The unique contribution of ion channels to platelet and megakaryocyte function

Summary. Ion channels are transmembrane proteins that play ubiquitous roles in cellular homeostasis and activation. In addition to their recognized role in the regulation of ionic permeability and thus membrane potential, some channel proteins possess intrinsic kinase activity, directly interact with integrins or are permeable to molecules up to ≈1000 Da. The small size and anuclear nature of the platelet has often hindered progress in understanding the role of specific ion channels in hemostasis, thrombosis and other platelet‐dependent events. However, with the aid of transgenic mice and ‘surrogate’ patch clamp recordings from primary megakaryocytes, important unique contributions to platelet function have been identified for several classes of ion channel. Examples include ATP‐gated P2X1 channels, Orai1 store‐operated Ca²⁺ channels, voltage‐gated Kv1.3 channels, AMPA and kainate glutamate receptors and connexin gap junction channels. Furthermore, evidence exists that some ion channels, such as NMDA glutamate receptors, contribute to megakaryocyte development. This review examines the evidence for expression of a range of ion channels in the platelet and its progenitor cell, and highlights the distinct roles that these proteins may play in health and disease.     

Evidence‐based recommendations for the monitoring and treatment of ankylosing spondylitis: results from the Australian 3E initiative in rheumatology

Aim: To develop a set of Australian recommendations for the monitoring and treatment of ankylosing spondylitis (AS) through systematic literature review combined with the opinion of practicing rheumatologists. Methods: A set of eight questions, four in each domain of monitoring and treatment, were formulated by voting and the Delphi method. The results of a systematic literature review addressing each question were presented to the 23 participants of the Australian 3E meeting. All participants were clinical rheumatologists experienced in the daily management of AS. Results: After three rounds of breakout sessions to discuss the findings of the literature review, a set of recommendations was finalized after discussion and voting. The category of evidence and strength of recommendation were determined for each proposal. The level of agreement among participants was excellent (mean 84%, range 64–100%). Conclusions: The 12 recommendations developed from evidence and expert opinion provide guidance for the daily management of AS patients. For most recommendations, we found a paucity of supportive evidence in the literature highlighting the need for additional clinical studies.     

LESIONS OF THE MID-SHAFT OF THE HUMERUS PRESENTING AS SHOULDER CAPSULITIS

We describe three patients who presented with pain and restrictionof movement at the shoulder suggestive of capsulitis, but provedto have lesions of the mid-shaft of the humerus. It is importantto be aware of the possibility of this cause of a ‘frozenshoulder’, since radiographs of the shoulder are usuallycropped at the mid-humerus and lesions at this level may easilybe missed. A radiograph of the entire humerus, or an isotopebone scan, may be more useful than repeated shoulder radiographsin patients whose shoulder symptoms do not respond to standardtreatment KEY WORDS: Shoulder joint, Humerus, Radiographs, Pain Department of Rheumatology, The Whittington Hospita HighgateHill, London N19 5NF     

111INDIUM-LABELLED POLYMORPHONUCLEAR LEUCOCYTE SCANS IN RHEUMATOID ARTHRITIS--AN IMPORTANT CLINICAL CAUSE OF FALSE POSITIVE RESULTS

The presence of rheumatoid arthritis in patients undergoing¹¹¹indium-labelled polymorphonuclear leucocyte scanning representsa source of possible diagnostic confusion. In such patients,the labelled cells frequently accumulate over the caecum andascending colon, despite the absence of obvious pathology ofthe large bowel. The aetiology of this effect is unknown. KEY WORDS: ¹¹¹Indium-labelled polymorphonuclear leucocytes, Rheumatoid arthritis     

Comparison of static friction with self-ligating,modified slot design and conventional brackets

Objective

To compare the static frictional forces generated at the bracket/wire interface of stainless steel brackets with different geometries and angulations, combined with orthodontic wires of different diameters.

Material and Methods

The frictional forces were evaluated with three different types of metal brackets: a passive self-ligating (SmartClip^TM, 3M/Unitek, Monrovia, USA), with a modified slot design (Mini Uni Twin^TM, 3M/Unitek, Monrovia, USA) and conventional (Kirium, Abzil, São José do Rio Preto, Brazil). The samples were mounted in a testing device with three different angulations and tested with 0.014" and 0.018" stainless steel wires (American Orthodontics, Sheboygan, USA). The static frictional force was measured using a universal testing machine (DL 500, EMIC^®, São José dos Pinhais, Brazil) with a crosshead speed of 1 mm/min. Statistical analysis was performed by two-way ANOVA followed by Bonferroni''s post hoc test.

Results

There was a significant difference (p<0.05) in static friction when the three types of brackets were tested with the same wire size. The wire diameter influenced friction only when the brackets had a 10º angulation (p<0.05). The angulation influenced friction (p<0.05) when the brackets were associated with a 0.018" wire.

Conclusion

Brackets with a modified slot design showed intermediate static frictional force values between the conventional and self-ligating brackets tested.