Sample records for cholinesterases

  1. Cholinesterase inhibitors from botanicals

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    Faiyaz Ahmed


    Full Text Available Alzheimer′s disease (AD is a progressive neurodegenerative disease, wherein a progressive loss of cholinergic synapses occurs in hippocampus and neocortex. Decreased concentration of the neurotransmitter, acetylcholine (ACh, appears to be critical element in the development of dementia, and the most appropriate therapeutic approach to treat AD and other form of dementia is to restore acetylcholine levels by inhibiting both major form of cholinesterase: Acetylcholinesterase (AChE and butyrylcholinesterase (BChE. Consequently, researches have focused their attention towards finding cholinesterase inhibitors from natural products. A large number of such inhibitors have been isolated from medicinal plants. This review presents a comprehensive account of the advances in field of cholinesterase inhibitor phytoconstituents. The structures of some important phytoconstituents (collected through are also presented and the scope for future research is discussed.

  2. Nonquaternary Cholinesterase Reactivators. (United States)


    1978, 34, 523. 30. Lehninger , A. L., " Biochemistry ," Worth Publ. Inc., New York, 1970, p. 161. 31. Green, A. L.; Smith, H. J.; Biochem. J., 1958, 68...nerve agent antidotes focuses on nonquaternary cholinesterase reactivators. In principle , it should be possible to find nonquaternary hydroximic acid...elicit pronounced physiological responses. In principle , it should be possible to develop nonquaternary AChE reactivators that would not only equal

  3. Cholinesterase inhibitors and memory. (United States)

    Pepeu, Giancarlo; Giovannini, Maria Grazia


    A consensus exists that cholinesterase inhibitors (ChEIs) are efficacious for mild to moderate Alzheimer's Disease (AD). Unfortunately, the number of non-responders is large and the therapeutic effect is usually short-lasting. In experimental animals, ChEIs exert three main actions: inhibit cholinesterase (ChE), increase extracellular levels of brain acetylcholine (ACh), improve cognitive processes, particularly when disrupted in models of AD. In this overview we shall deal with the cognitive processes that are improved by ChEI treatment because they depend on the integrity of brain cholinergic pathways and their activation. The role of cholinergic system in cognition can be investigated using different approaches. Microdialysis experiments demonstrate the involvement of the cholinergic system in attention, working, spatial and explicit memory, information encoding, sensory-motor gating, skill learning. No involvement in long-term memory has yet been demonstrated. Conversely, memory consolidation is facilitated by low cholinergic activity. Experiments on healthy human subjects, notwithstanding caveats concerning age, dose, and different memory tests, confirm the findings of animal experiments and demonstrate that stimulation of the cholinergic system facilitates attention, stimulus detection, perceptual processing and information encoding. It is not clear whether information retrieval may be improved but memory consolidation is reduced by cholinergic activation. ChEI effects in AD patients have been extensively investigated using rating scales that assess cognitive and behavioural responses. Few attempts have been made to identify which scale items respond better to ChEIs and therefore, presumably, depend on the activity of the cholinergic system. Improvement in attention and executive functions, communication, expressive language and mood stability have been reported. Memory consolidation and retrieval may be impaired by high ACh levels. Therefore, considering

  4. Cholinesterase modulations in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Ofek, Keren; Qvist, Tavs;


    The circulating cholinesterases acetyl- and butyrylcholinesterase may be suppressed and subsequently released from the brain in acute bacterial meningitis.......The circulating cholinesterases acetyl- and butyrylcholinesterase may be suppressed and subsequently released from the brain in acute bacterial meningitis....

  5. Partial purification and properties of flyhead cholinesterase

    NARCIS (Netherlands)

    Dauterman, W.C.; Talens, A; Asperen, K. van


    Housefly head cholinesterase was purified using the following steps: (1) freeze-drying of flyheads, (2) solubilization of the enzyme by butanol extraction, (3) ammonium sulphate precipitation at pH 7, (4) heat denaturation of proteins in the presence of acetylcholine for protection of the cholineste


    To assess the potential for using saliva in pesticide biomonitoring, the consistency of cholinesterase activity in human saliva collected over time was examined. In this pilot study, saliva was collected from 20 healthy adults once per week for 5 consecutive weeks using 2 differe...

  7. 21 CFR 862.3240 - Cholinesterase test system. (United States)


    ... is present at nerve endings and in erythrocytes (red blood cells) but is not present in plasma... obtained by this device are used in the diagnosis and treatment of cholinesterase inhibition disorders...

  8. Study of Serum Amylase and Serum Cholinesterase in Organophosphorus Poisoning

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    Sharan Badiger


    Full Text Available Background: Poisoning due to organophosphorus compounds is most commonly seen. Earlier plasma cholinesterase level was used to assess the severity of poisoning. Presently serum amylase is being recommended as a better indicator of severity. Aims and Objectives: To study plasma cholinesterase and serum amylase levels in acute organophosphorus and to correlate serum amylase levels with clinical severity and outcome. Material and Methods: A total of 80 patients in the study admitted to a tertiary care centre within 24 hours with a history of organophosphorus poisoning were included in study. Estimation of plasma cholinesterase and serum rd amylase was done at the time of admission, and on 3 th day and on 5 day. Results: Occurrence of organophosphorus poisoning was more common among age group 21-30 years and among males (57.5%. They were 25 (31.2% farmers, 23 (28.8% st u d e n ts, a n d 2 2 ( 2 7 . 5% h o u s ewi v e s. Monocrotophos (45.0% was commonly used compound. Mean value of plasma cholinesterase and serum amylase at admission are 3693 U/L, and 185.4 U/L. There was significant inhibition of plasma cholinesterase and elevation of serum amylase at th admission with return to normal values on 5 day. Conclusion: Plasma cholinesterase inhibition 200 U/L has been associated with poor prognosis and proneness to respiratory failure.

  9. Motor endplate cholinesterase in human skeletal muscle.

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    Full Text Available The activity and properties of cholinesterase (ChE of the motor endplate and its fractions were studied in isolated human skeletal muscle. This preparation was used since the ChE activity of the membrane preparation was localized only in the motor endplate. The endplate ChE was stable in the isolated membrane for 4 weeks at 4 degrees C. The specific activity of the extracted ChE of human muscle membrane was 29.6% higher than that of the original membrane. Studies with specific substrates and ChE inhibitors indicated that most of the ChE of human muscle membrane and its fractions was acetylcholinesterase, and that the minor component was pseudocholinesterase. A Michaelis-Menten constant of 3.82 mM was estimated in the endplate ChE, and 0.88 mM in the extracted ChE of the endplate. The extracted human endplate ChE was separated into three fractions by Sephadex G-200 chromatography, and into two fractions by acrylamide gel electrophoresis.

  10. Central cholinesterase inhibition enhances glutamatergic synaptic transmission. (United States)

    Kozhemyakin, Maxim; Rajasekaran, Karthik; Kapur, Jaideep


    Central cholinergic overstimulation results in prolonged seizures of status epilepticus in humans and experimental animals. Cellular mechanisms of underlying seizures caused by cholinergic stimulation remain uncertain, but enhanced glutamatergic transmission is a potential mechanism. Paraoxon, an organophosphate cholinesterase inhibitor, enhanced glutamatergic transmission on hippocampal granule cells synapses by increasing the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in a concentration-dependent fashion. The amplitude of mEPSCs was not increased, which suggested the possibility of enhanced action potential-dependent release. Analysis of EPSCs evoked by minimal stimulation revealed reduced failures and increased amplitude of evoked responses. The ratio of amplitudes of EPSCs evoked by paired stimuli was also altered. The effect of paraoxon on glutamatergic transmission was blocked by the muscarinic antagonist atropine and partially mimicked by carbachol. The nicotinic receptor antagonist α -bungarotoxin did not block the effects of paraoxon; however, nicotine enhanced glutamatergic transmission. These studies suggested that cholinergic overstimulation enhances glutamatergic transmission by enhancing neurotransmitter release from presynaptic terminals.

  11. [Pesticide detection in Costarican vegetables based on the inhibition of serum and erythrocytic human cholinesterases]. (United States)

    Nevermann, Karl Schosinsky; Guzmán, Eugenia Quintana


    A simple and low cost method able to detect the presence of pesticides, organophosphates and carbamates based on the inhibition of serum and erythrocytic cholinesterases, was used in lettuce (Lactuca sativa), cilantro (Coriandum santivum) and celery (Apium graveolens) obtained from the Ferias del Agricultor from Valle Central of Costa Rica. The percentage inhibition of cholinesterases is related to the presence of plaguicide in the vegetable. Thirteen percent of the analyzed samples were positive for plaguicides using serum cholinesterase and 33% for erythrocytic cholinesterase. Washing and cooking the vegetables does not eliminate the presence of plaguicides but they lower slightly the concentration. Statistical evidence (p = 0.0001) indicates that erythrocytic cholinesterase has higher analytical sensitivity than serum cholinesterase. It is very important to establish the degree of contamination with pesticides in these agricultural products because they are exposed to direct contamination by fumigation, soil contamination and irrigation water, and are products that are often consumed without adequate cooking and washing.

  12. Tracking the origin and divergence of cholinesterases and neuroligins: the evolution of synaptic proteins


    Lenfant, Nicolas; Hotelier, Thierry; Bourne, Yves; Marchot, Pascale; Chatonnet, Arnaud


    14. International Symposium on Cholinergic Mechanisms (ISCM), Hangzhou, 2013/05/05-9; A cholinesterase activity can be found in all kingdoms of living organism, yet cholinesterases involved in cholinergic transmission appeared only recently in the animal phylum. Among various proteins homologous to cholinesterases, one finds neuroligins. These proteins, with an altered catalytic triad and no known hydrolytic activity, display well-identified cell adhesion properties. The availability of compl...

  13. Molecular Biological Studies on the Biogenesis of Human Cholinesterases in vivo and as Directed by Cloned Cholinesterase DNA Sequences (United States)


    potentially be analogous to the well-known amplification of other genes that encode target proteins to toxic compounds. As such, it could provide cells the...occurring CHE inhibitors, including the steroidal glycoalkaloid solanine and its hydrolytic aglycone derivative solanidine, both of which may be...present in toxic concentrations in potatoes (63,64). 4.5 Suggestions for peptidase activity of cholinesterases Carboxy- and aminopeptidase activity from a

  14. Evaluation of Candidate Genes for cholinesterase Activity in Farmworkers Exposed to organophosphorous Pesticides-Association of SNPs in BCHE (United States)

    Background: Organophosphate pesticides act as cholinesterase inhibitors, and as such may give rise to potential neurological effects. Cholinesterase activity is a useful, indirect measurement of pesticide exposure, especially in high-risk individuals such as farmworkers. To und...

  15. Alterations of serum cholinesterase in patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Shan-Zhi Gu; Xin-Han Zhao; Ping Quan; Sheng-Bin Li; Bo-Rong Pan


    AIM: To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance.METHODS: The velocity method was adopted to detect the activity of serum CHE in patients with gastric cancer and in patients with non-malignant tumor as controls.RESULTS: The serum CHE activity in the treatment group was significantly lower than that in the control group with a very significant difference between the two groups (83.3:113.1,P = 0.0003). Age was significantly associated with the incidence of gastric caner.CONCLUSION: Serum CHE activity has a close relation with the incidence of gastric cancer.

  16. Automated conductimetric assay of human serum cholinesterase activity. (United States)

    Duffy, P; Wallach, J M


    Serum cholinesterase activity was determined by conductimetry using samples in the microliter range. Butyrylcholine iodide was demonstrated to be a convenient substrate for the conductimetric assay. Validation of the microassay was made by using either purified enzyme or control serum. In the range of 0-60 U/l, a linear relationship was demonstrated. Correlation with a reference spectrophotometric method was obtained with a slope of 1.18. An explanation of this value is proposed, as different hydrolysis rates were obtained with human sera, depending on the substrate used (butyrylthio- or butyryl-choline ester).

  17. A review on cholinesterase inhibitors for Alzheimer's disease. (United States)

    Anand, Preet; Singh, Baldev


    Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized by the deficits in the cholinergic system and deposition of beta amyloid (Aβ) in the form of neurofibrillary tangles and amyloid plaques. Since the cholinergic system plays an important role in the regulation of learning and memory processes, it has been targetted for the design of anti-Alzheimer's drugs. Cholinesterase inhibitors enhance cholinergic transmission directly by inhibiting the enzyme acetylcholinesterase (AChE) which hydrolyses acetylcholine. Furthermore, it has been also demonstrated that both acetylcholinesterase and butrylcholinesterase (BuChE) play an important role in Aβ-aggregation during the early stages of senile plaque formation. Therefore, AChE and BuChE inhibition have been documented as critical targets for the effective management of AD by an increase in the availability of acetylcholine in the brain regions and decrease in the Aβ deposition. This review discusses the different classes of cholinesterase inhibitors including tacrine, donepezil, rivastigmine, galantamine, xanthostigmine, para-aminobenzoic acid, coumarin, flavonoid, and pyrrolo-isoxazole analogues developed for the treatment of AD.

  18. Exposure of nonbreeding migratory shorebirds to cholinesterase-inhibiting contaminants in the western hemisphere (United States)

    Strum, K.M.; Hooper, M.J.; Johnson, K.A.; Lanctot, Richard B.; Zaccagnini, M.E.; Sandercock, B.K.


    Migratory shorebirds frequently forage and roost in agricultural habitats, where they may be exposed to cholinesterase-inhibiting pesticides. Exposure to organophosphorus and carbamate compounds, common anti-cholinesterases, can cause sublethal effects, even death. To evaluate exposure of migratory shorebirds to organophosphorus and carbamates, we sampled birds stopping over during migration in North America and wintering in South America. We compared plasma cholinesterase activities and body masses of individuals captured at sites with no known sources of organophosphorus or carbamates to those captured in agricultural areas where agrochemicals were recommended for control of crop pests. In South America, plasma acetylcholinesterase and butyrylcholinesterase activity in Buff-breasted Sandpipers was lower at agricultural sites than at reference sites, indicating exposure to organophosphorus and carbamates. Results of plasma cholinesterase reactivation assays and foot-wash analyses were inconclusive. A meta-analysis of six species revealed no widespread effect of agricultural chemicals on cholinesterase activity. however, four of six species were negative for acetylcholinesterase and one of six for butyrylcholinesterase, indicating negative effects of pesticides on cholinesterase activity in a subset of shorebirds. Exposure to cholinesterase inhibitors can decrease body mass, but comparisons between treatments and hemispheres suggest that agrochemicals did not affect migratory shorebirds' body mass. Our study, one of the first to estimate of shorebirds' exposure to cholinesterase-inhibiting pesticides, suggests that shorebirds are being exposed to cholinesterase- inhibiting pesticides at specific sites in the winter range but not at migratory stopover sites. future research should examine potential behavioral effects of exposure and identify other potential sitesand levels of exposure. ?? The Cooper Ornithological Society 2010.

  19. Cholinesterase activity of lamellated sensory corpuscles in the rat lip

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    II-Sei Watanabe


    Full Text Available Non-specific cholinesterase (ChE activity was demonstrated in lamellated sensory corpuscles of the rat lip by light and electron microscopy using Karnovsky and Root's method. ChE activity was present in the interlamellar spaces between neighbouring lamellae as well as in the periaxonal space between axon terminals and their adjacent lamellae. Reaction products of ChE activity were also deposited in some caveolae of the lamellar cell plasma membrane, and in the cisternae of the rough endoplasmic reticulum as well as in the nuclear envelope of lamellar cell bodies. No definite reaction products were detected within the axon terminals. These findings show that the lamellated corpuscles in the rat lip, like other mechanoreceptors, have an intense ChE activity which is mainly associated with lamellar cells. It can be said that ChE histochemistry is useful to detect mechanoreceptors. The functional significance of ChE in mechanoreceptors is discussed.

  20. Early appearance and possible roles of non-neuromuscular cholinesterases.

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    Carla eFalugi


    Full Text Available The biological function of the cholinesterase (ChE enzymes is well known and has been studied since the beginning of the XXth century; in particular, acetylcholinesterase (AChE, E.C. is an enzyme playing a key role in the modulation of neuromuscular impulse transmission. However, in the past decades, there has been increasing interest concerning its role in regulating non-neuromuscular cell-to-cell interactions mediated by intracellular ion concentration changes, like the ones occurring during gamete interaction and embryonic development. An understanding of the mechanisms of the cholinergic regulation of these events can help us foresee the possible impact on environmental and human health, including gamete efficiency and possible teratogenic effects on different models, and help elucidate the extent to which exposure to ChE inhibitors may affect human health.

  1. Cholinesterase inhibitory activity of chlorophenoxy derivatives-Histamine H3 receptor ligands. (United States)

    Łażewska, Dorota; Jończyk, Jakub; Bajda, Marek; Szałaj, Natalia; Więckowska, Anna; Panek, Dawid; Moore, Caitlin; Kuder, Kamil; Malawska, Barbara; Kieć-Kononowicz, Katarzyna


    In recent years, multitarget-directed ligands have become an interesting strategy in a search for a new treatment of Alzheimer's disease. Combination of both: a histamine H3 receptor antagonist/inverse agonist and a cholinesterases inhibitor in one molecule could provide a new therapeutic opportunity. Here, we present biological evaluation of histamine H3 receptor ligands-chlorophenoxyalkylamine derivatives against cholinesterases: acetyl- and butyrylcholinesterase. The target compounds showed cholinesterase inhibitory activity in a low micromolar range. The most potent in this group was 1-(7-(4-chlorophenoxy)heptyl)homopiperidine (18) inhibiting the both enzymes (EeAChE IC50=1.93μM and EqBuChE IC50=1.64μM). Molecular modeling studies were performed to explain the binding mode of 18 with histamine H3 receptor as well as with cholinesterases.

  2. [Study of the interaction of main potato glycoalkaloids in inhibition of immobilized butyryl cholinesterase]. (United States)

    Arkhypova, V M; Dziadevych, S V; Jaffrezic-Renault, N; Martelet, C; Soldatkin, O P


    The interaction of main potato glycoalkaloids alpha-solanine and alpha-chaconine in inhibition of horse serum butyryl cholinesterases immobilized on the pH-sensitive field-effect transistors has been investigated. The method of isobol diagram of Loewe and Muishnek has been used for interpretation of results. It has been shown the alpha-chaconine inhibits the immobilized bytyryl cholinesterases more strongly than alpha-solanine, and their mixture has the addition effect.

  3. International Meeting on Cholinesterases (5th) Held in Madras, India on 24-28 September, 1994. (United States)


    Masson3. 1- Lab. d’entomologie, Universith Paul Sabatier, 118 route de Narbonne, 31062 Toulouse, France; 2- Lab. IMRCP, groupe de Chimie organique ...LABELING STUDIES ON CHOLINESTERASES. Maurice Goeldner. Laboratoire de Chimie Bio- Organique , URA 1386 CNRS, Facult6 de Pharmacie, Universitd Louis...CHOLINESTERASES. Isabelle Schalk, Christine Loeb, Florian Nachon, Laurence Ehret-Sabatier and Maurice Goeldner. Laboratoire de Chimie Bio- Organique - URA

  4. [Interest of the cholinesterase assay during organophosphate poisonings]. (United States)

    Jalady, A-M; Dorandeu, F


    Cholinesterases are the main targets of organophosphorus compounds. The two enzymes present in the blood (butyrylcholinesterase, BChE; acetylcholinesterase, AChE) are biomarkers of their systemic toxicity. Activity of the plasma BChE is very often determined as it allows a rapid diagnostic of poisoning and is a marker of the persistence of the toxicant in the blood. The activity of the red blood cell AChE gives a better picture of the synaptic inhibition in the nervous system but the assay is less commonly available in routine laboratories. Better biomarker of the exposure, it allows a diagnosis of the severity of the poisoning and helps to assess the efficacy of oxime therapy. Besides the practical aspects of blood collection and sample processing, and the interpretation of the assays, this review stresses the complementarity of both enzyme assays and recalls their crucial interest for the confirmation of poisoning with an organophosphorus in a situation of war or terrorist attack and for the monitoring of occupational exposures.

  5. Behavioral changes and cholinesterase activity of rats acutely treated with propoxur. (United States)

    Thiesen, F V; Barros, H M; Tannhauser, M; Tannhauser, S L


    Early assessment of neurological and behavioral effects is extremely valuable for early identification of intoxications because preventive measures can be taken against more severe or chronic toxic consequences. The time course of the effects of an oral dose of the anticholinesterase agent propoxur (8.3 mg/kg) was determined on behaviors displayed in the open-field and during an active avoidance task by rats and on blood and brain cholinesterase activity. Maximum inhibition of blood cholinesterase was observed within 30 min after administration of propoxur. The half-life of enzyme-activity recovery was estimated to be 208.6 min. Peak brain cholinesterase inhibition was also detected between 5 and 30 min of the pesticide administration, but the half-life for enzyme activity recovery was much shorter, in the range of 85 min. Within this same time interval of the enzyme effects, diminished motor and exploratory activities and decreased performance of animals in the active avoidance task were observed. Likewise, behavioral normalization after propoxur followed a time frame similar to that of brain cholinesterase. These data indicate that behavioral changes that occur during intoxication with low oral doses of propoxur may be dissociated from signs characteristic of cholinergic over-stimulation but accompany brain cholinesterase activity inhibition.

  6. Brain cholinesterase response in the snakehead fish (Channa striata) after field exposure to diazinon. (United States)

    Nguyen, Van Cong; Nguyen, Thanh Phuong; Bayley, Mark


    The snakehead Channa striata is an economically important air-breathing fish species in the Mekong delta of Vietnam. Rice paddies, which are disturbed by the frequent application of agro-chemicals, are among the preferred habitats for this species during the rainy season. Diazinon is one of most commonly used chemicals in rice paddies. In the present study, exposure of adult snakehead fish to a single diazinon application in cages within a rice field resulted in long-term brain cholinesterase inhibition, while the water concentration of this insecticide fell below the detection limit within 3 days. In addition, incubation of brain homogenates with 2-PAM caused reactivation of the cholinesterase diazinon complex to within 80% of the control level. These experiments also showed that chemical ageing of the diazinon cholinesterase binding occurred, which may explain the long-term effects of this pesticide.

  7. Correlation between Cholinesterase and Paraoxonase 1 Activities: Case Series of Pesticide Poisoning Subjects

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    S Austin Richard


    Full Text Available Introduction: Acute exposure to pesticide due to suicidal poisoning is the most extensive cause of pesticide exposure, compared with all other causes including agricultural or industrial exposure. Organophosphate (OP and carbamate group of pesticides can inhibit acetylcholinesterase; on the other hand, paraoxonase1 can detoxify organophosphate poisoning by hydrolyzing organophosphate metabolites. Methods: We have compared the serum paraoxonase1 status and cholinesterase activity of subjects who attempted to commit suicide by consuming OP pesticide. Cholinesterase and paraoxonase1 activity were measured spectrophotometrically using butyrylthiocholine and phenyl acetate as substrates, respectively. Results: A positive correlation was found between serum paraoxonase1 activity and cholinesterase activity among pesticide consumed subjects. Conclusion: Our results suggest that subjects with higher paraoxonase1 activity may have a better chance of detoxifying the lethal effect of acute organophosphate poisoning.

  8. Serum Acetyl Cholinesterase as a Biomarker of Arsenic Induced Neurotoxicity in Sprague-Dawley Rats

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    Paul B. Tchounwou


    Full Text Available Arsenic is an environmental toxicant, and one of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which may cause severe injury/damage to the nervous system. The main objective of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of acetyl cholinesterase; a critical important nervous system enzyme that hydrolyzes the neurotransmitter acetylcholine. Four groups of six male rats each weighing an average 60 + 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW, one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthesia, blood specimens were immediately collected using heparinized syringes, and acetyl cholinesterase detection and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly decreased the activity of cholinesterase in the Sprague-Dawley rats. Acetyl cholinesterase activities of 6895 + 822, 5697 + 468, 5069 + 624, 4054 + 980, and 3158 + 648 U/L were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual decrease in acetyl cholinesterase activity with increasing doses of arsenic. These findings indicate that acetyl

  9. Molecular Cloning of Human Gene(s) Directing the Synthesis of Nervous System Cholinesterases (United States)


    Report No. 4 If MOLECULAR CLONING OF O HUMAN GENE(S) DIRECTING qTHE SYNTHESIS OF NERVOUS SYSTEM CHOLINESTERASES cc Annual/Final Report 0 N November...62734A I734A875 IAl 451 MOLECULAR CLONING OF HUMAN GEME(S) DIRECTING THE SYNTHESIS OF NERVOUS SYSTEM CHOLINESTERASE 12. PERSONAL AUTHOR(S) Hermona Soreq...important roles in regulating the pace and mode of function of particular types of synapses. For example, molecular cloning of the nicotinic (44-46) and the

  10. New method for the determination of the half inhibition concentration (IC50) of cholinesterase inhibitors. (United States)

    Kovárová, Markéta; Komers, Karel; Stepánková, Sárka; Parík, Patrik; Cegan, Alexander


    A new and simple analytical method is described for the determination of the IC50 values of the inhibitors of the hydrolysis of acetylcholine (ACh) or acetylthiocholine (ATCh) by cholinesterases. The method is based on monitoring the time course of the pH value during the uninhibited and inhibited reaction. It requires only a pH meter with a suitable pH measuring cell and a small thermostated stirred batch reactor. The method has been validated for twelve different types of cholinesterase inhibitors. The determined IC50 values are comparable to those obtained by independent, more complicated, and expensive methods (Ellman's and pH-stat).

  11. The Inhibitory Effect of Propranolol and Isoproterenol on Human Plasma Cholinesterase

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    Ali Awsat Mellati


    Full Text Available The effect of propranolol and isoproterenol on the hydrolysis of 4- nitrophenylbutyrate (PNPB by the purified human plasma cholinesterase was studied. During the hydrolysis of PNPB, enzyme obeyed to Michaelis-Menten model. Propranolol was found to be a competitive inhibitor, and isoproterenol yielded a complex inhibition pattern. It could be explained that the inhibitory effect of propranolol shows noncooperativity between subunits of human plasma cholinesterase upon binding of PNPB. In contrast, isoproternol inhibitory effects indicate more than one type of binding sites on this enzyme.

  12. [Change of cholinesterase relative activity under modulated ultra high frequency electromagnetic radiation in experiments in vitro]. (United States)

    Pashovkina, M S; Pashovkin, T N


    Changes in the activity of enzyme cholinesterase (ChE) have been experimentally investigated under the influence of amplitude-modulated super-high-frequency electromagnetic radiation (carrier frequency of 2.375 MHz; power flux density of 8 mW/cm2, 20 mW/cm2 and 50 mW/cm2; modulation frequency range 10 to 210 Hz; exposure time 5 min). The appearance of peaks of the cholinesterase increased relative activity, as well as the changes in the direction and intensity of the reaction associated with the modulation frequency and power flux are observed at equal power flux densities and exposure times.

  13. Crystal Structure of the Extracellular Cholinesterase-Like Domain from Neuroligin-2

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    Koehnke,J.; Jin, X.; Budreck, E.; Posy, S.; Scheiffele, P.; Hnoig, B.; Shapiro, L.


    Neuroligins (NLs) are catalytically inactive members of a family of cholinesterase-like transmembrane proteins that mediate cell adhesion at neuronal synapses. Postsynaptic neuroligins engage in Ca2+-dependent transsynaptic interactions via their extracellular cholinesterase domain with presynaptic neurexins (NRXs). These interactions may be regulated by two short splice insertions (termed A and B) in the NL cholinesterase domain. Here, we present the 3.3- Angstroms crystal structure of the ectodomain from NL2 containing splice insertion A (NL2A). The overall structure of NL2A resembles that of cholinesterases, but several structural features are unique to the NL proteins. First, structural elements surrounding the esterase active-site region differ significantly between active esterases and NL2A. On the opposite surface of the NL2A molecule, the positions of the A and B splice insertions identify a candidate NRX interaction site of the NL protein. Finally, sequence comparisons of NL isoforms allow for mapping the location of residues of previously identified mutations in NL3 and NL4 found in patients with autism spectrum disorders. Overall, the NL2 structure promises to provide a valuable model for dissecting NL isoform- and synapse-specific functions.

  14. Effects of Cholinesterase Inhibitors in Parkinson's Disease Dementia : A Review of Clinical Data

    NARCIS (Netherlands)

    van Laar, Teus; De Deyn, Peter Paul; Aarsland, Dag; Barone, Paolo; Galvin, James E.


    Aims: Cognitive impairment and dementia are common features of Parkinson's disease (PD). Patients with Parkinson's disease dementia (PDD) often have significant cholinergic defects, which may be treated with cholinesterase inhibitors (ChEIs). The objective of this review was to consider available ef

  15. Regional cholinesterase activity in white-throated sparrow brain is differentially affected by acephate (Orthene?) (United States)

    Vyas, N.B.; Kuenzel, W.J.; Hill, E.F.; Romo, G.A.; Komaragiri, M.V.S.


    Effects of a 14-day dietary exposure to an organophosphorus pesticide, acephate (acetylphosphoramidothioic acid O,S-dimethyl ester), were determined on cholinesterase activity in three regions (basal ganglia, hippocampus, and hypothalamus) of the white-throated sparrow, Zonotrichia albicollis, brain. All three regions experienced depressed cholinesterase activity between 0.5-2 ppm acephate. The regions exhibited cholinesterase recovery at 2-16 ppm acephate; however, cholinesterase activity dropped and showed no recovery at higher dietary levels (>16 ppm acephate). Evidence indicates that the recovery is initiated by the magnitude of depression, not the duration. In general, as acephate concentration increased, differences in ChE activity among brain regions decreased. Three terms are introduced to describe ChE response to acephate exposure: (1) ChE resistance threshold, (2) ChE compensation threshold, and (3) ChE depression threshold. It is hypothesized that adverse effects to birds in the field may occur at pesticide exposure levels customarily considered negligible.

  16. Potentially hazardous substances in surface waters. II. Cholinesterase inhibitors in Dutch surface waters

    NARCIS (Netherlands)

    Greve, P.A.; Freudenthal, J.; Wit, S.L.


    Several analytical methods were employed to determine the concentrations of cholinesterase inhibitors in several Dutch surface waters. An Auto-Analyzer method was used for screening purposes; thin-layer chromatography and gas-liquid chromatography-mass spectrometry were used for identification and q

  17. Design and Synthesis of Bifunctional Oxime Reactivators of OP- inhibited Cholinesterase (United States)


    military and civilian personnel. Reactivators of OP inhibited cholinesterases can serve as OP agent antidotes but can be limited by their poor...assisted bifunctional catalytic mechanism 46 O N O N OH 11 REPORTABLE OUTCOMES: None CONCLUSION: We have successfully evaluated the synthetic

  18. Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease. (United States)

    Patterson, C E; Todd, S A; Passmore, A P


    Factors that influence response to drug treatment are of increasing importance. We report an analysis of genetic factors affecting response to cholinesterase inhibitor therapy in 165 subjects with Alzheimer's disease (AD). The presence of apolipoprotein E ε4 (APOE ε4) allele was associated with early and late cognitive response to cholinesterase inhibitor treatment in mild AD (Mini-Mental State Examination (MMSE) ≥21) (P<0.01). In moderate-to-severe AD (MMSE ≤15), presence of the BCHE-K variant was associated with late response to cholinesterase inhibitor treatment (P=0.02). Testing for APOE and BCHE genotypes may be useful in therapeutic decision making.


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    Basavaraj R


    Full Text Available BACKGROUND AND OBJECTIVES: Organophosphorus compound poisoning is the most common medico toxic emergency in India the increase in pesticide use in agriculture has paralleled the increase in the use of these products for deliberate self-warm. Respiratory failure is the most common complication of OP poisoning leading to death. Early recognition and prompt ventilator support may improve survival. Owing to limited availability of resources, all OP poisoning patients are not managed in ICUs in Indian setup. It is therefore important that clinical features and criteria to predict the need for ventilator support be identified at initial examination. Hence this study was undertaken to assess the severity of organophosphorus compound poisoning both clinically by using Peradeniya scoring and by estimating serum choline esterase levels. METHODS: Cross sectional study was done at basaveswar teaching and general hospital attached to MR Medical College. Cases with history of exposure to organophosphorus compound within previous 24 hours were chosen after applying inclusion and exclusion criteria. Patients were evaluated for Peradeniya OP poisoning scale and serum cholinesterase levels for assessment of severity of poisoning. Serum cholinesterase levels and Peradeniya OP poisoning scale were studied to predict the need for ventilator support. The results were analyzed using Chi-square test. STATISTICAL ANALYSIS: It was done using pearson’s chi square test. RESULTS: In this study requirement of ventilator support was seen in 36% of patients. Mortality in our study was 18%. Only 15.6% of patients with mild grade of poisoning according to Peradeniya OP poisoning scale required ventilator support, whereas 84.4% did not require ventilator support. Most of patients with moderate (70.6% and severe poisoning (100% according to Peradeniya OP poisoning scale required ventilator support. 93.7% of patients with serum cholinesterase levels more than 50% did not require

  20. The use of cholinergic biomarker, cholinesterase activity of blue mussel Mytilus edulis to detect the effects of organophosphorous pesticides


    Yaqin, Khusnul


    The aim of the study was to investigate the effects of organophosphorous pesticide on the cholinesterase activity of different organs of Mytilus edulis. The mussels were exposed to serial dilutions of the pesticides (0, 50, 100, 200, 500, and 1000 ??g/l) for 96 h. A significant inhibition of the cholinesterase activity from gill occurred at the lowest concentration, which indicated that gill was the most sensitive organ. The moderate sensitive organs were foot and mantle, which we...

  1. Pesticide use and cholinesterase inhibition in small-scale agricultural workers in southern Brazil

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    Samuel Botião Nerilo


    Full Text Available A controlled cross-sectional study of family growers of fruit and vegetables was conducted between October 2009 and October 2010 to characterize the use of pesticides, establish the socio-demographic profile, and analyze cholinesterase activity in small-scale agricultural workers in Southern Brazil. Data was collected for 173 workers and 179 controls. A structured questionnaire was applied collecting socio-demographic information and determining knowledge and work practices in relation to pesticide use. The benchmarks for total cholinesterase (ChEs and butyrylcholinesterase (BuChE were obtained from the average enzymatic activity of the occupationally unexposed group (control. The mean age of the exposed population was 40.0 ± 11.2 years. The symptoms differed significantly (p30% of ChEs activity, whereas no workers showed high inhibition (>50% of BuChE. Potential factors involved include gender, education, pesticide orientation, exposure, and hygiene measures.

  2. The Multileveled Regulation of the Human Cholinesterase Genes and Their Protein Products (United States)


    present in all members of the Solanua plant family, including Solanin tuberosa (potatoes), and are likely to be present in extremely high and toxic ...and solanine -derived alkaloids 120 33. Conservation of substrate specificity and loss of substrate activation in AChE-BuChE chimera 121 34. Inhibition...for inhibition of the insect enzyme, with particular emphasis on low toxicity to humans. In addition, cholinesterase (ChZ) inhibitors are employed

  3. Serum and Plasma Cholinesterase Activity in the Cape Griffon Vulture (Gyps coprotheres). (United States)

    Naidoo, Vinny; Wolter, Kerri


    Vulture (Accipitridae) poisonings are a concern in South Africa, with hundreds of birds dying annually. Although some of these poisonings are accidental, there has been an increase in the number of intentional baiting of poached rhinoceros (Rhinocerotidae) and elephant (Elephantidae) carcasses to kill vultures that alert officials to poaching sites by circling overhead. The primary chemicals implicated are the organophosphorous and carbamate compounds. Although most poisoning events can be identified by dead vultures surrounding the scavenged carcass, weak birds are occasionally found and brought to rehabilitation centers for treatment. The treating veterinarian needs to make an informed decision on the cause of illness or poisoning prior to treatment. We established the reference interval for serum and plasma cholinesterase activity in the Cape Griffon Vulture ( Gyps coprotheres ) as 591.58-1,528.26 U/L, providing a clinical assay for determining potential exposure to cholinesterase-depressing pesticides. Both manual and automated samplers were used with the butyrylthiocholine method. Species reference intervals for both serum and plasma cholinesterase showed good correlation and manual and automated measurements yielded similar results.

  4. In vitro antioxidant, cholinesterase and tyrosinase inhibitory activities of Calophyllum symingtonianum and Calophyllum depressinervosum (Guttiferae)

    Institute of Scientific and Technical Information of China (English)

    Nurul Iman Aminudin; Farediah Ahmad; Muhammad Taher


    Objective:To screen the antioxidant, cholinesterase and tyrosinase enzymatic inhibition activities of the leaves and heartwood of Calophyllum symingtonianum (C. symingtonianum), and the bark of Calophyllum depressinervosum (C. depressinervosum). Methods: Samples of leaves and heartwood of C. symingtonianum and bark of C. depressinervosum were tested for their total phenolic content and in vitro antioxidant assay by 2,2-diphenyl-1-picrylhydrazyl radical scavenging andβ-carotene bleaching. Cholinesterase inhibition by Ellman’s method and tyrosinase inhibition using L-3,4-dihydroxyphenylalanine as a substrate were also tested. Results:All methanol extracts were found to exhibit strong 2,2-diphenyl-1-picrylhydrazyl radical scavenging effects. Extracts from the heartwood of C. symingtonianum gave a low IC50 (5.17±0.04) µg/mL followed by bark of C. depressinervosum [(7.30±0.14) µg/mL] and C. symingtonianum leaves [(15.70±1.43) µg/mL]. The methanol extract of C. depressinervosum bark showed 95.08% inhibition of β-carotene bleaching. All extracts showed moderate inhibition towards tyrosinase activity with an IC50 of more than 100 µg/mL. The methanol extract of C. depressinervosum stem bark showed the highest inhibition (78.46%) against butyrylcholinesterase. Conclusions:These results showed that both Calophyllum species are potential sources of antioxidant and cholinesterase inhibitors. Further study is needed for the isolation and characterization of the active metabolites responsible for both activities.

  5. Determination of cholinesterase levels of the employees working at the pharmaceutical sector and the patients suspected of being poisoned

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    Serdar Alp Suba��ı


    Full Text Available OBJECTIVE: The purpose of this work is measure tests using butyrylthiocholine as a substract and get the spectrofotometric results for dispersion level of Cholinesterase in people who is working in the pharmaceutical and agriculture sector, were chronicly affected bypesticide or patiences who are suspected to be poisoned by pesticide, who applied for the Consumer Safety Health Effects Research Laboratories RSHMB biological material lab, Ankara during the period 2008-2010.METHODS: The blood samples were analyzed by the biological materials laboratory. The plasmas Cholinesterase levels were measured with the kits Cholinesterase, butyrylthiocholine kinetic, Spınreact between 01.01.2008 - 17.07.2010; after 17.07.2010 Cholinesterase, butyrylthiocholine substrate, (Quimica clinica aplıcada S.A. The plazmas were seperated from the blood samples and preoperate on them with the spectrofotometric methods under the room temperature of 405nm and Cholinesterase, levels measured by quantitative analysed methodRESULTS: Evidence: In this research 1136 people whose Cholinesterase levels tested; applied to our center because of pestisit toxication. 367 (32,3 % were the ones who works for the pharmaceutical sector and intended to be under control, 769 (67,7% were the ones prediagnoised as poisoned. It has been detected that 222 (28,9% of them were in safe serum Cholinesterase measurement range. 119 (53,6 % of these people were women and majority of them 56 (25,2 % is in 10-19 age group. 347 (94,6 % people who is working either in the pharmaceutical or agriculture sector were in normal range and just 20 (5,4 % of them were in the toxicty range. The intoxicated workers were in the age group of 30-39.CONCLUSION: The Cholinesterase level of the persons, who sprayed or werepoisoned by insecticide containing organophosphate, is of utmost importance.In our research 547 patiente (71,1 % and 347 workers (94,6% were in normal range of cholinesterase level. This results

  6. Cholinesterase-inhibiting and genotoxic effects of acute carbofuran intoxication in man: a case report. (United States)

    Zeljezic, Davor; Vrdoljak, Ana Lucic; Kopjar, Nevenka; Radic, Bozica; Milkovic Kraus, Sanja


    Carbofuran belongs to the group of N-methylcarbamate insecticides used for the control of soil-dwelling and foliar-feeding insects in various crops; its consumption totals approximately 20,000 tonnes per year. Although the neurological effects on human beings have been well documented, little is known on its impact on the genome. A 38-year-old, healthy male worker employed in a carbofuran production facility accidentally inhaled the dust of the active ingredient carbofuran. Thirty minutes later, he experienced weakness, fatigue, perspiration, breathing difficulties, cephalalgia, disorientation, abdominal pain and vomiting. Blood samples were taken to measure cholinesterase activity, and to perform the alkaline comet assay and micronucleus assay combined with pancentromeric probes. Analyses were repeated 72 hr after intoxication and compared with the results obtained from regular monitoring conducted 10 days prior to the accident. Cholinesterase activity showed the highest correlation with the number of apoptotic cells, comet assay tail length, and number of long-tailed nuclei, suggesting that these are the genomic end-points primarily affected by carbofuran intake. Only a weak correlation was detected for the total number of micronuclei, centromere-containing micronuclei and nuclear buds. Since those end-points increased significantly 72 hr after the accident, they could be considered as late biomarkers of the effects of carbofuran intoxication. The results of this report suggest that, in the interests of higher standards in risk assessment and health hazard protection, periodical medical examination of carbamate-exposed populations should include genotoxicity testing in addition to the assessment of cholinesterase activity.

  7. Cholinesterase Activity in Health Workers Involved in Handling and Spraying of Organophosphorous Insecticides

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    Himanshu Madaan


    Full Text Available Background: Recent era of agricultural boon is partially the result of extensive use of insecticides and pesticides. But these compounds also have potential to significantly alter the ecosystem and can cause acute poisonings as well as long term detrimental health effects in humans. These compounds can cause toxicity through all routes of exposure. They exert their effect mainly by the inhibition of Acetylcholinesterase (AC hE, which functions by removing acetylcholine (AC h from its postsynaptic receptors. Aims and Objectives: Human exposure to Organophosphorous (OP pesticides can develop lowered cholinesterase levels. The aim of the present study was to estimate the plasma levels of AC hE in personnel involved in handling of these compounds, during the period of active spraying operations. Methodology: The present study was conducted on 38 subjects working as Multipurpose Health Workers (MPHW GROUP-1 and Field Workers (FW GROUP-2 involved in the actual spraying of the insecticides, in District Rohtak, Haryana, India to see the effect of exposure to OP insecticides. Plasma cholinesterase activity was measured by a kinetic method based on hydrolysis of butrylthiocholine. The data was statistically analyzed using SPSS statistical package (SPSS version 5.0. Results and interpretation: The mean cholinesterase activity in group-2 was lower by 27.76% than that in group-1 and this difference was statistically significant (p < 0.05. The workers involved in actual spraying of the insecticides had a more marked reduction in the levels of Plasma AC hE, compared to the workers involved only in the handling of the insecticides indicating that this group is at a bigger risk.

  8. Cholinesterase inhibition of birds inhabiting wheat fields treated with methyl parathion and toxaphene (United States)

    Niethammer, K.R.; Baskett, T.S.


    Red-winged blackbirds (Agelaius phoeniceus) and dickcissels (Spiza americana) inhabiting wheat fields treated with 0.67 kg AI/ha methyl parathion and 1.35 kg AI/ha toxaphene showed brain cholinesterase (ChE) inhibition compared with birds inhabiting untreated fields. Maximum inhibition occurred about five days after insecticide application. ChE activities again approached normal 10 days after treatment. ChE inhibition for dickcissels and red-winged blackbirds differed significantly (p<0.05); maximum inhibition for the former species was 74%, and for the latter, 40%. These differences could not be explained by the diets of the two species, as they were similar.

  9. Characterization and in vitro sensitivity of cholinesterases of gilthead seabream (Sparus aurata) to organophosphate pesticides. (United States)

    Albendín, G; Arellano, J M; Mánuel-Vez, M P; Sarasquete, C; Arufe, M I


    The characterization of cholinesterase activity in brain and muscle of gilthead seabream was carried out using four specific substrates and three selective inhibitors. In addition, K m and V max were calculated from the Michaelis-Menten equation for ASCh and BSCh substrates. Finally, the in vitro sensitivity of brain and muscle cholinesterases to three organophosphates (OPs) was also investigated by estimating inhibition kinetics. The results indicate that AChE is the enzyme present in the brain, whereas in muscle, a typical AChE form is present along with an atypical form of BChE. Very low ChE activity was found in plasma with all substrates used. The inhibitory potency of the studied OPs on brain and muscle AChEs based on bimolecular inhibition constants (k i ) was: omethoate < dichlorvos < azinphosmethyl-oxon. Furthermore, muscle BChE was found to be several orders of magnitude (from 2 to 4) more sensitive than brain and muscle AChE inhibition by dichlorvos and omethoate.

  10. Chemical and molecular aspects on interactions of galanthamine and its derivatives with cholinesterases. (United States)

    Gulcan, Hayrettin O; Orhan, Ilkay E; Sener, Bilge


    Dual action of galanthamine as potent cholinesterase inhibitor and nicotinic modulator has attracted a great attention to be used in the treatment of AD. Consequently, galanthamine, a natural alkaloid isolated from a Galanthus species (snowdrop, Amaryllidaceae), has become an attractive model compound for synthesis of its novel derivatives to discover new drug candidates. Numerous studies have been done to elucidate interactions between galanthamine and its different derivatives and the enzymes; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using in vitro and in silico experimental models. The in vitro studies revealed that galanthamine inhibits AChE in strong, competitive, long-acting, and reversible manner as well as BChE, although its selectivity towards AChE is much higher than BChE. The in silico studies carried out by employing molecular docking experiments as well as molecular dynamics simulations pointed out to existence of strong interactions of galanthamine with the active gorge of AChE, mostly of Torpedo californica (the Pasific electric ray) origin. In this review, we evaluate the mainstays of cholinesterase inhibitory action of galanthamine and its various derivatives from the point of view of chemical and molecular aspects.

  11. Synthesis, cholinesterase inhibition and molecular modelling studies of coumarin linked thiourea derivatives. (United States)

    Saeed, Aamer; Zaib, Sumera; Ashraf, Saba; Iftikhar, Javeria; Muddassar, Muhammad; Zhang, Kam Y J; Iqbal, Jamshed


    Alzheimer's disease is among the most widespread neurodegenerative disorder. Cholinesterases (ChEs) play an indispensable role in the control of cholinergic transmission and thus the acetylcholine level in the brain is enhanced by inhibition of ChEs. Coumarin linked thiourea derivatives were designed, synthesized and evaluated biologically in order to determine their inhibitory activity against acetylcholinesterases (AChE) and butyrylcholinesterases (BChE). The synthesized derivatives of coumarin linked thiourea compounds showed potential inhibitory activity against AChE and BChE. Among all the synthesized compounds, 1-(2-Oxo-2H-chromene-3-carbonyl)-3-(3-chlorophenyl)thiourea (2e) was the most potent inhibitor against AChE with an IC50 value of 0.04±0.01μM, while 1-(2-Oxo-2H-chromene-3-carbonyl)-3-(2-methoxyphenyl)thiourea (2b) showed the most potent inhibitory activity with an IC50 value of 0.06±0.02μM against BChE. Molecular docking simulations were performed using the homology models of both cholinesterases in order to explore the probable binding modes of inhibitors. Results showed that the novel synthesized coumarin linked thiourea derivatives are potential candidates to develop for potent and efficacious acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors.

  12. Evaluation of Antioxidant, Anti-cholinesterase, and Anti-inflammatory Effects of Culinary Mushroom Pleurotus pulmonarius (United States)

    Nguyen, Trung Kien; Im, Kyung Hoan; Choi, Jaehyuk; Shin, Pyung Gyun


    Culinary mushroom Pleurotus pulmonarius has been popular in Asian countries. In this study, the anti-oxidant, cholinesterase, and inflammation inhibitory activities of methanol extract (ME) of fruiting bodies of P. pulmonarius were evaluted. The 1,1-diphenyl-2-picryl-hydrazy free radical scavenging activity of ME at 2.0 mg/mL was comparable to that of butylated hydroxytoluene, the standard reference. The ME exhibited significantly higher hydroxyl radical scavenging activity than butylated hydroxytoluene. ME showed slightly lower but moderate inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase than galantamine, a standard AChE inhibitor. It also exhibited protective effect against cytotoxicity to PC-12 cells induced by glutamate (10~100 µg/mL), inhibitory effect on nitric oxide (NO) production and inducible nitric oxide synthase protein expression in lipopolysaccharide-stimulated RAW 264.7 macrophages, and carrageenan-induced paw edema in a rat model. High-performance liquid chromatography analysis revealed the ME of P. pulmonarius contained at least 10 phenolic compounds and some of them were identified by the comparison with known standard phenolics. Taken together, our results demonstrate that fruiting bodies of P. pulmonarius possess antioxidant, anti-cholinesterase, and inflammation inhibitory activities.

  13. Radiometric assay of red cell and plasma cholinesterase in pesticide appliers from Minnesota. (United States)

    Potter, W T; Garry, V F; Kelly, J T; Tarone, R; Griffith, J; Nelson, R L


    In this study we demonstrate the uses of radiometric assay to detect anticholinesterases in a human population (N = 80) exposed to a broad spectrum of pesticides. The assay is nondilutional. Therefore, anticholinesterase (AChE) agents with low binding affinity can be detected. Our initial results show statistically significant exposure-related decreases in either red cell (AChE) or plasma cholinesterase activity ((butyrl)cholinesterase; BuChE) occurred not only among pesticide appliers who use organophosphates, but also among appliers of the fumigant phosphine. These data extend earlier observations made in laboratory animals exposed to this fumigant. Significant exposure-related decreases in AChE activity were seen in herbicide appliers and appear to be associated with exposure to the herbicide 2-methoxy-3,6-dichlorobenzoic acid. There was no evidence of exposure-related decreases in BuChE activity in herbicide appliers. Our in vivo data, coupled with preliminary in vitro studies of phosphine (50% AChE inhibition, 10 ppm) and 2-methoxy-3,6-chlorobenzoic acid (50% AChE and BuChE inhibition, 70 ppm), suggest that the radiometric assay may be used to detect a broader spectrum of biologically active anticholinesterase agents.

  14. Use of cholinesterase activity in monitoring organophosphate pesticide exposure of cattle produced in tropical areas. (United States)

    Pardío, V T; Ibarra, N; Rodríguez, M A; Waliszewski, K N


    The use of cholinesterase activity as a biochemical method for monitoring organophosphate pesticide exposure in cattle is described herein. Determination of cholinesterase activity of whole blood, erythrocyte, and plasma was carried out according to the Ellman modified kinetic method. The mean baseline acetylcholinesterase activities of 9.549 +/- 3.619 IU/mL in whole blood, 9.444 +/- 3.006 IU/mL in erythrocytes, and 0.149 +/- 0.063 IU/mL in plasma were estimated for steers from the control group. Results of multivariate analysis showed that the general responses between the control and experimental groups (in vivo, monitoring and case studies) treated with Coumaphos and Fenthion were statistically different, and the general responses of these experimental groups were statistically different over time as well. Among the fractions that were analyzed, the erythrocyte acetylcholinesterase activity could be adequate for the diagnosis of exposure or acute poisoning in cattle as it showed a good within-run and between-run precision with CVs <10% better than those in plasma.


    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); ...


    Carbaryl is a widely used N-methyl carbamate pesticide that acts by inhibiting cholinesterases (ChE), which may lead to cholinergic toxicity. Flash evoked potentials (FEPs) are a neurophysiological response often used to detect central nervous system (CNS) changes following expos...

  17. Cholinesterase inhibitors and add-on nutritional supplements in Alzheimer's disease: a systematic review of randomized controlled trials. (United States)

    Rijpma, A; Meulenbroek, O; Olde Rikkert, M G M


    To date, single drug and nutrient-based interventions have failed to show a clinically relevant effect on Alzheimer's disease (AD). Multidomain interventions may alleviate symptoms and alter the disease course in a synergistic manner. This systematic review examines the effect of adding nutritional supplementation to cholinesterase inhibitors. A systematic PubMed and Cochrane search resulted in nine high quality studies. The studies had low to moderate risk of bias and focused on oxidative stress, homocysteine levels, membrane fluidity, inflammation and acetylcholine levels. Only the use of vitamin E supplements could reduce the rate of functional decline when combined with cholinesterase inhibitors in one study, whereas cognition was not affected in both this and other studies. None of the other nutritional supplements showed convincing evidence of a beneficial effect when combined with cholinesterase inhibitors. This shows that cognitive and functional improvement is difficult to achieve in patients with AD, despite epidemiological data and evidence of biological effects of nutritional supplements. Addressing one disease pathway in addition to cholinesterase inhibitor therapy is probably insufficient to alter the course of the disease. Personalized, multifactorial interventions may be more successful in improving cognition and daily functioning.

  18. Cholinesterase as inflammatory markers in a experimental infection by Trypanosoma evansi in rabbits

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    Márcio M. Costa


    Full Text Available The aim of this study is to evaluate the role of cholinesterases as an inflammatory marker in acute and chronic infection by Trypanosoma evansi in rabbits experimentally infected. Twelve adult female New Zealand rabbits were used and divided into two groups with 6 animals each: control group (rabbits 1-6 and infected group (rabbits 7-12. Infected group received intraperitoneally 0.5 mL of blood from a rat containing 108 parasites per animal. Blood samples used for cholinesterases evaluation were collected on days 0, 2, 7, 12, 27, 42, 57, 87, 102 and 118 days post-inoculation (PI. Increased activity (P0.05 was observed in the encephalic structures. The increased activities of AChE and BChE probably have a pro-inflammatory purpose, attempting to reduce the concentration of acetylcholine, a neurotransmitter which has an anti-inflammatory property. Therefore, cholinesterase may be inflammatory markers in infection with T. evansi in rabbits.O objetivo do presente estudo é avaliar o papel das colinesterases como marcadores inflamatórios nas fases aguda e crônica da infecção por T. evansi em coelhos infectados experimentalmente. Foram utilizados 12 coelhos adultos, fêmeas, da raça Nova Zelândia, divididos em dois grupos: um grupo controle, com seis animais (coelhos 1-6, e um grupo infectado, com seis animais (coelhos 7-12. Os animais pertencentes ao grupo infectados receberam, pela via intraperitoneal, 0,5 mL de sangue de rato contendo 108 tripanossomas por animal. Amostras do sangue utilizado para avaliação das colinesterases foram coletadas nos dias 0, 2, 7, 12, 27, 42, 57, 87, 102 e 118 pós-inoculação (PI. Aumento (P0,05 foi observada nas estruturas encefálicas. O aumento de atividade da AChE e BChE provavelmente tenha finalidade pró-inflamatória, a fim de reduzir as concentrações de acetilcolina, neurotransmissor que apresenta propriedade anti-inflamatória. Portanto, as colinesterases podem ser marcadores inflamatórios na infec

  19. Effects of repeated exposure of diazinon on cholinesterase activity and growth in snakehead fish (Channa striata). (United States)

    Cong, Nguyen Van; Phuong, Nguyen Thanh; Bayley, Mark


    The organophosphate insecticide diazinon is widely used in the Mekong river delta and often applied several times per rice crop. In the present study, juvenile snakehead fish Channa striata, which is a commercially important inhabitant of rice fields, were exposed twice to 4-day pulses of 0.016, 0.079 or 0.35mg/L of diazinon, separated by a 2 week interval to imitate the exposure conditions in the field. After the 4-day exposures to these environmentally realistic concentrations, the fish were moved to clean water for recovery. During this experiment, which lasted a total of 2 months, the individual growth rates and brain cholinesterase levels were measured. We show not only that diazinon caused long term inhibition of brain ChE activity, which was still significantly depressed at the termination of the experiment, but also that the highest of these realistic concentrations caused a significant 30% growth inhibition.

  20. Bisquaternary oximes as reactivators of tabun-inhibited human brain cholinesterases: an in vitro study. (United States)

    Kuca, Kamil; Jun, Daniel; Cabal, Jiri; Musilova, Lucie


    Intoxications caused by tabun nerve agent are generally very hard to treat by convential acetylcholinesterase (AChE) reactivators. Due to this, new AChE reactivators are still developed. In this study, we have tested three new promising bisquaternary AChE reactivators: K027, K033 and K048. These reactivators were previously tested on rat brain homogenate. To mimic reality, we studied the potency of these new oximes to reactivate tabun-inhibited human brain cholinesterases. As is evident from the results, reactivator K048 (reactivation 40%) surpassed all reactivators tested in this study [including the most promising ones, namely trimedoxime (37%) and obidoxime (33%)]. Moreover, if compared to our previous results from rat brain studies, species differences were demonstrated.

  1. Analysis of Amaryllidaceae alkaloids from Zephyranthes grandiflora by GC/MS and their cholinesterase activity

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    Lucie Cahlíková


    Full Text Available Amaryllidaceae are known as ornamental plants, furthermore some species of this family contain galanthamine, an acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease, and other alkaloids with interesting pharmacological activity. The chemical composition of alkaloids from Zephyranthes grandiflora Lindl. was analyzed by GC/MS. Seven known compounds, belonging to five structural types of Amaryllidaceae alkaloids, were identified. The alkaloid extract from the bulbs showed promising cholinesterase inhibitory activities against human blood acetylcholinesterase (HuAChE; IC50 39.2±3.0 µg/mL and human plasma butyrylcholinesterase (HuBuChE; IC50 356±9.3 µg/mL.

  2. Cholinesterase-inhibitory diterpenoids and chemical constituents from aerial parts of Caryopteris mongolica. (United States)

    Murata, Toshihiro; Selenge, Erdenechimeg; Oikawa, Saki; Ageishi, Keita; Batkhuu, Javzan; Sasaki, Kenroh; Yoshizaki, Fumihiko


    A diterpenoid diglucoside (12,19-di-O-β-D-glucopyranosyl-11-hydroxyabieta-8,11,13-triene-19-one), isoscutellarein 7-O-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranoside, isoscutellarein 7-O-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside, hypolaetin 7-O-[6″-O-(p-E-coumaroyl)]-β-D-glucopyranoside, hypolaetin 7-O-[6″-O-(E-caffeoyl)]-β-D-glucopyranoside, and 15 known compounds were isolated from aerial parts of the Mongolian medicinal plant Caryopteris mongolica. The cholinesterase-inhibitory activities of the constituents were estimated. The abietane diterpenoids (12-O-demethylcryptojaponol and 6α-hydroxydemethylcryptojaponol) showed potent inhibitory activity against acetylcholinesterase from human erythrocytes and electric eel, and against butyrylcholinesterase from horse serum.

  3. Cholinesterase inhibitory activity and chemical constituents of Stenochlaena palustris fronds at two different stages of maturity

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    Nelson Jeng-Yeou Chear


    Full Text Available Stenochlaena palustris fronds are popular as a vegetable in Southeast Asia. The objectives of this study were to evaluate the anticholinesterase properties and phytochemical profiles of the young and mature fronds of this plant. Both types of fronds were found to have selective inhibitory effect against butyrylcholinesterase compared with acetylcholinesterase. However, different sets of compounds were responsible for their activity. In young fronds, an antibutyrylcholinesterase effect was observed in the hexane extract, which was comprised of a variety of aliphatic hydrocarbons, fatty acids, and phytosterols. In the mature fronds, inhibitory activity was observed in the methanol extract, which contained a series of kaempferol glycosides. Our results provided novel information concerning the ability of S. palustris to inhibit cholinesterase and its phytochemical profile. Further research to investigate the potential use of this plant against Alzheimer's disease is warranted, however, young and mature fronds should be distinguished due to their phytochemical differences.

  4. Diazinon concentrations and blood cholinesterase activities in rats exposed to diazinon. (United States)

    Tomokuni, K; Hasegawa, T


    The tissue distribution of diazinon and the inhibition of blood cholinesterase (ChE) activity were investigated in male rats which received a single intraperitoneal (i.p.) dose of diazinon (100 mg/kg body wt) in olive oil. Diazinon concentration in the blood reached a maximum 1-2 h after dosing. Comparing the distribution of diazinon among liver, kidney and brain in treated rats, the diazinon residue was much greater in the kidney than in other organs, being 500 times that in the liver and 11 times that in the brain at 8 h after dosing. Erythrocyte and plasma ChE activities were inhibited rapidly, but ChE inhibition was greater in the erythrocytes than in plasma.

  5. Action of the herbicide butachlor on cholinesterases in the freshwater snail Pila globosa (Swainson). (United States)

    Rajyalakshmi, T; Srinivas, T; Swamy, K V; Prasad, N S; Mohan, P M


    Butachlor action on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activates in central nervous tissue of the snail Pila globosa was assayed following the method of ELLMAN et al1, in vitro by adding butachlor directly (10-100 mu moles), to tissue homogenates and in in vivo by exposing the snails to sub-lethal concentration (26.6 ppm) and taking out the tissue for experimentation at different intervals (3, 6, 12, 24 and 48 h) of exposure. The enzyme activities decreased in a dose-dependent manner in vitro, and up to 12-24 h in vivo after which they showed recovery towards the control. The inhibition of cholinesterases by butachlor in vitro indicates a direct action of the herbicide on these enzymes. Presumably butachlor exercises its neurotoxic effects through cholinergic impairment in a way similar to that of organophosphates and carbamates.

