Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Muscle injury and its role in the development of Type II paralysis was studied in 25 patients with acute organophosphate poisoning. All patients were assessed for severity of poisoning at admission and through the course of poisoning for the development and duration of intermediate syndrome (IS) (Type II paralysis). Blood levels of acetylcholinesterase, creatine kinase, creatine kinase MM, LDH and LDH5 were estimated through the course of the poisoning. Of the 25 patients, 22 were severely poisoned and 3 had mild to moderate poisoning. Severely poisoned patients had a significantly greater rate of developing intermediate syndrome (17/22) (P = 0.026). Type I paralysis and fasciculations occurred in 76 and 70.5% of patients who developed intermediate syndrome, in comparison to 38 and 50%, respectively, of those who did not develop intermediate syndrome. Weakness developed in the same groups of muscles in both Types I and II paralysis but was of longer duration in patients who developed Type II paralysis. Acetylcholinesterase was inhibited > 90% throughout the course of poisoning with greater inhibition in patients with longer duration intermediate syndrome. Muscle injury was seen in all patients beginning at admission, peaking over the first 5 days and then declining over the next 5 days. Temporal profiles of blood muscle isoenzymes showed significantly greater muscle injury in those patients with greater severity of poisoning at admission, those who developed intermediate syndrome and in patients with longer duration intermediate syndrome. The findings of this study suggest that Types I and II paralysis in organophosphate poisoning are not separate syndromes but a clinical continuum determined by the severity of poisoning. The magnitude of organophosphate exposure and of muscle injury during the cholinergic crises appears to determine the occurrence and severity of intermediate syndrome.
...
PMID:Muscle injury in organophosphorous poisoning and its role in the development of intermediate syndrome. 1256 81

Sublethal in vivo 24 h exposure to (40% and 80% of 24 h LC(50)) active fractions of Punica granatum bark or Canna indica root or in combination with other plant-derived molluscicides significantly inhibited the activity of acetylcholinesterase, acid/alkaline phosphatase, Na(+)K(+)ATPase and lactic dehydrogenase in the nervous tissue of Lymnaea acuminata. The inhibition kinetics of these enzymes indicates that active fractions of both the plants caused a competitive inhibition of AChE, LDH, ALP, ACP and Na(+)K(+)ATPase.
...
PMID:Enzyme inhibition by the molluscicidal agent Punica granatum Linn. bark and Canna indica Linn. root. 1530 5

A clinical study on the use of porous gelatin particles(sterile gelatin embolization material, YM 670, Gelpart) in transcatheter arterial embolization (TAE) was performed in patients with hepatocellular carcinoma, and the efficacy (embolization,anti-tumor effect, recanalization and operationality) and safety (tolerability) were studied. An additive agent comprising porous gelatin particles and low osmolarity contrast media was administered peripherally through a catheter into the hepatic artery proper of 63 patients with hepatocellular carcinoma. Good hepatic arterial embolization was confirmed in all cases (embolization: 100%), and a tumor necrosis effect was obtained in most cases (35/62 patients, 56.5%). Moreover, operationality was assessed as "highly easy to use" or "easy to use" in all cases. Frequencies of adverse events in which a relationship to TAE was not excluded and abnormalities of clinical laboratory data were high at 71.4% and 9 8.4%, respectively. The most common adverse reactions were pyrexia, abdominal pain, queasiness and blood pressure increase;abnormalities in clinical laboratory data included hepatic function with increased AST (GOT), increased ALT (GPT), decreased cholinesterase, increased LDH and increased total bilirubin. These adverse reactions and abnormalities in clinical laboratory data, however, were transient and attributed to the TAE procedure itself, and no adverse reactions related to YM 670 as an embolic material were observed. In addition, with regard to tolerability (safety), the treatment was assessed as suitable for use in all the present cases.
...
PMID:[Clinical study of porous gelatin sphere (YM 670) in transcatheter arterial embolization]. 1622 43

Although the effects of acute pesticide poisoning are well known for the pesticides most currently used, hardly any data exist on health effects after long-term low-dose exposures. Major unresolved issues include the effect of moderate exposure in the absence of poisoning. The increased utilization of pesticides other than organophosphates makes it even more difficult to find associations. In this study a cohort of 106 intensive agriculture workers were assessed twice during the course of a spraying season for changes in serum biochemistry, namely enzymes reflecting cytotoxicity (AST, ALT, LDH, CK, and amino-oxidase) and other biochemical parameters, such as markers of nephrotoxicity (urea, creatinine) and lipid profile (cholesterol and triglycerides). Several criteria for estimating pesticide exposure were used, the most important one being serum cholinesterase depression greater than 25% from baseline to peak exposure. Our results revealed an association of pesticide exposure with changes in AST (increased activity), LDH, and amino-oxidase (decreased activity) as well as with changes in serum creatinine and phosphorus (lower and higher levels, respectively). These results provide support for a very slight impairment of the liver function, but overall these findings are consistent with no clinically significant hepatotoxicity. Intriguingly, paraoxonase-1 R allele was found to be an independent predictor of higher rates of AST and lower rates of amino-oxidase, so that it may play a supporting role as an individual marker of susceptibility on pesticide-induced health effects. In conclusion, different biomarkers might be used to detect early biochemical effects of pesticides before adverse clinical health effects occur.
...
PMID:Influence of exposure to pesticides on serum components and enzyme activities of cytotoxicity among intensive agriculture farmers. 1662 Aug 8

