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)

Erythropoietin (EPO) is commonly used to treat anemias secondary to renal failure, malignancy, and AIDS. Although therapeutic complications are well described, overdose is rare. A 42-y-o man with AIDS confused his instructions for self-administration of interferon and EPO and began injecting himself daily with 10,000 units of EPO for several weeks. He presented with confusion, pain in his abdomen and feet, and a hemoglobin of 23.2 g/dLwith a hematocrit of 77.1%. The patient was treated with iv fluids, phlebotomy and 2 sessions of erythropheresis which removed 898 mL and 640 mL of red blood cells, respectively; his hemoglobin remained between 12-14 g/dL and symptoms resolved. His only sequelae involved skin loss over his toes, which did not require grafting. This rare case of EPO overdose highlights the complications of essential erythrocytosis, with central nervous system, peripheral, and presumed mesenteric ischemia.
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PMID:Erythropoietin overdose treated with emergent erythropheresis. 1204 68

Inappropriate imbalances between proteases and protease inhibitors are known to occur under cerebral ischemia and neurodegenerative processes, and could be contributors to various diseases that are characterized by excessive (ischemia, AIDS) or inadequate (cancer, autoimmunity) cell death. For instance, calpain is activated in various necrotic and apoptotic conditions, whereas caspase-3 is only activated in neuronal apoptosis. Caspases and calpains are cysteine proteases that require proteolytic cleavage for activation. The substrates cleaved by caspases include cytoskeletal and associated proteins, kinases, members of the Bcl-2 family of apoptosis-related proteins, presenilins, and DNA-modulating enzymes. Calpain substrates include cytoskeletal and associated proteins, kinases and phosphatases, membrane receptors and transporters, and steroid receptors. This article provides a review of the properties of caspases and calpains, their roles in cell death pathways following cerebral ischemia, and the substrates upon which they act. Because calpain inhibitors and caspase inhibitors appear to protect brain tissue by distinct mechanisms in cerebral ischemia, the possible therapeutic interactions between these drugs in a well-defined rodent model of global ischemia are briefly discussed and documented.
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PMID:Ischemic neuronal death in the rat hippocampus: the calpain-calpastatin-caspase hypothesis. 1282 32

Cystic pneumatosis (CP) is an uncommon but significant condition in adults in which gas is found in a linear or cystic form in the submucosa or the subserosa of the bowel wall. The diagnosis was made by conventional X-ray and confirmed by abdominal computed tomography. Benign pneumoperitoneum due to CP should be considered in the differential diagnosis of free intra-abdominal air after chemotherapeutic or immunosuppressive therapy. As such, pneumatosis intestinalis is only a sign and must be interpreted in light of the clinical findings because it may be found in various scenarios: in patients who are otherwise healthy, and associated with pyloric stenosis, jejunoileal bypass, progressive systemic sclerosis, transplantation, chemotherapy, immunosuppression (including AIDS), obstructive pulmonary disease and finally, as in our case, after liver transplantation. Since there were no signs of secondary complications such as peritonitis, ischemia, or perforation, conservative treatment with broad-spectrum antibiotics and parenteral nutrition was initiated.
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PMID:Cystic pneumatosis of the colon after liver transplantation. 1295 60

Advanced MRI techniques, such as MR spectroscopy, diffusion and perfusion MR imaging can give important in vivo physiological and metabolic information, complementing morphologic findings from conventional MRI in the clinical setting. Combining perfusion MRI and MR spectroscopy can help in patients with brain masses in who the pre-operative differential diagnosis is unclear. This review demonstrates the use of dynamic, susceptibility weighted, contrast-enhanced MR imaging (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI) to distinguish surgical from non-surgical lesions in the brain. There is overlap in the MRI appearance of many enhancing and ring-enhancing lesions such as gliomas, metastases, inflammatory lesions, demyelinating lesions, subacute ischemia, abscess and some AIDS related lesions. We review examples of histopathologically confirmed high-grade glioma, a middle cerebral artery territory infarct, a tumefactive demyelinating lesion and a metastasis for which conventional MR imaging (MRI) was non-specific and potentially misleading and demonstrate how DSC MRI and MRSI features were used to increase the specificity of neurodiagnosis. At several institutions, many patients routinely undergo MRI as well as MRSI and DSC MRI. Cerebral blood flow (CBF), mean transit time (MTT), and relative cerebral blood volume (rCBV) measurements are obtained from regions of maximal perfusion as determined from perfusion color overlay maps. Metabolite levels and ratios are determined for Choline (Cho), N-Acetyl Aspartate (NAA), Lactate and Lipids (LL). Metabolite levels are obtained by measuring the peak heights of each metabolite and the ratios are obtained from these measurements for Cho/Cr, Cho/NAA and NAA/Cr. Neurosurgical intervention carries substantial morbidity, mortality, financial and potential emotional cost to the patient and family. Making a pre-operative diagnosis allows the neurosurgeon to be confident in the choice of treatment plan for the patient and allays considerable patient anxiety. The utility of combining clinical findings with multi-parametric information from perfusion and spectroscopic MR imaging in differentiating surgical lesions from those which do not require surgical intervention is discussed.
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PMID:Differentiating surgical from non-surgical lesions using perfusion MR imaging and proton MR spectroscopic imaging. 1556 Jul 13