  6. Diagnosis of anticholinesterase poisoning in birds: Effects of environmental temperature and underfeeding on cholinesterase activity (United States)

    Rattner, B.A.


    Brain cholinesterase (ChE) activity has been used extensively to monitor exposure to organophosphorus (OP) and carbamate (CB) insecticides in wild birds. A series of factorial experiments was conducted to assess the extent to which noncontaminant-related environmental conditions might affect brain ChE activity and thereby confound the diagnosis of OP and CB intoxication. Underfeeding (restricting intake to 50% of control for 21 d or fasting for 1-3 d) or exposure to elevated temperature (36 + 1?C for 1 d) caused only slight reductions (10-17%) in brain AChE activity in adult male Japanese quail (Coturnix coturnix japonica). This degree of 'reduction' in brain AChE activity is considerably less than the 50% 'inhibition' criterion employed in the diagnosis of insecticide-induced mortality, but nevertheless approaches the 20% 'inhibition' level used as a conservative estimate of sublethal exposure to a known insecticide application.

  7. Temperature: a prolonged confounding factor on cholinesterase activity in the tropical reef fish Acanthochromis polyacanthus. (United States)

    Botté, Emmanuelle S; Smith-Keune, Carolyn; Jerry, Dean R


    Cholinesterase activity usually decreases in fish exposed to anticholinesterase compounds such as organophosphate and carbamate pesticides. Here we show that tropical reef fish Acanthochromis polyacanthus (or spiny damsel) also exhibits a decrease in ChE activity when exposed to elevated temperature from 28°C to 32°C or 34°C after 4 days. We further demonstrate that the decline persists even after 7 days of recovery at control temperature. This is the first report of a drop in ChE activity in fish as temperature increases. Our results strongly suggest the need for long-term monitoring of water temperature in the field prior to sampling A. polyacanthus for toxicology studies, as temperature is a prolonged and confounding factor for ChE activity in this species.

  8. Sex and storage affect cholinesterase activity in blood plasma of Japanese quail (United States)

    Hill, E.F.


    Freezing at -25?C had confounding effects on cholinesterase (ChE) activity in blood plasma from breeding female quail, but did not affect ChE activity in plasma from males. Plasma ChE activity of control females increased consistently during 28 days of storage while both carbamate- and cidrotophos-inhibited ChE decreased. Refrigeration of plasma at 4?C for 2 days had little effect of ChE activity. Plasma ChE activity was averaged about 34% higher in breeding males than in females. Extreme caution should be exercised in use of blood plasma for evaluation of anti ChE exposure in free-living birds.

  9. Cholinesterase activity in gilthead seabream (Sparus aurata) larvae: Characterization and sensitivity to the organophosphate azinphosmethyl. (United States)

    Arufe, M Isabel; Arellano, Juana M; García, Leticia; Albendín, Gemma; Sarasquete, Carmen


    Assessment of cholinesterase (ChE) inhibition is widely used as a specific biomarker for evaluating the exposure and effects of non-target organisms to anticholinesterase agents. Cholinesterase and carboxylesterase activities have been measured in larvae of gilthead seabream, Sparus aurata, during the endogenous feeding stage, and ChE was characterized with the aid of diagnostic substrates and inhibitors. The results of the present study showed that whole-body ChE of yolk-sac seabream larvae possesses typical properties of acetylcholinesterase (AChE) with a apparent affinity constant (K(m)) of 0.163+/-0.008 mM and a maximum velocity (V(max)) of 332.7+/-2.8 nmol/min/mg protein. Moreover, sensibility of this enzyme was investigated using the organophosphorus insecticide azinphosmethyl. Static-renewal toxicity tests were conducted over 72 h and larval survival and AChE inhibition were recorded. Mean mortality of seabream larvae increased with increasing concentrations of azinphosmethyl and exposure duration. The estimated 72-h LC50 value to azinphosmethyl was 4.59 microg/l (95% CI=0.46-8.71 microg/l) and inhibition of ChE activity gave an IC50 of 3.04 microg/l (95% CI=2.73-3.31 microg/l). Larvae exposed to azinphosmethyl for 72h showed a 70% inhibition of the whole-body acetylcholinesterase activity at approximately the LC50. In conclusion, the results of the present study suggested that monitoring ChE activity is a valuable tool indicating OP exposure in S. aurata larvae and that acetylthiocholine is the most appropriate substrate for assessing ChE inhibition in this early-life stage of the fish.

  10. Cholinesterase inhibition and behavioral toxicity of carbofuran on Oreochromis niloticus early life stages. (United States)

    Pessoa, P C; Luchmann, K H; Ribeiro, A B; Veras, M M; Correa, J R M B; Nogueira, A J; Bainy, A C D; Carvalho, P S M


    Nile tilapia Oreochromis niloticus at 9 days post-hatch were exposed in semi-static experiments to the carbamate insecticide carbofuran, which is applied in agricultural systems in Brazil. Although the molecular mechanism of carbofuran toxicity is well known, a detailed understanding of the ecological mechanisms through which carbofuran effects can propagate towards higher levels of biological organization in fish is incomplete. Mortality rates were quantified for larvae exposed for 96 h to 8.3, 40.6, 69.9, 140, 297 and 397 μg/L carbofuran, and the LC(50) 96 h was 214.7 μg/L. In addition, the biochemical biomarker cholinesterase inhibition and behavioral biomarkers related to vision, swimming, prey capture and predator avoidance were quantified in individual larvae, as well as their growth in weight. The behavioral parameters were quantified by analysis of digitally recorded videos of individual larvae within appropriate experimental setups. The activity of the enzyme cholinesterase decreased after exposure to carbofuran with a lowest observed effects concentration (LOEC) of 69.9 μg/L. Visual acuity deficits were detected after carbofuran exposure with a LOEC of 40.6 μg/L. Swimming speed decreased with carbofuran exposure, with a LOEC of 397.6 μg/L. The number of attacks to prey (Daphnia magna nauplii) decreased in larvae exposed to carbofuran, with a LOEC of 397.6 μg/L. Growth in weight was significantly reduced in a dose dependent manner, and all carbofuran groups exhibited a statistically significant decrease in growth when compared to controls (pcarbofuran, and the LOEC was 69.9 μg/L. These results show that exposure of sensitive early life stages of tilapia O. niloticus to sublethal concentrations of carbofuran can affect fundamental aspects of fish larval ecology that are relevant to recruitment of fish populations, and that can be better understood by the application of behavioral biomarkers.

  11. Salvia leriifolia Benth (Lamiaceae) extract demonstrates in vitro antioxidant properties and cholinesterase inhibitory activity. (United States)

    Loizzo, Monica R; Tundis, Rosa; Conforti, Filomena; Menichini, Federica; Bonesi, Marco; Nadjafi, Farsad; Frega, Natale Giuseppe; Menichini, Francesco


    The object of the present study was to investigate the in vitro antioxidant properties and cholinesterase inhibitory activity of Salvia leriifolia Benth extracts and fractions. The functional role of herbs and spices and their constituents is a hot topic in food-related plant research. Salvia species have been used since ancient times in folk medicine for cognitive brain function and have been subjected to extensive research. Thus, we hypothesize that S leriifolia, because of its functional properties, would be a good candidate to use as a nutraceutical product for improving memory in the elderly or patients affected by Alzheimer disease (ad). To test this hypothesis, we examined the cholinesterase inhibitory activity using the modified colorimetric Ellman's method against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The n-hexane exhibited the highest activity, with inhibitory concentration 50% (IC(50)) values of 0.59 and 0.21 mg/mL, for AChE and BChE, respectively. This extract was fractionated, and 9 of these fractions (A-I) were obtained and tested. Fraction G, characterized by the presence of sesquiterpenes as major components, was the most active against AChE (IC(50) = 0.05 mg/mL). Because oxidative stress is a critical event in the pathogenesis of AD, we decided to screen the antioxidant activity (AA) using 2,2-diphenyl-1-picrylhydrazyl test, β-carotene bleaching test, and bovine brain peroxidation (thiobarbituric acid) assay. The ethyl acetate extract showed the highest activity, with IC(50) values of 2 and 33 μg/mL on β-carotene bleaching test and thiobarbituric acid test, respectively. These results suggest potential health benefits of S leriifolia extracts. However, this finding requires additional investigation in vivo.

  12. Cholinesterase reactivators: the fate and effects in the organism poisoned with organophosphates/nerve agents. (United States)

    Bajgar, J; Kuca, K; Jun, D; Bartosova, L; Fusek, J


    Understanding the mechanism of action of organophosphates (OP)/nerve agents -- irreversible acetylcholinesterase (AChE, EC inhibition at the cholinergic synapses followed by metabolic dysbalance of the organism -- two therapeutic principles for antidotal treatment are derived. The main drugs are anticholinergics that antagonize the effects of accumulated acetylcholine at the cholinergic synapses and cholinesterase reactivators (oximes) reactivating inhibited AChE. Anticonvulsants such as diazepam are also used to treat convulsions. Though there are experimental data on a good therapeutic effects of reactivators, some attempts to underestimate the role of reactivators as effective antidotes against OP poisoning have been made. Some arguments on the necessity of their administration following OP poisoning are discussed. Their distribution patterns and some metabolic and pharmacological effects are described with the aim to resolve the question on their effective use, possible repeated administration in the treatment of OP poisoning, their peripheral and central effects including questions on their penetration through the blood brain barrier as well as a possibility to achieve their effective concentration for AChE reactivation in the brain. Reactivation of cholinesterases in the peripheral and central nervous system is described and it is underlined its importance for the survival or death of the organism poisoned with OP. Metabolization and some other effects of oximes (not connected with AChE reactivation) are discussed (e.g. forming of the phosphonylated oxime, parasympatholytic action, hepatotoxicity, behavioral changes etc.). An universality of oximes able to reactivate AChE inhibited by all OP is questioned and therefore, needs of development of new oximes is underlined.

  13. Hepatic cholinesterase of laying hens naturally infected by Salmonella Gallinarum (fowl typhoid). (United States)

    Da Silva, Aleksandro S; Boiago, Marcel M; Bottari, Nathieli B; do Carmo, Guilherme M; Alves, Mariana Sauzen; Boscato, Carla; Morsch, Vera M; Schetinger, Maria Rosa C; Casagrande, Renata A; Stefani, Lenita M


    Salmonella is a facultative intracellular pathogen that may cause foodborne gastroenteritis in humans and animals consisting of over 2000 serovars. The serovar Salmonella Gallinarum is an important worldwide pathogen of poultry. However, little is known on the mechanisms of pathogenesis of Salmonella in chickens. The aim of this study was to evaluate cholinesterase and myeloperoxidase activities in hepatic tissue of laying hens naturally infected by S. Gallinarum. Twenty positive liver samples for S. Gallinarum were collected, in addition to seven liver samples from healthy uninfected laying hens (control group). The right liver lobe was homogenized for analysis of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and myeloperoxidase (MPO), and the left lobe was divided into two fragments, one for histopathology and the other for Salmonella isolation. The results showed changes in AChE and BchE activity in the liver of infected laying hens compared to the control group (P liver samples. Infected animals showed increased MPO activity compared to healthy animals (P cells, macrophages,heterophils in the liver of infected hens. These findings suggest that the inflammatory process was attenuated providing a pro-inflammatory action of both enzyme analyzed in order to reduce the free ACh, a molecule which has an anti-inflammatory action. Therefore, our results lead to the hypothesis that cholinesterase plays an important role on the modulation of immune response against S. Gallinarum with an inflammatory effect, contributing to the response against this bacterium. This study should contribute to a better understanding on the pathogenic mechanisms involved in laying hens infected by S. Gallinarum.

  14. In vitro cholinesterase inhibitory and antioxidant effect of selected coniferous tree species

    Institute of Scientific and Technical Information of China (English)

    Fatma Sezer Senol; Ilkay Erdogan Orhan; Osman Ustun


    Objective: To explore cholinesterase inhibitory and antioxidant effect of six coniferous trees (Abies bornmulleriana, Picea pungens, Juniperus communis, Cedrus libani, Taxus baccata, and Cupressus sempervirens var. horizantalis). Methods: Acetone (Ace), ethyl acetate (EtOAc), and ethanol (EtOH) extracts prepared from the needles and shoots of the six coniferous trees were screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at 100 μg/mL. Antioxidant activity of the extracts was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and N,N-dimethyl-p-phenylendiamine (DMPD) radical scavenging, metal-chelation capacity, ferric-(FRAP) and phosphomolibdenum-reducing antioxidant power (PRAP) assays. All of the assays were performed in ELISA microplate reader. Total phenol and flavonoid amounts in the extracts were determined spectrophotometrically. Results: Among thirty-six extracts in total, the shoot-Ace extract of Cupressus sempervirens var. horizantalis exerted the highest inhibition against AChE [(54.84±2.51)%], while the needle-Ace extract of Cedrus libani was the most effective in inhibiting BChE [(67.54±0.30)%]. The highest DPPH radical scavenging effect, FRAP and PRAP was observed in the shoot-Ace and EtOAc extracts from Taxus baccata, whereas all the extracts showed a variable degree of scavenging effect against DPMD radical. The shoot-EtOAc extract of Cedrus libani had the highest metal-chelation capacity [(58.04±0.70)%]. The shoot extracts of Taxus baccata were determined to have the richest total phenol content, which may contribute to its marked antioxidant activity. Conclusions: The conifer species screened in this study may contain cholinesterase-inhibiting and antioxidant properties, which might be useful against Alzheimer’s disease.

  15. The Use of Pesticides Against Blood Cholinesterase Level (The Analytical Study on Farmers in Torpedo Village, Sabbang Sub District, Luwu Utara District

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    H. Hamsir Ahmad


    Full Text Available Blood Cholinesterase was a enzymes form of biological catalyst in the body's tissues role to keep the muscles, glands and nerve cells to work in an organized and harmonious. Blood Cholinesterase is an indicator of subclinical pesticide poisoning and it can be determined by examining blood Cholinesterase activity into someone. The purpose of this study was known the relationship use of pesticide on levels of blood Cholinesterase on a rice farmer in the village torpedo Sabbang sub district, Luwu Utara district. This type of research is analytic survey research with cross sectional study to determine the relationship use of pesticide on levels of blood Cholinesterase on a farmer in the village of torpedo Sabbang sub district, Luwu Utara. The number of samples in this study were 73 samples. The results showed that length use of pesticides by respondents have longer use than shorter use, but from the results of statistical tests Ho refused meaning there was no significant relationship between length use of pesticides with high levels of farmers blood Cholinesterase, P> 0.005. There was no significant relationship between how pesticides mixing with high levels of farmers blood Cholinesterase, based on the statistical test Ho rejected P> 0.005. There were still some farmers do not use PPE at the time of contact with the pesticide, but from the results of statistical tests Ho refused meaning there was no significant relationship between the use of PPE with high levels of farmers blood Cholinesterase, P> 0.005. Suggestions in the study was expected that health care workers to provide education on the dangers of pesticides on health. It was expected that farmers in the gathering / dispensing pesticides in order to follow the rules of the use of pesticides. It was expected to farmers to use personal protective equipment (PPE at the time of contact with the pesticide.

  16. Oxidation of cholinesterase-inhibiting pesticides: A simple experiment to illustrate the role of bioactivation in the toxicity of chemicals. (United States)

    Arufe; Romero; Gamero; Moreno


    A simple undergraduate laboratory experiment that can be used in Biochemistry and Toxicology courses to illustrate the importance of metabolic reactions in the toxicity of chemical substances is reported. It involves the experimental confirmation that oxidized phosphorothionate esters, commonly used as insecticides, are stronger cholinesterase inhibitors and therefore exhibit higher toxicity than do their sulphur analogs starting from which the first are formed by in vivo oxidative desulphuration. Two separated aliquots of a bovine blood sample are incubated with parathion and paraoxon, its oxygen analog, and compared for cholinesterase activity with "normal" blood. Previously, a standard sample of paraoxon was obtained by oxidation of the thiono group of parathion with bromine vapour by reaction TLC. The comparison of the inhibitory capacity of both compounds is made by a colorimetric procedure using acetylthiocholine as substrate of the enzyme and 5,5'-dithiobis-(2-nitrobenzoic acid) as chromogen.

  17. A Facile Ionic Liquid Promoted Synthesis, Cholinesterase Inhibitory Activity and Molecular Modeling Study of Novel Highly Functionalized Spiropyrrolidines

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    Abdulrahman I. Almansour


    Full Text Available A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC50 value of 1.57 µM against acethylcholinesterase (AChE. Molecular docking simulation for the most active compound was employed with the aim of disclosing its binding mechanism to the active site of AChE receptor.

  18. Mild versus moderate stages of Alzheimer's disease: three-year outcomes in a routine clinical setting of cholinesterase inhibitor therapy.


    Wattmo, Carina; Minthon, Lennart; Wallin, Åsa


    BACKGROUND: There is an increasing interest in cognitive and functional outcomes in the respective stages of Alzheimer's disease (AD) and in novel therapies particularly for the milder phases of AD. Our aim was to describe and compare various aspects of disease progression in patients with mild versus moderate AD in routine clinical practice of cholinesterase inhibitor (ChEI) therapy. METHODS: This 3-year, prospective, observational, multicentre study included 1021 participants. Of the...

  19. PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

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    Ellison, Corie A., E-mail: [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Crane, Alice L., E-mail: [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Bonner, Matthew R., E-mail: [Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Knaak, James B., E-mail: [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Browne, Richard W., E-mail: [Department of Biotechnical and Clinical Laboratory Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Lein, Pamela J., E-mail: [Department of Molecular Biosciences, University of California School of Veterinary Medicine, Davis, CA 95618 (United States); Olson, James R., E-mail: [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States)


    Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.

  20. Cognitive and affective changes in mild to moderate Alzheimer's disease patients undergoing switch of cholinesterase inhibitors: a 6-month observational study.

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    Gianfranco Spalletta

    Full Text Available Patients with Alzheimer's disease after an initial response to cholinesterase inhibitors may complain a later lack of efficacy. This, in association with incident neuropsychiatric symptoms, may worsen patient quality of life. Thus, the switch to another cholinesterase inhibitor could represent a valid therapeutic strategy. The aim of this study was to investigate the effectiveness of the switch from one to another cholinesterase inhibitor on cognitive and affective symptoms in mild to moderate Alzheimer disease patients. Four hundred twenty-three subjects were included from the EVOLUTION study, an observational, longitudinal, multicentre study conducted on Alzheimer disease patients who switched to different cholinesterase inhibitor due either to lack/loss of efficacy or response, reduced tolerability or poor compliance. All patients underwent cognitive and neuropsychiatric assessments, carried out before the switch (baseline, and at 3 and 6-month follow-up. A significant effect of the different switch types was found on Mini-Mental State Examination score during time, with best effectiveness on mild Alzheimer's disease patients switching from oral cholinesterase inhibitors to rivastigmine patch. Depressive symptoms, when measured using continuous Neuropsychiatric Inventory values, decreased significantly, while apathy symptoms remained stable over the 6 months after the switch. However, frequency of both depression and apathy, when measured categorically using Neuropsychiatric Inventory cut-off scores, did not change significantly during time. In mild to moderate Alzheimer disease patients with loss of efficacy and tolerability during cholinesterase inhibitor treatment, the switch to another cholinesterase inhibitor may represent an important option for slowing cognitive deterioration. The evidence of apathy stabilization and the positive tendency of depressive symptom improvement should definitively be confirmed in double-blind controlled

  1. Cognitive and affective changes in mild to moderate Alzheimer's disease patients undergoing switch of cholinesterase inhibitors: a 6-month observational study. (United States)

    Spalletta, Gianfranco; Caltagirone, Carlo; Padovani, Alessandro; Sorbi, Sandro; Attar, Mahmood; Colombo, Delia; Cravello, Luca


    Patients with Alzheimer's disease after an initial response to cholinesterase inhibitors may complain a later lack of efficacy. This, in association with incident neuropsychiatric symptoms, may worsen patient quality of life. Thus, the switch to another cholinesterase inhibitor could represent a valid therapeutic strategy. The aim of this study was to investigate the effectiveness of the switch from one to another cholinesterase inhibitor on cognitive and affective symptoms in mild to moderate Alzheimer disease patients. Four hundred twenty-three subjects were included from the EVOLUTION study, an observational, longitudinal, multicentre study conducted on Alzheimer disease patients who switched to different cholinesterase inhibitor due either to lack/loss of efficacy or response, reduced tolerability or poor compliance. All patients underwent cognitive and neuropsychiatric assessments, carried out before the switch (baseline), and at 3 and 6-month follow-up. A significant effect of the different switch types was found on Mini-Mental State Examination score during time, with best effectiveness on mild Alzheimer's disease patients switching from oral cholinesterase inhibitors to rivastigmine patch. Depressive symptoms, when measured using continuous Neuropsychiatric Inventory values, decreased significantly, while apathy symptoms remained stable over the 6 months after the switch. However, frequency of both depression and apathy, when measured categorically using Neuropsychiatric Inventory cut-off scores, did not change significantly during time. In mild to moderate Alzheimer disease patients with loss of efficacy and tolerability during cholinesterase inhibitor treatment, the switch to another cholinesterase inhibitor may represent an important option for slowing cognitive deterioration. The evidence of apathy stabilization and the positive tendency of depressive symptom improvement should definitively be confirmed in double-blind controlled studies.

  2. The Effect of Diazinon on Cholinesterase Activity in Plasma and Erythrocytes of Male and Female Rats and the Protective Role of Vitamin E

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    F. Rahimi Anbarkeh


    Full Text Available Introduction & Objective: Diazinon (DZN is an organophosphate insecticide that one of the mechanisms of toxicity is the inhibition of cholinesterase. The aim of the present study was to evaluate the effects of diazinon on cholinesterase activity in blood serum and erythrocytes of male and female rats and to assess the protective role of vitamin E. Materials & Methods: In this experimental study, 60 adult wistar rats including 30 male and 30 female rats were selected and divided into 5 groups (n = 6: control group (without any intervention, sham group (received only pure olive oil daily, experimental group 1 (DZN daily, 60 mg/kg, experimental group 2 (received DZN+ vitamin E daily, with the same dose and experimental group 3(received vitamin E daily 200 mg/kg. Diazinon and solvent were injected intraperitoneally and vitamin E was given by gavage. After 2 weeks 3 ml blood was taken from the heart tissue, and titrimetric and Ellman’s method respectively were used for serum and erythrocyte cholinesterases activity assay. Results: In both genders, due to administration of diazinon, we observed significant reduction in serum and erythrocytes cholinesterase activity. The use of vitamin E increased serum and erythrocytes cholinesterase activity in experimental group 2 of female rats but inhibition in erythrocyte and serum cholinesterase activity was not recovered in experimental group 2 of male rats. Conclusion: According to a further reduction of these enzymes activity in female rats with the use of diazinon, it can be concluded that female rats are more sensitive than male rats and it seems that vitamin E as an antioxidants has a protective effect on cholinesterase activity and reduces the toxicity of DZN. (Sci J Hamadan Univ Med Sci 2015; 21 (4:294-303

  3. Cholinesterase activities and sensitivity to pesticides in different tissues of silver European eel, Anguilla anguilla. (United States)

    Valbonesi, P; Brunelli, F; Mattioli, M; Rossi, T; Fabbri, E


    Cholinesterase (ChE) activities were characterized in silver European eel, Anguilla anguilla, grown in the brackish lagoon of Comacchio (Italy). All specimens were harvested at the "lavoriero", a traditional eel trapping weir that captures eels while leaving internal waters at the onset of reproductive migration. To our knowledge, no investigation on ChE was reported in silver eels. Therefore a first characterization of enzyme activity in muscle, brain, liver and plasma of silver eel was carried out, in the presence of different substrates, selective inhibitors, and four pesticides representative of the carbamate and organophosphate classes. Brain and white skeletal muscle showed similar ChE activities, 5- and 10-fold higher than those detected in liver and plasma, respectively. Km values of 0.31 and 0.30 mM, and Vmax values of 40.28 and 35.47 nmol min(-1) mg protein(-1) were obtained in brain and muscle ChE, respectively. Acetycholinesterase was the predominant ChE form in all tissues, as concluded by comparing the effects of BW 284c51, iso-OMPA and eserine. ChE activities in brain and muscle were significantly inhibited by in vitro treatment with pesticides, with the following order of potency: carbofuran>carbaryl>chlorpyrifos≥diazinon.

  4. A new approach to determining cholinesterase activities in samples of whole blood. (United States)

    Augustinsson, K B; Eriksson, H; Faijersson, Y


    A sensitive method, especially suitable for clinical laboratories, for the routine determination of cholinesterase activities in whole blood is presented. This method is based on the hydrolysis of propionylthiocholine and the spectrophotometric determination of the thiocholine produced by reaction with 4,4'-dithiodipyridine. The reaction product 4-thiopyridone has an absorption maximum at 324 nm, so that measurement in the presence of hemoglobin is possible. Propionylthiocholine is used at the substrate for both plasma butyrylcholinesterase and erythrocyte acetylcholinesterase. These two enzymes, in the relative amounts at which they are present in human blood, split this ester at about the same rate. Consequently, a first determination gives the total activity of which each individual activity is about 50%. A second determination in the presence of a selective inhibitor ("Astra 1397") for plasma butyrylcholinesterase gives the activity of the erythrocyte acetylcholinesterase. The difference between the two values represents the activity of the plasma enzyme. The validity of the method and the reliability of the results were checked with each blood sample in two ways: (1) by determining the activities of whole blood with an earlier gasometric technique which uses blood sample dried on filter paper; and (2) by measuring the activities in separated plasma and erythrocyte hemolysate eith propionylthiocholine as the substrate.

  5. Differential swimming performance of two natricine snakes exposed to a cholinesterase-inhibiting pesticide

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    Hopkins, W.A. [University of Georgia, Savannah River Ecology Laboratory, Wildlife Ecotoxicology and Physiological Ecology Program, PO Drawer E, Aiken, SC 29802 (United States)]. E-mail:; Winne, C.T. [University of Georgia, Savannah River Ecology Laboratory, Wildlife Ecotoxicology and Physiological Ecology Program, PO Drawer E, Aiken, SC 29802 (United States); DuRant, S.E. [University of Georgia, Savannah River Ecology Laboratory, Wildlife Ecotoxicology and Physiological Ecology Program, PO Drawer E, Aiken, SC 29802 (United States)


    Environmental contaminants have direct effects on organisms at the molecular, cellular, and tissue levels, but the net results of these sub-organismal effects are only consequential to exposed populations if they alter organism-level traits that ultimately influence fitness (e.g., growth, locomotor performance, reproduction, and survival). Here, we explore the possibility that the swimming performance of neonate black swamp snakes (Seminatrix pygaea) and diamondback water snakes (Nerodia rhombifer) may be affected by exposure to carbaryl (2.5 and 5.0 mg/L). The highest concentration of carbaryl caused greater reductions in swim velocity in S. pygaea than in N. rhombifer. Most individuals recovered from the effects of carbaryl on swimming performance within 96 h, but recovery was significantly slower in S. pygaea than in N. rhombifer. We hypothesize that the sensitivity of S. pygaea may arise from its highly permeable integument compared to other natricines. Our findings suggest that performance can serve as an ecologically relevant response to contaminant exposure in reptiles and warrants further study. - Exposure to a cholinesterase inhibitor reduces swimming velocity in snakes.

  6. The relationship between total cholinesterase activity and mortality in four butterfly species (United States)

    Bargar, Timothy A.


    The relationship between total cholinesterase activity (TChE) and mortality in four butterfly species (great southern white [Ascia monuste], common buckeye [Junonia coenia], painted lady [Vanessa cardui], and julia butterflies [Dryas julia]) was investigated. Acute contact toxicity studies were conducted to evaluate the response (median lethal dose [LD50] and TChE) of the four species following exposure to the organophosphate insecticide naled. The LD50 for these butterflies ranged from 2.3 to 7.6 μg/g. The average level of TChE inhibition associated with significant mortality ranged from 26 to 67%, depending on the species. The lower bounds of normal TChE activity (2 standard deviations less than the average TChE for reference butterflies) ranged from 8.4 to 12.3 μM/min/g. As a percentage of the average reference TChE activity for the respective species, the lower bounds were similar to the inhibition levels associated with significant mortality, indicating there was little difference between the dose resulting in significant TChE inhibition and that resulting in mortality.

  7. Toxicity and characterization of cholinesterase-inhibition induced by diisopropyl fluorophosphate in Artemia salina larvae. (United States)

    Sánchez-Fortún, S; Barahona, M V


    The acute toxicity of diisopropyl fluorophosphate (DFP) on three age classes of Artemia salina was evaluated. An increase in toxicity of this organophosphorous (OP) compound was found following longer development of A. salina larvae. The effects of pretreatment with the non-selective muscarinic antagonist atropine, the two reversible acetylcholinesterase inhibitors physostigmine and pyridostigmine, and the cholinesterase-reactivating oxime 2-pyridine aldoxime methoiodide (2-PAM), as individual and combined pretreatments, on DFP-induced lethality in 24h Artemia were also investigated. The lethal action of DFP was not prevented by pretreatment of 24h Artemia with atropine, physostigmine, and pyridostigmine, while 2-PAM proved effective against intoxication with this OP compound. The inhibitory effects of combinations of atropine (10(-5)M) plus 2-PAM or physostigmine were greater than those elicited by either drug alone, with the maximum protection afforded being 100%. Pretreatment with 2-PAM (10(-6)M) plus physostigmine or pyridostigmine was ineffective. These results suggest that the combinations of atropine plus 2-PAM or physostigmine are effective in the prevention of the lethal effects induced by DFP in A. salina larvae.

  8. Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet

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    Dimitrov Mitko


    Full Text Available Abstract Background N,N-Diethyl-3-methylbenzamide (deet remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system. Results By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase. Conclusion These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.

  9. The effects of chlorpyrifos on cholinesterase activity and foraging behavior in the dragonfly, Anax junius (Odonata) (United States)

    Brewer, S.K.; Atchison, G.J.


    We examined head capsule cholinesterase (ChE) and foraging behavior in nymphs of the dragonfly, Anax junius, exposed for 24 h to 0.2, 0.6 and 1.0 ??g l-1 of the organophosphorus (OP) insecticide, chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate]. The invertebrate community is an important component of the structure and function of wetland ecosystems, yet the potential effects of insecticides on wetland ecosystems are largely unknown. Our objectives were to determine if exposure to environmentally realistic concentrations of chlorpyrifos affected foraging behavior and ChE activity in head capsules of dragonfly nymphs. Nymphs were exposed to different concentrations of chlorpyrifos and different prey densities in a factorial design. ChE activities and foraging behaviors of treated nymphs were not statistically different (p ??? 0.05) from control groups. Prey density effects exerted a greater effect on dragonfly foraging than toxicant exposures. Nymphs offered higher prey densities exhibited more foraging behaviors but also missed their prey more often. High variability in ChE activities within the control group and across treated groups precluded determination of relationships between ChE and foraging behaviors. It appears that A. junius is relatively tolerant of chlorpyrifos, although the concentrations we tested have been shown in other work to adversely affect the prey base; therefore the introduction of this insecticide may have indirect adverse affects on top invertebrate predators such as Odonata.

  10. Antioxidant and cholinesterases inhibitory activities of Verbascum xanthophoeniceum Griseb. and its phenylethanoid glycosides. (United States)

    Georgiev, Milen; Alipieva, Kalina; Orhan, Ilkay; Abrashev, Radoslav; Denev, Petko; Angelova, Maria


    The members of Verbascum L. (Scrophulariaceae) are known to be rich in phenylethnoid glycosides, and among them Verbascum xanthophoeniceum is an endemic plant species for the Balkan region, Northwestern, and Southern Turkey. A scheme was developed for the isolation of the main active constituents that accumulate in plant aerial parts. The antioxidant activities of total methanol extracts, collected phenylethanoid glycosides fractions and specific active constituents (forsythoside B, verbascoside and leucosceptoside B) were then evaluated in 2,2'-diphenyl-1-picrylhydrazyl (DPPH·), oxygen radical absorbance capacity (ORACFL), hydroxyl radical averting capacity (HORACFL), ferric-reducing antioxidant power (FRAP), and superoxide anion (O2(-)) radical scavenging assays. In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChe) inhibitory activities of abovementioned extracts, fractions and isolated pure compounds were also examined. Depending on the method used, forsythoside B, verbascoside and leucosceptoside B proved to be effective radical scavengers and cholinesterases inhibitors. On the basis of these findings it can be proposed that in addition to providing a potent source of antimicrobial and anti-inflammatory compounds, Verbascum plants could serve as attractive mines of powerful antioxidants for various purposes.

  11. Characterization of catalytic efficiency parameters of brain cholinesterases in tropical fish. (United States)

    de Assis, Caio Rodrigo Dias; Linhares, Amanda Guedes; Oliveira, Vagne Melo; França, Renata Cristina Penha; Santos, Juliana Ferreira; Marcuschi, Marina; Carvalho, Elba Verônica Matoso Maciel; Bezerra, Ranilson Souza; Carvalho, Luiz Bezerra


    Brain cholinesterases from four fish (Arapaima gigas, Colossoma macropomum, Rachycentron canadum and Oreochromis niloticus) were characterized using specific substrates and selective inhibitors. Parameters of catalytic efficiency such as activation energy (AE), k(cat) and k(cat)/k(m) as well as rate enhancements produced by these enzymes were estimated by a method using crude extracts described here. Despite the BChE-like activity, specific substrate kinetic analysis pointed to the existence of only acetylcholinesterase (AChE) in brain of the species studied. Selective inhibition suggests that C. macropomum brain AChE presents atypical activity regarding its behavior in the presence of selective inhibitors. AE data showed that the enzymes increased the rate of reactions up to 10(12) in relation to the uncatalyzed reactions. Zymograms showed the presence of AChE isoforms with molecular weights ranging from 202 to 299 kDa. Values of k(cat) and k(cat)/k(m) were similar to those found in the literature.

  12. Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates. (United States)

    Chambers, Janice E; Meek, Edward C; Chambers, Howard W


    Current oxime reactivators for organophosphate-inhibited cholinesterase (ChE) do not effectively cross the blood-brain barrier and therefore cannot restore brain ChE activity in vivo. Our laboratories have studied highly relevant sarin and VX surrogates, which differ from their respective nerve agents only in the leaving group and thereby leave ChE phosphylated with the same chemical moiety as sarin and VX. Our laboratories have developed novel substituted phenoxyalkyl pyridinium oximes that lead to reduced ChE inhibition in the brains of rats challenged with a high sublethal dosage of the sarin surrogate, whereas 2-PAM did not, using a paradigm designed to demonstrate brain penetration. In addition, treatment of rats with these novel oximes is associated with attenuation of seizure-like behavior compared to rats treated with 2-PAM, providing additional evidence that the oximes penetrate the blood-brain barrier. Further, some of the oximes provided 24-h survival superior to 2-PAM, and shortened the duration of seizure-like behavior when rats were challenged with lethal dosages of the sarin and VX surrogates, providing additional support for the conclusion that these oximes penetrate the brain.

  13. Studies on combined effects of organophosphates or carbamates and morsodren in birds. II. Plasma and cholinesterase in quail fed morsodren and orally dosed with parathion or carbofuran (United States)

    Dieter, M.P.; Ludke, J.L.


    The degree of interaction between mercury and cholinesterase inhibiting pesticides was determined by comparing enzyme responses to sublethal dosages of parathion or carbofuran in quail fed 0.05, 0.5, or 5.0 ppm morsodren for 18 weeks. A statistically significant interaction was defined as greater brain cholinesterase inhibition in morsodren-fed than in clean-fed birds following pesticide dosage. The tissue residues of mercury that accumulated before significant mercury-parathion interactions occurred were higher than levels that might be expected in natural populations, but significant mercury-carbofuran interactions occurred in birds that had only accumulated 1.0 ppm liver mercury. The results indicate that indiscriminate usage of cholinesterase inhibiting pesticides are dangerous, since natural populations of fish-eating birds oftentimes contain this magnitude of mercury.

  14. Cholinesterase-like domains in enzymes and structural proteins: functional and evolutionary relationships and identification of a catalytically essential aspartic acid. (United States)

    Krejci, E; Duval, N; Chatonnet, A; Vincens, P; Massoulié, J


    Primary sequences of cholinesterases and related proteins have been systematically compared. The cholinesterase-like domain of these proteins, about 500 amino acids, may fulfill a catalytic and a structural function. We identified an aspartic acid residue that is conserved among esterases and lipases (Asp-397 in Torpedo acetylcholinesterase) but that had not been considered to be involved in the catalytic mechanism. Site-directed mutagenesis demonstrated that this residue is necessary for activity. Analysis of evolutionary relationships shows that the noncatalytic members of the family do not constitute a separate subgroup, suggesting that loss of catalytic activity occurred independently on several occasions, probably from bifunctional molecules. Cholinesterases may thus be involved in cell-cell interactions in addition to the hydrolysis of acetylcholine. This would explain their specific expression in well-defined territories during embryogenesis before the formation of cholinergic synapses and their presence in noncholinergic tissues. Images PMID:1862088

  15. Hormetic response of cholinesterase from Daphnia magna in chronic exposure to triazophos and chlorpyrifos

    Institute of Scientific and Technical Information of China (English)

    Shaonan Li; Yajun Tan


    In vivo activity of cholinesterase (ChE) in Daphnia magna was measured at different time points during 21-day exposure to triazophos and chlorpyrifos ranging from 0.05 to 2.50 μg/L and 0.01 to 2.00 μg/L, respectively.For exposure to triazophos, ChE was induced up to 176.5% at 1.5 μg/L and day 10 when measured by acetylthiocholine (ATCh), whereas it was induced up to 174.2% at 0.5 μg/L and day 10 when measured by butyrylthiocholine (BTCh).For exposure to chlorpyrifos, ChE was induced up to 134.0% and 160.5% when measured by ATCh and BTCh, respectivly, with both maximal inductions detected at 0.l μg/L and day 8.Obvious induction in terms of ChE activity was also detected in daphnia removed from exposures 24 hr after their birth and kept in a recovery culture for 21 days.Results indicated that the enzyme displayed symptoms of hormesis, a characteristic featured by conversion from low-dose stimulation to high-dose inhibition.In spite of that, no promotion in terms of reproduction rate and body size was detected at any tested concentrations regardless of whether the daphnia were collected at end of the 21-day exposure or at end of a 21-day recovery culture.This suggested that induction of ChE caused by anticholinesterases had nothing to do with the prosperity of the daphnia population.

  16. Novel Cholinesterase Inhibitors Based on O-Aromatic N,N-Disubstituted Carbamates and Thiocarbamates

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    Martin Krátký


    Full Text Available Based on the presence of carbamoyl moiety, twenty salicylanilide N,N-disubstituted (thiocarbamates were investigated using Ellman’s method for their ability to inhibit acetylcholinesterase (AChE and butyrylcholinesterase (BChE. O-Aromatic (thiocarbamates exhibited weak to moderate inhibition of both cholinesterases with IC50 values within the range of 1.60 to 311.0 µM. IC50 values for BChE were mostly lower than those obtained for AChE; four derivatives showed distinct selectivity for BChE. All of the (thiocarbamates produced a stronger inhibition of AChE than rivastigmine, and five of them inhibited BChE more effectively than both established drugs rivastigmine and galantamine. In general, 5-chloro-2-hydroxy-N-[4-(trifluoromethyl-phenyl]benzamide, 2-hydroxy-N-phenylbenzamide as well as N-methyl-N-phenyl carbamate derivatives led to the more potent inhibition. O-{4-Chloro-2-[(4-chlorophenylcarbamoyl]phenyl} dimethylcarbamothioate was identified as the most effective AChE inhibitor (IC50 = 38.98 µM, while 2-(phenylcarbamoylphenyl diphenylcarbamate produced the lowest IC50 value for BChE (1.60 µM. Results from molecular docking studies suggest that carbamate compounds, especially N,N-diphenyl substituted representatives with considerable portion of aromatic moieties may work as non-covalent inhibitors displaying many interactions at peripheral anionic sites of both enzymes. Mild cytotoxicity for HepG2 cells and consequent satisfactory calculated selectivity indexes qualify several derivatives for further optimization.

  17. Evaluation of flow injection analysis for determination of cholinesterase activities in biological material. (United States)

    Cabal, Jiri; Bajgar, Jiri; Kassa, Jiri


    The method for automatic continual monitoring of acetylcholinesterase (AChE) activity in biological material is described. It is based on flexible system of plastic pipes mixing samples of biological material with reagents for enzyme determination; reaction product penetrates through the semipermeable membrane and it is spectrophotometrically determined (Ellman's method). It consists of sampling (either in vitro or in vivo), adding the substrate and flowing to dialyzer; reaction product (thiocholine) is dialyzed and mixed with 5,5'-dithio-bis-2-nitrobenzoic acid (DTNB) transported to flow spectrophotometer. Flowing of all materials is realised using peristaltic pump. The method was validated: time for optimal hydratation of the cellophane membrane; type of the membrane; type of dialyzer; conditions for optimal permeation of reaction components; optimization of substrate and DTNB concentrations (linear dependence); efficacy of peristaltic pump; calibration of analytes after permeation through the membrane; excluding of the blood permeation through the membrane. Some examples of the evaluation of the effects of AChE inhibitors are described. It was demonstrated very good uniformity of peaks representing the enzyme activity (good reproducibility); time dependence of AChE inhibition caused by VX in vitro in the rat blood allowing to determine the half life of inhibition and thus, bimolecular rate constants of inhibition; reactivation of inhibited AChE by some reactivators, and continual monitoring of the activity in the whole blood in vivo in intact and VX-intoxicated rats. The method is simple and not expensive, allowing automatic determination of AChE activity in discrete or continual samples in vitro or in vivo. It will be evaluated for further research of cholinesterase inhibitors.

  18. Review of UV spectroscopic, chromatographic, and electrophoretic methods for the cholinesterase reactivating antidote pralidoxime (2-PAM). (United States)

    John, Harald; Blum, Marc-Michael


    Pralidoxime (2-PAM) belongs to the class of monopyridinium oximes with reactivating potency on cholinesterases inhibited by phosphylating organophosphorus compounds (OPC), for example, pesticides and nerve agents. 2-PAM represents an established antidote for the therapy of anticholinesterase poisoning since the late 1950s. Quite high therapeutic concentrations in human plasma (about 13 µg/ml) lead to concentrations in urine being about 100 times higher allowing the use of less sensitive analytical techniques that were used especially in the early years after 2-PAM was introduced. In this time (mid-1950s until the end of the 1970s) 2-PAM was most often analyzed by either paper chromatography or simple UV spectroscopic techniques omitting any sample separation step. These methods were displaced completely after the establishment of column liquid chromatography in the early 1980s. Since then, diverse techniques including cation exchange, size-exclusion, reversed-phase, and ligand-exchange chromatography have been introduced. Today, the most popular method for 2-PAM quantification is ion pair chromatography often combined with UV detection representing more than 50% of all column chromatographic procedures published. Furthermore, electrophoretic approaches by paper and capillary zone electrophoresis have been successfully used but are seldom applied. This review provides a commentary and exhaustive summary of analytical techniques applied to detect 2-PAM in pharmaceutical formulations and biological samples to characterize stability and pharmacokinetics as well as decomposition and biotransformation products. Separation techniques as well as diverse detectors are discussed in appropriate detail allowing comparison of individual preferences and limitations. In addition, novel data on mass spectrometric fragmentation of 2-PAM are provided.

  19. Cholinesterase inhibition modulates visual and attentional brain responses in Alzheimer's disease and health. (United States)

    Bentley, Paul; Driver, Jon; Dolan, Ray J


    Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are considered more responsive to pro-cholinergic therapy than characteristic memory disturbances. We hypothesised that neural responses in AD during visuo-attentional processing would be impaired relative to controls, yet partially susceptible to improvement with the cholinesterase inhibitor physostigmine. We studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI-scanning to enable within-subject placebo-controlled comparisons of effects of physostigmine on stimulus- and attention- related brain activations, plus between-group comparisons for these. Subjects viewed face or building stimuli while performing a shallow judgement (colour of image) or a deep judgement (young/old age of depicted face or building). Behaviourally, AD subjects performed slower than controls in both tasks, while physostigmine benefited the patients for the more demanding age-judgement task. Stimulus-selective (face minus building, and vice versa) BOLD signals in precuneus and posterior parahippocampal cortex were attenuated in patients relative to controls, but increased following physostigmine. By contrast, face-selective responses in fusiform cortex were not impaired in AD and showed decreases following physostigmine for both groups. Task-dependent responses in right parietal and prefrontal cortices were diminished in AD but improved following physostigmine. A similar pattern of group and treatment effects was observed in two extrastriate cortical regions that showed physostigmine-induced enhancement of stimulus-selectivity for the deep versus shallow task. Finally, for the healthy group, physostigmine decreased stimulus and task-dependent effects, partly due to an exaggeration of selectivity during the shallow relative to deep task. The differences in brain activations between groups and treatments were not attributable merely to performance (reaction time) differences. Our results demonstrate

  20. Partial protection from organophosphate-induced cholinesterase inhibition by metyrapone treatment

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    Radosław Świercz


    Full Text Available Background: Organophosphates are cholinesterase (ChE inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP poisoning symptomatology. In rodents, corticosterone (CORT is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentraion (the CORT response and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET [2-methyl-1,2-di(pyridin-3-ylpropan-1-one] blocks CORT synthesis by inhibiting steoid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP [2-chloro-1-(2,4-dichlorophenyl ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. Material and Methods: The purose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. Conclusion: The following was observed in the MET-treated rats: i no rise in plasma CORT concentration after the CVP administration, ii a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.

  1. Brain cholinesterases: III. Future perspectives of AD research and clinical practice. (United States)

    Shen, Z-X


    Alzheimer's disease (AD) is initially and primarily associated with the degeneration and alteration in the metabolism of cholinesterases (ChEs). The use of ChEs inhibitors to treat Alzheimer's condition, on the basis of the cholinergic hypothesis of the disease, is, therefore, without grounds. Most disturbing is the fact that the currently available anti-ChEs are designed to inhibit normal ChEs in the brain and throughout the body, but not the abnormal ones. Based on the acetylcholinesterase (AChE) deficiency theory, treatment should be designed to protect the cranial ChEs system from alteration and/or to help that system fight against degeneration through restoring its homeostatic action for brain structure and function instead. The overlap in the clinical, biochemical, molecular-cellular, and pathological alterations seen in patients with AD and individuals with many other brain disorders, which has bewildered many investigators, may now be explained by the shared underlying mismetabolism of brain ChEs. The abnormal metabolism of ChEs existing in asymptomatic subjects may indicate that the system is "at risk" and deserves serious attention. Future perspectives of ChEs research in vivo and in vitro in connection with AD and clinical diagnosis, prevention and treatment are proposed. Several potentially useful therapeutic and preventive means and pharmacological agents in this regard are identified and discussed, such as physical and intellectual stimulation, and a class of drugs including vitamin E, R-(-)-deprenyl (deprenyl, selegiline), acetyl L-carnitine, cytidine diphosphocholine (CDP-choline), centrophenoxine, L-phenylalanine, naloxone, galactose, and lithium, that have been proven to be able to stimulate AChE activity. Their working mechanisms may be through directly changing the configuration of AChE molecules and/or correcting micro- and overall environmental biological conditions for ChEs.

  2. Aging of cholinesterases phosphylated by tabun proceeds through O-dealkylation. (United States)

    Carletti, Eugénie; Li, He; Li, Bin; Ekström, Fredrik; Nicolet, Yvain; Loiodice, Mélanie; Gillon, Emilie; Froment, Marie T; Lockridge, Oksana; Schopfer, Lawrence M; Masson, Patrick; Nachon, Florian


    Human butyrylcholinesterase (hBChE) hydrolyzes or scavenges a wide range of toxic esters, including heroin, cocaine, carbamate pesticides, organophosphorus pesticides, and nerve agents. Organophosphates (OPs) exert their acute toxicity through inhibition of acetylcholinesterase (AChE) by phosphorylation of the catalytic serine. Phosphylated cholinesterase (ChE) can undergo a spontaneous, time-dependent process called "aging", during which the OP-ChE conjugate is dealkylated. This leads to irreversible inhibition of the enzyme. The inhibition of ChEs by tabun and the subsequent aging reaction are of particular interest, because tabun-ChE conjugates display an extraordinary resistance toward most current oxime reactivators. We investigated the structural basis of oxime resistance for phosphoramidated ChE conjugates by determining the crystal structures of the non-aged and aged forms of hBChE inhibited by tabun, and by updating the refinement of non-aged and aged tabun-inhibited mouse AChE (mAChE). Structures for non-aged and aged tabun-hBChE were refined to 2.3 and 2.1 A, respectively. The refined structures of aged ChE conjugates clearly show that the aging reaction proceeds through O-dealkylation of the P(R) enantiomer of tabun. After dealkylation, the negatively charged oxygen forms a strong salt bridge with protonated His438N epsilon2 that prevents reactivation. Mass spectrometric analysis of the aged tabun-inhibited hBChE showed that both the dimethylamine and ethoxy side chains were missing from the phosphorus. Loss of the ethoxy is consistent with the crystallography results. Loss of the dimethylamine is consistent with acid-catalyzed deamidation during the preparation of the aged adduct for mass spectrometry. The reported 3D data will help in the design of new oximes capable of reactivating tabun-ChE conjugates.

  3. Relation between dynamics, activity and thermal stability within the cholinesterase family. (United States)

    Trovaslet, Marie; Trapp, Marcus; Weik, Martin; Nachon, Florian; Masson, Patrick; Tehei, Moeava; Peters, Judith


    Incoherent neutron scattering is one of the most powerful tools for studying dynamics in biological matter. Using the cold neutron backscattering spectrometer IN16 at the Institut Laue Langevin (ILL, Grenoble, France), temperature dependence of cholinesterases' dynamics (human butyrylcholinesterase from plasma: hBChE; recombinant human acetylcholinesterase: hAChE and recombinant mouse acetylcholinesterase: mAChE) was examined using elastic incoherent neutron scattering (EINS). The dynamics was characterized by the averaged atomic mean square displacement (MSD), associated with the sample flexibility at a given temperature. We found MSD values of hAChE above the dynamical transition temperature (around 200K) larger than for mAChE and hBChE, implying that hAChE is more flexible than the other ChEs. Activation energies for thermodynamical transition were extracted through the frequency window model (FWM) (Becker et al. 2004) [1] and turned out to increase from hBChE to mAChE and finally to hAChE, inversely to the MSDs relations. Between 280 and 316K, catalytic studies of these enzymes were carried out using thiocholine esters: at the same temperature, the hAChE activity was systematically higher than the mAChE or hBChE ones. Our results thus suggest a strong correlation between dynamics and activity within the ChE family. We also studied and compared the ChEs thermal inactivation kinetics. Here, no direct correlation with the dynamics was observed, thus suggesting that relations between enzyme dynamics and catalytic stability are more complex. Finally, the possible relation between flexibility and protein ability to grow in crystals is discussed.

  4. Functional response to cholinesterase inhibitor therapy in a naturalistic Alzheimer’s disease cohort

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    Wattmo Carina


    Full Text Available Abstract Background Activities of daily living (ADL are an essential part of the diagnostic criteria for Alzheimer’s disease (AD. A decline in ADL affects independent living and has a strong negative impact on caregiver burden. Functional response to cholinesterase inhibitor (ChEI treatment and factors that might influence this response in naturalistic AD patients need investigating. The aim of this study was to identify the socio-demographic and clinical factors that affect the functional response after 6 months of ChEI therapy. Methods This prospective, non-randomised, multicentre study in a routine clinical setting included 784 AD patients treated with donepezil, rivastigmine or galantamine. At baseline and after 6 months of treatment, patients were assessed using several rating scales, including the Instrumental Activities of Daily Living (IADL scale, Physical Self-Maintenance Scale (PSMS and Mini-Mental State Examination (MMSE. Demographic and clinical characteristics were investigated at baseline. The functional response and the relationships of potential predictors were analysed using general linear models. Results After 6 months of ChEI treatment, 49% and 74% of patients showed improvement/no change in IADL and in PSMS score, respectively. The improved/unchanged patients exhibited better cognitive status at baseline; regarding improved/unchanged PSMS, patients were younger and used fewer anti-depressants. A more positive functional response to ChEI was observed in younger individuals or among those having the interaction effect of better preserved cognition and lower ADL ability. Patients with fewer concomitant medications or those using NSAIDs/acetylsalicylic acid showed a better PSMS response. Conclusions Critical characteristics that may influence the functional response to ChEI in AD were identified. Some predictors differed from those previously shown to affect cognitive response, e.g., lower cognitive ability and older age

  5. Different sensitivities of rat skeletal muscles and brain to novel anti-cholinesterase agents, alkylammonium derivatives of 6-methyluracil (ADEMS) (United States)

    Petrov, Konstantin A; Yagodina, Lilia O; Valeeva, Guzel R; Lannik, Natalya I; Nikitashina, Alexandra D; Rizvanov, Albert A; Zobov, Vladimir V; Bukharaeva, Ellya A; Reznik, Vladimir S; Nikolsky, Eugeny E; Vyskočil, František


    BACKGROUND AND PURPOSE The rat respiratory muscle diaphragm has markedly lower sensitivity than the locomotor muscle extensor digitorum longus (EDL) to the new acetylcholinesterase (AChE) inhibitors, alkylammonium derivatives of 6-methyluracil (ADEMS). This study evaluated several possible reasons for differing sensitivity between the diaphragm and limb muscles and between the muscles and the brain. EXPERIMENTAL APPROACH Increased amplitude and prolonged decay time of miniature endplate currents were used to assess anti-cholinesterase activity in muscles. In hippocampal slices, induction of synchronous network activity was used to follow cholinesterase inhibition. The inhibitor sensitivities of purified AChE from the EDL and brain were also estimated. KEY RESULTS The intermuscular difference in sensitivity to ADEMS is partly explained caused by a higher level of mRNA and activity of 1,3-bis[5(diethyl-o-nitrobenzylammonium)pentyl]-6-methyluracildibromide (C-547)-resistant BuChE in the diaphragm. Moreover, diaphragm AChE was more than 20 times less sensitive to C-547 than that from the EDL. Sensitivity of the EDL to C-547 dramatically decreased after treadmill exercises that increased the amount of PRiMA AChE(G4), but not ColQ AChE(A12) molecular forms. The A12 form present in muscles appeared more sensitive to C-547. The main form of AChE in brain, PRiMA AChE(G4), was apparently less sensitive because brain cholinesterase activity was almost three orders of magnitude more resistant to C-547 than that of the EDL. CONCLUSIONS AND IMPLICATIONS Our findings suggest that ADEMS compounds could be used for the selective inhibition of AChEs and as potential therapeutic tools. PMID:21232040

  6. The role of serum cholinesterase activity and S100B protein in the evaluation of organophosphate poisoning. (United States)

    Yardan, T; Baydin, A; Acar, E; Ulger, F; Aygun, D; Duzgun, A; Nar, R


    The aim of this study was to investigate the role of serum cholinesterase (SChE) activity and S100B protein in the evaluation of patients with acute organophosphate (OP) poisoning. Patients with acute OP poisoning admitted to the emergency department were included in this cross-sectional study. Twenty healthy volunteers served as controls. The SChE activity and serum S100B were determined on admission. Patients were divided into two groups (low severity and high severity). Thirty-six patients diagnosed with acute OP poisoning were enrolled. Serum S100B concentrations were higher in patients than in the control group (p poisoning.

  7. HPTLC Fingerprinting and Cholinesterase Inhibitory and Metal-Chelating Capacity of Various Citrus Cultivars and Olea europaea

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    Fatma Sezer Senol


    Full Text Available Inhibitory activity of thirty-one ethanol extracts obtained from albedo, flavedo, seed and leaf parts of 17 cultivars of Citrus species from Turkey, the bark and leaves of Olea europaea L. from two locations (Turkey and Cyprus as well as caff eic acid and hesperidin was tested against acetylcholinesterase (AChE and butyrylcholinesterase (BChE, related to the pathogenesis of Alzheimer’s disease, using ELISA microtiter assays at 500 μg/mL. Metal-chelating capacity of the extracts was also determined. BChE inhibitory effect of the Citrus sp. extracts was from (7.7±0.7 to (70.3±1.1 %, whereas they did not show any inhibition against AChE. Cholinesterase inhibitory activity of the leaf and bark ethanol extracts of O. europaea was very weak ((10.2±3.1 to (15.0±2.3 %. The extracts had either no or low metal-chelating capacity at 500 μg/mL. HPTLC fingerprinting of the extracts, which indicated a similar phytochemical pattern, was also done using the standards of caffeic acid and hesperidin with weak cholinesterase inhibition. Among the screened extracts, the albedo extract of C. limon ‘Interdonato’, the flavedo extracts of ‘Kara Limon’ and ‘Cyprus’ cultivars and the seed extract of C. maxima appear to be promising as natural BChE inhibitors.

  8. Cholinesterase inhibitory activity and structure elucidation of a new phytol derivative and a new cinnamic acid ester from Pycnanthus angolensis

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    Taiwo O. Elufioye

    Full Text Available ABSTRACT The leaves of Pycnanthus angolensis (Welw. Warb., Myristicaceae, are used as memory enhancer and anti-ageing in Nigerian ethnomedicine. This study aimed at evaluating the cholinesterase inhibitory property as well as isolates the bioactive compounds from the plant. The acetylcholinesterase and butyrylcholinesterase inhibitory potentials of extracts, fractions, and isolated compounds were evaluated by colorimetric and TLC bioautographic assay techniques. The extract inhibited both enzymes with activity increasing with purification, ethyl acetate fraction being most active fraction at 65.66 ± 1.06% and 49.38 ± 1.66% against acetylcholinesterase and butyrylcholinesterase, respectively while the supernatant had 77.44 ± 1.18 inhibition against acetylcholinesterase. Two new bioactive compounds, (2E, 18E-3,7,11,15,18-pentamethylhenicosa-2,18-dien-1-ol (named eluptol and [12-(4-hydroxy-3-methyl-oxo-cyclopenta-1,3-dien-1yl-11-methyl-dodecyl](E-3-(3,4-dimethylphenylprop-2-enoate (named omifoate A were isolated from the plant with IC50 of 22.26 µg/ml (AChE, 34.61 µg/ml (BuChE and 6.51 µg/ml (AChE, 9.07 µg/ml (BuChE respectively. The results showed that the plant has cholinesterase inhibitory activity which might be responsible for its memory enhancing action, thus justifying its inclusion in traditional memory enhancing preparations

  9. CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters. (United States)

    Malm, J; Kristensen, B; Ekstedt, J; Adolfsson, R; Wester, P


    Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion.

  10. Phytochemical profile of a blend of black chokeberry and lemon juice with cholinesterase inhibitory effect and antioxidant potential. (United States)

    Gironés-Vilaplana, Amadeo; Valentão, Patrícia; Andrade, Paula B; Ferreres, Federico; Moreno, Diego A; García-Viguera, Cristina


    In this study, black chokeberry concentrate was added (5% w/v) to lemon juice, since previous reports suggested potential health benefits of this blend. The phytochemical composition, antioxidant capacity (scavenging of DPPH, superoxide and hydroxyl radicals, and hypochlorous acid), and inhibitory activity against cholinesterase of the new blend were determined and compared with those of lemon juice and chokeberry in citric acid (5%). The chokeberry concentrate, rich in cyanidin-glycosides, quercetin derivatives, and 3-O-caffeoylquinic acid, and lemon juice, possessing flavones, flavanones, quercetin derivates, and hydroxycinnamic acids, were characterised. The new drink showed a higher antioxidant effect than the chokeberry or lemon controls for all the tested methods, except for hypochlorous acid, in which lemon juice displayed higher activity. Both the lemon juice and chokeberry controls inhibited acetylcholinesterase and butyrylcholinesterase, and this effect was increased in the new mixtures. The results of the different radical scavenging assays indicate that the lemon-black chokeberry (5% w/v) mixture was more antioxidative than the respective controls separately. Moreover, their inhibition of cholinesterase is of interest regarding neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, or senile dementia.

  11. Cholinesterase activity as a biomarker of pesticide exposure in Allolobophora chlorotica earthworms living in apple orchards under different management strategies. (United States)

    Denoyelle, Renaud; Rault, Magali; Mazzia, Christophe; Mascle, Odile; Capowiez, Yvan


    The present study used cholinesterase (ChE) activity in earthworms as a biomarker of pesticide exposure at 17 apple orchards using different pest protection strategies (organic, integrated pest management [IPM], conventional, and abandoned) located within a 300-km(2) subregion near Avignon in southeastern France). The most common earthworm species in the 17 orchards was Allolobophora chlorotica. We examined inherent variability in ChE activity that might be attributable to soil characteristics and found that differences in soil structure or type did not significantly influence ChE activity. Furthermore, there was no relation between ChE specific activity and earthworm weight, and thus activity does not require correction for weight. Ten earthworms were collected in two successive months (April and May 2003) from each of the 17 orchards. Compared to the activity in worms from the control abandoned orchards, ChE activity was significantly decreased in earthworms from half the IPM and conventional orchards in April and all these orchards in May. Notably, ChE activity was also lower in earthworms from three organic orchards during May. No relation was observed between ChE decrease and the number of treatments (total or only organophosphorous and carbamate pesticides). Cholinesterase activity in earthworms from abandoned orchards varied between the two collecting periods, illustrating the difficulty in obtaining reference values for the use of ChE as a biomarker in field studies.

