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)

Patients with human immunodeficiency virus (HIV) have various coagulation abnormalities as well as increased risk for development of clinical thrombosis and subsequent embolic events. We report acute lower leg ischemia caused by spontaneous atheroembolism with no identifiable source in a young patient with HIV infection. Treatment included percutaneous mechanical thrombectomy and thrombolysis, which reversed the arterial ischemia. Physicians should be aware of thromboembolic disease as a possible complication of HIV.
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PMID:Spontaneous arterial thrombosis in a patient with human immunodeficiency virus infection: successful treatment with pharmacomechanical thrombectomy. 1289 Nov 27

A 57-year-old man with human immunodeficiency virus (HIV) infection was evaluated in October 1997 with complaints of weakness of the right lower extremity. A chest computerized axial tomographic scan revealed a type I aortic dissection. He underwent surgical repair including resuspension of the aortic valve and placement of a 32-mm interposition graft between the aortic root and the transverse arch. Postoperatively he required abdominal aorta fenestration and stenting for ischemia of the left lower extremity. Follow-up magnetic resonance imaging 3(1)/(2) years postoperatively showed a normal-sized ascending and transverse aorta and the residual dissection in the descending thoracic and abdominal aorta. The thoracic and abdominal aorta diameters have remained stable. Select patients with type I aortic dissection and HIV infection are candidates for surgical repair.
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PMID:Repair type I aortic dissection in a patient with human immunodeficiency virus infection. 1296 29

A powerful artificial anti-apoptotic factor will be useful for the reproductive therapies for many diseases by prolonging survival of stem cells. For constructing it, we designed the super anti-apoptotic factor by disturbing three intramolecular polar interactions among alpha-helix structures of Bcl-xL. The resultant mutant Bcl-xL, named FNK, was expected to make the pore-forming domain more mobile and flexible than the wild-type. When overexpressed in Jurkat cells, FNK was markedly more potent in prolonging survival following apoptosis-inducing treatment with a kind of cell death cytokines (anti-Fas), a protein kinase inhibitor (staurosporine), cell cycle inhibitors (TN-16, camptothecin, hydroxyurea and trichostatin A) or oxidative stress (hydrogen peroxide and paraquat) than wild-type Bcl-xL. Furthermore, the transfectants of FNK became more resistant against a calcium ionophore and even a heat treatment than wild-type Bcl-xL. In addition, FNK showed marked anti-apoptotic activity in CHO and Jurkat cells deprived of serum. Thus, FNK may be the first mutant generated by site-directed mutagenesis of Bcl-xL with an enhance gain-of-function phenotype. Next, we tried to transduce the FNK protein into cells. Protein therapeutics has the advantage of delivering proteins in a short period of time. We have engineered the anti-apoptotic bcl-x gene to generate the super anti-apoptotic factor, FNK, with a more powerful cytoprotective activity. In this study, we fused the protein transduction domain (PTD) of the HIV/Tat protein to FNK, and used the construct in an animal model of ischemic brain injury. When added into culture media of human neuroblastoma cells and rat neocortical neurons, PTD-FNK rapidly transduced into cells and localized to mitochondria within 1 hr. It protected the neuroblastomas and neurons against staurosporine-induced apoptosis and glutamate-induced excitotoxicity, respectively. The cytoprotective activity of PTD-FNK was found at concentrations as low as 0.3 pM. Additionally, PTD-FNK affected the cytosolic movement of calcium ions, which may relate to its neuroprotective action. Immunohistochemical analysis revealed that myc-tagged PTD-FNK (PTD-myc-FNK) injected intraperitoneally into mice can have access into brain neurons. When injected intraperitoneally into gerbils, PTD-FNK prevented delayed neuronal death in the hippocampus caused by transient global ischemia. These results suggest that PTD-FNK has a potential for clinical utility as a novel protein therapeutic strategy to prevent cell death in the brain. Thus, the protein delivery system will be useful to make cells survived for a long time during the differentiation of stem cells in the reproductive therapies.
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PMID:[Development of the protein therapeutics using the super anti-cell death factor FNK]. 1457 48

The Bcl-2 family of proteins regulates apoptosis chiefly by controlling mitochondrial membrane permeability. It has previously been shown that the BH4 domain of Bcl-2/Bcl-xL is essential for the prevention of apoptotic mitochondrial changes, including the release of cytochrome c and apoptotic cell death. We have previously reported that BH4 peptide fused to the protein transduction domain of HIV-1 TAT protein (TAT-BH4) significantly inhibits etoposide-induced apoptosis in a cell line. This time, we investigated whether TAT-BH4 peptide was cytoprotective in ex vivo and in vivo rodent models. Intraperitoneal injection of TAT-BH4 peptide greatly inhibited X-ray-induced apoptosis in the small intestine of mice and partially suppressed Fas-induced fulminant hepatitis. In addition, this peptide markedly suppressed heart failure after ischemia-reperfusion injury in isolated rat heart, probably by preventing mitochondrial dysfunction. These findings demonstrate that TAT-BH4 peptide exerts anti-apoptotic activity both in vivo and ex vivo, and imply that it may be a useful therapeutic agent for diseases involving mitochondrial dysfunction and apoptosis.
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PMID:BH4-domain peptide from Bcl-xL exerts anti-apoptotic activity in vivo. 1462 84

