Oxime Treatment Research Articles

Organofosfat Zehirlenmesi Olan Kritik Hastalarda Plazmaferez ve Standart Tedavinin Serum Psödokolinesteraz ve Eritrosit Asetilkolinesteraz Düzeyleri Üzerindeki Etkisinin Standart Tedavi ile Karşılaştırılması: Randomize Kontrollü, Açık Etiketli, Klinik Çalışma

Objective: Organophosphates are the insecticides commonly used worldwide. Inadequate treatment in organophosphates poisoning increases morbidity, and mortality. Purpose of the work was to determine the effect of standard treatment alone versus standard treatment plus plasmapheresis on the levels of serum pseudo-cholinesterase, and erythrocyte acetyl cholinesterase in severe patients with organophosphates poisoning. Material and Method: This research is a prospective study. Patients diagnosed with organophosphates poisoning were included in the work. The patients were divided into two groups as the intervention group, and the standard group. The intervention group, plasmapheresis was performed in addition to the standard treatment. Results: The research was conducted with forty cases. (Intervention group n:21, standard group n:19). Serum pseudo-cholinesterase values were 482.5 u/L at baseline, 3723 u/L after plasmapheresis. Erythrocyte acetyl cholinesterase values were 1.91 u/mL on admission, 2.53 u/mL after plasmapheresis. Erythrocyte acetyl cholinesterase and serum pseudo-cholinesterase values were compared between the two groups daily from the admission of patients to intensive care units during the first 5 days, and on the last day in the intensive care units. There was no statistical difference between two groups (p> 0.05), except for the second day. It was observed that there was a statistically significant difference between the pseudo-cholinesterase values in the second day comparison of both groups (p=0.028). Conclusion: In conclusion, plasmapheresis treatment may contribute positively to pseudo-cholinesterase level. This treatment may have provided additional time for the organophosphates to be eliminated from the body. Although acetyl cholinesterase reactivation is achieved with oxime treatment, the clinical effect of this treatment is not clear.

Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells.

Chemical proteomics is a powerful technology that can be used in the studies of the functions of uncharacterized proteins in the human proteome. It relies on a suitable bioconjugation strategy for protein labeling. This could be either a UV-responsive photo-crosslinker or an electrophilic warhead embedded in chemical probes that can form covalent bonds with target proteins. Here, we report a new protein-labeling strategy in which a nitrile oxide, a highly reactive intermediate that reacts with proteins, can be efficiently generated by the treatment of oximes with a water-soluble and a minimally toxic oxidant, phenyliodine bis (trifluoroacetate) (PIFA). The resulting intermediate can rapidly bioconjugate with amino acid residues of target proteins, thus enabling target identification of oxime-containing bioactive molecules. Excellent chemoselectivity of cysteine residues by the nitrile oxide was observed, and over 4000 reactive and/or accessible cysteines, including KRAS G12C, have been successfully characterized by quantitative chemical proteomics. Some of these residues could not be detected by conventional cysteine reagents, thus demonstrating the complementary utility of this method.

Stabilizing and upregulating Axin with tankyrase inhibitor reverses 5-fluorouracil chemoresistance and proliferation by targeting the WNT/caveolin-1 axis in colorectal cancer cells.

Chemoresistance is a main obstacle for colorectal cancer treatment. In this study, we evaluated the effects and mechanisms of the WNT/β-catenin signaling pathway on the chemoresistance of SW480 and SW620 colorectal cancer cells. The activity of β-catenin was activated/inhibited by the small molecule compound GSK-3 inhibitor 6-bromo-indirubin-3'-oxime and the tankyrase inhibitor XAV939. The downstream target genes of the WNT/β-catenin signaling pathway were screened using a cDNA microarray and bioinformatics analysis. Apoptosis induced by 5-Fu, cell cycle distribution and expression levels of WNT/β-catenin/TCF12/caveolin-1 and multidrug resistance proteins were examed by flow cytometry and western blot after β-catenin activation/inhibition and caveolin-1 overexpression/interference. The effect and mechanism of XAV939 on proliferation and apoptosis induced by 5-Fu in xenograft tumors of nude mice were evaluated by immunohistochemistry and TUNEL staining. 6-Bromo-indirubin-3'-oxime treatment increased β-catenin expression by regulating GSK-3β phosphorylation, accompanied by upregulation of TCF12, caveolin-1, P-gp, and MRP2 and downregulation of apoptosis induced by 5-Fu. Conversely, XAV939 treatment decreased β-catenin expression by upregulating Axin, accompanied by downregulation of TCF12, Caveolin-1, P-gp, and MRP2 and upregulation of apoptosis induced by 5-Fu. The caveolin-1 gene was identified as an important downstream gene of the WNT/β-catenin signaling pathway. Caveolin-1 overexpression upregulated β-catenin expression, increased P-gp and MRP2 expression and decreased apoptosis induced by 5-Fu; conversely, caveolin-1 interference caused the opposite effects. In addition, in vivo experiments showed that XAV939 treatment reduced β-catenin expression, increased apoptosis induced by 5-Fu and repressed xenograft tumor growth. Our findings suggested that inhibition of WNT/β-catenin/TCF12/caveolin-1 provides a new promising therapeutic strategy for colorectal cancer treatment.

