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)

Myocardial injury from ischemia can be aggravated by reperfusion of the jeopardized area. The precise underlying mechanisms have not been clearly defined, but proinflammatory events including complement activation play important roles. Cardioprotection by complement inhibition inter alia C1-esterase-inhibitor (C1-INH) was examined in several experimental models and under clinical conditions with ischemia and reperfusion. C1-INH reduced local anaphylatoxin release revealing the importance of the classical complement pathway. Inhibition of local complement activation was accompanied by improvement of myocardial function and perfusion of the previously ischemic myocardium. Leukocyte endothelial cell-cell interaction was strikingly reduced in the reperfused tissues as afflection of anti-inflammatory effect.
 ...
PMID:C1-esterase inhibitor in ischemia and reperfusion. 1239 15

To determine the role of inhibition of complement activation in the contractile function of skeletal muscle ischemia-reperfusion (I/R) injury, the rat extensor digitorum longus (EDL) muscles underwent 3 h ischemia and received human C1-esterase inhibitor (C1-INH, 100 IU/kg), a synthetic C1q A chain peptide with a similar inhibitory effect on activated C1 (peptide, 5 mg/kg), or human serum albumin control. Results showed a significant overall increase in tetanic contractile forces of the reperfused EDL in both C1-INH and peptide groups compared to controls. Maximum improvement occurred with peptide treatment at 120-Hz stimulation, with an increase in force from 38 +/- 4% of normal in controls to 52 +/- 4% in peptide-treated rats. There were no significant differences between C1-INH and peptide groups. Plasma C3 and C4 activities were significantly increased in both treated groups, suggesting inhibition of complement activation. Our results suggest that complement activation is involved in I/R injury, and inhibition of complement activation may therefore represent a potential therapeutic approach to reducing or preventing I/R injury.
 ...
PMID:C1-esterase inhibitor and a novel peptide inhibitor improve contractile function in reperfused skeletal muscle. 1470 72

To analyze the retention process of technetium-99m ethyl cysteinate dimer (99mTc-ECD) in normal and ischemic lesions, we developed a super rapid dynamic SPECT system based on the CERASPECT (DSI, Inc., Waltham, MA, USA). The system made it possible to take a SPECT series every 2 seconds. Each SPECT series contains a maximum of 16 slices (6.6 mm slice interval) in a matrix size of 32 x 32. The sensitivity of this system is 175 kcps/MBq/ml/cm slice thickness, and resolution is 12 mm FWHM at the center of a 20 cm(phi) water phantom. Using the super rapid SPECT system, the kinetic behavior of the 99mTc-ECD during retention in normal and ischemic lesions was analyzed. Twenty patients with ischemic lesions that were clearly demonstrated by 133Xe-rCBF (regional cerebral blood flow) SPECT but unclear on static 99mTc-ECD SPECT were examined. For the dynamic SPECT, 700 MBq of 99mTc-ECD was injected intravenously, and dynamic SPECT data were acquired every 2 seconds during a 90-second period. The serial dynamic SPECT and time-activity curves at some lesions with reduced rCBF and at the contralateral normal brain were analyzed. These dynamic SPECT data were compared with conventional static 99mTc-ECD SPECT and quantitative 133Xe-rCBF SPECT. All of mildly or moderately reduced rCBF lesions on the 133Xe-rCBF SPECT were recognized as low activity regions only at the early phase (during about 2-20 sec or less), with the lesions then gradually vanishing. These lesions were not recognized on the conventional static SPECT taken after the dynamic study. The time-activity curve at the reduced rCBF lesion was lower than that of contralateral normal brain at the early phase, and overtook the activity in the normal region with a gradual increase. The early phase images of 99mTc-ECD SPECT within 20 seconds by the super rapid dynamic SPECT were very useful to the same extent as the 133Xe-rCBF SPECT for detecting mild or moderate ischemic lesions. This study suggests that esterase activity, participating in the ECD retention mechanism, may be tolerable to mild or moderate ischemia. This tolerance may be the main cause of the nonlinear relationship between ECD accumulation and cerebral blood flow.
 ...
PMID:Development of "super rapid dynamic SPECT," and analysis of retention process of 99mTc-ECD in ischemic lesions: comparative study with 133Xe SPECT. 1551 48

The rat with permanent occlusion of the bilateral common carotid arteries (2VO) is useful model for the study of dementia. The expression changes of amyloid precursor protein (APP), secretase, alpha7 nicotinic acetylcholine receptor (alpha7NicR) and acetylcholine esterase (AChE), which are involved in Alzheimer's disease, were examined by quantitative RT/PCR in this model rat brain. The expression of APP, alpha7NicR and secretase were increased 4 d after 2VO. The alpha7NicR level at 2 d after operation already tended to increase. These result suggest that alpha7NicR expression was enhanced at early stage of brain ischemia. Using this model to find drugs which regulate the alpha7NicR expression will be useful to assay the materials with anti-dementive effect.
 ...
PMID:Expression changes of the mRNA of Alzheimer's disease related factors in the permanent ischemic rat brain. 1557 24

