Achilles tendon material properties are greater in the jump leg of jumping athletes.

PURPOSE: The Achilles tendon (AT) must adapt to meet changes in demands. This study explored AT adaptation by comparing properties within the jump and non-jump legs of jumping athletes. Non-jumping control athletes were included to control limb dominance effects. METHODS: AT properties were assessed in the preferred (jump) and non-preferred (lead) jumping legs of male collegiate-level long and/or high jump (jumpers; n=10) and cross-country (controls; n=10) athletes. Cross-sectional area (CSA), elongation, and force during isometric contractions were used to estimate the morphological, mechanical and material properties of the ATs bilaterally. RESULTS: Jumpers exposed their ATs to more force and stress than controls (all p≤0.03). AT force and stress were also greater in the jump leg of both jumpers and controls than in the lead leg (all p<0.05). Jumpers had 17.8% greater AT stiffness and 24.4% greater Young's modulus in their jump leg compared to lead leg (all p<0.05). There were no jump versus lead leg differences in AT stiffness or Young's modulus within controls (all p>0.05). CONCLUSION: ATs chronically exposed to elevated mechanical loading were found to exhibit greater mechanical (stiffness) and material (Young's modulus) properties.

A new approach for the investigation of reperfusion-related brain injury.

Effective stroke therapies require recanalization of occluded cerebral blood vessels; however, early reperfusion can cause BBB (blood-brain barrier) injury, leading to cerebral oedema and/or devastating brain haemorrhage. These complications of early reperfusion, which result from excess production of ROS (reactive oxygen species), significantly limit the benefits of stroke therapies. Here, we summarize some of the findings that lead to the development of a novel animal model that facilitates identification of specific free radical-associated components of the reperfusion injury process and allows therapeutic interventions to be assessed. In this model, KO (knockout) mice containing 50% activity of the mitochondrial antioxidant manganese-SOD (superoxide dismutase) (SOD2-KO) undergo transient focal ischaemia followed by reperfusion. These animals have delayed (>24 h) BBB breakdown associated with activation of matrix metalloproteinase-9, inflammation and a high brain haemorrhage rate. These adverse consequences are absent from wild-type littermates, SOD2 overexpressors and minocycline-treated SOD2-KO animals. In addition, using microvessel isolations following in vivo ischaemia/reperfusion, we were able to show that the tight junction membrane protein, occludin, is an early and specific target in ROS-mediated microvascular injury. This new model is ideal for studying ischaemia/reperfusion-induced vascular injury and secondary brain damage and offers a unique opportunity to evaluate free radical-based neurovascular protective strategies.

Estrogens and hematopoiesis: characterization and studies on the mechanism of neutropenia.

The effect of ES upon hematopoiesis was studied following 4 to 24 weeks of administration in adult female mice. ES produced osteosclerosis, hepatomegaly, splenomegaly with an increase in splenic erythropoiesis mild anemai, and a relatively stable, moderately severe neutropenia. Intact and splenectomized mice failed to develop hepatic hematopoiesis to compensate for these blood changes. The neutropenia was characterized by a proportionally normal-sized marginal granulocyte pool and a reduced marrow granulocyte reserve in the marrow, cellularity, peroxidase-positive cells. CFU-S, and CFU-GM declined during 4 to 12 weeks of study in the same study period, splenic granulocytopoiesis increased as measured by these perameters, but it only partially compensated for the neutropenia. CSA was present in serum, and no inhibitors of in vitro granulocytopoiesis were detected. The direct addition of E3S to normal murine marrow cells in vitro failed to inhibit CFU=GM proliferation. Daily ES administration failed to inhibit in vivo granulocytopoiesis in diffusion chambers. These studies suggest that ES-induced neutropenia is not due to direct inhibition of CFU-S or CFU-GM proliferation or differentiation to mature granulocytes and by implication, suggest that it may be mediated through effects on the hematopoietic microenvironment.

Response of hepatic hematopoiesis to whole body irradiation.

Extensive hepatic erythropoiesis, granulocytopoiesis and megakaryocytopoiesis occur in adult mice given methylcellulose (MC). This appears to be a compensatory response to MC induced hemolytic anemia and thrombocytopenia. The present study was undertaken to evaluate the effects of whole body irradiation (WBI) upon established hepatic hematopoiesis (HH) as well as its effect when given before the induction of HH. Established hepatic erythroid and granulocytic foci were significantly decreased 24 hours after 100 or 300 rads. The DO for erythroid and granulocytic foci was 107 +/- 10 rads and 95 +/- 20 rads respectively, similar to those reported for murine marrow and spleen cell CFUS. Megakaryocytes were more radioresistant, gradually declining over 7 days to 50% of control values following 100 rads and with a DO of 347 +/- 7 rads; suggesting a differential radiation sensitivity compared to erythroid and granulocytic foci. WBI, 100 and 300 rads, given before MC failed to prevent subsequent development of HH although both marrow and spleen responses were reduced. Hepatic granulocytic foci and marrow peroxidase positive cells were reduced by such treatment while erythroid and megakaryocytic foci were similar to controls. This suggests that irradiation damaged stem cells responded to MC with increased erythropoiesis and megakaryocytopoiesis at the expense of granulopoiesis.