  12. Pharmacokinetics and effects on serum cholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric mice transplanted with human hepatocytes. (United States)

    Suemizu, Hiroshi; Sota, Shigeto; Kuronuma, Miyuki; Shimizu, Makiko; Yamazaki, Hiroshi


    Organophosphorus pesticides acephate and chlorpyrifos in foods have potential to impact human health. The aim of the current study was to investigate the pharmacokinetics of acephate and chlorpyrifos orally administered at lowest-observed-adverse-effect-level doses in chimeric mice transplanted with human hepatocytes. Absorbed acephate and its metabolite methamidophos were detected in serum from wild type mice and chimeric mice orally administered 150mg/kg. Approximately 70% inhibition of cholinesterase was evident in plasma of chimeric mice with humanized liver (which have higher serum cholinesterase activities than wild type mice) 1day after oral administrations of acephate. Adjusted animal biomonitoring equivalents from chimeric mice studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Estimated plasma concentrations of acephate and chlorpyrifos in humans were consistent with reported concentrations. Acephate cleared similarly in humans and chimeric mice but accidental/incidental overdose levels of chlorpyrifos cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in mice. The data presented here illustrate how chimeric mice transplanted with human hepatocytes in combination with a simple PBPK model can assist evaluations of toxicological potential of organophosphorus pesticides.

  13. Comparison of cholinesterase activities in the excretion-secretion products of Trichinella pseudospiralis and Trichinella spiralis muscle larvae

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    Ros-Moreno R.M.


    Full Text Available The presence of cholinesterases (ChE is reported in T. pseudospiralis excretion-secretion products (ESP by spectrophotometry method, using acetylthiocholine (ATCI and butyrilthiocholine (BTCI as substrates. By inhibition assays, we found that T. pseudospiralis release both acetyl- and butiryl-cholinesterases (AchE and BchE, respectively. The sedimentation coefficientes of these enzymes were determined by sucrose density gradient. We studied the in vivo ChE secretion by immunoblot assays using AchE from Electrophorus (electric eel and sera from normal or infected mice with T. pseudospiralis or T. spiralis. The presence of anti-AchE antibodies was only demonstrated in the sera from T. pseudospiralis infected mice. Moreover the in vivo secretion was corroborated by the high difference determinate between the ChE activity of the immuno complexes from T. pseudospiralis infected sera and the immunocomplexes from T. spiralis infected sera as well as normal sera. Finally, we analyzed the effect of the organophosphate NeguvónR (metrifonate on the ChE activity from the J. pseudospiralis ESP. The drug inhibits in part this activity. Moreover NeguvónR (metrifonate showed a high activity against the T. pseudospiralis viability.

  14. Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials.

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    Roberto Raschetti


    Full Text Available BACKGROUND: Mild cognitive impairment (MCI refers to a transitional zone between normal ageing and dementia. Despite the uncertainty regarding the definition of MCI as a clinical entity, clinical trials have been conducted in the attempt to study the role of cholinesterase inhibitors (ChEIs currently approved for symptomatic treatment of mild to moderate Alzheimer disease (AD, in preventing progression from MCI to AD. The objective of this review is to assess the effects of ChEIs (donepezil, rivastigmine, and galantamine in delaying the conversion from MCI to Alzheimer disease or dementia. METHODS AND FINDINGS: The terms "donepezil", "rivastigmine", "galantamine", and "mild cognitive impairment" and their variants, synonyms, and acronyms were used as search terms in four electronic databases (MEDLINE, EMBASE, Cochrane, PsycINFO and three registers: the Cochrane Collaboration Trial Register, Current Controlled Trials, and Published and unpublished studies were included if they were randomized clinical trials published (or described in English and conducted among persons who had received a diagnosis of MCI and/or abnormal memory function documented by a neuropsychological assessment. A standardized data extraction form was used. The reporting quality was assessed using the Jadad scale. Three published and five unpublished trials met the inclusion criteria (three on donepezil, two on rivastigmine, and three on galantamine. Enrolment criteria differed among the trials, so the study populations were not homogeneous. The duration of the trials ranged from 24 wk to 3 y. No significant differences emerged in the probability of conversion from MCI to AD or dementia between the treated groups and the placebo groups. The rate of conversion ranged from 13% (over 2 y to 25% (over 3 y among treated patients, and from 18% (over 2 y to 28% (over 3 y among those in the placebo groups. Only for two studies was it possible to derive point

  15. Adverse Drug Reactions Reported With Cholinesterase Inhibitors : An Analysis of 16 Years of Individual Case Safety Reports From VigiBase

    NARCIS (Netherlands)

    Kroeger, Edeltraut; Mouls, Marie; Wilchesky, Machelle; Berkers, Mieke; Carmichael, Pierre-Hugues; van Marum, Rob; Souverein, Patrick; Egberts, Toine; Laroche, Marie-Laure


    Background: No worldwide pharmacovigilance study evaluating the spectrum of adverse drug reactions (ADRs) induced by cholinesterase inhibitors (ChEI) in Alzheimer's disease has been conducted since their emergence on the market. Objective: To describe ChEI related ADRs in Alzheimer's disease (donepe

  16. Cholinesterases: structure of the active site and mechanism of the effect of cholinergic receptor blockers on the rate of interaction with ligands

    Energy Technology Data Exchange (ETDEWEB)

    Antokhin, A M; Gainullina, E T; Taranchenko, V F [Federal State Agency ' 27 Scientific Centre of Ministry of Defence of the Russian Federation' (Russian Federation); Ryzhikov, S B; Yavaeva, D K [Department of Physics, M.V.Lomonosov Moscow State University (Russian Federation)


    Modern views on the structure of cholinesterase active sites and the mechanism of their interaction with organophosphorus inhibitors are considered. The attention is focused on the mechanism of the effect of cholinergic receptor blockers, acetylcholine antagonists, on the rate of interaction of acetylcholine esterase with organophosphorus inhibitors.


    The effects of N-methyl carbamate pesticides on the photic after discharge (PhAD) of flash evoked potentials (FEPs) and the relationship between inhibition of brain cholinesterase (ChE) activity and the PhAD were evaluated. FEPs were recorded in Long Evans rats treated with physo...

  18. [The high-pressure chemistry, barophysiological chemistry, comparative enzymology of cholinesterase the 100th anniversary from the birth of A. P. Brestkin]. (United States)

    Rozengart, E V


    There are exposed the main landmarks of the scientific biography of Professor Aleksandr Pavlovich Brestkin, connected with his investigations in the field of chemistry of high pressures, physiological chemistry of caisson disease, kinetics of esterase catalysis, and in comparative enzymology of cholinesterases.

  19. Differential acetyl cholinesterase inhibition by volatile oils from two specimens of Marlierea racemosa (Myrtaceae) collected from different areas of the Atlantic Rain Forest. (United States)

    Souza, Amanda; Silva, Michelle C; Cardoso-Lopes, Elaine M; Cordeiro, Inês; Sobral, Marcos E G; Young, Maria Cláudia M; Moreno, Paulo R H


    The volatile oil composition and anti-acetyl cholinesterase activity were analyzed in two specimens of Marlierea racemosa growing in different areas of the Atlantic Rain Forest (Cananéia and Caraguatatuba, SP, Brazil). Component identifications were performed by GC/MS and their acetyl cholinesterase inhibitory activity was measured through colorimetric analysis. The major constituent in both specimens was spathulenol (25.1% in Cananéia and 31.9% in Caraguatatuba). However, the first one also presented monoterpenes (41.2%), while in the Carguatatuba plants, this class was not detected. The oils from the plants collected in Cananéia were able to inhibit the acetyl cholinesterase activity by up to 75%, but for oils from the other locality the maximal inhibition achieved was 35%. These results suggested that the monoterpenes are more effective in the inhibition of acetyl cholinesterase activity than sesquiterpenes as these compounds are present in higher amounts in the M. racemosa plants collected in Cananéia.


    Propoxur is a widely used N-methyl carbamate pesticide that acts by inhibiting cholinesterases (ChE), which may lead to cholinergic toxicity. Flash evoked potentials (FEPs) are a neurophysiological response following stimulation of the visual system with flashes of light. They ar...

  1. Cholinesterase Inhibition and Depression of the Photic After Discharge of Flash Evoked Potentials Following Acute or Repeated Exposures to a Mixture of Carbaryl and Propoxur (United States)

    While information exists regarding inhibition of cholinesterase (ChE) activity, little is known about neurophysiological changes produced by a mixture of N-methyl carbamate pesticides. Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration o...

  2. Effect of temperature and pH on carbamoylation and phosphorylation of serum cholinesterases. Theoretical interpretation of activation energies in complex reactions (United States)

    Simeon, Vera; Reiner, Elsa; Vernon, C. A.


    1. The effect of temperature and pH was studied on the kinetics of inhibition of horse serum and human serum cholinesterase by four organophosphorus compounds and five carbamates. 2. For all compounds, and at each pH and temperature, the inhibition followed the kinetics of a bimolecular reaction with the inhibitor in excess, and with a negligible concentration of the Michaelis complex. 3. The second-order rate constants (ka) for inhibition of human serum cholinesterase by one organophosphate and one carbamate increased from 5° to 40°C with an apparent activation energy of 46kJ/mol (11kcal/mol). 4. The ka constant for inhibition of horse serum cholinesterase increased with temperature from 5° to 30°C, and then decreased from 30° to 40°C. The theoretical interpretation of such an unusual effect of temperature is derived. 5. The increase of ka with pH (human serum cholinesterase) followed the dissociation curve for a single group on the enzyme (pK7.5). 6. Rate constants for decarbamoylation (k+3) were determined, and the time-course of inhibition was calculated from the ka and k+3 constants. PMID:4677141

  3. The Determination of the Whole Blood Cholinesterase Activities of Tree Shrews%树鼩全血胆碱酯酶活性测定分析

    Institute of Scientific and Technical Information of China (English)

    木云珍; 曹慧芳; 周肇晏; 杨彤; 王婧; 李波


    目的 测定分析树鼩全血胆碱酯酶活性.方法 采用WS/T66-1996全血胆碱酯酶活性的羟胺-三氯化铁分光光度法测定10只树鼩和10只小鼠全血胆碱酯酶活性.结果 树鼩的全血胆碱酯酶活性个体差异比小鼠小,树鼩全血胆碱酯酶活性(μmol/mL全血,37℃,30min)绝对值为94.15±4.65,大于小鼠的平均值78.22±8.77,差异具有统计学意义(P<0.05).结论 树鼩在全血胆碱酯酶活性相关研究方面是较好的实验动物.%Objective To determine and analyse the whole blood cholinesterase activities of Tree Shrews. Method The whole blood cholinesterase activities of 10 rats and 10 Tree Shrews were determinted by WS/T66-1996 hydroxylamine hydrochloride- ferric chloride Spectrophotometer. Results The tree shrew's whole blood cholinesterase activity (μmol/mL, 37℃, 30 min) was 94.15± 4.65 , which was higher than mouse's whole blood cholinesterase activity (78.22± 8.77), the difference was statistically significant (P<0.01). Conclusion Tree shrews are excellent experimental animals for the related research on the whole blood cholinesterase activities.

  4. Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Noll Campbell


    Full Text Available Noll Campbell1, Amir Ayub2, Malaz A Boustani2, Chris Fox3, Martin Farlow4, Ian Maidment3, Robert Howard51Wishard Health Services, Indianapolis, Indiana; 2Indiana University Center for Aging Research, Regenstrief Institute, Inc., Indianapolis, Indiana; 3University of Kent, Kent, United Kingdom; 4Indiana University School of Medicine, Indianapolis, Indiana; 5King’s College, London, United KingdomObjective: To determine the efficacy of cholinesterase inhibitors (ChEIs in improving the behavioral and psychological symptoms of dementia (BPSD in patients with Alzheimer’s disease (AD.Data sources: We searched MEDLINE, Cochrane Registry, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL from 1966 to 2007. We limited our search to English Language, full text, published articles and human studies.Data extraction: We included randomized, double-blind, placebo-controlled trials evaluating the efficacy of donepezil, rivastigmine, or galantamine in managing BPSD displayed by AD patients. Using the United States Preventive Services Task Force (USPSTF guidelines, we critically appraised all studies and included only those with an attrition rate of less than 40%, concealed measurement of the outcomes, and intention to treat analysis of the collected data. All data were imputed into pre-defined evidence based tables and were pooled using the Review Manager 4.2.1 software for data synthesis.Results: We found 12 studies that met our inclusion criteria but only nine of them provided sufficient data for the meta-analysis. Among patients with mild to severe AD and in comparison to placebo, ChEIs as a class had a beneficial effects on reducing BPSD with a standard mean difference (SMD of −0.10 (95% confidence interval [CI]; −0.18, −0.01 and a weighted mean difference (WMD of −1.38 neuropsychiatry inventory point (95% CI; −2.30, −0.46. In studies with mild AD patients, the WMD was −1.92 (95% CI; −3.18, −0.66; and in studies

  5. Predictive value of serum cholinesterase for the prognosis of aged patients with systemic inflammatory response syndrome

    Institute of Scientific and Technical Information of China (English)

    JIN Qi-hui; HE Xiao-jun; LI Tian-lang; CHEN Huai-hong


    Background Some studies found that cholinesterase (ChE) can be an independent risk factor for patients with multiple organ dysfunction syndrome.To assess aged patients with systemic inflammatory response syndrome (SIRS) early and predict their prognosis,the predictive value of ChE for the prognosis of aged patients with SIRS was analyzed.Methods From September 2009 to September 2010,all aged patients with SIRS in the ICU of the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed if they met inclusion criteria:patients aged >65 years and met American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria for SIRS.Serum ChE,albumin,D-dimer,lactic acid and C-reactive protein (CRP) were measured,and the Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ and Glasgow Coma Scale (GCS) scores were evaluated within the first 24 hours in the ICU.Fisher's exact test was used for comparison of the primary disease between the deceased group and surviving group.For comparison of study variables between the two groups,the Student's t test or Mann-Whitney U test was used.Multivariate significance was tested with binary Logistic regression analysis.Results The clinical data of 124 aged patients with SIRS were collected and analyzed.Sixty-six patients (46 male,20female,mean age (78.70±8.08) years) who died were included in the deceased group and 58 patients (34 male,24female,mean age (76.02±6.57) years) who survived were included in the surviving group.There were no significant differences in age,gender,APACHE Ⅱ score and GCS score between the deceased group and surviving group (all P>0.05),but there were significant differences in lactic acid (P=0.011),D-dimer (P=0.011),albumin (P=0.007),CRP (P=0.008),and ChE (P <0.0001).The correlation analysis showed that the APACHE Ⅱ score and CRP were not correlated with ChE (both P <0.05).D-dimer and albumin were correlated with Ch

  6. Ferulic acid-carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents. (United States)

    Fang, Lei; Chen, Mohao; Liu, Zhikun; Fang, Xubin; Gou, Shaohua; Chen, Li


    In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid-carbazole hybrid compounds were designed and synthesized. Ellman's assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC50 1.9μM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture.

  7. Identifying motor and sensory myelinated axons in rabbit peripheral nerves by histochemical staining for carbonic anhydrase and cholinesterase activities (United States)

    Riley, Danny A.; Sanger, James R.; Matloub, Hani S.; Yousif, N. John; Bain, James L. W.


    Carbonic anhydrase (CA) and cholinesterase (CE) histochemical staining of rabbit spinal nerve roots and dorsal root ganglia demonstrated that among the reactive myeliated axons, with minor exceptions, sensory axons were CA positive and CE negative whereas motor axons were CA negative and CE positive. The high specificity was achieved by adjusting reaction conditions to stain subpopulations of myelinated axons selectively while leaving 50 percent or so unstained. Fixation with glutaraldehyde appeared necessary for achieving selectivity. Following sciatic nerve transection, the reciprocal staining pattern persisted in damaged axons and their regenerating processes which formed neuromas within the proximal nerve stump. Within the neuromas, CA-stained sensory processes were elaborated earlier and in greater numbers than CE-stained regenerating motor processes. The present results indicate that histochemical axon typing can be exploited to reveal heterogeneous responses of motor and sensory axons to injury.

  8. Reactivation of human brain homogenate cholinesterases inhibited by Tabun using newly developed oximes K117 and K127. (United States)

    Kuca, Kamil; Cabal, Jiri; Jung, Yung Sik; Musilek, Kamil; Soukup, Ondrej; Jun, Daniel; Pohanka, Miroslav; Musilova, Lucie; Karasová, Jana; Novotný, Ladislav; Hrabinova, Martina


    Newly developed acetylcholinesterase reactivators K117 [1,5-bis(4-hydroxyiminomethylpyridinium)-3-oxapentane dichloride] and K127 [(1-(4-hydroxyiminomethylpyridinium)-5-(4-carbamoylpyridinium)-3-oxapentane dibromide)] were tested for their potency to reactivate tabun-inhibited human brain cholinesterases. Pralidoxime and trimedoxime were chosen as standard reference reactivators. Human tissue was used, as that was closer on the real treatment of human beings. As a result, oxime K127 was found as the best tested reactivator according to the constant k(r), characterizing the overall reactivation process. On the contrary, the maximal reactivation ability expressed as percentage of reactivation was the best for trimedoxime. This differences were caused as a result of using the enzyme from different species. Due to this, experiments on human tissue should be conducted after in vitro and in vivo tests on animals to eliminate such important failures of promising oximes.

  9. Characterization of plasma cholinesterase from the White stork (Ciconia ciconia) and its in vitro inhibition by anticholinesterase pesticides. (United States)

    Oropesa, Ana-Lourdes; Gravato, Carlos; Sánchez, Susana; Soler, Francisco


    Blood plasma cholinesterase (ChE) activity is a sensitive biomarker of exposure to organophosphorus (OP) and carbamate (CB) insecticides in vertebrates. Several studies indicate that more than one ChE form may be present in blood of birds. In this study the predominant ChE activity (acetylcholinesterase - AChE- or butyrylcholinesterase - BChE-), the range of ChE activity as well as ChE age-dependent changes in non-exposed individuals of White stork (Ciconia ciconia) have been established. The in vitro sensitivity of ChE to OP and CB insecticides such as paraoxon-methyl, carbofuran and carbaryl was also investigated. Plasma ChE was characterised using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three ChE inhibitors (eserine sulphate, BW284C51 and iso-OMPA). The results indicated that propionylthiocholine was the preferred substrate by plasma cholinesterase followed by acetylcholine and butyrylcholine and the predominant enzymatic activity in plasma of White storks was BChE. Normal plasma BChE activity in White stork was 0.32±0.01μmol/min/ml for adults and 0.28±0.03μmol/min/ml for juveniles. So, the age had no significant effect on the range of BChE activity. The study on the in vitro inhibitory potential of tested anticholinesterase pesticides on plasma ChE activity revealed that paraoxon-methyl is the most potent inhibitor followed by carbofuran and finally by carbaryl. The percentage of in vitro plasma ChE inhibition was observed to be similar between adults and juveniles.

  10. Effect of cholinesterase inhibitor galanthamine on circulating tumor necrosis factor alpha in rats with lipopolysaccharide induced peritonitis

    Institute of Scientific and Technical Information of China (English)

    LIU Zhi-hai; MA Yue-feng; WU Jun-song; GAN Jian-xin; XU Shao-wen; JIANG Guan-yu


    Background The nervous system, through the vagus nerve and its neurotransmitter acetylcholine, can down-regulate the systemic inflammation in vivo, and recently, a role of brain cholinergic mechanisms in activating this cholinergic anti-inflammatory pathway has been indicated. Galanthamine is a cholinesterase inhibitor and one of the centrally acting cholinergic agents available in clinic. This study aimed to evaluate the effect of galanthamine on circulating tumor necrosis factor alpha (TNF-α) in rats with lipopolysaccharide-induced peritonitis and the possible role of the vagus nerve in the action of galanthamine.Methods Rat models of lipopolysaccharide-induced peritonitis and bilateral cervical vagotomy were produced. In the experiment 1, the rats were randomly divided into control group, peritonitis group, and peritonitis groups treated with three dosages of galanthamine. In the experiment 2, the rats were randomly divided into sham group, sham plus peritonitis group, sham plus peritonitis group treated with galanthamine, vagotomy plus peritonitis group, and vagotomy plus peritonitis group treated with galanthamine. The levels of plasma TNF-α were determined in every group. Results The level of circulating TNF-α was significantly increased in rats after intraperitoneal injection of endotoxin. Galanthamine treatment decreased the level of circulating TNF-α in rats with lipopolysaccharide-induced peritonitis, and there was significant difference compared with rats with lipopolysaccharide-induced peritonitis without treatment. The 3 mg/kg dosage of galanthamine had the most significant inhibition on circulating TNF-α level at all the three tested doses. Galanthamine obviously decreased the TNF-α level in rats with lipopolysaccharide-induced peritonitis with sham operation, but could not decrease the TNF-α level in rats with lipopolysaccharide-induced peritonitis with vagotomy. Conclusion Cholinesterase inhibitor galanthamine has an inhibitory effect on TNF

  11. Chronic exposure to cigarette smoke during gestation results in altered cholinesterase enzyme activity and behavioral deficits in adult rat offspring: potential relevance to schizophrenia. (United States)

    Zugno, Alexandra I; Fraga, Daiane B; De Luca, Renata D; Ghedim, Fernando V; Deroza, Pedro F; Cipriano, Andreza L; Oliveira, Mariana B; Heylmann, Alexandra S A; Budni, Josiane; Souza, Renan P; Quevedo, João


    Prenatal cigarette smoke exposure (PCSE) has been associated with physiological and developmental changes that may be related to an increased risk for childhood and adult neuropsychiatric diseases. The present study investigated locomotor activity and cholinesterase enzyme activity in rats, following PCSE and/or ketamine treatment in adulthood. Pregnant female Wistar rats were exposed to 12 commercially filtered cigarettes per day for a period of 28 days. We evaluated motor activity and cholinesterase activity in the brain and serum of adult male offspring that were administered acute subanesthetic doses of ketamine (5, 15 and 25 mg/kg), which serves as an animal model of schizophrenia. To determine locomotor activity, we used the open field test. Cholinesterase activity was assessed by hydrolysis monitored spectrophotometrically. Our results show that both PCSE and ketamine treatment in the adult offspring induced increase of locomotor activity. Additionally, it was observed increase of acetylcholinesterase and butyrylcholinesterase activity in the brain and serum, respectively. We demonstrated that animals exposed to cigarettes in the prenatal period had increased the risk for psychotic symptoms in adulthood. This also occurs in a dose-dependent manner. These changes provoke molecular events that are not completely understood and may result in abnormal behavioral responses found in neuropsychiatric disorders, such as schizophrenia.

  12. Plasma cholinesterase inhibition in the clay-colored robin (Turdus grayi) exposed to diazinon in maradol papaya crops in Yucatan, Mexico (United States)

    Cobos, V.M.; Mora, M.A.; Escalona, G.


    The use of organophosphorous pesticides in agriculture can result in intoxication of birds foraging in sprayed crops. Effects on birds resulting from pesticide intoxication are varied and include behavioral and reproductive effects, including death. One widely used insecticide in Maradol papaya crops is diazinon which has been associated with various incidents of intoxication and death of wild birds. The objective of this study was to evaluate the impact of diazinon application to papaya crops on plasma cholinesterase activity of the clay-colored robin (Turdus grayi). We captured clay-colored robins foraging in a papaya crop the following day after the field had been sprayed with diazinon at a dose of 1.5 kg/ha during March and May, respectively. We took a blood sample from the brachialis vein of the birds captured and measured plasma enzymatic activity. The plasma samples from birds used as controls were taken during the same time period and were analyzed in a similar way. Enzymatic activity of males was greater than that of females (53,52%) and mean cholinesterase inhibition was 49.43%. Cholinesterase inhibition was greater during May than in March probably due to more continuous exposure and ingestion of the insecticide through food and possible absorption through the skin. This degree of enzymatic inhibition is possibly affecting the behavior of the clay-colored robin and could result in death in severe cases.

  13. Inhibition and recovery of maternal and fetal cholinesterase enzyme activity following a single cutaneous dose of methyl parathion and diazinon, alone and in combination, in pregnant rats. (United States)

    Abu-Qare, A W; Abou-Donia, M B


    Pregnant Sprague-Dawley rats (14-18 days of gestation) were treated with a single cutaneous subclinical dose(s) of 10 mg kg(-1) (15% of LD(50)) of methyl parathion (O,O-dimethyl O-4-nitrophenyl phosphorothioate) and 65 mg kg(-1) (15% of LD(50)) of diazinon (O,O)-diethyl O-2-isopropyl-6-methylpyrimidinyl phosphorothioate, and their combination. Animals were sacrificed at 1, 2, 4, 12, 24, 48, 72, and 96 h after dosing. Inhibition of maternal and fetal cholinesterase enzyme activity has been determined. Methyl parathion significantly inhibited maternal and fetal brain acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) activity within 24 h after dosing. Diazinon and a mixture of methyl parathion and diazinon caused lesser inhibition compared with methyl parathion alone. Recovery of maternal and fetal brain AChE activity was in the order of diazinon > combination of diazinon and methyl parathion > methyl parathion 96 h after dosing. Although fetal plasma BuChE activity recovered to 100% of control within 96 h of application, maternal BuChE activity remained inhibited to 55% and 32% of control 96 h after application of methyl parathion and a mixture of methyl parathion and diazinon, respectively. Following a single dermal dose of methyl parathion, the activity of maternal liver BuChE was 63% of control 2 h after dosing, whereas inhibition of placental AChE or BuChE activity occurred 12 and 1 h following a single dose of methyl parathion, corresponding to activities of 63% and 54% of control, respectively. Diazinon, alone or in combination with methyl parathion, did not inhibit significantly the maternal liver BuChE or placental AChE and BuChE activity. The results suggest that dermal application of a single dose of methyl parathion and diazinon, alone or in combination, has an easy access into maternal and fetal tissues, resulting in inhibition of cholinesterase enzymes. The lower inhibitory effect of the combination of methyl parathion and diazinon

  14. Transthyretin as a potential CSF biomarker for Alzheimer's disease and dementia with Lewy bodies: effects of treatment with cholinesterase inhibitors

    DEFF Research Database (Denmark)

    Schultz, K; Nilsson, K; Nielsen, Jørgen Erik


    BACKGROUND: Previous studies have indicated that transthyretin (TTR) levels in cerebrospinal fluid (CSF) are altered in depression and dementia. The present study aimed to investigate whether CSF TTR can be used to discriminate between patients with Alzheimer's disease (AD) and patients with deme......BACKGROUND: Previous studies have indicated that transthyretin (TTR) levels in cerebrospinal fluid (CSF) are altered in depression and dementia. The present study aimed to investigate whether CSF TTR can be used to discriminate between patients with Alzheimer's disease (AD) and patients...... with dementia with Lewy bodies (DLB) with or without medication, as well as to reveal whether CSF TTR correlates with depression in dementia. METHODS: CSF samples from 59 patients with AD, 13 patients with DLB and 13 healthy controls were collected, and biochemical analysis was performed. Subjects were assessed...... for the presence of depression. RESULTS: No significant differences in CSF TTR were found between AD, DLB, and control subjects or between depressed and non-depressed dementia patients. Interestingly, we found a significant reduction in CSF TTR (14%) in AD patients who were medicated with cholinesterase inhibitors...

  15. Monitoring exposure of northern cardinals, Cardinalis cardinalis, to cholinesterase-inhibiting pesticides: enzyme activity, reactivations, and indicators of environmental stress. (United States)

    Maul, Jonathan D; Farris, Jerry L


    Northern cardinals (Cardinalis cardinalis) frequently use agricultural field edges in northeast Arkansas, USA, and may be at risk of exposure to cholinesterase (ChE)-inhibiting pesticides. We monitored northern cardinal exposure to ChE-inhibiting pesticides by comparing plasma total ChE (TChE) activity to reference-derived benchmarks and TChE reactivations. Total ChE and acetylcholinesterase (AChE) were measured for 128 plasma samples from 104 northern cardinals from nine study sites. Of birds sampled from sites treated with ChE-inhibiting pesticides, 4.3% of the samples had TChE activities below the diagnostic threshold (2 standard deviations [SD] below the reference mean) and 8.7% of the samples had TChE reactivations. No difference was found in TChE (p = 0.553) and AChE (p = 0.288) activity between treated and reference sites; however, activity varied among treated sites (p = 0.003). These data do not suggest uniform exposure to individuals, but rather exposure was variable and likely influenced by mitigating factors at individual and site scales. Furthermore, monitoring of TChE reactivation appeared to be a more sensitive indicator of exposure than the diagnostic threshold. Fluctuating asymmetry (FA) was greater at agricultural sites than reference sites (p = 0.016), supporting the hypothesis that FA may be useful for assessing a combination of habitat- and contaminant-related environmental stress.

  16. The Use of Selected Biomarkers, Phagocytic and Cholinesterase Activity to Detect the Effects of Dimethoate on Marine Mussel (Mytilus edulis

    Directory of Open Access Journals (Sweden)



    Full Text Available Effects of organophosphorous pesticide, dimethoate on blue mussels, Mytilus edulis using selected biomarkers have been studied. Mussels were exposed to serial dilutions of dimethoate, 7.88, 15.75, 31.35, and 63.00 µg/l including positive and negative controls for 14 days. The suppression effects of dimethoate on phagocytic activity significantly occurred at two lowest concentrations of dimethoate (7.88 and 15.75 µg/l, but stimulation effects significantly emerged at the following highest concentrations (31.35 and 63.00 µg/l. The declining tendency of the cholinesterase (ChE activity (23% lower than the control appeared when mussels exposed to 7.88 and 15.75 µg/l dimethoate. Moreover, the significant inhibition of the ChE activity occurred at 31.35 µg/l dimethoate exposure. This study suggested that the phagocytic and the ChE activity are useful biomarkers for assessing the affects of organophosporous pesticide, dimethoate on neuro-immune system of blue mussels, M. edulis.

  17. Assessment of antioxidant, anti-inflammatory, anti-cholinesterase and cytotoxic activities of pomegranate (Punica granatum) leaves. (United States)

    Bekir, Jalila; Mars, Mohamed; Souchard, Jean Pierre; Bouajila, Jalloul


    This study evaluated antioxidant, anti-inflammatory, anti-cholinesterase and cytotoxic activities of extracts with different polarities (hexane, dichloromethane, ethyl acetate, ethanol and methanol) obtained from Punica granatum leaves. Total phenolics (8.8-127.3mg gallic acid equivalent/g dry weight), flavonoids (1.2-76.9mg quercetin equivalent/g dry weight), tannins (63.7-260.8mg catechin equivalent/kg dry weight) and anthocyanins (0.41-3.73mg cyanidin-3-glucoside equivalent/g dry weight) of different extracts were evaluated. The methanolic extract presented a good IC50 by DPPH and ABTS assays (5.62 and 1.31mg/l respectively). The strongest 5-lipoxygenase (5-LOX), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition activities were obtained for the ethanol extract (IC50 values of 6.20, 14.83 and 2.65mg/l, respectively) and the best cytotoxic activity against MCF-7 cells was obtained for the methanol extract (IC50=31mg/l). These important biological activities showed that P. granatum leaves could be a potential source of the active molecules intended for applications in pharmaceutical industry, but only after additional in vivo experiments.

  18. Acetylcholine muscarinic receptors and response to anti-cholinesterase therapy in patients with Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Derek [Department of Psychiatry, Stobhill Hospital, Glasgow (United Kingdom); Chisholm, Jennifer A.; Patterson, Jim; Wyper, David [Department of Clinical Physics, Southern General Hospital, Glasgow, G51 4TF (United Kingdom); Owens, Jonathan; Pimlott, Sally [Department of Clinical Physics, Western Infirmary, Glasgow (United Kingdom)


    An acetylcholine deficit remains the most consistent neurotransmitter abnormality found in Alzheimer's disease and various therapeutic agents have been targeted at this. In this study we investigated the action of Donepezil, a cholinesterase inhibitor that has few side-effects. In particular we set out to investigate whether muscarinic acetylcholine receptor (mAChR) availability influences the response to this therapy. We used the novel single-photon emission tomography (SPET) tracer (R,R)[{sup 123}I]I-quinuclidinyl benzilate (R,R[{sup 123}I]I-QNB), which has high affinity for the M1 subtype of mAChR. Regional cerebral perfusion was also assessed using technetium-99m hexamethylpropylene amine oxime. We investigated 20 patients on Donepezil treatment and ten age-matched controls. The results showed a reduction in (R,R)[{sup 123}I]I-QNB binding in the caudal anterior cingulate in patients compared with controls and relatively high binding in the putamen and rostral anterior cingulate, suggesting a relative sparing of mAChR in these regions. The main finding of the study was that mAChR availability as assessed by (R,R)[{sup 123}I]I-QNB binding did not distinguish responders from non-responders. Interestingly, we found that the extent of cognitive improvement showed no positive correlation with (R,R)[{sup 123}I]I-QNB binding in any brain region but was inversely related to binding in the insular cortex. This suggests that, within the advised cognitive performance band for use of Donepezil, response is greater in those patients with evidence of a more marked cholinergic deficit. A larger study should investigate this. (orig.)

  19. Integrated Lateral Flow Test Strip with Electrochemical Sensor for Quantification of Phosphorylated Cholinesterase: Biomarker of Exposure to Organophosphorus Agents

    Energy Technology Data Exchange (ETDEWEB)

    Du, Dan; Wang, Jun; Wang, Limin; Lu, Donglai; Lin, Yuehe


    An integrated lateral flow test strip with electrochemical sensor (LFTSES) device with rapid, selective and sensitive response for quantification of exposure to organophosphorus (OP) pesticides and nerve agents has been developed. The principle of this approach is based on parallel measurements of post-exposure and baseline acetylcholinesterase (AChE) enzyme activity, where reactivation of the phosphorylated AChE is exploited to enable measurement of total amount of AChE (including inhibited and active) which is used as a baseline for calculation of AChE inhibition. Quantitative measurement of phosphorylated adduct (OP-AChE) was realized by subtracting the active AChE from the total amount of AChE. The proposed LFTSES device integrates immunochromatographic test strip technology with electrochemical measurement using a disposable screen printed electrode which is located under the test zone. It shows linear response between AChE enzyme activity and enzyme concentration from 0.05 to 10 nM, with detection limit of 0.02 nM. Based on this reactivation approach, the LFTSES device has been successfully applied for in vitro red blood cells inhibition studies using chlorpyrifos oxon as a model OP agent. This approach not only eliminates the difficulty in screening of low-dose OP exposure because of individual variation of normal AChE values, but also avoids the problem in overlapping substrate specificity with cholinesterases and avoids potential interference from other electroactive species in biological samples. It is baseline free and thus provides a rapid, sensitive, selective and inexpensive tool for in-field and point-of-care assessment of exposures to OP pesticides and nerve agents.

  20. Altered quantities and in vivo activities of cholinesterase from Daphnia magna in sub-lethal exposure to organophosphorus insecticides. (United States)

    Liu, Hongcui; Yuan, Bingqiang; Li, Shaonan


    For investigating relationship between activity of cholinesterase (ChE) and ambient concentration of anticholinesterases, Daphnia magna had been exposed for 21 day to sub-lethal concentrations, i.e. 1/6 EC(50), 1/36 EC(50), and 1/216 EC(50), of either triazophos or chlorpyrifos. Samples were taken at different points of time for measuring total activity and immunoreactive content of ChE and actual concentrations of the anticholinesterases. A type of antigen formerly developed by immunizing mice with purified ChE was utilized in this study to establish an indirect non-competitive ELISA for measuring immunoreactive content of ChE in Daphnia. Studies showed that for apparent activity, i.e. activity that was scaled with total protein, the insecticides caused 5.2-6.9 percent inhibition and 17.0-17.7 percent inductions during the 21 d exposure, whereas for inherent activity, i.e. activity that was scaled with immunoreactive protein, no induction was detected during the exposure. Accompanied by up to 65.9 percent and 68.0 percent promotion in terms of the immunoreactive content, up to 42.8 percent and 44.6 percent inhibition in terms of the inherent activity was indicated, respectively, for triazophos and chlopyrifos. Judged by measured concentrations, the inherent activity recovered faster than the rate of dissipation of the anticholinesterases. Result of the study suggested that the inherent activity was more sensitive than the apparent one in predicting sub-lethal and/or long-term stress of anticholinesterases. It also suggested that apart from promotion in terms of content of the ChE, the Daphnia developed capacities to block bio-concentration of anticholinesterases, and these capacities would make it liable to underestimate ambient concentration of anticholinesterases along with the time of exposure.

  1. Characterisation of cholinesterases and evaluation of the inhibitory potential of chlorpyrifos and dichlorvos to Artemia salina and Artemia parthenogenetica. (United States)

    Varó, I; Navarro, J C; Amat, F; Guilhermino, L


    In this study, the acute toxicity of the organophosphorous pesticides dichlorvos and chlorpyrifos to two different species of Artemia (A. salina and A. parthenogenetica) was evaluated. In addition, the in vivo effect of these two pesticides on cholinesterase (ChE) activity of both A. salina and A. parthenogenetica was also determined. The characterisation of the ChE, using different substrates and specific inhibitors, and the normal range of activity in non-exposed individuals were previously investigated for both species. The results obtained indicate that the ChE of A. salina is different from that of A. parthenogenetica and that both enzymes cannot be classified neither as acetylcholinesterase nor as butyrylcholinesterase since they show intermediary characteristics between the two vertebrate forms. The range of normal ChE activity was 2.65+/-0.15 U/mg protein for A. salina, and 3.69+/-0.17 U/mg protein for A. parthenogenetica. Significant in vivo effects of both pesticides on Artemia ChE activity were found, at concentrations between 5.38 and 9.30 mg/l for dichlorvos and between 1.85 and 3.19 mg/l for chlorpyrifos. Both Artemia species are resistant to these pesticides and they are able to survive with more than 80% ChE inhibition. However, A. parthenogenetica is more resistant than A. salina, with about a 95% reduction in its ChE activity respect to the control for nauplii exposed to the median lethal concentrations (LC50), without lethal effects after 24 h of exposure.

  2. Efficacy of novel phenoxyalkyl pyridinium oximes as brain-penetrating reactivators of cholinesterase inhibited by surrogates of sarin and VX. (United States)

    Chambers, Janice E; Chambers, Howard W; Funck, Kristen E; Meek, Edward C; Pringle, Ronald B; Ross, Matthew K


    Pyridinium oximes are strong nucleophiles and many are effective reactivators of organophosphate-inhibited cholinesterase (ChE). However, the current oxime reactivators are ineffective at crossing the blood-brain barrier and reactivating brain ChE in the intact organism. Our laboratories have developed a series of substituted phenoxyalkyl pyridinium oximes (US patent 9,227,937 B2) with the goal of identifying reactivators effective in crossing the blood-brain barrier. The first 35 of the series were found to have similar in vitro efficacy as reactivators of ChE inhibited by a sarin surrogate (phthalimidyl isopropyl methylphosphonate, PIMP) or a VX surrogate (nitrophenyl ethyl methylphosphonate, NEMP) in bovine brain preparations as previously observed in rat brain preparations. A number of these novel oximes have shown the ability to decrease the level of ChE inhibition in the brains of rats treated with a high sublethal dosage of either a sarin surrogate (nitrophenyl isopropyl methylphosphonate, NIMP) or the VX surrogate NEMP. Levels of reactivation at 2 h after oxime administration were up to 35% while the currently approved therapeutic, 2-PAM, yielded no reduction in brain ChE inhibition. In addition, there was evidence of attenuation of seizure-like behavior with several of the more effective novel oximes, but not 2-PAM. Therefore these novel oximes have demonstrated an ability to reactivate inhibited ChE in brain preparations from two species and in vivo data support their ability to enter the brain and provide a therapeutic action. These novel oximes have the potential to be developed into improved antidotes for nerve agent therapy.

  3. An unexpected plasma cholinesterase activity rebound after challenge with a high dose of the nerve agent VX. (United States)

    Dorandeu, F; Foquin, A; Briot, R; Delacour, C; Denis, J; Alonso, A; Froment, M T; Renault, F; Lallement, G; Masson, P


    Organophosphorus chemical warfare agents (nerve agents) are to be feared in military operations as well as in terrorist attacks. Among them, VX (O-ethyl-S-[2-(diisopropylamino)ethyl] methylphosphonothioate) is a low volatility liquid that represents a percutaneous as well as an inhalation hazard if aerosolized. It is a potent irreversible cholinesterase (ChE) inhibitor that causes severe signs and symptoms, including respiratory dysfunction that stems from different mechanisms. VX-induced pulmonary oedema was previously reported in dogs but mechanisms involved are not well understood, and its clinical significance remains to be assessed. An experimental model was thus developed to study VX-induced cardiovascular changes and pulmonary oedema in isoflurane-anaesthetized swine. In the course of this study, we observed a fast and unexpected rebound of plasma ChE activity following inhibition provoked by the intravenous injection of 6 and 12 microg kg(-1) of VX. In whole blood ChE activity, the rebound could stay unnoticed. Further investigations showed that the rebound of plasma esterase activity was neither related to spontaneous reactivation of ChE nor to VX-induced increase in paraoxonase/carboxylesterase activities. A bias in Ellman assay, haemoconcentration or severe liver cytolysis were also ruled out. All in all, these results suggest that the rebound was likely due to the release of butyrylcholinesterase into the blood stream from ChE producing organs. Nature of the organ(s) and mechanisms involved in enzyme release will need further investigations as it may represent a mechanism of defence, i.e. VX scavenging, that could advantageously be exploited.


    Directory of Open Access Journals (Sweden)

    Prashant S


    Full Text Available BACKGROUND : Organophosphorus (OP poisoning is a major public health problem in developing world. OP pesticides inhibit carboxylic esterase enzymes including plasma cholinesterase (PChE. Clinical manifestations following OP poisoning can be associated with the extent of decrease of PChE. This study was designed to investigate the relevance of diastolic function of the heart, severity of diastolic dysfunction and the reversibility of dysfunction in organophosphoru s compound poisoning patients in relation to plasma cholinesterase (PChE levels with the treatment. MATERIALS AND METHODS : 76 patients admitted with organophosphorus compound poisoning were evaluated for diastolic dysfunction by echocardiography. Clinical features and the nature of compound involved were recorded. Severity of diastolic dysfunction was assessed. Cholinesterase levels were assessed. Initially there was worsening of diastolic function. As the treatment progressed, there was improvement in the pattern of diastolic dysfunction with the corresponding improvement in cholinesterase level and clinical improvement. This was a cross - sectional study which was conducted from 1st January 2014 to February 2015. RESULTS : In total, mean age of patients were 31.2 (range : 19 - 46 years. Majority of patients were females (68.4%, and agricultural workers (75%. Main clinical findings at the time of admission were congested conjunctiva (83%, pin point pupil (89%, lacrimation (78%, vomiting (69%, non - reactive pupil (85%, respiratory distress (65% and abdominal pain (45%. Mean (SD PChE at 6 hours post - exposure was 3242.6 IU/L. At presentation, cyanosis, muscle weakness, convulsion, respiratory distress and fasciculation were related to cases with >75%reducti on of PChE, while, constricted and nonreactive pupil, lacrimation and congested conjunctivae were related to cases with 50 - 75% reduction and abdominal pain, dryness of conjunctiva, vomiting and diarrhea were related to <50

  5. Effect of a mixture of pyridostigmine and atropine on forced expiratory volume (FEV1), and serum cholinesterase activity in normal subjects

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B F; Gefke, Kaj; Mosbech, H


    Pyridostigmine 0.143 mg kg-1 (maximum 10 mg) and atropine 0.0143 mg kg-1 (maximum 1 mg) were administered i.v. to six healthy male volunteers. Peripheral venous blood samples were drawn for measurement of serum cholinesterase activity. Maximum inhibition of the enzyme was found 5 min after...... injection with a decrease to 27 +/- 5% (mean +/- SEM) of the original activity. Forced expiratory volume in the first 1s (FEV1) was measured at fixed time intervals for 90 min. No decrease in FEV1 was observed; on the contrary, there was a small increase. We conclude that atropine effectively antagonizes...

  6. One-pot synthesis of tetrazole-1,2,5,6-tetrahydronicotinonitriles and cholinesterase inhibition: Probing the plausible reaction mechanism via computational studies. (United States)

    Hameed, Abdul; Zehra, Syeda Tazeen; Abbas, Saba; Nisa, Riffat Un; Mahmood, Tariq; Ayub, Khurshid; Al-Rashida, Mariya; Bajorath, Jürgen; Khan, Khalid Mohammed; Iqbal, Jamshed


    In the present study, one-pot synthesis of 1H-tetrazole linked 1,2,5,6-tetrahydronicotinonitriles under solvent-free conditions have been carried out in the presence of tetra-n-butyl ammonium fluoride trihydrated (TBAF) as catalyst and solvent. Computational studies have been conducted to elaborate two plausible mechanistic pathways of this one-pot reaction. Moreover, the synthesized compounds were screened for cholinesterases (acetylcholinesterase and butyrylcholinesterase) inhibition which are consider to be major malefactors of Alzheimer's disease (AD) to find lead compounds for further research in AD therapy.

  7. Brain choline acetyltransferase and muscarinic receptor sites, brain and liver cholinesterases in precocial Acomys cahirinus and altricial rat during post-natal development. (United States)

    Michalek, H; Pintor, A; Fortuna, S; Bisso, G M


    Brain choline acetyltransferase, acetylcholinesterase with its molecular forms, and muscarinic receptor sites, as well as liver total cholinesterases were evaluated during the first postnatal month in pups of a precocial (Acomys cahirinus) and altricial (rat) murid species. At birth the levels of brain cholinergic markers were higher in the Acomys than in the rat, but in adulthood the differences were smaller or even reversed. The postnatal increase up in the markers to weaning was considerably more pronounced in the rat. However, substantial variations in the patterns of development of the three cholinergic markers within and between species were observed. Liver cholinesterases were considerably higher in Acomys than in rats at all ages investigated. These and literature data are discussed in relation to postnatal, post-conception and post-organogenesis age of pups belonging to the two species. The variability of the ontogenetic patterns between the enzymes suggests that there is some biological control of individual rates of maturation and that it is necessary to be careful in broadly interpreting growth patterns across organs within the same species and across species.

  8. Impact of repeated nicotine and alcohol coexposure on in vitro and in vivo chlorpyrifos dosimetry and cholinesterase inhibition. (United States)

    Lee, S; Poet, T S; Smith, J N; Hjerpe, A L; Gunawan, R; Timchalk, C


    Chlorpyrifos (CPF) is an organophosphorus insecticide, and neurotoxicity results from inhibition of acetylcholinesterase (AChE) by its metabolite, chlorpyrifos-oxon. Routine consumption of alcohol and tobacco modifies metabolic and physiological processes impacting the metabolism and pharmacokinetics of other xenobiotics, including pesticides. This study evaluated the influence of repeated ethanol and nicotine coexposure on in vivo CPF dosimetry and cholinesterase (ChE) response (ChE- includes AChE and/or butyrylcholinesterase (BuChE)). Hepatic microsomes were prepared from groups of naive, ethanol-only (1 g/kg/d, 7 d, po), and ethanol + nicotine (1 mg/kg/d 7 d, sc)-treated rats, and the in vitro metabolism of CPF was evaluated. For in vivo studies, rats were treated with saline or ethanol (1 g/kg/d, po) + nicotine (1 mg/kg/d, sc) in addition to CPF (1 or 5 mg/kg/d, po) for 7 d. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), in blood and urine and the plasma ChE and brain acetylcholinesterase (AChE) activities were measured in rats. There were differences in pharmacokinetics, with higher TCPy peak concentrations and increased blood TCPy AUC in ethanol + nicotine groups compared to CPF only (approximately 1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain AChE activities after ethanol + nicotine treatments showed significantly less inhibition following repeated 5 mg CPF/kg dosing compared to CPF only (96 ± 13 and 66 ± 7% of naive at 4 h post last CPF dosing, respectively). Although brain AChE activity was minimal inhibited for the 1-mg CPF/kg/d groups, the ethanol + nicotine pretreatment resulted in a similar trend (i.e., slightly less inhibition). No marked differences were observed in plasma ChE activities due to the alcohol + nicotine treatments. In vitro, CPF metabolism was not markedly affected by repeated ethanol or both ethanol + nicotine exposures. Compared with a previous study of nicotine and CPF exposure, there were no

  9. Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur. (United States)

    Padilla, S; Marshall, R S; Hunter, D L; Lowit, A


    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r(2)=0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r(2)=0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides.


    Carbaryl and propoxur are N-methyl carbamate pesticides (NMCs) which are part of the EPA’s cumulative risk assessments for NMCs. These NMCs inhibit cholinesterase (ChE) activity and may lead to cholinergic disruption of CNS function. We used decreases in the PhAD of FEPs to indic...

  11. Nonquaternary Cholinesterase Reactivators. (United States)


    C2H5O(e)P(O)OX + H20 - products (15) K BOX __a__ OX + H+ (16) Equations (7) and (8) show the reaction of enzyme (EOH) with EPMP to yield ethyl ...kinetics. The reactivation of ethyl methylphosphonyl-AChE proceeds via the mechanism shown in equation (14): K rr OX + EOP [OX°EOP] - EOP + products (14... ether eluant. The crude product was dissolved in a minimal amount of ether and placed on a silica-gel column. Fractions of 40 mL were collected and

  12. Scutellarin protects against Aβ-induced learning and memory deficits in rats: involvement of nicotinic acetylcholine receptors and cholinesterase

    Institute of Scientific and Technical Information of China (English)

    Li-li GUO; Zhi-zhong GUAN; Yong-lin WANG


    increased,but were significantly decreased in the plasma,as compared to the control and the sham operation groups.Scu or piracetam treatment restored the activities in brain and plasma nearly to the levels in the control group.Conclusion:The results suggest that Scu may rescue some of the deleterious effects of Aβ,possibly by stimulating nAChR protein translation and regulating cholinesterase activity.

  13. Toxicity of parathion on embryo and yolk-sac larvae of gilthead seabream (Sparus aurata l.): effects on survival, cholinesterase, and carboxylesterase activity. (United States)

    Arufe, M Isabel; Arellano, Juana M; Albendín, Gemma; Sarasquete, Carmen


    This study was conducted to examine the acute toxicity of the organophosphorus pesticide (OP) parathion on embryos and yolk-sac larvae of gilthead seabream (Sparus aurata), and to investigate the effects of this compound on cholinesterase and carboxylesterase activity of seabream larvae in the phase of endogenous feeding. The 72-h LC50 for yolk-sac larvae (0.523 mg L⁻¹) was about two-fold lower than the 48-h LC50 for embryos (1.005 mg L⁻¹). Parathion significantly inhibited the activity of ChE and CaE activity in yolk sac larvae but there were not significant differences in the sensitivity of both esterases to parathion as inferred by their 72-h IC50 values. Larvae exposed to parathion for 72 h showed a 70% inhibition of the whole body acetylcholinesterase at approximately the LC50.

  14. Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property. (United States)

    Liu, Zhikun; Fang, Lei; Zhang, Huan; Gou, Shaohua; Chen, Li


    Total sixteen tacrine-curcumin hybrid compounds were designed and synthesized for the purpose of searching for multifunctional anti-Alzheimer agents. In vitro studies showed that these hybrid compounds showed good cholinesterase inhibitory activity. Particularly, the potency of K3-2 is even beyond tacrine. Some of the compounds exhibited different selectivity on acetylcholinesterase or butyrylcholinesterase due to the structural difference. Thus, the structure and activity relationship is summarized and further discussed based on molecular modeling studies. The ORAC and MTT assays indicated that the hybrid compounds possessed pronounced antioxidant activity and could effectively protect PC12 cells from the H2O2/Aβ42-induced toxicity. Moreover, the hybrid compounds also showed positive metal ions-chelating ability in vitro, suggesting a potential to halt ion-induced Aβ aggregation. All the obtained results demonstrated that the tacrine-curcumin hybrid compounds, in particular compound K3-2, can be considered as potential therapeutic agents for Alzheimer's disease.

  15. The tissue distribution of diazinon and the inhibition of blood cholinesterase activities in rats and mice receiving a single intraperitoneal dose of diazinon. (United States)

    Tomokuni, K; Hasegawa, T; Hirai, Y; Koga, N


    The tissue distribution of diazinon and the inhibition of cholinesterase (ChE) activities in plasma, erythrocyte and brain were investigated using male rats and mice which received a single intraperitoneal (i.p.) dose of diazinon (20 or 100 mg/kg body wt) in olive oil. The blood diazinon level was estimated to reach a maximum at 1-2 h after the i.p. administration. It was demonstrated that the diazinon residue levels are the highest in the kidney, when comparing the distribution of diazinon among liver, kidney and brain in the animals after dosing. It was indicated that the ChE inhibition by diazinon exposure is greater in the plasma than in the erythrocytes for male mice, while its inhibition is greater in the erythrocytes for male rats. Brain ChE activity was also inhibited markedly in the mice after dosing.

  16. In vitro reactivation potency of acetylcholinesterase reactivators--K074 and K075--to reactivate tabun-inhibited human brain cholinesterases. (United States)

    Kuca, Kamil; Cabal, Jiri; Jun, Daniel; Musilek, Kamil


    In this work, two oximes for the treatment of tabun-inhibited acetylcholinesterase (AChE; EC, K074 (1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide) and K075 ((E)-1,4-bis(4-hydroxyiminomethylpyridinium)but-2-en dibromide), were tested in vitro as reactivators of AChE. Comparison was made with currently used AChE reactivators (pralidoxime, HI-6, methoxime and obidoxime). Human brain homogenate was taken as an appropriate source of the cholinesterases. As resulted, oxime K074 appears to be the most potent reactivator of tabun-inhibited AChE, with reactivation potency comparable to that of obidoxime. A second AChE reactivator, K075, does not attain as great a reactivation potency as K074, although its maximal reactivation (17%) was achieved at relevant concentrations for humans.

  17. Tabun-inhibited rat tissue and blood cholinesterases and their reactivation with the combination of trimedoxime and HI-6 in vivo. (United States)

    Bajgar, Jiri; Karasova, Jana Zdarova; Kassa, Jiri; Cabal, Jiri; Fusek, Josef; Blaha, Vaclav; Tesarova, Sandra


    Up to now, intensive attempts to synthesize a universal reactivator able to reactivate cholinesterases inhibited by all types of nerve agents/organophosphates were not successful. Therefore, another approach using a combination of two reactivators differently reactivating enzyme was used: in rats poisoned with tabun and treated with combination of atropine (fixed dose) and different doses of trimedoxime and HI-6, changes of acetylcholinesterase activities (blood, diaphragm and different parts of the brain) were studied. An increase of AChE activity was observed following trimedoxime treatment depending on its dose; HI-6 had very low effect. Combination of both oximes showed potentiation of their reactivation efficacy; this potentiation was expressed for peripheral AChE (blood, diaphragm) and some parts of the brain (pontomedullar area, frontal cortex); AChE in the basal ganglia was relatively resistant. These observations suggest that the action of combination of oximes in vivo is different from that observed in vitro.

  18. RBC acetyl cholinesterase: A poor man′s early diagnostic biomarker for familial alzheimer′s and Parkinson′s disease dementia

    Directory of Open Access Journals (Sweden)

    Himmatrao Saluba Bawaskar


    Full Text Available Objective: Analysis of red blood cell acetyl cholinesterase (AChE in a familial Alzheimer′s diseases (AD Parkinson′s disease dementia (PDD and their first generation. Setting: General hospital, Mahad district, Raigad. Patients and Methods: Clinically diagnosed patients of AD and PDD and their asymptomatic relatives. Their blood was collected in EDTA tube and transferred to laboratory at Mumbai. Result: Median red blood cell (RBC cholinesterase levels amongst PDD, their first generation asymptomatic relatives, familial AD, asymptomatic relatives of AD, healthy controls, farmers exposed to pesticides (positive control and other neurological condition without dementia (hypertension with TIA 1, sub-dural hematoma 2, hypothyroid 1, non-familial unilateral parkinsonism without dementia 3, writers cramps 2, hyponitremia 1 and cerebral palsy with non-fluent aphasia 1. Median values of RBC AChE were 19086.78 U/L, 15666.05 U/L, 9013.11 U/L, 7806.19 U/L, 14334.57 U/L, 9785.05 U/L and 13162.60 U/L, respectively. As compared to controls, RBC AChE levels were statistically significant among PDD (P = 0.004 and significantly lowered among familial AD patients (P = 0.010, relatives of patients (P = 0.010. Interpretations: Below the normal RBC AChE level is a potential biomarker in asymptomatic relatives of familial AD patients. RBC AChE is raised than normal level in patients suffering from PDD, where AChE inhibitors are helpful. However, RBC AChE level below the normal where AChE inhibitor may not be effective.

  19. Interactions of butane, but-2-ene or xylene-like linked bispyridinium para-aldoximes with native and tabun-inhibited human cholinesterases. (United States)

    Calić, Maja; Bosak, Anita; Kuca, Kamil; Kovarik, Zrinka


    Kinetic parameters were evaluated for inhibition of native and reactivation of tabun-inhibited human erythrocyte acetylcholinesterase (AChE, EC and human plasma butyrylcholinesterase (BChE, EC by three bispyridinium para-aldoximes with butane (K074), but-2-ene (K075) or xylene-like linker (K114). Tested aldoximes reversibly inhibited both cholinesterases with the preference for binding to the native AChE. Both cholinesterases showed the highest affinity for K114 (K(i) was 0.01 mM for AChE and 0.06 mM for BChE). The reactivation of tabun-inhibited AChE was efficient by K074 and K075. Their overall reactivation rate constants were around 2000 min(-1)M(-1), which is seven times higher than for the classical bispyridinium para-aldoxime TMB-4. The reactivation of tabun-inhibited AChE assisted by K114 was slow and reached 90% after 20 h. Since the aldoxime binding affinity of tabun-inhibited AChE was similar for all tested aldoximes (and corresponded to their K(i)), the rate of the nucleophilic displacement of the phosphoryl-moiety from the active site serine was the limiting factor for AChE reactivation. On the other hand, none of the aldoximes displayed a significant reactivation of tabun-inhibited BChE. Even after 20 h, the reactivation maximum was 60% for 1 mM K074 and K075, and only 20% for 1 mM K114. However, lower BChE affinities for K074 and K075 compared to AChE suggest that the fast tabun-inhibited AChE reactivation by these compounds would not be obstructed by their interactions with BChE in vivo.

  20. Aging mechanism of butyrylcholinesterase inhibited by an N-methyl analogue of tabun: implications of the trigonal-bipyramidal transition state rearrangement for the phosphylation or reactivation of cholinesterases. (United States)

    Nachon, Florian; Carletti, Eugenie; Worek, Franz; Masson, Patrick


    Cholinesterases are the main target of organophosphorus nerve agents (OPs). Their inhibition results in cholinergic syndrome and death. The enzymes are inhibited by phosphylation of the catalytic serine enzyme, but can be reactivated by oximes to some extent. However, phosphylated cholinesterases undergo a side reaction that progressively prevents their reactivatability. This unimolecular reaction, termed "aging", has been investigated for decades. It was shown that most OP-ChE conjugates aged by O-dealkylation of an alkoxy substituent of the phosphorus atom, a mechanism involving the stabilization of a transient carbocation. In this paper we present structural data supporting a substitution-based mechanism for aging of the huBChE conjugate of an N-mono-methyl analogue of tabun. This mechanism involves an adjacent nucleophilic attack followed by Berry pseudorotation. A similar adjacent attack and subsequent rearrangement of the transition state have been recently proposed for tabun phosphylation of AChE. We suggest that a similar mechanism is also possible for oxime reactivation of phosphylated cholinesterases. This opens new perspectives in terms of reactivator design.

  1. Effect of APOE and CHRNA7 genotypes on the cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease. (United States)

    Braga, Ianna Lacerda Sampaio; Silva, Patricia Natalia; Furuya, Tatiane Katsue; Santos, Leonardo Caires; Pires, Belisa Caldana; Mazzotti, Diego Robles; Bertolucci, Paulo Henrique; Cendoroglo, Maysa Seabra; Smith, Marília Cardoso


    The loss of cholinergic transmission is considered to be an important cause of Alzheimer's disease (AD). Treatment with acetyl cholinesterase inhibitors (ChEIs) shows benefits; however, great heterogeneity has been observed in patient responses. We evaluated apolipoprotein E (APOE) and α7 nicotinic receptor (CHRNA7) single-nucleotide polymorphisms (SNPs) and associated these SNPs with pharmacological responses to ChEIs in a Brazilian population with AD. We studied 177 outpatients using ChEIs, and they were classified as responders and nonresponders according to variation in Mini-Mental State Examination (MMSE) status. The analysis of APOE genotypes showed that patients with the ε4 allele had a worse response than those without the ε4 allele. We observed an association between the CHRNA7 T allele and a better response to treatment with ChEIs in patients with mild AD (MMSE ≥ 20). The SNP rs6494223 of CHRNA7 as well as APOEε4 could be useful for understanding the response to ChEI treatment in patients with AD.

