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)

Infection-related vasculitis constitutes the most common cause of secondary vasculitis. A great variety of microorganisms can induce directly or indirectly inflammatory vascular damage resulting in vascular occlusion, tissue ischemia, and necrosis. In the developed world hepatitis B and C-related vasculitis remain the most common clinical syndromes, while HIV-associated vasculitis remains a concern in developing countries.
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PMID:Infection-related vasculitis. 1604 31

Both in vivo models of ischemia/reperfusion and in vitro models of hypoxia (H)/reoxygenation (R) have demonstrated the crucial role of the Rac1-regulated NADPH oxidase in the production of injurious reactive oxygen species (ROS) by vascular endothelial cells (ECs). Since membrane lipid peroxidation has been established as one of the mechanisms leading to cell death, we examined lipid peroxidation in H/R-exposed cultured human umbilical vein ECs (HUVECs) and the role of Rac1 in this process. H (24 h at 1% O2)/R (5 min) caused an increase in intracellular ROS production compared to a normoxic control, as measured by dichlorofluorescin fluorescence. Nutrient deprivation (ND; 24 h), a component of H, was sufficient to induce a similar increase in ROS under normoxia. Either H(24 h)/R (2 h) or ND (24 h) induced increases in lipid peroxidation of similar magnitude as measured by flow cytometry of diphenyl-1-pyrenylphosphine-loaded HUVECs and Western blotting analysis of 4-hydroxy-2-nonenal-modified proteins in cell lysates. In cells infected with a control adenovirus, H (24 h)/R (2 h) and ND (24 h) resulted in increases in NADPH-dependent superoxide production by 5- and 9-fold, respectively, as measured by lucigenin chemiluminescence. Infection of HUVECs with an adenovirus that encodes the dominant-negative allele of Rac1 (Rac1N17) abolished these increases. Rac1N17 expression also suppressed the H/R- and ND-induced increases in lipid peroxidation. In conclusion, ROS generated via the Rac1-dependent pathway are major contributors to the H/R-induced lipid peroxidation in HUVECs, and ND is able to induce Rac1-dependent ROS production and lipid peroxidation of at least the same magnitude as H/R.
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PMID:Rac1 inhibition protects against hypoxia/reoxygenation-induced lipid peroxidation in human vascular endothelial cells. 1609 26

Foals may present to a referral hospital with the primary diagnosis of uroperitoneum (UP), or they may develop UP while hospitalized for other reasons. Historical, physical, laboratory, and diagnostic variables of foals presenting with UP were compared to those developing UP while hospitalized. Emphasis was placed on the presence of electrolyte abnormalities, evidence of sepsis or infection, and development of anesthetic complications during surgical correction of the defect. Foals developing UP while in the hospital frequently had a history of dystocia and presented at a very young age (< 48 hours) with primary clinical signs compatible with intrauterine compromise or presumed hypoxic or ischemic insult with or without sepsis. Foals referred with suspected UP often had additional problems unrelated to the urinary system. These foals had hyponatremia and hyperkalemia on presentation, whereas foals receiving intravenous fluid therapy consisting of a balanced electrolyte solution did not develop the classical pattern of electrolyte abnormalities, yet a similar increase in serum creatinine and, frequently, decreasing urine production were noted. Infection was present in 63% of the foals, and 78% of foals revealed signs suggestive of sepsis or infection. Intrauterine compromise, presumed hypoxia or ischemia, and sepsis may predispose foals to development of UP. Anesthetic complications occurred in 16% of the foals undergoing surgical correction of the defect, although hyperkalemia was only present in half of the foals with anesthetic complications.
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PMID:Uroperitoneum in 32 foals: influence of intravenous fluid therapy, infection, and sepsis. 1635 86