We report a 75-year-old man with the liver cirrhosis of Child-Pugh B who underwent nephrectomy. Preoperative serum examination revealed increases in GOT, GPT, LDH and total bilirubin, decreases in cholinesterase and albumin, and prolongation of prothrombin time. We selected spinal anesthesia using bupivacaine and fentanyl rather than epidural anesthesia in combination with isoflurane inhalation anesthesia to supplement intra-operative anesthesia and post-operative pain relief. We explained the risks of blood coagulopathy and the predictable venous dilatation in the epidural space to the patient and relatives on obtaining informed consent. The surgery was completed uneventfully in 2.5 hours. Post-operative pain control was satisfactory and hepatic dysfunction did not deteriorate in the postoperative period.
...
PMID:[Combination of spinal and inhalation anesthesia for nephrectomy in a cirrhotic patient]. 1724 50

The synthesis, molecular modeling, and pharmacological analysis of new multipotent simple, and readily available 2-aminopyridine-3,5-dicarbonitriles (3-20), and 2-chloropyridine-3,5-dicarbonitriles (21-28), prepared from 2-amino-6-chloropyridine-3,5-dicarbonitrile (1) and 2-amino-6-chloro-4-phenylpyridine-3,5-dicarbonitrile (2) is described. The biological evaluation showed that some of these molecules were modest inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), in the micromolar range. The 2-amino (3, 4), and 2-chloro derivatives 21-23, 25, 26 were AChE selective inhibitors, whereas 2-amino derivatives 5, 14 proved to be selective for BuChE. Only inhibitor 24 was equipotent for both cholinesterases. Kinetic studies on compound 23 showed that this compound is a mixed-type inhibitor of AChE showing a K(i) of 6.33 microM. No clear SAR can be obtained form these data, but apparently, compounds bearing small groups such as the N,N'-dimethylamino or the pyrrolidino, regardless of the presence of a 2-amino, or 6-chloro substituent in the pyridine ring, preferentially inhibit AChE. Molecular modeling on inhibitors 4, 5, 22, and 23 has been carried out to give a better insight into the binding mode on the catalytic active site (CAS), and peripheral anionic site (PAS) of AChE. The most important differences in the observed binding relay on the modifications of the group at C2, as the amino group forms two hydrogen bonds that direct the binding mode, while in the case of compounds with a chlorine atom, this is not possible. The neuroprotective profile of these molecules has been investigated. In the LDH test, only compounds 26, 3, 22, and 24 showed neuroprotection with values in the range 37.8-31.6% in SH-SY5Y neuroblastoma cells stressed with a mixture of oligomycin-A/rotenone, but in the MTT test only compound 17 (32.9%) showed a similar profile. Consequently, these compounds can be considered as attractive multipotent therapeutic molecules on two key pharmacological receptors playing key roles in the progress of Alzheimer, that is, cholinergic dysfunction and oxidative stress, and neuronal vascular diseases.
...
PMID:Multipotent drugs with cholinergic and neuroprotective properties for the treatment of Alzheimer and neuronal vascular diseases. I. Synthesis, biological assessment, and molecular modeling of simple and readily available 2-aminopyridine-, and 2-chloropyridine-3,5-dicarbonitriles. 2065 95

An in vitro model system has been developed to establish dose-response relationships of mercuric chloride (HgCl(2)) and methylmercuric chloride (HgCH(3)Cl). Mouse neuroblastoma cell cultures (Neuro-2a) were exposed for 24 hr and cytotoxic effects evaluated with eight different endpoints. Toxic indicators assessed in the in vitro test system were as follows: cell proliferation by quantification of total protein content; cytoplasmic membrane integrity by cytosolic lactate dehydrogenase leakage; lysosomal membrane stability by hexosaminidase release; lactate dehydrogenase activity; mitochondrial succinate dehydrogenase activity; relative neutral red uptake by lysosomes; lysosomal hexosaminidase sphingolipid degradation activity; acetylcholinesterase activity. The toxicity of the two chemical species of mercury on neuroblastoma cells differed. HgCl(2) inhibited LDH activity specifically and very potently. Gross disruption of cytoplasmic membrane was accompanied by stimulation of hexosaminidase. HgCH(3)Cl was 50 times more toxic than HgCl(2) to cell proliferation and also caused important alterations in both membrane stability and metabolic activities over a narrow range of doses. The data suggest that HgCl(2) acts mainly on cell membranes and LDH, whereas, although HgCH(3)Cl is more cytotoxic, it does not affect any of the above-mentioned endpoints as specifically.
...
PMID:In vitro effects of mercuric chloride and methylmercury chloride on neuroblastoma cells. 2073 14