Recent studies have shown that hyperbaric oxygen therapy (HBOT) reduces neutrophil endothelial adherence in venules and also blocks the progressive arteriolar vasoconstriction associated with ischemia-reperfusion (I-R) injury in the extremities and the brain. In order to elucidate the effects of HBOT after I-R in digestive organs, particularly in the liver, we evaluated the following: 1) the relationship between timing of HBOT and tissue damage; and 2) HBOT's effects on neutrophil sequestration. Using a hepatic I-R (45 minute) model in male rats, survival rate, liver tissue damage, and neutrophil accumulation within the sinusoids in the HBOT-treated group (Group H) were compared to those in the nontreated group (Group C). For the HBOT-treated group, HBOT was administered as 100% oxygen, at 2.5 atm absolute, for 60 minutes. When HBOT was given 30 minute after I-R, the survival rate was much better in Group H than in Group C. HBOT performed within 3 hours of I-R markedly suppressed increases in the malondialdehyde level in tissues of the liver and lessened the congestion in the sinusoids. In addition, HBOT just after I-R caused decreased number of cells stained by the naphthol AS-D chloroacetate esterase infiltrating into the sinusoids. HBOT 3 hours after reperfusion, however, showed no clear effects upon neutrophil sequestration compared to Group C. These results indicate that HBOT performed within 3 hours of I-R alleviates hepatic dysfunction and improves the survival rate after I-R. Herein, we propose 1 possible mechanism for these beneficial effects: early HBOT given before neutrophil-mediated injury phase may suppress the accumulation of neutrophils after I-R. In conclusion, we believe that the present study should lead to an improved understanding of HBOT's potential role in hepatic surgery.
 ...
PMID:Effects of hyperbaric oxygen exposure on experimental hepatic ischemia reperfusion injury: relationship between its timing and neutrophil sequestration. 1631 98

The nervous system is highly sensitive to various environmental stresses, such as ischemia. Stress response mechanisms that result in neuroprotection, including the induction of heat shock proteins (HSP), are not well understood. We examined the effect of KNK437, a compound that inhibits the synthesis of inducible heat shock proteins, on neuronal differentiation in rat pheochromocytoma PC12 cells. KNK437 decreased the expression of HSP70, and induced the neurite outgrowth of PC12 cells in the absence of stress stimulation, although with lower efficacy than nerve growth factor (NGF). Neurite outgrowth stimulated by KNK437 and NGF was blocked by inhibitors of ERK mitogen-activated protein (MAP) kinase, p38 MAP kinase, and glycogen synthase kinase 3beta signaling pathways. NGF, and not KNK437, induced acetylcholine esterase (AChE) activity, a functional differentiation marker, indicating that KNK437 utilizes a mechanism distinct from that of NGF. KNK437 enhanced the activity of low dose NGF treatment on neurite outgrowth induction and ERK phosphorylation in PC12 cells, a finding that identifies KNK437 as a possible nerve regeneration agent. This compound may be a useful tool for the investigation of neuronal differentiation and neuroprotection against environmental stress.
 ...
PMID:The heat shock protein inhibitor KNK437 induces neurite outgrowth in PC12 cells. 1705 58

Activated complement contributes significantly to reperfusion injury after ischemia. This study explores functional consequences of C1-esterase inhibitor (C1-INH) treatment after superior mesenteric artery occlusion (SMAO)/reperfusion using intravital microscopy. Thirty anesthetized, spontaneously breathing, male Sprague-Dawley rats underwent SMAO for 60 min followed by reperfusion (4 h). C1-esterase inhibitor (100 and 200 IU/kg body weight) or saline (0.9%) was given as a single bolus before reperfusion. Sham-operated animals (n = 10) without SMAO served as controls. Systemic hemodynamics were monitored continuously, arterial blood gases analyzed intermittently, and leukocyte/endothelial interactions in the mesenteric microcirculation quantified at intervals using intravital microscopy. Ileal lipid-binding protein (I-LBP) levels were determined from serum samples with an enzyme-linked immunosorbent assay at the end of the experiments. C1-esterase inhibitor restored microcirculatory perfusion to baseline levels in a dose-dependent manner and reduced adherent leukocytes after SMAO/reperfusion to similar levels in both C1-INH-treated groups during reperfusion. Furthermore, C1-INH treatment efficiently prevented metabolic acidosis, reduced the need for intravenous fluids to support blood pressure, and decreased I-LBP levels in a dose-dependent manner. Survival rates were 100% in controls and after 200 IU/kg C1-INH, 90% after 100 IU/kg C1-INH, and 30% in saline-treated animals. C1-esterase inhibitor bolus infusion efficiently blunted functional consequences of mesenteric ischemia/reperfusion with I-LBP, proving to be a valuable serum marker mirroring the effect of ischemia/reperfusion and treatment at the end of the experiments.
 ...
PMID:C1-esterase inhibitor reverses functional consequences of superior mesenteric artery ischemia/reperfusion by limiting reperfusion injury and restoring microcirculatory perfusion. 1717 84