Wound healing during the diabetic foot disease is indicated to in-patient treatment in case of non-healing wound, in case of serious infection and/or critical ischemia and in case of necessity of surgical treatment. Diabetic foot disease is the main reason for in-patient treatment of people with diabetes, which our experience confirms. Chronic wound is characterised by non-healing for at least 4 weeks. Ischemia and recurrent trauma caused by incomplete off-loading, prolong inflammation and infection are the main reasons for difficult healing of chronic wound. Infection is also leading cause for prolonged hospitalisation of patients with diabetic foot disease. Local decrease of grow factors and increase of tissue protease are characteristics of chronic wound. The process of wound healing is characterized by a cascade of interrelated events involving infection and inflammatory factors. The results of these investigations led to the moist wound healing concept and use of growth factors and bioengineered skin substitutes. We have good experience with the use of xenotransplant skin substitues in the treatment of diabetic foot. Off loading techniques including total contact casting, local therapy by debridement and skin substitutes had the best evidence based efficacy. We are introducing new method of the treatment of diabetic foot--VAC--vacuum assisted closure. The fundamental principle in the therapy during in-patient period, is comprehensive approach; the omitting of any of the principle of the therapy--e.g. the off-loading of the ulcers, the infection and ischemia control, may contribute to its failure.
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PMID:[Healing of skin lesions in diabetic foot syndrome during hospitalization]. 1677 Oct 90

EXECUTIVE SUMMARY: 1. Foot infections in patients with diabetes cause substantial morbidity and frequent visits to health care professionals and may lead to amputation of a lower extremity. 2. Diabetic foot infections require attention to local (foot) and systemic (metabolic) issues and coordinated management, preferably by a multidisciplinary foot-care team (A-II). The team managing these infections should include, or have ready access to, an infectious diseases specialist or a medical microbiologist (B-II). 3. The major predisposing factor to these infections is foot ulceration, which is usually related to peripheral neuropathy. Peripheral vascular disease and various immunological disturbances play a secondary role. 4. Aerobic Gram-positive cocci (especially Staphylococcus aureus) are the predominant pathogens in diabetic foot infections. Patients who have chronic wounds or who have recently received antibiotic therapy may also be infected with Gram-negative rods, and those with foot ischemia or gangrene may have obligate anaerobic pathogens. 5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signs and symptoms of inflammation. Laboratory (including microbiological) investigations are of limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6. Send appropriately obtained specimens for culture before starting empirical antibiotic therapy in all cases of infection, except perhaps those that are mild and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging studies may help diagnose or better define deep, soft-tissue purulent collections and are usually needed to detect pathological findings in bone. Plain radiography may be adequate in many cases, but MRI (in preference to isotope scanning) is more sensitive and specific, especially for detection of soft-tissue lesions (A-I). 8. Infections should be categorized by their severity on the basis of readily assessable clinical and laboratory features (B-II). Most important among these are the specific tissues involved, the adequacy of arterial perfusion, and the presence of systemic toxicity or metabolic instability. Categorization helps determine the degree of risk to the patient and the limb and, thus, the urgency and venue of management. 9. Available evidence does not support treating clinically uninfected ulcers with antibiotic therapy (D-III). Antibiotic therapy is necessary for virtually all infected wounds, but it is often insufficient without appropriate wound care. 10. Select an empirical antibiotic regimen on the basis of the severity of the infection and the likely etiologic agent(s) (B-II). Therapy aimed solely at aerobic Gram-positive cocci may be sufficient for mild-to-moderate infections in patients who have not recently received antibiotic therapy (A-II). Broad-spectrum empirical therapy is not routinely required but is indicated for severe infections, pending culture results and antibiotic susceptibility data (B-III). Take into consideration any recent antibiotic therapy and local antibiotic susceptibility data, especially the prevalence of methicillin-resistant S. aureus (MRSA) or other resistant organisms. Definitive therapy should be based on both the culture results and susceptibility data and the clinical response to the empirical regimen (C-III). 11. There is only limited evidence with which to make informed choices among the various topical, oral, and parenteral antibiotic agents. Virtually all severe and some moderate infections require parenteral therapy, at least initially (C-III). Highly bioavailable oral antibiotics can be used in most mild and in many moderate infections, including some cases of osteomyelitis (A-II). Topical therapy may be used for some mild superficial infections (B-I). 12. Continue antibiotic therapy until there is evidence that the infection has resolved but not necessarily until a wound has healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 12 weeks usually suffices, but some require an additional 12 weeks; for moderate and severe infections, usually 24 weeks is sufficient, depending on the structures involved, the adequacy of debridement, the type of soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis, generally at least 46 weeks is required, but a shorter duration is sufficient if the entire infected bone is removed, and probably a longer duration is needed if infected bone remains (B-II). 13. If an infection in a clinically stable patient fails to respond to 1 antibiotic courses, consider discontinuing all antimicrobials and, after a few days, obtaining optimal culture specimens (C-III). 14. Seek surgical consultation and, when needed, intervention for infections accompanied by a deep abscess, extensive bone or joint involvement, crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II). Evaluating the limb's arterial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the field should be recruited by the foot-care team, if possible. 15. Providing optimal wound care, in addition to appropriate antibiotic treatment of the infection, is crucial for healing (A-I). This includes proper wound cleansing, debridement of any callus and necrotic tissue, and, especially, off-loading of pressure. There is insufficient evidence to recommend use of a specific wound dressing or any type of wound healing agents or products for infected foot wounds. 16. Patients with infected wounds require early and careful follow-up observation to ensure that the selected medical and surgical treatment regimens have been appropriate and effective (B-III). 17. Studies have not adequately defined the role of most adjunctive therapies for diabetic foot infections, but systematic reviews suggest that granulocyte colony-stimulating factors and systemic hyperbaric oxygen therapy may help prevent amputations (B-I). These treatments may be useful for severe infections or for those that have not adequately responded to therapy, despite correcting for all amenable local and systemic adverse factors. 18. Spread of infection to bone (osteitis or osteomyelitis) may be difficult to distinguish from noninfectious osteoarthropathy. Clinical examination and imaging tests may suffice, but bone biopsy is valuable for establishing the diagnosis of osteomyelitis, for defining the pathogenic organism(s), and for determining the antibiotic susceptibilities of such organisms (B-II). 19. Although this field has matured, further research is much needed. The committee especially recommends that adequately powered prospective studies be undertaken to elucidate and validate systems for classifying infection, diagnosing osteomyelitis, defining optimal antibiotic regimens in various situations, and clarifying the role of surgery in treating osteomyelitis (A-III).
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PMID:Diagnosis and treatment of diabetic foot infections. 1547 38

