OBJECTIVEInhibition of acetylcholinesterase (AChE) in human brain caused by phoxim or phoxim oxon, their reactivation with oxime and aging of phosphorylated AChE were studied and compared in vitro.

METHODSMicro-colorispectrophotometric assay was used to determine the activity of AChE.

RESULTSThe pI(50) of inhibition of AChE in human brain by phoxim and phoxim oxon were 5.39 and 5.77, respectively, whereas the pI(90) were 4.60 and 5.00, respectively. The reactivation rate of 0.1 mmol/L of pralidoxime (2-PAM), obidoxime (LüH(6)), trimedoxime (TMB-4) and pyramidoxime (HI-6) for phoxim-inhibited AChE in human brain was 65%, 97%, 91% and 56%, respectively, and their reactivation rate for phoxim oxon-inhibited AChE in human brain was 97%, 87%, 99% and 89%, respectively. The optimal reactivator for phoxim and phoxim oxon-inhibited AChEs was LüH(6) and TMB-4, respectively. The half aging time of phoxim and phoxim oxon inhibited phosphorylated AChEs were 39 and 28 hours, respectively, and the 99% aging time were 256 and 186 hours, respectively.

CONCLUSIONSLüH(6) or TMB-4 should be used at the earlier as possible after poisoning with phoxim and phoxim oxon, and the reactivator should be consecutively used for more than seven days, even after their acute symptoms have been well controlled.

Acetylcholinesterase ; metabolism ; Brain ; drug effects ; enzymology ; Cholinesterase Inhibitors ; pharmacology ; Cholinesterase Reactivators ; pharmacology ; Enzyme Stability ; Humans ; In Vitro Techniques ; Obidoxime Chloride ; pharmacology ; Organothiophosphorus Compounds ; pharmacology ; Oximes ; pharmacology ; Paraoxon ; pharmacology ; Pralidoxime Compounds ; pharmacology ; Time Factors ; Trimedoxime ; pharmacology

PURPOSE: The optimal dose of oximes for use in the treatment of organophosphorus pesticide poisoning has not been conclusively established. In this retrospective study, we assessed the effectiveness of the use of high-dose pralidoxime infusion in treating organophosphorus pesticide poisoning. METHODS: From January 1998 to December 2009, 71 patients visited the hospital Emergency Department (ED) as a result of organophosphate pesticide intoxication. All of these patients received an initial bolus of 2 g of pralidoxime as the first step of treatment. Patients who then received continuous infusion of pralidoxime at a dose of 500 mg/hr were entered into study group 1 (low dose), and those treated by continuous infusion of pralidoxime at a dose of 1000 mg/hr were entered into study group 2 (high-dose). Plasma cholinesterase activities for each patient were evaluated at ED arrival and re-evaluated 24 hours after pralidoxime infusion. The effectiveness of the two treatment modalities was gauged by comparing the required duration of mechanical ventilation, time spent in the intensive care unit (ICU) and total time spent in the hospital. RESULTS: The mean duration of mechanical ventilation was 9.98+/-6.47 days for group 1 and 4.39+/-6.44 days for group 2. The respective mean duration of time spent in ICU and the total number of days in the hospital were 16.38+/-18.84 days and 21.87+/-20.16 days for group 1, and 7.83+/-9.99 days and 11.71+/-13.53 days for group 2. High-dose pralidoxime treatment was associated with shorter required durations for mechanical ventilation, ICU and hospital stay. In addition, plasma cholinesterase reactivation rates were higher for those patients receiving high-dose pralidoxime treatment. CONCLUSION: The results suggest that high-dose pralidoxime treatment has greater efficacy for patients suffering from organophosphorus pesticide poisoning.
Cholinesterases ; Emergencies ; Humans ; Intensive Care Units ; Length of Stay ; Organophosphates ; Oximes ; Plasma ; Pralidoxime Compounds ; Resin Cements ; Respiration, Artificial ; Retrospective Studies ; Stress, Psychological

In a continuation of our studies to discover bioactive secondary metabolites from marine sources, we further investigated samples from a tryptamine and phenyl-alkane producing sponge, which resulted in the isolation of four uncommon small molecules and five nucleosides. Their structures were determined to be 7,8-dihydroimidazo[1,5-c]pyrimidin-5(6H)-one (1), 5-chlorocavernicolin (2), maleimide-5-oxime (3), 3-methylmaleimide-5-oxime (4), uridine (5), 2'-deoxyuridine (6), thymidine (7), adenine (8), and adenosine (9) by spectroscopic analyses. The isolated compounds were evaluated for inhibitory activity against soluble epoxide hydrolase (sEH) as well as the Wnt/beta-catenine signaling pathway.
Adenine ; Adenosine ; Nucleosides* ; Oximes* ; Porifera* ; Thymidine ; Uridine