The present experiments were carried out to provide direct in vivo evidence for the involvement of c-Jun N-terminal kinase (JNK) in the induction of ischemic brain injury. Malonate, which produces lesions similar to those of focal ischemia-reperfusion by a reversible inhibition of succinate dehydrogenase in mitochondria, was injected into the left striatum in the rat brain without or with the simultaneous injection of a cell permeable peptidic JNK inhibitor, (L)-HIV-TAT48-57-PP-JBD20. Two regions of malonate-induced brain injury were visualized as a hyperintense region with surrounding hypointense regions by apparent diffusion coefficient mapping magnetic resonance imaging. The JNK inhibitor significantly counteracted both hyper- and hypointense regions at the early stage of brain injury. Histological examination clarified that the inhibitor suppressed the induction of coagulation necrosis and spongy degeneration at early and late stages.
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PMID:Protection against malonate-induced ischemic brain injury in rat by a cell-permeable peptidic c-Jun N-terminal kinase inhibitor, (L)-HIV-TAT48-57-PP-JBD20, observed by the apparent diffusion coefficient mapping magnetic resonance imaging method. 1505 Jul 11

The blood-brain barrier (BBB) is a diffusion barrier, which impedes influx of most compounds from blood to brain. Three cellular elements of the brain microvasculature compose the BBB-endothelial cells, astrocyte end-feet, and pericytes (PCs). Tight junctions (TJs), present between the cerebral endothelial cells, form a diffusion barrier, which selectively excludes most blood-borne substances from entering the brain. Astrocytic end-feet tightly ensheath the vessel wall and appear to be critical for the induction and maintenance of the TJ barrier, but astrocytes are not believed to have a barrier function in the mammalian brain. Dysfunction of the BBB, for example, impairment of the TJ seal, complicates a number of neurologic diseases including stroke and neuroinflammatory disorders. We review here the recent developments in our understanding of the BBB and the role of the BBB dysfunction in CNS disease. We have focused on intraventricular hemorrhage (IVH) in premature infants, which may involve dysfunction of the TJ seal as well as immaturity of the BBB in the germinal matrix (GM). A paucity of TJs or PCs, coupled with incomplete coverage of blood vessels by astrocyte end-feet, may account for the fragility of blood vessels in the GM of premature infants. Finally, this review describes the pathogenesis of increased BBB permeability in hypoxia-ischemia and inflammatory mechanisms involving the BBB in septic encephalopathy, HIV-induced dementia, multiple sclerosis, and Alzheimer disease.
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PMID:The blood-brain barrier: an overview: structure, regulation, and clinical implications. 1520 56

Pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), and peptide histidine-isoleucine (PHI) belong to a structurally related family of polypeptides present in many regions of the central and peripheral nervous system. The neuroprotective potential of PACAP, VIP, and PHI has become a matter of intensive investigations in many animal models. In vitro studies revealed that PACAP protects neurons against apoptosis occurring naturally during CNS development and apoptosis induced by a series of neurotoxins, such as ethanol, hydrogen peroxide (H2O2), prion protein, beta-amyloid, HIV envelope glycoprotein (gp120), potassium ion deficit, and high glutamate concentrations. Similarly, in vivo investigations conducted in models of ischemia and Parkinson's disease confirmed the neuroprotective properties of PACAP. It was revealed that the anti-apoptotic action of PACAP can be directly associated with the activation of signal transduction pathways preventing apoptosis in neurons or involve glial cells capable of releasing other neuroprotective factors affecting neurons. In contrast to PACAP, the neuroprotective action of VIP depends mainly on stimulation of astrocytes to produce and secrete factors of extremely high neuroprotective potential, including activity-dependent neurotrophic factor (ADNF) and activity-dependent neuroprotective protein (ADNP). It was shown that ADNF and ADNP, as well as their shortened derivatives ADNF-9 and NAP, prevent neurons from electrical blockade, excitotoxicity, apoE deficiency, glucose deficit, ischemia, toxic action of ethanol, beta-amyloid, and gp120. The neuroprotective potential of PHI has not been as thoroughly investigated yet, but recent data have confirmed that this peptide can also function as a neuroprotectant. It is thought that PACAP, VIP, and possibly PHI may serve as a goal of modern therapeutic strategies in various neurodegenerative disorders.
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PMID:[Neuroprotective role of PACAP, VIP, and PHI in the central nervous system]. 1557 49