Infections are important risk factors of perinatal brain injury. However, under certain circumstances, inflammation mediates preconditioning and provides protection to the immature brain. Recent experimental studies have examined the interaction of lipopolysaccharide (LPS) with other events. Evidence demonstrates that LPS administered 24h before hypoxia-ischemia in 7-day-old rats provides neuroprotection, which is associated with up-regulation of endogenous corticosterone but is also linked to significant cerebral gene regulation. Gene ontology analysis reveals that the most over-represented genes belong to immune and inflammatory processes. However, a number of cell death/survival genes, including complement component 1, complement component 3, aquaporin 4, epidermal growth factor receptor pathway substrate 15 and PYD and CARD domain containing are also significantly up-regulated 24h following LPS exposure. These results suggest that in addition to immune-related activation, transcription of cell death pathways may be important in LPS-induced preconditioning in the immature brain.
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PMID:Inflammation-induced preconditioning in the immature brain. 1732 46

Sickle cell disease results from the presence of abnormal beta globin chains within hemoglobin and may be manifested in anemia, vaso-occlusion, and superimposed infection. The gene that causes sickle cell disease is particularly prevalent in populations of African origin; approximately 8% of African Americans and 40% of the members of some African tribes carry the gene for hemoglobin S. Over time, the disease produces various musculoskeletal abnormalities as a result of chronic anemia; these include marrow hyperplasia, reversion of yellow marrow to red marrow, and, occasionally, extramedullary hematopoiesis. Familiarity with the imaging features of sickle cell disease is important for the diagnosis and management of complications. Ischemia and infarction are common complications that may have long-term effects on the growth of bone; these conditions have characteristic radiographic appearances. Infection may be more difficult to identify. Both infection and infarction may occur in muscle and soft tissue alone, without involving bone. However, osteomyelitis must be diagnosed early and treated immediately to prevent bone destruction and deformity; therefore, care must be taken to achieve an accurate diagnosis by identifying or excluding bone involvement. The clinical and radiographic features of acute osteomyelitis may be particularly difficult to distinguish from those of bone infarction. In that context, magnetic resonance (MR) imaging may be useful. At MR imaging, findings of cortical defects, adjacent fluid collections in soft tissue, and bone marrow enhancement are suggestive of infection.
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PMID:Musculoskeletal manifestations of sickle cell disease. 1762 Apr 64

