nodes within 30 min after injection. In conclusion, the administration of repeated doses of the H5N1/AS03 vaccine was well tolerated in the rabbit, and was primarily associated with transient mild inflammation at the injection site and draining lymph nodes. The biodistribution kinetics of AS03 constituents in the mouse were consistent with AS03 inducing this pattern of inflammation.

Oxorhenium-mediated assembly of noncyclic selective integrin antagonists: a combinatorial approach.

The parallel oxorhenium-mediated assembly of 288 noncyclic RGD analogues is reported. All complexes contain a NS(2) +S chelating motif that enables the unambiguous coordination of the oxorhenium and oxotechnetium cores. In this study, "modules S" contain a variety of pending guanidinium groups whereas the "NS(2) modules" are made of a series of N-acylated amino acids. Combination of sets of "NS(2) " and "S modules" together with tetrabutylammonium tetrachlorooxorhenate gave the corresponding oxorhenium complexes in good yields and satisfactory purities. Evaluation of these metalloconstructs towards integrins α(V) ß(3) , α(IIb) ß(3) , and α(V) ß(5) led to the identification of micromolar and submicromolar antagonists of theses integrins. These compounds exhibit interesting selectivities and promise attractive applications for the molecular imaging of integrin-dependent pathologies.

Dynamic combinatorial self-assembly of cyclophilin hCyp-18 ligands through oxorhenium coordination.

The dynamic combinatorial assembly of independent modules A and B through oxorhenium(V) coordination by a NS2+S motif in the presence of cyclophilin hCyp-18-an important peptidyl-prolyl isomerase-was investigated. Increasing glutathione (GSH) concentrations were used to dissociate [ARe(V)OB] complexes that displayed low affinity for hCyp-18. Conversely, coordinates that displayed submicromolar affinities for hCyp-18 were protected against thiol exchange and could be detected by LC-MS. Determination of the GSH concentration that decreased the extracted ionic current of the complex by 50 % (CC(50)) enabled the selection of three oxorhenium coordinates that were shown to bind to the active site of hCyp-18 and to inhibit its peptidyl-prolyl isomerase activity in the micromolar to submicromolar range.

Implication of cysteine residues in the selection of oxorhenium inhibitors of cyclophilin hCyp18.

The dynamic combinatorial assembly of libraries of modular cyclophilin hCyp18 oxorhenium inhibitors of general formula [A˙ReO˙B] was accelerated by addition of increasing concentrations of hCyp18 ('Cyclophilin Enhancing Effect', CEE). This result suggested that modules assembly might proceed through an in situ coordination chemistry process. However, we observed that the CEE was not strictly related to the affinity of the complexes for hCyp18. The CEE was not altered by cyclosporine A, a potent competitive inhibitor of hCyp18. The use of a non-degassed buffer caused a fall in complexation yields that could be reversed upon addition of hCyp18. All these data suggested that the CEE results from a partial protection of exogenous thiols against reoxidation. As anticipated, carbamido-methylation of cyclophilin Cys52 and Cys62 residues with iodoacetamide annihilated the CEE. All these results highlight the role of hCyp18 in maintaining chemical modules in a reduced state.

Chelate oxorhenium to assemble new integrin antagonists.

Assembly of independent chemical modules through oxorhenium coordination by a NS(2)+S chelation motif was applied to the synthesis of RGD (Arg-Gly-Asp) analogs. Modules were assembled through oxorhenium chelation to give a series of 18 metal complexes in good yields and satisfactory purities. Screening of these oxorhenium coordinates as antagonists of integrins αVß3, αIIbß3 and αVß5 led to the identification of 3 bioactive compounds that exhibit submicromolar affinities for the 3 integrins. Preliminary studies showed that the corresponding oxotechnetium complexes are stable in mice plasma and therefore could be proposed for the molecular imaging of pathologies that overexpress integrins αVß3 and αVß5.

Synthesis, metal complexation and biological evaluation of a novel semi-rigid bifunctional chelating agent for 99mTc labelling.

A novel bifunctional chelating agent bearing an aromatic ring has been synthesised and characterised. This ligand formed well-defined oxorhenium complexes. The analogous 99mTcO-complex was obtained in an excellent yield with high radiochemical purity (>95%). The biodistribution of the 99mTc-complex after intravenous injection studied in normal rats showed that the activity was excreted mainly via renal-urinary pathway indicating its use for labelling peptides with 99mTc.

Synthesis and structural characterization of new oxorhenium and oxotechnetium complexes with XN2S-tetradentate semi-rigid ligands (X = O, S, N).

Twelve novel oxo-technetium and oxo-rhenium complexes based on N2S2-, N2SO- or N3S-tetradentate semi-rigid ligands have been synthesised and studied herein. By reacting the ligands with a slight excess of suitable [MO]3+ precursor (ReOCl3(PPh3)2 or [NBu4][99gTcOCl4]), the monoanionic complexes of general formula [MO(Ph-XN2S)]- could be easily produced in high yield. The complexes have been characterized by means of IR, electrospray mass spectrometry, elemental analysis, NMR and conductimetry. The crystal structures of [PPh4][ReO(Ph-ON2S)] 1b and [NBu4][99gTcO(Ph-ON2S)] 1c have been established. The [MO]3+ moiety was coordinated via the two deprotonated amide nitrogens, the oxygen and the terminal sulfur atoms in 1b and 1c. In both compounds, the ON2S coordination set is in the equatorial plane, and the complexes adopted a distorted square-pyramidal geometry with an axial oxo-group. The chemical and structural identity of the different prototypic complexes (rhenium, 99gTc complexes and their corresponding 99mTc radiocomplexes) have been also established by a comparative HPLC study.

Design and synthesis of a novel family of semi-rigid ligands: versatile compounds for the preparation of 99mTc radiopharmaceuticals.

Synthetic pathways to a range of novel semi-rigid tetradentate ligands, with sulfur, amido or amino donor groups, designed to coordinate technetium 99m have been developed. The technetium-99m complexes have been prepared and their stabilities in serum and by metathesis reaction via cysteine exchange reactions were compared. HPLC comparison of two (99m)Tc-complexes and their rhenium analogues led to the first proof of the nature of our radioactive complexes.