  2. Parathion, a cholinesterase-inhibiting plaguicide induces changes in tertiary villi of placenta of women exposed: a scanning electron microscopy study. (United States)

    Levario-Carrillo, M; Feria-Velasco, A; De Celis, R; Ramos-Martínez, E; Córdova-Fierro, L; Solís, F J


    The objective of this work was to describe the anatomy of placentas from women who were at risk of exposure to parathion during their pregnancy, when examined with the light and scanning electron microscopes. Twenty term placentas were analyzed; 10 from women living in an agricultural area, who were at risk of exposure to parathion during their pregnancy, and 10 from women living in an urban area, not expressly exposed to pesticides. Each sample was examined with both light and scanning electron microscopes. Cholinesterase activity was significantly reduced in blood from women of the exposed group. In some placentas of women exposed to parathion, recent microinfarctions, microcalcifications and increased deposition of fibrinoid material were seen, along with a larger proportion of atypical characteristics of villi, such as bullous and balloon-like formations with nonhomogeneous surface, and other areas devoid of microvilli. These observations suggest that in chronic exposure to pesticides, the rate of atypical characteristics of placental villi increases, which could be related to changes in the fetus biology. In this study, one newborn from the exposed group showed intrauterine growth retardation and another one, some signs of hypoxia.

  3. Relationship between serum cholinesterase level and urinary bladder activity in patients with or without overactive bladder and/or neurogenic bladder. (United States)

    Sugaya, Kimio; Onaga, Tomohiro; Nishijima, Saori; Miyazato, Minoru; Oshiro, Yoshinori; Hokama, Sanehiro; Uchida, Atsushi; Ogawa, Yoshihide


    We compared the serum cholinesterase (ChE) level and various parameters between patients with or without overactive bladder (OAB) and/or neurogenic bladder (NB). A total of 258 patients who met the following criteria were enrolled: the presence/absence of OAB and/or NB was documented, laboratory data were available, and liver and renal functions were normal. Patients were divided into the 3 groups: 1) a NB+/OAB+ group who had both NB and OAB, 2) a NB-/OAB+ group who had OAB alone, and 3) an OAB- group who did not have OAB. The relationship between the presence of OAB and various biochemical parameters were examined, as well as the therapeutic outcome in relation to the same biochemical parameters. Forty-three patients had both NB and OAB (NB+/OAB+), 66 patients had OAB without NB (NB-/OAB+), and 149 patients had no OAB (OAB-). Serum ChE, total protein, and albumin levels were lower in the NB-/OAB+ group than the NB+/OAB+ group or the OAB- group. In the NB-/OAB+ group, a higher serum albumin or ChE level was associated with a better therapeutic outcome. These results suggest that a decrease of serum ChE level is related to the occurrence of OAB and the poor response to treatment in OAB patients without NB.


    Vaughan-Higgins, Rebecca; Vitali, Simone; Reiss, Andrea; Besier, Shane; Hollingsworth, Tom; Smith, Gerard


    Published avian reference ranges for plasma cholinesterase (ChE) and brain acetylcholinesterase (AChE) are numerous. However, a consistently reported recommendation is the need for species- and laboratory-specific reference ranges because of variables, including assay methods, sample storage conditions, season, and bird sex, age, and physiologic status. We developed normal reference ranges for brain AChE and plasma total ChE (tChE) activity for Carnaby's Black-Cockatoos (Calyptorhynchus latirostris) using a standardized protocol (substrate acetylthiocholine at 25 C). We report reference ranges for brain AChE (19-41 μmol/min per g, mean 21±6.38) and plasma tChE (0.41-0.53 μmol/min per mL, mean 0.47±0.11) (n=15). This information will be of use in the ongoing field investigation of a paresis-paralysis syndrome in the endangered Carnaby's Black-Cockatoos, suspected to be associated with exposure to anticholinesterase compounds and add to the paucity of reference ranges for plasma tChE and brain AChE in Australian psittacine birds.

  5. A longitudinal study of risk factors for community-based home help services in Alzheimer’s disease: the influence of cholinesterase inhibitor therapy

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    Wattmo C


    Full Text Available Carina Wattmo, Elisabeth Paulsson, Lennart Minthon, Elisabet LondosClinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Malmö, SwedenBackground: To investigate the long-term effects of cholinesterase inhibitor (ChEI therapy and the influence of sociodemographic and clinical factors on the use of community-based home help services (HHS by patients with Alzheimer’s disease (AD.Methods: This 3-year, prospective, multicenter study included 880 AD patients treated with donepezil, rivastigmine, or galantamine in a routine clinical setting. At baseline and every 6 months, the patients were assessed with several rating scales, including the Mini-Mental State Examination, Instrumental Activities of Daily Living (IADL, and Physical Self-Maintenance Scale. Doses of ChEI and amounts of HHS per week were recorded. Cox regression models were used to predict the time to HHS, and multiple linear regression was used to predict the volume of HHS used.Results: During the study, 332 patients (38% used HHS. Factors that both postponed HHS use and predicted lower amounts of HHS were higher doses of ChEIs, better IADL ability, and living with family. Men, younger individuals, and those with a slower IADL decline showed a longer time to HHS, whereas female sex, a lower cognitive status, or more medications at baseline predicted fewer hours of HHS.Conclusions: Higher doses of ChEI might reduce the use of HHS, possibly reducing the costs of community-based care. Female spouses provide more informal care than do male spouses, so the likelihood of using HHS is greater among women with AD. The "silent group" of more cognitively impaired and frail elderly AD patients receives less HHS, which might precipitate institutionalization.Keywords: cognition, activities of daily living, treatment effect, gender, predictors

  6. Kinetics and molecular docking studies of loganin, morroniside and 7-O-galloyl-D-sedoheptulose derived from Corni fructus as cholinesterase and β-secretase 1 inhibitors. (United States)

    Bhakta, Himanshu Kumar; Park, Chan Hum; Yokozawa, Takako; Min, Byung-Sun; Jung, Hyun Ah; Choi, Jae Sue


    We evaluated the major active components isolated from Corni Fructus: loganin, morroniside, and 7-O-galloyl-D-sedoheptulose as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) for use in Alzheimer's disease treatment. These compounds exhibited predominant cholinesterase (ChEs) inhibitory effects with IC50 values of 0.33, 3.95, and 10.50 ± 1.16 µM, respectively, for AChE, and 33.02, 37.78, and 87.94 ± 4.66 µM, respectively, for BChE. Kinetics studies revealed that loganin and 7-O-galloyl-D-sedoheptulose inhibited AChE with characteristics typical of mixed inhibitors, while morroniside was found to be a noncompetitive inhibitor against AChE and also exerted mixed BChE inhibitory activities. For BACE1, loganin showed noncompetitive type inhibitory effects, while morroniside and 7-O-galloyl-D-sedoheptulose were found to be mixed inhibitors. Furthermore, these compounds exhibited dose-dependent inhibitory activity with ONOO(-)-mediated protein tyrosine nitration. Molecular docking simulation of these compounds demonstrated negative binding energies for ChEs, and BACE1, indicating high affinity and tighter binding capacity for the active site of the enzyme. Loganin was the most potent inhibitor against both ChEs and BACE1. The data suggest that these compounds together can act as a triple inhibitor of AChE, BChE, and BACE1, providing a preventive and therapeutic strategy for Alzheimer's disease treatment.

  7. Qualitative and quantitative two-dimensional thin-layer chromatography/high performance liquid chromatography/diode-array/electrospray-ionization-time-of-flight mass spectrometry of cholinesterase inhibitors. (United States)

    Mroczek, Tomasz


    Recently launched thin-layer chromatography-mass spectrometry (TLC-MS) interface enabling extraction of compounds directly from TLC plates into MS ion source was unusually extended into two-dimensional thin-layer chromatography/high performance liquid chromatography (2D, TLC/HPLC) system by its a direct connection to a rapid resolution 50×2.1mm, I.D. C18 column compartment followed by detection by diode array (DAD) and electrospray ionisation time-of-flight mass spectrometry (ESI-TOF-MS). In this way, even not separated bands of complicated mixtures of natural compounds could be analysed structurally, only within 1-2min after development of TLC plates. In comparison to typically applied TLC-MS interface, no ion suppression for acidic mobile phases was observed. Also, substantial increase in ESI-TOF-MS sensitivities and quality of spectra, were noticed. It has been utilised in combination with TLC- based bioautographic approaches of acetylcholinesterase (AChE) inhibitors, However, it can be also applied in any other procedures related to bioactivity (e.g. 2,2-Diphenyl-1-picryl-hydrazyl-DPPH screen test for radicals). This system has been also used for determination of half maximal inhibitory concentration (IC50 values) of the active inhibitor-galanthamine, as an example. Moreover, AChE inhibitory potencies of some of purified plant extracts, never studied before, have been quantitatively measured. This is first report of usage such the 2D TLC/HPLC/MS system both for qualitative and quantitative evaluation of cholinesterase inhibitors in biological matrices.

  8. It All Starts at the Ends: Multifaceted Involvement of C- and N-Terminally Modified Cholinesterases in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Amit Berson


    Full Text Available In Alzheimer’s disease (AD, premature demise of acetylcholine-producing neurons and the consequent decline of cholinergic transmission associate with the prominent cognitive impairments of affected individuals. However, the enzymatic activities of acetylcholinesterase (AChE and butyrylcholinesterase (BChE are altered rather late in the disease progress. This raised questions regarding the causal involvement of AChE and BChE in AD. Importantly, single nucleotide polymorphisms (SNPs, alternative splicing, and alternate promoter usage generate complex expression of combinatorial cholinesterase (ChE variants, which called for testing the roles of specific variants in AD pathogenesis. We found accelerated amyloid fibril formation in engineered mice with enforced over-expression of the AChE-S splice variant which includes a helical C-terminus. In contrast, the AChE-R variant, which includes a naturally unfolded C-terminus, attenuated the oligomerization of amyloid fibrils and reduced amyloid plaque formation and toxicity. An extended N-terminus generated by an upstream promoter enhanced the damage caused by N-AChE-S, which in cell cultures induced caspases and GSK3 activation, tau hyperphosphorylation, and apoptosis. In the post-mortem AD brain, we found reduced levels of the neuroprotective AChE-R and increased levels of the neurotoxic N-AChE-S, suggesting bimodal contribution to AD progress. Finally, local unwinding of the α-helical C-terminal BChE peptide and loss of function of the pivotal tryptophan at its position 541 impair amyloid fibril attenuation by the common BChE-K variant carrying the A539T substitution, in vitro. Together, our results point to causal yet diverse involvement of the different ChEs in the early stages of AD pathogenesis. Harnessing the neuroprotective variants while reducing the levels of damaging ones may hence underlie the development of novel therapeutics.

  9. In vivo Alterations in Glutathione-Related Processes, Lipid Peroxidation, and Cholinesterase Enzyme Activities in the Liver of Diazinon-Exposed Oreochromis niloticus. (United States)

    Uner, Nevin; Sevgiler, Yusuf; Durmaz, Hülya; Piner, Petek


    ABSTRACT Although its usage is partially banned in developed countries, organophosphate (OP) pesticide diazinon finds extensive agricultural application in our country (Turkey). This study was conducted to evaluate the effects of diazinon on total glutathione (tGSH), GSH-related enzymes, cholinesterase (ChE) enzyme activities, and lipid peroxidation in the liver of Oreochromis niloticus, a freshwater fish, as a model organism. Fish were exposed to 0.1, 1, and 2 mg/L sublethal concentrations of diazinon for 1, 7, 15, and 30 days. Total GSH levels, GSH-related enzyme and ChE-specific activities, and malondialdehyde (MDA) levels were analyzed using spectrophotometric methods. tGSH levels are decreased at 1 day, while they were increased in the long-term period. GSH-related enzyme activities are affected by diazinon exposure, except glutathione reductase (GR; EC Diazinon displayed an oxidative stress-inducing potential and it increased lipid peroxidation. Similar inhibition levels were observed in acetylcholinesterase (AChE; EC and butyrylcholinesterase (BChE; EC enzyme activities, and these inhibitions were not dose dependent. ChE inhibition-related oxidative stress was observed using its correlation with elevated tGSH levels and increased glutathione S-transferase (GST; EC enzyme activities; that reflects the diazinon-induced oxidative stress in the liver of O. niloticus. According to the results of the present study, tGSH level and GST-specific activity are suitable for reflecting the toxic effects of diazinon in fish.

  10. Cholinesterase activity in the tissues of bivalves Noah's ark shell (Arca noae) and warty venus (Venus verrucosa): characterisation and in vitro sensitivity to organophosphorous pesticide trichlorfon. (United States)

    Perić, Lorena; Ribarić, Luka; Nerlović, Vedrana


    Cholinesterase (ChE, EC activity was investigated in gills and adductor muscle of two bivalve species: Arca noae and Venus verrucosa. The properties of ChEs were investigated using acetylcholine iodide (ASCh), butyrylcholine iodide (BSCh) and propionylcholine iodide (PrSCh) as substrates and eserine, BW254c51 and iso-OMPA as specific inhibitors. The highest level of ChE activity in crude tissue extracts was detected with PrSCh followed by ASCh, while values obtained with BSCh were apparently low, except in A. noae adductor muscle. The enzyme activity in A. noae gills and V. verrucosa gills and adductor muscle was significantly inhibited by BW254c51, but not with iso-OMPA. ChE activity in adductor muscle of A. noae was significantly reduced by both diagnostic inhibitors. The effect of organophosphorous pesticide trichlorfon on ChE activity was investigated in vitro in both species as well as in the gills of mussels Mytilus galloprovincialis. The highest sensitivity of ChE to trichlorfon was observed in A. noae gills and adductor muscle (IC50 1.6×10(-7)M and 1.1×10(-7)M, respectively), followed by M. galloprovincialis gills (IC50 1.0×10(-6)M) and V. verrucosa gills and adductor muscle (IC50 1.7×10(-5)M and 0.9×10(-5)M, respectively). The results of this study suggest the potential of ChE activity measurement in the tissues of A. noae as effective biomarker of OP exposure in marine environment.

  11. In vivo evaluation of cholinesterase activity, oxidative stress markers, cyto- and genotoxicity of K048 oxime–a promising antidote against organophosphate poisoning. (United States)

    Zunec, Suzana; Kopjar, Nevenka; Zeljezić, Davor; Kuca, Kamil; Musilek, Kamil; Lucić Vrdoljak, Ana


    K048 is a member of K-oximes, a new oxime class that has recently been confirmed effective against poisoning by the nerve agent tabun and several pesticides. The toxicity profile of the K048 oxime has not been fully characterized and its optimal therapeutic dose has not yet been established. Earlier studies report excellent results with K048 in reactivating tabun-phosphorylated AChE and in the therapy of tabun-poisoned mice. It possesses a low acute toxicity and exerts an acceptable toxicity profile on isolated human peripheral blood lymphocytes in vitro. Intraperitoneal administration of K048 in rats resulted in an LD50 of 238.3 mg/kg. In this in vivo study, we investigated cholinesterase (ChE) activity and oxidative stress marker levels (lipid peroxidation and superoxide dismutase activity) in the plasma of exposed rats after administering the compound at 25% of its LD50. Lymphocyte viability was evaluated using an acridine orange/ethidium bromide in situ fluorescent assay. The levels of primary DNA damage in rat white blood cells were measured using the alkaline comet assay. The compound applied at 25% of its LD50 did not significantly affect ChE activity and lipid peroxidation and did not cause significant changes in the SOD activity in plasma. The cytotoxicity profile of K048 in the tested dose was also acceptable, and it did not possess significant DNA-damaging potential. The obtained results are promising for further evaluations of the K048 oxime, which should include tests on a broader concentration range and longer incubation times.

  12. Development of a Physiologically Based Pharmacokinetic and Pharmacodynamic Model to Determine Dosimetry and Cholinesterase Inhibition for a Binary Mixture of Chlorpyrifos and Diazinon in the Rat

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    Timchalk, Chuck; Poet, Torka S.


    Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models have been developed and validated for the organophosphorus (OP) insecticides chlorpyrifos (CPF) and diazinon (DZN). Based on similar pharmacokinetic and mode of action properties it is anticipated that these OPs could interact at a number of important metabolic steps including: CYP450 mediated activation/detoxification, and blood/tissue cholinesterase (ChE) binding/inhibition. We developed a binary PBPK/PD model for CPF, DZN and their metabolites based on previously published models for the individual insecticides. The metabolic interactions (CYP450) between CPF and DZN were evaluated in vitro and suggests that CPF is more substantially metabolized to its oxon metabolite than is DZN. These data are consistent with their observed in vivo relative potency (CPF>DZN). Each insecticide inhibited the other’s in vitro metabolism in a concentration-dependent manner. The PBPK model code used to described the metabolism of CPF and DZN was modified to reflect the type of inhibition kinetics (i.e. competitive vs. non-competitive). The binary model was then evaluated against previously published rodent dosimetry and ChE inhibition data for the mixture. The PBPK/PD model simulations of the acute oral exposure to single- (15 mg/kg) vs. binary-mixtures (15+15 mg/kg) of CFP and DZN at this lower dose resulted in no differences in the predicted pharmacokinetics of either the parent OPs or their respective metabolites; whereas, a binary oral dose of CPF+DZN at 60+60 mg/kg did result in observable changes in the DZN pharmacokinetics. Cmax was more reasonably fit by modifying the absorption parameters. It is anticipated that at low environmentally relevant binary doses, most likely to be encountered in occupational or environmental related exposures, that the pharmacokinetics are expected to be linear, and ChE inhibition dose-additive.

  13. Dynamic changes of serum cholinesterase activity after severe trauma%严重创伤后血清胆碱酯酶活性的动态变化

    Institute of Scientific and Technical Information of China (English)

    Li BA; Ding-qian WU; An-yu QIAN; Mao ZHANG; Bing XIONG


    Objective: The aim of the present study was to examine dynamic changes in serum cholinesterase (ChE) activity during early-stage severe trauma and the clinical significance of these changes. Methods: This prospective, observational study included 81 patients with severe trauma who were treated between October 2011 and April 2013 in the emergency intensive care unit (EICU) of a university-affiliated, tertiary-care, grade A general hospital in China. Serum ChE activity was measured on Days 1, 3, and 7 post-injury. The correlation of dynamic changes in serum ChE activity with trauma severity and prognosis was assessed. Correlations between changes in serum ChE activity after injury and albumin (ALB), prealbumin (PAB), transferrin (TRF), and C-reactive protein (CRP) levels were also analyzed. Results: Serum ChE activity in trauma patients was 42.3%–50.2% lower on Days 1, 3, and 7 compared with the control (P25 subgroup. ChE activity was significantly lower in both the death and the ISS>25 subgroups than in the survival and ISS≤25 subgroups on Days 1, 3, and 7 after injury. Activity was negatively correlated with ISS and acute physiology and chronic health evaluation III (APACHE III) at al time points. When comparing the receiver operating characteristic (ROC) curves for predicting prognosis, the area under the curve (AUC) in the plot of serum ChE was similar to the AUCs in plots of ISS and APACHE III, but significantly smaler than the AUC in the plot of the trauma and injury severity score (TRISS). Serum ChE activity was positively correlated with ALB, PAB, and TRF at al time points post-injury. Activity was not significantly correlated with CRP on Day 1, but was significantly and negatively correlated with CRP on Days 3 and 7. Conclusions: There is a significant decrease in serum ChE activity after severe trauma. Serum ChE may be regarded as a negative acute phase protein (APP) and the dynamic changes in serum ChE may be useful as an auxiliary indicator for

  14. Depression of the photic after discharge of flash evoked potentials by physostigmine, carbaryl and propoxur, and the relationship to inhibition of brain cholinesterase. (United States)

    Mwanza, Jean-Claude; Finley, Dana; Spivey, Christopher L; Graff, Jaimie E; Herr, David W


    The effects of N-methyl carbamate pesticides on the photic after discharge (PhAD) of flash evoked potentials (FEPs) and the relationship between inhibition of brain cholinesterase (ChE) activity and the PhAD were evaluated. FEPs were recorded in Long Evans rats treated with physostigmine (s.c.) 0, 0.05, 0.1, 0.2 or 0.3mg/kg (free base), in an ascorbic acid/saline vehicle, carbaryl (p.o.) 0, 1, 3, 10, 30, 50 or 75 mg/kg, or propoxur (p.o.) 0, 0.3, 3, 10, 20, 30, or 40 mg/kg in a corn oil vehicle. Physostigmine served as positive control based on literature data. Early (e.g. peak N(36)) and late FEP components (peak N(166) and PhAD) are related to the initial retino-geniculate afferent volley and higher cortical processing of visual information, respectively. Compared to controls, the PhAD duration decreased following treatment with 0.1 and 0.3mg/kg physostigmine, 7 5 mg/kg carbaryl or 30 mg/kg propoxur. Lesser changes were noted in FEP amplitudes or peak latencies. Treatment with 0.2 or 0.3 mg/kg physostigmine increased peak N(36) latency. Peak N(166) latency increased only following exposure to 40 mg/kg propoxur. None of the compounds altered peak N(36) or N(166) amplitudes. Hypothermia was observed at doses greater than 0.05 mg/kg physostigmine, at 30 or 50 mg/kg carbaryl, and after treatment with 10, 20 or 40 mg/kg propoxur. Inhibition of brain ChE activity occurred at dosages greater than 0.05 mg/kg physostigmine, 1mg/kg carbaryl, and 0.3 mg/kg propoxur. Linear regression analysis indicated that the decrease in PhAD duration correlated with decrease in brain ChE activity. The results indicate that at 30 min after treatment, inhibition of brain ChE activity did not affect cortical processing of the input from the retino-geniculate volley (evidenced by unaltered peak N(36) amplitude). However, the data suggest that disruption of cortical processing of visual signals related to FEP late components, as indicated by depression of the PhAD, was related to inhibition

  15. 磷化铝中毒抑制大鼠胆碱酯酶及阿托品和氯解磷啶的作用%Cholinesterase inhibition by aluminium phosphide poisoning in rats and effects of atropine and pralidoxime chloride

    Institute of Scientific and Technical Information of China (English)

    Shivani MHrRA; Sharda Shah PESHIN; Shyam Bala LALL


    AIM: To investigate the cholinesterase inhibition and effect of atropine and pralidoxime (PAM) treatment on the survival time in the rat model of aluminium phosphide (ALP) poisoning. METHODS: The rats were treated with AlP (10 mg/kg; 5.55×LD50; ig) and the survival time was noted. The effect of atropine (1 mg/kg, ip) and PAM (5 mg/kg, ip) was noted on the above. Atropine and PAM were administered 5 min after AlP. Plasma cholinesterase levels were measured spectrophotometrically in the control and AlP treated rats 30 min after administration. RESULTS: Treaanent with atropine and PAM increased the survival time by 2.5 fold (1.4 h ±0.3 h vs 3.4 h±2.5 h, P<0.01) in9 out of 15 animals and resulted in total survival of the 6 remaining animals. Plasma cholinesterase levels were inhibited by 47%, (438±74) U/L in AlP treated rats as compared tocontrol (840±90) U/L (P<0.01). CONCLUSION: This preliminary study concludes that AlP poisoning causes cholinesterase inhibition and responds to treatment with atropine and PAM.

  16. Pulmonary Toxicity of Cholinesterase Inhibitors (United States)


    to the more active and potent form (paraoxon) was demon-1956; Lubash and Clark, 1960; Sidell, 1967). strated to take place in the liver (Diggle and...chlorpyrifos, parathion, and diazinon inhibit this M2 muscarinic stimulation and 2-PAM to reactivate the inhib- receptor population. ited AChE. For the

  17. Study of the correlation between blood cholinesterases activity, urinary dialkyl phosphates, and the frequency of micronucleated polychromatic erythrocytes in rats exposed to disulfoton

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    Mariane Gonçalves Santos


    Full Text Available Organophosphates (OPs are widely used as pesticides, and its urinary metabolites as well as the blood cholinesterases (ChEs activity have been reported as possible biomarkers for the assessment of this pesticide exposure. Moreover, the OPs can induce mutagenesis, and the bone marrow micronucleus test is an efficient way to assess this chromosomal damage. This paper reports a study carried out to verify the correlation among the disulfoton exposure, blood ChEs activity, urinary diethyl thiophosphate (DETP, and diethyl dithiophosphate (DEDTP, as well as micronucleated polychromatic erythrocytes (MNPCEs frequency. Four groups of rats (n=12 were exposed to disulfoton at 0, 2.8, 4.7, and 6.6 mg kg-1 body weight. The blood ChEs activity, urinary DETP and DEDTP concentrations, and MNPCEs frequency were determined. It was observed that the plasmatic and erythrocytary ChEs activity decreased from 2.9% to 0.5% and from 35.9 to 3.3%, respectively, when the disulfoton dose was increased from 0 to 6.6 mg kg-1 (correlation of 0.99. Urinary DETP and DEDTP concentrations, as well as the MNPCEs frequency, increased from 0 to 6.58 µg mL-1, from 0 to 0.04 µg mL-1, and from 0 to 1.4%, respectively, when the disulfoton dose was increased from 0 to 6.58 mg kg-1 body weight.Os organofosforados (OPs são amplamente usados como praguicidas e a atividade da colinesterase sanguínea bem como os metabólitos urinários desses praguicidas têm sido reportados como biomarcadores eficazes para avaliar casos de exposição. Além disso, os OPs podem induzir mutagênese e o teste de micronúcleo de medula óssea é uma boa alternativa para avaliar os danos cromossômicos. Esse artigo reporta um estudo sobre a correlação entre a exposição a dissulfoton, a atividade da colinesterase sanguínea, a excreção urinária de dietil tiofosfato e dietil ditiofosfato e a frequência de micronúcleos em eritrócitos policromáticos. Quatro grupos de ratos (n=12 foram expostos a

  18. In Vitro Comparison of Two Most Promising H-Oximes (HI-6 and HLö-7) and Currently Commercially Available Reactivators Pralidoxime and Obidoxime in Reactivation of Cyclosarin-Inhibited Human Cholinesterases. (United States)

    Kuca, Kamil; Cabal, Jiri; Jun, Daniel; Koleckar, Vit


    ABSTRACT This study describes the evaluation of the in vitro ability of two acetylcholinesterase (EC reactivators, HI-6 and HLö-7, very promising at present, to reactivate human brain cholinesterases inhibited by the nerve agent cyclosarin. The results obtained (percentage of reactivation and appropriate constants characterizing the whole reactivation process) were compared with two currently available reactivators on the market: pralidoxime and obidoxime. It is clear that both promising oximes surpassed the potency of standard reactivators, especially at human relevant concentrations (10(-4) M and lower). Because of the prohibition of such experiments on humans, data obtained in this study could be used as input data for prediction of in vivo action of these drugs in future.

  19. Atividade colinesterásica cerebral e comportamento de ratos após exposição perinatal ao diclorvós Brain cholinesterase activity and the behavior of rats after perinatal exposure to dichlorvos

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    Jaqueline Pérola de Souza


    Full Text Available O organofosforado diclorvós impregnado em coleiras plásticas é um recurso utilizado em medicina veterinária que visa ao controle de ectoparasitas de cães e gatos. O objetivo deste trabalho foi avaliar os efeitos do uso de coleiras plásticas impregnadas com diclorvós (8,37% em ratas Wistar durante o período de gestação e lactação, como possível fonte de alterações comportamentais e da atividade colinesterásica cerebral dos filhotes. Na desmama, não houve diferença na atividade colinesterásica cerebral entre as mães tratadas com diclorvós e o grupo controle, bem como entre os respectivos filhotes. O tratamento com diclorvós também não influenciou no comportamento geral dos animais, avaliado no campo aberto, nem no nível de ansiedade testado no labirinto em cruz elevado, ambos aos 35 dias pós-natal.The organophosphate dichlorvos impregnated into plastic collars (8.37% is used in veterinary practice as an alternative for the control of ectoparasites in dogs and cats. The aim of this work was to determine the possible toxic effects of these collars in female Wistar rats during pregnancy and lactation, as a possible cause of alterations in brain cholinesterase activity and behavior of offspring. At weaning, there was no difference in brain cholinesterase activity between control and treated dams, nor between their respective offspring as well. The treatment did not affect the general behavior of the offspring, when evaluated in the open field, nor anxiety in the elevated plus-maze, both evaluated on the 35th postnatal day.

  20. 庫存血液膽碱酯酶水平變化及其在重症有機磷中毒搶救中應用選擇%Alteration of Banked Blood Cholinesterase Level and Its Significance in Emergency Treatment of Acute Organophosphorus Pesticide Poisoning

    Institute of Scientific and Technical Information of China (English)

    鍾沛霖; 王勤鷹; 盛慧球


    目的觀察庫血保存天數與血漿膽碱酯酶(CHE)水平變化關係;探討重症有機磷農藥中毒(AOPP)搶救中合理選擇血源.方法輸血前隨機留取保留不同天數的庫血測定血漿CHE值;血液中心採血當日留取正常人血漿、即日測定CHE值作對照組.CHE測定用BM公司膽碱酯酶試劑盒,Roch公司的Cobas-FaraⅡ自動分析儀測定.結果庫血保存天數為第一天的血漿CHE值與正常對照組比較無顯著差異(p>o.05),其他各組均顯著低於對照組(P>0.05).各組與正常對照組相比較其下降百分比約19%-83%.保存天數與CHE值呈負相關(r=-0.7929,P<0.01).曲線回歸Y=-1 823.3Ln(X)+6229.4.結論隨採血後庫血保存天數的增加,血漿CHE值逐漸下降.在重度AOPP搶救中,以使用保留天數為一天以內新鮮血液最為適宜,以免浪費血源,貽( )搶救時機.本報告為強調輸入新鮮血液,保證高活性膽碱酯酶輸入提供實驗依據,並可供臨床參考.%Objective To observe the relationship between the preservation days of banked blood and the alteration level of plasma cholinesterase(CHE) with the aim of making proper selection of banked blood in emergency treatment of acute organophosphorus pesticide poisoning (AOPP). Methods We selected at random the banked blood that has been stored for different length of time before blood transfusion so as to determine the plasma cholinesterase value. The normal plasma cholinesterase value was determined on blood samples in the Blood Center which served as a control group. The cholinesterase value was determined with a kit of the BM Company and the Cobas-Fara Ⅱ automatic analysis of the Roch Company. Results It was found that there was no significant difference of plasma cholinesterase value between the one-day banked blood and the normal control group (P>0.05), but the plasma cholinesterase values of the other experiment groups were all significantly lower than that of the control group(P<0.05). As

  1. Colinesterasas eritrocitaria y plasmática en trabajadores con enfermedades crónicas controladas y en usuarios de medicamentos Erythrocytic and plasmatic cholinesterases in workers with chronic controlled diseases and in users of medicines

    Directory of Open Access Journals (Sweden)

    Jaime Carmona Fonseca


    nunca hubo diferencia significativa. Tampoco hubo diferencias importan-tes cuando se procedió a comparar los valores enzimáticos entre personas con una enfermedad específica y quienes no la tenían, excepto en el caso de «anemia». CONCLUSIONES: los niveles de colinesterasas eritrocitaria y plasmática son similares entre trabajadores sanos o con enfermedades crónicas controladas, con o sin drogas. PROBLEM: Physiological values of cholinesterase are known in healthy population, but limited information on them is available in individuals with chronic, controlled diseases, either with or without medication. OBJECTIVES: To measure erythrocytic and plasmatic cholinesterase levels in active workers who met the following conditions: to be feeling well and active at their jobs at the time of the study; to suffer from some disease that was under control either with or without medication; not to have been exposed to pesticides based on cholinesterase inhibitors. METHODOLOGY: A survey was carried out among workers affiliated to the Social Security Institute in Antioquia, Colombia, to identify those suffering from some disease and who had it under control. Acetylcholinesterase and butyrylcholinesterase levels were determined using two techniques for the former and three for the latter. Surveyed workers belonged to two different parts of Antioquia, namely: the Aburra Valley and the Near East region. The study sample was made up by 827 persons, 19% of which informed to be suffering from some disease. RESULTS: Prevalence of disease in the Aburra Valley workers was 30% and in those from the Near East region, 9% (p = 0.0000000. The list of their diseases included 13 different ones, the most frequent of which were: hypertension (29%, “liver disease” (16%, anemia (10%, and arthritis (10%. Out of the 827 people, 127 (15% were under some kind of medication at the moment of the study; of them, 85% were being treated with only one drug. Eight per cent were diseased and under

  2. Brain cholinesterase reactivation as a marker of exposure to anticholinesterase pesticides: a case study in a population of yellow-legged gull Larus michahellis (Naumann, 1840) along the northern coast of Portugal. (United States)

    Santos, Cátia S A; Monteiro, Marta S; Soares, Amadeu M V M; Loureiro, Susana


    Between late 2010 to early 2011, an increased mortality in gulls was observed along the northern coast of Portugal, with individuals exhibiting neurologic disorders consistent with an eventual anticholinesterase pesticide poisoning event. To clarify if this mortality was related to organophosphate (OP) and/or carbamate (CB) poisoning, chemical and spontaneous cholinesterase (ChE) reactivation was tested in the brain of the yellow-legged gull (Larus michahellis). Initial brain ChE activity in L. michahellis was 40.92 ± 5.23 U/mg of protein (average ± SE). Following chemical and spontaneous reactivation, ChE activity increased in average 70.38 ± 48.59% and 131.95 ± 92.64%, respectively. ChE reactivation was found to decrease at increasing concentrations of the oxime pyridine-2-aldoxime methochloride and dilution factor, underscoring the importance of first optimizing the assay conditions prior to its use on bird species. These results suggest that birds analysed could have been exposed to OP and CB pesticide compounds and that in most cases CB exposure appeared to be the main cause of birds poisoning. These results are an important contribution to environmental monitoring as it demonstrates the suitability of L. michaellis as sentinel species of OP and CB pesticides within an urban environment.

  3. Depressão vascular no idoso: resposta ao tratamento antidepressivo associado a inibidor das colinesterases Vascular depression in elderly: response to treatment with antidepressant associated to cholinesterase inhibitor

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    Ricardo Barcelos


    Full Text Available CONTEXTO: Entre os transtornos neuropsiquiátricos ocasionados por eventos cerebrovasculares, a depressão vascular é pouco diagnosticada por médicos não especialistas, causando aumento da morbimortalidade de pacientes idosos. CASO CLÍNICO: Trata-se de um paciente com 67 anos que apresentou resposta parcial a tratamento com inibidores da recaptura de serotonina e efeitos adversos autonômicos graves com outros antidepressivos. A adição de rivastigmina ao citalopram promoveu sucesso terapêutico, com redução de 23 para 7 pontos, na escala de Hamilton para depressão. DISCUSSÃO: O resultado obtido traz novas perspectivas para o tratamento da depressão vascular, sendo necessários ensaios clínicos controlados que evidenciem o benefício da adição dos inibidores das colinesterases aos antidepressivos no tratamento destes pacientes.CONTEXT: Among neuropsychiatric disorders caused by cerebrovascular factors, vascular depression is diagnosed in a small degree by general practitioners, causing morbid-mortality increase in elderly. CASE REPORT: That is a case of a 67 year-old-man with partial response after treatment with a Selective Serotonin Receptors Inhibitor, and severe autonomic adverse effects with other antidepressants. The addition of rivastigmine to citalopram resulted in a therapeutic success, with a reduction of 23 to 7 points on the Hamilton Depressive Scale (HAM-D. DISCUSSION: The result obtained brings new perspectives to the treatment of vascular depression, providing that randomized controlled trials with larger sample sizes confirm the positive effect of the addition of a cholinesterase inhibitor to antidepressants in the treatment of these patients.

  4. Susceptibility to Phoxim and Acetyl Cholinesterase Activity of The Red Imported Fire Ant (Solenopsis invicta Buren)%红火蚁对辛硫磷敏感性及其乙酰胆碱酯酶活性的研究

    Institute of Scientific and Technical Information of China (English)

    苗建忠; 马伏宁; 曾鑫年


    用点滴法测定了辛硫磷对红火蚁不同品级的毒力,并用乙酰硫代胆碱-二硫双对硝基苯甲酸法(ASCh-DTNB法)测定了各品级乙酰胆碱酯酶(acetyl cholinesterase,AChE)的活性,以探明蚁群中不同品级个体对辛硫磷的敏感性差异及其与靶标酶的关系.毒力测定结果表明,处理后24 h,辛硫磷对工蚁、兵蚁、有翅雄蚁、有翅雌蚁和蚁后的毒力(LC50值)分别为1.04、2.06、7.38、9.39和7.81 μg/ml,显示不同品级红火蚁对辛硫磷的敏感性差异非常大,其中工蚁最敏感,而有翅雌蚁蚁后敏感性最低.靶标酶活性测定结果表明,红火蚁不同品级个体中乙酰胆碱酯酶的活性存在极大差异,其中以有翅雄蚁的总活性最低,为0.0469 nmol/(min·头),而以有翅雌蚁的最高,为14.8929 nmol/(min·头).不同品级红火蚁对辛硫磷的敏感性与其乙酰胆碱酯酶活性不存在显著相关性(r=0.7456).

  5. Research on Cholinesterase Inhibitory Action and Chemical Constituents in the Volatile Oil of Radix Peucedani%前胡挥发油胆碱酯酶抑制作用及化学成分研究

    Institute of Scientific and Technical Information of China (English)

    刘亚旻; 宋波; 李宗阳; 姜保平; 潘瑞乐


    Using micro plate high-throughput screening assay to investigate the cholinesterase inhibitory action, and analyzing the main chemical constituents in the volatile oil of Radix Peucedani by the means of Gas Chromatography-Masa Spectrometer combined with Kovats index. The result shows that the volatile oil of Radix Peucedani has significant inhibitory activities of both Acetylcholinesterase ( AChE) and Butyr-ylcholinesterase (BuChE) ,the inhibition ratio of which were (63.76±1.99) % ,(51.53 ±1.70) % .respectively, when the content of the volatile oil of Radix Peucedani was lμL/mL. Meanwhile,32 main chemical constituents in the volatile oil of Radix Peueedani has been identified,the main constituents are alpha-pinene, beta-pinene, myrcene, 1 -Methyl-3 - (1 -methylethyl) -benzene, (R ) -1 -Methyl-4- (1 -methyl-ethenyl)-cyclohexene,2-(4-Methtlcyclohex-3-enyl)-propan-2-ol,2-hydroxyl-5-methyl-acetophenone,etc. The result suggests that Radix Peucedani maybe have a certain curative effect on neurodegenerative diseases,such as Alzheimer's disease.%运用微孔高通量筛选方法研究前胡挥发油胆碱酯酶抑制活性,并用气相色谱-质谱联用技术辅以Kovats 指数鉴定挥发油的主要化学成分.结果显示前胡挥发油对乙酰胆碱酯酶和丁酰胆碱酯酶均具有明显的抑制作用,当前胡挥发油浓度为1 μL/mL时,其抑制率分别为(63.76±1.99)%和(51.53±1.70)%;其挥发油共鉴定出32种化学成分,主要有α-蒎烯、左旋-β-蒎烯、月桂烯、1-甲基-3-(1-甲基乙基)苯、(R)-1-甲基-4-(1-甲基乙烯基)环己烯、萜品醇、2-羟基-5-甲基苯乙酮等.本研究结果提示前胡有可能对老年痴呆等神经退行性疾病有一定的治疗作用.

  6. New cholinesterase inhibitory constituents from Lonicera quinquelocularis.

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    Dilfaraz Khan

    Full Text Available A phytochemical investigation on the ethyl acetate soluble fraction of Lonicera quinquelocularis (whole plant led to the first time isolation of one new phthalate; bis(7-acetoxy-2-ethyl-5-methylheptyl phthalate (3 and two new benzoates; neopentyl-4-ethoxy-3, 5-bis (3-methyl-2-butenyl benzoate (4 and neopentyl-4-hydroxy-3, 5-bis (3-methyl-2-butenyl benzoate (5 along with two known compounds bis (2-ethylhexyl phthalate (1 and dioctyl phthalate (2. Their structures were established on the basis of spectroscopic analysis and by comparison with available data in the literature. All the compounds (1-5 were tested for their acetylcholinesterase (AChE and butyrylcholinesterase (BChE inhibitory activities in dose dependent manner. The IC50 (50% inhibitory effect values of compounds 3 and 5 against AChE were 1.65 and 3.43 µM while the values obtained against BChE were 5.98 and 9.84 µM respectively. Compounds 2 and 4 showed weak inhibition profile.

  7. Multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease: design, synthesis, biochemical evaluation, ADMET, molecular modeling, and QSAR analysis of novel donepezil-pyridyl hybrids

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    Bautista-Aguilera OM


    Full Text Available Oscar M Bautista-Aguilera,1,* Gerard Esteban,2,* Mourad Chioua,1 Katarina Nikolic,3 Danica Agbaba,3 Ignacio Moraleda,4 Isabel Iriepa,4 Elena Soriano,5 Abdelouahid Samadi,1 Mercedes Unzeta,2 José Marco-Contelles1 1Laboratory of Medicinal Chemistry (Institute of General Organic Chemistry [IQOG], National Research Council [CSIC], Madrid, Spain; 2Department of Biochemistry and Molecular Biology, Institute of Neurosciences, Autonomous Barcelona University, Barcelona, Spain; 3Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia; 4Department of Organic Chemistry, Faculty of Pharmacy, University of Alcalá, Ctra Barcelona, Alcalá de Henares, Spain; 5Synthesis, and Structure of Organic Compounds (SEPCO (IQOG, CSIC, Madrid, Spain *These authors have equally contributed to this work Abstract: The design, synthesis, and biochemical evaluation of donepezil-pyridyl hybrids (DPHs as multipotent cholinesterase (ChE and monoamine oxidase (MAO inhibitors for the potential treatment of Alzheimer’s disease (AD is reported. The 3D-quantitative structure-activity relationship study was used to define 3D-pharmacophores for inhibition of MAO A/B, acetylcholinesterase (AChE, and butyrylcholinesterase (BuChE enzymes and to design DPHs as novel multi-target drug candidates with potential impact in the therapy of AD. DPH14 (­Electrophorus electricus AChE [EeAChE]: half maximal inhibitory concentration [IC50] =1.1±0.3 nM; equine butyrylcholinesterase [eqBuChE]: IC50 =600±80 nM was 318-fold more potent for the inhibition of AChE, and 1.3-fold less potent for the inhibition of BuChE than the reference compound ASS234. DPH14 is a potent human recombinant BuChE (hBuChE inhibitor, in the same range as DPH12 or DPH16, but 13.1-fold less potent than DPH15 for the inhibition of human recombinant AChE (hAChE. Compared with donepezil, DPH14 is almost equipotent for the inhibition of hAChE, and 8.8-fold more potent for h

  8. TLC Bioautographic Method for Activity Screening of Natural Acetyl Cholinesterase In-hibitors from Xinjiang Mohe-Tobacco%薄层色谱生物自显影法筛选新疆莫合烟天然乙酰胆碱酯酶抑制剂的活性成分

    Institute of Scientific and Technical Information of China (English)

    王健; 朱萍萍; 倪国柱; 温琳豫; 支玲; 胡曙晨


    Objective To explain nicotine in tobacco can reduce the incidence of degenerative diseases,perform the activity screening of acetyl cholinesterase inhibitors of Xinjiang's unique Mohe-tobacco for illuminating the action mechanism. Methods The thin layer chromatography(TLC)bioautographic method combining TLC with biological activity assay was used to conduct the activity screening of extract solution of Xinjiang Mohe-tobacco. Results Nicotine in the extract solution of Xinjiang Mohe-tobacco appeared the white spots on the purple background by the TLC bioautography,indicating that which possesses the activity,but the white spots were weak, indicating that the nicotine content in the extract solution was unable to reach the significant inhibiting concentration,its activity was lower than that of the reference substance huperzine A;the DPPH development method revealed that the extraction solution of Xinjiang Mohe-tobacco simultaneously possesses the better antioxidant activity. Conclusion Nicotine in Xinjiang Mohe-tobacco can be com-bined with acetyl cholinesterase and inhibits its activity. The TLC bioautographic method is easy to operate with high sensitivity and specificity in the activity screening for natural acetyl cholinesterase inhibitor.%目的:为阐明烟草中的烟碱降低退行性疾病发病率的作用机理,对新疆特有的莫合烟进行天然乙酰胆碱酯酶抑制剂的活性筛选。方法采用薄层色谱分离和生物活性测定相结合的薄层色谱生物自显影技术,对新疆莫合烟提取液进行活性筛选。结果新疆莫合烟提取液中的烟碱通过薄层色谱生物自显影,在紫色背景下出现白色斑点,表明具有活性;但白色斑点较弱,表明提取液中的烟碱含量无法达到显著的抑制浓度,较对照品石杉碱甲活性偏低;2,2-二苯基苦基苯肼自由基( DPPH )显色法表明新疆莫合烟提取液同时具有较好的抗氧化活性。结论新疆莫合烟中的

  9. 多发伤患者血清胆碱酯酶与急性期蛋白的相关性%Relationship between serum cholinesterase and acute-phase proteins in patients with multiple trauma

    Institute of Scientific and Technical Information of China (English)

    巴立; 张茂; 沈凌炜; 吴定钱; 干建新; 徐少文


    和第7天显著低于存活组,CRP仅在第7天显著高于存活组,Logistic回归分析提示仅血清ChE和PAB是判断预后的独立因素. 结论 血清ChE可视为负急性期蛋白的一种,在反映多发伤病情严重度和预测患者转归中的综合价值要优于其他主要APP.%Objective To investigate the relationship between serum cholinesterase(ChE) and acute-phase proteins in patients with multiple trauma, then to evaluate their significance to judge prognosis. Method It's a prospective observation study. Patients with multiple trauma admitted to emergency intensive care unit,Second Af-filiated Hospital, Zhejiang Universieg, school of medicihe within 24 h after trauma from Oct. 2005 to Oct. 2007 were enrolled. And those with chronic liver disease, touching orgnaophosphorus, active tuberculosis, tumor, in-fection of major organ before trauma, liver injury or age < 18 year were excluded. Among 81 patients, 57 were male and24 female. The average age was (46±18) years, and the average injury severity score was (34.0±11.9).Seventy six healthy were selected as controls, 53 male and 23 female, with an average age of (44±16)years. The exclusion standards were the same as those in patients. Both groups had same gender proportion and age. Senum ChE and acute-phase proteins(APP) including albumin(ALB), prealbumin(PAB), transferrin(TRF),C-reactive protein(CRP) in patients were detected at 1, 3, 7 d after trauma. The acute physiology and chronic health evaluation Ⅲ (APACHEⅢ) was recorded simuhancously. Serum ChE, ALB, PAB, TRF, CRP in the controls were also detected. All of these indexes in the controls were compared with thoses in patients by t test or rank surn test. The dynamic changes of serum ChE and APPs in patients were analyzed by one way repeated mea-sures ANOVA. The relationships between serum ChE and those APPs and the relationships between APACHE Ⅲ and these indexes were analyzed by Pearson correlation analysis. We also compared these indexes

  10. The changes and clinical significance of isocitra te dehydrogenase and cholinesterase in sera of the aged patients with chronic li ver diseases%老年慢性肝病患者血清ICDH、CHE的变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    王立强; 续薇; 魏静根; 孙晓玲; 迟宝荣; 刘霓


    Objective To expflore the changes and clinical significan ce of isocitrate dehydrogenase(ICDH) and cholinesterase(CHE) in sera of aged pat ients with chronic liver diseases.Methods Examining ICDH and CHE in sera of 70 aged patient s with chronic liver diseases and 54 normal cases as a control.Results The activities of ICDH and CHE in sera of aged pa tients with chronic liver diseases were much lower and higher respectively than those of control group (P<0.01).Both of ICDH and CHE were negatively corr elated (P<0.05).Conclusions ICDH and CHE were sensitive markers of reflec ting the damage and liver synthetic metabolism of liver cell.It was important to detect the ICDH and CHE for judging the degree of chronic liver diseases and tr eating effect.%目的 探讨老年慢性肝病患者血清异柠檬酸脱氢酶(ICDH)和胆碱脂酶(CH E)的变化及临床意义。方法 对70例老年慢性肝病患者及54例健康老人血清中ICDH和CHE活性进行检测。结果 老年慢性肝病患者血清中CHE活性明显低于正常对照组,且随病情加重降低更为明显(P<0.01);血清中ICDH活性明显高于正常对照组,且随病情加重而升高更为明显(P<0.01)。结论 ICDH和CHE是反映肝实质细胞受损害及其合成代谢能力下降的敏感指标。检测ICDH、CHE的变化可以反映肝病发展的程度,对判定治疗效果及预后有重要意义。

  11. Behavior of cholinesterase and liver mitochondrial function in dogs submitted to normothermic ischemia and reperfusion Colinesterase e função mitocondrial hepática em cães submetidos a isquemia normotérmica e reperfusão do fígado

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    Luis Pinto Fernandes


    Full Text Available PURPOSE: The plasmatic activity of the cholinesterase (CHE and the liver mitochondrial function, expressed by the ratio of respiratory control (RCR, were studied during normothermic ischemia. METHODS: Sixteen adult mongrels, eight females and eight males were submitted to ischemia by clamping of the hepatic artery, portal vein and infrahepatic inferior vena cava, infra-hepatic, for two h, follwed by reperfusion for 1 h. The CHE and the mitochondrial function were evaluated at 60 and 120 min. of ischemia and at 15 and 60 minutes of reperfusion. RESULTS: The CHE decreased, significantly, during ischemia and in reperfusion. The RCR was decreased at 120 min. of ischemia, returning to the initial values on reperfusion. CONCLUSION: In this study, the CHE was a sensitive indicator of ischemic injury , suggesting irreversibility of ischemia injury. The RCR, by other side, showed a greater sensibility than the CHE in detection sense, during the studied period, the reversibility of the hepatic ischemic injury.OBJETIVO: A atividade plasmática da colinesterase (CHE e a função mitocondrial do fígado expressa pela RCR- razão de controle respiratório mitocondrial foram estudadas durante a isquemia/reperfusão hepáticas. MÉTODOS: Dezesseis cães adultos sem raça definida (oito machos e oito fêmeas foram submetidos a isquemia normotérmica por pinçamento do pedículo hepático e da veia cava inferior infra-hepática por 2 horas, seguida de 15 e 60 minutos de reperfusão.A CHE e a RCR foram avaliadas após 60 e 120 minutos de isquemia e após 15 e 60 minutos de reperfusão. RESULTADOS: Os níveis de CHE diminuíram significativamente na isquemia e reperfusão.A RCR diminuiu após 120 minutos de isquemia retornando a níveis semelhantes ao controle após a reperfusão. CONCLUSÃO: A CHE foi sensível para indicar a lesão isquêmica, sugerindo irreversibilidade da lesão. Já a RCR foi mais sensível no sentido de detectar a reversibilidade da les

  12. Synthesis and cholinesterase inhibition of cativic acid derivatives. (United States)

    Alza, Natalia P; Richmond, Victoria; Baier, Carlos J; Freire, Eleonora; Baggio, Ricardo; Murray, Ana Paula


    Alzheimer's disease (AD) is a neurodegenerative disorder associated with memory impairment and cognitive deficit. Most of the drugs currently available for the treatment of AD are acetylcholinesterase (AChE) inhibitors. In a preliminary study, significant AChE inhibition was observed for the ethanolic extract of Grindelia ventanensis (IC₅₀=0.79 mg/mL). This result prompted us to isolate the active constituent, a normal labdane diterpenoid identified as 17-hydroxycativic acid (1), through a bioassay guided fractionation. Taking into account that 1 showed moderate inhibition of AChE (IC₅₀=21.1 μM), selectivity over butyrylcholinesterase (BChE) (IC₅₀=171.1 μM) and that it was easily obtained from the plant extract in a very good yield (0.15% w/w), we decided to prepare semisynthetic derivatives of this natural diterpenoid through simple structural modifications. A set of twenty new cativic acid derivatives (3-6) was prepared from 1 through transformations on the carboxylic group at C-15, introducing a C2-C6 linker and a tertiary amine group. They were tested for their inhibitory activity against AChE and BChE and some structure-activity relationships were outlined. The most active derivative was compound 3c, with an IC₅₀ value of 3.2 μM for AChE. Enzyme kinetic studies and docking modeling revealed that this inhibitor targeted both the catalytic active site and the peripheral anionic site of this enzyme. Furthermore, 3c showed significant inhibition of AChE activity in SH-SY5Y human neuroblastoma cells, and was non-cytotoxic.

  13. [Ligands of cholinesterases of ephedrine and pseudoephedrine structure]. (United States)

    Basova, N E; Kormilitsin, B N; Perchenok, A Yu; Rozengatt, E V; Saakov, V S; Suvorov, A A


    The paper is a review of literature data on interaction of the mammalian erythrocyte acetylcholinesterase and blood serum butyrylcholinesterase with a group of isomer complex ester derivatives (acetates, propionates, butyrates, valerates, and isobutyrates) of bases and iodomethylates of ephedrine and its enantiomer pseudoephedrine. For 20 alkaloid monoesters, parameters of enzymatic hydrolysis are determined and their certain specificity toward acetylcholinesterase is revealed, whereas 5 diesters of iodomethylates of pseudoephedrine were hydrolyzed only by butyrylcholinesterase. The studied 20 aklaloid diesters and 10 trimethylammonium derivatives turned out to be non-competitive reversible inhibitors of acetylcholinesterase and competitive inhibitors of butyrylcholinesterase. The performed for the first time isomer and enantiomer analysis "structure-efficiency" has shown that in most cases it is possible to state the greater comlementarity of the catalytical surface of enzymes for ligands of the pseudoephedrine structure, such differentiation being realized more often at the reversible inhibition of enzymes. pseudoephedrine.

  14. An Evaluation of Blood Cholinesterase Testing Methods for Military Health (United States)


    biochips are fabricated on the basis of Bio-MicroElectroMechanical System concepts and employ an immunoassay detection technology. The project was...glutamic oxaloacetic transaminase; GPT, Glutamic pyruvic transaminase; Hb , hemoglobin; HbA1c, hemoglobin A1c; Hct, hematocrit; HDL, high density

  15. Structural elements regulating amyloidogenesis: a cholinesterase model system.

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    Létitia Jean

    Full Text Available Polymerization into amyloid fibrils is a crucial step in the pathogenesis of neurodegenerative syndromes. Amyloid assembly is governed by properties of the sequence backbone and specific side-chain interactions, since fibrils from unrelated sequences possess similar structures and morphologies. Therefore, characterization of the structural determinants driving amyloid aggregation is of fundamental importance. We investigated the forces involved in the amyloid assembly of a model peptide derived from the oligomerization domain of acetylcholinesterase (AChE, AChE(586-599, through the effect of single point mutations on beta-sheet propensity, conformation, fibrilization, surfactant activity, oligomerization and fibril morphology. AChE(586-599 was chosen due to its fibrilization tractability and AChE involvement in Alzheimer's disease. The results revealed how specific regions and residues can control AChE(586-599 assembly. Hydrophobic and/or aromatic residues were crucial for maintaining a high beta-strand propensity, for the conformational transition to beta-sheet, and for the first stage of aggregation. We also demonstrated that positively charged side-chains might be involved in electrostatic interactions, which could control the transition to beta-sheet, the oligomerization and assembly stability. Further interactions were also found to participate in the assembly. We showed that some residues were important for AChE(586-599 surfactant activity and that amyloid assembly might preferentially occur at an air-water interface. Consistently with the experimental observations and assembly models for other amyloid systems, we propose a model for AChE(586-599 assembly in which a steric-zipper formed through specific interactions (hydrophobic, electrostatic, cation-pi, SH-aromatic, metal chelation and polar-polar would maintain the beta-sheets together. We also propose that the stacking between the strands in the beta-sheets along the fiber axis could be stabilized through pi-pi interactions and metal chelation. The dissection of the specific molecular recognition driving AChE(586-599 amyloid assembly has provided further knowledge on such poorly understood and complicated process, which could be applied to protein folding and the targeting of amyloid diseases.

  16. BACE1 and cholinesterase inhibitory activities of Nelumbo nucifera embryos. (United States)

    Jung, Hyun Ah; Karki, Subash; Kim, Ji Hye; Choi, Jae Sue


    The aim of the present study was to evaluate the comparative anti-Alzheimer's disease (AD) activities of different parts of Nelumbo nucifera (leaves, de-embryo seeds, embryos, rhizomes, and stamens) in order to determine the selectivity and efficient use of its individual components. Anti-AD activities of different parts of N. nucifera were evaluated via inhibitory activities on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) along with scavenging activity on peroxynitrite (ONOO(-)). Among the evaluated parts of N. nucifera, the embryo extract exhibited significant inhibitory potential against BACE1 and BChE as well as scavenging activity against ONOO(-). Thus, the embryo extract was selected for detailed investigation on anti-AD activity using BACE1- and ChEs-inhibitory assays. Among the different solvent-soluble fractions, the dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n-butanol (n-BuOH) fractions showed promising ChEs and BACE1 inhibitory activities. Repeated column chromatography of the CH2Cl2, EtOAc and n-BuOH fractions yielded compounds 1-5, which were neferine (1), liensinine (2), vitexin (3), quercetin 3-O-glucoside (4) and northalifoline (5). Compound 2 exhibited potent inhibitory activities on BACE1, AChE, and BChE with respective IC50 values of 6.37 ± 0.13, 0.34 ± 0.02, and 9.96 ± 0.47 µM. Likewise, compound 1 showed potent inhibitory activities on BACE1, AChE, and BChE with IC50 values of 28.51 ± 4.04, 14.19 ± 1.46, and 37.18 ± 0.59 µM, respectively; the IC50 values of 3 were 19.25 ± 3.03, 16.62 ± 1.43, and 11.53 ± 2.21 µM, respectively. In conclusion, we identified potent ChEs- and BACE1-inhibitory activities of N. nucifera as well as its isolated constituents, which may be further explored to develop therapeutic and preventive agents for AD and oxidative stress related diseases.

  17. Gravidade das intoxicações por inseticidas inibidores das colinesterases no noroeste do estado do Paraná, Brasil Gravedad de las intoxicaciones por insecticidas inhibidores de colinesterasa en el noroeste del estado do Paraná, Brasil Severity of the intoxications by cholinesterase inhibitor insecticides registered in the nothwest of the state of Paraná, Brasil

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    Magda Lúcia Félix de Oliveira


    clasificadas como severas. La alta incidencia de intoxicación grave y mortalidad sugieren estrategias preventivas referidas a la utilización de estos insecticidas, objetivando restringir el acceso indiscriminado a estos potentes agentes tóxicos.This article has as objective the discussion of the severity of intoxications by cholinesterase inhibitor insecticides, which happened in the Northwest of Paraná, Brasil, starting from an exploratory descriptive study, with retrospective analysis of epidemiological data sheets of the Intoxications Control Center in the University Hospital of Maringá, Paraná, Brasil, referring to patients intoxicated from January, 1994 to December, 2005. 529 cases were analyzed, 168 (31,7% for organophosphates and 167 (31,5% for carbamates. The suicide attempt represented 257 cases (48,5%, the occupational exposure 140 (26,5%, and the accidental 124 (23,5%. Comparing the number of severe intoxications and deaths, it was verified from 100% of deaths to cases severe occupational exposure, 20% for the suicide attempt and 7,5% deaths for the accidental intoxications classified as severe. The high incidence of serious intoxication and mortality suggest preventive strategies in respect of the usage of the insecticides, aiming to restrict the indiscriminate access to these powerful toxic agents.

