Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

Experimental loss of menisci, cartilage and subchondral bone gradually increases anteroposterior knee laxity

Purpose: Anteroposterior knee stability is a relevant factor for the decision-making process of various surgical procedures. In degenerative joints when the implantation of unicompartimental prostheses or corrective osteotomies of the limb are planned, the integrity of the anteroposterior stability with an intact ACL has been regarded as a necessary prerequisite. We hypothesise that joint degeneration, however, may influence the anteroposterior knee laxity. Therefore, we set out to test this hypothesis simulating a progressively ‘degenerated’ joint in an experimental cadaveric setting. Methods: Twelve intact transfemorally resected Thiel-fixated cadaver knee joints were divided into 2 groups for manipulation in the medial or lateral compartment. In each knee, we performed (1) unilateral total meniscectomy; (2) simulation of advanced osteoarthritis, by unilateral total cartilage debridement; (3) simulation of a unilateral tibial impression fracture, by resection of 5 mm of the tibial plateau; (4) transection of the ACL. The KT-1000 arthrometer was used to measure the extent of anteroposterior translation at 30° of knee flexion. Results: The mean value for tibial anteroposterior translation before intervention was 3.2 mm (SD: ±0.8). The mean translation after each intervention was 4.6 mm (SD: ±0.9; +44%; n.s.) after meniscectomy, 5.9 mm (SD: ±1.5; +84%; P < 0.05) after cartilage debridement, 8 mm (SD: ±1.5; +150%; P < 0.01) after bone debridement, and finally 9.7 mm (SD: ±2.2; +203%; P < 0.05) after resection of the ACL. There were no significant differences between the medial and lateral compartment. Conclusion: In absence of massive osteophytes or capsular shrinkage, rapid loss of meniscus, cartilage and particularly loss of subchondral bone may result in a massive increase in anteroposterior translation, mimicking a tear of the ACL. In such a situation, a false positive impression of a ligamentous injury may arise, and decision making is falsely directed away from totally or partially knee joint-preserving procedures. Therefore, in degenerate joints, clinical evaluation of anteroposterior stability should rather rely on the presence of a firm stop than an overall increased joint translation

Opening wedge osteotomy of the first cuneiform for the treatment of hallux valgus

We performed an opening wedge osteotomy of the first cuneiform for the correction of all degrees of hallux valgus deformities. A wedge-shaped graft maintained the open wedge osteotomy and decreased the metatarsocuneiform joint inclination to correct the main angles of the hallux valgus. This procedure was performed for 101 feet of 63 patients (two men and 61 women). Fifteen feet benefited from a shortening of P1. The average age was 42 (16 to 84) years with a mean follow-up of 7.7 (1.5 to 14.8) years. We evaluated the M1-P1 and the M1-M2 angles, the joint congruency and the position of the lateral sesamoid. The clinical examination was graded by the AOFAS score which includes comprehensive assessment of pain, function and alignment and the subjective assessment of patients. The clinical AOFAS score improved from 35.24 points preoperatively to 86.36 postoperatively and from 33.25 to 88.03 points in severe deformity. The subjective rating was 44.44% excellent, 41.27% good, 9.52% fair and 4.76% poor. The M1-P1 angle improved from 29.38° to 16.28° and the M1-M2 angle from 14.36° to 10.34°. In the 42 severe feet deformity, these angles improved respectively from 45.58° to 19.58° and from 18.51° to 11.16°. This technique allowed an accurate correction of the main angles of hallux valgus with different degrees of deformity and avoided the complications related to different types of osteotomies achieved along the first metatarsal. After a long follow-up, we demonstrated a durable result while 86% of patients proved excellent and good results according to the AOFAS score

A new ambulatory system for comparative evaluation of the three-dimensional knee kinematics, applied to anterior cruciate ligament injuries.

The aim of this study was to develop an ambulatory system for the three-dimensional (3D) knee kinematics evaluation, which can be used outside a laboratory during long-term monitoring. In order to show the efficacy of this ambulatory system, knee function was analysed using this system, after an anterior cruciate ligament (ACL) lesion, and after reconstructive surgery. The proposed system was composed of two 3D gyroscopes, fixed on the shank and on the thigh, and a portable data logger for signal recording. The measured parameters were the 3D mean range of motion (ROM) and the healthy knee was used as control. The precision of this system was first assessed using an ultrasound reference system. The repeatability was also estimated. A clinical study was then performed on five unilateral ACL-deficient men (range: 19-36 years) prior to, and a year after the surgery. The patients were evaluated with the IKDC score and the kinematics measurements were carried out on a 30 m walking trial. The precision in comparison with the reference system was 4.4 degrees , 2.7 degrees and 4.2 degrees for flexion-extension, internal-external rotation, and abduction-adduction, respectively. The repeatability of the results for the three directions was 0.8 degrees , 0.7 degrees and 1.8 degrees . The averaged ROM of the five patients' healthy knee were 70.1 degrees (standard deviation (SD) 5.8 degrees), 24.0 degrees (SD 3.0 degrees) and 12.0 degrees (SD 6.3 degrees for flexion-extension, internal-external rotation and abduction-adduction before surgery, and 76.5 degrees (SD 4.1 degrees), 21.7 degrees (SD 4.9 degrees) and 10.2 degrees (SD 4.6 degrees) 1 year following the reconstruction. The results for the pathologic knee were 64.5 degrees (SD 6.9 degrees), 20.6 degrees (SD 4.0 degrees) and 19.7 degrees (8.2 degrees) during the first evaluation, and 72.3 degrees (SD 2.4 degrees), 25.8 degrees (SD 6.4 degrees) and 12.4 degrees (SD 2.3 degrees) during the second one. The performance of the system enabled us to detect knee function modifications in the sagittal and transverse plane. Prior to the reconstruction, the ROM of the injured knee was lower in flexion-extension and internal-external rotation in comparison with the controlateral knee. One year after the surgery, four patients were classified normal (A) and one almost normal (B), according to the IKDC score, and changes in the kinematics of the five patients remained: lower flexion-extension ROM and higher internal-external rotation ROM in comparison with the controlateral knee. The 3D kinematics was changed after an ACL lesion and remained altered one year after the surgery