Infant, Newborn ; Humans ; Imidazoles/therapeutic use* ; Oximes/therapeutic use*

The six patients included in this study had painful dysesthesia, resulting from vascular lesions in or near the thalamus, confirmed by computerized tomography(CT) brain scan. Using hexamethyl propyleneamine oxime(HM-PAO) single photon emission computed tomography(SPECT) brain scanning, regional cerebral perfusion(rCP) was demonstrated. In contrast to three patients with lesions near the thalamus who showed symmetrical cortical radioactivity, the other three patients with thalamic lesions revealed decreased rCP in the ipsilateral cerebral cortex on HM-PAO brain SPECT. We thought that the loss of afferent activating stimuli from the thalamus led to decreased cortical neuronal activity and the following hypoperfusion. In patients with thalamic syndrome resulting from thalamic lesions, the role of the remote effect of the thalamic damage and consequent cortical deregulation in the development of thalamic pain and/or neuropsychological symptoms cannot be excluded completely.
Brain/*radionuclide imaging ; Female ; Human ; Male ; Middle Age ; Organotechnetium Compounds ; Oximes ; Pain/etiology ; Syndrome ; Technetium/diagnostic use ; Technetium Tc 99m Exametazime ; Thalamic Diseases/*radionuclide imaging ; Tomography, Emission-Computed, Single-Photon

We used single photon emission computed tomography (SPECT) with technetium-99m hexamethylpropylene amine oxime (99mTc-HM-PAO) in 14 studies on 6 patients with delayed neurologic sequelae from carbon monoxide (CO) poisoning to determine whether any changes in cerebral blood flow could be correlated with clinical or computed tomographic evidence of delayed deficits. Among the six initial CT brain scans, two showed low density of both basal ganglia and two showed decreased density of the cerebral white matter. There was no correlation between the clinical outcome and the findings of the follow-up CT brain scans. Of the two SPECTS with 99mTc-HM-PAO performed during acute anoxic insult, one showed focal hypoperfusion which appeared 20 days prior to the onset of delayed neurologic sequelae after CO poisoning. Seven SPECTs in the six patients performing the delayed phase showed diffuse patched patterns of hypoperfusion which improved on follow-up images. There was good correlation between the clinical outcome and the findings of the 99mTc-HM-PAO SPECT. In preliminary conclusion, 9Tc-HM-PAO brain SPECT can be used for predicting or evaluating the outcome of delayed neurologic sequelae after CO poisoning. Cerebral vascular changes may be the possible cause of hypoperfusion in patients with CO poisoning.
Adult ; Aged ; Brain Diseases/etiology/*radionuclide imaging ; Carbon Monoxide Poisoning/*complications ; Female ; Humans ; Middle Aged ; Organotechnetium Compounds/*diagnostic use ; Oximes/*diagnostic use ; Predictive Value of Tests ; Technetium Tc 99m Exametazime ; Time Factors ; *Tomography, Emission-Computed, Single-Photon

Organophosphate (OP) pesticides are the most common source of human toxicity globally, causing high mortality and morbidity despite the availability of atropine as a specific antidote and oximes to reactivate acetylcholinesterase. The primary toxicity mechanism is inhibition of acetylcholinesterase (AchE), resulting in accumulation of the neurotransmitter, acetylcholine, and abnormal stimulation of acetylcholine receptors. Thus, the symptoms (muscarinic, nicotinic, and central nervous system) result from cholinergic overactivity because of AchE inhibition. OP can also cause rhabdomyolysis, pancreatitis, parotitis, and hepatitis. OP therapy includes decontamination, supportive therapy, and the use of specific antidotes such as atropine and oximes. However, there has been a paucity of controlled trials in humans. Here we evaluated the literature for advances in therapeutic strategies for acute OP poisoning over the last 10 years.
Acetylcholine ; Acetylcholinesterase ; Antidotes ; Atropine ; Decontamination ; Hepatitis ; Humans ; Neurotransmitter Agents ; Oximes ; Pancreatitis ; Parotitis ; Pesticides ; Receptors, Cholinergic ; Rhabdomyolysis