  18. 急性缺糖缺氧通过增强胆碱酯酶表达促进肾小管细胞的炎性损伤%Acute oxygen and glucose deprivation promotes inflammatory injury of renal tubular cells by enhancing the expression of cholinesterase

    Institute of Scientific and Technical Information of China (English)

    吴明; 吴乐锋; 李明利; 陆俊福; 赖凯; 徐迹; 刘芬; 冯永文


    Objective To investigate the injury mechanism of renal tubular cells induced by acute oxygen and glucose depri-vation. Methods Isolation and culture of rat kidney macrophages and renal epithelial cells,constructing co-cultivating model of lacking Oxygen and sugar(Oxygen and glucose deprivation,OGD),Cells were devided into control group and OGD group,and were given OGD treatment for 1 hour,and then carried out normal culture for up to 24 hours in each group. the expression of TNF al-pha,IL-1 beta,IL-10 in supernatant fluid was detected by ELISA,the viability of renal tubular cells was determined by MTT,the expression of mRNA and protein of acetylcholine esterase (AChE) were determined by RT-qPCR and Western Blot respectively. Results The levels of TNF alpha (pg/ml) in the supernatant fluid in cultivation system were (231.67±36.28) in control group VS (428.67±43.16)(P<0.05) in OGD group,the levels of IL-1β (pg/ml) were (116.67±21.64) in control group VS (219.63±43.86) in OGD group(P<0.05),the levels of IL-10 (pg/ml) were (235.67±39.35) in control group VS (432.67±49.72) in OGD group (P<0. 01). The viability of renal tubular cells was (88.41±18.25) VS (46.98±13.87)(P<0.01);The levels of mRNA and protein of AChE in OGD group were higher than those in control group,they were raised (3.82±0.73) and (2.17±0.46) times respectively (P<0.01). Conclusion Acute oxygen and glucose deprivation enhances the expression of cholinesterase in renal macrophages ,the acute in-jury of renal tubular cells induced by OGD was mediated through inflammatory mediators.%目的:探讨急性缺糖缺氧导致肾小管细胞损伤的机制。方法分离培养大鼠肾内巨噬细胞、肾小管上皮细胞,构建两者共培养(transwell)模型,细胞分成对照组及缺糖缺氧(Oxygen and glucose deprivation,OGD)组,给予缺糖缺氧处理细胞1h后再正常培养24h,ELISA法检测两组上清液TNF-α,IL-1β和IL-10的浓度,噻唑蓝(MTT)检测肾小

  19. The value of determination of serum cholinesterase levels in judgment of severity and prognosis in patients with severe pneumonia%血清胆碱酯酶含量对重症肺炎患者 病情和预后的评估价值

    Institute of Scientific and Technical Information of China (English)

    莫新; 唐皓; 曾丽金; 卢惠娴; 郭丽冰; 马中富


    Objective To investigate the value of serum cholinesterase (S-ChE) levels in judgment of severity and prognosis in patients with severe pneumonia. Methods The clinical data of patients with severe pneumonia, who were admitted to the Department of Internal Medicine in the First Affiliated Hospital of Sun Yat-sen University, or the Department of Neurology in the Third People's Hospital of Foshan from May 2011 to May 2015, whose hospital time was longer than 24 hours, were retrospectively analyzed. They were divided into survival group and death group according to the final outcome. Lab data, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, multiple organ dysfunction syndrome (MODS) score, the improved pneumonia score of British Thoracic Society (confusion, uremia, respiratory, blood pressure, age 65 years, CURB-65), and S-ChE levels of all patients were collected after they were hospitalized into the intensive care unit (ICU) within 24 hours. Independent risk factors for prognosis were analyzed by binary logistic regression analysis, and receiver operating characteristic curve (ROC) was plotted. Best truncation point analysis was used to compare their estimated value for prognosis of patients with severe pneumonia. Results Eighty-six patients with severe pneumonia were studied. Among them 46 patients survived, and 40 patients died. By the single factor analysis, the following lab data in the death group were found significantly lower than those in the survival group: S-ChE levels (kU/L: 2.748±0.826 vs. 4.489±1.360, t' = 7.274, P = 0.000), arterial partial pressure of oxygen [PaO2 (mmHg, 1 mmHg = 0.133 kPa): 52.55±18.29 vs. 60.83±16.65, t = 2.196, P = 0.031], oxygenation index (mmHg: 114.20±48.01 vs. 167.10±69.68, t' = 4.229, P = 0.000), and carbon dioxide combining power [CO2-CP (mmol/L): 22.85±5.44 vs. 26.00±7.63, t' = 2.225, P = 0.029]. The following clinical data were significantly higher in the death group than those in the survival

  20. Correlation of serum cholinesterase and acute physiology and chronic health evaluation Ⅱscore and multiple organ dysfunction syndrome score in patients with severe pneumonia%重症肺炎患者血清胆碱酯酶含量变化及其与急性病生理学和长期健康评价Ⅱ评分、多器官功能障碍综合征评分的相关性研究

    Institute of Scientific and Technical Information of China (English)

    莫新; 梁艳冰; 陈志斌; 李振宇; 杨冰玉; 马中富


    Objective To observe the change of serum cholinesterase (S-ChE) levels in patients with severe pneumonia and its correlativity with acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score and multiple organ dysfunction syndrome (MODS) score. Methods A total of 86 patients with severe pneumonia were enrolled in this study as the severe pneumonia group, and divided into the survival group (46 cases) and death group (40 cases). And 100 patients with common pneumonia (common pneumonia group) and 124 people with health examination normal (control group) were served as control. The S-ChE levels were collected and APACHE Ⅱ score and MODS score were calculated after the patients were hospitalized in ICU within 24 hours. The Pearson correlation was used to analyze the association between S-ChE level and APACHE Ⅱ score as well as MODS score. Results The S-ChE levels in the severe pneumonia group, common pneumonia group and control group were (3 679 ± 1 433) U/L, (5 142 ± 1 884) U/L, (8 469 ± 1 377) U / L, respectively, and the S-ChE levels in the severe pneumonia group were much lower than those in the common pneumonia group and control group (all P<0.05). Meanwhile, the S-ChE levels in the death group [(2 748 ± 826) U/L vs. (4 489 ± 1 360) U/L, t=7.041, P<0.001] were much lower, whereas the APACHEⅡscores (26 ± 5 vs. 16 ± 5, t=8.540, P<0.001) and MODS scores (8.15 ± 2.49 vs. 4.35 ± 2.01,t=7.832, P<0.001) were higher than those in the survival group. The Pearson correlation showed that the S-ChE levels were negative related with APACHEⅡscore (r=-0.437, P<0.05) and MODS score (r=-0.337, P<0.05). Conclusion The S-ChE levels in patients with severe pneumonia decrease remarkedly, which can reflect the severity of severe pneumonia and have negative correlation with APACHE Ⅱscore or MODS score.%目的探讨重症肺炎患者血清胆碱酯酶(S-ChE)含量的变化及其与急性病生理学和长期健康评价Ⅱ(APACHEⅡ)评分、多器

  1. Molecular Cloning of the Human Genes(s) Directing the Synthesis of Nervous System Cholinesterases. (United States)


    AD-8163 229 MOLECULAR CLONING OF THE HUMAN GENES(S) DIRECTING THE 1/1 SYNTHESIS OF NERYOU.. (U) NEIZMANN INST OF SCIENCE REHOVOT (ISRAEL) DEPT OF...allelic polymrpism for the human genes coding for particular ChEs (8), and molecular cloning studies indicate that various human ChEs are produced from...H-2-Krelated molecule by molecular cloning . Im=m-jgenetics 14, 383-397. 86. Mykleboet, 0., Williamson, B., Markham, A.F., Myklebost, S.R., Rogers, J

  2. In-vitro Evaluation and Molecular Docking Studies of Some Schiff Bases as Cholinesterase Inhibitor

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    Saurabh Kumar Sinha


    Full Text Available Some new Schiff bases of 4-aminopyridine were synthesized and evaluated for antiamnesic and cognition enhancing activity. In the current study to further understand the mechanism of action of these derivatives we have evaluated in-vitro acetycholinesterase (AChE and butyrylcholinesterase (BChE inhibitory activity. Enzyme kinetics and docking studies were performed for all compounds to observe their nature of inhibition. The IC50 value of synthesized compounds showed maximum activity of compound 4APg compared to standard drug donepezil and rivastigmine whereas its kinetic analysis of enzyme inhibition demonstrated non-competitive inhibition for both enzymes AChE and BChE. The docking study confirmed their consensual interaction with AChE and BChE active sites justifying the experimental outcome.


    Concern over the lack of available endpoints to assess peripheral nervous system dysfunction after pesticide exposure has led to the search for new laboratory models. Recently our lab adapted the in vivo clinical practice of stimulation single fiber electromyography (SFEMG) for u...

  4. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine

    Institute of Scientific and Technical Information of China (English)

    Rui WANG; Han YAN; Xi-can TANG


    Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase (AChE). Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier, higher oral bioavailability, and longer duration of AChE inhibitory action. HupA has been found to improve cognitive deficits in a broad range of animal models. HupA possesses the ability to protect cells against hydrogen peroxide, β-amyloid protein (or peptide), glutamate,ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53, and caspase-3, protect mitochondria, upregulate nerve growth factor and its receptors, and interfere with amyloid precursor protein metabolism. Antagonizing effects of HupA on N-methyl-D-aspartate receptors and potassium currents may also contribute to its neuroprotection as well. Pharmacokinetic studies in rodents, canines, and healthy human volunteers indicated that HupA was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate with the property of slow and prolonged release after oral administration. Animal and clinical safety tests showed that HupA had no unexpected toxicity, particularly the dose-limiting hepatotoxicity induced by tacrine. The phase Ⅳ clinical trials in China have demonstrated that HupA significantly improved memory deficits in elderly people with benign senescent forgetfulness, and patients with Alzheimer disease and vascular dementia, with minimal peripheral cholinergic side effects and no unexpected toxicity. HupA can also be used as a protective agent against organophosphate intoxication.

  5. In-vitro Evaluation and Molecular Docking Studies of Some Schiff Bases as Cholinesterase Inhibitor



    Some new Schiff bases of 4-aminopyridine were synthesized and evaluated for antiamnesic and cognition enhancing activity. In the current study to further understand the mechanism of action of these derivatives we have evaluated in-vitro acetycholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. Enzyme kinetics and docking studies were performed for all compounds to observe their nature of inhibition. The IC50 value of synthesized compounds showed maximum activity of comp...

  6. Abietane-type diterpenoids from the roots of Caryopteris mongolica and their cholinesterase inhibitory activities. (United States)

    Murata, Toshihiro; Ishikawa, Yoshinobu; Saruul, Erdenebileg; Selenge, Erdenechimeg; Sasaki, Kenroh; Umehara, Kaoru; Yoshizaki, Fumihiko; Batkhuu, Javzan


    Eleven abietane-type diterpenoids and two known abietanes were isolated from the roots of Caryopteris mongolica, and their structures were characterized. The absolute configurations at C-5 and C-10 were determined from the NMR data, including from the nuclear Overhauser effect and CD spectra, and the absolute configuration of C-16 in the hydroxypropyl group was determined via a modified Mosher's method. Furthermore, the previously unknown absolute configuration of the C-15 of cyrtophyllone B was determined to be in an R-configuration using X-ray crystallography. To estimate the preventive effects of the isolates for neurodegenerative disease development, their inhibitory activities against acetylcholinesterase (AChE) from human erythrocytes and butyrylcholinesterase (BChE) from horse serum were evaluated.


    Directory of Open Access Journals (Sweden)

    C. Ariza


    Full Text Available La determinación de la actividad colinesterasa (ChE en animales domésticos es de importancia en diagnóstico e investigación. El presente trabajo tuvo como objetivo principal la determinación de la línea base de actividad ChE plasmática (acetilcolines-terasa, AChE y butirilcolinesterasa, BChE en 60 caballos Silla Argentino muestreados en fincas de equinos ubicadas en Bogotá (Colombia y sus alrededores. Las actividades catalíticas de AChE y BChE plasmáticas fueron medidas mediante espectrofotome-tría visible (405 nm. Los valores promedio ± desviación estándar de actividad AChE (nmols/ml/ min para machos (n=32 fueron 1566 ± 301. En intervalos de edad, los resultados fueron, 0.5–5 años: 1526 ± 295, 6–10 años: 1532 ± 313, 11-15 años: 1615 ± 279, y > 15 años: 1617 ± 335. En hembras (n=28, la actividad AChE fue 1323 ± 432, con valores en intervalos de edad, 0.5-5 años: 719 ± 108, 6–10 años: 1603 ± 313, 11–15 años: 1225 ± 294, > 15 años: 1519 ± 369. La BChE en machos fue 3304 ± 822; con intervalos de edad, 0.5-5 años: 3383 ± 715, 6–10 años: 3360 ± 766, 11-15 años: 3267 ± 1064, > 15 años: 3206 ± 861. En hembras, la BChE fue 3097 ± 432, con intervalos de edad: 0.5-5 años: 2467 ± 981, 6–10 años: 3668 ± 750, 11-15 años: 3238 ± 979, y > 15 años: 3015 ± 925. La actividad AChE fue significativamente diferente entre machos y hembras (test t, p < 0.05 y en ambos géneros al comparar los grupos etáreos (ANAVA, p < 0.05. BChE tuvo valores más altos que AChE, sin embargo, no en forma significativa cuando se compararon los resultados entre los dos géneros, ni cuando se compararon los grupos etáreos en los dos géneros. En una prueba adicional, 15 muestras fueron tomadas al azar y mantenidas a 4oC durante 72 horas para ser anali-zadas cada 24 horas; AChE y BChE no mostraron variaciones significativas entre las mediciones hechas en este período de tiempo. El presente estudio permitió determinar lineas base de los dos tipos de colinesterasas plasmáticas en caballos tipo silla Argentino con el propósito de ofrecer valores de referencia con fines diagnósticos y comparativos para clínicos e investigadores.

  8. Cholinesterase Structure: Identification of Mechanisms and Residues Involved in Organophosphate Inhibition and Enzyme Reactivation (United States)


    with 18 U.S.C. Section 1734 solely to indicate this fact. ing protected from solvent (20). t Present address: Dept. of Oral and Maxillofacial Surgery...acyl pocket loop (Trp2S6-Ser 29 8). This finding, when viewed with contemporary structures, sug- This conformational change coupled with solvent... Pathological Aspects. P. Universidad Catholica de Chile-FONDAP Biomedicina, 2004, pp. 43-48; R.Y.Y. Chan, C. Boudreau-Larivi&re, L.A. Angus, F. Mankal, B.J

  9. Cholinesterase Structure: Identification of Residues and Domains Affecting Organophosphate Inhibition and Catalysis (United States)


    269-274, 1997. ISSN 0006-2952/97/$17.00 + 0.00 "© 1997 Elsevier Science Inc . All rights reserved. PII S0006-2952(97)00180-9 ELSEVIER Mutant...potential candidates for pre- or post-exposure treatment for OP toxicity. BIOCHEM PHARMACOL 54;2:269-274, 1997. © 1997 Elsevier Science Inc . KEY WORDS

  10. Recent Knowledge on Medicinal Plants as Source of Cholinesterase Inhibitors for the Treatment of Dementia. (United States)

    Tundis, Rosa; Bonesi, Marco; Menichini, Francesco; Loizzo, Monica R


    Dementia is becoming a major public health problem worldwide. The most common form of dementia is Alzheimer's disease (AD), characterized by a deficient cholinergic transmission, deposition of amyloid plaques and neurofibrillary tangles, and neuro-inflammation that result in progressive degeneration and/or death of nerve cells and cognitive impairment. At present, AD cannot be prevented or cured, so the symptomatic relief obtainable by the use of acetylcholinesterase (AChE) inhibitors is one of the therapeutic strategies. Accumulated evidence suggests that naturally occurring compounds may potentially improve memory and cognitive function, and prevent neurodegeneration. Even today the search for new neuroprotective agents of natural origin is very active. The neuroprotective effects of medicinal plants covering studies of the last years will be summarized and discussed in this review choosing a family classification with particular emphasis on extracts and isolated compounds as promising new drugs. The search of a multifunctional potential anti-AD agent able to act on different crucial targets, such as galanthamine, quercetin and timosaponin AIII, could be a useful approach to recognizing therapeutics against AD.

  11. Cholinesterase activity as a device for biomonitoring pesticide exposure in the freshwater mussel Elliptio complanata (United States)

    US Fish and Wildlife Service, Department of the Interior — A die-off of freshwater mussels in 1990, attributed to anticholinesterase pesticide contamination of a North Carolina stream, has led the National Biological Service...

  12. Toxicodynamic analysis of the combined cholinesterase inhibition by paraoxon and methamidophos in human whole blood

    NARCIS (Netherlands)

    Bosgra, S.; Eijkeren, J.C.H. van; Schans, M.J. van der; Langenberg, J.P.; Slob, W.


    Theoretical work has shown that the isobole method is not generally valid as a method for testing the absence or presence of interaction (in the biochemical sense) between chemicals. The present study illustrates how interaction can be tested by fitting a toxicodynamic model to the results of a mixt

  13. Refinement of structural leads for centrally acting oxime reactivators of phosphylated cholinesterases. (United States)

    Radić, Zoran; Sit, Rakesh K; Kovarik, Zrinka; Berend, Suzana; Garcia, Edzna; Zhang, Limin; Amitai, Gabriel; Green, Carol; Radić, Bozica; Fokin, Valery V; Sharpless, K Barry; Taylor, Palmer


    We present a systematic structural optimization of uncharged but ionizable N-substituted 2-hydroxyiminoacetamido alkylamine reactivators of phosphylated human acetylcholinesterase (hAChE) intended to catalyze the hydrolysis of organophosphate (OP)-inhibited hAChE in the CNS. Starting with the initial lead oxime RS41A identified in our earlier study and extending to the azepine analog RS194B, reactivation rates for OP-hAChE conjugates formed by sarin, cyclosarin, VX, paraoxon, and tabun are enhanced severalfold in vitro. To analyze the mechanism of intrinsic reactivation of the OP-AChE conjugate and penetration of the blood-brain barrier, the pH dependence of the oxime and amine ionizing groups of the compounds and their nucleophilic potential were examined by UV-visible spectroscopy, (1)H NMR, and oximolysis rates for acetylthiocholine and phosphoester hydrolysis. Oximolysis rates were compared in solution and on AChE conjugates and analyzed in terms of the ionization states for reactivation of the OP-conjugated AChE. In addition, toxicity and pharmacokinetic studies in mice show significantly improved CNS penetration and retention for RS194B when compared with RS41A. The enhanced intrinsic reactivity against the OP-AChE target combined with favorable pharmacokinetic properties resulted in great improvement of antidotal properties of RS194B compared with RS41A and the standard peripherally active oxime, 2-pyridinealdoxime methiodide. Improvement was particularly noticeable when pretreatment of mice with RS194B before OP exposure was combined with RS194B reactivation therapy after the OP insult.

  14. Pesticide Exposure, Behavior of Farmer, and Activity of Cholinesterase Enzyme in Blood of Fertile Women Farmers

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    Deni Abdul Rahman


    Petani perempuan usia subur berisiko mengalami penurunan aktivitas kolinesterase akibat pajanan pestisida. Penelitian ini bertujuan untuk menganalisis hubungan antara pajanan pestisida dan perilaku pemajan terhadap aktivitas kolinesterase petani perempuan usia subur di Desa Kedunguter. Penelitian ini menggunakan desain potong lintang pada 94 petani perempuan usia subur tahun 2015. Pengumpulan data dilakukan secara observasi, wawancara, dan uji kolinesterase. Analisis data menggunakan uji kai kuadrat dan hasil analisis menunjukkan hubungan signifikan antara jenis pestisida, waktu kerja, penggunaan sarung tangan, perilaku mencuci tangan terhadap aktivitas kolinesterase petani perempuan usia subur. Hasil analisis pada penelitian ini menunjukkan bahwa variabel waktu kerja memiliki nilai odds ratio (OR tertinggi, yaitu OR = 14,072 sehingga waktu kerja merupakan variabel paling dominan dalam memengaruhi enzim kolinesterase. Penelitian ini menyarankan agar petani perempuan usia subur tidak bekerja lebih dari enam jam per hari.

  15. Characterization of cholinesterases present in brain and muscle tissues of juvenile blue shark (Prionace glauca

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    Luís Miguel Fonseca Alves


    Regarding the in vitro exposure to chlorpyrifos-oxon, we have observed a dose-response pattern showing higher ChE inhibitions with increasing pesticide concentrations and with more than 90% inhibition in the highest concentrations, which reveals the potential of this biomarker for biomonitoring studies and contaminant effect assessment in the blue shark.

  16. Retrospective detection of exposure to organophosphorus anti-cholinesterases: Mass spectrometric analysis of phosphylated human butyrylcholinesterase

    NARCIS (Netherlands)

    Fidder, A.; Hulst, A.G.; Noort, D.; Ruiter, R. de; Schans, M.J. van der; Benschop, H.P.; Langenberg, J.P.


    In this paper a novel and general procedure is presented for detection of organophosphate-inhibited human butyrylcholinesterase (HuBuChE), which is based on electrospray tandem mass spectrometric analysis of phosphylated nonapeptides obtained after pepsin digestion of the enzyme. The utility of this

  17. Effect of Several New and Currently Available Oxime Cholinesterase Reactivators on Tabun-intoxicated Rats

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    Jiri Kassa


    Full Text Available The therapeutical efficacies of eleven oxime-based acetylcholinesterase reactivators were compared in an in vivo (rat model study of treatment of intoxication caused by tabun. In this group there were some currently available oximes (obidoxime, trimedoxime and HI-6 and the rest were newly synthesized compounds. The best reactivation efficacy for acetylcholinesterase in blood (expressed as percent of reactivation among the currently available oximes was observed after administration of trimedoxime (16% and of the newly synthesized K127 (22432 (25%. The reactivation of butyrylcholinesterase in plasma was also studied; the best reactivators were trimedoxime, K117 (22435, and K127 (22432, with overall reactivation efficacies of approximately 30%. Partial protection of brain ChE against tabun inhibition was observed after administration of trimedoxime (acetylcholinesterase 20%; butyrylcholinesterase 30% and obidoxime (acetylcholinesterase 12%; butyrylcholinesterase 16%.


    Very little is known about the effects of chronic exposure to relatively low levels of anticholinesterase insecticides or how the effects of chronic exposure compare to higher, intermittent exposure of the same compound for the same duration. To that end, we exposed adult male ra...

  19. Neuropathy Target Esterase in Brain Function and Deterioration Caused by Cholinesterase Inhibiting Chemicals (United States)


    Warfare Agents: Toxicology and Treatment (Wiley, New York). 3. Taylor, P. (2001) in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, eds...Hardman, J. G., Limbird, L. E. & Gilman , A. G. (McGraw– Hill, New York), 10th Ed., pp. 175–191. 4. Johnson, M. K. & Glynn, P. (2001) in Handbook of

  20. Compounds from the aerial parts of Piper bavinum and their anti-cholinesterase activity. (United States)

    Dung, Hoang Viet; Cuong, To Dao; Chinh, Nguyen Minh; Quyen, Do; Kim, Jeong Ah; Byeon, Jeong Su; Woo, Mi Hee; Choi, Jae Sui; Min, Byung Sun


    A new alkenylphenol, bavinol A (1), together with six known compounds (2-7) were isolated from the aerial parts of Piper bavinum (Piperaceae). The chemical structures of these compounds were determined by spectroscopic analyses including 2D NMR spectroscopy. The anti-Alzheimer effects of compounds 1-7 were evaluated from acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity assays. Bavinol A (1), ampelopsin (3), and violanthin (4) exhibited AChE inhibitory activities with IC50 values of 29.80, 59.47 and 79.80 μM. Compound 1 also showed the most potent BChE inhibitory activity with an IC50 value of 19.25 μM.

  1. Novel series of tacrine-tianeptine hybrids: Synthesis, cholinesterase inhibitory activity, S100B secretion and a molecular modeling approach. (United States)

    Ceschi, Marco Antonio; da Costa, Jessie Sobieski; Lopes, João Paulo Bizarro; Câmara, Viktor Saraiva; Campo, Leandra Franciscato; Borges, Antonio César de Amorim; Gonçalves, Carlos Alberto Saraiva; de Souza, Daniela Fraga; Konrath, Eduardo Luis; Karl, Ana Luiza Martins; Guedes, Isabella Alvim; Dardenne, Laurent Emmanuel


    Tianeptine was linked to various 9-aminoalkylamino-1,2,3,4-tetrahydroacridines using EDC·HCl/HOBt to afford a series of tacrine-tianeptine hybrids. The hybrids were tested for their ability to inhibit AChE and BuChE and IC50 values in the nanomolar concentration scale were obtained. AChE molecular modeling studies of these hybrids indicated that tacrine moiety interacts in the bottom of the gorge with the catalytic active site (CAS) while tianeptine binds to peripheral anionic site (PAS). Furthermore, the compounds 2g and 2e were able to reduce the in vitro basal secretion of S100B, suggesting its therapeutic action in some cases or stages of Alzheimer's disease.

  2. Ionic liquid mediated synthesis and molecular docking study of novel aromatic embedded Schiff bases as potent cholinesterase inhibitors. (United States)

    Abd Razik, Basma M; Osman, Hasnah; Basiri, Alireza; Salhin, Abdussalam; Kia, Yalda; Ezzat, Mohammed Oday; Murugaiyah, Vikneswaran


    Novel aromatic embedded Schiff bases have been synthesized in ionic liquid [bmim]Br and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activities. Among the newly synthesized compounds, 5f, 5h and 7j displayed higher AChE enzyme inhibitory activities than standard drug, galanthamine, with IC50 values of 1.88, 2.05 and 2.03μM, respectively. Interestingly, all the compounds except for compound 5c displayed higher BChE inhibitories than standard with IC50 values ranging from 3.49 to 19.86μM. Molecular docking analysis for 5f and 7j possessing the most potent AChE and BChE inhibitory activities, disclosed their binding interaction templates to the active site of AChE and BChE enzymes, respectively.

  3. Anti-oxidative and cholinesterase inhibitory effects of leaf extracts and their isolated compounds from two closely related Croton species. (United States)

    Ndhlala, Ashwell R; Aderogba, Mutalib A; Ncube, Bhekumthetho; Van Staden, Johannes


    A comparative evaluation of the antioxidant and acetylcholinesterase inhibitory activity of the leaf extracts of Croton gratissimus and Croton zambesicus (subgratissimus) and compounds isolated from the extracts was carried out to determine their potential and suitability or otherwise as a substitute for each other in the management of oxidative and neurodegenerative conditions. Different antioxidant assays (DPPH, FRAP, β-carotene-linoleic and the lipid peroxidation models) and the microplate assay for acetylcholinesterase (AChE) inhibition were carried out separately to study the activities of the crude leaf extracts and four solvent fractions from each of the two Croton species. Bioassay guided fractionation was used to target antioxidant constituents of the crude extracts and ethyl acetate fractions of 20% aqueous methanol extract of C. gratissimus on silica gel and Sephadex LH-20 columns resulted in the isolation of kaempferol-3-O-β-6''(p-coumaroyl) glucopyranoside (tiliroside, 2), apigenin-6-C-glucoside (isovitexin, 3) and kampferol (4). The extract of C. zambesicus yielded quercetin-3-O-β-6''(p-coumaroyl) glucopyranoside-3'-methyl ether (helichrysoside- 3'-methyl ether, 1), kaempferol-3-O-β-6''(p-coumaroyl) glucopyranoside (tiliroside, 2) and apigenin-6-C-glucoside (isovitexin, 3). Three of the isolated compounds and their different combinations were also included in the bioassays. In all the assays performed, the antioxidant capacity and AChE inhibitory effects of C. zambesicus extracts were weaker than those of C. gratissimus. This suggests that C. gratissimus may not be substituted by C. zambesicus, despite the similarity in some of their constituents. Generally, the combinations made from the isolated compounds showed better activities in most of the assays compared to the individual isolated compounds. This suggests mechanisms such as synergism and/or additive effects to be taking place. This study established low, moderate and high antioxidant activities as well as AChE inhibitory effects by the crude extracts, fractions, compounds and compound combinations. This means some of the extracts, isolated compounds and compound combinations could be useful in the management of neurodegenerative conditions and serve as sources of natural neurodegenerative agents.

  4. Susceptibility of the aging Brown Norway rat to carbaryl, an anti-cholinesterase-based insecticide: Thermoregulatory and cardiovascular responses. (United States)

    The proportion of aged in the United States is projected to expand markedly for the next several decades. Hence, the U.S.EPA is assessing if the aged are more susceptible to environmental toxicants. The thermoregulatory and cardiovascular responses of young adult, mature adult, a...

  5. QSAR, docking, dynamic simulation and quantum mechanics studies to explore the recognition properties of cholinesterase binding sites. (United States)

    Correa-Basurto, J; Bello, M; Rosales-Hernández, M C; Hernández-Rodríguez, M; Nicolás-Vázquez, I; Rojo-Domínguez, A; Trujillo-Ferrara, J G; Miranda, René; Flores-Sandoval, C A


    A set of 84 known N-aryl-monosubstituted derivatives (42 amides: series 1 and 2, and 42 imides: series 3 an 4, from maleic and succinic anhydrides, respectively) that display inhibitory activity toward both acetylcholinesterase and butyrylcholinesterase (ChEs) was considered for Quantitative structure-activity relationship (QSAR) studies. These QSAR studies employed docking data from both ChEs that were previously submitted to molecular dynamics (MD) simulations. Donepezil and galanthamine stereoisomers were included to analyze their quantum mechanics properties and for validating the docking procedure. Quantum parameters such as frontier orbital energies, dipole moment, molecular volume, atomic charges, bond length and reactivity parameters were measured, as well as partition coefficients, molar refractivity and polarizability were also analyzed. In order to evaluate the obtained equations, four compounds: 1a (4-oxo-4-(phenylamino)butanoic acid), 2a ((2Z)-4-oxo-4-(phenylamino)but-2-enoic acid), 3a (2-phenylcyclopentane-1,3-dione) and 4a (2-phenylcyclopent-4-ene-1,3-dione) were employed as independent data set, using only equations with r(m(test))²>0.5. It was observed that residual values gave low value in almost all series, excepting in series 1 for compounds 3a and 4a, and in series 4 for compounds 1a, 2a and 3a, giving a low value for 4a. Consequently, equations seems to be specific according to the structure of the evaluated compound, that means, series 1 fits better for compound 1a, series 3 or 4 fits better for compounds 3a or 4a. Same behavior was observed in the butyrylcholinesterase (BChE). Therefore, obtained equations in this QSAR study could be employed to calculate the inhibition constant (Ki) value for compounds having a similar structure as N-aryl derivatives described here. The QSAR study showed that bond lengths, molecular electrostatic potential and frontier orbital energies are important in both ChE targets. Docking studies revealed that despite the multiple conformations obtained through MD simulations on both ChEs, the ligand recognition properties were conserved. In fact, the complex formed between ChEs and the best N-aryl compound reproduced the binding mode experimentally reported, where the ligand was coupled into the choline-binding site and stabilized through π-π interactions with Trp82 or Trp86 for BChE and AChE, respectively, suggesting that this compound could be an efficient inhibitor and supporting our model.

  6. Dimethoate affects cholinesterases in Folsomia candida and their locomotion--false negative results of an avoidance behaviour test. (United States)

    Pereira, Cecília M S; Novais, Sara C; Soares, Amadeu M V M; Amorim, Mónica J B


    The main mode of action of organophosphate insecticides is to inhibit acetylcholinesterase (AChE), which causes neuromuscular paralysis leading ultimately to death. The collembolan Folsomia candida is an important and standard test species in ecotoxicology, where effects on avoidance behaviour are assessed. Being related to insects they represent potential targets of insecticides such as the organophosphate dimethoate. In the present study we exposed F. candida to dimethoate having 2 main aims: 1) to assess the ability of F. candida to avoid it, and 2) to assess its effect on the cholinergic synapses to explore the link. For the latter, several sub-steps were needed: a) to characterise the existing ChE types and b) assess ChE activity (via exposure in vitro and in vivo). No avoidance was observed within the tested concentration range (0-0.32-1-3.2-10-32 mg/kg), in fact an apparent "attraction" (more animals on the spiked side) was observed. As expected, there was a significant decrease of AChE activities (AChE being the main ChE type) with an increase of dimethoate dose (IC(50)=1.4 mg/kg). Further, post-exposure video records showed that organisms were still alive in the spiked soil but lacked the locomotion ability (immobilised). The AChE inhibition correlated positively with immobilisation. Hence, this observation also showed that the apparent "attraction" behaviour observed in the avoidance test is rather a direct effect of not being able to escape due to paralysis hence a false-negative avoidance. This can constitute a confounding factor in an avoidance behaviour test and consequent interpretation, which is not accounted for at present.

  7. Anti-Oxidative and Cholinesterase Inhibitory Effects of Leaf Extracts and Their Isolated Compounds from Two Closely Related Croton Species

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    Johannes Van Staden


    Full Text Available A comparative evaluation of the antioxidant and acetylcholinesterase inhibitory activity of the leaf extracts of Croton gratissimus and Croton zambesicus (subgratissimus and compounds isolated from the extracts was carried out to determine their potential and suitability or otherwise as a substitute for each other in the management of oxidative and neurodegenerative conditions. Different antioxidant assays (DPPH, FRAP, β-carotene-linoleic and the lipid peroxidation models and the microplate assay for acetylcholinesterase (AChE inhibition were carried out separately to study the activities of the crude leaf extracts and four solvent fractions from each of the two Croton species. Bioassay guided fractionation was used to target antioxidant constituents of the crude extracts and ethyl acetate fractions of 20% aqueous methanol extract of C. gratissimus on silica gel and Sephadex LH-20 columns resulted in the isolation of kaempferol-3-O-β-6''(p-coumaroyl glucopyranoside (tiliroside, 2, apigenin-6-C-glucoside (isovitexin, 3 and kampferol (4. The extract of C. zambesicus yielded quercetin-3-O-β-6''(p-coumaroyl glucopyranoside-3'-methyl ether (helichrysoside- 3'-methyl ether, 1, kaempferol-3-O-β-6''(p-coumaroyl glucopyranoside (tiliroside, 2 and apigenin-6-C-glucoside (isovitexin, 3. Three of the isolated compounds and their different combinations were also included in the bioassays. In all the assays performed, the antioxidant capacity and AChE inhibitory effects of C. zambesicus extracts were weaker than those of C. gratissimus. This suggests that C. gratissimus may not be substituted by C. zambesicus, despite the similarity in some of their constituents. Generally, the combinations made from the isolated compounds showed better activities in most of the assays compared to the individual isolated compounds. This suggests mechanisms such as synergism and/or additive effects to be taking place. This study established low, moderate and high antioxidant activities as well as AChE inhibitory effects by the crude extracts, fractions, compounds and compound combinations. This means some of the extracts, isolated compounds and compound combinations could be useful in the management of neurodegenerative conditions and serve as sources of natural neurodegenerative agents.

  8. OHOLO Conference (36th): Multidisciplinary Approaches to Cholinesterase Functions Held in Eilat, Israel on April 6 - 10, 1992. (United States)


    Caenorhabditis elegans. A4. - Bank, Gina - Cloning and Analysis of the Acetylcholinesterase Gene of Ceratitis capitata (medfly) A5.- Bartels, C., T...FOR THE 36th OHOLO CONFERENCE CLONING AND ANALYSIS OF THE ACETYLCHOLINESTERASE GENE OF Ceratitis capitata (inedfly) Gina Banks, I.M.B.B., P.O. B. 1527...Heraklion 711 10, Crete, Greece Sequence data has been determined for the acetylcholinesterase (AChE) gene from Ceratitis capitata (medfly), the

  9. PRO-2-PAM: The First Therapeutic Drug for Reactivation of Organo-Phosphate-Inhibited Central (Brain) and Peripheral Cholinesterases (United States)


    the H&E and fluoro-jade stained slides, respectively. The middle lobe of the piriform cortex, a distinct brain region known to be sensitive to OP...U /m g Figure 8. H & E stain of guinea pig brain, 40x magnification of the piriform cortical neuron layer (“A”; see Methods section 2.5). (a...receiving DFP followed by the oxime 2-PAM. Black arrow points to piriform neurons. (a) ControlPiriform cortical neuron layer (b) DFP (c) DFP, then pro-2

  10. Evaluation of Antioxidant, Cholinesterase Inhibitory and Antimicrobial Properties of Mentha longifolia subsp. noeana and Its Secondary Metabolites

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    Abdulselam Ertaş


    Full Text Available The aim of the present study was to determine the chemical structures of the isolated compounds, the essential oil and fatty acid compositions of Mentha longifolia subsp. noeana with their biological activities. Ursolic acid (1, u vaol (2, stigmast-5-ene-3 b -yl formate (3, stigmast-5-en-3-one (4, b -sitosterol (5, bis(2-ethylhexyl benzene-1,2-dicarboxylate (6,hexacosyl (E-ferulate (7 and 5-hydroxy-6,7,3',4'-tetramethoxy flavone (8 were obtained from the aerial parts. The compounds (2-4, 6, 7 were isolated for the first time from a Mentha species. Palmitic acid (40.8% was the major component of the non-polar fraction obtained from the petroleum ether extract. Pulegone (32.3% was the main constituent of the essential oil which exhibited strong butyrylcholinesterase inhibitory activity (77.36 ± 0.29%, moderate antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans. The methanol extract showed 80% inhibition of lipid peroxidation, and the acetone extract possessed moderate DPPH free radical scavenging activity (60% inhibition at 100 m g/mL.

  11. Brain cholinesterase response in the snakehead fish (Channa striata) after field exposure to diazinon

    DEFF Research Database (Denmark)

    van Cong, Nguyen; Phuong, Nguyen Thanh; Bayley, Mark


    The snakehead Channa striata is an economically important air-breathing fish species in the Mekong delta of Vietnam. Rice paddies, which are disturbed by the frequent application of agro-chemicals, are among the preferred habitats for this species during the rainy season. Diazinon is one of most...

  12. Prophylactic administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone. (United States)

    Lorke, Dietrich E; Nurulain, Syed M; Hasan, Mohamed Y; Kuča, Kamil; Petroianu, Georg A


    Poisoning with organophosphorus compounds (OPCs) poses a serious threat worldwide. OPC-induced mortality can be significantly reduced by prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors. The only American Food and Drug Administration (FDA)-approved substance for such pre-treatment (to soman exposure) is presently pyridostigmine, although its efficacy is controversial. In search for more efficacious and broad-spectrum alternatives, we have assessed in vivo the mortality-reducing efficacy of a group of five compounds with known AChE inhibitory activity (pyridostigmine, physostigmine, ranitidine, tacrine and K-27), when given in equitoxic dosage (25% of LD01 ) 30 min before exposure to the OPC terbufos sulfone. Protection was quantified in rats by determining the relative risk of death (RR) using Cox analysis, with RR = 1 for animals given only terbufos sulfone, but no pre-treatment. All tested AChE inhibitors reduced terbufos sulfone-induced mortality significantly (p ≤ 0.05) as compared with the non-treatment group (RR = 1: terbufos sulfone only). Best in vivo protection from terbufos sulfone-induced mortality was achieved, when K-27 was given before terbufos sulfone exposure (RR = 0.06), which was significantly (P ≤ 0.05) superior to the pre-treatment with all other tested compounds, for example tacrine (RR = 0.21), pyridostigmine (RR = 0.28), physostigmine (RR = 0.29) and ranitidine (RR = 0.33). The differences in efficacy between tacrine, pyridostigmine, physostigmine and ranitidine were not statistically significant. Prophylactic administration of an oxime (such as K-27) in case of imminent OPC exposure may be a viable option.

  13. Is there a relationship between the blood cholinesterase and QTc interval in the patients with acute organophosphate poisoning? (United States)

    Baydin, A; Aygun, D; Yazici, M; Karatas, A; Deniz, T; Yardan, T


    Organophosphates cause poisoning as a result of the excessive accumulation of acetylcholine at the cholinergic synapses due to inhibition of acetylcholinesterase (ChE). In the literature, it has been reported that there have been electrocardiographic abnormalities, including QT-interval prolongation in most patients with acute organophosphate poisoning (OPP), and a relation between blood ChE level and clinical severity in acute OPP. The aim of this study is to assess the relationship between blood ChE level and QTc interval in the patients with acute OPP. This retrospective study consists of 20 patients admitted to the emergency intensive care unit. A total of 93 QTc interval and blood ChE measures obtained on the same day from 20 cases were compared for their correlation. There were prolonged QTc intervals in 35.4% of the ECGs. There was a negative correlation between QTc interval and blood ChE measures. In following up the patients with acute OPP, QTc interval may be useful when blood ChE levels are low and may provide complementary information concerning the severity of poisoning. However, further prospective studies, supporting the present results, are needed.

  14. Effects of structural modifications on the metal binding, anti-amyloid activity, and cholinesterase inhibitory activity of chalcones. (United States)

    Fosso, Marina Y; LeVine, Harry; Green, Keith D; Tsodikov, Oleg V; Garneau-Tsodikova, Sylvie


    As the number of individuals affected with Alzheimer's disease (AD) increases and the availability of drugs for AD treatment remains limited, the need to develop effective therapeutics for AD becomes more and more pressing. Strategies currently pursued include inhibiting acetylcholinesterase (AChE) and targeting amyloid-β (Aβ) peptides and metal-Aβ complexes. This work presents the design, synthesis, and biochemical evaluation of a series of chalcones, and assesses the relationship between their structures and their ability to bind metal ions and/or Aβ species, and inhibit AChE/BChE activity. Several chalcones were found to exhibit potent disaggregation of pre-formed N-biotinyl Aβ1-42 (bioAβ42) aggregates in vitro in the absence and presence of Cu(2+)/Zn(2+), while others were effective at inhibiting the action of AChE.

  15. Effect of coumaphos on cholinesterase activity, hematology, and biochemical blood parameters of bovines in tropical regions of Mexico. (United States)

    Pardío, Violeta T; Ibarra, Nelly De J; Waliszewski, Krzysztof N; López, Karla M


    To assess the effect of coumaphos [O-(3-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl) O,O-diethyl phosphorothioate] exposure on physiological responses during bovine production, acetylcolinesterase (AChE) and butyrylcholinesterase (BuChE) activities were measured in whole blood, erythrocytes, and plasma of healthy male steers (Bos Taurus x Bos indicus) sprayed with coumaphos at a non-lethal dose of 1 mg kg(- 1) body weight per day once every 14 (in vivo group) or 21 days (southern and central groups). Coumaphos topically administered at 1 mg/kg body weight per day to cattle under normal management practices in tropical areas produced a significant inhibition in erythrocyte (RBC) AChE and BuAChE activities when compared to baseline levels. RBC-AChE activity for the in vivo group decreased 71.3% (P < 0.05) and BuChE activity 59.1% (P < 0.05); RBC-AChE activity decreased 55.1% (P < 0.05) (southern group) and 43.4% (P < 0.05) (central group). Compared to the control specimens, steers from in vivo, southern, and central groups after 150 days of exposure had lower (P < 0.05) leukocyte count, absolute lymphocyte, erythrocyte, and platelet counts. Decreases in RBC-AChE activities correlated with decreased lymphocyte (r = 1.000, p = 0.01), erythrocyte (r = 1.000, p = 0.003), and platelet counts (r = 0.841, p = 0.036). Significantly increased BUN levels (P < 0.05) correlated with the decrease in RBC-AChE activities (r = - 0.997, p = 0.047) and with the decrease in absolute red blood cell (r = - 0.883, p = 0.020) and lymphocyte (r = - 0.825, p = 0.043) counts; increased (P < 0.05) total plasma protein levels correlated with the decrease in RBC-AChE activities (r = -0.998, p = 0.043), absolute red blood cell (r = - 0.998, p = 0.040), lymphocyte (r = - 0.893, p = 0.017), and platelet (r = -0.855, p = 0.030) counts. The physiological responses correlated with the erythrocyte acetylcholinesterase inhibition could be considered as early indicators or warning responses of bovine exposures to organophosphorus pesticides (OPs).

  16. Kinetics and molecular docking studies of cholinesterase inhibitors derived from water layer of Lycopodiella cernua (L.) Pic. Serm. (II). (United States)

    Hung, Tran Manh; Lee, Joo Sang; Chuong, Nguyen Ngoc; Kim, Jeong Ah; Oh, Sang Ho; Woo, Mi Hee; Choi, Jae Sue; Min, Byung Sun


    Acetylcholinesterase (AChE) inhibitors increase the availability of acetylcholine in central cholinergic synapses and are the most promising drugs currently available for the treatment of Alzheimer's disease (AD). Our screening study indicated that the water fraction of the methanolic extract of Lycopodiella cernua (L.) Pic. Serm. significantly inhibited AChE in vitro. Bioassay-guided fractionation led to the isolation of a new lignan glycoside, lycocernuaside A (12), and fourteen known compounds (1-11 and 13-15). Compound 7 exhibited the most potent AChE inhibitory activity with an IC50 value of 0.23 μM. Compound 15 had the most potent inhibitory activity against BChE and BACE1 with IC50 values of 0.62 and 2.16 μM, respectively. Compounds 4 and 7 showed mixed- and competitive-type AChE inhibition. Compound 7 noncompetitively inhibited BChE whereas 15 showed competitive and 8, 13, and 14 showed mixed-type inhibition. The docking results for complexes with AChE or BChE revealed that inhibitors 4, 7, and 15 stably positioned themselves in several pocket/catalytic domains of the AChE and BChE residues.

  17. In vitro Inhibition of Acetyl Cholinesterase, Lipoxygenase, Xanthine Oxidase and Antibacterial Activities of Five Indigofera (Fabaceae Aqueous Acetone Extracts from Burkina Faso

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    C.E. Lamien


    Full Text Available The aim of this study is to evaluate the inhibition of oxidative stress related enzymes of aqueous acetone extracts, as well as antibacterial activity from five Indigofera species well-known medicinal plant from Burkina. Also are investigated in this study the potential contribution of tannins and of flavonol in these activities Particularly, aqueous acetone extracts were investigated for their Lipoxygenase (LOX, Xanthine Oxidase (XO and Acetylcholinesterase (AChE inhibitions that are implied in inflammation, gout and Alzheimer’s etiology diseases. Interestingly, I. macrocalyx which had the highest flavonol content (of all showed more inhibition against LOX and XO (51.16 and 77.33% respectively. Our study showed a significant correlation between XO inhibition and total flavonol content (R2 = 0.9052. AChE was low sensible to all extracts. In contrast, the extracts were rich in tannin compounds especially in I. tinctoria extract. And results of the in vitro antibacterial activities of these extracts against five bacteria showed that all bacteria were sensible to all extracts particularly S. typhimurium and B. cereus. Our results suggest that the five studied species prove to be good sources of inhibition of the three enzymes involved in oxidative stress and also to have some antibacterial properties. That is what probably explains their uses in folk medicine, singularly, in the treatment of gout, dysentery and anti-inflammatory diseases.

  18. Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors (United States)


    Acetylcholinesterase (AChE) is the physiologically important target for organophosphorus toxicants (OP) including nerve agents and pesticides. Butyrylcholinesterase (BChE) in blood serves as a bioscavenger that protects AChE in nerve synapses from inhibition by OP. Mass spectrometry methods can detect exposure to OP by measuring adducts on the active site serine of plasma BChE. Genetic variants of human AChE and BChE do exist, but loss of function mutations have been identified only in the BCHE gene. The most common AChE variant, His353Asn (H322N), also known as the Yt blood group antigen, has normal AChE activity. The most common BChE variant, Ala567Thr (A539T) or the K-variant in honor of Werner Kalow, has 33% reduced plasma BChE activity. The genetic variant most frequently associated with prolonged response to muscle relaxants, Asp98Gly (D70G) or atypical BChE, has reduced activity and reduced enzyme concentration. Early studies in young, healthy males, performed at a time when it was legal to test nerve agents in humans, showed that individuals responded differently to the same low dose of sarin with toxic symptoms ranging in severity from minimal to moderate. Additionally, animal studies indicated that BChE protects from toxicants that have a higher reactivity with AChE than with BChE (e.g., nerve agents) but not from toxicants that have a higher reactivity with BChE than with AChE (e.g., OP pesticides). As a corollary, we hypothesize that individuals with genetic variants of BChE may be at increased risk of toxicity from nerve agents but not from OP pesticides. PMID:27551784

  19. Synthesis and evaluation of 7-substituted coumarin derivatives as multimodal monoamine oxidase-B and cholinesterase inhibitors for the treatment of Alzheimer's disease. (United States)

    Joubert, Jacques; Foka, Germaine B; Repsold, Benjamin P; Oliver, Douglas W; Kapp, Erika; Malan, Sarel F


    A series of 7-substituted coumarin derivatives were designed and synthesised to display ChE and MAO-B inhibitory activity. The compounds consisted out of a coumarin structure (MAO-B inhibitor) and benzyl-, piperidine-, N-benzylpiperidine- or p-bromo-N-benzylpiperizine moiety, resembling the N-benzylpiperidine function of donepezil (ChE inhibitor), connected via an alkyl ether linkage at the 7 position. The biological assay results indicated that all the compounds (1-25) displayed selective inhibition to hMAO-B over hMAO-A, with the benzyloxy series (1-8, 10-13) showing nano-molar hMAO-B inhibition (IC50: 0.5-73 nM). Limited ChE inhibitory activity was however observed for the benzyloxy series with the exception of 2 and especially 3 showing selective BuChE inhibition. From this series 3 showed the best multifunctional activity (eqBuChE IC50 = 0.96 μM, hMAO-A IC50 = 2.13 μM, hMAO-B IC50 = 0.0021 μM). Within the N-benzylpiperidine (16-19) and p-bromo-N-benzylpiperizine (21-24) series the compounds in general showed moderate ChE and MAO-B inhibitory activity. Of these compounds 19 was the most potent multifunctional agent showing good eeAChE and eqBuChE inhibition (IC50 = 9.10 μM and 5.90 μM, respectively), and relatively potent and selective hMAO-B inhibition (IC50 = 0.30 μM, SI = >33). Molecular modeling revealed that 19 was able to bind simultaneously to the CAS, mid-gorge and PAS sites of AChE and BuChE suggesting that it will be able to inhibit AChE induced Aβ aggregation. From this study, compounds that 3 and 19 can be considered as promising multifunctional lead compounds.

  20. Effects of Nanosilver Exposure on Cholinesterase Activities, CD41, and CDF/LIF-Like Expression in ZebraFish (Danio rerio Larvae

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    Marzhan Myrzakhanova


    Full Text Available Metal nanosolicoparticles are suspected to cause diseases in a number of organisms, including man. In this paper, we report the effects of nanosilver (Ag, 1–20 nm particles on the early development of the zebrafish, a well-established vertebrate model. Embryos at the midgastrula stage were exposed to concentrations ranging from 100 to 0.001 mg/L to verify the effects on different endpoints: lethality, morphology, expression of cholinergic molecules, and development of the immune system. (1 Relative risk of mortality was exponential in the range between 0.001 and 10 mg/L. Exposure to 100 mg/L caused 100% death of embryos before reaching the tail-bud stage. (2 Developmental anomalies were present in the 72 h larvae obtained from embryos exposed to nanosilver: whole body length, decreased eye dimension, and slow response to solicitation by gentle touch with a needle tip, with a significant threshold at 0.1 mg/L. (3 Dose-dependent inhibition of acetylcholinesterase activity was significant among the exposures, except between 1 mg/L and 10 mg/L. (4 The distribution of CD41+ cells and of CDF/LIF-like immunoreactivity was altered according to the Ag concentration. The possible effect of nanosilver in impairing immune system differentiation through the inhibition of molecules related to the cholinergic system is discussed.

  1. Low level nose-only exposure to the nerve agent soman: Toxicokinetics of soman stereoisomers and cholinesterase inhibition in atropinized guinea pigs

    NARCIS (Netherlands)

    Benschop, H.P.; Trap, H.C.; Spruit, H.E.T.; Wiel, H.J. van der; Langenberg, J.P.; Jong, L.P.A. de


    In order to initiate a quantitative basis for the toxicology of low level exposure to nerve agents, the toxicokinetics of soman stereoisomers during nose-only exposure for 5 h to 20 ppb (160 μg/m3) of C(±)P(±)- soman in air were studied in restrained, anesthetized, and atropinized guinea pigs. The c

  2. Age and Heat Stress Related Changes in Monoamine Contents and Cholinesterase Activity in Some Central Nervous System Regions of Albino Rat Newborns

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    M. Bahgat


    Full Text Available The normal monoamine [norepinephrine (NE, epinephrine (E, dopamine (DA and serotonin (5-HT] contents and cholinestrase (chE activity were significantly and gradually increased with age progress between postnatal days 7 and 21 in cerebrum, cerebellum, medulla oblongata and spinal cord of rat newborns. The daily exposure of the newborns to 401C for 2 h induced deteriorated effects and the withdrawal period of 7 days failed to return these altered variables to normal levels. On the other hand, the high temperature exerted its most potent decreased effect on monoamine contents at 21 days old. This decrease may be attributed to the elevated activity of monoamine oxidase and/or the decreased activity of the key enzymes responsible for monoamine synthesis. The chE activity exhibited different effects in the tested CNS regions as a result of high temperature exposure; the enzyme activity was decreased markedly at days 7, 14 and 21 in cerebellum and medulla oblongata and lowered only at days 7 and 14 in cerebrum and at day 14 in spinal cord. The subsequent withdrawal for 7 days beyond day 21 produced marked weakening of effect of high temperature exposure on monoamine contents in all examined CNS regions except NE and 5-HT contents in cerebellum and DA level in medulla oblongata. In spite of this attenuation, the values recorded in the withdrawal group were still significantly lower than the normal levels. On the other hand, the chE activity became more deleteriously affected at day 28 in the treated CNS regions except in the medulla oblongata where it was profoundly ameliorated after the withdrawal period.


    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  4. Effects of Endurance Training on A12 Acetyl Cholinesterase Activity in Fast and Slow-Twitch Skeletal Muscles of Male Wistar Rats

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    Ali Gorzi


    Full Text Available Background: Endurance training improves the activity of G4 type acetylcholine esterase (AchE in muscle fibres. The purpose of this study was to investigate the effects of 8 weeks of endurance training (ET on activity of A12 type of AchE in Flexor Hallucis Longus (FHL and Soleus (SOL muscles of rats. Materials and Methods: 16 male wistar rats (age: 10 weeks and weight: 172.17±10.080 gr, were randomly divided in 2 groups (control; N=8 and ET; N=8. Training group carried out 8 weeks (5 session/week of endurance training on animal treadmill with speed of 10 m/min for 30 min at the first week which was gradually increased to 30 m/min for 60 min (70-80% of VO2max at the last week. Forty eight hours after last session of training, FHL and Sol muscles of animals were moved out under sterilized situation by cutting on posterio-lateral side of hind limb. For separating AchE subunits, homogenization and electrophoresis (0.06 non-denaturaing polyacrilamide methods were used. AchE activity was measured by Elisa kit.Results: The activity of this protein significantly (p=0.017 increased in SOL muscle of ET group by 119%, but did not changed in FHL. In both groups (ET and Con, FHL muscle had significantly (ET: p=0.028 and Con p=0.01 higher basic levels of AchE activity compared to SOL muscle. This significant increase in AchE of SOL might be indicative of responsiveness of AchE of this muscle following endurance training for improving acetylcholine (Ach cycle in neuromuscular junction.Conclusion: Endurance training might increase the A12 type AchE activity to improve the Ach cycle as part of the adaptation of neuromuscular junction to increased level of physical activity.

  5. [Dementia with Lewy bodies; 2 patients with exacerbation due to an atypical antipsychotic, but with a favorable response to the cholinesterase inhibitor rivastigmine

    NARCIS (Netherlands)

    Scheepmaker, A.J.T.M.; Horstink, M.W.I.M.; Hoefnagels, W.H.L.; Strijks, F.E.


    In two patients, men aged 80 and 75 years with cognitive deterioration, hallucinations and parkinsonism, the clinical diagnosis 'dementia with Lewy bodies' was established. Treatment with an atypical antipsychotic, risperidone and olanzapine respectively, resulted in an exacerbation of the parkinson

  6. Use of cholinesterase activity as a biomarker of pesticide exposure used on Costa Rican banana plantations in the native tropical fish Astyanax aeneus (Günther, 1860). (United States)

    Mena, F; Azzopardi, M; Pfennig, S; Ruepert, C; Tedengren, M; Castillo, L E; Gunnarsson, J S


    In Costa Rica, thousands of tones of agricultural pesticides have been used for decades and their use is continuously increasing due to intensive and expanding production of coffee, pineapple, rice, ornamental plants and bananas. The objective of this study was to evaluate whether choline esterase (ChE) activity could be used as a biomarker of exposure to pesticides in the Costa Rican native fish Astyanax aeneus (characidae). Three methods used in order to evaluate the ChE biomarker were as follows: Laboratory studies where A. aeneus was exposed to organophosphate pesticide (ethoprophos); In situ 48 hr exposure assessment using caging experiments with fish exposed upstream and downstream of banana plantations and ChE activity estimation of in fish captured directly at sites with different degrees of pesticide exposure. Results from the laboratory studies showed that ChE activity in both brain and muscle tissue was significantly lower in fish exposed to ethoprophos than in controls. Fish from the caging experiments showed no difference in ChE activity neither in brain nor in muscle tissue between the four tested sites and was attributed to the short duration of the exposure. Asignificant difference in ChE activity was determined in muscle of fish captured from Laguna Madre de Dios compared to fish from Canal Batán. Although our laboratory results revealed that ChE activity in A. aeneus was highly responsive to ethoprophos, results from field experiments were less conclusive and showed that the captured fish showed large variability in ChE activity and that more research is needed before ChE activity can be used as reliable biomarker of pesticide exposure.

  7. Plasma cholinesterase activity as a biomarker for quantifying exposure of green sturgeon to carbaryl following applications to control burrowing shrimp in Washington State. (United States)

    Troiano, Alexandra T; Grue, Christian E


    Willapa Bay (Washington State, USA) has been 1 of the rare intertidal locations where large-scale pesticide applications occur. Until recently, carbaryl was applied to control burrowing shrimp that decrease commercial oyster productivity. The bay is a critical habitat for green sturgeon (Acipenser medirostris), an anadromous species listed as threatened under the US Endangered Species Act. However, the hazard that carbaryl poses is unknown. Surrogate seawater-acclimated white sturgeon (A. transmontanus) were exposed to 0 μg L(-1) , 30 μg L(-1) , 100 μg L(-1) , 300 μg L(-1) , 1000 μg L(-1) , and 3000 μg L(-1) carbaryl for 6 h, and brain acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) activities were measured. Enzyme recovery was measured in an additional cohort exposed to 1000 μg L(-1) carbaryl for 6 h. Activity of AChE was reduced (p ≤ 0.001) at concentrations ≥ 100 μg L(-1) with recovery in the 1000 μg L(-1) cohort by 72 h. Surprisingly, BChE activity was greater than controls at concentrations ≥ 300 μg L(-1) (p > 0.05), a finding confirmed in additional fish exposed to 3000 μg L(-1) for 6 h (+30%, p sturgeon before and 4 d to 5 d after application of carbaryl in Willapa Bay. Activity of BChE after application was reduced 28% (p white sturgeon exposed to carbaryl indicates that further studies are needed to better understand the risk carbaryl exposure poses to green sturgeon. Environ Toxicol Chem 2016;35:2003-2015. © 2015 SETAC.

  8. Acute exposure to fenthion in juveniles of white cachama (Piaractus brachypomus: toxic effects, changes in cholinesterase activity and potential use in environmental monitoring

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    Borbón Javier F.


    Full Text Available Fenthion is an organophosphate insecticide used worldwide that may pollute waters after itsapplication causing potential problems in public health and poisoning in domestic and wildlifeanimals. Objective: to evaluate toxic effects, butyrylcholinesterase activity (BChE and use inenvironmental monitoring, 34 juveniles of white cachama (Piaractus brachypomus were distributedin 3 groups (control, 0,13 ppm and 2 ppm fenthion for 96 h. Materials and methods: fishwere exposed in 10-gallon tanks; symptoms, gross lesions post-mortem, viscerosomatic index(VSI and plasma BChE activity were evaluated. Mean comparisons for each variable amongtreatments were performed (ANOVA, α=0,05. Results: severe signs were seen in 3 specimens(3/11 of 2 ppm fenthion between 11 and 34 h of exposure. These signs were frantic swimming,muscle tremors and loss of swimming axis. In 0,13 ppm, mild to moderate signs (tremors andcaudal fin flapping were observed in some of the fish. The VSI (control = 5,3 ± 0,5; 0,13 ppm= 6,9 ± 0,3 and 2 ppm = 7,3 ± 0,6 was significantly different between exposed to fenthion andcontrols. BChE activity (control = 185,0 ± 20,4; 0,13 ppm = 12,5 ± 2,3 and 2 ppm = 9,8 ± 1,8nmoles / ml plasma / min showed significant inhibition in exposed to fenthion as compared tocontrols. Conclusions: the present work confirmed the toxic effects of fenthion in white cachamajuveniles. Results found in BChE activity suggest its use in environmental monitoring as a goodbiomarker of organophosphates waterborne exposure.

  9. Cholinesterase inhibition and depression of the photic after discharge of flash evoked potentials following acute or repeated exposures to a mixture of carbaryl and propoxur. (United States)

    Mwanza, Jean-Claude; Lyke, Danielle F; Hertzberg, Richard C; Haber, Lynne; Kohrman-Vincent, Melissa; Li, Ruosha; Pan, Yi; Lyles, Robert H; Simmons, Jane Ellen; Macmillan, Denise K; Zehr, R Dan; Swank, Adam E; Herr, David W


    Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration of the photic after discharge (PhAD) of flash evoked potentials (FEPs). In the current studies, we compared the effects of acute or repeated exposure to a mixture of carbaryl and propoxur (1:1.45 ratio; propoxur:carbaryl) on the duration of the PhAD and brain ChE activity in Long Evans rats. Animals were exposed (po) either to a single dose (0, 3, 10, 45 or 75 mg/kg), or 14 daily dosages (0, 3, 10, 30, 45 mg/kg), of the mixture. Acute and repeated treatment with 3mg/kg (or greater) of the mixture produced dose-related inhibition of brain ChE activity. Compared to controls, the PhAD duration decreased after acute administration of 75 mg/kg or repeated treatment with 30 mg/kg of the mixture. The linear relationship between the percent of control brain ChE activity and the PhAD duration was similar for both exposure paradigms. Dose-response models for the acute and repeated exposure data did not differ for brain ChE activity or the duration of the PhAD. Repeated treatment with the mixture resulted in slightly less (13-22%) erythrocyte ChE inhibition than acute exposure. Both acute and repeated treatment resulted in dose-additive results for the PhAD duration and less than dose-additive responses (6-16%) for brain ChE activity for the middle range of dosages. Acute treatment resulted in greater than dose-additive erythrocyte ChE inhibition (15-18%) at the highest dosages. In contrast, repeated treatment resulted in less than dose-additive erythrocyte ChE inhibition (16-22%) at the middle dosages. Brain and plasma levels of propoxur and carbaryl did not differ between the acute and repeated dosing paradigms. In summary, a physiological measure of central nervous system function and brain ChE activity had similar responses after acute or repeated treatment with the carbamate mixture, and brain ChE showed only small deviations from dose-additivity. Erythrocyte ChE activity had larger differences between the acute and repeated treatment paradigms, and showed slightly greater deviations from dose-additivity. Because these treatments utilized larger dosages than anticipated environmental exposures, concern for non-additive effects in humans is minimized. The small magnitude of the deviations from dose-additivity also suggest that in the absence of repeated exposure data, results from an acute study of readily reversible carbamate toxicity can be used to estimate the response to repeated daily exposures.

