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)

The oxygenation of arachidonic acid by lipoxygenases results in the formation of HPETEs (hydroperoxyeicosatetraenoic acids), the first products of the LOX pathway. These compounds are short lived and are catabolised into various families of more stable compounds of which the HETEs, hepoxilins, lipoxins and leukotrienes have been identified so far. The development of new techniques have helped to identify and understand the structures of various HPETEs and only recently the biological effects of HPETEs and their various catabolites are being unraveled. Although lipoxygenases are ubiquitous, not all tissues possess the same spectrum of lipoxygenase enzymes. Hence different HPETEs can be formed in different tissues. Recent studies have revealed that HPETEs or products derived from them possess a diversity of important biological properties including the regulation of electrolyte flux and eicosanoid and corticosterone syntheses, release of histamine, regulation of oocyte maturation and release of various reproductive hormones. HPETEs appear to be involved in some pathological conditions viz, skin psoriasis, Clarkson's disease, nerve injury and spinal cord ischemia. These novel eicosanoids are associated with the release of insulin as well as renin. Recently HPETEs have been suggested to act as second messengers in the Aplysia sensory neurons and its catabolite, hepoxilin, has been demonstrated to have effects on mammalian hippocampal neurons. The purpose of this review is to provide a brief summary of the formation of the HPETEs and the various families of compounds derived from them as well as the various types of biological activities for these products described so far.
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PMID:Biosynthesis, catabolism, and biological properties of HPETEs, hydroperoxide derivatives of arachidonic acid. 251 25

Cyclic GMP levels in epidermis of normal subjects and of psoriatic patients were measured with a highly sensitive radioimmunoassay method. Technical improvements for the assay are 2-fold: (1) skin samples were frozen in vivo before biopsy and local injection of any anesthetic was avoided to overcome ischemia effect which could lower cyclic GMP artificially; (2) epidermis was microdissected to avoid contamination of dermis and keratin layers. The results show that on a per mg tissue dry weight basis the cyclic GMP levels are about 200 fmol in the involved lesional epidermis and 70 fmol in the uninvolved or normal epidermis. Similarly increases in the cyclic GMP levels in the lesional epidermis are observed when the data are expressed either on a DNA or protein basis. The cyclic GMP level in normal epidermis from nonpsoriatic subjects is the same as that in the uninvolved epidermis of psoriasis patients.
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PMID:Epidermal cyclic GMP is increased in psoriasis lesions. 625 90

Phosphocreatine molecules (PCR) in skin regenerate adenosine triphosphate and help cutaneous tissue survive ischemia associated with skin flaps, grafts, and hair transplantation procedures. In addition, PCR concentration in psoriasis is elevated many times above normal, indicating either overproduction of PCR by mitochondrial creatine phosphokinase (CPK) enzymes or a defect in cytosol CPK enzymatic activity. Skin CPK isoenzymes, before this study, have not been identified. Herein, for the first time, cytosol CPK enzymatic activity was measured in normal and psoriatic, involved and uninvolved skin, skin tumors, and mouse skin and keratinocyte cell cultures. Creatine phosphokinase MM is the major isoenzyme in normal, uninvolved psoriatic and mouse skin. Total CPK enzymatic activity was increased in psoriasis and skin tumors. These data clearly indicate that increased PCR concentration in a psoriatic skin is not a result of decreased cytosol CPK enzymatic activity.
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PMID:Identification and activity of cytosol creatine phosphokinase enzymes in normal and diseased skin. 798 27

Leukocyte recruitment from the circulation into inflammatory tissues requires a series of soluble and cell-bound signals between the responding leukocyte and vascular endothelial barrier. Chemotactic factors are believed to be responsible for this selective adhesion and transmigration. A superfamily of small, soluble, structurally-related molecules called 'chemokines' have been identified and shown to selectively promote the rapid adhesion and chemotaxis of a variety of leukocyte subtypes both in vivo and in vitro. Chemokines are produced by almost every cell type in the body in response to a number of inflammatory signals, in particular those which activate leukocyte-endothelial cell interactions. These molecules also appear to play important roles in hematopoesis, cellular activation, and leukocyte effector functions. In addition, chemokines have been found in the tissues of a variety of disease states characterized by distinct leukocytic infiltrates, including rheumatoid arthritis, sepsis, atherosclerosis, asthma, psoriasis, ischemia/reperfusion injury, HIV replication, and a variety of pulmonary disease states. This review will primarily focus on the role of chemokines in cell adhesion and trafficking as well as their role as effector molecules.
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PMID:Chemokine-leukocyte interactions. The voodoo that they do so well. 902 58

Aggregation and disaggregation kinetics of erythrocytes in samples of whole blood were studied using a backscattering nephelometry technique. Blood was drawn from normal subjects and from patients suffering from different diseases: chronic glomerulonephritis, systemic lupus erythematosus, hereditary hypercholesterolemia, pulmonary hypertension, intestinal tumors preoperatively (age > 60 years), psoriasis, psoriatic arthritis, ischemia and ischemia with diabetes. Blood samples of healthy donors were used as controls. The backscattering signal in the erythroaggregometer was processed according to algorithms yielding quantitative data on the full amplitude of aggregation, characteristic times of spontaneous aggregation, average hydrodynamic strength of all aggregates and, whenever possible, additionally, strength of the largest aggregates. The obtained results confirm that the complexity of erythrocyte aggregation kinetics requires multiparametric description which, when applied to clinical material, enables the differentiation of aggregation characteristics between diseases.
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PMID:Clinical application of the measurement of spontaneous erythrocyte aggregation and disaggregation. A pilot study. 969 29