The majority of mitochondrial proteins are encoded by nuclear genes and synthesized in the cytosol as preproteins containing a mitochondria import sequence. Preproteins traverse the outer mitochondrial membrane in an unfolded state and then translocate through the inner membrane into the matrix via import machinery that includes mitochondrial heat shock protein 70 (mtHSP70). Neonatal rat cardiac myocytes (NCM) infected with an adenoviral vector expressing mtHSP70 or an empty control (Adv(-)) for 48 h were submitted to 8 h of simulated ischemia (hypoxia) followed by 16 h of reperfusion (reoxygenation). Infection with mtHSP70 virus yielded an increase in mtHSP70 protein in NCM mitochondria compared with Adv(-) (P < 0.05). Cell viability after simulated ischemia/reperfusion (I/R) was decreased in both Adv(-) and mtHSP70 groups, relative to control (P < 0.05), but mtHSP70-infected NCM had enhanced viability after I/R relative to Adv-infected NCM (P < 0.05). Simulated I/R caused an increase in reactive oxygen species generation and lipid peroxidation in Adv-infected NCM (P < 0.05, for both) that was not observed in mtHSP70-infected NCM. Mitochondrial complex III and IV activities were greater in mtHSP70-infected NCM after simulated I/R compared with Adv(-) (P < 0.05 for both). After simulated I/R, ATP content increased in mtHSP70-infected NCM, compared with Adv(-) (P < 0.05). Apoptotic markers were decreased in mtHSP70-infected NCM compared with Adv(-) after simulated I/R (P < 0.05). These results indicate that overexpression of mtHSP70 protects the mitochondria against damage from simulated I/R that may be due to a decrease in reactive oxygen species leading to preservation of mitochondrial complex function activities and ATP formation.
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PMID:Mitochondria protection from hypoxia/reoxygenation injury with mitochondria heat shock protein 70 overexpression. 1798 16

Infection, ischemia, trauma, and neoplasia elicit a similar inflammatory response in the CNS characterized by activation of microglia, the resident CNS monocyte. The molecular events leading from CNS injury to the activation of innate immunity is not well understood. We show here that the intracellular chaperone heat shock protein 60 (HSP60) serves as a signal of CNS injury by activating microglia through a toll-like receptor 4 (TLR4)-dependent and myeloid differentiation factor 88 (MyD88)-dependent pathway. HSP60 is released from CNS cells undergoing necrotic or apoptotic cell death and specifically binds to microglia. HSP60-induced synthesis of neurotoxic nitric oxide by microglia is dependent on TLR4. HSP60 induces extensive axonal loss and neuronal death in CNS cultures from wild-type but not TLR4 or MyD88 loss-of-function mutant mice. This is the first evidence of an endogenous molecular pathway common to many forms of neuronal injury that bidirectionally links CNS inflammation with neurodegeneration.
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PMID:A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS. 1832 79

STAT3 is a major signaling molecule for many neurotrophic factors but its direct role in the protection of neurons in response to stress has not been addressed. We have studied the role of STAT3 in protecting retinal neurons from damage induced by ischemia/reperfusion and glutamate excitotoxicity by using adenovirus constructs to introduce active, normal or inactive STAT3 into retinal ganglion cells in culture and cells of the ganglion cell layer in the intact retina. Transient ischemia/reperfusion was induced in adult CD1 mice by elevating the intraocular pressure to the equivalent of 120mmHg for 60min, followed by a return to normal pressure. The levels, activation and distribution of STAT3 protein were evaluated by Western blot and immunocytochemistry. A transient peak of STAT3 activation was seen at 24h post ischemia and a strong increase in STAT3 protein levels 24h later. The increase in levels of STAT3 was detected in both ganglion cell bodies and processes in the plexiform layers by immunocytochemistry. The time course of STAT3 increase was slower than the time course of ganglion cell death as measured by TUNEL assay. Intravitreal injection of NMDA led to peak increases in activated STAT3 and STAT3 at 12 and 24h post insult respectively. Purified RGCs were infected with recombinant wild-type STAT3, constitutively active and dominant negative forms of STAT3 adenoviruses or control empty virus and then treated with glutamate. Surviving infected cells were counted 24 and 48h later. Infection with constitutively active STAT3 gave substantial protection when compared to the other constructs. Similarly, intravitreal injection of constitutively active STAT3 adenovirus one day before ischemia-reperfusion resulted in a decreased neural cell death in the ganglion cell layer compared with GFP adenovirus control. Our results suggest that persistent activation of STAT3 by neurotrophic factors provides strong neuroprotection and will be an effective strategy in a number of chronic retinal diseases.
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PMID:STAT3 activation protects retinal ganglion cell layer neurons in response to stress. 1847 11


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