Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of A(2A) adenosine receptors (A(2A)-AR) by ATL-146e (formerly DWH-146e) prevents inflammatory cell activation and adhesion. Recurrent ischemia-reperfusion (I/R) of the skin results in pressure ulcer formation, a major clinical problem. ATL-146e was evaluated in a novel reproducible rat model of pressure ulcer. A 9-cm(2) region of dorsal rat skin was cyclically compressed at 50 mmHg using a surgically implanted metal plate and an overlying magnet to generate reproducible tissue necrosis. Osmotic minipumps were implanted into 24 rats divided into four equal groups to infuse vehicle (control), ATL-146e (0.004 microg x kg(-1) x min(-1)), ATL-146e plus an equimolar concentration of A(2A) antagonist, ZM-241385, or ZM-241385 alone. Each group received 10 I/R cycles. In non-I/R-treated skin, ATL-146e has no effect on blood flow. I/R-treated skin of the ATL-146e group compared with the vehicle group had 65% less necrotic area, 31% less inhibition of average skin blood flow, and fewer extravasated leukocytes (23 +/- 3 vs. 49 +/- 6 per 500 microm(2)). These data suggest that ATL-146e, acting via an A(2A)-AR, reduces leukocyte infiltration and is a potent prophylactic for I/R injury in skin.
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PMID:Selective A(2A) adenosine receptor activation reduces skin pressure ulcer formation and inflammation. 1140 70

Pressure ulcers are common debilitating complications of diabetes that are caused by tissue ischemia. Skin blood flow in response to locally applied pressure might be impaired in diabetic patients because of the combined effects of a typically low skin temperature and alterations in microcirculatory function, and could be worsened by neuropathy. We measured skin blood flow by laser Doppler flowmetry over the internal anklebone in response to local pressure applied at 5.0 mmHg/min in three groups of diabetic patients (with clinical and subclinical neuropathy and without neuropathy) and in healthy matched control subjects at usual room temperature. Compared with in matched control subjects with comparable skin temperatures (29.3 +/- 0.4 vs. 28.7 +/- 0.4 degrees C), in diabetic patients the skin blood flow response to locally applied pressure was further impeded, even in those without neuropathy. Indeed, skin blood flow decreased significantly from baseline at much lower applied pressure (7.5 mmHg) in diabetic subjects, again even in those without neuropathy, than in control subjects (48.8 mmHg). The large difference between these pressures could partially explain diabetic patients' high risk of developing decubitus and plantar ulcers.
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PMID:Early decrease of skin blood flow in response to locally applied pressure in diabetic subjects. 1191 47

Ischemia-reperfusion plays a certain role in causing skin damage associated with pressure sores. In this study, changes in cutaneous hemodynamics during reperfusion were investigated in young and older rats. After cessation of 1-hour or 2-hour ischemia, the skin blood flow increased transiently (postischemic hyperemia) and quickly returned to the baseline in young and older rats. After 4-hour ischemia, however, the postischemic hyperemia was reduced in both groups, and the skin blood flow decreased below the baseline for a few hours in older rats. The skin blood flow tolerated well the repeated exposures to 1-hour ischemia in both groups. In 2-hour ischemia experiments, the postischemic hyperemia was preserved after the second ischemic period in young rats but not in older rats. These results suggest that the tolerance of skin microcirculation to ischemia-reperfusion may decrease with increasing age.
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PMID:Age-dependent changes of postischemic reperfusion in rat skin. 1254 11

This study determined the incidence, pivotal events, etiology, and levels of amputation in a prospectively followed cohort of 400 people with diabetes and a prior healed foot ulcer who participated in a randomized footwear trial. Participants were seen every 17 weeks for 2 years. Subjects with foot lesions were referred to their healthcare provider for treatment. In this cohort, 11 participants required lower limb amputation (rate 13.8 per 1000 person-years). Pivotal event analysis revealed that only one amputation was related to footwear, six amputations were due to non-footwear-related minor environmental trauma, two were due to progression of vascular disease (dry gangrene from critical ischemia), one was due to a self-care injury while cutting the toenails, and one was due to a decubitus ulcer. Previously proposed strategies to reduce the amputation rates in individuals with diabetes have focused heavily on footwear and education. However, even with this emphasis, amputation rates in the United States are still high. This study suggests that the prevention of minor environmental trauma, including household accidents, merits additional attention. We believe that further efforts to reduce amputation rates for individuals with diabetes will need to emphasize the prevention of minor trauma, especially in those already compromised with neuropathy and vascular disease.
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PMID:Minor environmental trauma and lower extremity amputation in high-risk patients with diabetes: incidence, pivotal events, etiology, and amputation level in a prospectively followed cohort. 1452 19

