Jack Martin

Corporate Health: A Result of Employee Fitness

Employees and management alike reap the benefits of industry fitness programs: increased productivity, reduced medical costs-and better health.

Mitochondrial mechanisms and therapeutics in ischaemia reperfusion injury

Acute kidney injury (AKI) remains a major problem in critically unwell children and young adults. Ischaemia reperfusion (IR) injury is a major contributor to the development of AKI in a significant proportion of these cases and mitochondria are increasingly recognised as being central to this process through generation of a burst of reactive oxygen species early in reperfusion. Mitochondria have additionally been shown to have key roles in downstream processes including activation of the immune response, immunomodulation, and apoptosis and necrosis. The recognition of the central role of mitochondria in IR injury and an increased understanding of the pathophysiology that undermines these processes has resulted in identification of novel therapeutic targets and potential biomarkers. This review summarises a variety of therapeutic approaches that are currently under exploration and may have potential in ameliorating AKI in children in the future.

Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA

Hydrogen sulfide (H2S) is produced endogenously in vivo and has multiple effects on signaling pathways and cell function. Mitochondria can be both an H2S source and sink, and many of the biological effects of H2S relate to its interactions with mitochondria. However, the significance of mitochondrial H2S is uncertain, in part due to the difficulty of assessing changes in its concentration in vivo. Although a number of fluorescent H2S probes have been developed these are best suited to cells in culture and cannot be used in vivo. To address this unmet need we have developed a mitochondria-targeted H2S probe, MitoA, which can be used to assess relative changes in mitochondrial H2S levels in vivo. MitoA comprises a lipophilic triphenylphosphonium (TPP) cation coupled to an aryl azide. The TPP cation leads to the accumulation of MitoA inside mitochondria within tissues in vivo. There, the aryl azido group reacts with H2S to form an aryl amine (MitoN). The extent of conversion of MitoA to MitoN thus gives an indication of the levels of mitochondrial H2S in vivo. Both compounds can be detected sensitively by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the tissues, and quantified relative to deuterated internal standards. Here we describe the synthesis and characterization of MitoA and show that it can be used to assess changes in mitochondrial H2S levels in vivo. As a proof of principle we used MitoA to show that H2S levels increase in vivo during myocardial ischemia.

Allograft rejection is associated with development of functional IgE specific for donor MHC antigens

Background: Donor‐specific antibodies of the IgG isotype are measured routinely for diagnostic purposes in renal transplant recipients and are associated with antibody‐mediated rejection and long‐term graft loss. Objective: This study aimed to investigate whether MHC‐specific antibodies of the IgE isotype are induced during allograft rejection. Methods: Anti‐MHC/HLA IgE levels were measured in sera of mice grafted with skin or heart transplants from various donor strains and in sera of kidney transplant patients with high levels of HLA IgG. Mediator release was triggered in vitro by stimulating basophils that were coated with murine or human IgE‐positive serum, respectively, with specific recombinant MHC/HLA antigens. Kidney tissue samples obtained from organ donors were analyzed by using flow cytometry for cells expressing the high‐affinity receptor for IgE (Fc&egr;RI). Results: Donor MHC class I– and MHC class II–specific IgE was found on acute rejection of skin and heart grafts in several murine strain combinations, as well as during chronic antibody‐mediated heart graft rejection. Anti‐HLA IgE, including donor HLA class I and II specificities, was identified in a group of sensitized transplant recipients. Murine and human anti‐MHC/HLA IgE triggered mediator release in coated basophils on stimulation with specific MHC/HLA antigens. HLA‐specific IgE was not linked to atopy, and allergen‐specific IgE present in allergic patients did not cross‐react with HLA antigens. Fc&egr;RI+ cells were found in the human renal cortex and medulla and provide targets for HLA‐specific IgE. Conclusion: These results demonstrate that MHC/HLA‐specific IgE develops during an alloresponse and is functional in mediating effector mechanisms. GRAPHICAL ABSTRACT Figure. No caption available.

Augustus Thorndike: Sportsmedicine Pioneer

Teacher, innovator, researcher, and sideline physician, Gus Thorndike has been in the vanguard of sportsmedicine all his professional life.

'Bart' Quigley: Sportsmedicine Pioneer.

Dissatisfied with casts and conservative treatment for torn knee ligaments, Bart Quigley introduced surgical repair to the armamentarium of sportsmedicine-and touched off a volcano of criticism.