Cervical cancer cell proliferation inhibition by vanillin oxime through HIF‑1α expression inhibition, ERK1/2 and Akt protein down-regulation.

Cervical cancer is a frequently reported cancer of reproductive tract in females and is worldwide 4th most common malignant tumor. The present study investigated the effect of vanillin oxime on proliferation of cervical cancer cells. Vanillin oxime treatment led to suppression of Caski cell proliferation but could not affect proliferation of (HCvEpC) cells at the tested (2 to 10 μM) concentrations. In vanillin oxime treated Caski cells ROS level showed an increase with enhancement in concentration from 2 to 10 μM. Vanillin oxime treatment significantly (P<0.0487) lowered the count of colonies and inhibited invasive abilities of Caski cells. Treatment with vanillin oxime caused a significant (P<0.0487) suppression in HIF‑1α expression in Caski cells. Caski cell apoptotic count reached to 8.76% and 48.65%, on incubation with 2 and 10 μM concentrations of vanillin oxime respectively. After treatment with vanillin oxime a prominent reduction in MMP-2 and -9 levels was observed in Caski cells. A prominent reduction in p-ERK1/2 and p-Akt levels was observed in Caski cells after treatment with vanillin oxime. Vanillin oxime inhibits cervical cancer proliferation, invasive abilities, induces apoptotic signalling, and elevates ROS production. Therefore, vanillin oxime may be developed as an effective therapeutic agent for treatment of cervical cancer.

In silico Study of Potential Non-oxime Reactivator for Sarin-inhibited Human Acetylcholinesterase

The search for new compounds other than oxime as potential reactivator that is effective upon organophosphate poisoning treatments is desired. The less efficacy of oxime treatment has been the core factor. Fourteen compounds have been screened via in silico approach for their potential as sarin-inhibited human acetylcholinesterase poisoning antidotes. The selection of the compounds to be synthesized based on this computational screening, reduces the time and cost needed. To perform the docking study of sarin-inhibited acetylcholinesterase and reactivator-sarin inhibited acetylcholinesterase complexations, a bioinformatics tool was used. Estimation of the nucleophilic attack distance and binding energy of fourteen potential compounds with sarin inhibited acetylcholinesterase complexes to determine their antidote capacities was carried out using Autodock. A commercially available antidote, 2-PAM was used for the comparison. The best docked-pose was further examined with molecular dynamics simulation. Apart from being lipophilic, a compound with a carboxylic acid, (R)-Boc-nipecotic acid is shown to exhibit 6.29 kcal/mol binding energy with 8.778 Å distance of nucleophilic attack. The stability and flexibility of the sarin-inhibited acetylcholinesterase, complexed with (R)-Boc-nipecotic acid suggests this compound should be tested experimentally as a new, promising antidote for sarin-inhibited acetylcholinesterase poisoning.

The tertiary oxime monoisonitrosoacetone penetrates the brain, reactivates inhibited acetylcholinesterase, and reduces mortality and morbidity following lethal sarin intoxication in guinea pigs

