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)

Small molecules inhibiting hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are the focus of drug development efforts directed toward the treatment of ischemia and metabolic imbalance. A cell-based reporter produced by fusing HIF-1 alpha oxygen degradable domain (ODD) to luciferase was shown to work as a capture assay monitoring stability of the overexpressed luciferase-labeled HIF PHD substrate under conditions more physiological than in vitro test tubes. High throughput screening identified novel catechol and oxyquinoline pharmacophores with a "branching motif" immediately adjacent to a Fe-binding motif that fits selectively into the HIF PHD active site in in silico models. In accord with their structure-activity relationship in the primary screen, the best "hits" stabilize HIF1 alpha, upregulate known HIF target genes in a human neuronal line, and exert neuroprotective effects in established model of oxidative stress in cortical neurons.
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PMID:Utilization of an in vivo reporter for high throughput identification of branched small molecule regulators of hypoxic adaptation. 2041

A 56-year-old man with rheumatoid arthritis developed emotional lability and myoclonic seizure in the left arm, followed by fever and generalized convulsion. Brain magnetic resonance imaging (MRI) revealed leptomeningeal lesions with abnormal enhancement. MRI lesions were localized predominantly in the right cerebral subarachnoid spaces. Electroencephalogram showed epileptogenic focus at the right frontal and central points. After administration of valproate sodium improved convulsion and myoclonus, single photon emission computed tomography (SPECT) using N-isopropyl-p-(123)I-iodoamphetamine was performed. Brain SPECT displayed hypoperfusion predominantly in the right cerebral hemisphere. Cerebrospinal fluid (CSF) disclosed mild pleocytosis and marked elevations of interleukin-6 levels. Repeated CSF analyses showed cytology of class I and negative results for infectious pathogens. Methylprednisolone pulse therapy (1 g for 3 days, iv) and subsequent prednisolone administration (daily 50 mg, po) ameliorated neurological symptoms dramatically. Prednisolone was tapered to 20 mg/day for 5 months. Leptomeningeal MRI lesions were attenuated gradually followed by restoration of cerebral hypoperfusion on SPECT. He was diagnosed as rheumatoid leptomeningitis (RLM). Although clinical features of RLM exhibited variable deficits of the central nervous system (CNS), MRI failed to detect the corresponding CNS lesions. We first highlighted neuroradiological changes of cerebral hypoperfusion and leptomeningeal lesions in RLM. These neuroimages of our patient supported that leptomeningeal inflammation and the adjacent cerebrocortical ischemia could cause encephalitis-like symptoms in RLM patients.
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PMID:Rheumatoid leptomeningitis: radiological alteration of cerebral hypoperfusion and subarachnoid lesions. 2082 56

Common, noncentral nervous system medical conditions linked with cognitive impairment in adults and the elderly include: acute respiratory distress syndrome; cancer; chronic kidney disease; chronic obstructive pulmonary disease; coronary heart disease; hypertension; obesity (bariatric surgical candidates); obstructive sleep apnea; and type 2 diabetes. Cross-condition comparison of the nature and frequency of cognitive impairment is difficult as these conditions often coexist, and there exists no consensus as to the definition of cognitive impairment, nor the optimal number and type of neuropsychological tests required for evaluation. There is as yet no clear evidence for condition-specific profiles of cognitive impairment. Rather, a generalized profile consisting of subclinical levels of impairment in attention, processing speed, executive, and memory functions from bilateral frontal-subcortical ischemia fits across all conditions. This profile: occurs only in subgroups of patients; is inconsistently related to measures of illness severity; is unrelated to patient self-report or level of functional independence; is exacerbated by very high levels of emotional distress; and is reversible in some cases but can also progress to frank neurological disease (dementia) in others, especially the elderly, when multiple conditions coexist, and/or when medical condition severity progresses.
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PMID:Cognitive impairment in common, noncentral nervous system medical conditions of adults and the elderly. 2121 18

NADPH oxidase (Nox) has a dedicated function of generating reactive oxygen species (ROS). Accumulating evidence suggests that Nox has an important role in signal transduction in cellular stress responses. We have reviewed the current evidence showing that the Nox system can be activated by a collection of chemical, physical, and biological cellular stresses. In many circumstances, Nox activation fits to the cellular stress response paradigm, in that (1) the response can be initiated by various forms of cellular stresses; (2) Nox-derived ROS may activate mitogen-activated protein kinases (extracellular signal-regulated kinase, p38) and c-Jun NH(2)-terminal kinase, which are the core of the cell stress-response signaling network; and (3) Nox is involved in the development of stress cross-tolerance. Activation of the cell survival pathway by Nox may promote cell adaptation to stresses, whereas Nox may also convey signals toward apoptosis in irreversibly injured cells. At later stage after injury, Nox is involved in tissue repair by modulating cell proliferation, angiogenesis, and fibrosis. We suggest that Nox may have an integral role in cell stress responses and the subsequent tissue repair process. Understanding Nox-mediated redox signaling mechanisms may be of prominent significance at the crossroads of directing cellular responses to stress, aiming at either enhancing the stress resistance (in such situations as preventing ischemia-reperfusion injuries and accelerating wound healing) or sensitizing the stress-induced cytotoxicity for proliferative diseases such as cancer. Therefore, an optimal outcome of interventions on Nox will only be achieved when this is dealt with in a timely and disease-and stage-specific manner.
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PMID:NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair. 2122 61

