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)

This article focuses on the medical diseases that not only lead to cerebrovascular complications, but at times initially manifest as cerebral infarction. Specifically, I examine the relationships between stroke and various medical diseases (inflammatory disease, migraine and other vasoconstrictive disorders, congenital heart disease, connective tissue disorders, infectious disease, malignancy, and polycystic kidney disease). Many of these conditions may cause cerebrovascular ischemia via nonatherosclerotic mechanisms. Understanding these relationships between stroke and medical disease will allow the reader to better recognize etiologic relationships, and thereby reach more accurate diagnoses.
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PMID:Stroke as a complication of medical disease. 1937 Apr 95

A dysregulated host immune response, as opposed to the intrinsic virulence of a microbial pathogen induces a large part of the pathology seen in infectious diseases. However, current therapies are designed to target the pathogen rather than the underlying pathogenic mechanisms responsible for the manifestation of the pathology. Recent studies have highlighted the role of endothelial cell alteration in the pathology induced in sepsis and cerebral malaria. The endothelial onslaught described, is similar to that seen during ischemia reperfusion in stroke. Protecting endothelial cell membranes during sepsis and cerebral malaria, using citicoline in the same way as in stroke, has thus emerged as a new strategy that needs to be evaluated urgently. Citicoline is a natural compound that is registered for use in ischemic stroke, head trauma and neurological disorders. It enters the phosphatidylcholine synthesis pathway as a rate-limiting step and is involved in the modulation of a large number of metabolic pathways and neurotransmitter levels, and also in the biosynthesis of phospholipids in neuronal membranes. This short review highlights the potential role of citicoline as part of adjunct therapy in the treatment of infectious diseases.
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PMID:Citicoline (CDP-choline): What role in the treatment of complications of infectious diseases. 1940 Nov 46

Myocardial infarction and stroke are exaggerated by rupture of atherosclerotic lesions. Rupture-sensitive plaques have a specific composition which renders them vulnerable, but additional factors (acute infection, higher sympathetic activity, excessive increase of blood pressure or exposure to a variety of drugs) are needed to set off the event. Toll-like receptors are important components of the innate and adaptive immune system and seem to be a potential link between inflammation, infectious disease and atherosclerosis. In addition to classical bacterial and viral antigens, several endogenous ligands (HSP, ox-LDL, apoptotic cells) have also been proposed to react to TLRs. There is accumulating evidence substantiating the contribution of the TLR-signaling pathway not only in the initiation but also in the progression of atherosclerosis. TLRs also play a key role in the development of tissue ischemia. Apoptosis and inflammation comprise two important indicators of plaque instability, and trigger factors augmenting rapidly TLR signaling can lead to aggravation of plaque-rupture. Due to their multiplex involvement in ischemic conditions, Toll-like receptors may be a promising target for therapeutic intervention. In situations such as acute coronary syndrome, in which inhibition of the inflammatory cascade is warranted, the administration of TLR-blocking agents as adjuvant therapy and the clinical usefulness of this association should be considered.
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PMID:Toll-like receptors: link between "danger" ligands and plaque instability. 1951 53

Prostate cancer tumor growth and neovascularization is promoted by an interplay between migratory tumor stromal cells such as specialized tumor-associated macrophages (TAMs) and circulating endothelial precursor cells (CEPs). As vehicles for tumor therapy, human CEPs are relatively easy to isolate from peripheral blood, are able to proliferate long-term in vitro, are amenable to viral manipulation, and preferentially home to regions of ischemia found in growing tumors. We show here that human peripheral blood CEPs expanded ex vivo migrate to prostate cancer cells in vitro and efficiently home to human prostate tumor xenografts in vivo. Infection of precursors ex vivo with an adenovirus constructed to secrete a soluble form of the colony-stimulating factor-1 receptor CD115 that inhibits macrophage viability and migration in vitro significantly decreases the number of TAMs in xenografts (p < .05), reduces proliferation (p < .01) and vascular density (p < .03), and suppresses the growth of xenografts (p < .03). These data show for the first time that targeting stromal cell processes with cellular therapy has the potential to retard prostate tumor growth.
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PMID:Adenoviral-mediated endothelial precursor cell delivery of soluble CD115 suppresses human prostate cancer xenograft growth in mice. 1952 14

