Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major role of reactive oxygen species (ROS) in the pathomechanism of ischemia have been widely recognized. Still, measurements of the precise time course and regional distribution of ischemia-induced ROS level changes in acute brain slices have been missing. By using acute hippocampal slices and the fluorescent dye CM-H2DCFDA, we showed that reoxygenation after in vitro ischemia (oxygen-glucose deprivation; OGD) increased ROS levels in the hippocampal CA1 layers vulnerable to ischemia but did not have significant effects in the resistant stratum granulosum in the dentate gyrus (DG). Production of ROS started during OGD, but, contrary to reoxygenation, it manifested as a ROS level increase exclusively in the presence of catalase and glutathione peroxidase inhibition. The mechanism of ROS production involves the activation of NMDA receptors and nitric oxide synthases. The inhibition of ROS response by either AP-5 or L-NAME together with the ROS sensitivity profile of the dye suggest that peroxynitrite, the reaction product of superoxide and nitric oxide, plays a role in the response. Direct visualization of layer-specific effects of ROS production and its scavenging, shown for the first time in acute hippocampal slices, suggests that distinct ROS homeostasis may underlie the different ischemic vulnerability of CA1 and DG.
 ...
PMID:Layer-specific differences in reactive oxygen species levels after oxygen-glucose deprivation in acute hippocampal slices. 1820 24

Analysis of changes after ischemia-reperfusion (IR) attack to the small intestine leads to multiple organ dysfunction (multiple organ dysfunction syndrome, MODS) and the subsequent death of patients is a topic for discussion. IR stress affects the endoplasmic reticulum (ER). ER dysfunction induces responses through kinases activation that stimulate anti-apoptotic mechanism, for example Grp78 (Bip) (Yeung et al., 2008) and pro-apoptotic mechanism, for example, activation Gadd153 (Chop) (Allyson et al., 2007). We analyzed the impact of IR damage of epithelium of the small intestine of rats after 1 h ischemia and subsequent 1 h, 24 h and 30 days of reperfusion on the level of apoptotic genes expression (Gadd153) and (Bip). In this study we used RT-PCR for detection of changes in gene expression. Significantly increased levels of mRNA for Gadd153 gene were detected after 1 h ischemia and 1 h reperfusion. The mRNA level of Grp78 gene was increased 24 h after ischemia comparing with the control groups. After 30 days of reperfusion Grp78 was at the level of control groups. Still, it is necessary to analyze the changes in the damaged tissue at the molecular level to define possible pathways leading to the tissue protection.
 ...
PMID:Analysis of changes in pro (Gadd153) and anti apoptotic (Grp78) gene expression after ischemic-reperfusion injury of the small intestine. 2118 63

Peri-implant tissue reactions in failed total ankle replacement (TAR) are characterized by early developing peri-implant osteolysis. The hypothesis of the study was that this reaction is mediated by receptor activator of nuclear factor kappa B ligand (RANKL). Samples of peri-prosthetic tissues from failed TAR implants were stained for macrophages, RANKL, its receptor RANK and osteoprotegerin (OPG), and compared to control samples. The failed TAR implants were surrounded by implant capsule, synovial lining-like interface membrane or necrotic tissues. Infiltrating scavenger receptor I positive CD163(+) macrophages were frequent, in particular around necrotic soft tissues or bone sequestrate, and possibly in part formed due to ischemia and mechanical factors. In contrast, implant-derived wear debris was scanty. Still many RANK(+) macrophages were often seen in close contact with RANKL(+) mesenchymal cells, whereas OPG was mostly located at a distance in vascular endothelial cells. Foreign body giant cells were frequent. RANKL seems to stimulate locally accumulated CD163(+) RANK-expressing cells to fusion, which leads to the local formation of multinuclear foreign body giant cells (and probably of osteoclasts). Therefore, peri-implant osteolysis in early TAR implant failure seems to be caused by the RANKL-driven chronic foreign body inflammation directed against, not implant-derived particles, but against necrotic autologous tissues.
 ...
PMID:RANKL in the osteolysis of AES total ankle replacement implants. 2262 31