Apoptosis of cholinergic neurons is one of the core hallmarks of Alzheimer's disease. SH-SY5Y neuroblastoma cells differentiated to the cholinergic phenotype were exposed to 100nM staurosporine. Over a treatment period of 24h, the pro- and anti-apoptotic factors, caspase-3 and Bcl-2, as well as LDH release as a measure of cell viability, were assessed in conjunction with the number of apoptotic cells by means of fluorescence-activated cell sorting. Caspase-3 activity and LDH release increased by 30% and 20% over controls, respectively, while Bcl-2 levels rose by 200% over controls. Furthermore, staurosporine treatment resulted in decreased acetylcholinesterase (AChE) enzymatic activity and decreased protein levels of the AChE splice variant tailed AChE (AChE-T). Only a slight increase in levels of readthrough AChE (AChE-R) was observed. Likewise, staurosporine reduced levels and activity of the cholinergic players choline acetyltransferase and high affinity choline uptake. The present study demonstrates that treatment with staurosporine leads to apoptotic events, which, however, are not reflected in the increased AChE activity and the alterations of AChE isoforms expression that are usually seen in apoptotic conditions. The effects of various additional phosphorylation inhibitors on AChE activity suggest that these unexpected cholinergic effects, firstly, are linked to the impact of staurosporine on phosphorylation and, secondly, reveal themselves in a first phase of cellular adaption that precedes neurotoxicity and subsequent cell death.
...
PMID:Staurosporine-induced apoptosis presents with unexpected cholinergic effects in a differentiated neuroblastoma cell line. 2284 91

The biochemical responses in muscle, such as the enzymatic activities of acetylcholinesterase, lactate dehydrogenase and isocitrate dehydrogenase, were studied in sole (Solea senegalensis) collected in Huelva estuary (SW Spain), in the vicinity of a petrochemical and mining industry. The sampling sites showed different type and degree of pollution. The results demonstrated significant differences in muscle activities of AChE and IDH in Odiel and Tinto Rivers compared to control fish. LDH activity did not show any difference between sampling sites. Significant correlations were established between some biomarkers and heavy metals: AChE was correlated with Pb, Cd and Cu concentrations in water; IDH activity was correlated with Cd and Cu concentrations in water and As, Pb and Cd concentrations in sediments; LDH activity was correlated with As and Zn concentration in water and Cd concentration in sediment. Only one correlation was established between the biomarkers analysed and the concentrations of PAHs: benzo(b)fluoranthene concentration in sediment and IDH.
...
PMID:Biomarkers responses in muscle of Senegal sole (Solea senegalensis) from a heavy metals and PAHs polluted estuary. 2285 14

The use of nanotechnology has led to rapid growth in various areas. Manganese oxide (MnO2) nanomaterials (NMs) are typically used for biomedical applications. However, characterizing the potential human health effects of MnO2 NMs is required before fully exploiting these materials. The aim of this study was to investigate the acute oral toxicity of MnO2 NMs and MnO2-bulk particles in female albino Wistar rats. The genotoxic effects were examined using comet, micronucleus and chromosomal aberration assays. Nanosized MnO2 (45nm) significantly (p<0.01) increased DNA damage in peripheral blood leukocytes and micronuclei and enhanced chromosomal aberrations in the bone marrow cells at 1000mg/kg bw. These findings showed that the neurotoxicity of MnO2-45nm in the brain and red blood cells, as determined through acetylcholinesterase activity, was significantly (p<0.01) inhibited at 1000 and 500mg/kg bw doses. MnO2-45nm disrupted the physicochemical state and neurological system of the animals through alterations in ATPases via the total Na(+)-K(+), Mg(2+) and Ca(2+) levels in the brain P2 fraction. In addition, 500 and 1000mg/kg bw doses of MnO2-45nm caused significant changes in AST, ALT and LDH levels in the liver, kidney and serum of treated rats. Significant tissue distribution was found in all tissues in a dose- and time-dependent manner. MnO2-45nm exhibited much higher absorptivity and tissue distribution compared with MnO2-bulk. A large fraction of MnO2-45nm was cleared in the urine and feces. The histopathological analysis revealed that MnO2-45nm caused alterations in the liver, spleen and brain. These findings will provide fundamental information regarding the potential toxicities and biodistribution of nano and bulk MnO2 generated through acute oral treatment.
...
PMID:Genotoxicity of nano- and micron-sized manganese oxide in rats after acute oral treatment. 2361 23


<< Previous 1 2 3 4 5 6 7 Next >>

---