  10. Effects of the insecticide, orthene, on unconfined populations of the meadow vole (Microtus pennsylvanicus). I. Capture/recapture procedures; II. Residues and cholinesterase inhibition (United States)

    Jett, D.A.


    In 1982 and 1983. the population demography of M. pennsylvanicus was not altered significantly by single or double applications of Orthene. Although inconsistencies in population size, survival, and recruitment were not explained by differences between control and experimental grids in breeding, emigration, interspecific competition, or pesticide-induced mortality, there may have been fundamental microhabitat differences between grids in both years, and this is supported by prespray data. Slight differences between grids may also reflect the random error associated with the models used to estimate parameters. No evidence was found to indicate an effect on relative weight change or average distances moved. The level of brain AChE in 1982 during sequential days after spraying was significantly lower than control levels. However, this inhibition was not enough to cause direct mortality. Recovery of brain AChe was gradual, probably reflecting continual re-exposure through the diet. Acephate and methamidophos residues were present in the vegetation collected from sprayed areas immediately following treatment, but were reduced or absent after 8 days. AChE inhibition in 1982 and 1983 extended beyond the disappearance of residues in the vegetation. Residues were only present in the G.l. tracts of voles collected immediately following treatment due to rapid metabolism and excretion. Levels in the vegetation and G.l. tracts in 1982 and 1983 were well below the rat oral LD50 of acephate. It is concluded that Orthene applied at recommended levels, in a single or double treatment, should not affect unconfined populations of M. pennsylvanicus in Maryland old-field habitats. Furthermore, this study confirms this method as a sensitive means to determine the overall impact of insecticides on wildlife populations. However, caution must be exercised to insure that all control and experimental areas are closely scrutinized for habitat differences.

  11. Activity of cholinesterases, pyruvate kinase and adenosine deaminase in rats experimentally infected by Fasciola hepatica: Influences of these enzymes on inflammatory response and pathological findings. (United States)

    Baldissera, Matheus D; Bottari, Nathieli B; Mendes, Ricardo E; Schwertz, Claiton I; Lucca, Neuber J; Dalenogare, Diessica; Bochi, Guilherme V; Moresco, Rafael N; Morsch, Vera M; Schetinger, Maria R C; Rech, Virginia C; Jaques, Jeandre A; Da Silva, Aleksandro S


    The aim of this study was to investigate acetylcholinesterase (AChE) in total blood and liver tissue; butyrylcholinesterase (BChE) in serum and liver tissue; adenosine deaminase (ADA) in serum and liver tissue; and pyruvate kinase (PK) in liver tissue of rats experimentally infected by Fasciola hepatica. Animals were divided into two groups with 12 animals each, as follows: group A (uninfected) and group B (infected). Samples were collected at 20 (A1 and B1;n=6 each) and 150 (A2 and B2; n=6 each) days post-infection (PI). Infected animals showed an increase in AChE activity in whole blood and a decrease in AChE activity in liver homogenates (P<0.05) at 20 and 150 days PI. BChE and PK activities were decreased (P<0.05) in serum and liver homogenates of infected animals at 150 days PI. ADA activity was decreased in serum at 20 and 150 days PI, while in liver homogenates it was only decreased at 150 days PI (P<0.05). Aspartate aminotransferase and alanine aminotransferase activities in serum were increased (P<0.05), while concentrations of total protein and albumin were decreased (P<0.05) when compared to control. The histological analysis revealed fibrous perihepatitis and necrosis. Therefore, we conclude that the liver fluke is associated with cholinergic and purinergic dysfunctions, which in turn may influence the pathogenesis of the disease.

  12. In vitro antioxidant and inhibitory activity of water decoctions of carob tree (Ceratonia siliqua L.) on cholinesterases, α-amylase and α-glucosidase. (United States)

    Custódio, Luísa; Patarra, João; Alberício, Fernando; Neng, Nuno Rosa; Nogueira, José Manuel Florêncio; Romano, Anabela


    This work reports the in vitro inhibitory activity of water decoctions of leaves, germ flour, pulp, locust bean gum and stem bark of carob tree on α-amylase, α-glucosidase, acetylcholinesterase and butyrylcholinesterase. The antioxidant activity and the chemical characterisation of the extracts made by spectrophotometric assays and by high-performance liquid chromatography are also reported. Leaves and stem bark decoctions strongly inhibited all the enzymes tested, had significant antioxidant activity and the highest total phenolics content. The major compounds were identified as gallic acid in the leaves and gentisic acid in the stem bark.

  13. In Vivo Reactivation by Oximes of Inhibited Blood, Brain and Peripheral Tissue Cholinesterase Activity Following Exposure to Nerve Agents in Guinea Pigs (United States)


    peripheral tissues and the blood components . A “+” sign was assigned for each of the peripheral tissues or blood com- ponents, when an oxime treatment...reactivation by oxime treatments in peripheral tissues and blood components following exposure to GB, GF, VR, and VXa. A. Peripheral tissues (diaphragm...tissues (A) or blood components (B), an oxime treatm ign. When an oxime treatment did not significantly reactivate a nerve agent-inhib ll four nerve

  14. Synthesis and Biological Evaluation of Benzochromenopyrimidinones as Cholinesterase Inhibitors and Potent Antioxidant, Non-Hepatotoxic Agents for Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Youssef Dgachi


    Full Text Available We report herein the straightforward two-step synthesis and biological assessment of novel racemic benzochromenopyrimidinones as non-hepatotoxic, acetylcholinesterase inhibitors with antioxidative properties. Among them, compound 3Bb displayed a mixed-type inhibition of human acetylcholinesterase (IC50 = 1.28 ± 0.03 μM, good antioxidant activity, and also proved to be non-hepatotoxic on human HepG2 cell line.

  15. Pharmacokinetics and pharmacodynamics of mivacurium in young adult and elderly patients

    DEFF Research Database (Denmark)

    Østergaard, Doris; Viby-Mogensen, Jørgen; Pedersen, N.A.


    age factors; butyrylcholinesterase; cholinesterase; dose-response curves; enzymes; metabolites; mivacurium; neuromuscular relaxants; pharmacodynamics; pharmacokinetics; pharmacology; pseudocholinesterase; stereoisomers......age factors; butyrylcholinesterase; cholinesterase; dose-response curves; enzymes; metabolites; mivacurium; neuromuscular relaxants; pharmacodynamics; pharmacokinetics; pharmacology; pseudocholinesterase; stereoisomers...

  16. An easy method for the determination of active concentrations of cholinesterase reactivators in blood samples: Application to the efficacy assessment of non quaternary reactivators compared to HI-6 and pralidoxime in VX-poisoned mice. (United States)

    Calas, André-Guilhem; Dias, José; Rousseau, Catherine; Arboléas, Mélanie; Touvrey-Loiodice, Mélanie; Mercey, Guillaume; Jean, Ludovic; Renard, Pierre-Yves; Nachon, Florian


    Organophosphorus nerve agents, like VX, are highly toxic due to their strong inhibition potency against acetylcholinesterase (AChE). AChE inhibited by VX can be reactivated using powerful nucleophilic molecules, most commonly oximes, which are one major component of the emergency treatment in case of nerve agent intoxication. We present here a comparative in vivo study on Swiss mice of four reactivators: HI-6, pralidoxime and two uncharged derivatives of 3-hydroxy-2-pyridinaldoxime that should more easily cross the blood-brain barrier and display a significant central nervous system activity. The reactivability kinetic profile of the oximes is established following intraperitoneal injection in healthy mice, using an original and fast enzymatic method based on the reactivation potential of oxime-containing plasma samples. HI-6 displays the highest reactivation potential whatever the conditions, followed by pralidoxime and the two non quaternary reactivators at the dose of 50 mg/kg bw. But these three last reactivators display equivalent reactivation potential at the same dose of 100 μmol/kg bw. Maximal reactivation potential closely correlates to surviving test results of VX intoxicated mice.

  17. Correction of organophosphate-induced neuromuscular blockade by diphenhydramine. (United States)

    Clemmons, R M; Meyer, D J; Sundlof, S F; Rappaport, J J; Fossler, M E; Hubbell, J; Dorsey-Lee, M R


    Dogs exposed to topical organophosphate (fenthion) developed decreased plasma and muscle cholinesterase activities. After 2 doses were applied (1 week between doses), plasma concentrations declined 80% and muscle cholinesterase activity was reduced by 56%. Decremental responses to repetitive nerve stimulation developed after fenthion administration. Diphenhydramine, but not placebo, corrected the electrical abnormalities caused by organophosphate application, but without altering plasma or muscle cholinesterase activity. Control dogs housed in the same kennel demonstrated a slight decrease (18%) of plasma cholinesterase, which indicates that there may be potential cross contamination. Diphenydramine may be effective in treating organophosphate-induced neuromuscular weakness which is refractory to other forms of therapy.

  18. Distribution and substrate specificity of esterases in the housefly, Musca domestica L.

    NARCIS (Netherlands)

    Asperen, K. van


    Housefly homogenates perform high cholinesterase and ali-esterase activity. Warburg-manometric studies show that acetylcholine, acetyl-β-methylcholine, butyrylcholine, and benzoylcholine are exclusively hydrolysed by a cholinesterase, the properties of which are more or less comparable to those of t

  19. US Army Biomedical Laboratory Annual Progress Report, Fiscal Year 1980 (United States)


    Psychopharmacoloqia. 11, 435-438 B, (1967). 110. Riter, L., Talens , G. & Woolley, D. Parathion administration in the monkey and recovery of blood cholinesterases and...Reiter, L., Talens , G. and Woolley, D. Acute and subacute parathion treatment: Effects on cholinesterase activities and learning in mice. Toxicol. Appl

  20. Butyrylcholinesterase as a Therapeutic Drug for Protection Against Percutaneous VX (United States)


    Larison, D.M. Maxwell, M.R. Murphy, M. Schutz, K. Waibel, A.D. Wolfe A.D., Cholinesterases as scavengers for organophosphorous compounds: protection...scavengers for organophosphorous agents, in: J. Massoulie, F. Bacou, E. Barnard, A. Chatonnet, B.P. Doctor, D.M. Quinn (Eds.), Cholinesterases: Structure

  1. Generation of Recombinant Human AChE OP-Scavengers with Extended Circulatory Longevity (United States)


    positions of analogous residues in TcAChE according to the recommended nomenclature (Massoulie et al., 1992) 99 contributing to the inherent...1997). A single amino acid substitution Gly117His confers phosphotriesterase (organophosphorus acid anhydride hydrolase) activity on human...Silman, I. and Taylor, P. (1992) Recommendations for nomenclature in cholinesterases, in Multidisciplinary Approaches to Cholinesterase Functions

  2. Cardiale neveneffecten van cholinesteraseremmers : een reden tot terughoudendheid in voorschrijven?

    NARCIS (Netherlands)

    Salarbaks, A M; Boomkamp-Snoeren, C M; van Puijenbroek, E; Jansen, P A F; van Marum, R J


    Cholinesterase inhibitors are prescribed in the treatment of mild to moderate Alzheimer's dementia. Little is known about the cardiac safety of these drugs. We present two different cases in which cardiac events occurred during the use of a cholinesterase inhibitor. The pathophysiology, the effects

  3. Carboxylic ester hydrolases in the thyroid gland of the guinea-pig. A light microscopic study

    DEFF Research Database (Denmark)

    Kirkeby, S


    The location of cholinesterase and non-specific esterase in the thyroid gland of the guniea-pig was studied with the light microscope. It was found that the idoxyl method for non-specific esterase activity under special conditions is superior to the cholinesterase method in a number of respects f...

  4. Natural Detoxification Capacity to Inactivate Nerve Agents Sarin and VX in the Rat Blood

    Directory of Open Access Journals (Sweden)

    Jiří Bajgal


    Full Text Available Background: The method of continual determination of the rat blood cholinesterase activity was developed to study the changes of the blood cholinesterases following different intervetions. Aims: The aim of this study is registration of cholinesterase activity in the rat blood and its changes to demonstrate detoxification capacity of rats to inactivate sarin or VX in vivo. Methods: The groups of female rats were premedicated (ketamine and xylazine and cannulated to a. femoralis. Continual blood sampling (0.02 ml/min and monitoring of the circulating blood cholinesterase activity were performed. Normal activity was monitored 1–2 min and then the nerve agent was administered i.m. (2× LD50. Using different time intervals of the leg compression and relaxation following the agent injection, cholinesterase activity was monitored and according to the inhibition obtained, detoxification capacity was assessed. Results: Administration of sarin to the leg, then 1 and 5 min compression and 20 min later relaxation showed that further inhibition in the blood was not observed. On the other hand, VX was able to inhibit blood cholinesterases after this intervention. Conclusions: The results demonstrated that sarin can be naturally detoxified on the contrary to VX. Described method can be used as model for other studies dealing with changes of cholinesterases in the blood following different factors.

  5. 胆碱酯酶抑制剂治疗阿尔茨海默病神经精神症状和功能损害的效果汇总分析%Efficacy of Cholinesterase Inhibitors in the Treatment of Neuropsychiatric Symptoms and Functional Impairment in Alzheimer Disease A Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Nhi-Ha Trinh; Jennifer Hoblyn; Subhanjoy Mohanty; Kristine Yaffe


    背景:胆碱酯酶抑制剂是阿尔茨海默病(Alzheimer disease,AD)认知症状的主要治疗药物。胆碱能功能障碍也可能导致神经精神和功能缺陷,但胆碱酯酶抑制剂随机对照试验的结果并不一致。目的:进行系统综述和汇总分析,定量显示胆碱酯酶抑制剂治疗轻至中度AD病人神经精神症状和功能减退的疗效。资料来源:我们应用MEDLINE(1966年1月-2001年12月)、在线论文摘要、PSYCHINFO、BIOSIS、PubMed和Cochrane对照试验登记查找相关试验的文献。我们检索了英语和非英语综述文章,从综述、研究原著及其他相关论文收集参考文献。我们查找了已发表和未发表的试验报告,并与研究者和制药公司取得联系。研究选择:我们入选平行组或交叉随机、双盲、安慰剂对照试验29项,参试者为诊断为轻至中度疑似AD并接受胆碱酯酶抑制剂治疗1个月以上的门诊病人。16项试验包括神经精神症状指标,18项试验包括功能指标。数据提取:两位研究者(N.H.T.和J.H.)分别提取研究方法、偏倚来源和预后指标。神经精神症状的预后采用神经精神症状调查表(NPI,0—120分)和阿尔茨海默病评估量表中的非认知量表(ADAS—noncog,0~50分)进行测定,并采用加权平均差法进行分析。功能的预后采用数项日常生活活动(ADL)量表或器械辅助日常生活活动(IADL)量表测定,用标准平均差法分析。数据综合:关于神经精神症状预后,10项试验有ADAS—noncog测定结果,6项试验有NPI测定结果。与安慰剂相比,随机使用胆碱酯酶抑制剂的病人NPI测定改善了1.72分(95%可信区间[CI],0.87~2.57分),A.DAS—noncog测定改善了0.03分(95%CI,0.00—0.05分)。关于生理功能预后,14项试验采用ADL量表,13项试验采用IADL量表。与安慰剂相比,随机使用胆碱酯酶抑制剂的病人ADL量表测定改善了0.1SDs(95%CI,0.00—0.19SDs),IADL量表测定改善了0.09SDs(95%CI,0.01~0.17SDs)。各种胆碱酯酶抑制剂的疗效无差异。结论:上述结果表明,胆碱酯酶抑制剂对AD病人的神经精神症状和功能预后有一定效果。今后的研究应致力于如何将这种改善转化为病人生活质量、医疗保健机构入住和保健提供者负担等方面的长期后果。

  6. Changed activity of cholinesterase and expression of nicotinic acetylchiline receptor in blood from the patients with vascular dementia%血管性痴呆患者血中胆碱酯酶活性及神经型尼古丁受体mRNA表达水平变化

    Institute of Scientific and Technical Information of China (English)

    肖雁; 张蓝江; 齐晓岚; 单可人; 况时祥; 刘芳; 官志忠


    目的 探讨血管性痴呆(vascular dementia,VD)患者血中胆碱酯酶活性及神经型尼古丁乙酰胆碱能受体(nicotinic acetyleholine receptor,nAchR)mRNA表达的变化.方法 分组比较测定59例血管性痴呆、33例正常老年人空腹血浆胆碱酯酶浓度及血液白细胞nAchRa4、β2亚单位mRNA表达水平.结果 血管性痴呆组与对照组乙酰胆碱酯酶活性分别为(1.70±1.17nmol/min/ml,2.18±0.87nmol/min/ml),VD组与对照组相比差异有显著性(P<0.05);VD组与对照组丁酰胆碱酯酶活性分别为(61.08±38.23nmol/min/ml,70.41+28.82nmol/min/ml),相比差异无显著性(P<0.05).乙酰胆碱酯酶及丁酰胆碱酯酶均无性别的差异;VD患者血液白细胞nAchR a4亚单位mRNA表达水平(0.926±0.411)较正常对照组(1.41±0.22)降低(P<0.05);VD患者nAchR β2亚单位mR-NA表达水平(2.14±0.18)与正常对照组(2.19±0.16)差异无显著性(P<0.05).结论 血管性痴呆患者血浆乙酰胆碱酯酶活性和血液白细胞中nAehR α4亚单位mRNA表达水平较正常对照老年人降低,但丁酰胆碱酯酶和nAeh β2 mRNA无改变,这些变化可能对血管性痴呆的诊断有一定临床意义.

  7. Drug Profile : Transdermal Rivastigmine Patch in the Treatment of Alzheimer Disease

    NARCIS (Netherlands)

    Emre, Murat; Bernabei, Roberto; Blesa, Rafael; Bullock, Roger; Cunha, Luis; Daniels, Hugo; Dziadulewicz, Edward; Foerstl, Hans; Froelich, Lutz; Gabryelewicz, Tomasz; Levin, Oleg; Lindesay, James; Martinez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus


    Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transder

  8. COGNOS : Care for People With Cognitive Dysfunction A National Observational Study

    NARCIS (Netherlands)

    Mets, Tony; De Deyn, Peter P.; Pals, Philippe; De Lepeleire, Jan; Vandewoude, Maurits; Ventura, Manfredi; Ivanoiu, Adrian; Albert, Adelin; Seghers, An-Katrien


    Care plans are intended to improve the independence and functioning of patients with cognitive dysfunction and support the caregivers involved. They are an integral part of the Belgian reimbursement procedure for cholinesterase inhibitors. This nationwide, multicenter, observational study examined t

  9. SwissProt search result: AK107259 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107259 002-125-G11 (P32752) Cholinesterase (EC (Acylcholine acylhydrolase) ( esterase II) (Butyrylcholine esterase) (Pseudocholinesterase) (Fragment) CHLE_PIG 5e-18 ...

  10. [Plasma cholesterol determination in birds--a diagnostic tool for detection of organophosphate and carbamate intoxication]. (United States)

    Kiesau, B; Kummerfeld, N


    An investigation was done on the clinical usefulness of the dry chemistry analyzer Vitros DT 60 II for determination of avian plasma cholinesterase. The analytical reliability of the method, evaluated by precision and accuracy, proved to be high for plasma of numerous pet and wild birds. Values of normal plasma-cholinesterase activity were established for different psittacine and European wild birds. Significant differences in physiologic plasma-cholinesterase activity were noted between closely related species as well as between juvenile and adult birds. These findings emphasize the necessity to use control values of the same species and age group for comparison. Dry chemistry plasma-cholinesterase determination can be used as a diagnostic tool for detection of organophosphate and carbamate poisonings in the majority of investigated birds.


    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

  12. New generic approach to the treatment of organophosphate poisoning : Adenosine receptor mediated inhibition of ACh-release

    NARCIS (Netherlands)

    van Helden, HPM; Moor, E; Westerink, BHC; Bruijnzeel, PLB


    Current treatment of acute organophosphate (OP) poisoning includes a combined administration of a cholinesterase reactivator (oxime), a muscarinic receptor antagonist (atropine) and an anticonvulsant (diazepam). This treatment is not adequate since it does not prevent neuronal brain damage and incap

  13. Drug: D07613 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07613 Drug Carbaryl (BAN); Carbaril; Flea and tick powder [veterinary] (TN) C12H11...NO2 201.079 201.2212 D07613.gif Insecticide Same as: C07491 carbamate insecticide cholinesterase inhibitor veterinary

  14. Drug: D04292 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available .gif Galanthus woronowii [TAX:197699] Alzheimer's disease treatment [cholinesterase inhibitor] [DS:H00056] S...d metabolism hsa04725(43) Cholinergic synapse Genomic biomarker: CYP2D6 [HSA:1565] map07056 Agents for Alzheimer

  15. Myasthenia Gravis (MG): Medical Management (United States)

    ... most commonly used is pyridostigmine (Mestinon) . Cholinesterase inhibitors boost ACh levels not only at the neuromuscular junction but also in the autonomic nervous system (which controls involuntary bodily functions). Sometimes the ...

  16. Persistent symptoms in agricultural workers exposed to organophosphate pesticides


    Martha E. Palacios N; María P. Paz


    Objective: to evaluate the prevalence of these symptoms and their relationship with pesticide exposure and the cholinesterase levels in agricultural workers. Methodology: an analytical cross-sectional study conducted in Mexico. Cholinesterase concentration and symptom frequency were assessed for 106 agricultural workers. Exposure was defined with a composed index of 15 variables. Results: symptom prevalence was 52 out of 100 workers. 31% of workers had 1 to 3 of the symptoms, 16% had 4 to 9 ...

  17. Selective inhibition of butyrylcholinesterase in vivo in horses by the feed-through larvacide Equitrol. (United States)

    Karanth, Subramanya; Holbrook, Todd; MacAllister, Charles; Pope, Carey N


    The organophosphate insecticide tetrachlorvinphos (TCVP, Rabon) is the active ingredient in "feed-through" larvacides (e.g., Equitrol) for fly control around horse stables. As with other organophosphates, TCVP elicits toxicity by inhibiting acetylcholinesterase, leading to accumulation of the neurotransmitter acetylcholine and cholinergic signs. Relatively little is known, however, on the effects of TCVP-containing larvacides on acetylcholinesterase or other esterases in horses. Previous in vitro studies indicated that horse plasma cholinesterase activity was substantially (>10,000-fold) more sensitive than erythrocyte cholinesterase activity to inhibition by TCVP. In the current study, we examined the relative proportion of acetylcholinesterase and butyrylcholinesterase activities in horse plasma and muscle, and evaluated the in vivo effects of Equitrol on target and non-target esterases following oral feeding in horses. In vitro inhibition studies suggested that essentially all cholinesterase activity in horse plasma was butyrylcholinesterase, while muscle contained >90% acetylcholinesterase activity. For in vivo studies, adult, male horses (364-590kg; n=3/treatment group) were given either sweet feed alone or sweet feed supplemented with Equitrol daily for 21 consecutive days at the recommended rate. Clinical signs (vital signs, abdominal auscultation, ophthalmic exam, body temperature) were recorded on a daily basis. Heparinized blood samples were taken at days -1, 1, 3, 7, 21, 28, and 42 while muscle (semimembranosus) biopsies were taken under aseptic conditions on days -1 and 21. No signs of overt toxicity were noted at any time during the study. Plasma cholinesterase activity was significantly inhibited (33%) in larvacide-treated horses as early as one day after treatment and peak inhibition (69-71%) was noted at days 7 and 21. Following cessation of dosing, plasma cholinesterase activity recovered (46% and 83% of control on days 28 and 42, respectively

  18. Assessment of acetylcholinesterase and butyrylcholinesterase activities in blood plasma of agriculture workers

    Directory of Open Access Journals (Sweden)

    V Dhananjayan


    Full Text Available Background: Cholinesterase determination indicates whether the person has been under pesticide exposure is not. It is recommended that the worker′s cholinesterase level should be assessed for workers at a pesticide applied region. Hence, cholinesterase activities in blood samples of agricultural workers exposed to vegetables and grape cultivation with age matched, unexposed workers, who never had any exposure to pesticides, were estimated. Methods: The detailed occupational history and lifestyle characters were obtained by questionnaire. Cholinesterase activity was determined by the method of Ellman as modified by Chambers and Chambers. Results: AChE was ranging from 1.65 to 3.54μmoles/min/ml in exposed subjects where as it was ranged from 2.22 to 3.51μmoles/min/ml in control subjects. BChE activity was ranging from 0.16 to 5.2μmoles/min/ml among exposed subjects, where as it was ranged from 2.19 to 5.06μmoles/min/ml in control subjects. The results showed statistically significant reduction in enzyme activities (AChE 14%; BChE 56% among exposed subjects. Conclusion: It was concluded that the reduction in cholinesterase activity may lead to varieties of effects. Hence it is compulsory to use protective gadgets during pesticide spray. Further a continuous biomonitoring study is recommended to assess pesticide exposure.

  19. Evidence for the activation of organophosphate pesticides by cytochromes P450 3A4 and 2D6 in human liver microsomes. (United States)

    Sams, C; Mason, H J; Rawbone, R


    The role of specific cytochrome P450 isoforms in catalysing the oxidative biotransformation of the organophosphorothioate pesticides parathion, chlorpyrifos and diazinon into structures that inhibit cholinesterase has been investigated in human liver microsomes using chemical inhibitors. Pesticides were incubated with human liver microsomes and production of the anticholinergic oxon metabolite was investigated by the inhibition of human serum cholinesterase. Quinidine and ketoconazole at 10 micromol/l inhibited oxidative biotransformation. Compared to control incubations (no inhibitor) where cholinesterase activity was inhibited to between 1 and 4% of control levels, incorporation of the CYP2D6 inhibitor quinidine into the microsomal incubation resulted in cholinesterase activity of 50% for parathion, 38% for diazinon and 30% for chlorpyrifos. Addition of the CYP3A4 inhibitor ketoconazole to microsomal incubations resulted in 66% cholinesterase activity with diazinon, 20% with parathion and 5% with chlorpyrifos. The unexpected finding that CYP2D6, as well as CYP3A4, catalysed oxidative biotransformation was confirmed for chlorpyrifos and parathion using microsomes prepared from a human lymphoblastoid cell line expressing CYP2D6. While parathion has been investigated only as a model compound, chlorpyrifos and diazinon are both very important, widely used pesticides and CYP2D6 appears to be an important enzyme in their bioactivation pathway. CYP2D6 is polymorphic and hence may influence individual susceptibility to exposure to chlorpyrifos and diazinon as well as other structurally similar pesticides.


    Directory of Open Access Journals (Sweden)

    Dewi Susanna


    Full Text Available Organophosphate Pesticide Exposure Effects toward Inhibition of Blood Cholinesterase Activity among Vegetable Farmers. Organophosphate pesticides can inhibit blood cholinesterase in human body. This study aimed to find relationship between length of exposure of organophosphate pesticides with cholinesterase enzyme activity in the farmers’ blood. The study was conducted at the Joint Farmers Group in Kelurahan Campang year 2009 using cross-sectional study design and sampling by the simple random sampling method (56 respondents. Data collection was carried out by interview and blood cholinesterase was measured using the Livibond Cholinesterase Test Kit AF267. Results showed that 100% farmers were poisoned, with 71.4% suffer from light-over-exposure and 28.6% moderate-over exposure. Bivariate test analysis using chi-square test showed that there are no statistically significant relationship between the length of exposure (year of working as pesticide farmer, spraying time per week, and the last time spraying with poisoning level (over-exposure probable and serious-over exposure. It takes the role of government to educate and trained farmers how to use pesticide safely and the importance of personal protective equipment to reduce the poisoning level.

  1. Acute behavioral toxicity of carbaryl and propoxur in adult rats. (United States)

    Ruppert, P H; Cook, L L; Dean, K F; Reiter, L W


    Motor activity and neuromotor function were examined in adult CD rats exposed to either carbaryl or propoxur, and behavioral effects were compared with the time course of cholinesterase inhibition. Rats received an IP injection of either 0, 2, 4, 6 or 8 mg/kg propoxur or 0, 4, 8, 16 or 28 mg/kg carbaryl in corn oil 20 min before testing. All doses of propoxur reduced 2 hr activity in a figure-eight maze, and crossovers and rears in an open field. For carbaryl, dosages of 8, 16 and 28 mg/kg decreased maze activity whereas 16 and 28 mg/kg reduced open field activity. In order to determine the time course of effects, rats received a single IP injection of either corn oil, 2 mg/kg propoxur or 16 mg/kg carbaryl, and were tested for 5 min in a figure-eight maze either 15, 30, 60, 120 or 240 min post-injection. Immediately after testing, animals were sacrificed and total cholinesterase was measured. Maximum effects of propoxur and carbaryl on blood and brain cholinesterase and motor activity were seen within 15 min. Maze activity had returned to control levels within 30 and 60 min whereas cholinesterase levels remained depressed for 120 and 240 min for propoxur and carbaryl, respectively. These results indicate that both carbamates decrease motor activity, but behavioral recovery occurs prior to that of cholinesterase following acute exposure.

  2. The exploration of mechanism of cactus rescue organophosphorus pesticides poisoning rabbits%仙人掌解救有机磷农药中毒家兔机制探究

    Institute of Scientific and Technical Information of China (English)

    杨佳颜; 罗丽霞; 熊伟; 刘帆; 曹弟勇


      目的探讨仙人掌联合用药在有机磷中毒过程中对胆碱酯酶活性的影响。方法对家兔进行肝素化后,测其胆碱酯酶活性,进行有机磷农药灌胃,使胆碱酯酶活性为正常的50%以下,用仙人掌及其联合用药的方法解救,再测量胆碱酯酶活性。结果仙人掌单独使用可使有机磷农药中毒的家兔胆碱酯酶活性恢复,作用接近于解磷定,但恢复速度慢。%  objective to explore the Cactus combined with medicine in organic phosphorus poisonning effects on cholinesterase activity in the process. Methods: after heparin rabbit, measuring cholinesterase activity, intragastric infusion with organic phosphorus pesticide, when cholinesterase activity below normal 50%, Rescue with cactus and their combination , and then measuring cholinesterase activity.Results: Cactus is used alone can make the cholinesterase activity of rabbit with organic phosphorus pesticide poisoning's recovery, role closer to pralidoxime, but slowly.

  3. Effect of methyl parathion on the muscle and brain acetylcholinesterase activity of matrinxã (Brycon cephalus

    Directory of Open Access Journals (Sweden)

    Almeida Luciana Cristina de


    Full Text Available Farming of the freshwater fish is emerging in Brazil and many species from the wild are promising. The teleost matrinxã (Brycon cephalus holds several characteristics such as fast growth rate, high commercial value and adaptability to artificial raring conditions, which make it a promising species for commerce. The use of pesticides in aquatic environment is frequent in Brazil, and methyl parathion is very common in aquaculture. We have determined the enzymatic activity of acetyl cholinesterase in white muscle and brain of matrinxã exposed to 2ppm of environmental methyl parathion for 24 hours. There was 64% and 69% of acetyl cholinesterase inhibition in muscle and brain respectively. These activities were not recovered after 8 days from exposure to this pesticide. It can be concluded that acetyl cholinesterase from those tissues was inhibited by small amounts of methyl parathion, and the main effect was observed in the brain.

  4. Rivastigmine in the treatment of hypersexuality in Alzheimer disease. (United States)

    Canevelli, Marco; Talarico, Giuseppina; Tosto, Giuseppe; Troili, Fernanda; Lenzi, Gian Luigi; Bruno, Giuseppe


    Inappropriate sexual behaviors (ISB) represent uncommon and often misdiagnosed clinical disorders among patients with Alzheimer disease. So far, no randomized clinical trials regarding the treatment of ISB in demented people have been conducted, but available data from case series and isolated case reports suggest the efficacy of selective serotonin reuptake inhibitors (SSRIs), antipsychotics, antiandrogens, and H2-receptor antagonists. Controversial data exist on the therapeutic influence of cholinesterase inhibitors on sexual disorders. In the present article, we describe the case of an Alzheimer disease patient presenting hypersexuality, successfully treated with rivastigmine. Thus, we perform a revision of the existing literature regarding the therapeutical effect of cholinesterase inhibitors in the treatment of ISB.

  5. Design, Synthesis and Evaluation of Novel Tacrine-Ferulic Acid Hybrids as Multifunctional Drug Candidates against Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Yingbo Fu


    Full Text Available Five novel tacrine-ferulic acid hybrid compounds (8a–e were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE and butyryl cholinesterase (BuChE, reducing self-induced β-amyloid (Aβ aggregation and chelating Cu2+ were evaluated in vitro. Among them, 8c and 8d displayed the higher selectivity in inhibiting AChE over BuChE. Moreover, 8d also showed dramatic inhibition of self-Aβ aggregation, activity of chelating Cu2+ and activity against Aβ-induced neurotoxicity in Neuro-2A cells.

  6. Interaction of nerve agent antidotes with cholinergic systems. (United States)

    Soukup, O; Tobin, G; Kumar, U K; Binder, J; Proska, J; Jun, D; Fusek, J; Kuca, K


    The poisoning with organophosphorus compounds represents a life threatening danger especially in the time of terroristic menace. No universal antidote has been developed yet and other therapeutic approaches not related to reactivation of acetylcholinesterase are being investigated. This review describes the main features of the cholinergic system, cholinergic receptors, cholinesterases and their inhibitors. It also focuses on the organophosphorus nerve agents, their properties, effects and a large part describes various possibilities in treatments, mainly traditional oxime therapies based on reactivation of AChE. Furthermore, non-cholinesterase coupled antidotal effects of the oximes are thoroughly discussed. These antidotal effects principally include oxime interactions with muscarinic and nicotinic receptors.

  7. [Effects of repeated sevoflurane anesthesia on hepatic and renal function in a pediatric patient]. (United States)

    Tanikawa, M; Mitsuhata, H; Shimizu, R; Akazawa, S; Fukuda, H; Saitoh, K; Hirabayashi, Y; Togashi, H


    A 10-yr-old boy with an injured lower extremity received sevoflurane anesthesia 5 times within 40 days. Laboratory tests for hepatic and renal function i.e., serum transaminase (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyl transpeptidase), serum cholinesterase, plasma protein, serum cholinesterase, serum bilirubine, serum lactic dehydrogenase, serum prothrombin time, blood urea nitrogen, serum creatinine, beta 2-microglobulin, N-acetyl-D-glucosamidase and 24 hr-creatinine clearance remained within normal ranges throughout his perioperative period. Repeated sevoflurane anesthesia did not exert any adverse effect on hepatic and renal function in this patient.

  8. Diagnosis of Intoxication by the Organophosphate VX: Comparison Between an Electrochemical Sensor and Ellman´s Photometric Method


    Kamil Kuca; Martina Hrabinova; Miroslav Pohanka


    An electrochemical sensor is introduced as a tool applicable for diagnosis of intoxication by cholinesterase inhibitors caused by the well-known nerve agent VX. The traditional Ellman method was chosen for comparison with the sensor's analytical parameters. Both methods are based on estimation of blood cholinesterase inhibition as a marker of intoxication. While Ellman´s method provided a limit of detection of 5.2´10-7 M for blood containing VX, the electrochemical sensor was able to de...

  9. In Vivo Effects of Oxygen at Varying Pressures on Erythrocytes and Brain. (United States)


    during exposure to OHP. 3. Demonstration of in vivo inhibition of RBC cholinesterase by OHP and definition that it was due to peroxides. 4. First proof...hyperoxia. Aerospace Med. 45:1273-1275, 1974. 31. Hirszel, P., Maher , J. F., Tempel, G. E°., and Mengel , C. E.: Effect of hemodialysis on factors

  10. First in human study with a prodrug of galantamine : Improved benefit-risk ratio?

    NARCIS (Netherlands)

    Baakman, Anne C.; 't Hart, Ellen; Kay, Denis G.; Stevens, Jasper; Klaassen, Erica S.; Maelicke, Alfred; Groeneveld, Geert J.


    AbstractIntroduction Gln-1062 (Memogain) is a pharmacologically inactive prodrug of galantamine. Owing to its lipophilic nature, it preferentially enters the brain, where it is cleaved into active galantamine. Gln-1062 is expected to have fewer peripheral side effects than other cholinesterase inhib

  11. Spatial discrimination deficits by excitotoxic lesions in the MORRIS WATER ESCAPE TASK

    NARCIS (Netherlands)

    Spowart-Manning, L.; Staay, van der F.J.


    The effects of the cholinesterase inhibitors (ChEI) metrifonate and donepezil were assessed on spatial performance of rats with bilateral lesions of the entorhinal cortex (EC), which is thought to model early changes in the brains of patients suffering from Alzheimer's disease. In the present study,

  12. Treatment with rivastigmine or galantamine and risk of urinary incontinence : results from a Dutch database study

    NARCIS (Netherlands)

    Kroger, Edeltraut; Van Marum, Rob; Souverein, Patrick; Carmichael, Pierre Hugues; Egberts, Toine


    Treatment of Alzheimer disease (AD) with cholinesterase inhibitors (ChEIs) may increase the risk of urinary incontinence (UI). Objective: To assess whether ChEI use was associated with the risk of UI among older patients with AD. Methods: A crossover cohort study using the PHARMO Record Linkage Syst

  13. Persistent symptoms in agricultural workers exposed to organophosphate pesticides

    Directory of Open Access Journals (Sweden)

    Martha E. Palacios N


    Full Text Available Objective: to evaluate the prevalence of these symptoms and their relationship with pesticide exposure and the cholinesterase levels in agricultural workers. Methodology: an analytical cross-sectional study conducted in Mexico. Cholinesterase concentration and symptom frequency were assessed for 106 agricultural workers. Exposure was defined with a composed index of 15 variables. Results: symptom prevalence was 52 out of 100 workers. 31% of workers had 1 to 3 of the symptoms, 16% had 4 to 9 of them and 5% had 10 or more of the symptoms. There was an association, p = 0.03, between days of exposure and persistent symptoms. Likewise, there was an association between exposure level and the presence of probable and specific symptoms. Patients with the highest exposure level had 20% more chances of exhibiting symptoms. Cholinesterase concentration ranges were normal. Anemia was detected in 28% of the population. It was three times as frequent in females as in males (p < 0.001. Conclusions: it was possible to identify the increase of persistent symptoms in workers with cholinesterase levels that are usually considered to be normal.

  14. Effect of small concentrations of sulfur dioxide during chronic poisoning on the immunologic reactivity of rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Navrotzky, V.K.


    A concentration of 0.018 to 0.022 mg SO/sub 2//liter decreased agglutination titer of rabbit blood serum to immunization with typhoid vaccine 4 to 8 times and reduced duration of high titer 3 to 4 times. Titer of blood complement was not altered. SO/sub 2/ poisoning increases both blood acetylcholine and cholinesterase activity.

  15. Biodegradation and anticholinesrerase activity of methyl isocyanate in the aquatic environment of Bhopal

    Digital Repository Service at National Institute of Oceanography (India)

    SenGupta, R.; Sarkar, A.; Kureishy, T.W.

    of Bhopal, Puntius ticto was found to be the most susceptible to MIC-poisoning. There is a change in the values of pH, ammonia-nitrogen and urea-nitrogen concentrations in the Lower Lake water. The cholinesterase activities of different tissues of various...

  16. Effect of Malathion on the Microbial Ecology of Activated Sludge (United States)


    the 1800s with French organic chemist P. Clermont synthesizing the first cholinesterase inhibitor, TEPP. In 1932, a German chemist first described...nitrogen compounds for energy consumption. These can be further subdivided into ammonia oxidizers and nitrite oxidizers. Ammonia oxidizers, including...class). Nitrospira (Nitrospira phylum) is also a nitrite oxidizer. The ammonia oxidizers are lithotrophic bacteria that oxidize ammonia into nitrite


    Enzymatic test kits, generally designed to be handheld and portable, detect the presence of chemical agents, carbamate pesticides, and/or organophosphate pesticides by relying on the reaction of the cholinesterase enzyme. Under normal conditions, the enzyme reacts as expected wi...

  18. Variation of Musca domestica L. acetylcholinesterase in Danish housefly populations

    DEFF Research Database (Denmark)

    Kristensen, Michael; Huang, Jing; Qiao, Chuan-Ling;


    Anti-cholinesterase resistance is in many cases caused by modified acetylcholinesterase (MACE). A comparison was made of toxicological data and AChE activity gathered from 21 field populations and nine laboratory strains of houseflies, Musca domestica L., to elucidate the best way of generating d...

  19. Development and Application of a Method for Toxicological Assessment of Occupational Exposures to Chemicals in Marine Operations. Addendum. (United States)


    protects against hepat- ic necrosis induced by carbon tetrachloride and against acute necrosis of the biliary epithelium following administration of a...retention of bile salts and bilirubin. The jaundice, resulting from retention of bilirubin, resembles that produced by extrahepatic biliary obstruction... ileus bromide Cholinesterase Transient muscle weakness inhibitors N- (pesticides) Magnesium sulfate Central depression and neuromuscular block Quinine

  20. Does Early-Life Exposure to Organophosphate Insecticides Lead to Prediabetes and Obesity?


    Slotkin, Theodore A.


    Human exposures to organophosphate insecticides are ubiquitous. Although regarded as neurotoxicants, increasing evidence points toward lasting metabolic disruption from early-life organophosphate exposures. We gave neonatal rats chlorpyrifos, diazinon or parathion in doses devoid of any acute signs of toxicity, straddling the threshold for barely-detectable cholinesterase inhibition. Organophosphate exposure during a critical developmental window altered the trajectory of hepatic adenylyl cyc...

  1. Perspectives on the Use of Scopolamine as an Adjunct Treatment to Enhance Survival Following Organophosphorus Nerve Agent Poisoning (United States)


    cholinesterase activity by a,cû-bis-(4-hydroxyiminomethylpyridinium) alkanes in vitro. J Appl Biomed 2003; 1: 207-11. 32. Bartling A, Worek F, Szinicz L...inhibited guinea pig and human acetylcholinesterases by oximes. Biochemistry 2007; 46: 11771-9. 882 MILITARY MEDICINE, Vol. 175, November 2010 Copyright

  2. A Pharmacokinetic Study of the Effects of Stress and Exercise on Chemical Exposure (United States)


    Functions,” Fundamental and Applied Toxicology, 16: 288-298 (1991). Abou-Donia, Mohamed B., Kenneth R. Wilmarth, Ali A. Abdel-Rahman, Karl F. Jensen...Marcello. “Cholinesterase Inhibition: Complexities in Interpretation,” Clinical Chemistry, 41: 1814-1818 (1995). Loewenstein -Lichtenstein, Yael

  3. Errorless practice as a possible adjuvant to donepezil in Alzheimer's disease. (United States)

    Rothi, Leslie J Gonzalez; Fuller, Renee; Leon, Susan A; Kendall, Diane; Moore, Anna; Wu, Samuel S; Crosson, Bruce; Heilman, Kenneth M; Nadeau, Stephen E


    Six individuals with probable Alzheimer's disease (AD) participated in a phase 1 study employing a repeated measures, parallel baseline design testing the hypothesis that error-free experience during word production practice combined with an acetyl cholinesterase inhibitor would improve confrontation naming ability. While acetyl cholinesterase inhibitors are safe and delay cognition decline associated with AD, improvement over baseline cognition is less evident; clinically significant cognitive deficits persist and progress. Both animal and clinical research strongly implicate acetylcholine in learning, a form of neuroplasticity. In clinical practice, however, people with AD are given cholinergic medications without concomitant systematic/targeted retraining. In this study six participants with probable AD and taking donepezil participated in targeted word production practice using an errorless learning strategy. Results showed that combining behavioral enrichment training and an acetyl cholinesterase inhibitor resulted in significant improvements in verbal confrontation naming of trained items for three of six participants. Differences in baseline dementia severity, living conditions, and medications may have influenced the training response. Detection of substantial treatment effects in 50% of subjects suggests further language treatment studies in AD in combination with an acetyl cholinesterase inhibitor are warranted and provide useful information on inclusion/exclusion criteria for use in subsequent studies.

  4. Development of a Model for Nerve Agent Inhalation in Conscious Rats (United States)


    Toxicol Mech Meth 14:183–94. Bajgar J. (2004). Organophosphates /nerve agent poisoning : mechanism of action, diagnosis, prophylaxis, and treatment. Adv...See reprint. 15. SUBJECT TERMS Chemical warfare, cholinesterases, inhalation exposure, nerve agents, organophosphates , vapor 16. SECURITY...exposure system for assessing respiratory toxicity of vaporized chemical agents in untreated, non-anesthetized rats. The organophosphate diisopropyl

  5. Recognition and Management of Pesticide Poisonings. Third Edition. (United States)

    Morgan, Donald P.

    This manual aids health professionals in recognizing and treating pesticide poisonings. Suggested treatments are appropriate for implementation in the small hospitals and clinics which usually receive the victims of pesticide poisoning. Classes of compounds covered include: (1) organophosphate cholinesterase-inhibiting pesticides; (2) carbamate…

  6. Anticholinesterases: Medical applications of neurochemical principles

    Energy Technology Data Exchange (ETDEWEB)

    Millard, C.B.; Broomfield, C.A.


    Cholinesterases form a family of serine esterases that arise in animals from at least two distinct genes. Multiple forms of these enzymes can be precisely localized and regulated by alternative mRNA splicing and by co- or posttranslational modifications. The high catalytic efficiency of the cholinesterases is quelled by certain very selective reversible and irreversible inhibitors. Owing largely to the important role of acetylcholine hydrolysis in neurotransmission, cholinesterase and its inhibitors have been studied extensively in vivo. In parallel, there has emerged an equally impressive enzyme chemistry literature. Cholinesterase inhibitors are used widely as pesticides; in this regard the compounds are beneficial with concomitant health risks. Poisoning by such compounds can result in an acute but usually manageable medical crisis and may damage the ONS and the PNS, as well as cardiac and skeletal muscle tissue. Some inhibitors have been useful for the treatment of glaucoma and myasthenia gravis, and others are in clinical trials as therapy for Alzheimer`s dementia. Concurrently, the most potent inhibitors have been developed as highly toxic chemical warfare agents. We review treatments and sequelae of exposure to selected anticholinesterases, especially organophosphorus compounds and carbamates, as they relate to recent progress in enzyme chemistry.

  7. The evaluation of the reactivating and therapeutic efficacy of two novel oximes (K361 and K378) in comparison with the oxime K203 and trimedoxime in tabun-poisoned rats and mice. (United States)

    Kassa, Jiri; Sepsova, Vendula; Tumova, Martina; Musilek, Kamil; Horova, Anna


    The potency of two newly developed oximes (K361 and K378) to reactivate tabun-inhibited cholinesterase and to reduce acute toxicity of tabun was compared with the oxime K203 and trimedoxime using in vivo methods. The study determining percentage of reactivation of tabun-inhibited diaphragm cholinesterase in poisoned rats showed that the reactivating efficacy of the oxime K378 is slightly lower than the reactivating potency of the oxime K203 and trimedoxime while the ability of the oxime K361 to reactivate tabun-inhibited cholinesterase is markedly lower compared with the oxime K203 and trimedoxime. In the brain, the potency of both newly developed oximes to reactivate tabun-inhibited cholinesterase was negligible. The therapeutic efficacy of both newly developed oximes roughly corresponds to their weak reactivating efficacy. Their potency to reduce acute toxicity of tabun was significantly lower compared with the oxime K203 as well as trimedoxime. In conclusion, the reactivating and therapeutic potency of both newly developed oximes does not prevail the effectiveness of the oxime K203 and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning.

  8. Improved Logistics for Chemical and Biologics Decontamination for Deployed Military (United States)


    electrophilic phosphate nerve agents and other cholinesterase inhibitors as well as mustards and related blister agents, chloroformates, phosgene, methyl...agents and decontamination processes in support of delisting waste streams at the uU.S. Army Dugway proving ground, Utah” (Environmental Assessment

  9. Effects of selected metal oxide nanoparticles on Artemia salina larvae: evaluation of mortality and behavioural and biochemical responses. (United States)

    Gambardella, Chiara; Mesarič, Tina; Milivojević, Tamara; Sepčić, Kristina; Gallus, Lorenzo; Carbone, Serena; Ferrando, Sara; Faimali, Marco


    The aim was to investigate the toxicity of selected metal oxide nanoparticles (MO-NPs) on the brine shrimp Artemia salina, by evaluating mortality and behavioural and biochemical responses. Larvae were exposed to tin(IV) oxide (stannic oxide (SnO2)), cerium(IV) oxide (CeO2) and iron(II, III) oxide (Fe3O4) NPs for 48 h in seawater, with MO-NP suspensions from 0.01 to 1.0 mg/mL. Mortality and behavioural responses (swimming speed alteration) and enzymatic activities of cholinesterase, glutathione-S-transferase and catalase were evaluated. Although the MO-NPs did not induce any mortality of the larvae, they caused changes in behavioural and biochemical responses. Swimming speed significantly decreased in larvae exposed to CeO2 NPs. Cholinesterase and glutathione-S-transferase activities were significantly inhibited in larvae exposed to SnO2 NPs, whereas cholinesterase activity significantly increased after CeO2 NP and Fe3O4 NP exposure. Catalase activity significantly increased in larvae exposed to Fe3O4 NPs. In conclusion, swimming alteration and cholinesterase activity represent valid endpoints for MO-NP exposure, while glutathione-S-transferase and catalase activities appear to be NP-specific.

  10. Evaluation of nootropic activity of Curcuma longa leaves in diazepam and scopolamine-induced amnesic mice and rats

    Directory of Open Access Journals (Sweden)

    Nayana Reddy


    Conclusion: This could be by inhibiting the levels of cholinesterase concentration of enzyme and thereby increasing the concentration of acetylcholine level in brain and improving cognition-memory performance. [Int J Basic Clin Pharmacol 2015; 4(4.000: 714-719


    Oxidative stress (OS) plays an important role in susceptibility and disease in old age. Understanding age-related susceptibility is crucial in assessing the human health risks of chemicals. Growing evidence implicates as in carbamate toxicity in addition to cholinesterase-inhibit...

  12. A new coumarin from Murraya paniculata. (United States)

    Choudhary, Muhammad Iqbal; Azizuddin; Khalid, Asaad; Sultani, Shaikh Ziauddin; Atta-ur-Rahman


    A new natural product, 2'-O-ethylmurrangatin (1) was isolated along with two previously known compounds murranganone (2) and paniculatin (3) from the leaves of Murraya paniculata. The structure of compound 1 was elucidated with the help of spectroscopic studies and by chemical reactions. Compounds 2 and 3 have been found to be cholinesterase inhibitors.

  13. Drug: D02173 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available NO3. HBr 367.0783 368.2655 D02173.gif Alzheimer's disease treatment [cholinesterase inhibitor] [DS:H00056] T...phospholipid metabolism hsa04725(43) Cholinergic synapse Genomic biomarker: CYP2D6 [HSA:1565] map07056 Agents for Alzheimer

  14. Structural study of the complex stereoselectivity of human butyrylcholinesterase for the neurotoxic V-agents

    NARCIS (Netherlands)

    Wandhammer, M.; Carletti, E.; Schans, M.J. van der; Gillon, E.; Nicolet, Y.; Masson, P.; Goeldner, M.; Noort, D.; Nachon, F.


    Nerve agents are chiral organophosphate compounds (OPs) that exert their acute toxicity by phosphorylating the catalytic serine of acetylcholinesterase (AChE). The inhibited cholinesterases can be reactivated using oximes, but a spontaneous time-dependent process called aging alters the adduct, lead

  15. Interactions of organophosphates with keratins in the cornified epithelium of human skin

    NARCIS (Netherlands)

    Verstappen, D.R.W.; Hulst, A.G.; Fidder, A.; Vermeulen, N.P.E.; Noort, D.


    Methods to unequivocally assess and quantify exposure to organophosphate anti-cholinesterase agents are highly valuable, either from a biomonitoring or a forensic perspective. Since for both OP pesticides and various nerve agents the skin is a predominant route of entry, we hypothesized that protein

  16. Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii (United States)

    Sparling, D.W.; Fellers, G.


    Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24 h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations. ?? 2006 Elsevier Ltd. All rights reserved.

  17. Beverages of lemon juice and exotic noni and papaya with potential for anticholinergic effects. (United States)

    Gironés-Vilaplana, Amadeo; Valentão, Patrícia; Andrade, Paula B; Ferreres, Federico; Moreno, Diego A; García-Viguera, Cristina


    Lemon (Citrus limon (L.) Burm. f.) juice beverages enriched either with noni (Morinda citrifolia L.) (LN) or papaya (Carica papaya L.) (LP), were characterized by HPLC-DAD-ESI/MS(n), the antioxidant capacity was evaluated by (DPPH·), superoxide (O2(·-)), hydroxyl radicals (·OH) and hypochlorous acid (HOCl) assays, and their potential as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors was also assessed. The fruits are rich in a wide range of bioactive phenolics. Regarding DPPH·, ·OH and HOCl assays, the LP displayed strong activity, and LN was the most active against O2(·-). Concerning cholinesterases, LP was the most active, mainly due to lemon juice contribution. The effect on the cholinesterases was not as strong as in previous reports on purified extracts, but the bioactive-rich beverages offer the possibility of dietary coadjutants for daily consumption of health-promoting substances by adults with aging-related cognitive or physical disorders.

  18. 7-Methoxytacrine-p-Anisidine Hybrids as Novel Dual Binding Site Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment

    Directory of Open Access Journals (Sweden)

    Jan Korabecny


    Full Text Available Alzheimer’s disease (AD is a debilitating progressive neurodegenerative disorder that ultimately leads to the patient’s death. Despite the fact that novel pharmacological approaches endeavoring to block the neurodegenerative process are still emerging, none of them have reached use in clinical practice yet. Thus, palliative treatment represented by acetylcholinesterase inhibitors (AChEIs and memantine are still the only therapeutics used. Following the multi-target directed ligands (MTDLs strategy, herein we describe the synthesis, biological evaluation and docking studies for novel 7-methoxytacrine-p-anisidine hybrids designed to purposely target both cholinesterases and the amyloid cascade. Indeed, the novel derivatives proved to be effective non-specific cholinesterase inhibitors showing non-competitive AChE inhibition patterns. This compounds’ behavior was confirmed in the subsequent molecular modeling studies.

  19. [Usefulness of branched-chain amino acid (BCAA)-enriched nutrient mixture for nutritional treatment undergoing endoscopic treatment for esophageal varices]. (United States)

    Shibata, Naozumi; Matsui, Hidetaka; Takeshita, Eiji; Yokota, Tomoyuki; Higaki, Naoyuki; Murakami, Hidehiro; Ikeda, Yoshiou; Minami, Hisaka; Matsuura, Bunzo; Onji, Morikazu


    We investigated the alteration of nutritional status in 144 patients who were treated for the first time with endoscopic sclerotherapy or endoscopic variceal ligation during their therapies. The serum levels of albumin, cholinesterase and total cholesterol were compared before and after treatment. The serum level of cholinesterase declined significantly. To investigate the impact of aging on the changes of nutritional status we divided all patients into two groups: (1) under 65 years, and (2) over 65 years. The decline of serum albumin of elderly patients (n=65) was significantly greater than that of younger patients (n=79). A branched-chain amino acid (BCAA)-enriched nutrient mixture for nutritional treatment significantly suppressed the decline of serum albumin in elderly patients. Nutritional treatment with a BCAA-enriched nutrient mixture should be considered during endoscopic therapy for esophageal varices, especially in elderly patients.

  20. Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii. (United States)

    Sparling, D W; Fellers, G


    Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations.

  1. Kindling: a pharmacological approach. (United States)

    Wasterlain, C G; Morin, A M; Jonec, V


    Injection of a few nanomoles of the muscarinic agonists carbamylcholine, muscarine or (+)-acetyl-beta-methylcholine once a day into the rat amygdala was initially subconvulsive, but on repetition led to the progressive development of kindled epileptic seizures. This behaviour was stereospecific, was potentiated by the cholinesterase inhibitor physostigmine, and was blocked by the muscarinic antagonists atropine, QNB and scopolamine. The kindling potencies of cholinergic muscarinic agonists and antagonists paralleled their relative affinities for muscarinic receptors in vitro. No changes in muscarinic receptors, in cholinesterase or in choline acetyltransferase were observed in kindled brains after a stimulation-free period of at least 1 week. These data support the aggregate hypothesis of epileptogenesis and suggest that abnormal activity through a particular group of muscarinic synapses can be sufficient to generate an epileptic focus.

  2. Acupuncture on Gnosia and Acetylcholinesterase in Senile Dementia Patients

    Institute of Scientific and Technical Information of China (English)

    TANG Yong; YU Shu-guang; CHEN Jin; ZHANG Wei


    Purpose To observe the effect of acupuncture on gnosia and acetylcholinesterase in patients with senile dementia. Methods Eight patients diagnosed with mild or moderate senile dementia were treated by acupuncture of Sishencong ( Ex-HN 1 ), Shenmen ( HT 7) and Taixi ( KI 3) for I month; gnosia was evaluated by Mini-mental state examination before and after the treatment; plasma acetylcholin esterase activity was measured by flourier before and after the treatment. Results There was a significant difference in gnosia between pre- and post--treatment with acupuncture (P<0.01); there was no significant difference in acetyl- cholinesterase activity between pre- and posttreatment ( P>0.05 ). Conclusion Acupuncture has a certain improving effect on gnosia in senile dementia;one month's acupuncture treatment had little effect on plasma acetyl-cholinesterase activity.

  3. Chronic effect of waterborne colloidal silver nanoparticles on plasma biochemistry and hematology of rainbow trout (Oncorhynchus mykiss

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    Seyed Ali Johari


    Full Text Available Objective: To investigate the possible effects of silver nanoparticles (AgNPs on some blood and plasma indices of rainbow trout (Oncorhynchus mykiss. Methods: Hence, fish were exposed for 21 days to sub-lethal concentrations of colloidal AgNPs and blood parameters including erythrocyte size and hematocrit, plasma parameters including cholinesterase, cortisol, sodium, chloride, and potassium, and also silver concentration in plasma were measured following the 11th and 21st days of exposure. Results: According to the results of present study, higher concentrations of AgNPs had more significant effects on plasma biochemistry and hematology of trout. The greatest impacts were decline of chloride ions and increase of cortisol and cholinesterase. Also fish exposed to AgNPs significantly increased silver concentration in the plasma. Conclusions: Further studies are needed to identify appropriate blood biomarkers following fish exposed to nanomaterials, especially AgNPs.

  4. Chronic effect of waterborne colloidal silver nanoparticles on plasma biochemistry and hematology of rainbow trout (Oncorhynchus mykiss)

    Institute of Scientific and Technical Information of China (English)

    Seyed Ali Johari; Mohammad Reza Kalbassi


    Objective: To investigate the possible effects of silver nanoparticles (AgNPs) on some blood and plasma indices of rainbow trout (Oncorhynchus mykiss). Methods: Hence, fish were exposed for 21 days to sub-lethal concentrations of colloidal AgNPs and blood parameters including erythrocyte size and hematocrit, plasma parameters including cholinesterase, cortisol, sodium, chloride, and potassium, and also silver concentration in plasma were measured following the 11th and 21st days of exposure. Results:According to the results of present study, higher concentrations of AgNPs had more significant effects on plasma biochemistry and hematology of trout. The greatest impacts were decline of chloride ions and increase of cortisol and cholinesterase. Also fish exposed to AgNPs significantly increased silver concentration in the plasma. Conclusions:Further studies are needed to identify appropriate blood biomarkers following fish exposed to nanomaterials, especially AgNPs.

  5. Anticholinesterase activity of fluorochloronitroacetic acid esters

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, Yu.Ya.; Brel, V.K. Martynov, I.V.


    Results are presented from pharmacologic and biochemical experiments leading to the conclusion that fluorochloronitroacetic acid esters have anticholinesterase activity. Since the esters caused muscular weakness in mice, experiments were performed on isolated tissue preparation. The biochemical experiments consisted of finding the biomolecular constants of irreversible inhibition of acetylcholinesterase by the esters, using acetylcholinesterase from human erythrocytes, as well as horse serum cholinesterase. The ethyl and n-propyl esters of halogen nitroacetic acid were used in all experiments. It was found that the propyl ester caused an increase in the force of individual contractions in the isolated muscle specimens, plus an inability of the muscle to retain tetanus. The substances were determined to have an anticholinesterase effect. The mechanism of cholinesterase inhibition is not yet known. It is probable that the substances acylate the serine hydroxyl of the esterase center of the cholinestersase. 7 references, 1 figure.

  6. Tissue distribution of human acetylcholinesterase and butyrylcholinesterase messenger RNA

    Energy Technology Data Exchange (ETDEWEB)

    Jbilo, O.; Barteles, C.F.; Chatonnet, A.; Toutant, J.P.; Lockridge, O.