Perinatal hypoxia-ischemia is a major cause of acute mortality in newborns and cognitive and motor impairments in children. Cerebral hypoxia-ischemia leads to excitotoxicity and necrotic and apoptotic cell death, in which mitochondria play a major role. Increased resistance against major damage can be achieved by preconditioning triggered by subtle insults. CO, a toxic molecule that is also generated endogenously, may have a role in preconditioning as low doses can protect against inflammation and apoptosis. In this study, the role of CO-induced preconditioning on neurons was addressed in vitro and in vivo. The effect of 1 h of CO treatment on neuronal death (plasmatic membrane permeabilization and chromatin condensation) and bcl-2 expression was studied in cerebellar granule cells undergoing to glutamate-induced apoptosis. CO's role was studied in vivo in the Rice-Vannucci model of neonatal hypoxia-ischemia (common carotid artery ligature +75 min at 8% oxygen). Apoptotic cells, assessed by Nissl staining were counted with a stereological approach and cleaved caspase 3-positive profiles in the hippocampus were assessed. Apoptotic hallmarks were analyzed in hippocampal extracts by Western Blot. CO inhibited excitotoxicity-induced cell death and increased Bcl-2 mRNA in primary cultures of neurons. In vivo, CO prevented hypoxia-ischemia induced apoptosis in the hippocampus, limited cytochrome c released from mitochondria and reduced activation of caspase-3. Still, Bcl-2 protein levels were higher in hippocampus of CO pre-treated rat pups. Our results show that CO preconditioning elicits a molecular cascade that limits neuronal apoptosis. This could represent an innovative therapeutic strategy for high-risk cerebral hypoxia-ischemia patients, in particular neonates.
 ...
PMID:Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia. 2295 2

Fractures of the proximal humerus commonly affect elderly patients. The vast majority of proximal humeral fractures result from low-energy trauma in presence of osteoporosis. Incidence of proximal humeral fractures dramatically increased over the last decades. Recent epidemiological studies expect a rather stagnant incidence. Diversity of fracture types attenuates reliability of available classification systems. Even though, predictive morphologic criteria have been detected enabling a prognostic assessment. A short or absent metaphyseal head extension and disruption of the medial periosteal hinge reliably predict ischemia of the humeral head fragment. Still, humeral head necrosis may be prevented in early reduction and fixation. The range of treatment options consists of non-operative therapy, minimal-invasive osteosynthesis, open reduction and plate fixation, intramedullary nailing and primary arthroplasty. Most proximal humeral fractures in the elderly are stable injuries and can be successfully treated by non-operative means. Operative treatment of displaced, unstable fractures should resort to the least invasive procedure providing adequate reduction and fixation stability. To date, open reduction and locking plate osteosynthesis represents the standard operative procedure in displaced three- and four-part fractures. However, a number of risk factors may promote fixation failure or impair functional outcome, most important low local bone mineral density, residual varus displacement of the humeral head, insufficient restoration of medial calcar support, humeral head ischemia and insufficient fracture reduction. Innovation of fixation techniques (e. g. angular stable locking systems and bone augmentation) will further expand indications for operative fracture treatment. Outcome of hemiarthroplasty is closely related to anatomical tuberosity healing and restoration of rotator cuff function. Reverse shoulder arthroplasty may provide satisfactory shoulder function in geriatric patients, rotator cuff dysfunction or failure of first-line treatment. Choice of treatment should be individualized and base on careful evaluation of patient-specific, fracture-specific and surgeon-specific aspects.
 ...
PMID:Treatment of proximal humeral fractures - a review of current concepts enlightened by basic principles. 2298 Sep 28

Mitochondrial dynamics is a recent topic of research in the field of cardiac physiology. The study of mechanisms involved in the morphological changes and in the mobility of mitochondria is legitimate since the adult cardiomyocytes possess numerous mitochondria which occupy at least 30% of cell volume. However, architectural constraints exist in the cardiomyocyte that limit mitochondrial movements and communication between adjacent mitochondria. Still, the proteins involved in mitochondrial fusion and fission are highly expressed in these cells and could be involved in different processes important for the cardiac function. For example, they are required for mitochondrial biogenesis to synthesize new mitochondria and for the quality-control of the organelles. They are also involved in inner membrane organization and may play a role in apoptosis. More generally, change in mitochondrial morphology can have consequences in the functioning of the respiratory chain, in the regulation of the mitochondrial permeability transition pore (MPTP), and in the interactions with other organelles. Furthermore, the proteins involved in fusion and fission of mitochondria are altered in cardiac pathologies such as ischemia/reperfusion or heart failure (HF), and appear to be valuable targets for pharmacological therapies. Thus, mitochondrial dynamics deserves particular attention in cardiac research. The present review draws up a report of our knowledge on these phenomena.
 ...
PMID:Mitochondrial dynamics in the adult cardiomyocytes: which roles for a highly specialized cell? 2367 54