Complement activation has been implicated in disease states such as hereditary angioedema, ischemia-reperfusion injury, acute respiratory distress syndrome, and acute transplant rejection. Even though the complement cascade provides several protein targets for potential therapeutic intervention only two complement inhibitors have been approved so far for clinical use including anti-C5 antibodies for the treatment of paroxysmal nocturnal hemoglobinuria and purified C1-esterase inhibitor replacement therapy for the control of hereditary angioedema flares. In the present study, optimization of potency and physicochemical properties of a series of thiophene amidine-based C1s inhibitors with potential utility as intravenous agents for the inhibition of the classical pathway of complement is described.
 ...
PMID:Biphenylsulfonyl-thiophene-carboxamidine inhibitors of the complement component C1s. 1824 91

Activation of the complement cascade represents an important event during ischemia/reperfusion injury (IRI). This work was designed to investigate the role of the membrane attack complex (MAC; C5b-9) in the pathogenesis of hepatic IRI. Livers from B&W/Stahl/rC6(+) and C6(-) rats were harvested, stored for 24 hours at 4 degrees C, and then transplanted [orthotopic liver transplantation (OLT)] to syngeneic recipients. There were 4 experimental groups: (1) C6(+)-->C6(+), (2) C6(+)-->C6(-), (3) C6(-)-->C6(+), and (4) C6(-)-->C6(-). At day +1, C6(-) OLTs showed decreased vascular congestion/necrosis, contrasting with extensive necrosis in C6(+) livers, that was independent of the recipient C6 status (Suzuki score: 7.2 +/- 0.9, 7.3 +/- 1.3, 4.5 +/- 0.6, and 4.8 +/- 0.4 for groups 1-4, respectively, P < 0.05). The liver function improved in recipients of C6(-) grafts (serum glutamic oxaloacetic transaminase: 2573 +/- 488, 1808 +/- 302, 1170 +/- 111, and 1188 +/- 184 in groups 1-4, respectively, P < 0.05). Intragraft macrophage infiltration (ED-1 immunostaining) and neutrophil infiltration (myeloperoxidase activity) were reduced in C6(-) grafts versus C6(+) grafts (P = 0.001); these data were confirmed by esterase staining (naphthol). The expression of proinflammatory interferon-gamma, interleukin-1beta, and tumor necrosis factor messenger RNA/protein was also reduced in C6(-) OLTs in comparison with C6(+) OLTs. Western blot-assisted expression of proapoptotic caspase-3 was decreased in C6(-) OLTs versus C6(+) OLTs (P = 0.006), whereas antiapoptotic Bcl-2/Bag-1 was enhanced in C6(-) OLTs compared with C6(+) OLTs (P = 0.001). Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining of apoptotic cells was enhanced (P < 0.05) in C6(+) OLTs compared with C6(-) OLTs. Thus, the terminal products of the complement system are essential in the mechanism of hepatic IRI. This is the first report using a clinically relevant liver cold ischemia model to show that local MAC inhibition attenuates IRI cascade in OLT recipients.
 ...
PMID:The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury. 1866 46

It will be vital to the practical activity of every forensic and/or clinical pathologist to be able to answer three questions regarding the reconstruction of a lethal event: the type and cause of death, as well as the survival time. The authors offer an overview of the application of selected morphological techniques in general forensic neuropathology, techniques that provide answers to some of the main questions in forensic neurotraumatology. The methods are illustrated by individual cases of lethal gunshot injury to the head from low velocity handguns. Besides the general forensic tasks of interpretation of the crime scene and postmortem external examination of the victim's body a computed tomography is recommended for documentation and reconstruction of the missile track. The microscopic techniques involve Nissl-stain for neurons, hematoxylin and eosin for delayed ischemic neuronal alterations, microtubule-associated protein (MAP) expression for acute neuronal ischemia, luxol-fast-blue-stain for myelin destruction (and demyelination), silver-stain for axons, beta-amyloid precursor protein (beta-APP) for axonal injury, glial fibrillary acidic protein (GFAP) for astrocytic characterization, naphthol AS-D-chloroacetate esterase for neutrophilic infiltration and CD68-expression for microglial reaction. The pattern of methods lead--in the case of gunshot injury as well as in any traumatic impact to the head--to answers according the extent of tissue destruction (and the cause of death), the biometric reconstruction of the criminal event, and the timing of (gunshot) wounds of the brain. These methods will be indispensable for the preparation of future neuropathological expert reports addressing questions of type of injury, the consequent pathological symptoms, timing of the injury, and the cause of death.
 ...
PMID:Routine techniques in forensic neuropathology as demonstrated by gunshot injury to the head. 1927 84


<< Previous 1 2 3 4 5 Next >>