We evaluated immediate and long-term results of percutaneous transluminal angioplasty (PTA) and stent placement to treat stenotic and occluded arteries in patients with chronic mesenteric ischemia. Fourteen patients were treated by 3 exclusive celiac artery (CA) PTAs (2 stentings), 3 cases with both Superior Mesenteric Artery (SMA) and CA angioplasties, and 8 exclusive SMA angioplasties (3 stentings). Eleven patients had atheromatous stenoses with one case of an early onset atheroma in an HIV patient with antiphospholipid syndrome. The other etiologies of mesenteric arterial lesions were Takayashu arteritis (2 cases) and a postradiation stenoses (1 case). Technical success was achieved in all cases. Two major complications were observed: one hematoma and one false aneurysm occurring at the brachial puncture site (14.3%). An immediate clinical success was obtained in all patients. During a follow-up of 1-83 months (mean: 29 months), 11 patients were symptom free; 3 patients had recurrent pain; in one patient with inflammatory syndrome, pain relief was obtained with medical treatment; in 2 patients abdominal pain was due to restenosis 36 and 6 months after PTA, respectively. Restenosis was treated by PTA (postirradiation stenosis), and by surgical bypass (atheromatous stenosis). Percutaneous endovascular techniques are safe and accurate. They are an alternative to surgery in patients with chronic mesenteric ischemia due to short and proximal occlusive lesions of SMA and CA.
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PMID:Endovascular treatment of chronic mesenteric ischemia: results in 14 patients. 1557 41

This investigation was carried out on 851 consecutive judicial autopsies of drug addicts who died mostly of heroin overdose from 1977 to 1996. Research of anti-HIV/HBV/HCV antibodies was performed, and histologic sections were retrospectively reviewed. More than 65% were HBV/HCV-positive and about 17% HIV-positive; females were HIV-positive more often than males. Intracranial microhemorrhages were frequently found; cerebral infectious diseases were rare. Inflammatory heart lesions, myocardial fibrosis, and acute ischemia were common. Interstitial nephritis (found in about 8%) was more frequent in females, in older patients, and in those carrying HIV infection; glomerular sclerosis was detected in about 12%. Acute bronchitis and/or pneumonia was demonstrated in 12%, without significant association with HIV infection; pulmonary hemorrhages, foreign body granulomas, and food aspiration were also commonly seen; hyperplasia of pulmonary perivascular lymphatic tissue was rather characteristic. Liver was carrying steatosis in 66.3% and/or hepatitis in 64.5%; acute hepatitis was more frequent in females, chronic hepatitis in older subjects and in those proven positive for hepatotropic viruses; cirrhosis occurred more often in older patients, in those carrying virus infection, and in consumers of nonnarcotics drugs such as ethanol. No pathologic finding was clearly related to drug abuse; therefore, during autopsy, drug addiction can be suspected, but anamnestic and circumstantial data are needed to lead pathologists to request toxicologic analysis to ascertain the cause of death. The present investigation emphasizes that, in addition to the risk of death by overdose, the high incidence of acute and chronic diseases could seriously undermine the health status of heroin and/or other drug consumers.
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PMID:Histopathological findings in 851 autopsies of drug addicts, with toxicologic and virologic correlations. 1589 41

Ischemic preconditioning is a powerful endogenous phenomenon in which brief periods of a sub-toxic ischemic insult induce robust protection against future, lengthy, lethal ischemia. The cardioprotective effects of ischemic preconditioning are manifest in all species studied so far, including humans. The ability to reproduce the cardioprotective effects of ischemic preconditioning with pharmacological agents raises the possibility that a drug may ultimately be introduced into clinical practice to treat human hearts undergoing ischemia/reperfusion. This chapter focuses on erythropoietin (Epo), a drug that has already been approved for humans and is in current use for the treatment of anemia associated with chronic renal failure, HIV infection, cancer patients on chemotherapy, and to reduce allogenic blood transfusion in surgery patients. Several recent studies have suggested that this cytokine possesses properties far beyond its capacity to produce red blood cells such as the ability to protect tissues including brain, kidney and heart against injury caused by ischemia/reperfusion. Cardioprotection conferred by Epo has been shown to be equal in magnitude to that conferred by ischemic preconditioning. However, the underlying mechanisms by which Epo protects the heart against injury caused by ischemia remain unknown.
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PMID:Erythropoietin mimics ischemic preconditioning. 1592 56


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