    Tissue distribution of human acetyicholinesterase and butyryicholinesterase messenger RNA. 1 Cholinesterase inhibitors occur naturally in the calabar bean (eserine), green potatoes (solanine), insect-resistant crab apples, the coca plant (cocaine) and snake venom (fasciculin). There are also synthetic cholinesterase inhibitors, for example man-made insecticides. These inhibitors inactivate acetyicholinesterase and butyrylcholinesterase as well as other targets. From a study of the tissue distribution of acetylcholinesterase and butyrylcholinesterase mRNA by Northern blot analysis, we have found the highest levels of butyrylcholinesterase mRNA in the liver and lungs, tissues known as the principal detoxication sites of the human body. These results indicate that butyrylcholinesterase may be a first line of defense against poisons that are eaten or inhaled.

  7. Diagnosis of Intoxication by the Organophosphate VX: Comparison Between an Electrochemical Sensor and Ellman´s Photometric Method

    Directory of Open Access Journals (Sweden)

    Kamil Kuca


    Full Text Available An electrochemical sensor is introduced as a tool applicable for diagnosis of intoxication by cholinesterase inhibitors caused by the well-known nerve agent VX. The traditional Ellman method was chosen for comparison with the sensor's analytical parameters. Both methods are based on estimation of blood cholinesterase inhibition as a marker of intoxication. While Ellman´s method provided a limit of detection of 5.2´10-7 M for blood containing VX, the electrochemical sensor was able to detect 4.0´10-7 M. Good correlation between both methods was observed (R = 0.92. The electrochemical sensor could be considered a convenient tool for a fast yet accurate method, easily available for field as well as laboratory use. Time and cost savings are key features of the sensor-based assay.

  8. Toxic Chemicals in the Soil Environment. Volume 2. Interactions of Some Toxic Chemicals/Chemical Warfare Agents and Soils (United States)


    cholinesterase inhibitors . At least one, armin (O-ethyl’,ethyl 0,p-nit rophenyl phosphonate), is among the moot .powerful known choliniesterase inhibitor ...and is equivalent to the nerve 4 agents (Feat and Schmidt, 1973). All have been used as growth Inhibitors or terminators for some organisms...there was inhibition of the urease and oxidase enzymes. 2.2.4 Effects of Ozone and Sunlight on Orgenophoapborua Pesticides Spencer et al. (1980

  9. Research progress of donepezil for treating mild to moderate Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Xin-xin LI


    Full Text Available Donepezil is the second generation of cholinesterase inhibitors (ChEIs, which has a good effect on mild to moderate Alzheimer's disease (AD. In recent years, there were a lot of studies on the mechanism of donepezil. This paper mainly introduces the diagnosis and treatment situation of AD in China, and the action mechanism of donepezil in the treatment of mild to moderate AD. DOI: 10.3969/j.issn.1672-6731.2017.02.012

  10. Odmerjanje zdravil za zdravljenje Alzheimerjeve in Parkinsonove bolezni: Dosage regimens of drugs used in the treatment of Alzheimer's and Parkinson's disease:


    Locatelli,Igor; MRHAR, ALEŠ


    Pharmacotherapy of Alzheimer's (AD) and Parkinson's disease (PD) is stillinergic drugs that can provide continuous dopaminergic stimulation symptomatic. In the initiation phase of the pharmacotherapy the dose of the majority of these drugs is kept low and it should be gradually increased until the optimal clinical effect is reached. Cholinesterase inhibitors such asdonepezil, galantamine, and rivastigmine represent the first class of drugs approved for the treatment of mild to moderate AD, wh...

  11. Raptor toxicology. (United States)

    Redig, Patrick T; Arent, Lori R


    Birds of prey have demonstrated the negative impact that toxic agents can cause on animal populations and ecosystem dynamics. Lead, cholinesterase inhibitors (eg, organophosphates, carbamates), and anticoagulant rodenticides (eg, brodifacoum) are the most common toxic agents that currently affect the health of wild birds of prey in the United States. For raptors held in captivity, the list of toxic agents expands and includes toxic inhalants such as carbon monoxide and polytetrafluoroethylene. This article provides diagnostic and treatment guidelines for the toxic agents discussed.

  12. On the Reducible Character of Haldane-Radić Enzyme Kinetics to Conventional and Logistic Michaelis-Menten Models

    Directory of Open Access Journals (Sweden)

    Mihai V. Putz


    Full Text Available The conceptual and practical issues regarding the reduction of the Haldane-Radić enzymic mechanism, specific for cholinesterase kinetics, to the consecrated or logistically modified Michaelis-Menten kinetics, specific for some mutant enzymes, are here clarified as due to the limited initial substrate concentration, through detailed initial rate and progress curve analysis, even when other classical conditions for such equivalence are not entirely fulfilled.

  13. On the reducible character of Haldane-Radić enzyme kinetics to conventional and logistic Michaelis-Menten models. (United States)

    Putz, Mihai V


    The conceptual and practical issues regarding the reduction of the Haldane-Radić enzymic mechanism, specific for cholinesterase kinetics, to the consecrated or logistically modified Michaelis-Menten kinetics, specific for some mutant enzymes, are here clarified as due to the limited initial substrate concentration, through detailed initial rate and progress curve analysis, even when other classical conditions for such equivalence are not entirely fulfilled.

  14. 全科医生处方集

    Institute of Scientific and Technical Information of China (English)



    阿尔茨海默病一胆碱酯酶抑制剂Alzheimer’s Disease-Cholinesterase Inhibitors注意:避免合并应用抗胆碱能药物。哮喘/COPD患者慎用。胆碱酯酶抑制剂与美金刚合用尚未发现不良药物相互作用。

  15. Defence Reporter. Winter 2012 (United States)


    and GD-induced neuromuscular blockade produced by dichloride and dimethane sulphonate salts of HI-6 and P2S in guinea pig diaphragm preparations...inhibited neuromuscular function in guinea pig diaphragm preparations. Experiments were designed to measure recovery due to cholinesterase reactivation in...encouragement to engage in exercise, dietary provision and nutritional education and provision of services and facilities to lead a healthy lifestyle

  16. Cholinergic enhancement augments magnitude and specificity of visual perceptual learning in healthy humans


    Rokem, Ariel; Michael A Silver


    Learning through experience underlies the ability to adapt to novel tasks and unfamiliar environments. However, learning must be regulated so that relevant aspects of the environment are selectively encoded. Acetylcholine (ACh) has been suggested to regulate learning by enhancing the responses of sensory cortical neurons to behaviorally-relevant stimuli [1]. In this study, we increased synaptic levels of ACh in the brains of healthy human subjects with the cholinesterase inhibitor donepezil (...

  17. [Two treated cases of botulism]. (United States)

    Işik, N; Elibol, B; Oztekin, N S; Zileli, T


    Botulism is a severe neuroparalytic disease caused by the neurotoxins of Clostridium botulinum which exert their effects on peripheral nerve junctions. Guillain-Barre syndrome, Myasthenia Gravis, acute Poliomyelitis and diphtheria must be considered in the differential diagnosis. In this study we have discussed two patients who were treated in our clinic, the differential diagnosis and the role of anti-Cholinesterase drugs in the treatment.

  18. Toxicological Properties of the Organophosphorus Insecticide Dimethoate (United States)

    Sanderson, D. M.; Edson, E. F.


    The results are presented of extensive toxicological studies on the systemic organophosphate insecticide dimethoate, and compared with published results from other laboratories. It behaves as a typical indirect anticholinesterase, by conversion in the liver to at least four short-lived active metabolites, whose hydrolysis products are rapidly excreted, mainly in the urine. The acute oral toxicity of dimethoate is low in mammals but higher in avians. Dermal absorption is notably slow and dermal toxicity correspondingly low. Cumulative dosing of rats and guinea-pigs gave no cholinesterase inhibition at 0·7 and 4 mg./kg./day respectively. Dietary feeding to growing rats caused no cholinesterase inhibition at 0·5 mg./kg./day and no other effect at 10 times this dose. The main plant metabolite is identical with one formed in the liver, and comparative feeding tests with normal dimethoate and that partly metabolized in vegetation showed that residue analysis determined total hazard. Tests on humans, some with 32P-labelled material, confirmed that metabolism and urinary excretion are very rapid, that skin absorption is very slow, and that at least 2·5 mg., and probably up to 18 mg., could be ingested daily for at least three weeks without cholinesterase inhibition or other effects. Vapour hazards proved negligible. Oral toxicity was not potentiated by any of 17 other insecticides. The earliest detectable effect of dimethoate poisoning was always erythrocyte cholinesterase inhibition. Symptoms of poisoning could be effectively treated by atropine but not by oxime therapy. No known cases of occupational poisoning have occurred during five years' commercial usage of dimethoate. PMID:14106136

  19. Methomyl-Induced Severe Acute Pancreatitis: Possible Etiological Association


    Ioannides M; Christodoulides P; Symeonides M; Vounou E; Tsikkos S; Achillews G; Koukouvas M; Makrides C


    CONTEXT: N-methyl carbamate insecticides are widely used in homes, gardens and agriculture. They share the capacity to inhibit cholinesterase enzymes with organophosphates and therefore share similar symptomatology during acute and chronic exposures. One of the serious effects of organophosphate and carbamate intoxication is the development of acute pancreatitis and subsequent intrapancreatic fluid formation. CASE REPORT: An 18-year old Caucasian man was admitted to our Intensive Care Unit wi...

  20. Donepezil in the treatment of musical hallucinations. (United States)

    Ukai, Satoshi; Yamamoto, Masakiyo; Tanaka, Michio; Shinosaki, Kazuhiro; Takeda, Masatoshi


    Musical hallucinations (MH) typically occur among elderly individuals and are associated with hearing impairment. The authors describe a patient with features of typical MH who was successfully treated with donepezil, a cholinesterase inhibitor, as a combination therapy and who has not shown any subsequent cognitive decline for approximately 5 years. The efficacy of donepezil in this patient indicates that age-dependent dysfunction of cholinergic neurons might be related to the development of MH.

  1. A study of serum psedocholinesterase levels following diazinon poisoning in relation to liver function-prognostic and therapeutic value


    K. Swarnalatha; B. Surya Prakasa Rao; S. Sharon Sonia


    Background: To study serum pseudo-cholinesterase (PChE) levels as an index of liver injury in individuals with diazinon poisoning with or without alcoholism. It gives the knowledge of the therapeutic efficacy and severity of liver dysfunction. Methods: Blood samples were taken from normal male adults as control and PChE is estimated. Blood samples were taken from diazinon poisoning patients from local hospitals on the 1st day and on 5th day for pseudocholinesterase estimation. Another grou...

  2. Effect of pretreatment with hepatic microsomal enzyme inducers on the toxicity of diazinon in calves. (United States)

    Abdelsalam, E B; Ford, E J


    The pretreatment of calves with a single dose of 10 mg kg-1 dieldrin or 21 daily doses of 10 mg kg-1 phenobarbitone increased the toxicity of diazinon as reflected by the development of more severe clinical signs and greater depression in whole blood cholinesterase activity in the pretreated calves. Induction by dieldrin or phenobarbitone of the hepatic microsomal enzyme amidopyrine-N-demethylase was also accompanied by a concurrent rise in the liver carboxylesterase activity.

  3. Alzheimer’s Dementia: Current Data Review


    Uzun, Suzana; Kozumplik, Oliver; Folnegović-Šmalc, Vera


    The review focuses on current data on Alzhemier’s dementia, a clinical syndrom characterised with acquired deterioration of cognitive functioning and emotional capacities, which impaires everyday activity and quality of life. Alzheimer’s dementia is the most common type of dementia in clinical surveys. The diagnosis of Alzheimer’s dementia is primarily based on symptoms and signs and memory impairment is clinically most signifficant. Cholinesterase inhibitors – donepezil, rivastig...

  4. Evaluation of the antiamnesic effects of Phyllanthus amarus in mice.



    Alzheimer’s disease is a progressive neurodegenerative disorder characterized by a gradual decline in memory. Phyllanhus amarus is commonly known as bhumi amla in India and is traditionally used since centuries in ayurveda medicine. The present study was undertaken to investigate the effects of Phyllanhus amarus (PA) on cognitive functions and brain cholinesterase activity in mice. Elevated plus maze and passive avoidance paradigm were employed to evaluate learning and memory parameters. Thre...

  5. Detecting Industrial Chemicals in Water With Microbial Fuel Cells and Artificial Neural Networks (United States)


    Transfer FM First Moment mA milli-Ampere MFC Microbial Fuel Cell NADH Nicotinamide adenine dinucleotide PA Peak Area PH...transfer of electrons across the inner membrane. Nicotinamide adenine dinucleotide (NADH) derived from the oxidation of organic matter is taken up by...filters (Mahle et al., 2003). It is a weak cholinesterase inhibitor and is an irritant of the skin , eyes, mucous membranes and upper respiratory tract


    Directory of Open Access Journals (Sweden)

    Gopal Reddy


    Full Text Available Organophosphorus poisoning is the most common poisoning in India because of its easy availability. Anaesthesiologists may come across rarely to give anaesthesia for emergency life - saving surgeries. Problems while anaesthetising an emergency patient following organophosphorous poisoning are many. Necessary precautions are to be taken while anaesthetising the patient. During anaesthesia many drugs are used which are linked with acetylcholine, cholinesterase and other cardio - vascul ar effects.

  7. An Atypical Cutaneous Reaction to Rivastigmine Transdermal Patch

    Directory of Open Access Journals (Sweden)

    T. Grieco


    Full Text Available Rivastigmine is a cholinesterase inhibitor which improves cognitive function and is currently being used in patients with mild to moderate Parkinson's and Alzheimer's dementia. This drug can be given orally or topically, as transdermal patch. The latter form is currently used for most excellent compliance and few side effects. The most common cutaneous side effects are irritative dermatitis. We report the second case of active sensitization by the rivastigmine-patch in a patient suffering from Alzheimer's dementia.

  8. 転移性骨腫瘍で発症した細小肝細胞癌の1例



    A 68-year-old male was referred to our clinic because of pain of left tuber of ischium. Bone roentgenogram of pelvis showed destructive change of the left pubic bone. Laboratory data on admission showed positive anti-HCV antibody, elevation of protein induced by vitamin K antagonists-Ⅱ (PIVKA-Ⅱ), elevation of GOT and GPT, depression of cholinesterase, and hypergammaglobulinemia. Biopsy of the pubic bone suggested metastasis of hepatocellular carcinoma, whereas no masses were detected by compu...

  9. Polyketides from the plant endophytic fungus Cladosporium sp. IFB3lp-2. (United States)

    Wuringege; Guo, Zhi-Kai; Wei, Wei; Jiao, Rui-Hua; Yan, Tong; Zang, Le-Yun; Jiang, Rong; Tan, Ren-Xiang; Ge, Hui-Ming


    Chemical study of the ethyl acetate extract of the plant endophytic fungus Cladosporium sp. (strain no. IFB3lp-2) yielded three new polyketides (1-3), together with nine known compounds. All of the structures were elucidated on the basis of spectroscopic methods. The isolated compounds were screened for their cytotoxic, antiviral, and acetyl cholinesterase inhibitory activities. Regretfully, no compounds showed any significant activity in these assays.

  10. Pancreatic Pseudocyst after Acute Organophosphate Poisoning


    Kawabe, Ken; Ito, Tetsuhide; Arita, Yoshiyuki; Sadamoto, Yojiro; Harada, Naohiko; Yamaguchi, Koji; Tanaka, Masao; Nakano, Itsuro; Nawata, Hajime; Takayanagi, Ryoichi


    Acute organophosphate poisoning(OP) shows several severe clinical symptoms due to its strong blocking effect on cholinesterase. Acute pancreatitis is one of the complications associated with acute OP, but this association still may not be widely recognized. We report here the case of a 73-year-old man who had repeated abdominal pain during and after the treatment of acute OP. Hyperamylasemia and a 7-cm pseudocyst in the pancreatic tail were noted on investigations. We diagnosed pancreatic pse...

  11. Exploring the role of BCHE in the onset of Diabetes, Obesity and Neurological Disorders


    Rao, Allam Appa; Jyothsna, Gundlapally; Shalini, Pulipati; Kumar, Amit; Bhattacharya, Anupam; Kashyap, Amita


    Diabetes, Obesity and Neurological disturbances, most often show co-occurrence. There has been an extensive research in this domain, but the exact mechanism underlying the co-occurrence of the three conditions is still an enigma. The current paper is an approach to establish the role of Butyryl cholinesterase (BCHE) in Diabetes, Obesity and Neurological disorders by performing a comparative analysis with Neuroligin (NLGN2) a protein belonging to the same family. BCHE has its role in glucose r...

  12. Simulating Nutritional Awareness and Action in Military Populations (United States)


    OCCURRING TOXICANTS IN FOOD (Cont’d) FACTOR DISEASE POTENTIAL FOOD Chymotrypsin Growth retardation Cholinesterase Solanine Glycosides Cyanogens... toxic . A number of these natural chemicals are simply not perceived by the consumer. Examples of these are given in TABLE 1 where the composition of the...consequence in terms of lethality. We are also aware that certain foods may contain naturally occurring toxicants . These toxicants are more apt to be

  13. CG-MS/MS Analyses of Biological Samples in Support of Developmental Toxic Effects on Whole-Body Exposure of Rats to GB (United States)


    Organophosphorothioate Insecticides . Toxicology 1991, 68, 51–61. Rice, D.; Barone, S. Jr. Critical Periods of Vulnerability for the Developing Nervous System...J.A.; King, J.M. Age- related Differences in Soman Toxicity and in Blood and Brain Regional Cholinesterase Activity . Brain Res. Bull. 1990, 24...Organophosphates. Toxicol. Appl. Pharmacol. 2004, 198, 132–151. Sterri, S.H.; Berge, G.; Fonnum, F. Esterase Activities and Soman Toxicity in

  14. Investigation of the toxicity of some organophosphorus pesticides in a repeated dose study in rats. (United States)

    Baconi, Daniela Luiza; Bârcă, Maria; Manda, Gina; Ciobanu, Anne Marie; Bălălău, C


    The study aimed to the investigation of the toxicity of organophosphorus pesticides malathion (MLT) and diazinon (DZN) in Wistar rats in a repeated dose study for 35 days. MLT and DZN in corn oil vehicle were oral administered. Body and organs weights, plasma and brain cholinesterase activities, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, histopathological changes in liver and kidney, and some parameters of the immune function, such as leukocyte formula, spleen weight and cellularity, spleen lymphocytes proliferation in response to concanavalin A (Con A) were investigated; the potential oxidative stress (malondialdehyde in plasma and brain, and blood catalase activity) was also evaluated. No clinical toxicity signs attributed to pesticides were noted; no significant changes in the organ weights have been found. Body weight tends slightly to increase, predominantly in DZN treated rats. The results suggest that plasma cholinesterase is more susceptible than brain cholinesterase to the inhibitory effect of DZN and MLT. Other serum biochemical parameters showed no significant difference. DZN produced a marked increase of the number of spleen lymphocytes without a significant gain of the relative spleen weight. The both pesticides produced an increase of the number of mononuclear cells÷weight spleen. The splenic lymphocyte proliferation has not been influenced by MLT or DZN treatment. Histopathological observations identified some changes (vasodilatation, microvacuoles, and granular dystrophy) in the liver, with MLT, inducing macrovacuolar steatosis. The study indicates that repeated exposure, at subclinical doses, to organophosphorus MLT and DZN causes some biochemical, histopathological and immune alterations in rats.

  15. Preventive Role of Indian Black Pepper in Animal Models of Alzheimer’s Disease (United States)

    Suresh, RN; MK, Jayanthi; HL, Kalabharathi; AM, Satish; VH, Pushpa


    Introduction: Dementia is the clinical symptom of alzheimer’s disease. Brain cholinesterase levels and behavioural changes are the markers for Alzheimer’s disease and aluminium chloride is one causative agent for polymerization of tau protein and amyloid plaque formation in Alzheimer’s disease. Effect of piper nigrum and its role in prevention of alzhimer’s disease and symptoms are well linked in this study. Aim: To study the effect of piper nigrum for the prevention of alzheimer’s associated histopathological, biochemical and behaviour changes in rat model. Materials and Methods: Twenty four rats were taken in this study. Their baseline behavioural parameters were noted and group was separated randomly in four. Rats were pretreated with piper nigrum and Alzheimer’s disease was induced. Biochemical and histopathological changes were noted at the end of experiment. Results: There was marked decrease in cholinesterase level, amyloidal plaque formation in rats brain who were pretreated with piper nigrum. At the same time there was decrease in escape latency time (ELT) and increase in memory in piper treated rats. Conclusion: Piper nigrum prove to be effective for prevention of Alzheimer’s disease. This finding has to be confirmed with studies including larger population. Further research on cholinesterase inhibitors, role of flavonoids on prevention of neurodegeneration in Alzheimer’s disease can be encouraged. PMID:26023568

  16. [Cholinergic system of the heart]. (United States)

    Kučera, Matej; Hrabovská, Anna


    The cholinergic system of the heart can be either of neuronal or non-neuronal origin. The neuronal cholinergic system in the heart is represented by preganglionic parasympathetic pathways, intracardiac parasympathetic ganglia and postganglionic parasympathetic neurons projecting to the atria, SA node and AV node. The non-neuronal cholinergic system consists of cardiomyocytes that have complete equipment for synthesis and secretion of acetylcholine. Current knowledge suggests that the non-neuronal cholinergic system in the heart affects the regulation of the heart during sympathetic activation. The non-neuronal cholinergic system of the heart plays also a role in the energy metabolism of cardimyocites. Acetylcholine of both neuronal and non-neuronal origin acts in the heart through muscarinic and nicotinic receptors. The effect of acetylcholine in the heart is terminated by cholinesterases acetylcholinesterase and butyrylcholinesterase. Recently, papers suggest that the increased cholinergic tone in the heart by cholinesterase inhibitors has a positive effect on some cardiovascular disorders such as heart failure. For this reason, the cholinesterase inhibitors might be used in the treatment of certain cardiovascular disorders in the future.

  17. Skin decontamination of mustards and organophosphates: comparative efficiency of RSDL and Fuller's earth in domestic swine. (United States)

    Taysse, L; Daulon, S; Delamanche, S; Bellier, B; Breton, P


    Research in skin decontamination and therapy of chemical warfare agents has been a difficult problem due to the simultaneous requirement of rapid action and non-aggressive behaviour. The aim of this study was to compare the performance of two decontaminating systems: the Canadian Reactive Skin Decontaminant Lotion (RSDL) and the Fuller's Earth (FE). The experiment was conducted with domestic swine, as a good model for extrapolation to human skin. RSDL and FE were tested against sulphur mustard (SM), a powerful vesicant, and VX, a potent and persistent cholinesterase inhibitor. When used 5 min after contamination, the results clearly showed that both systems were active against SM (10.1 mg/cm(2)) and VX (0.06 mg/cm(2)). The potency of the RSDL/sponge was statistically better than FE against skin injury induced by SM, observed 3 days post-exposure. RSDL was rather more efficient than FE in reducing the formation of perinuclear vacuoles and inflammation processes in the epidermis and dermis. Against a severe inhibition (67%) of plasmatic cholinesterases induced by VX poisoning, the potencies of the RSDL/sponge and FE were similar. Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin.

  18. Pharmacokinetics and toxicodynamics of pralidoxime effects on paraoxon-induced respiratory toxicity. (United States)

    Houzé, Pascal; Mager, Donald E; Risède, Patricia; Baud, Frédéric J


    Empirical studies suggest that the antidotal effect of pralidoxime depends on plasma concentrations with therapeutic effects associated with concentrations above 4 mg/l. The purpose of this study was to determine the pharmacokinetic-toxicodynamic (PK-TD) relationships for the antidotal effect of pralidoxime on paraoxon-induced toxicity in rats. Diethylparaoxon inactivation of whole-blood cholinesterase activity was studied both in vitro and in male Sprague-Dawley rats. Toxin-induced respiratory effects were measured via whole-body plethysmography in control and pralidoxime-treated animals (50 mg/kg im injection). In the in vitro analysis, cholinesterase reactivation by pralidoxime in blood-poisoned diethylparaoxon (10nM) was proportional to the logarithm of drug concentrations. A mechanism-based TD model was developed, which well described the inhibition of cholinesterases by diethylparaoxon and reactivation with pralidoxime. The in vitro pralidoxime EC(50) was estimated to be 4.67 mg/l. Animals exposed to diethylparaoxon exhibited a decrease in respiratory rate and an increase in expiratory time, and pralidoxime treatment resulted in a rapid complete but transient (antidotal effects, which explained the complex relationship between drug exposure and pharmacological response profile. This study provides insights into the role of oxime-rescue of paraoxon-induced toxicity, and the final PK-TD model might prove useful in optimizing the design and development of such therapy.

  19. Postoperative Delirium in Elderly Patients Undergoing Hip Fracture Surgery in the Sugammadex Era: A Retrospective Study

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    Chung-Sik Oh


    Full Text Available Background. Residual neuromuscular block (NMB after general anesthesia has been associated with pulmonary dysfunction and hypoxia, which are both associated with postoperative delirium (POD. We evaluated the effects of sugammadex on POD in elderly patients who underwent hip fracture surgery. Methods. Medical records of 174 consecutive patients who underwent hip fracture surgery with general anesthesia were reviewed retrospectively to compare the perioperative incidence of POD, pulmonary complications, time to extubation, incidence of hypoxia, and laboratory findings between patients treated with sugammadex and those treated with a conventional cholinesterase inhibitor. Results. The incidence of POD was not significantly different between the two groups (33.3% versus 36.5%, resp.; P=0.750. Postoperative pulmonary complications and laboratory findings did not showed significant intergroup difference. However, time to extubation (6 ± 3 versus 8 ± 3 min; P<0.001 and the frequency of postoperative hypoxia were significantly lower (23% versus 43%; P=0.010 in the sugammadex group than in the conventional cholinesterase inhibitor group. Conclusion. Sugammadex did not reduce POD or pulmonary complications compared to conventional cholinesterase inhibitors, despite reducing time to extubation and postoperative hypoxia in elderly patients who underwent hip fracture surgery under general anesthesia.

  20. Health Aspects of Organophosphorous Pesticides in Asian Countries

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    B Balali-Mood


    Full Text Available Organophosphorous (OP pesticides are used frequently in agriculture, particularly in Asian countries over the pastdecades. Poisoning by these agents, either as acute or chronic in these nations, is a serious health problem. OP pesticidesresidue in fruits and vegetables that may not induce early clinical features, could also affect the human health.Therefore, medical and health professionals should be aware and learn more on the toxicology, prevention and proper management of OP poisoning. The well-known mechanism of OP toxicity is the inhibition of acetyl cholinesterase,resulting in an accumulation of acetylcholine and continued stimulation of acetylcholine receptors. Therefore, they arealso called anticholinesterase agents. Determination of blood acetyl cholinesterase and butyryl cholinesterase activities remains a mainstay for the rapid initial screening of OP pesticides. Quantitative analysis of OP and their degradation products in plasma and urine by mass spectrometric methods is a more specific method, but is expensive and limited to specialized laboratories. Therefore, history of OP pesticides exposure and clinical manifestations of a cholinergic syndrome is sufficient for management of the exposed patients. However, electrophysiological tests may be requiredfor the diagnosis of delayed neuropathy of OP poisoning. The standard management of OP poisoning includes decontamination,atropine sulphate with an oxime. Recent advances focus on blood alkalinisation and magnesium sulphate as promising adjunctive therapies. Preventive measures in OP exposure are of great importance in human health in developing countries. Therefore, regulations and controls on safe use of OP particularly in Asian countries are recommended.

  1. Pharmacists Adolf Schall and Ernst Ratzlaff and the synthesis of tabun-like compounds: a brief history. (United States)

    Petroianu, G A


    The history of the synthesis of organophosphate inhibitors of cholinesterase starting with the synthesis of tetraethyl-pyrophosphate by Moschnin(e) and de Clermont and leading to the recognition about half a century later of the toxicity of the phosphor ester by Lange and von Krueger has been told in great detail previously. An almost parallel history -described originally by Bo Holmstedt--exists for organophosphonate inhibitors of cholinesterase starting with the synthesis (1898) in Rostock of diethylamido-ethoxy-phosphoryl-cyanide by the pharmacist Adolph Schall (1870-1957), a graduate student of August Michaelis (1847-1916), the re-examination of the chemical structure of the Schall compound (1903) by Michaelis, recognition (1937) of the toxicity of class by Gerhard Schrader (1903-1990) and confirmation (1951) of the structure by Bo Holmstedt (1919-2002). This short report attempts to shed some light on the life of the pharmacists and chemists involved in the synthesis of the first P-CN organophosphonate inhibitor of cholinesterase, focusing on the two less known pharmacists, the graduate students of Professor Michaelis Adolph Schall and Ernst Ratzlaff (1870-1948).

  2. Sublethal responses of wolf spiders (Lycosidae) to organophosphorous insecticides. (United States)

    Van Erp, S; Booth, L; Gooneratne, R; O'Halloran, K


    The activities of cholinesterase (ChE) and glutathione S-transferase (GST) enzymes were assessed in the wolf spider (Lycosa hilaris) as biomarkers of organophosphate contamination in agricultural ecosystems. Spiders were exposed to simulated field rates of two commercially available organophosphorous insecticides [Basudin (diazinon) and Lorsban (chlorpyrifos)] under laboratory conditions. In terms of survival, chlorpyrifos and diazinon were more toxic to male than to female wolf spiders, but gender-specific differences in ChE activities were not evident. Cholinesterase activity in male spiders was inhibited to 14% and 61% of control activity by Basudin and Lorsban, respectively. Gluthathione S-transferase activity was not affected by either pesticide. Mortality and biomarker responses in the wolf spider were further investigated following the application of Basudin to pasture. Wolf spiders were deployed into field mesocosms; after 24 h mortality was 40%, and surviving spiders displayed significant inhibition of ChE activity (87%) compared with controls. Cholinesterase activity in spiders exposed for subsequent 24- or 48-h time periods was monitored until it returned to control levels 8 days post-application. Inhibition of ChE activity after a single application of Basudin indicate the potential use of this enzyme in wolf spiders as a biomarker for evaluating organophosphate contamination.

  3. Pesticide exposure, risk factors and health problems among cutflower farmers: a cross sectional study

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    Del Prado-Lu Jinky


    Full Text Available Abstract This was a cross-sectional study which aimed to determine associations between hematologic indices such as red blood cell cholinesterase (RBC and mean corpuscular volume (MCV, with illnesses related to pesticide exposure among cutflower farmers in La Trinidad, Benguet. One hundred two (102 randomly selected cutflower farmers underwent comprehensive, personal physical health and laboratory examinations and answered a questionnaire on work practices and illness. Majority were males (52% and most belonged to the 20–35 age group (45%. Majority of exposed farmers were symptomatic, with most common complaints being headache (48%, easy fatigability (46.1% and cough (40.2%. Analysis showed that RBC cholinesterase levels were positively associated with age (p = 0.02, and selling pesticide containers (p = 0.008. number of years of using pesticides (p = 0.022, use of contaminated cloth (p = 0.033, incorrect mixing of pesticides (p = 0.041, sex (p = 0.002 and illness due to pesticides (p = 0.005 were correlated with abnormal MCV. Significant associations were also found for hemoglobin, hematocrit, RBC, white blood cell (WBC and platelet count. Predictors of RBC cholinesterase were years of pesticide use (p = 0.037 and abnormalities on health (p = 0.029. The findings of the study can be used for information dissemination and pesticide reduction programs for the cutflower farmers.

  4. Galantamine improves sleep quality in patients with dementia. (United States)

    Naharci, Mehmet Ilkin; Ozturk, Ahmet; Yasar, Halit; Cintosun, Umit; Kocak, Necmettin; Bozoglu, Ergun; Tasci, Ilker; Doruk, Huseyin


    The purpose of the study was to evaluate the influences of cholinesterase inhibitors on sleep pattern and sleep disturbance. A total of 87 mild to moderate stage dementia patients who were not on cholinesterase enzyme inhibitor and memantine treatment were included in the study. The dementia patients were treated with donepezil, galantamine or rivastigmine, depending on the preference of the clinician. Fifty-five dementia patients (63.2 %) completed the study. Twenty-three elderly subjects, who had normal cognitive functions, were included in the study as the control group. The Pittsburgh Sleep Quality Index was used for evaluating the sleep quality at the beginning and at the final assessment. The improvement in sleep quality was better with regard to changes in Pittsburgh Sleep Quality Index scores with galantamine treatment compared to the donepezil and the control groups. A significant decrease in Pittsburgh Sleep Quality Index scores was detected in the galantamine group after treatment. Although statistically not significant, rivastigmine decreased and donepezil increased the Pittsburgh Sleep Quality Index scores after treatment. Dementia patients who had a poor sleep quality (n: 36), the rate of improvement in sleep disturbance was 81.8 % in the galantamine group, 75 % in the rivastigmine, and 50 % in the donepezil group. Galantamine may be the first choice of cholinesterase inhibitor in mild to moderate dementia patients in terms of improving sleep quality.

  5. Sensitivity of the sea snail Gibbula umbilicalis to mercury exposure--linking endpoints from different biological organization levels. (United States)

    Cabecinhas, Adriana S; Novais, Sara C; Santos, Sílvia C; Rodrigues, Andreia C M; Pestana, João L T; Soares, Amadeu M V M; Lemos, Marco F L


    Mercury contamination is a common phenomenon in the marine environment and for this reason it is important to develop cost-effective and relevant tools to assess its toxic effects on a number of different species. To evaluate the possible effects of Hg in the sea snail Gibbula umbilicalis, animals were exposed to increasing concentrations of the contaminant in the ionic form for 96 h. After this exposure period, mortality, feeding and flipping behavior, the activity of the biomarkers glutathione S-transferase, superoxide dismutase, catalase, lactate dehydrogenase and cholinesterase, the levels of lipid peroxidation and cellular energy allocation were measured. After 96 h of exposure to the highest Hg concentration (≈LC20), there was a significant inhibition of the cholinesterase activity as well as impairment in the flipping behavior and post-exposure feeding of the snails. Cholinesterase inhibition was correlated with the impairment of behavioral responses also caused by exposure to Hg. These endpoints, including the novel flipping test, revealed sensitivity to Hg and might be used as relevant early warning indicators of prospective effects at higher biological organization levels, making these parameters potential tools for environmental risk assessment. The proposed test species showed sensitivity to Hg and proved to be a suitable and resourceful species to be used in ecotoxicological testing to assess effects of other contaminants in marine ecosystems.

  6. Changes of learning and memory ability and brain nicotinic receptors of rat offspring with coal burning fluorosis

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    Gui, C.Z.; Ran, L.Y.; Li, J.P.; Guan, Z.Z. [Guiyang Medical College, Guiyang (China). Dept. of Pathology


    The purpose of the investigation is to reveal the mechanism of the decreased ability of learning and memory induced by coal burning fluorosis. Ten offspring SD rats aged 30 days, who were born from the mothers with chronic coal burning fluorosis, and ten offspring with same age from the normal mothers as controls were selected. Spatial learning and memory of the rats were evaluated by Morris Water Maze test. Cholinesterase activity was detected by photometric method. The expressions of nicotinic acetylcholine receptors (nAChRs) at protein and mRNA levels were detected by Western blotting and Real-time PCR, respectively. The results showed that in the rat offspring exposed to higher fluoride as compared to controls, the learning and memory ability declined; the cholinesterase activities in the brains were inhibited; the protein levels of alpha 3, alpha 4 and alpha 7 nAChR subunits were decreased which showed certain significant correlations with the declined learning and memory ability; and the mRNA levels of alpha 3 and alpha 4 nAChRs were decreased, whereas the alpha 7 mRNA increased. The data indicated that coal burning fluorosis can induce the decreased ability of learning and memory of rat offspring, in which the mechanism might be connected to the changed nAChRs and cholinesterase.

  7. Atividade colinesterásica no plasma e em eritrócitos de portadores de megacolo chagásico

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    Valdemar Hial


    Full Text Available A atividade colinesterásica foi medida no plasma e em eritrócitos de 32 indivíduos. Em 16 pacientes, seguramente portadores de megacolo chagásico, os níveis de colinestera- se no plasma (1.540 ±318 Ul/L e nos eritrócitos (53,2 ±9,1 Ul/g Hb estavam significativamente diminuídos, quando comparados com os níveis enzimáticos no plasma (2.554 ± 826 Ul/L e nos eritrócitos (63,6 ±11 Ul/g Hb do grupo controle (n=16. Os resultados mostram um paralelismo entre a atividade colinesterásica sistêmica e os achados histopato lógicos.Cholinesterase activity was measured in the plasma and erythrocytes from 32 individuals. The 16patients, in whon the diagnosis of Chagasic megacolon confirmed, hada significantly lower concentration of the enzyme both in plasma (1.540 ± 318 Yl/L and erythrocytes (53.2 ± 9.1 Ul/g Hb when compared with the 16 Controls in whom, the plasma and erythrocyte cholinesterase leveis were, respectively, 2.554 ± 823and 63.6 ± 11 Ul/g Hb. The results show a correlation between the systemic cholinesterase activity and the histopathological findings.

  8. Hydrogen peroxide potentiates organophosphate toxicosis in chicks

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    Banan K. Al-Baggou


    Full Text Available Objective: The purpose of the present study was to examine the effect of hydrogen peroxide(H2O2 on the acute toxicity of organophosphate insecticides dichlorvos and diazinon and their inhibitoryactions on plasma, brain and liver cholinesterase activities. Material and Methods: H2O2 was given indrinking water (0.5% v/v for 2 weeks in unsexed day old chicks, a regimen known to induce oxidativestress in this species. A control group received drinking tap water. All experiments were conducted onthe chicks at the age of 15 days after exposure to H2O2. The acute (24 h oral LD50 values of dichlorvosand diazinon in the insecticidal preparations as determined by the up-and-down method in the controlchicks were 9.4 and 15.6 mg/kg, respectively. Results: The poisoned chicks manifested signs ofcholinergic toxicosis within one hour after the dosing including salivation, lacrimation, gasping, frequentdefecation, drooping of wings, tremors, convulsions and recumbency. The acute (24 h oral LD50 valuesof dichlorvos and diazinon in chicks provided with H2O2 were reduced to 3.5 and 6.5 mg/kg, by 63 and58%, respectively when compared to respective control LD50 values. The intoxicated chicks also showedcholinergic signs of toxicosis as described above. Plasma, brain and liver cholinesterase activities of thechicks exposed to H2O2 were significantly lower than their respective control (H2O values by 25, 28 and27%, respectively. Oral dosing of chicks with dichlorvos at 3 mg/kg significantly inhibited cholinesteraseactivities in the plasma, brain and liver of both control (42-67% and H2O2-treated (15-59% chicks.Diazinon at 5 mg/kg, orally also inhibited cholinesterase activities in the plasma, brain and liver of bothcontrol (36-66% and H2O2-treated (15-30% chicks. In the H2O2 groups, dichlorvos inhibition of livercholinesterase activity and diazinon inhibition of liver and brain cholinesterase activities weresignificantly lesser than those of the respective values of

  9. Neuroprotective Role of Novel Triazine Derivatives by Activating Wnt/β Catenin Signaling Pathway in Rodent Models of Alzheimer's Disease. (United States)

    Sinha, Anshuman; Tamboli, Riyaj S; Seth, Brashket; Kanhed, Ashish M; Tiwari, Shashi Kant; Agarwal, Swati; Nair, Saumya; Giridhar, Rajani; Chaturvedi, Rajnish Kumar; Yadav, Mange Ram


    It has been reported in the literature that cholinesterase inhibitors provide protection in Alzheimer's disease (AD). Recent reports have implicated triazine derivatives as cholinesterase inhibitors. These findings led us to investigate anti-cholinestrase property of some novel triazine derivatives synthesized in this laboratory. In vitro cholinesterase inhibition assay was performed using Ellman method. The potent compounds screened out from in vitro assay were further evaluated using scopolamine-induced amnesic mice model. Further, in vitro reactive oxygen species (ROS) scavenging and anti-apoptotic property of the potent compounds were demonstrated against Aβ1-42-induced neurotoxicity in rat hippocampal cells. Their neuroprotective role was assessed using Aβ1-42-induced Alzheimer's-like phenotype in rats. Further, the role of compounds on the activation of the Wnt/β-catenin pathway was studied. The results showed that the chosen compounds are having protective effect in Alzheimer's-like condition; the ex vivo results advocated their anti-cholinestrase and anti-oxidant activities. Treatment with TRZ-15 and TRZ-20 showed neuroprotective ability of the compounds as evidenced from the improved cognitive ability in the animals, and decrease in Aβ1-42 burden and cytochrome c and cleaved caspase-3 levels in the brain. This study also demonstrates positive involvement of the novel triazine derivatives in the Wnt/β-catenin pathway. Immunoblot and immunofluorescence data suggested that ratio of pGSK3/GSK3 and β-catenin got dramatically improved after treatment with TRZ-15 and TRZ-20. TRZ-15 and TRZ-20 showed neuroprotection in scopolamine-induced amnesic mice and Aβ1-42-induced Alzheimer's rat model and also activate the Wnt/β-catenin signaling pathway. These findings conclude that TRZ-15 and TRZ-20 could be a therapeutic approach to treat AD.

  10. Sex-, tissue-, and exposure duration-dependent effects of imidacloprid modulated by piperonyl butoxide and menadione in rats. Part I: oxidative and neurotoxic potentials. (United States)

    Yardimci, Mustafa; Sevgiler, Yusuf; Rencuzogullari, Eyyup; Arslan, Mehmet; Buyukleyla, Mehmet; Yilmaz, Mehmet


    Earlier research has evidenced the oxidative and neurotoxic potential of imidacloprid, a neonicotinoid insecticide, in different animal species. The primary aim of this study was to determine how metabolic modulators piperonyl butoxide and menadione affect imidacloprid's adverse action in the liver and kidney of Sprague-Dawley rats of both sexes. The animals were exposed to imidacloprid alone (170 mg kg⁻¹) or in combination with piperonyl butoxide (100 mg kg⁻¹) or menadione (25 mg kg⁻¹) for 12 and 24 h. Their liver and kidney homogenates were analysed spectrophotometrically for glutathione peroxidase, glutathione S-transferase, catalase, total cholinesterase specific activities, total glutathione, total protein content, and lipid peroxidation levels. Imidacloprid displayed its prooxidative and neurotoxic effects predominantly in the kidney of male rats after 24 h of exposure. Our findings suggest that the observed differences in prooxidative and neurotoxic potential of imidacloprid could be related to differences in its metabolism between the sexes. Co-exposure (90-min pre-treatment) with piperonyl butoxide or menadione revealed tissue-specific effect of imidacloprid on total cholinesterase activity. Increased cholinesterase activity in the kidney could be an adaptive response to imidacloprid-induced oxidative stress. In the male rat liver, co-exposure with piperonyl butoxide or menadione exacerbated imidacloprid toxicity. In female rats, imidacloprid+menadione co-exposure caused prooxidative effects, while no such effects were observed with imidacloprid alone or menadione alone. In conclusion, sex-, tissue-, and duration-specific effects of imidacloprid are remarkable points in its toxicity.

  11. Chronic treatment with taurine after intracerebroventricular streptozotocin injection improves cognitive dysfunction in rats by modulating oxidative stress, cholinergic functions and neuroinflammation. (United States)

    Reeta, K H; Singh, Devendra; Gupta, Y K


    The present study investigated the neuroprotective effects of taurine, an essential amino acid for growth and development of central nervous system. Intracerebroventricular streptozotocin (ICV-STZ) model of cognitive impairment was used in male Wistar rats (270 ± 20 g). Morris water maze, elevated plus maze and passive avoidance paradigm were used to assess cognitive performance. Taurine (40, 60 and 120 mg/kg) was administered orally for 28 days following STZ administration on day 1. Oxidative stress parameters (malondialdehyde, glutathione, nitric oxide and superoxide dismutase) and cholinesterases (acetylcholinesterase and butyrylcholinesterase) activity were measured at end of the study in the cortex and hippocampus. Levels of TNF-α, IL-1β, expression of rho kinase-II (ROCK-II), glycogen synthase kinase-3β (GSK-3β) and choline acetyltransferase (ChAT) were studied in cortex and hippocampus. STZ caused significant cognitive impairment as compared to normal control. Chronic administration of taurine attenuated STZ-induced cognitive impairment. Increased oxidative stress and increased levels of TNF-α, IL-1β induced by STZ were also significantly attenuated by taurine. Taurine significantly (p < 0.05) decreased the STZ-induced increased expression of ROCK-II in cortex and hippocampus. Further, STZ-induced increased activity of cholinesterases was significantly (p < 0.001) mitigated by taurine. STZ decreased the expression of ChAT in hippocampus which was significantly (p < 0.05) reversed by taurine. However, GSK-3β expression was not altered by either STZ or taurine. The present study indicates that taurine exerts a neuroprotective role against STZ-induced cognitive impairment in rats. This effect is probably mediated by modulating oxidative stress, cholinesterases, inflammatory cytokines and expression of ROCK-II. Thus, this study suggests a potential of chronic taurine administration in cognitive impairment of Alzheimer's type.

  12. Biosensor based on Butyrylcholinesterase for Detection of Carbofuran (United States)

    Dey, Mousumi; Bhuvanagayathri, R.; Daniel, David K.


    Esterase enzymes play an important role in biology because they are responsible for the hydrolysis of choline esters. In their absence, the original state of the post synaptic membranes cannot be reestablished. Therefore, the aim of the work is to study the inhibiting action exerted by the group of compounds on these enzymes. Among these class of inhibiting compounds, pesticides are important because of the potential danger as a result of their large scale use in agriculture. Pesticides are generally determined using liquid or gas chromatography methods with various detection techniques. These methods are very sensitive and discriminating, however they require sample pretreatment such as extraction, preconcentration and clean up, which are skilled techniques and high cost treatment and also time consuming. In this study, acetyl cholinesterase and butyrylcholinesterase based biosensors have emerged as a promising tool for the detection and characterization of pesticides which are inhibitors of these enzymes. Although the physiological function of butyrylcholinesterase in comparison with acetyl cholinesterase is ambiguous, it has larger substrate specificity towards choline esters. Therefore, the development of a more selective electrode against choline, can lead to more sensitive determination of the inhibitor being investigated. Hence in the present work, a method based on inhibition of butyrylcholinesterase was attempted for quantification of carbofuran on the basis of cholinesterase inhibition. Butyrylcholinesterase with an activity of 10.2 units/mg was immobilized on a solid surface by cross linking with glutaraldehyde. The immobilized system was calibrated by correlating the inhibition of the butyrylcholinesterase activity with varying concentrations of the butyryl choline chloride and carbofuran. The sensing mechanism was investigated for its response to carbofuran concentrations ranging from 125 to 1,000 ppm. The effects of butyryl choline chloride

  13. Contributing Factors for Morbidity and Mortality in Patients with Organophosphate Poisoning on Mechanical Ventilation: A Retrospective Study in a Teaching Hospital (United States)

    Patil, Gurulingappa; Nikhil, M.


    Introduction One of the most common causes of poisoning in agricultural based developing countries like India is due to Organophosphorus (OP) compound. Its widespread use and easy availability has increased the likelihood of poisoning with these compounds. Aim To study the morbidity and mortality in patients with acute OP poisoning requiring mechanical ventilation. Materials and Methods This was a retrospective study constituting patients of all age groups admitted to the Intensive Care Unit (ICU) with diagnosis of OP poisoning between January 2015 to December 2015. Of 66 OP poisoning cases those patients who went against medical advice, 20 were excluded from the study and thus 46 patients were included. Diagnosis was performed from the history taken either from the patient or from the patient’s relatives and presenting symptoms. Demographic data, month of the year, age of patient, mode of poisoning, cholinesterase levels, duration of mechanical ventilation and mortality were recorded. Data are presented as mean±SD. Results A 97.83% (45/46) of cases were suicidal. Out of 46, 9 were intubated and mechanically ventilated. Duration of mechanical ventilation varied from less than 48 hours to more than 7 days. Mortality rate was 50%, 0% and 100% in those who required mechanical ventilation for more than 7 days, 2 to 7 days and poisoning, cholinesterase levels and duration of ventilation were independent predictors of death and all of them contributed to the mortality. Overall mortality rate in those who required mechanical ventilation was 22.22%. Conclusion Morbidity and mortality due to OP poisoning is directly proportional to the age, severity of poisoning and duration of mechanical ventilation and inversely proportional to serum cholinesterase level. PMID:28208980

  14. Crocin Restores Hypotensive Effect of Subchronic Administration of Diazinon in Rats

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    Marjan Razavi


    Full Text Available Objective(s: In this study, the effects of crocin against subchronic toxicity of diazinon (DZN on systolic blood pressure (SBP and heart rate (HR were evaluated in rats. Materials and Methods: Rats were equally divided into 7 groups; control (corn oil, DZN (15 mg/kg, crocin (each group received 12.5, 25 or 50 mg/kg crocin plus DZN, vitamin E (200 IU/kg plus DZN and crocin (50 mg/kg treated groups.  Rats were given DZN via gavage once a day for 4 weeks. Vitamin E (three times per week and crocin (once a day were intraperitoneally injected to rats for 4 weeks. Plasma cholinesterase activity (Elman method, malondealdehyde (MDA levels in the aortic tissue (Thiobarbituric acid reactive substances or TBARS method; SBP and HR (tail cuff method were evaluated at the end of 4th week. Results: A significant decrease in cholinesterase activity was observed in DZN group (P< 0.001. Crocin did not show any effects on cholinesterase activity. DZN increased MDA levels in aortic tissue (P< 0.001 in comparison with control group. Crocin and vitamin E plus DZN decreased MDA elevation induced by DZN in aortic tissue. DZN significantly reduced SBP (P< 0.01 and increased HR (P< 0.001 in comparison with control. Concurrent administration of crocin and DZN, improved the reduction of SBP and the elevation of HR induced by DZN in rat. Crocin alone did not have any effect on SBP and HR. Conclusion: This study showed that concurrent administration of crocin and DZN could restore the effects of subchronic DZN administration on SBP and HR in rats.

  15. Protective effect of berberine, an isoquinoline alkaloid ameliorates ethanol-induced oxidative stress and memory dysfunction in rats. (United States)

    Patil, Shaktipal; Tawari, Santosh; Mundhada, Dharmendra; Nadeem, Sayyed


    Memory impairment induced by ethanol in rats is a consequence of changes in the CNS that are secondary to impaired oxidative stress and cholinergic dysfunction. Treatment with antioxidants and cholinergic agonists are reported to produce beneficial effects in this model. Berberine, an isoquinoline alkaloid is reported to exhibit antioxidant effect and cholinesterase (ChE) inhibitor activity. However, no report is available on the influence of berberine on ethanol-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in ethanol-induced rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameter of oxidative stress and cholinesterase (ChE) activity as a marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Forty five days after ethanol treated rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25-100mg/kg, p.o., once a day for 45days) improved cognitive performance, and lowered oxidative stress and ChE activity in ethanol treated rats. In another set of experiments, berberine (100mg/kg) treatment during training trials also improved learning and memory, and lowered oxidative stress and ChE activity. Chronic treatment (45days) with vitamin C, and donepezil during training trials also improved ethanol-induced memory impairment and reduced oxidative stress and/or cholinesterase activity. In conclusion, the present study demonstrates that treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in ethanol treated rats.

  16. Acetylcholinesterase assay for cerebrospinal fluid using bupivacaine to inhibit butyrylcholinesterase

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    Anders Jens


    Full Text Available Abstract Background Most test systems for acetylcholinesterase activity (E.C. are using toxic inhibitors (BW284c51 and iso-OMPA to distinguish the enzyme from butyrylcholinesterase (E.C. which occurs simultaneously in the cerebrospinal fluid. Applying Ellman's colorimetric method, we were looking for a non-toxic inhibitor to restrain butyrylcholinesterase activity. Based on results of previous in vitro studies bupivacaine emerged to be a suitable inhibitor. Results Pharmacokinetic investigations with purified cholinesterases have shown maximum inhibition of butyrylcholinesterase activity and minimal interference with acetylcholinesterase activity at bupivacaine final concentrations between 0.1 and 0.5 mmol/l. Based on detailed analysis of pharmacokinetic data we developed three equations representing enzyme inhibition at bupivacaine concentrations of 0.1, 0.2 and 0.5 mmol/l. These equations allow us to calculate the acetylcholinesterase activity in solutions containing both cholinesterases utilizing the extinction differences measured spectrophotometrically in samples with and without bupivacaine. The accuracy of the bupivacaine-inhibition test could be confirmed by investigations on solutions of both purified cholinesterases and on samples of human cerebrospinal fluid. If butyrylcholinesterase activity has to be assessed simultaneously an independent test using butyrylthiocholine iodide as substrate (final concentration 5 mmol/l has to be conducted. Conclusions The bupivacaine-inhibition test is a reliable method using spectrophotometrical techniques to measure acetylcholinesterase activity in cerebrospinal fluid. It avoids the use of toxic inhibitors for differentiation of acetylcholinesterase from butyrylcholinesterase in fluids containing both enzymes. Our investigations suggest that bupivacaine concentrations of 0.1, 0.2 or 0.5 mmol/l can be applied with the same effect using 1 mmol/l acetylthiocholine iodide as substrate.

  17. Eye-related visual hallucinations: consider 'Charles Bonnet syndrome'. (United States)

    Cinar, Nilgun; Sahin, Sevki; Karsidag, Sibel


    The Charles Bonnet Syndrome (CBS) is typically characterized by visual hallucinations in elderly people without cognitive defects. This article presents the case of an 80-year-old male patient with a one-year history of visual hallucinations, secondary to glaucoma, in both eyes. Neither a dopamine agonist nor cholinesterase inhibitor therapy improved his symptoms. In this case, the hallucinations were gradually improved after administration of a GABAergic drug, pregabalin, for diabetic polyneuropathy. Placebo-controlled clinical trials would be needed to support this effect of pregabalin, as suggested by this association.

  18. Mortality of passerines adjacent to a North Carolina corn field treated with granular carbofuran. (United States)

    Augspurger, Tom; Smith, Milton R.; Meteyer, Carol U.; Converse, Kathryn A.


    Red-winged blackbirds (Agelaius phoeniceus) were collected during an epizootic in southeastern North Carolina (USA). Activity of brain cholinesterase (ChE) was inhibited by 14 to 48% in three of five specimens, and returned to normal levels after incubation. Gastrointestinal tracts were analyzed for 30 anti-ChE agents. Carbofuran, the only compound detected, was present in all specimens at levels from 5.44 to 72.7 μg/g wet weight. Application of granular carbofuran in an adjacent corn field, results of necropsy examinations, and chemical analyses are consistent with a diagnosis of carbofuran poisoning in these specimens.

  19. Enhanced depletion of glutathione and increased liver oxidative damage in aflatoxin-fed mice infected with Plasmodium berghei

    DEFF Research Database (Denmark)

    Ankrah, N A; Sittie, A; Addo, P G;


    The effect of dietary aflatoxins B1 and G1 and Plasmodium berghei infection on glutathione (GSH) levels and liver status in mice was investigated. Three days after intraperitoneal injection of 0.1 x 10(6) parasitized red blood cells into the mice, there was a significant fall in blood glutathione...... levels accompanied by a significant increase in serum cholinesterase and liver malonic dialdehyde levels in the mice fed aflatoxin compared with those in the control group. The results suggested that malaria parasites can enhance depletion of host glutathione and oxidative damage of the liver in mice fed...... low levels of aflatoxins....

  20. 有机磷杀虫药中毒

    Institute of Scientific and Technical Information of China (English)


    有机磷杀虫药(organophosphorous insecticides,OPI)中毒主要通过抑制体内胆碱酯酶(cholinesterase,ChE)活性,失去分解乙酰胆碱(acetylcholine,ACh)能力,引起体内生理效应部位ACh大量蓄积,使胆碱能神经持续过度兴奋,表现毒蕈碱样、烟碱样和中枢神经系统等中毒症状和体征.严重者常死于呼吸衰竭.

  1. Cyanide poisoning of a Cooper’s hawk (Accipiter cooperii) (United States)

    Franson, J Christian


    A Cooper’s hawk (Accipiter cooperii) was found dead in a ditch leading from a heap leach pad at a gold mine in Nevada. Observations at autopsy included an absence of external lesions, traces of subcutaneous and coronary fat, no food in the upper gastrointestinal tract, and no lesions in the viscera. Cyanide concentrations (µg/g ww) were 5.04 in blood, 3.88 in liver, and 1.79 in brain. No bacteria or viruses were isolated from tissues, and brain cholinesterase activity was within the normal range for a Cooper’s hawk.

  2. Exposure to pesticides in agriculture: a survey of spraymen using dimethoate in the Sudan (United States)

    Copplestone, J. F.; Fakhri, Z. I.; Miles, J. W.; Mitchell, C. A.; Osman, Y.; Wolfe, H. R.


    There is a need for objective data on the exposure of spraymen to pesticides in agriculture in order to assess minimum requirements for practicable protection in tropical areas. To provide data, a survey was carried out in the Sudan on spraymen using dimethoate. No cholinesterase depressions were found and the calculated dose received by each man per day was within safe limits in the circumstances of this survey. Respiratory exposure was only a minor part of total exposure. The methodology of such surveys is discussed and the need for the use of a standard protocol is emphasized. PMID:1088104

  3. Drug: D07869 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07869 Drug Donepezil (INN); Donaz (TN) C24H29NO3 379.2147 379.492 D07869.gif Nootr...PTICS N06D ANTI-DEMENTIA DRUGS N06DA Anticholinesterases N06DA02 Donepezil D07869 Donepezil (INN) USP drug c...lassification [BR:br08302] Antidementia Agents Cholinesterase Inhibitors Donepezil D07869 Donepez...terase (AChE) [HSA:43] [KO:K01049] Donepezil [ATC:N06DA02] D07869 Donepezil (INN) CAS: 120014-06-4 PubChem:

  4. Eye-related visual hallucinations: Consider ′Charles Bonnet syndrome′

    Directory of Open Access Journals (Sweden)

    Nilgun Cinar


    Full Text Available The Charles Bonnet Syndrome (CBS is typically characterized by visual hallucinations in elderly people without cognitive defects. This article presents the case of an 80-year-old male patient with a one-year history of visual hallucinations, secondary to glaucoma, in both eyes. Neither a dopamine agonist nor cholinesterase inhibitor therapy improved his symptoms. In this case, the hallucinations were gradually improved after administration of a GABAergic drug, pregabalin, for diabetic polyneuropathy. Placebo-controlled clinical trials would be needed to support this effect of pregabalin, as suggested by this association.

  5. Alkaloids from stems of Esenbeckia leiocarpa Engl. (Rutaceae) as potential treatment for Alzheimer disease. (United States)

    Cardoso-Lopes, Elaine Monteiro; Maier, James Andreas; da Silva, Marcelo Rogério; Regasini, Luis Octávio; Simote, Simone Yasue; Lopes, Norberto Peporine; Pirani, José Rubens; Bolzani, Vanderlan da Silva; Young, Maria Cláudia Marx


    Esenbeckia leiocarpa Engl. (Rutaceae), popularly known as guarantã, goiabeira, is a native tree from Brazil. Bioactivity-guided fractionation of the ethanol stems extract afforded the isolation of six alkaloids: leiokinine A, leptomerine, kokusaginine, skimmianine, maculine and flindersiamine. All isolated compounds were tested for acetyl cholinesterase inhibition, in vitro and displayed anticholinesterasic activity. The alkaloid leptomerine showed the highest activity (IC₅₀ = 2.5 mM), similar to that of the reference compound galanthamine (IC₅₀ = 1.7 mM). The results showed for the first time the presence of alkaloids leptomerine and skimmianine in E. leiocarpa (Engl.) with potent anticholinesterasic activity.

  6. A comparative study on esterases from three species of Raillietina. (United States)

    Balasubramanian, M P; Dhandayuthapani, S; Nellaiappan, K; Ramalingam, K


    The multiplicity of soluble esterases in Raillietina tetragona, R. echinobothrida and R. cesticillus was studied by use of slab polyacrylamide gel electrophoresis. Five fractions of esterase activity were observed in R. tetragona, seven in R. echinobothrida and three in R. cesticillus. The various fractions of esterase activity of closely related species of Raillietina showed differential behaviour towards various chemicals. Based on the inhibitory effect of inhibitors p-CMB, EDTA, malathion, silver nitrate and eserine sulphate, the various esterases have been classified into arylesterase, carboxylesterase, acetylesterase and cholinesterase.

  7. Improving Blood Monitoring of Enzymes as Biomarkers of Risk from Anticholinergic Pesticides and Chemical Warfare Agents (United States)


    One approach would be to use the colorimetric two substrate ( diazinon -oxon and paraoxon) PON1 assay (Richter, et al., 2004, Costa, et al., 2005a...and, its limited usefulness as a test of liver function. J Lab Clin Med 40:692–702. Harris, E.K. (1974). Effects of intra- and interindividual varia...Vorhaus, L.J., II, Scudamore, H.H., Kark, R.M. (1950). Measurement of serum cholinesterase activty in the study of disease of the liver and biliary

  8. Histological and histochemical studies on the innervation of the respiratory organs of Calotes versicolor Daud. (Agamidae, Lacertilia). (United States)

    Mathur, R; Kumar, S; Sharma, M C


    A study on the innervation of the respiratory organs of Calotes versicolor has been made using cholinesterase and silver reduction techniques. The tracheal and bronchial plexuses have been described. A number of nerve terminations along with synapses are reported. ChE activity has been observed on the periphery of the alveoli which is believed to be of importance in controlling the acetylcholine level, acting as a general tissue enzyme to prevent excessive accumulation of acetylcholine. Vascular nerve supply has been found to be largely of vagal origin.