The brain is a critical target for the toxic action of organophosphorus (OP) inhibitors of acetylcholinesterase (AChE) such as the nerve agent sarin. However, the available oxime antidote 2-PAM only reactivates OP-inhibited AChE in peripheral tissues. Monoisonitrosoacetone (MINA), a tertiary oxime, reportedly reactivates AChE in the central nervous system (CNS). The current study investigated whether MINA would be beneficial as a supplemental oxime treatment in preventing lethality and reducing morbidity following lethal sarin exposure, MINA supplement would improve AChE recovery in the body, and MINA would be detectable in the CNS. Guinea pigs were exposed to sarin and treated with atropine sulfate and 2-PAM at one minute. Additional 2-PAM or MINA was administered at 3, 5, 15, or 30 min after sarin exposure. Survival and morbidity were assessed at 2 and 24 h. AChE activity in brain and peripheral tissues was evaluated one hour after MINA and 2-PAM treatment. An in vivo microdialysis technique was used to determine partitioning of MINA into the brain. A liquid chromatography-tandem mass spectrometry method was developed for the analysis of MINA in microdialysates. MINA-treated animals exhibited significantly higher survival and lower morbidity compared to 2-PAM-treated animals. 2-PAM was significantly more effective in reactivating AChE in peripheral tissues, but only MINA reactivated AChE in the CNS. MINA was found in guinea pig brain microdialysate samples beginning at ~10 min after administration in a dose-related manner. The data strongly suggest that a centrally penetrating oxime could provide significant benefit as an adjunct to atropine and 2-PAM therapy for OP intoxication.

Broad Spectrum Treatment for Ocular Insult Induced by Organophosphate Chemical Warfare Agents.

Warfare organophosphates nerve agents constitute one of the prime threats to mankind on the battlefield and in the scenario of civilian terror. Exposure toorganophosphate (OP) nerve agents dose-dependently result in incapacitation. They affect multiple organs, but the eye is one of the first and most frequently affected. Ocular OP insult may result in long-term miosis, impaired visual function, and ocular pain thus inducing functional incapacitation. The currently recommended military medical doctrine of using 1% atropine eye drops is far from being the optimal treatment. Although effective in reducing ocular pain and the miotic response, this treatment induces long-term mydriasis and cycloplegia promoting photophobia and restricted accommodation, which may result in further impairment in visual function. An optimal treatment must ameliorate the long-term ocular insult enabling rapid return of normal visual function, while avoiding the induction of mydriasis and cycloplegia side effects, which could possibly worsen the visual performance. Optimal treatment should also keep effects of misuse to a minimum. Work done in recent years examined treatments with various anticholinergic drugs alone or used in combination with oxime treatments and may offer improved efficacy in ameliorating the ocular insult. This review is a summary of the applied research in animals and will discuss clinical implications and possible alterations in treatment protocols following OP exposure. Taken together the data points toward the use of topical low concentrations of potent anticholinergic ophthalmic drops such as atropine or homatropine, which rapidly ameliorate the long-term OP-induced ocular insult.

Caspases as prognostic markers and mortality predictors in acute organophosphorus poisoning

BackgroundOrganophosphorus (OP) compounds have been widely available for decades in agriculture for crop protection and as cheap pest controllers, which increases the rate of exposure and poisoning cases. Using serum cholinesterase as prognostic markers for the acute OP toxicity is controversial; therefore, we aim to find out prognostic biomarkers that best correlate with mortality and outcomes of patients with acute OP toxicity. Levels of serum oxidative stress biomarkers (malondialdehyde (MDA) and total antioxidant capacity (TAC)) and activity of the apoptotic biomarkers (caspase 3 and caspase 9) and pseudo-cholinesterase (p.ChE) were performed. Also, we evaluated the apoptotic capacity through determining the genotoxic effects and chromosomal abnormalities among OP intoxicated patients. ResultsWe found the activity of caspases and serum MDA and TAC were significantly increased after OP poisoning and decreased after the appropriate atropine and oxime treatment course. The ROC curve suggested caspases as mortality and outcome predictive markers for acute OP poisoning patients. However, OP poisoning cases before treatment showed significant DNA damage, and they did not show any chromosomal aberration. ConclusionThe mentioned results strongly suggest apoptotic-related markers (caspase 3, caspase 9) as prognostic markers for evaluation of the treatment, outcomes, and mortality rate in the acute OP toxicity patients.