All the currently available evidence suggests that the two types of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), involve a conflict between the immune system of the intestinal mucosa and intraluminal antigens, mainly the intestinal microflora, which are normally tolerated by the immune system. This conflict is modulated by numerous environmental factors and a clear polygenetic predisposition. The present article reviews the behavior of all the etiologic circumstances (microbial, genetic and environmental) and subsequently analyzes the possible pathogenic factors in which the etiologies can be found, namely: dysfunction of the intestinal epithelium, innate immune system alterations, and distortion of the cellular and humoral arms of the acquired immune system. The role of tissue ischemia in CD and expression of "extraintestinal inflammatory metastases", both in CD and UC, are briefly discussed. Finally, the view that IBD may be a spectrum of pathological processes provoked by distinct etiopathogenic factors and the possible biological significance of the growing incidence of this disease in the western world, coinciding with the decline in infectious diseases in this geographical area, are discussed.
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PMID:[Multifactorial etiology and pathogenic factors in inflammatory bowel disease]. 1964 92

Reactive oxygen and nitrogen species (ROS and RNS) are produced by metabolism of normal cells. However, in liver diseases, redox is increased thereby damaging the hepatic tissue; the capability of ethanol to increase both ROS/RNS and peroxidation of lipids, DNA, and proteins was demonstrated in a variety of systems, cells, and species, including humans. ROS/RNS can activate hepatic stellate cells, which are characterized by the enhanced production of extracellular matrix and accelerated proliferation. Cross-talk between parenchymal and nonparenchymal cells is one of the most important events in liver injury and fibrogenesis; ROS play an important role in fibrogenesis throughout increasing platelet-derived growth factor. Most hepatocellular carcinomas occur in cirrhotic livers, and the common mechanism for hepatocarcinogenesis is chronic inflammation associated with severe oxidative stress; other risk factors are dietary aflatoxin B(1) consumption, cigarette smoking, and heavy drinking. Ischemia-reperfusion injury affects directly on hepatocyte viability, particularly during transplantation and hepatic surgery; ischemia activates Kupffer cells which are the main source of ROS during the reperfusion period. The toxic action mechanism of paracetamol is focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-p-benzoquinone imine to cellular proteins as the main cause of hepatic cell death; intracellular steps critical for cell death include mitochondrial dysfunction and, importantly, the formation of ROS and peroxynitrite. Infection with hepatitis C is associated with increased levels of ROS/RNS and decreased antioxidant levels. As a consequence, antioxidants have been proposed as an adjunct therapy for various liver diseases.
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PMID:Role of free radicals in liver diseases. 1994 Nov 70

MicroRNAs (miRNAs) are non-coding single-stranded RNAs with about 21~23 nucleotides in length, which originate from encoding genes in nucleus. miRNAs play an inhibitory role in gene expression in a post-transcriptional level by partially complementary binding to the 3' unstranlated region (UTR) of target mRNAs. Large bodies of evidence have shown that miRNAs were involved in various diseases, such as cancer, infectious diseases, diabetes etc, and rising as critical modulators of pathological processes. Lately, some highlight articles revealed that the altered expression of miRNAs such as miR-1, miR-133, miR-21, miR-208 etc in hearts also contributed to cardiovascular diseases, such as heart ischemia, cardiac hypertrophy, and arrhythmias. Moreover, miRNAs were also identified to regulate heart development. These exciting findings not only improve our understanding of the molecular mechanisms of heart diseases, but also provide a new class of potential molecular targets. miRNAs, for the development of novel agents to treat heart diseases. Here, we summarized the recent discoveries about the role of miRNAs in cardiac physiological and pathological functions, and then discussed about their therapeutic potentials for heart diseases.
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PMID:The roles of microRNAs in heart diseases: a novel important regulator. 2001 39