BACKGROUND: Spectacle contact allergy is not infrequent. The fine scratches on the spectacle frames which may play a role in the sensitization to the potential allergenic components have not been studied. OBJECTIVE: We sought the relationship between the scratches on the spectacle frames and the allergic contact dermatitis (ACD) in the Republic of Korea. METHODS: A total of 42 Korean patients with ACD at the spectacle contact sites were enrolled. Their spectacle frames were examined with the dimethylglyoxime (DMG) test and analyzed by the scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). Patch tests (thin-layer rapid use epicutaneous test [TRUE tests]) were performed to identify the skin allergens. RESULTS: The DMG-positive spectacle frames were identified in 78.5% of the frames. The SEM results showed that there were more scratches on the skin-contacting parts of the spectacle frames than the non-skin-contacting parts of the same frames. In the EDS findings, the mean nickel content (weight, %) of the spectacle frames was 15.7+/-5.5, and the mean chromium content was 20.3+/-3.4 at the skin-contacting parts. In the TRUE tests, nickel sulphate was the most common allergen (31 cases, 73.8%), and potassium dichromate was the second (9 cases, 21.4%). Three patients presented simultaneous positive reactions with nickel sulphate and potassium dichromate. CONCLUSION: Minor visible and non-visible fine scratches on the spectacle frames may present the provocation factors of the ACD. Nickel sulphate was the most common allergen suspected of provoking the spectacle frame-induced ACD, followed by potassium dichromate.
Chromium ; Dermatitis, Allergic Contact ; Humans ; Hypersensitivity ; Microscopy, Electron, Scanning ; Nickel ; Oximes ; Patch Tests ; Potassium ; Potassium Dichromate ; Skin ; Spectrum Analysis

AIMTo study the synthetic method and antibacterial activity of amino-heterocyclic compounds coupled oxime-ether group.

METHODSThe treatment of 4-amino-3-methyl-5-mercapto-s-triazole (3) with beta-chlorophenyl-propanone to form amino-s-triazole sulfanylphenyl-propanone (4) sequentially followed by oximation with hydroxyl-amine to produce the oximes (5) and etherification with various oxadiazole chloromethanes (6a - j) to yield the title compounds (1a - j). The in vitro antibacterial activities of all newly synthesized compounds were tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method.

RESULTSTwelve new compounds including two intermediates were synthesized and their structures were confirmed by IR, 1H NMR, MS and elemental analyses. The ten title compounds exhibited the potential antibacterial activities in vitro.

CONCLUSIONTheses compounds should be optimized.

Anti-Bacterial Agents ; chemical synthesis ; pharmacology ; Oxadiazoles ; chemical synthesis ; pharmacology ; Oximes ; chemical synthesis ; pharmacology ; Triazoles ; chemical synthesis ; pharmacology

Although methidathion is an organophosphate insecticide, it is different from the other organophosphates in terms of toxicity. Because of its relatively high fat solubility, the apparent volume of methidathion distribution throughout the body is very high, indicating that hemoperfusion is not effective in removing this organophosphate from the body. Redistribution of methidathion from fat to blood can also occur when plasma levels diminish. Additionally, acetylcholinesterase aging, which is the loss of an alkyl side chain that prevents reactivation by oximes, is very rapid so that the effective reactivation by oximes is thwarted. Thus, methidathion's effect on acetylcholinesterase inhibition is long lasting, particularly with a high dose. In addition to its parasympatholytic effect and ability to induce muscle paralysis, methidathion poisoning is associated with a profound and long-lasting circulatory collapse due to sympathetic ganglion blockade. This report presents the case of a 55-year-old man who accidentally ingested a high dose of methidathion. He later developed enteroinvasive aspergillosis infection-induced multiple bowel perforations on two separate occasions while on mechanical ventilator support, resulting in a fatal outcome. The renin-angiotensin axis activated by sympathetic ganglion blockade may have reduced the patient's splanchnic blood flow, contributing to translocation of endotoxin. Also, the effect of excessive acetylcholine on non-neuronal acetylcholine receptors may have contributed to the development of fatal enteroinvasive aspergillosis in this patient.
Acetylcholine ; Acetylcholinesterase ; Aging ; Aspergillosis ; Fatal Outcome ; Ganglia ; Ganglia, Sympathetic ; Hemoperfusion ; Humans ; Middle Aged ; Organophosphate Poisoning ; Organophosphates ; Oximes ; Paralysis ; Parasympatholytics ; Plasma ; Poisoning* ; Receptors, Cholinergic ; Shock ; Solubility ; Ventilators, Mechanical