(3Z)-5-Chloro-3-(Hydroxyimino)indolin-2-one attenuates hyperglycemia, increased hepatic glycogen content and hepatic damage induced by malathion acute exposure in rats

BackgroundOrganophosphorus pesticides (OP’s) are heavily constituted in agriculture, gardens, home and veterinary and although it is useful, there are concerns about the environment, safety and health of human and animals. In this study, we investigated the effects of a new oxime, (3Z)-5-Chloro-3-(Hydroxyimino)indolin-2-one (OXIME) against the alterations induced by malathion, an OP insecticide, acute exposure on markers of hepatic damage, glucose homeostasis, oxidative stress in rats cholinesterase (ChE) activity in rats.MethodsAdult male Wistar rats were divided into four groups: Control; Malathion; OXIME; and Malathion+OXIME. Twelve hours after co-treatment with malathion (250 mg/kg, i.p.) and/or OXIME (50 mg/kg, i.g.), the plasma and liver samples were collected for biochemical analyses.ResultsThe OXIME blocked the increase of plasma markers of hepatic function (AST and ALP) and the enzymatic inhibition of catalase and glutathione reductase in the liver of malathion-treated rats. Moreover, the hepatic cholinesterases inhibition induced by malathion acute exposure was suppressed by OXIME treatment. As assessed, a single dose of OXIME lowered the glycemia levels and hepatic glycogen content enhanced by malathion.ConclusionsThis study suggests promise effects of (3Z)-5-Chloro-3-(Hydroxyimino) indolin-2-one against the hyperglycemia and the hepatic damage induced by malathion acute exposure, as well as its use as a ChE activity reactivator.

Evaluating the broad-spectrum efficacy of the acetylcholinesterase oximes reactivators MMB4 DMS, HLö-7 DMS, and 2-PAM Cl against phorate oxon, sarin, and VX in the Hartley guinea pig

Organophosphorus (OP) compounds, including pesticides and chemical warfare nerve agents (CWNA), are threats to the general population as possible weapons of terrorism or by accidental exposure whether through inadvertent release from manufacturing facilities or during transport. To mitigate the toxicities posed by these threats, a therapeutic regimen that is quick-acting and efficacious against a broad spectrum of OPs is highly desired. The work described herein sought to assess the protective ratio (PR), median effective doses (ED50), and therapeutic index (TI = oxime 24-h LD50/oxime ED50) of MMB4 DMS, HLö-7 DMS, and 2-PAM Cl against the OPs sarin (GB), VX, and phorate-oxon (PHO). All OPs are representative of the broader classes of G and V chemical warfare nerve agents and persistent pesticides. MMB4 DMS and HLö-7 DMS were previously identified as comparative efficacy leads warranting further evaluations. 2-PAM Cl is the U.S. FDA-approved standard-of-care oxime therapy for OP intoxication. Briefly, PRs were determined in male guinea pigs by varying the subcutaneously (SC) delivered OP dose followed then by therapy with fixed levels of the oxime and atropine (0.4 mg/kg; administered intramuscularly [IM]). ED50s were determined using a similar approach except the OP dose was held constant at twice the median lethal dose (2 × LD50) while the oxime treatment levels were varied. The ED50 information was then used to calculate the TI for each OP/oxime combination. Both MMB4 DMS and HLö-7 DMS provided significant protection, i.e., higher PR against GB, VX, and PHO when compared to atropine controls, but significance was not readily demonstrated across the board when compared against 2-PAM Cl. The ED50 values of MMB4 DMS was consistently lower than that of the other oximes against all three OPs. Furthermore, based on those ED50s, the TI trend of the various oximes against both GB and VX was MMB4 DMS > HLö-7 DMS > 2-PAM Cl, while against PHO, MMB4 DMS > 2-PAM Cl > HLö-7 DMS.

Efficacy of two anthelmintic treatments, spinosad/milbemycin oxime and ivermectin/praziquantel in dogs with natural Toxocara spp. infection

Toxocara canis is one of the most important zoonotic parasites of dogs. The aim of the present study was to compare the efficacy of spinosad/milbemycin oxime and ivermectin/praziquantel in dogs naturally infected with Toxocara spp. We studied 200 dogs with a positive diagnosis of Toxocara spp. Through coproparasitoscopic analysis, two study groups of 100 dogs each were assigned: spinosad/milbemycin oxime at a dose of 30–60mg/kg and 0.75–1.0mg/kg, respectively, or ivermectin/praziquantel administered at a dose of 0.2mg/kg and 5mg/kg, respectively. Both groups received a single dose. Three stool samples, one at day 0 before treatment, and at 14 and 28days post-treatment were examined using concentration-flotation techniques. In both treatments, the number of Toxocara spp. eggs decreased; with spinosad/milbemycin oxime treatment, eggs decreased by 87% at 14days (P=0.008) and 94% at 28days after treatment, compared with 71% at day 14 and 88% at day 28 in dogs medicated with ivermectin/praziquantel. The spinosad/milbemycin oxime treated group showed a greater decrease in the number of Toxocara spp. positive dogs compared to the group receiving ivermectin/praziquantel.