The dynamic and multiple functions of p53, together with its involvement in the most common non-infectious diseases, underscore the need to elucidate the complexity of the p53 regulatory networks. Pathological conditions such as cancer, neurodegeneration, ischemia, cholestasis, and atherosclerosis are all strongly associated with deregulated levels of apoptosis in which p53 dysfunction has a prominent role. We will highlight recent developments of p53-induced apoptosis in human diseases, with a focus on modulation of liver cell apoptosis. In addition, we will discuss controversies arising from widespread p53 activation as a therapeutic approach to cancer. Recent studies have provided relevant and unprecedented information about mechanistic antiapoptotic functions of the endogenous bile acid, ursodeoxycholic acid (UDCA), suggesting that the finely tuned, complex control of p53 by Mdm-2 (mouse double minute-2, an oncoprotein) is a key step in UDCA modulation of p53-triggered apoptosis. We will also review recent therapeutic strategies and clinical applications of targeted agents, their safety, and efficacy, with particular emphasis on potential benefits of UDCA.
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PMID:The role of p53 in apoptosis. 2019 41

Cyclooxygenase-2 (COX-2) activity has been implicated in the pathogenesis of ischemic injury, but the exact mechanisms responsible for its toxicity remain unclear. Infection of primary neurons with an adenovirus expressing wild type (WT) COX-2 increased the susceptibility of neurons to hypoxia. Infection with an adenoviral vector expressing COX-2 with a mutation at the cyclooxygenase site did not increase susceptibility to hypoxia, whereas over-expression of COX-2 with a mutation in the peroxidase site produced similar susceptibility to hypoxia as WT COX-2. Primary neuronal cultures obtained from transgenic mice bearing a mutation in the COX-2 cylooxygenase site were protected from hypoxia. Mice with a mutation in the cyclooxygenase site had smaller infarctions 24 h after 70 min of middle cerebral artery occlusion than WT control mice. COX-2 activity had no effect on the formation of protein carbonyls. Ascorbate radicals were detected by electron paramagnetic resonance as a product of recombinant COX-2 activity and were blocked by COX-2 inhibitors. Similarly, formation of ascorbate radicals was inhibited in the presence of COX-2 inhibitors and in homogenates obtained from COX-2 null mice. Taken together, these results indicate that the cyclooxygenase activity of COX-2 is necessary to exacerbate neuronal hypoxia/ischemia injury rather than the peroxidase activity of the enzyme.
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PMID:The cyclooxygenase site, but not the peroxidase site of cyclooxygenase-2 is required for neurotoxicity in hypoxic and ischemic injury. 2023 88

A new era in thalassemia and other transfusional iron loading conditions was highlighted during the 18th International Conference on Chelation (ICOC) with reports that all excess iron accumulated from transfusions could be removed using the ICOC combination protocol of deferiprone (L1) (80-100 mg/kg/day) and subcutaneous deferoxamine (DFO) (40-60 mg/kg/day, at least 3 days per week), and that normal range body iron store levels (NRBISL) could be maintained using L1 monotherapy. Hundreds of patients in Cyprus, Greece, Italy, UK and elsewhere, maintain NRBISL, some for more than 9 years, and without complications. This gold standard of complete iron overload treatment is likely to change current practices, aims and protocols because it could prevent and also reverse cardiac, liver, endocrine and other organ complications as well as the incidence of infections and hepatocellular carcinomas. The overall morbidity and mortality in thalassemia and other transfusional iron loading conditions is expected to be substantially reduced. New applications of chelating drugs include renal, neurodegenerative, infectious diseases and ischemia reperfusion injury patients. Ethical questions have been raised on the role of pharmaceutical companies, the clinicians and the Hippocratic oath in relation to chelation therapy.
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PMID:The 18th ICOC Proceedings in Athens, Greece: New breakthrough in thalassemia leading to the complete treatment of iron overload and to hundreds of patients achieving and maintaining normal body iron stores. Ethical questions on chelation therapy. 2052 9


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