The incidence of arterial ischemic stroke (AIS) in childhood (about 2-13 per 100,000 children a year) is much lower than the incidence in the adult population. Still, adverse outcomes of acute brain ischemia in childhood include death (10% of AIS children), neurological sequel, epileptic seizures (over 50%) and recurrence (over 20%). The knowledge of childhood stroke etiopathogenesis is still insufficient and the diagnostic and therapeutic procedures--controversial. Risk factors for childhood stroke differ from those observed in adults due to differing exposure to external risk factors. The most frequently reported risk factors for pediatric ischemic stroke are cerebral arteriopathies and vascular malformations, cardiac diseases, infections, traumas and metabolic diseases. Because of its multifactorial etiology pediatric AIS probably has a multigenic inheritance pattern. The genetic susceptibility to AIS may be determined by specific polymorphic variants encoding markers of hemostasis regulation and they are some of the most important targets in searching for genetic determinants in pediatric AIS. The authors have reviewed the recent literature on risk factors of childhood ischemic stroke with the focus on genetic factors like polymorphisms of genes encoding coagulation factors II, V, VII and XIII, MTHFR, fibrinogen beta, and compared them with the results performed in adult patients.
 ...
PMID:The role of genetic risk factors in arterial ischemic stroke in pediatric and adult patients: a critical review. 2458 18

Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling and crosstalk with other signaling networks. The extensively studied MAPKs ERK1/2, p38, JNK, and ERK5, demonstrate unique intracellular signaling mechanisms, responding to a myriad of mitogens and stressors and influencing the signaling of cardiac development, metabolism, performance, and pathogenesis. Definitive relationships between MAPK signaling and cardiac dysfunction remain elusive, despite 30 years of extensive clinical studies and basic research of various animal/cell models, severities of stress, and types of stimuli. Still, several studies have proven the importance of MAPK crosstalk with mitochondria, powerhouses of the cell that provide over 80% of ATP for normal cardiomyocyte function and play a crucial role in cell death. Although many questions remain unanswered, there exists enough evidence to consider the possibility of targeting MAPK-mitochondria interactions in the prevention and treatment of heart disease. The goal of this review is to integrate previous studies into a discussion of MAPKs and MAPK-mitochondria signaling in cardiac diseases, such as myocardial infarction (ischemia), hypertrophy and heart failure. A comprehensive understanding of relevant molecular mechanisms, as well as challenges for studies in this area, will facilitate the development of new pharmacological agents and genetic manipulations for therapy of cardiovascular diseases.
 ...
PMID:Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: therapeutic perspectives. 2492

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties.
 ...
PMID:[The role of mesenchymal stromal cells in solid organ transplantation]. 2527 70

Chronic mesenteric ischemia (CMI) results from insufficient oxygen delivery or utilization to meet metabolic demand. Two main mechanisms may lead to mesenteric ischemia: occlusion in the arteries or veins of the gastrointestinal tract, or reduced blood flow from shock states or increased intra-abdominal pressure, so-called non-occlusive mesenteric ischemia. Severe stenoses in the three main mesenteric vessels as demonstrated with CT-angiography or MR-angiography are sufficient to proof mesenteric ischemia, for example in patients who present with weight loss, postprandial pain and diarrhea. Still in many clinical situations mesenteric ischemia is only one of many possible explanations. Especially in patients with a single vessel stenosis in the celiac artery or superior mesenteric artery with postprandial pain, mesenteric ischemia remains a diagnosis of probability or assumption without functional proof of actual ischemia. This review is aimed to provide an overview of all past, present and future ways to functionally proof CMI.
 ...
PMID:Functional testing in the diagnosis of chronic mesenteric ischemia. 2839 89


<< Previous 1 2 3 4 Next >>