Although it is well recognized that pressure-induced ischemia initiates the formation of pressure ulcers, the many complex mechanisms responsible for the pathogenesis of these ulcers remain poorly understood. It has been reported that chronic ulcers contain an elevated level of proteolytic enzymes, especially neutrophil-derived matrix metalloproteinase-8 and elastase. This evidence suggests that neutrophils are a major component in the pathogenesis of chronic pressure ulcers. Therefore, this study characterized the cellular components of chronic pressure ulcers. Three-millimeter biopsies (6 mm deep) from granulation tissue in pressure ulcers were obtained from 11 patients. A total of 14 biopsies were obtained from these 11 patients for analysis. A portion of each specimen was fixed in formalin for routine histology. Other portions of biopsies were frozen for analysis of myeloperoxidase activity. In addition, cells on the surfaces of the ulcers were collected by lavage for histologic characterization. Routine histologic analysis of all 14 biopsies of the pressure ulcers showed regions near the surface of each that contained dense neutrophil infiltration associated with edema and apparent marked matrix dissociation. In the deeper regions there was an increased density of blood vessels, and many contained rounded endothelial cells surrounded by migrating neutrophils. Cells collected by lavage from the ulcer surface were prepared by Cytospin and found to be greater than 95% neutrophils with occasional large macrophages actively phagocytosing depleted neutrophils. In addition, there was a significant correlation of myeloperoxidase activity with actual neutrophil counts in the ulcer biopsies further confirming the dense presence of neutrophils. These studies directly show that there is extensive neutrophil infiltration in chronic pressure ulcer granulation tissue. Furthermore, the persistence of neutrophils and their destructive enzymes appears responsible for the extensive matrix dissociation and thus contributes to the chronicity of these ulcers.
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PMID:Excessive neutrophils characterize chronic pressure ulcers. 1461 91

Pressure sores affecting muscles are severe injuries associated with ischemia, impaired metabolic activity, excessive tissue deformation, and insufficient lymph drainage caused by prolonged and intensive mechanical loads. We hypothesize that mechanical properties of muscle tissue change as a result of exposure to prolonged and intensive loads. Such changes may affect the distribution of stresses in soft tissues under bony prominences and potentially expose additional uninjured regions of muscle tissue to intensified stresses. In this study, we characterized changes in tangent elastic moduli and strain energy densities of rat gracilis muscles exposed to pressure in vivo (11.5, 35, or 70 kPa for 2, 4, or 6 h) and incorporated the abnormal properties that were measured in finite element models of the head, shoulders, pelvis, and heels of a recumbent patient. Using in vitro uniaxial tension testing, we found that tangent elastic moduli of muscles exposed to 35 and 70 kPa were 1.6-fold those of controls (P < 0.05, for strains </=5%) and strain energy densities were 1.4-fold those of controls (P < 0.05, for strains >/=5%). Histological (phosphotungstic acid hematoxylin) evaluation showed that this stiffening accompanied extensive necrotic damage. Incorporating these effects into the finite element models, we were able to show that the increased muscle stiffness in widening regions results in elevated tissue stresses that exacerbate the potential for tissue necrosis. Interfacial pressures could not predict deep muscle (e.g., longissimus or gluteus) stresses and injuring conditions. We conclude that information on internal muscle stresses is required to establish new criteria for pressure sore prevention.
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PMID:Mechanical compression-induced pressure sores in rat hindlimb: muscle stiffness, histology, and computational models. 1476 84

