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591.
Atherosclerotic diseases are responsible for a significant part of morbidity and mortality in western countries. According to the classical views, atherosclerotic lesions develop as the result of an inflammatory process initiated by endothelial damage. The discovery that bone marrow-derived cells participate in endothelial repair and new vessel growth has changed the pathogenetic models of cardiovascular disease. These cells, termed endothelial progenitor cells (EPCs), represent the endogenous endothelial regenerative capacity and the ability to form new collateral vessels. In this review we describe how quantitative and qualitative alterations of EPCs have a significant role in virtually all stages of the atherosclerotic process and in the clinical manifestations of the diseases: starting from the impact of risk factors on EPCs, through the mechanisms that link EPC reduction/dysfunction to plaque formation, and finally to the clinical syndromes. An attempt to diverge our attention from the vessel wall to the bloodstream reveals a central role of EPCs in atherogenesis. 相似文献
592.
593.
Although the dominant approach to drug development is the design of compounds selective for a given target, compounds targeting more than one biological process may have superior efficacy, or alternatively a better safety profile than standard selective compounds. Here, this possibility has been explored with respect to the endocannabinoid system and pain. Compounds inhibiting the enzyme fatty acid amide hydrolase (FAAH), by increasing local endocannabinoid tone, produce potentially useful effects in models of inflammatory and possibly neuropathic pain. Local increases in levels of the endocannabinoid anandamide potentiate the actions of cyclooxygenase inhibitors, raising the possibility that compounds inhibiting both FAAH and cyclooxygenase can be as effective as non-steroidal anti-inflammatory drugs but with a reduced cyclooxygenase inhibitory ‘load’. An ibuprofen analogue active in models of visceral pain and with FAAH and cyclooxygenase inhibitory properties has been identified. Another approach, built in to the experimental analgesic compound N-arachidonoylserotonin, is the combination of FAAH inhibitory and transient receptor potential vanilloid type 1 antagonist properties. Although finding the right balance of actions upon the two targets is a key to success, it is hoped that dual-action compounds of the types illustrated in this review will prove to be useful analgesic drugs. 相似文献
594.
Helton LA Defino C Fernando PS Herrero Carlos FEW Romeiro 《Indian Journal of Orthopaedics》2007,41(4):337-345
Background:
A short vertebral arthrodesis has been one of the objectives of the surgical treatment of fractures of the thoracolumbar spine. We present here clinical, functional and radiographic outcome obtained after monosegmental fixation (single posterior or combined anterior and posterior) of specific types of unstable thoracolumbar fractures.Materials and Methods:
Twenty four patients with fractures of the thoracolumbar spine submitted to monosegmental surgical treatment (Group I - 18 single posterior monosegmental fixations and Group II - 6 combined anterior and posterior fixations) were retrospectively evaluated according to clinical, radiographic and functional parameters. The indication for surgery was instability or neurological deficit. All the procedures were indicated and performed by the senior surgeon (Helton LA Defino).Results:
The patients from group I were followed-up from 2 to 12 years (mean: 6.65±2.96). The clinical, functional and radiographic results show that a single posterior monosegmental fixation is adequate and a satisfactory procedure to be used in specific types of thoracolumbar spine fractures, The patients from group II were followed-up from 9 to 15 years (mean: 13 ± 2,09 years). On group II the results of clinical evaluation showed moderate indices of residual pain and of satisfaction with the final result. The values obtained by functional evaluation showed that 66.6% of the patients were unable to return to their previous job and presented a moderate disability index (Oswestry = 16.6) and a significant reduction of quality of life based on the SF-36 questionnaire. Radiographic evaluation showed increased kyphosis of the fixed vertebral segment during the late postoperative period, accompanied by a reduction of the height of the intervertebral disk.Conclusion:
It is possible to stabilize the fractures which have an anterior good load-bearing capacity by a standalone posterior monosegmental fixation. However this procedure, even with an anterior support is not suitable for fracture involving the vertebral body. 相似文献595.
Diabetes triggers endothelial dysfunction, which is linked to increased risk of cardiovascular diseases. Stem and progenitor cells from the bone marrow are involved in the maintenance of vascular integrity. Diabetic patients show a dysfunction of these cells, which might represent a novel pathophysiological mechanism of vascular disease. Specifically, stem and progenitor cells fail to egress from the bone marrow (BM) due to BM pathological alterations and unresponsiveness to mobilizing stimuli. In this review, we describe impaired stem cell mobilization in diabetes as a mechanism of failed vascular repair and we provide evidence that pharmacological strategies can restore mobilization. We discuss recent advances in the knowledge of aberrant organization of the diabetic BM and its implications for impaired mobilization. Finally, we describe in detail the pharmacological exploitation of the G-CSF/DPP-4(CD26)/SDF-1α axis as a novel strategy to improve mobilization and attain vascular repair in diabetes. 相似文献
596.