A 37-year-old woman with psoriasis arthropathica associated with aortic regurgitation underwent replacement of her aortic valve. The serum rheumatic factor was negative. HLA-B 27 was demonstrated in HLA analysis. She experienced a sudden onset of dyspnea and cardiac arrest in the hospital. She was hospitalized and found to have severe aortic regurgitation. She had her aortic valve replaced. We paid attention to management of blood pressure not to trigger cardiac ischemia and of skin lesion not to trigger infection and the worsening of skin condition. There are few reports of HLA-B 27 positive psoriasis arthropathica accompanied by aortic regurgitation. However, the present case may suggest that the cardiac study may be required for HLA-B 27 positive psoriasis arthropathica.
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PMID:[Anesthetic management of a patient with psoriasis arthropathica]. 1043 24

The beta2 integrin leukocyte function antigen-1 (LFA-1) has an important role in the pathophysiology of inflammatory and autoimmune diseases. Here we report that statin compounds commonly used for the treatment of hypercholesterolemia selectively blocked LFA-1-mediated adhesion and costimulation of lymphocytes. This effect was unrelated to the statins' inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A reductase; instead it occurred via binding to a novel allosteric site within LFA-1. Subsequent optimization of the statins for LFA-1 binding resulted in potent, selective and orally active LFA-1 inhibitors that suppress the inflammatory response in a murine model of peritonitis. Targeting of the statin-binding site of LFA-1 could be used to treat diseases such as psoriasis, rheumatoid arthritis, ischemia/reperfusion injury and transplant rejection.
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PMID:Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. 1138 5

In the last decade it has become well established that in the skin, nitric oxide (NO), a diffusable gas, mediates various physiologic functions ranging from the regulation of cutaneous blood flow to melanogenesis. If produced in excess, NO combines with superoxide anion to form peroxynitrite (ONOO-), a cytotoxic oxidant that has been made responsible for tissue injury during shock, inflammation and ischemia-reperfusion. The opposite effects of NO and ONOO- on various cellular processes may explain the 'double-edged sword' nature of NO depending on whether or not cellular conditions favour peroxynitrite formation. Peroxynitrite has been shown to activate the nuclear nick sensor enzyme, poly(ADP-ribose) polymerase (PARP). Overactivation of PARP depletes the cellular stores of NAD+, the substrate of PARP, and the ensuing 'cellular energetic catastrophy' results in necrotic cell death. Whereas the role of NO in numerous skin diseases including wound healing, burn injury, psoriasis, irritant and allergic contact dermatitis, ultraviolet (UV) light-induced sunburn erythema and the control of skin infections has been extensively documented, the intracutaneous role of peroxynitrite and PARP has not been fully explored. We have recently demonstrated peroxynitrite production, DNA breakage and PARP activation in a murine model of contact hypersensitivity, and propose that the peroxynitrite-PARP route represents a common pathway in the pathomechanism of inflammatory skin diseases. Here we briefly review the role of NO in skin pathology and focus on the possible roles played by peroxynitrite and PARP in various skin diseases.
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PMID:Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin. 1210 57

The ubiquitin-proteasome pathway has a central role in the selective degradation of intracellular proteins. Among the key proteins modulated by the proteasome are those involved in the control of inflammatory processes, cell cycle regulation, and gene expression. Consequently proteasome inhibition is a potential treatment option for cancer and inflammatory conditions. Thus far, proof of principle has been obtained from studies in numerous animal models for a variety of human diseases including cancer, reperfusion injury, and inflammatory conditions such as rheumatoid arthritis, asthma, multiple sclerosis, and psoriasis. Two proteasome inhibitors, each representing a unique chemical class, are currently under clinical evaluation. Velcade (PS-341) is currently being evaluated in multiple phase II clinical trials for several solid tumor indications and has just entered a phase III trial for multiple myeloma. PS-519, representing another class of inhibitors, focuses on the inflammatory events following ischemia and reperfusion injury. Since proteasome inhibitors exhibit anti-inflammatory and antiproliferative effects, diseases characterized by both of these processes simultaneously, as is the case in rheumatoid arthritis or psoriasis, might also represent clinical opportunities for such drugs.
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PMID:Proteasome inhibition: a new anti-inflammatory strategy. 1270 Aug 91

As our understanding of integrins as multifunctional adhesion and signaling molecules has grown, so has their recognition as potential therapeutic targets in human diseases. Leukocyte integrins are of particular interest in this regard, as they are key molecules in immune-mediated and inflammatory processes and are thus critically involved in diverse clinical disorders, ranging from asthma to atherosclerosis. Antagonists that interfere with integrin-dependent leukocyte trafficking and/or post-trafficking events have shown efficacy in multiple preclinical models, but these have not always predicted success in subsequent clinical trials (e.g., ischemia-reperfusion disorders and transplantation). However, recent successes of integrin antagonists in psoriasis, inflammatory bowel disease, and multiple sclerosis demonstrate the tremendous potential of antiadhesion therapy directed at leukocyte integrins. This article will review the role of the leukocyte integrins in the inflammatory process, approaches to targeting leukocyte integrins and their ligands, and the results of completed clinical trials.
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PMID:Targeting leukocyte integrins in human diseases. 1554 73


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