Green synthesis of 2-pyrazinones in deep eutectic solvents: From α-chloro oximes to peptidomimetic scaffolds

A novel and green synthesis of 2-pyrazinones in deep eutectic solvents (DESs) is described. Treatment of aromatic α-chloro oximes with aliphatic amines at 110 °C in choline chloride based DESs resulted in a straightforward and efficient assembly of 1,3,5-trisubstituted-2(1H)-pyrazinones. The protocol, featuring mild reaction conditions and avoiding common volatile organic solvents, affords a safe and sustainable approach to original peptidomimetic scaffolds.

N-Radical Initiated Aminosulfonylation of Unactivated C(sp3)-H Bond through Insertion of Sulfur Dioxide.

N-Radical initiated aminosulfonylation of unactivated C(sp3)-H bond through insertion of sulfur dioxide in the presence of visible light is reported. O-Aryl oximes react with DABCO·(SO2)2 smoothly at room temperature under blue LED irradiation without any metals or photoredox catalysts, generating diverse 5,6-dihydro-4H-1,2-thiazine 1,1-dioxides in good yield. Additionally, this approach can be extended to the synthesis of 1H-benzo[d][1,2]thiazine 2,2-dioxides. During the reaction process, an N-radical is initiated by the treatment of O-aryl oximes with DABCO·(SO2)2 under visible-light irradiation. It is followed by aminosulfonylation of a nearby C(sp3)-H bond through 1,5-hydrogen atom transfer with accompanying insertion of sulfur dioxide to provide 1,2-thiazine 1,1-dioxide derivatives.

Biochemical and histopathological changes in the brain of albino rats treated with profenofos and the possible protective effect of vitamins C and E

Objective The aim of this study was to evaluate the changes in the brain of albino rats treated with profenofos and the possible protective effect of vitamins C and E against the acute effect of profenofos. Background During the last decades the use of pesticides has increased steadily in developing countries in an effort to increase food production and control vector-borne diseases in plants. Organophosphorus (OP) compounds are widely used in agriculture as insecticides. OP poisoning is common due to its wide availability. Profenofos is a widely used insecticide and has been classified as moderately hazardous. OP pesticides are known to inhibit cholinesterase activity in target tissues. Oxidative stress is one of the possible mechanisms that could be involved in OP toxicity. Patients and methods Eighty adult male albino rats were divided randomly into four main groups: the control group (I), the profenofos toxicity group (group II), the profenofos + antidote-treated group (group III), and the profenofos + antidote + antioxidant-treated group (group IV). Each treated group was divided equally into two subgroups. Ten rats from each subgroup were killed after 24 h to demonstrate the toxicity. The other 10 rats were killed after 7 days to demonstrate the recovery. Brain samples were obtained for biochemical, histopathological, and immunohistochemical studies. Results Acute exposure to profenofos causes biochemical and histopathological changes in brain tissue. These changes were minimized with atropine and oxime treatment. However, this recovery was more prominent in the group administered vitamins C and E. Conclusion Treatment with vitamins C and E exerts an antioxidative effect and this may be responsible for the amelioration of profenofos-provoked toxicity.

Efforts toward treatments against aging of organophosphorus-inhibited acetylcholinesterase.

Aging is a dealkylation reaction of organophosphorus (OP)-inhibited acetylcholinesterase (AChE). Despite many studies to date, aged AChE cannot be reactivated directly by traditional pyridinium oximes. This review summarizes strategies that are potentially valuable in the treatment against aging in OP poisoning. Among them, retardation of aging seeks to lower the rate of aging through the use of AChE effectors. These drugs should be administered before AChE is completely aged. For postaging treatment, realkylation of aged AChE by appropriate alkylators may pave the way for oxime treatment by neutralizing the oxyanion at the active site of aged AChE. The other two strategies, upregulation of AChE expression and introduction of exogenous AChE, cannot resurrect aged AChE but may compensate for lowered active AChE levels by in situ production or external introduction of active AChE. Upregulation of AChE expression can be triggered by some peptides. Sources of exogenous AChE can be whole blood or purified AChE, either from human or nonhuman species.