For decades severe tubular necrosis has been the hallmark of experimental models of acute renal failure (ARF), such as prolonged ischemia and reflow. This fits well with the still widely used traditional clinical term 'acute tubular necrosis'. Nevertheless, the rareness of tubular necrosis in human kidney biopsies in the background of hypoxic, toxic and septic AKI led to the adoption of a new term, 'acute kidney injury' (AKI), which refers to such clinical scenarios irrespective of the renal morphology. Indeed, experimental AKI models, which have more limited acute renal parenchymal compromise, underscore the focal and regional tissue injury patterns that range from adaptive stress response, through cellular dysfunction, apoptotic cell death and frank acute tubular necrosis. Such stress and injury patterns, short of necrosis, may go unnoticed morphologically and even functionally, and may even confer resistance to subsequent insults. Herein we describe the spectrum of what we call 'sublethal injury', referring to a condition, which by itself is insufficient to produce cellular death, but may or may not produce organ failure. Such sublethal injury can be detected by overt morphological changes, by the upregulation of cell survival factors, and by recently developed biomarkers and imaging techniques of organ physiology and dysfunction. The use of combined sublethal insults in animal models is an attempt to replicate the clinical situation of comorbidities, a circumstance which underlies most situations of AKI. This review will discuss the definition of such sublethal injury and the modes of its detection.
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PMID:Acute kidney injury: lessons from experimental models. 2125 27

Cerebral sinovenous thrombosis in neonatal period may cause neurological impairment, epilepsy, and lead to stroke. It is caused primarily by coagulopathy of numerous reasons, occasionally perinatal asphyxia, traumatic delivery and hyperhomocysteinemia. Dandy-Walker malformation is characterized by agenesis or hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle, and enlargement of the posterior fossa. Dandy-Walker malformation, variant, and mega cisterna magna represent a spectrum of developmental anomalies. Insults to developing cerebellar hemispheres and the fourth ventricle are believed to be the cause of malformation. Our patient was born from noncomplicated pregnancy, noncomplicated nontraumatic vaginal delivery at term, excellent Apgar scores, without peculiarities in clinical status. She was brest-fed by the 42nd hour of life when she had rightsided seizures during sleep that repeated for five times in next 24 hours. Brain Ultrasound (US) revealed clot in left lateral ventricle, slight dilatation of left ventricle, both sided periventricular echodensity, ischemia, slight enlargement of forth ventricle and a bit smaller cerebellum. There was no visible flow through left transverse, superior sagittal and straight sinus. Magnetic Resonance (MRI) confirmed the finding and showed thrombosis of left and right transverse venous sinuses and confluence of sinuses. Electroencephalogram (EEG) showed leftsided focal changes. The newborn was treated with phenobarbiton for 8 days and had no convulsions during that period. All coagulation parameters, homocistein, lipoproteins (a) and D-dimers were normal. There were no mutations on FV R506Q, PT 20210A, MTHFR 677C/T. No antiphospholipides were found. Heart US showed no structural anomalies. No other patology or risk factors were present at the time. Before discharge, US showed hydrocephalus. Flow in affected sinuses was visible with color Doppler. MRI showed recanalization of affected sinuses, also hydrocephalus and presentation of Dandy Walker On EEG there was borderline finding. Due to progression of hydrocephalus ventriculo-peritoneal shunt was placed. In age of 1 year EEG was slower for age but without focus. Neurological development was normal for age. The question is whether this child had intrauterine insult and inception of Dandy Walker with further postnatal progress of thrombosis and evolution to full picture of Dandy Walker with hydrocephalus OR thrombosis that led to development of hydrocephalus and Dandy Walker malformation in this child were accidental coexistance.
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PMID:Coexistance of cerebral sinovenous thrombosis and Dandy Walker malformation in newborn. 2164 52

