The bone marrow provides inflammatory cells and endothelial progenitor cells to healing cutaneous wounds. To further explore the bone marrow contribution to skin and healing wounds, we used a chimeric mouse model in which the bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice is transplanted into normal C57BL mice. We found that normal skin is a target organ for bone marrow–derived cells from both the hematopoietic and the mesenchymal stem cell pool. We present evidence that the bone marrow contribution to normal skin and the healing cutaneous wound is substantially greater than the previously recognized CD45+ subpopulation, where 15%–20% of the spindle‐shaped dermal fibroblasts were bone marrow–derived (EGFP+). Furthermore, the bone marrow–derived cells were able to contract a collagen matrix and transcribe both collagen types I and III, whereas the skin‐resident cells transcribed only collagen type I. Whereas endothelial progenitor cells were found early during the wound repair process, bone marrow–derived endothelial cells were not seen after epithelialization was complete. Our data show that wound healing involves local cutaneous cells for reconstituting the epidermis but distant bone marrow–derived cells and the adjacent uninjured dermal mesenchymal cells for reconstituting the dermal fibroblast population.
We describe the clinical course of three patients who developed spontaneous coronary artery dissection. All patients were young women, one 9 weeks pregnant. All presented with chest pain; one died suddenly proving refractory to resuscitation, another developed unstable angina culminating in myocardial infarction, cardiogenic shock and death, and the third patient underwent coronary artery bypass grafting following diagnosis of a spontaneous coronary dissection of the left anterior descending artery at angiography. Pathological findings in the two fatal cases are reported. This condition, although rare, is a prominent cause of ischaemic coronary events in young women, when it is frequently associated with pregnancy or the puerperium. Most patients die suddenly, but a clinical spectrum is seen including stable and unstable angina, myocardial infarction and cardiogenic shock. The left anterior descending artery is most frequently affected. The classical histological finding is that of a large haematoma occupying the outer third of the media resulting in complete compression of the true lumen. The cause of spontaneous dissection remains unclear but theories of aetiology include a medial eosinophilic angiitis, pregnancy-induced degeneration of collagen in conjunction with the stresses of parturition, and rupture of the vasal vasorum. The diagnosis must be considered when a patient presents with a suggestive clinical profile. Urgent angiography should be undertaken to establish the diagnosis and consideration given to the need for coronary artery bypass grafting, which has been successfully employed in a number of patients. The uneventful long-term survival of cases treated conservatively has been reported.
Taurine and glutamine are the most abundant intracellular free amino acids in mammalian hearts where changes in their intracellular concentrations are likely to influence a number of cellular activities. In this study we investigated the effects of ischaemia and reperfusion on the intracellular concentrations of taurine and glutamine in the hearts of patients undergoing coronary artery bypass surgery using cold crystalloid or cold blood cardioplegic solutions. Ischaemic arrest (30 min), using cold crystalloid cardioplegic solution (n = 19), decreased the intracellular concentrations (micromol/g wet weight) of taurine (from 9.8 +/- 0.8 to 7.7 +/- 0.7, P < 0.05) and glutamine (8.7 +/- 0.5 to 7.2 +/- 0.6). After 20 min of normothermic reperfusion the fall in taurine and glutamine was maintained (7.5 +/- 0.5 and 7.4 +/- 0.7 for taurine and glutamine respectively). Myocardial ischaemic arrest with cold blood cardioplegic solution (n = 16) did not cause a significant fall in tissue taurine or glutamine. However, on reperfusion there was a marked fall in the intracellular concentrations of taurine (9.4 +/- 0.5 to 6.5 +/- 0.7) and glutamine (8.0 +/- 0.7 to 5.8 +/- 0.4). The fall in amino acids was associated with a fall in ATP and a rise in tissue lactate. This work demonstrates that irrespective of the cardioplegic solution used to arrest the heart, there is a marked fall in tissue taurine and glutamine which may influence the extent of recovery following surgery. The fall in taurine is largely due to efflux whereas changes in glutamine are due to both transport and metabolism. Ischaemia, hypothermia and changes in the transmembrane concentration gradients are the likely factors responsible for the changes in tissue amino acids.
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