Deep tissue injury: how deep is our understanding?

Deep pressure ulcers, necessarily involving deep tissue injury (DTI), arise in the muscle layers adjacent to bony prominences because of sustained loading. They represent a serious type of pressure ulcer because they start in underlying tissues and are often not visible until they reach an advanced stage, at which time treatment becomes problematic. Underlying mechanisms of DTI require further investigation if appropriate preventive measures are to be determined. The present commentary illustrates a hierarchic research approach selected to study these mechanisms. To differentiate between the individual roles of deformation and ischemia in the onset of skeletal muscle damage, 2 complementary approaches have been selected. In an in vivo animal model, the effects of ischemia combined with deformation and ischemia per se were studied. An in vitro muscle model was used to study the separate effects of deformation and several aspects of ischemia, including hypoxia, glucose depletion, and tissue acidification, in more detail. Based on the results of both models a sequence of events leading to cell necrosis is proposed. Deformation levels exceeding a threshold value can result in rapid tissue damage that may persist, whereas ischemia has a more gradual effect as a result of glucose depletion and tissue acidificatio

Protective effect of caspase inhibition on compression-induced muscle damage

There are currently no effective therapies for treating pressure-induced deep tissue injury. This study tested the efficacy of pharmacological inhibition of caspase in preventing muscle damage following sustained moderate compression. Adult Sprague-Dawley rats were subjected to prolonged moderate compression. Static pressure of 100 mmHg compression was applied to an area of 1.5 cm 2 in the tibialis region of the right limb of the rats for 6 h each day for two consecutive days. The left uncompressed limb served as intra-animal control. Rats were randomized to receive either vehicle (DMSO) as control treatment (n= 8) or 6 mg kg -1 of caspase inhibitor (z-VAD-fmk; n= 8) prior to the 6 h compression on the two consecutive days. Muscle tissues directly underneath the compression region of the compressed limb and the same region of control limb were harvested after the compression procedure. Histological examination and biochemical/molecular measurement of apoptosis and autophagy were performed. Caspase inhibition was effective in alleviating the compression-induced pathohistology of muscle. The increases in caspase-3 protease activity, TUNEL index, apoptotic DNA fragmentation and pro-apoptotic factors (Bax, p53 and EndoG) and the decreases in anti-apoptotic factors (XIAP and HSP70) observed in compressed muscle of DMSO-treated animals were not found in animals treated with caspase inhibitor. The mRNA content of autophagic factors (Beclin-1, Atg5 and Atg12) and the protein content of LC3, FoxO3 and phospho-FoxO3 that were down-regulated in compressed muscle of DMSO-treated animals were all maintained at their basal level in the caspase inhibitor treated animals. Our data provide evidence that caspase inhibition attenuates compression-induced muscle apoptosis and maintains the basal autophagy level. These findings demonstrate that pharmacological inhibition of caspase/apoptosis is effective in alleviating muscle damage as induced by prolonged compression. ©2011 The Authors. Journal compilation © 2011 The Physiological Society.Link_to_subscribed_fulltex

A thorough study of a Paratylenchus

In glasshouses practising monoculture of butterhead lettuce in Belgium, high densities of pin nematodes (Paratylenchusspp.) are frequently associated with reduced plant growth. Growers currently apply chemical soil disinfestation measures to manage this problem, although stricter phytosanitary regulations are forcing a shift towards integrated management. Efficient implementation of such management requires knowledge about the factors influencing nematode population dynamics, and the damage threshold for lettuce. The nematode populations in five Belgian glasshouses were monitored for at least 1 year by frequently soil sampling at 0-30 cm and 30-60 cm depth. An undescribed species of Paratylenchuswas identified in all glasshouses based on morphological and molecular features. High nematode densities (>20,000 (100 ml soil)(-1)) occurred in winter and spring. Chemical soil disinfestation lowered these populations greatly, although up to 14% survived in the deeper soil layer. After soil steaming under negative pressure, no pin nematodes were found. After 2 months of black fallow pin nematode densities were reduced by 50%-76%. Lamb's lettuce, parsley and wild rocket were found to be poor hosts in a pot experiment, while reproduction factors (P-f/P-i) on lettuce cultivars varied between 1 and 3. In three experiments with butterhead lettuce 'Cosmopolia' in pots with a series of 9 or 10 densities of Paratylenchussp. [up to 35,000 (100 ml soil)(-1)], no damage to lettuce heads was observed. However, root weight and root quality were reduced, and the corresponding damage thresholds were rather low [1,754 and 362Paratylenchussp. (100 ml soil)(-1), respectively]. Management strategies such as crop rotation, soil disinfestation or fallow are recommended to avoid pin nematode population build-up