The symptoms of Takayasu arteritis (TA) are related to end organ ischemia. Here we present a patient with convulsions and intracranial involvement. A 15-year-old young woman was admitted with the complaint of convulsions since one and a half months previously. Her physical examination showed absent pulses and unobtainable blood pressure in both arms. Electroencephalography was normal. An arcus aorto-abdominal aortography, performed for TA prediagnosis, revealed that the subclavian artery ended as a stump at its origin on the right and was occluded by tapering on the left. Arcus aorta was normal. The right renal artery was occluded up to 80-90%. Magnetic resonance imaging of the brain revealed abnormal signal intensity in the deep white matter bilaterally. Cerebral catheter angiography showed focal stenosis of cerebral vessels; it was classified as type V according to the classification of the Takayasu Conference of 1994. A diagnosis of TA was made and 1 mg/kg steroid was given, and after a month methotrexate (15 mg/week) was added. On the tenth treatment day her pulse could be revealed. During the control period she had no convulsion. In young patients TA should be kept in mind as a rare cause in convulsion etiology. Intracranial involvement of TA must be evaluated especially if there is a headache and convulsion.
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PMID:Takayasu arteritis with intracranial involvement mimicking epilepsy: case report and review of the literature. 2167 74

Convulsions are one of the frequently seen problems for a neurologist in the daily routine. It is difficult to distinguish the seizure from pseudo-seizure because of lack of conclusive tests. The aim of this study is to investigate the relationship between seizure types and seizure periods by studying IMA serum levels in children having seizure. Two groups were included (patients and control) in our study. The patient group consisted of the children admitted to Pediatric Emergency Care during January 2008-January 2010 with seizure and the control group consisted of healthy children. Serum Ischemia modified albumin (IMA) level in the group having seizures was 99.7 and 83.2U/ml in the control group. In the comparison of the patient and control groups, significant differences were found between their IMA values (p=0.000). There was a significant difference between IMA values of the group having generalized tonic-clonic seizures and those of the control group (p=0.001). In comparison of the IMA values of the group having febrile convulsions and those of the control group, a significant difference was determined (p=0.011). It has been shown that if the seizure was prolonged over 5 min, IMA level increased, and there was a significant difference between the groups experiencing over 5 min of seizures and the groups experiencing less than 5 min of seizures (p=0.001). An increase in IMA levels in febrile convulsion supports the hypoxia development in the brain during the seizure. Serum IMA levels increased with the elongation of the seizure period and may be an indicator for status epilepticus.
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PMID:Ischemia-modified albumin levels in children having seizure. 2329 Dec 21

The 18 kDa translocator protein (TSPO) is able to modulate several mitochondria-related cell death processes due to close association with proteins and other molecules involved to the mitochondrial permeability transition pore. In this way, herein we review cell death mechanisms targeting mitochondria, including programmed cell death type I, II and III. Several proteins involved in these cell death processes and with a possible interplay with the TSPO are also discussed including the voltage dependent anion channel, the adenine nucleotide transporter, cardiolipin, and the Bcl-2 family proteins. Noteworthy, TSPO has been also implicated in various other functions including mitochondrial respiration, immune and phagocytic host-defense response, microglial activation, inflammation, cell growth and differentiation, cancer, cell proliferation, ischemia, and mental and neuropathological disorders. We focused in recent studies of the TSPO particularly on cancer and neurodegeneration, thus presenting the TSPO as a core element in the role of mitochondria in diseases and related processes. Clinical benefit may be attainable by increasing pharmacological knowledge related to the TSPO. Recent patents typically relate to diagnosis and treatment of TSPO-related pathological conditions including cancer, and inflammatory conditions, as well as disorders associated with central nervous system, such as neurodegeneration, convulsions, anxiety, mental disorders, and dementia.
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PMID:Role of mitochondrial translocator protein (18 kDa) on mitochondrial- related cell death processes. 2336 81

Diabetic uremic syndrome (DUS) is an increasingly reported acute neurometabolic cerebral disease with characteristic clinical and imaging features. Clinical spectrum includes a wide range of movement disorders such as acute parkinsonism. Imaging studies show reversible (with hemodialysis) bilateral lesions in the lenticular nuclei. DUS pathophysiology has not been entirely clarified yet. Our case study shows certainly that LN lesions are characterized with increased lactate peak with MR spectroscopy and decreased perfusion in computerized tomography perfusion along with increased diffusion with apparent diffusion coefficient (ADC) mapping in the subacute phase of the syndrome. Abnormalities were almost normalized quickly after metabolic control by hemodialysis. Together with reports indicating that a deficit of glucose use exacerbated with acute increase of uremic toxins in bilateral LN, observed changes (lactate peak and hypoperfusion) led us to state that a primary metabolic depression may cause this syndrome. Metabolic depression is probably due to uncompensated uremic toxin accumulation related mitochondrial supression and/or dysfunction. This definition fits well to the other elements of DUS such as ADC evolution and marked lesion regression. Our single case study is not supportive of other previously credited mechanisms such as microvascular dysfunction related focal ischemia or hypoperfusion, prolonged uremic toxin related histotoxic hypoxia, central pontine myelinolysis-like demyelination and posterior leukoencephalopathy spectrum disorder related vasogenic edema.
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PMID:Diabetic uremic syndrome studied with cerebral MR spectroscopy and CT perfusion. 2395 92


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