Ring expansions of acyloxy nitroso compounds

Treatment of cyclopentanone and cyclobutanone-derived oximes with lead(IV) tetraacetate gives the bright blue acyloxy nitroso compounds, which upon basic hydrolysis yields the ring expansion product cyclic hydroxamic acids in 12–81% yield. Reactions of substituted cyclopentanones provide ring expanded products where the –NOH group regioselectively inserts to the more substituted position and gives a better yield compared to the treatment of the same ketone with a basic solution of Piloty’s acid. Reaction of phosphines with acyloxy nitroso compounds generally generates a ring-expanded Beckmann rearrangement product that can be hydrolyzed to the corresponding lactam. Acyloxy nitroso compounds that undergo rapid hydrolysis to HNO do not show this ring expansion reactivity. These results further demonstrate the versatility of acyloxy nitroso compound to yield structurally complex materials.

Synergism Between Anticholinergic and Oxime Treatments Against Sarin-Induced Ocular Insult in Rats.

Eye exposure to the extremely toxic organophosphorus sarin results in long-term miosis and visual impairment. As current treatment using atropine or homatropine eye drops may lead to considerable visual side effects, alternative combined treatments of intramuscular (im) oximes (16.8 µmol/kg, im) with atropine (0.5 mg/kg, im) or with the short acting antimuscarinic tropicamide (0.5%; w/v) eye drops were thus evaluated. The combined treatments efficacy following topical exposure to sarin (1 µg) was assessed by measuring pupil width and light reflex using an infra-red based digital photographic system. Results showed that the combined treatment of various oximes with atropine or with topical tropicamide eye drops rapidly reversed the sarin-induced miosis and presented a long-term improvement of 67-98% (oxime+tropicamide) or 84-109% (oxime+atropine) in pupil widening as early as 10-min following treatment. This recovery was shown to persist for at least 8-h following exposure. All combined treatments facilitated the ability of the iris to contract following sarin insult as tested by a light reflex response.Our findings emphasize the high efficacy of im oxime treatment combined with either atropine im or tropicamide eye drops in counteracting sarin-induced ocular insult. Therefore, in a mass casualty scenario the systemic combined treatment may be sufficient to ameliorate sarin-induced ocular insult with no need for additional, topical anticholinergic treatment at least in the initial stage of intoxication. For very mild casualties, who are unlikely to receive im treatment, the combined oxime (im) with topical tropicamide treatment may be sufficient in ameliorating the ocular insult.

ChemInform Abstract: Scalable, Transition‐Metal‐Free Direct Oxime O‐Arylation: Rapid Access to O‐Arylhydroxylamines and Substituted Benzo[b]furans.

AbstractA broad spectrum of O‐aryloximes is readily available on treatment of inexpensive oximes with symmetrical diaryliodonium salts in the absence of a transition metal.

Efficacy assessment of a combined anticholinergic and oxime treatment against topical sarin‐induced miosis and visual impairment in rats

Eye exposure to the organophosphorus (OP) irreversible cholinesterase inhibitor sarin results in long-term miosis and impaired visual function. We have previously shown that tropicamide is better at ameliorating this insult than topical atropine or cyclopentolate. However, to minimize side effects associated with repeated tropicamide applications and high treatment doses, we evaluated the effects of oximes (ChE re-activators) alone and combined with tropicamide at ameliorating OP-induced ocular impairments. Rats were topically exposed to sarin, followed by topical treatment with various oximes alone or in combination with tropicamide. Pupil width and light reflex were measured by an infrared-based digital photograph system, while visual performance was assessed by employing the cueing version of the Morris water maze (MWM). Oxime treatment following sarin ocular exposure induced a slow persistent pupil widening with efficacy in the order of HLö-7 > HI-6 > obidoxime = TMB-4 = MMB-4. In the light reflex test, the ability of the iris to contract following oxime treatment was mostly impaired at 1 h and was back to normal at 4 h following sarin exposure. All oxime treatments ameliorated the sarin-induced visual impairment as tested in the visual task (MWM). The combined topical treatment of tropicamide with an oxime induced a rapid improvement in pupil widening, light reflex and visual performance, and enabled a reduction in tropicamide dose. The use of tropicamide combined with an oxime should be considered as the topical treatment of choice against the toxic effects of ocular OP exposure.

Synthesis of sterically hindered ketones from aldehydes via O-silyl oximes

A mild and efficient method to synthesize sterically hindered ketones from aldehydes via O-silyl oximes was developed. Treatment of O-triphenylsilylated oximes with alkyl iodides in the presence of triethyl borane afforded the corresponding ketones.