Becaplermine gel (Regranex) is an hydrogel which contains 100 microg of Platelet Derived Growth Factor-BB (rhPDGF-BB) per gram. Regranex is presented in 15-gram multidose tubes. It has been approved as adjuvant treatment for neuropathic diabetic ulcerations of less than 5 cm2, extending into the subcutaneous tIssue, in the absence of ischemia, in conjunction with a standardised program of appropriate wound care, (control of infection, sharp debridement, provision of a moist environment and avoidance of pressure on the wound). PDGF-BB promotes cutaneous wound healing by increasing proliferation and migration of dermal fibroblasts and extracellular matrix deposition. PDGF also promotes chemotaxis of neutrophils, monocytes and smooth muscle cells in wounds. Topical application of rhPDGF-BB speeds wound healing and promotes granulation tIssue formation, synthesis of extracellular matrix and the inflammatory phase of the wound healing process in healthy and healing-impaired animal models. In clinical trials in humans, accelarated healing has been demonstrated in patients with lower extremity diabetic neuropathic ulcers and decubitus sores by increasing granulation tIssue formation and epithelialization. Local toxicity studies in humans were negative (repeated becaplermin gel application under occlusion to intact or abraded skin, dermal sensitization tests). Pharmacokinetic studies in humans have shown that systemic absorption after topical applications was minimal. In trials, systemic and local tolerance were excellent. Reported adverse effects were similar in incidence and in nature in all groups. The 0.01% Regranex gel is safe and easy to use, with single daily application. It is currently the only commercially available topical growth factor for use in cutaneous wound healing.
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PMID:[Becaplermin gel (Regranex gel)]. 1525 9

The formation of pressure ulcers and other skin wounds is considered to be a multifactorial process. Cycles of ischemia-reperfusion have been considered to be significant contributing factors in the pathogenesis of pressure ulcers. This study reports the development of a reproducible murine model of ischemia-reperfusion injury by the external application of magnets. Mice were sedated with 50% CO2:50% O2 for 50-60 s. Dorsal hair was shaved and the area cleaned. The skin was gently pulled and placed between two round ceramic magnetic plates (5 x 12 mm diameter, 2.4 g weight, 1000 G magnetic force). The resultant "pinch" procedure was designed to leave a 5-mm skin bridge between the magnets, creating 50 mm Hg pressure between the plates. Three 12-h ischemia-reperfusion cycles were employed to cause pressure ulcer formation. Animals tolerated the procedure well. They returned to normal activity a few minutes after magnet placement. The lesions reached their maximum at 10 days postinjury. Full-thickness skin loss with damage and necrosis of subcutaneous tissue (ulcer stage 3) was observed in all cases, reaching a mean stage score of 3.6 +/- 0.6 of based on a 0-5 scale for extent of injury by visual assessment. Thus, an inexpensive, reproducible murine pressure ulcer model was developed, which results in graded injury without long-term immobilization of the animals. This method will facilitate the development of new prevention and management strategies.
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PMID:Development of a simple, noninvasive, clinically relevant model of pressure ulcers in the mouse. 1537 Nov 64

Necrotizing enterocolitis continues to be a common and life-threatening gastrointestinal emergency in the low birth weight infant. Prematurity, ischemia, enteral feeding, and infectious disease have been identified as common risk factors, however the exact cause of NEC other than prematurity is yet to be identified. Good assessment skills by the nurse are imperative, because clinical signs of NEC can be both subtle and catastrophic. Frequent radiographs are essential for the diagnosis of NEC and ongoing assessment of neonates diagnosed with NEC. Radiographs including an abdominal flat plate examination and a left lateral decubitus film to evaluate for free air should be obtained every 6-8 hours in the neonates with Stages II and III NEC.
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PMID:Pathophysiology and current management of necrotizing enterocolitis. 1571 34

The aim of this study was to establish a pressure ulcer model that visualizes the microcirculation, and to examine the participation of ischemia-reperfusion injury in the pathophysiology of pressure ulcers. An original system composed of a new skin fold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia-reperfusion injury, animals were divided into two groups: the compression-release group (n = 8), in which the animals received four cycles of compression-release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group (n = 8) in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day 1 (35 hours) after the first evaluation. The cyclic compression-release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia-reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. This finding supports the significant contribution of ischemia-reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.
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PMID:Analysis of ischemia-reperfusion injury in a microcirculatory model of pressure ulcers. 1582 47


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