The review present the literature data and the authors findings on perspective technologies for design of active chemical and natural compounds based on small molecules for highly specific therapy and correction of a wide variety of pathophysiological conditions in humans, that show overlapping development processes and have common mediators. The following strategies are discussed: chemogenomics strategy using computer screening libraries for generating of small molecule compounds with advantageous properties; strategy of chemokine network that provide control of many processes, from immunosurveillance to inflammation and from viral infections to cancer; strategy of using cytochrome P450 enzymes that guarantee maximum bioavailability of drugs and prevent their interaction and toxic effect; strategy of using superoxide dismutase enzymes (SOD) correcting superoxide anions overproduction in tissue injury and inflammation, from ischemia, organ transplantation to AIDS and cancer; strategy of telomer maintenance directed to anticancer and antiviral therapy as well as to correction of the aging processes; and strategy of short interfering RNAs capable to induce intracellular immunity to antigens of various origin.
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PMID:[Perspective technologies for drug design]. 1630 41

The p53-upregulated modulator of apoptosis (Puma), a BH3-only member of the Bcl-2 protein family, is required for p53-dependent and -independent forms of apoptosis and has been implicated in the pathomechanism of several diseases, including cancer, acquired immunodeficiency syndrome, and ischemic brain disease. The role of Puma in cardiomyocyte death, however, has not been analyzed. On the basis of the ability of Puma to integrate diverse cell death stimuli, we hypothesized that Puma might be critical for cardiomyocyte death upon ischemia-reperfusion (I/R) of the heart. Here we show that hypoxia-reoxygenation of isolated cardiomyocytes led to an increase in Puma mRNA and protein levels. Moreover, if Puma was delivered by an adenoviral construct, cardiomyocytes died by apoptosis. Under ATP-depleted conditions, however, Puma overexpression primarily induced necrosis, suggesting that Puma is involved in the development of both types of cell death. Consistent with these findings, targeted deletion of Puma in a mouse model attenuated both apoptosis and necrosis. When the Langendorff ex vivo I/R model was used, infarcts were approximately 50% smaller in Puma(-/-) than in wild-type mice. As a result, after I/R, cardiac function was significantly better preserved in Puma(-/-) mice than in their wild-type littermates. Our study thus establishes Puma as an essential mediator of cardiomyocyte death upon I/R injury and offers a novel therapeutic target to limit cell loss in ischemic heart disease.
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PMID:Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion. 1677 23

Nitric oxide (NO) is a gas with diverse biological activities produced from arginine by nitric oxide synthetase (NOS). The loss of retinal ganglion cells is a hallmark of many ophthalmic diseases including glaucoma, retinal ischemia due to central artery occlusion and anterior ischemic optic neuropathy. It may well be significant in optic neuritis, optic nerve, trauma and AIDS. NO appears to be involved in the regulation of intraocular pressure, in the modulation of ocular blood flow and in apoptosis. This article gives a short and simplified overview of the biochemistry of NO and its role in physiology and pathogenesis of ocular diseases.
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PMID:[The role of nitric oxide in physiology and pathogenesis of ocular diseases]. 1688 53

The need to develop a blood substitute is now urgent because of the increasing concern over Europe's BSE outbreak and the worldwide HIV/AIDS epidemic, which have cut blood supplies. Extracellular soluble hemoglobin has long been studied for its possible use as a safe and effective alternative to blood transfusion, but this has met with little success. Clinical trials have revealed undesirable side effects-oxidative damage and vasoconstriction-that hamper the application of cell-free hemoglobin as a blood substitute. We have addressed these problems and have found a new promising extracellular blood substitute: the natural giant extracellular polymeric hemoglobin of the polychaete annelid Arenicola marina. Here we show that it is less likely to cause immunogenic response; its functional and structural properties should prevent the side effects often associated with the administration of extracellular hemoglobin. Moreover, its intrinsic properties are of interest for other therapeutic applications often associated with hemorrhagic shock (ischemia reperfusion, treatment of septic shock and for organ preservation prior to transplantation). Moreover, using natural hemoglobin is particularly useful since recombinant DNA techniques could be used to express the protein in large quantities.
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PMID:Arenicola marina extracellular hemoglobin: a new promising blood substitute. 1689 13

Case reports have previously been published describing various complications of cytomegalovirus (CMV) and mucormycosis in patients with HIV/AIDS. We describe the first case of CMV vasculitis and mucormycosis coinfection resulting in necrotizing myofascial cellulitis in an extremity in late stage HIV/AIDS. In AIDS patients, CMV reactivates when the CD4 count falls to less than 50 cells/microL (normal, 720-1440 cells/microL). Transient episodes of neutropenia in patients with HIV/AIDS who have low CD 4 cell counts are a predisposing factor for mucormycosis. These predisposing conditions were both present in our patient. Our case raises the question of CMV vasculitis leading to tissue ischemia as a possible contributing factor to the mucormycosis superinfection.
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PMID:Cytomegalovirus vasculitis and mucormycosis coinfection in late-stage HIV/AIDS. 1730 93

One major pathogenesis in degenerative disorders of the central nervous system (CNS), including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and ischemia, is the oxidative stress induced by reactive oxygen species (ROS). The present study investigated the protective effect of colloidal silver, which is widely marketed as a dietary supplement for diseases like diabetes, AIDS, cancer, and various infections, upon the oxidative brain damage induced by H(2)O(2) or naphthazarin treatment. LDH release from primary cultured astrocytes was enhanced by naphthazarin treatment, and this elevation of the LDH concentration in medium was blocked by colloidal silver treatment. However, hydrogen peroxide was little affected by the colloidal silver. Fluorescence of DCF (peroxides) increased in astrocytes incubated with hydrogen peroxide or naphthazarin compared to the control. When exposed to naphthazarin-induced cells, ROS formation appeared to be reduced by colloidal silver. However, intracellular ROS formation in hydrogen peroxide-treated cells slightly reduced by colloidal silver. These results suggest that colloidal silver has a protective activity against the oxidative stress induced by naphthazarin, but not by hydrogen peroxide.
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PMID:Effect of colloidal silver against the cytotoxicity of hydrogen peroxide and naphthazarin on primary cultured cortical astrocytes. 1736 22


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