  9. The fine structure of the excretory system in adult Nippostrongylus brasiliensis (Nematoda) and a suggested function for the 'excretory glands'. (United States)

    Lee, D L


    The ultrastructure of the excretory system, including the subventral glands, of the nematode Nippostrongylus brasiliensis has been described. The walls of the lateral excretory canals contain canaliculi which open into the lumen of the canal. It is suggested that these canals play a role in osmoregulation and excretion. The sub-ventral glands contain two types of secretory granule and contain non-specific esterase, cholinesterase and aminopeptidase. It is suggested that these glands are not excretory but play an important role in feeding.

  10. Biological effects of short-term, high-concentration exposure to methyl isocyanate. II. Blood chemistry and hematologic evaluations.


    Troup, C M; Dodd, D E; Fowler, E H; Frank, F R


    Human, rat, and guinea pig packed erythrocytes exposed to 100, 500, or 1000 ppm of methyl isocyanate (MIC) vapor in vitro showed a concentration-related inhibition of cholinesterase (ChE) activity. Rat and guinea pig packed erythrocytes showed an almost complete inhibition of ChE activity at 2000 ppm. In vitro exposures of human and guinea pig blood to 1000 or 2000 ppm of MIC vapor resulted in qualitative alterations in the electrophoretic mobility of hemoglobin (Hb) as measured by citrated a...

  11. Safety profile of Cerebrolysin: clinical experience from dementia and stroke trials. (United States)

    Thome, J; Doppler, E


    The safety of Cerebrolysin has been shown through many years of clinical use, observations from postmarketing surveillance studies, and safety data from randomized, controlled clinical trials. The reported events showed that adverse reactions to Cerebrolysin were generally mild and transient. Most common adverse events included vertigo, agitation and feeling hot. In the controlled clinical trials analyzed for this report, the incidence of adverse events was similar in Cerebrolysin- and placebo-treated groups. Cerebrolysin seems to be safe when used in combination with recombinant tissue-type plasminogen activator or cholinesterase inhibitors such as donepezil or rivastigmine. To our knowledge, Cerebrolysin was not associated with major changes in vital signs or laboratory parameters.

  12. DOMINO-AD protocol: donepezil and memantine in moderate to severe Alzheimer's disease – a multicentre RCT

    Directory of Open Access Journals (Sweden)

    Lindesay James


    Full Text Available Abstract Background Alzheimer's disease (AD is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil. Method DOMINO-AD is a pragmatic, 15 centre, double-blind, randomized, placebo controlled trial. Patients with AD, currently living at home, receiving donepezil 10 mg daily, and with Standardized Mini-Mental State Examination (SMMSE scores between 5 and 13 are being recruited. Each is randomized to one of four treatment options: continuation of donepezil with memantine placebo added; switch to memantine with donepezil placebo added; donepezil and memantine together; or donepezil placebo with memantine placebo. 800 participants are being recruited and treatment continues for one year. Primary outcome measures are cognition (SMMSE and activities of daily living (Bristol Activities of Daily Living Scale. Secondary outcomes are non-cognitive dementia symptoms (Neuropsychiatric Inventory, health related quality of life (EQ-5D and DEMQOL-proxy, carer burden (General Health Questionnaire-12, cost effectiveness (using Client Service Receipt Inventory and

  13. Utilização de técnicas eletroanalíticas na determinação de pesticidas em alimentos

    Directory of Open Access Journals (Sweden)

    Galli Andressa


    Full Text Available The aim of this work is to discuss selected applications of electroanalytical techniques for the detection of pesticides in foods and beverages, published in the last ten years. The applications involved different working electrodes for the electroanalytical determination of pesticides, namely amperometric biosensors, cholinesterase-based biosensors, polymer-modified electrodes, ultramicroelectrodes and hanging mercury drop electrodes. They were used for several voltammetric and amperometric techniques in different analytical procedures for the detection and quantification of different classes of pesticides in different food matrices.

  14. Distinctive Effect of Donepezil Treatment on P300 and N200 Subcomponents of Auditory Event-Related Evoked Potentials in Alzheimer Disease Patients



    Background Latency of P300 subcomponent of event-related potentials (ERPs) increases in Alzheimer disease (AD) patients, which correlate well with cognitive impairment. Cholinesterase inhibitors (ChEIs) reduce P300 latency in AD patients with parallel improvement in cognition. It is not known whether N200 response to ChEIs is similar to that of P300. The aim of this study was to evaluate and compare characteristics of P300 and N200 in AD patients, treatment-naïve and on stable donepezil treat...

  15. ORIGINAL ARTICLE: Acute Poisoning with Organophosphorus Pesticide: Patients Admitted to A Hospital in Bijapur, Karnataka.

    Directory of Open Access Journals (Sweden)

    Indira A. Hundekari


    Full Text Available Background: Organophosphorus compounds are the pesticides most often involved in human poisoning. Toxicity of these compounds is due to the inhibition of acetyl cholinesterase at cholinergic junctions of the nervous system. Aims & Objectives: Toxicities of OP pesticidescause adverse effects on many organs and systems hence the present study was planned to study the plasma Cholinesterase, serumcholesterol and thyroid function tests in acute organophosphorus pesticide poisoning. Materials and Methods: Plasma ChE, serumcholesterol and serum triiodothyronine, thyroxine, and thyroid stimulating hormone levels were estimated using standard methods.Result: In our study we found the maximum (95% cases were suicidal poisoning. We found that the incidence of poisoning was more common among age group between 15-35 years and males (57% were more likely to attempt suicide as compared to females (38%. Among the organophosphorus compounds the most commonly used were dimethoate,monocrotophos, chlorpyriphos. 79% organophosphorus poisoned patients recovered, while 21% died. Plasma Cholinesterase levels were significantly (p<0.001 decreased in all grades of organophosphate poisoning as compared to controls. Inhibition of Plasma Cholinesterase occurs at the time of admission due to toxic effect of organophosphorus compounds; but the levels significantly (p<0.001 normalized after treatment i.e. on the last day of hospitalization. Serum total cholesterol levels significantly decreased (p<0.001 in all grades of organophosphate poisoning cases as compared to controls without any change after treatment as compared with the patients before treatment. There was a slight and nonsignificant decrease in serum triiodothyronine and serum thyroxine levels in organophosphorus poisoning cases without anysignificant change in serum thyroid stimulating hormone levels as compared to control. The organophosphorus poisoned patients after treatment do not show more changes in their

  16. An Adult Patient with Ocular Myasthenia and Unusually Long Spontaneous Remission

    Directory of Open Access Journals (Sweden)

    Jasem Al-Hashel


    Full Text Available A male patient developed ocular myasthenia gravis (MG at the age of 33. He was anti-acetylcholine receptor antibody (anti-AChR Ab negative. He received cholinesterase blocker for 5 months and went into a complete clinical remission that lasted untreated for 17 years. He relapsed recently with ocular symptoms only. He is now anti-AChR Ab positive and SFEMG is abnormal in a facial muscle. The patient is controlled with steroids. He had one of the longest spontaneous remissions reported in the natural history of MG, particularly unusual for an adult with the disease.

  17. Myasthenia gravis with presynaptic neurophysiological signs: Two case reports and literature review. (United States)

    Alboini, Paolo Emilio; Damato, Valentina; Iorio, Raffaele; Luigetti, Marco; Evoli, Amelia


    The distinction between myasthenia gravis and Lambert-Eaton myasthenic syndrome is based on clinical, neurophysiological and immunological features. We hereby report two cases with a clinical diagnosis of myasthenia gravis and neurophysiological features consistent with a pre-synaptic neuromuscular transmission defect. Both patients had increased anti-acetylcholine receptor antibody titres and showed a good response to cholinesterase inhibitors, along with a >100% facilitation of the compound muscle action potential on electrophysiological studies. We provide a review of English literature studies on co-existing features of myasthenia gravis and Lambert-Eaton myasthenic syndrome, and discuss diagnostic controversies.

  18. Acetylcholinesterase and Acetylcholine Receptor (United States)


    placing the ester group at th- estera - tic site. K. values for AcCh and DMBAc are similar, indicating no substantial coulombic effe,-t, and the...V. P. (1950) Biochim. BioDhys. Acta 4, 543-558. 2. "Studies on Cholinesterase. VII. The Active Surface of Acetylcholine Esterase Derived from Effects...L., Chang, H. W., and Chen-, Y. T. (1972) J. Biol. Chem. 247, 1555-1565. 42. "Rapid and Complete Purification of Acetylcholin- esterases of Electric

  19. Treatment of post-electroconvulsive therapy delirium and agitation with donepezil. (United States)

    Logan, Christopher J; Stewart, Jonathan T


    Delirium and agitation are commonly encountered after administration of electroconvulsive therapy (ECT). Management is generally fairly straightforward, although some patients may have a severe, prolonged, or refractory course. We recently cared for a 65-year-old man who consistently developed severe and very prolonged post-ECT delirium that did not respond to typical pharmacological agents; the duration of delirium was dramatically shortened by the addition of donepezil. Cholinesterase inhibitors may have a place in mitigating severe and prolonged post-ECT delirium.

  20. Occupational pesticide intoxications among farmers in Bolivia: a cross-sectional study

    DEFF Research Database (Denmark)

    Jørs, Erik; Morant, Rafael Cervantes; Aguilar, Guido Condarco


    from 48 villages in the temperate and subtropical valleys in the eastern part of the Andes Mountains in Bolivia. Of these 171 male farmers using pesticides in their agricultural production were used in the statistical analysis, including linear- and logistic regression analysis. RESULTS: This study...... with spraying operations. The risk of experiencing symptoms and the serum cholinesterase activity were influenced by whether or not organophosphates were used and the number of times sprayed. The experience of symptoms was moreover influenced by the hygienic and personal protective measures taken during...

  1. Intrinsic innervation of the uterus in guinea pig and rat. (United States)

    Mustafa, F; Fatani, J A; el-Eishi, H; el-Badawi, M G


    The pattern of distribution of cholinergic and adrenergic nerves in the uterus of albino rats and guinea pigs was examined histochemically. In the albino rat, the uterus was found well-innervated by both adrenergic and cholinergic nerves with a clear regional variation. Dense innervation was demonstrated at the tubal and cervical ends of the uterus and in the cervix. Cholinergic nerves supplying the glands were more numerous than the adrenergic nerves which were relatively few. In the guinea-pigs, the uterus was richly innervated by adrenergic nerves with a clear regional variation. No cholinesterase-positive nerves or nerve cells were demonstrated.

  2. Potential of organic bio processed materials for bioremediation (bio stimulation) of chloropyrifos contaminated soil for food safety

    Energy Technology Data Exchange (ETDEWEB)

    Kadian, N.; Malik, A.; Satya, S.; Dureja, P.


    Chloropyrifos (CPF), a well-known neutronic agent, causes inhibition of some important enzymes such as acetyl-cholinesterase, ATPase, cholesterol ester-hydrolase. It can pass through the placenta in to the body of fetus and target more on developing brains and new born. Its metabolites are detected in the air, in amniotic fluid and in infant meconium. The inherent persistency of CPF may ensure long-term pest control, but enhances the risk of uptake (by edible plants) and subsequent bioaccumulation. (Author)

  3. Dansk Kolinesterase Kartotek udreder patienter med forlænget paralyse efter suxamethon og mivacurium

    DEFF Research Database (Denmark)

    Eskildsen, Katrine Zwicky; Gätke, Mona Ring


    The Danish Cholinesterase Research Unit (DCRU) is a nationwide unit for patients carrying mutations in the butyrylcholinesterase enzyme (BChE). BChE hydrolyzes the neuromuscular blocking drugs succinylcholine and mivacurium. Patients with mutations in the butyrylcholinesterase gene are at risk of...... of experiencing a prolonged effect of the drugs, such as weakness or paralysis for hours. In order to diagnose the referred patients correctly, DCRU combines results such as BChE activity, genotyping, pedigree and clinical reactions to succinylcholine or mivacurium....

  4. Dansk Kolinesterase Kartotek udreder patienter med forlænget paralyse efter suxamethon og mivacurium

    DEFF Research Database (Denmark)

    Eskildsen, Katrine Zwicky; Gätke, Mona Ring


    The Danish Cholinesterase Research Unit (DCRU) is a nationwide unit for patients carrying mutations in the butyrylcholinesterase enzyme (BChE). BChE hydrolyzes the neuromuscular blocking drugs succinylcholine and mivacurium. Patients with mutations in the butyrylcholinesterase gene are at risk of...... of experiencing a prolonged effect of the drugs, such as weakness or paralysis for hours. In order to diagnose the referred patients correctly, DCRU combines results such as BChE activity, genotyping, pedigree and clinical reactions to succinylcholine or mivacurium....

  5. Serum chemistry reference values in adult Japanese quail (Coturnix coturnix japonica) including sex-related differences. (United States)

    Scholtz, N; Halle, I; Flachowsky, G; Sauerwein, H


    Serum chemistry reference values may provide useful information about the physical condition of individuals, making them a useful tool in differentiating normal and healthy animals from abnormal or diseased states. For Japanese quail that are used for producing eggs and meat for human consumption and also as laboratory animals, we aimed to extend the available array of reference values and to compare 16-wk-old adult male versus female birds. In the present study, clinical chemistry data (albumin, total protein, glucose, uric acid, cholesterol, bilirubin, cholinesterase, creatinine, triglycerides, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase) in blood serum from up to 125 male and 151 female Japanese quail were established. Statistical comparisons were made between male and female birds. Aspartate aminotransferase, alanine aminotransferase, glucose, cholinesterase, and bilirubin values were higher (P sex-based differences were observed for creatinine and uric acid. The reference values provided are relevant in particular for the use of quail as laboratory animals when responses to specific treatments have to be monitored and appraised.

  6. Plasma enzyme activities in coturnix quail fed graded doses of DDE, polychlorinated biphenyl, malathion, and mercuric chloride (United States)

    Dieter, M.P.


    Male Coturnix quail (Coturnix coturnix japonica) were fed diets for 12 weeks containing graded levels of DDE, polychlorinated biphenyl (Aroclor 1254), malathion, and mercuric chloride. Birds were bled prior to exposure and at 2, 4 and 12 weeks, and the plasma used to measure the activities of creatine kinase, aspartate aminotransferase, cholinesterase, fructose-diphosphate aldolase, and lactate dehydrogenase. Abnormal activity of certain plasma enzymes was noted in birds after 2 and 4 weeks, but these changes were not proportional to dose or exposure time. At 12 weeks increases in each of the activities of plasma enzymes of birds fed organochlorines, and decreases in cholinesterase activity of birds fed malathion or mercuric chloride, were proportional to the log dose of the respective agents. In addition, the pattern of enzyme responses in the 4 experimental groups had changed, and was illustrative of the specific type of substance that had been fed. The data suggest that qualitative and quantitative identification of environmental contaminants in birds, and perhaps a variety of wild animals, may be possible by utilization of multiple plasma enzyme assays. Residue analyses after 12 weeks of feeding showed that DDE accumulated in carcasses and livers at concentrations up to 4-fold higher than those in the diets. In contrast residues of Aroclor 1254 attained in carcasses were identical to, and in livers one-half of, the concentration in the feed. Mercury did not accumulate as much in the tissues; residues attained were one-twentieth or less of those in the feed.


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    Full Text Available The aim of this trial was to determine the toxic effect of OMS-43 on spraymen and inhabitants. The spraying operation lasted for 30 successive days, and two teams consisting of 20 spraymen, 2 mixers, 4 foremen and team leaders were engaged in this operation. The operators were under systematic and closed clinical observation and cholinesterase determination (tintometric method during the operation as well as, in some cases, two months after. In spite of the rigid instructions given to the spraymen to follow the necessary precautions, there were 42 cases of clinical symptoms. In some individuals several relapses occurred during the operation. No complaints or cholinesterase depression was observed during the first 2- week exposure. The main clinical symptoms were headache, giddiness, nausea and abdominal cramps; some workers felt weakness. Diarrhea was reported among two cases and was treated with Enterovioform (Ciba.A drop in whole blood CHE was seen among both mixers accompanied by clinical symptoms. One of the mixers left his job when his CHE was depressed to 12.5. Out of 20 spraymen, 8 showed depression of CHE in some cases with clinical symptoms. This study showed that the use of Sumithion under local conditions (sub- tropics, hot dry season was safe for residents, but its toxic effect on operators should be considered and further toxicological investigations are requires under tropical conditions.

  8. Altitude acclimatization improves submaximal cognitive performance in mice and involves an imbalance of the cholinergic system. (United States)

    Guerra-Narbona, R; Delgado-García, J M; López-Ramos, J C


    The aim of this work was to reveal a hypothetical improvement of cognitive abilities in animals acclimatized to altitude and performing under ground level conditions, when looking at submaximal performance, once seen that it was not possible when looking at maximal scores. We modified contrasted cognitive tasks (object recognition, operant conditioning, eight-arm radial maze, and classical conditioning of the eyeblink reflex), increasing their complexity in an attempt to find performance differences in acclimatized animals vs. untrained controls. In addition, we studied, through immunohistochemical quantification, the expression of choline acetyltransferase and acetyl cholinesterase, enzymes involved in the synthesis and degradation of acetylcholine, in the septal area, piriform and visual cortexes, and the hippocampal CA1 area of animals submitted to acute hypobaric hypoxia, or acclimatized to this simulated altitude, to find a relationship between the cholinergic system and a cognitive improvement due to altitude acclimatization. Results showed subtle improvements of the cognitive capabilities of acclimatized animals in all of the tasks when performed under ground-level conditions (although not before 24 h), in the three tasks used to test explicit memory (object recognition, operant conditioning in the Skinner box, and eight-arm radial maze) and (from the first conditioning session) in the classical conditioning task used to evaluate implicit memory. An imbalance of choline acetyltransferase/acetyl cholinesterase expression was found in acclimatized animals, mainly 24 h after the acclimatization period. In conclusion, altitude acclimatization improves cognitive capabilities, in a process parallel to an imbalance of the cholinergic system.


    Directory of Open Access Journals (Sweden)



    Full Text Available Organophosphorus poisoning is the most common medico toxic emergency in India. Respiratory failure is the most common complication of OP compound leading to death. Early recognition and prompt ventilation may improve survival. The aim of the study was to correlate between the clinical score described by Peradenya Organophosphorus Poisoning (POP scale, glasgow coma scale (GCS and serum Pseudocholinesterase level at presentation, ventilator requirement and the outcome. This sectional study conducted at tertiary care centre, Nagpur from October 2011 to September 2013. 40 patients fulfilled the inclusion criteria and included in the study. Majority of patients were in younger age group with male preponderance. Agriculture is the most common occupation found in the patients in the study. Mortality was found in 17.5% patients and mortality was found to be higher in patients with severe grade of Paradeniya poisoning scale (score > or = 7 and severe grade of Glasgow coma scale (score < or = 8. Patients with normal cholinesterase levels showed significantly higher chances of survival as compared to those with less than 10% of the normal cholinesterase levels. Patients with severe grade of POP scale and GCS needed ventilatory support more frequently than patients with mild to moderate grade. Thus GCS, POP scale and Pseudocholinesterase levels can very well be used in assessing prognosis and mortality of patients of OP poisoning.

  10. Relationship between organochlorine pesticides and stress indicators in hawksbill sea turtle (Eretmochelys imbricata) nesting at Punta Xen (Campeche), Southern Gulf of Mexico. (United States)

    Tremblay, Nelly; Ortíz Arana, Alejandro; González Jáuregui, Mauricio; Rendón-von Osten, Jaime


    Data on the impact of environmental pollution on the homeostasis of sea turtles remains scarce, particularly in the Southern Gulf of Mexico. As many municipalities along the coastline of the Yucatan Peninsula do not rely on a waste treatment plant, these organisms could be particularly vulnerable. We searched for relationships between the presence of organochlorine pesticides (OCP) and the level of several oxidative and pollutant stress indicators of the hawksbill sea turtle (Eretmochelys imbricata) during the 2010 nesting season at Punta Xen (Campeche, Mexico). Of the 30 sampled sea turtles, endosulfans, aldrin related (aldrin, endrin, dieldrin, endrin ketone, endrin aldehyde) and dichlorodiphenyldichloroethylene (DDT) families were detected in 17, 21 and 26, respectively. Significant correlation existed between the size of sea turtles with the concentration of methoxychlor, cholinesterase activity in plasma and heptachlors family, and catalase activity and hexachlorohexane family. Cholinesterase activity in washed erythrocytes and lipid peroxidation were positively correlated with glutathione reductase activity. Antioxidant enzyme actions seem adequate as no lipids damages were correlated with any OCPs. Future studies are necessary to evaluate the effect of OCPs on males of the area due to the significant detection of methoxychlor, which target endocrine functioning and increases its concentration with sea turtles size.

  11. Rivastigmine for the treatment of dementia associated with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Jennifer L Reingold


    Full Text Available Jennifer L Reingold, John C Morgan, Kapil D SethiMovement Disorders Program, Department of Neurology, Medical College of Georgia, Augusta, GA, USAAbstract: Parkinson’s disease (PD afflicts millions of people worldwide and leads to cognitive impairment or dementia in the majority of patients over time. Parkinson’s disease dementia (PDD is characterized by deficits in attention, executive and visuospatial function, and memory. The clinical diagnostic criteria and neuropathology surrounding PDD remain controversial with evidence of overlap among PDD, dementia with Lewy bodies (DLB and Alzheimer’s disease (AD. Cortical cholinergic deficits are greater in PDD than in AD, and are well-correlated with the cognitive and neuropsychiatric dysfunction that occurs in PDD. Inhibition of acetylcholine metabolism is therefore a practical therapeutic strategy in PDD. This review examines current evidence for rivastigmine (a cholinesterase/butyrylcholinesterase inhibitor treatment in PDD. In addition to its efficacy, we examine the safety profile, side effects, and cost effectiveness of rivastigmine in PDD. Rivastigmine provides modest benefit in PDD and further long-term studies are needed to determine the effectiveness and safety of rivastigmine over time. Tolerability is a problem for many PDD patients treated with rivastigmine. Future studies of rivastigmine in PDD should focus on pragmatic outcomes such as time to need for nursing home placement, pharmacoeconomic outcomes and simultaneous patient/caregiver quality of life assessments.Keywords: Parkinson’s disease, dementia, rivastigmine, cholinesterase inhibitor

  12. Efficacy and Tolerability of a Combination Treatment of Memantine and Donepezil for Alzheimer’s Disease: A Literature Review Evidence (United States)

    Riverol, Mario; Slachevsky, Andrea; López, Oscar L.


    INTRODUCTION Two types of drugs have been approved for the symptomatic treatment of Alzheimer’s disease (AD): the cholinesterase inhibitors (ChEIs) and memantine. There is a growing interest to know whether the combination of these drugs is safe and if it adds any clinical benefit to patients. OBJECTIVE To systematically review published medical literature assessing the efficacy and tolerability of a combination treatment of memantine and donepezil in AD patients. METHODS We searched PubMed for English and Spanish-language literature, using the terms “Alzheimer’s disease,” “cholinesterase inhibitors,” “donepezil,” and “memantine.” Our review focused on clinical trials and observational studies. RESULTS Eleven publications representing seven unique studies were selected for this review. Three were randomized double-blind, placebo-controlled trials and four were observational studies. CONCLUSIONS Available data revealed that the combination of memantine and donepezil slowed down cognitive decline, prolonged functional independence, and improved behavioral symptoms in patients with moderate to severe AD. The long-term use of the dual therapy decreased the risk of nursing home admission. More longitudinal studies are needed to further examine the role of combined therapy in the management of AD patients. PMID:25302109

  13. Enhancement of parathion toxicity to quail by heat and cold exposure (United States)

    Rattner, B.A.; Becker, J.M.; Nakatsugawa, T.


    Effects of ambient temperature on the acute oral toxicity of parathion were investigated in Japanese quail (Coturnix japonica) maintained at thermoneutral temperature ( C) or exposed to elevated ( C) or reduced ( C) temperatures commonly encountered by free-ranging wild birds. Based upon estimates of the median lethal dosage, there was up to a two-fold enhancement of parathion toxicity in birds chronically exposed to heat or cold. Twenty-four hours after administration of a low dosage (4 mg/kg body wt, po), there was markedly greater cholinesterase inhibition in surviving heat-exposed quail compared with those reared at C (e.g., brain acetylcholinesterase depression of 42% versus 12%). There were no differences in hepatic activities of parathion oxidase, paraoxonase, or paraoxon deethylase which could account for greater toxicity to chronically heat-exposed birds. In contrast, 4 mg parathion/kg wt elicited less plasma cholinesterase inhibition in cold-exposed quail compared to thermoneutral controls (e.g., depression after 24 hr). Increased liver weight and a doubling of paraoxonase activity may have been associated with greater tolerance to sublethal doses of parathion in chronically cold-exposed quail. These findings, together with limited field observations, indicate that the hazard associated with anticholinesterase exposure of wild birds is substantially influenced by environmental temperature.

  14. Cognitive dysfunction and its determinants in patients with neurocysticercosis

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    Vinod Varghese


    Full Text Available Introduction: Neurocysticercosis (NCC is the most common parasitic infection of man. In addition to a headache, seizures, and focal deficits, this is associated with significant cognitive dysfunction. Many studies revealed that the number and location of lesions are not always responsible for cognitive dysfunction. Cholinesterase and pseudocholinesterase are found in the walls of the cysticercus which could contribute to cholinergic depletion and thus cognitive dysfunction. Patients and Methods: A total of 43 patients who presented with NCC were evaluated for cognitive deficits, as well as cholinesterase levels in cerebrospinal fluid (CSF with control CSF from patients undergoing spinal anesthesia. Blood levels of interleukin-10 and tumor necrosis factor alpha were also estimated and correlated with cognitive deficits. Results: There is a mild increase in the acetylcholinesterase in CSF of patients compared to controls, but it did not correlate with cognitive deficits. There is an increase in interleukins to a significant level which correlates with vesicular stage of the organism and cognitive impairment. The number of lesions also correlated with cognitive impairment even though the location did not. The domains of cognitive deficits seen are sustained attention, category fluency, verbal working memory, planning, set shifting, verbal learning, visual memory, and construction. Discussion and Conclusion: NCC is associated with multi-domain cognitive impairment correlates with vescicular stage, proinflammatory cytokines and number of lesions but not location, vesicular stage, and proinflammatory cytokines.

  15. Esterase’s properties in commonly used Indian spices for Alzheimer’s disease model

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    Prabha M


    Full Text Available Esterase family of Hydrolases such as Acetylcholinesterase (AchE,Butyrylcholinesterase (BchE and Carboxyl esterase (CE havebeen estimated in Alzheimer’s disease (AD model, normal brain ofstriatum, frontal cortex, hippocampus and in liver. In AD a loss ofacetylcholine activity directly correlates with memory dysfunctiondue to the activation of acetylcholinesterase andbutyrylcholinesterase enzymes. Therefore the effective treatmentmethods include restoration of cholinergic function and elevation ofACh level through inhibiting AChE and BChE. Hence to inhibitthese enzymes four commonly used Indian kitchen spices viz.,Cuminum cyminum, Elettaria cardamomum, Cinnamomum verum,Syzygium aromaticum were selected because the extracts of thesespices contain cholinesterase inhibitory activity in vitro. Thesespices were extracted with cold and hot aqueous solution and theanti- cholinesterase potential was measured in vitro. Elettariacardamomum cold extract showed significant inhibition for AchE inall regions of brain for control and AD. Whereas Cinnamomumverum hot extract showed elevated activity for carboxyl esterasewhich is a neuroprotective factor. These findings suggest thatdietary supplementation of cardamom and cinnamon in moderateamounts may aid in prevention delay in onset of AD.

  16. Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by Soman. (Reannouncement with new availability information)

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    Sparenborg, S.; Brennecke, L.H.; Jaax, N.K.; Braitman, D.J.


    The involvement of the NMDA receptor in the neurotoxicity induced by soman, an organophosphorus compound which irreversibly inhibits cholinesterase, was studied in guinea pigs. The drug MK-801 (0.5, 1 or 5 mg/kg, i.p.) was given as a pretreatment before a convulsant dose of soman or as a post treatment (30, 100 or 300 micron g/kg, i.m.) 5 min after the development of soman-induced status epilepticus. Pyridostigmine, atropine and pralidoxime chloride were also given to each subject to counteract the lethality of soman. All subjects that were challenged with soman and given the vehicle for MK-801 (saline) exhibited severe convulsions and electrographic seizure activity. Neuronal necrosis was found in the hippocampus, amygdala, thalamus and the pyriform and cerebral cortices of those subjects surviving for 48 hr. Pretreatment with 0.5 or 1 mg/kg doses of MK-801 did not prevent nor delay the onset of seizure activity but did diminish its intensity and led to its early arrest. At the largest dose (5 mg/kg), MK-801 completely prevented the development of seizure activity and brain damage. Post treatment with MK-801 prevented, arrested or reduced seizure activity, convulsions and neuronal necrosis in a dose-dependent manner. The NMDA receptor may play a more critical role in the spread and maintenance, rather than the initiation of cholinergically-induced seizure activity....Seizure-related brain damage, Organophosphorus compound, Nerve agent, Cholinesterase inhibition, Excitotoxicity, Guinea pig.

  17. Environmental exposure to organophosphate pesticides: assessment of endocrine disruption and hepatotoxicity in pregnant women. (United States)

    Cecchi, A; Rovedatti, M G; Sabino, G; Magnarelli, G G


    In utero exposure is the first point of contact with environmental xenobiotics that may affect the maternal-placental-fetal balance. Considering that maternal pathophysiological changes affect intrauterine development, this pilot study was conducted to address how environmental exposure to organophosphate pesticides (OPs) during pregnancy may contribute to maternal endocrine disruption and disturbed hepatic function. A prospective study was carried out with pregnant women (n=97) living in a rural area of the Rio Negro province where OPs are intensively applied throughout 6 months of the year. Blood samples were obtained and biomarkers of OPs exposure (cholinesterases and β-glucuronidase), cortisol (CT) and progesterone (PG) levels, as well as glycemia, were determined. Parameters of liver injury were assayed by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT); liver function was assayed by measuring albumin. Biomonitoring carried out during the pre-spraying period (PreS) and spraying period (SP) showed that the population studied was exposed to OPs, proven by the fact that plasma (PCh) and erythrocyte cholinesterase (AChE) decreased very significantly (pnormal values for the general population, the increase in CT in the maternal compartment may lead to impaired newborn health later in life.

  18. Eleutheroside B or E enhances learning and memory in experimentally aged rats★ (United States)

    Huang, Debin; Hu, Zehua; Yu, Zhaofen


    Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer's disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E (50, 100, 200 mg/kg), and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons. PMID:25206404

  19. Eleutheroside B or E enhances learning and memory in experimentally aged rats. (United States)

    Huang, Debin; Hu, Zehua; Yu, Zhaofen


    Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer's disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E (50, 100, 200 mg/kg), and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.

  20. Cholinergic enzymes and inflammatory markers in rats infected by Sporothrix schenckii. (United States)

    Castro, Veronica S P; Da Silva, Aleksandro S; Costa, Márcio M; Paim, Francine C; Alves, Sydney H; Lopes, Sonia T A; Silva, Cássia B; Wolkmer, Patrícia; Castro, Jorge Luiz C; Cecco, Bianca S; Duarte, Marta M M F; Schetinger, Maria Rosa C; Graça, Dominguita L; Andrade, Cinthia M


    The aim of this study was to evaluate the cholinesterase activity in serum, whole blood, and lymphocytes, as well as to verify its relation to immune response in rats experimentally infected by Sporothrix schenckii. For this study, 63 Wistar rats (Rattus norvegicus), male, adult were divided into three groups: the negative control group (GC: n = 21), the group infected subcutaneously (GSC: n = 21), and the group infected intraperitoneally (GIP: n = 21). The groups were divided into subgroups and the following variables were evaluated at 15, 30, and 40 days post-infection (PI): acetylcholinesterase (AChE) activity in lymphocytes and whole blood, butyrylcholinesterase (BChE) activity in serum, cytokines levels (IL-1, IL-6, TNFα, and INF-γ), immunoglobulins levels (IgA, IgG, IgM, and IgE), and protein profile by electrophoresis. Both infected groups showed increased levels of inflammatory parameters (P schenckii infections in animals. Therefore, it is concluded that cholinesterase has an important modulatory role in the immune response during granulomatous infection by S. schenckii.

  1. Molecular targets for organophosphates in the central nervous system. Midterm report, 18 May 1995-17 November 1996

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    Albuquerque, E.X.


    In this study, the patch-clamp technique was used as an approach to evaluate the pre- and postsynaptic effects of VX and soman on synaptic currents of cultured hippocampal neurons. Compared to control, the frequency of the currents mediated by the activation of GABA or glutamate receptors was increased in a concentration-dependent manner from 200% to 550%, when exposed to VX from 10 nM to 1 pM. The effect of VX was observed in the presence of TTX and atropine, indicating that it was a presynaptic effect unrelated to the activation of muscarinic receptors. In addition, it was found that the dlhydron-B-erythroldine did not prevent or abolished the effects of VX. Because, either soman or acetylcholine at high concentrations, applied for 5 to 10 min to the cultured neurons did not mimic the potentiation of transmitter release induced by VX, it was concluded that the presynaptic effect of VX was unrelated to the inhibition of cholinesterase enzyme. At the concentrations studied, VX and soman did not change the post-synaptic properties of GABAA, NMDA, and AMPA receptors. The effect of VX was markedly reduced when the extracellular calcium was removed, but was unaffected when the calcium channel blocker verapamil was added to the preparation. The present findings shows that VX exerts a presynaptic effect unrelated to cholinesterase enzyme that is unaffected by the common antidote atropine used for treating intoxication with VX.

  2. New beverages of lemon juice enriched with the exotic berries maqui, açaı́, and blackthorn: bioactive components and in vitro biological properties. (United States)

    Gironés-Vilaplana, Amadeo; Valentão, Patrícia; Moreno, Diego A; Ferreres, Federico; García-Viguera, Cristina; Andrade, Paula B


    Following previous research on lemon juice enriched with berries, the aim of this work was to design new blends based on lemon juice mixed with different edible berries of exotic and national origin: maqui ( Aristotelia chilensis (Molina) Stuntz), açaı́ ( Euterpe oleracea Mart.), and blackthorn ( Prunus spinosa L.). The phytochemical characterization of controls and blends was performed by HPLC-DAD-ESI/MS(n). Their antioxidant capacity against DPPH, superoxide, and hydroxyl radicals and hypochlorous acid and their potential to inhibit cholinesterases were also assessed. The profiling of the red fruits and lemon revealed a wide range of bioactive phenolics. The novel beverage based on lemon juice and maqui berry (LM) was the most interesting blend in terms of antioxidant capacity. Berry control samples displayed reduced effects on acetylcholinesterase and butyrylcholinesterase, the lemon juice control being always the most active. This activity was also remarkable for lemon-blackthorn (LB) and lemon-açaı́ (LA) blends, the last being the most effective inhibitor of cholinesterases among all samples. The results suggested that lemon juice enriched with berries could be of potential interest in the design of new drinks with a nutritive related function on health for chronic diseases.

  3. Evaluation of the antiamnesic effects of Phyllanthus amarus in mice.

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    Hanumanthachar Joshi


    Full Text Available Alzheimer’s disease is a progressive neurodegenerative disorder characterized by a gradual decline in memory. Phyllanhus amarus is commonly known as bhumi amla in India and is traditionally used since centuries in ayurveda medicine. The present study was undertaken to investigate the effects of Phyllanhus amarus (PA on cognitive functions and brain cholinesterase activity in mice. Elevated plus maze and passive avoidance paradigm were employed to evaluate learning and memory parameters. Three doses (50, 100 and 200 mg/kg, p.o. of aqueous extract of PA were administered for 8 successive days to both young and aged mice. PA (50, 100 and 200 mg/kg produced a dose-dependent improvement in memory scores of young and older mice. PA also reversed successfully the amnesia induced by scopolamine (0.4 mg/kg, i.p. and diazepam (1 mg/kg, i.p.. Interestingly, brain acetyl cholinesterase activity was also reduced. The underlying mechanism of action for the observed nootropic effect may be attributed to pro-cholinergic activity exhibited by PA in the present study. Therefore, it would be worthwhile to explore the therapeutic potential of PA in the management of patients with cognitive disorders.

  4. Evaluation of the antiamnesic effects of Phyllanthus amarus in mice

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    Hanumanthachar Joshi


    Full Text Available Alzheimer’s disease is a progressive neurodegenerative disorder characterized by a gradual decline in memory. Phyllanhus amarus is commonly known as bhumi amla in India and is traditionally used since centuries in ayurveda medicine. The present study was undertaken to investigate the effects of Phyllanhus amarus (PA on cognitive functions and brain cholinesterase activity in mice. Elevated plus maze and passive avoidance paradigm were employed to evaluate learning and memory parameters. Three doses (50, 100 and 200 mg/kg, p.o. of aqueous extract of PA were administered for 8 successive days to both young and aged mice. PA (50, 100 and 200 mg/kg produced a dose-dependent improvement in memory scores of young and older mice. PA also reversed successfully the amnesia induced by scopolamine (0.4 mg/kg, i.p. and diazepam (1 mg/kg, i.p.. Interestingly, brain acetyl cholinesterase activity was also reduced. The underlying mechanism of action for the observed nootropic effect may be attributed to pro-cholinergic activity exhibited by PA in the present study. Therefore, it would be worthwhile to explore the therapeutic potential of PA in the management of patients with cognitive disorders.

  5. MR Prediction of Liver Function and Pathology Using Gd-EOB-DTPA: Effect of Liver Volume Consideration

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    Dai Shimamoto


    Full Text Available Purpose. To evaluate whether the diagnostic performance of Gd-EOB-DTPA-enhanced MRI in evaluating liver function and pathology is improved by considering liver volume (LV. Methods. This retrospective study included 104 patients who underwent Gd-EOB-DTPA-enhanced MRI before liver surgery. For each patient, using the precontrast and hepatobiliary phase images, we calculated the increase rate of the liver-to-spleen signal intensity ratio (LSR, that is, the “ΔLSR,” and the increase rate of the liver-to-muscle signal intensity ratio (LMR, that is, the “ΔLMR.” ΔLSR × LV and ΔLMR × LV were also calculated. The correlation of each MR parameter with liver function data or liver pathology was assessed. The correlation coefficients were compared between ΔLSR (ΔLMR and ΔLSR (ΔLMR × LV. Results. The correlation coefficient between ΔLSR (ΔLMR × LV and cholinesterase was significantly higher than that between ΔLSR (ΔLMR and cholinesterase. The correlation coefficient between ΔLSR (ΔLMR × LV and the degree of fibrosis or necroinflammatory activity was significantly lower than that between ΔLSR (ΔLMR and the degree of fibrosis or necroinflammatory activity. Conclusion. The inclusion of liver volume may improve Gd-EOB-DTPA-based predictions of liver function, but not in predictions of liver pathology.

  6. Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents

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    Mehlika Dilek Altıntop


    Full Text Available New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl-1-([1,1′-biphenyl]-4-ylmethylenethiosemicarbazide (5 was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells. Compound 5 increased early and late apoptosis in A549 and C6 cells. Compound 5 also caused disturbance on mitochondrial membrane potential and showed DNA synthesis inhibitory activity in A549 and C6 cells. Compound 5 was investigated for SIRT1 inhibitory activity to provide mechanistic insight and for that purpose docking studies were also performed for this compound on SIRT1. On the other hand, compound 5 did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between anticancer activity of compound 5 and cholinesterases.

  7. Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii

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    Sparling, D.W. [Cooperative Wildlife Research Laboratory, Department of Zoology and Center for Ecology, Southern Illinois University, LS II, MS6504, Carbondale, IL 62901 (United States)]. E-mail:; Fellers, G. [Western Ecology Research Center, U.S. Geological Survey, Point Reyes National Seashore, Point Reyes, CA 94956 (United States)


    Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24 h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations. - Laboratory tests on the toxicity of OP insecticides and their oxons suggest that they may be acutely lethal to amphibians at ecologically relevant concentrations.

  8. Evaluation of the effect of Ferula asafoetida Linn. gum extract on learning and memory in Wistar rats

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    Full Text Available Objective: Memory loss is universal and is the first symptom to manifest in majority of the patients suffering from Alzheimer′s disease. This study is designed to investigate the effect of Ferula asafoetida linn. (F. foetida extract on learning and memory in rats. Materials and Methods: Learning and memory were evaluated using elevated plus maze and passive avoidance paradigm after the oral administration of two doses (200 mg/kg and 400 mg/kg of F. foetida aqueous extract with rivastigmine as positive control. Brain cholinesterase activity, serum thiols and cholesterol were also estimated. Results: Extract produced significant improvement in memory score i.e. step through latency at 400 mg/kg dose in passive avoidance model (P< 0.05 and dose-dependent improvement of transfer latency in elevated plus maze model (P< 0.001. Dose-dependent inhibition of brain cholinesterase (P< 0.001 and significant improvement in antioxidant levels (P< 0.05 were also noted. Conclusions: Memory enhancing potential of F. foetida can be attributed to acetylcholinesterase inhibiting and antioxidant properties. Hence, dietary usage of F. foetida is beneficial and can also be employed as an adjuvant to existing anti-dementia therapies.

  9. Eleutheroside B or E enhances learning and memory in experimentally aged rats

    Institute of Scientific and Technical Information of China (English)

    Debin Huang; Zehua Hu; Zhaofen Yu


    Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer's disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E (50, 100, 200 mg/kg), and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.

  10. Methyl parathion and fenvalerate toxicity in American kestrels: Acute physiological responses and effects of cold (United States)

    Rattner, B.A.; Franson, J.C.


    Physiological and toxicological effects of p.o. methyl parathion (0.375-3.0 mg/kg) or fenvalerate (1000-4000 mg/kg) were examined over a 10-h period in American kestrels (Falco sparverius) maintained in thermoneutral (22?C) and cold (-5?C) environments. Methyl parathion was highly toxic (estimated median lethal dose of 3.08 mg/kg, 95% confidence limits of 2.29 -4.14 mg/kg), producing dose-dependent inhibition of brain and plasma cholinesterase activity, hyperglycemia, and elevated plasma corticosterone concentration. Brain and plasma cholinesterase inhibition in excess of 50% was associated with transient but pronounced hypothermia 2 h after intubation, although the magnitude of this response was yariable. Fenvalerate, at doses far exceeding those encountered in the environment, caused mild intoxication and elevated plasma alanine aminotransferase activity. Cold intensified methyl parathion toxicity, but did not affect that of fenvalerate. Thus, it would appear that organophosphorus insecticides pose far greater hazard than pyrethroids to raptorial birds.

  11. Galantamine-ER for the treatment of mild-to-moderate Alzheimer’s disease

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    Ben Seltzer


    Full Text Available Ben SeltzerGeriatric Research, Education and Clinical Center, VA Boston Healthcare System, Department of Neurology, Harvard Medical School, Boston, MA, USAAbstract: An extended release form of the cholinesterase inhibitor (ChEI drug galantamine (galantamine-ER was developed, chiefly to increase adherence to medication regimes in patients with mild-to-moderate Alzheimer’s disease (AD. Except for predicted differences in (Cmax and tmax, comparable doses of once daily galantamine-ER and regular, immediate release galantamine, (galantamine-IR, are pharmacologically equivalent. A 24-week randomized, double-blind, placebo-and active-controlled, multicenter phase III trial, which compared galantamine-IR, galantamine-ER and placebo in subjects with mild to moderate AD (mini-mental state examination [MMSE] score range, 10 to 24 showed that both formulations of galantamine were significantly better than placebo in terms of cognition, although not with regard to global change. There was no difference in drug-related adverse events between galantamine-ER and galantamine-IR. Since its release onto the market galantamine-ER has enjoyed wide popularity and a recent surveillance study suggests that it has the highest 1-year persistence rate of all the ChEIs.Keywords: galantamine, cholinesterase inhibitors, Alzheimer’s disease

  12. Determination of 3,5,6-trichloro-2-pyridinol levels in the urine of termite control workers using chlorpyrifos.

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    Full Text Available Chlorpyrifos, an organophosphorus insecticide, has been used to control termites since regulatory measures against the use of chlordanes were taken in September, 1986. We developed an improved gas chromatographic (GC method for the assay of 3,5,6-trichloro-2-pyridinol (TCP in the urine to use in the biological monitoring of exposure to chlorpyrifos. Urinary TCP was separated and determined accurately (C.V., 4% with high sensitivity (detection limit, 10 ng/ml and recovery (recovery greater than 90% using a wide bore capillary column (WBC column. The accuracy and precision of the present GC method are satisfactory. The time course of urinary excretion of TCP was followed in workers. The urinary TCP level was low in the off-season and high in the busy season. Variation in the urinary TCP level corresponded to the termite control season and the length of the working period. The urinary TCP level showed a change reciprocal to the variations in the plasma cholinesterase activity. From these results, it is surmised that the urinary TCP level represents the extent of exposure to chlorpyrifos. The decrease in the level of cholinesterase activity is suggested to be due to exposure to chlorpyrifos. Determination of the urinary TCP level by GC using a WBC column is useful in the biological monitoring of chlorpyrifos in termite control workers and potentially has practical application to health care.

  13. Antiamnesic potential of Murraya koenigii leaves. (United States)

    Vasudevan, Mani; Parle, Milind


    Murraya koenigii leaves commonly known as curry patta are added routinely to Indian gravy and vegetarian dishes as a favorite condiment. The effects of Murraya koenigii leaves (MKL) on cognitive functions, total serum cholesterol level and brain cholinesterase activity in young and aged mice fed orally with a diet containing 2%, 4% and 8% w/w of MKL for 30 days consecutively, were investigated. The memory scores were measured using various exteroceptive and interoceptive behavioral models. The MKL diets produced a significant dose-dependent improvement in the memory scores of young and aged mice and significantly reduced the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Also, brain cholinesterase activity and total cholesterol levels were reduced by the MKL diets. The underlying mechanism of action for the observed nootropic effect may be attributed to pro-cholinergic activity and a cholesterol lowering property. Therefore, it would be worthwhile to investigate specifically the therapeutic potential of MKL in the management of Alzheimer patients.

  14. Does organophosphate poisoning cause cardiac injury? (United States)

    Aghabiklooei, Abbas; Mostafazadeh, Babak; Farzaneh, Esmaeil; Morteza, Afsaneh


    Organophosphates are insecticides which are widely used as a suicidal agent in Iran. They are associated with different types of cardiac complications including cardiac arrest and arrhythmia, however their role in cardiac injury is not known yet. The aim of this study was to investigate the presence of myocardial damage in patients with cholinesterase poisoning.It was a prospective study conducted from January 2008 to March 2010. Cohorts of patients with cholinesterase poisoning due to suicidal attempt who have been referred to Loghman hospital were selected. Patients who have taken more than one poison or were used concomitant drugs were excluded. Physical examination was performed on admission to discover warning sign. Peripheral arterial blood gases, creatine kinase, creatine kinase-myocardial band, troponin-T measurements were performed in all cases. There were 24 patients, 7 of them women, with the mean age of 41.2±15.05 who were included in this study. Non-survivors had significantly higher levels of systolic blood pressure, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide, bicarbonate Glasgow Coma Scale scoring and longer duration of mechanical ventilation. Our findings showed that cardiac injury is an important cause of death in organophosphate poisoning. It could be hypothesized that cardiac injury is a strong predictor of death in patients with organophosphate poisoning.

  15. The possible role of intravenous lipid emulsion in the treatment of chemical warfare agent poisoning

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    Arik Eisenkraft


    Full Text Available Organophosphates (OPs are cholinesterase inhibitors that lead to a characteristic toxidrome of hypersecretion, miosis, dyspnea, respiratory insufficiency, convulsions and, without proper and early antidotal treatment, death. Most of these compounds are highly lipophilic. Sulfur mustard is a toxic lipophilic alkylating agent, exerting its damage through alkylation of cellular macromolecules (e.g., DNA, proteins and intense activation of pro-inflammatory pathways. Currently approved antidotes against OPs include the peripheral anticholinergic drug atropine and an oxime that reactivates the inhibited cholinesterase. Benzodiazepines are used to stop organophosphate-induced seizures. Despite these approved drugs, efforts have been made to introduce other medical countermeasures in order to attenuate both the short-term and long-term clinical effects following exposure. Currently, there is no antidote against sulfur mustard poisoning. Intravenous lipid emulsions are used as a source of calories in parenteral nutrition. In recent years, efficacy of lipid emulsions has been shown in the treatment of poisoning by fat-soluble compounds in animal models as well as clinically in humans. In this review we discuss the usefulness of intravenous lipid emulsions as an adjunct to the in-hospital treatment of chemical warfare agent poisoning.

  16. Crystal structure, phytochemical study and enzyme inhibition activity of Ajaconine and Delectinine (United States)

    Ahmad, Shujaat; Ahmad, Hanif; Khan, Hidayat Ullah; Shahzad, Adnan; Khan, Ezzat; Ali Shah, Syed Adnan; Ali, Mumtaz; Wadud, Abdul; Ghufran, Mehreen; Naz, Humera; Ahmad, Manzoor


    The Crystal structure, comparative DFT study and phytochemical investigation of atisine type C-20 diterpenoid alkaloid ajaconine (1) and lycoctonine type C-19 diterpenoid alkaloid delectinine (2) is reported here. These compounds were isolated from Delphinium chitralense. Both the natural products 1 and 2 crystallize in orthorhombic crystal system with identical space group of P212121. The geometric parameters of both compounds were calculated with the help of DFT using B3LYP/6-31+G (p) basis set and HOMO-LUMO energies, optimized band gaps, global hardness, ionization potential, electron affinity and global electrophilicity are calculated. The compounds 1 and 2 were screened for acetyl cholinesterase and butyryl cholinesterase inhibition activities in a dose dependent manner followed by molecular docking to explore the possible inhibitory mechanism of ajaconine (1) and delectinine (2). The IC50 values of tested compounds against AChE were observed as 12.61 μM (compound 1) and 5.04 μM (compound 2). The same experiments were performed for inhibition of BChE and IC50 was observed to be 10.18 μM (1) and 9.21 μM (2). Promising inhibition activity was shown by both the compounds against AChE and BChE in comparison with standard drugs available in the market such as allanzanthane and galanthamine. The inhibition efficiency of both the natural products was determined in a dose dependent manner.

  17. Inhibition of acetylcholinesterase in guppies (Poecilia reticulata) by chlorpyrifos at sublethal concentrations: Methodological aspects

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    van der Wel, H.; Welling, W.


    Acetylcholinesterase activity is a potential biochemical indicator of toxic stress in fish and a sensitive parameter for testing water for the presence of organophosphates. A number of methodological aspects regarding the determination of the in vivo effect of chlorpyrifos on acetylcholinesterase in guppies have been investigated. It was found that with acetylthiocholine as a substrate, the contribution of pseudocholinesterase to the total cholinesterase activity can be neglected. Protection of acetylcholinesterase of guppies exposed to chlorpyrifos from additional, artifactual in vitro enzyme inhibition during homogenization is necessary. Very low concentrations of acetone in the exposure medium, resulting from dilution of the stock solution of chlorpyrifos in acetone, can result in large decreases in the oxygen content of this medium. This may affect the uptake rate of the toxic compound and, thereby, cholinesterase inhibition. Very low, sublethal concentrations of chlorpyrifos result in high inhibition levels of acetylcholinesterase (80-90%) in guppies within 2 weeks of continuous exposure. Recovery of the enzyme activity occurs after the exposed animals are kept in clean medium for 4 days, but the rate of recovery is considerably lower than the rate of inhibition.

  18. Cognitive Dysfunction and its Determinants in Patients with Neurocysticercosis (United States)

    Varghese, Vinod; Chandra, Sadanandavalli Retnaswami; Christopher, Rita; Rajeswaran, Jamuna; Prasad, Chandrajit; Subasree, R.; Issac, Thomas Gregor


    Introduction: Neurocysticercosis (NCC) is the most common parasitic infection of man. In addition to a headache, seizures, and focal deficits, this is associated with significant cognitive dysfunction. Many studies revealed that the number and location of lesions are not always responsible for cognitive dysfunction. Cholinesterase and pseudocholinesterase are found in the walls of the cysticercus which could contribute to cholinergic depletion and thus cognitive dysfunction. Patients and Methods: A total of 43 patients who presented with NCC were evaluated for cognitive deficits, as well as cholinesterase levels in cerebrospinal fluid (CSF) with control CSF from patients undergoing spinal anesthesia. Blood levels of interleukin-10 and tumor necrosis factor alpha were also estimated and correlated with cognitive deficits. Results: There is a mild increase in the acetylcholinesterase in CSF of patients compared to controls, but it did not correlate with cognitive deficits. There is an increase in interleukins to a significant level which correlates with vesicular stage of the organism and cognitive impairment. The number of lesions also correlated with cognitive impairment even though the location did not. The domains of cognitive deficits seen are sustained attention, category fluency, verbal working memory, planning, set shifting, verbal learning, visual memory, and construction. Discussion and Conclusion: NCC is associated with multi-domain cognitive impairment correlates with vescicular stage, proinflammatory cytokines and number of lesions but not location, vesicular stage, and proinflammatory cytokines. PMID:27114627

  19. Lipophilic properties of anti-Alzheimer's agents determined by micellar electrokinetic chromatography and reversed-phase thin-layer chromatography. (United States)

    Godyń, Justyna; Hebda, Michalina; Więckowska, Anna; Więckowski, Krzysztof; Malawska, Barbara; Bajda, Marek


    Lipophilicity as one of the most important physicochemical properties of the biologically active compounds is closely related to their pharmacokinetic parameters and therefore, it is taken into account at the design stage of new drugs. Among the novel, fast and reliable methods for determination of the lipophilicity of compounds micellar electrokinetic chromatography (MEKC) is considered to be an appropriate one for bioactive molecules, as it closely mimics the physiological conditions. In this paper MEKC was used for the estimation of log P values for 49 derivatives of phthalimide, tetrahydroisochinoline and indole, designed and synthesized as potential anti-Alzheimer's agents with cholinesterase inhibitory activity. RP-TLC method was applied for determination of another lipophilicity descriptor - RM0 . The results of both experimental methods were compared with each other giving satisfactory correlation (R = 0.784), and with computational methods (Marvin, ChemOffice Software) resulting in weaker correlation (R = 0.466 - 0.687). The lipophilicity-activity relationship was finally established, showing significant influence of lipophilicity on cholinesterase inhibition in some subgroups of phthalimide derivatives. This article is protected by copyright. All rights reserved.

  20. Traditionally Used Lathyrus Species: Phytochemical Composition, Antioxidant Activity, Enzyme Inhibitory Properties, Cytotoxic Effects, and in silico Studies of L. czeczottianus and L. nissolia (United States)

    Llorent-Martínez, Eulogio J.; Zengin, Gokhan; Fernández-de Córdova, María L.; Bender, Onur; Atalay, Arzu; Ceylan, Ramazan; Mollica, Adriano; Mocan, Andrei; Uysal, Sengul; Guler, Gokalp O.; Aktumsek, Abdurrahman


    Members of the genus Lathyrus are used as food and as traditional medicines. In order to find new sources of biologically-active compounds, chemical and biological profiles of two Lathyrus species (L. czeczottianus and L. nissolia) were investigated. Chemical profiles were evaluated by HPLC-ESI-MSn, as well as by their total phenolic and flavonoid contents. In addition, antioxidant, enzyme inhibitory, and cytotoxic effects were also investigated. Antioxidant properties were tested by using different assays (DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelation). Cholinesterases (AChE and BChE), tyrosinase, α-amylase, and α-glucosidase were used to evaluate enzyme inhibitory effects. Moreover, vitexin (apigenin-8-C-glucoside) and 5-O-caffeoylquinic acid were further subjected to molecular docking experiments to provide insights about their interactions at molecular level with the tested enzymes. In vitro cytotoxic effects were examined against human embryonic kidney cells (HEK293) by using iCELLigence real time cell analysis system. Generally, L. czeczottianus exhibited stronger antioxidant properties than L. nissolia. However, L. nissolia had remarkable enzyme inhibitory effects against cholinesterase, amylase and glucosidase. HPLC-ESI-MSn analysis revealed that flavonoids were major components in these extracts. On the basis of these results, Lathyrus extracts were rich in biologically active components; thus, these species could be utilized to design new phytopharmaceutical and nutraceutical formulations. PMID:28289386


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    Obed Ahmed Ansari, J.S. Tripathi and Sayema Ansari


    Full Text Available Life expectancy is increasing as a result of advancement in medical science and the availability of better healthcare services. As the risk of dementia increases with increasing age, the number of persons with dementia in the general population is also rising. Alzheimer’s disease is the most common form of dementia, accounting for approximately 70% of the dementia cases. So far, efforts to find a cure for Dementia have been disappointing, and the drugs currently available to treat the disease address only its symptoms and with limited effectiveness. Apart from genetic susceptibility, chronic exposure to other toxins, free -radical damage, Diabetes, high blood pressure, and high cholesterol, high homocysteine level are the major risk factors for Alzheimer’s and stroke-related dementia. Reducing oxidative stress by anti-oxidants, protecting brain inflammatory lesions using anti-inflammatory drugs and facilitation of brain cholinergic neurotransmission with anti-cholinesterase are some positive approaches to management for dementia especially in Alzheimer’s disease. Saraswata ghrita, a polyherbal medhya compound drug used in traditional medicine for cognition and memory related problems is blended with the drugs, which exert a variety of pharmacological actions including anti-inflammatory, anti-amyloidogenic, anti-cholinesterase, hypolipidemic, and antioxidant properties. This paper encompasses the brief descriptive information of different scientific studies on various ingredients of Saraswata ghrita.


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    Ladde Shivakumar


    Full Text Available The learning and memory is closely associated with the functional status of the central cholinergic system and others monoamines. Based on literature in ayurveda, SHRUSHTI a Herbal Pharma Industry of Bangalore has come out with the Polyherbal formulation SR-105 for Memory enhancing activity; consisting of plant ingredients like Convolvulus miorophyllus, Celastrus paniculata, Acorus calamus and Bacopa monniera. Hence in the present work an effort has been made to identify the Memory enhancing activity of SR-105 in experimental animals studies i.e., scopolamine-induced amnesia on active avoidance paradigm and inhibition of cholinesterase activity in rats brain. The LD50 studies of SR-105 were conducted according to OECD guidelines No.425; up to 2000 mg/kg the formulation had not produced any mortality. Piracetam and the different doses of polyherbal formulation SR-105 treated groups had shown decreased the time spent in shock zone and number of errors on active avoidance paradigm and also shows dose dependent inhibition of cholinesterase enzyme activity. In the light of above, it may be worthwhile to explore the potential of this SR-105 polyherbal formulation in the management of Alzheimer’s disease.

  3. Lycopene modulates cholinergic dysfunction, Bcl-2/Bax balance, and antioxidant enzymes gene transcripts in monosodium glutamate (E621) induced neurotoxicity in a rat model. (United States)

    Sadek, Kadry; Abouzed, Tarek; Nasr, Sherif


    The effect of monosodium glutamate (MSG) on brain tissue and the relative ability of lycopene to avert these neurotoxic effects were investigated. Thirty-two male Wistar rats were distributed into 4 groups: group I, untreated (placebo); group II, injected with MSG (5 mg·kg(-1)) s.c.; group III, gastrogavaged with lycopene (10 mg·kg(-1)) p.o.; and group IV received MSG with lycopene with the same mentioned doses for 30 days. The results showed that MSG induced elevation in lipid peroxidation marker and perturbation in the antioxidant homeostasis and increased the levels of brain and serum cholinesterase (ChE), total creatine phosphokinase (CPK), creatine phosphokinase isoenzymes BB (CPK-BB), and lactate dehydrogenase (LDH). Glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities and gene expression were increased and glutathione content was reduced in the MSG-challenged rats, and these effects were ameliorated by lycopene. Furthermore, MSG induced apoptosis in brain tissues reflected in upregulation of pro-apoptotic Bax while lycopene upregulated the anti-apoptotic Bcl-2. Our results indicate that lycopene appears to be highly effective in relieving the toxic effects of MSG by inhibiting lipid peroxidation and inducing modifications in the activity of cholinesterase and antioxidant pathways. Interestingly, lycopene protects brain tissue by inhibiting apoptosis signaling induced by MSG.

  4. Physiological measures of neurotoxicity of diazinon and malathion to larval rainbow trout (Oncorhynchus mykiss) and their correlation with behavioral measures (United States)

    Beauvais, S.L.; Jones, S.B.; Brewer, S.K.; Little, E.E.


    Relations between neurotoxicants and changes in physiological parameters and behavior were investigated in larval rainbow trout (RBT; Oncorhynchus mykiss) exposed to sublethal concentrations of two organophosphate pesticides (OPs). Fish were exposed to diazinon and malathion in static-renewal experiments. After exposures for 24, 96, or 96 h, followed by 48 h of recovery, individual RBT were videotaped to assess locomotory behaviors. Brain tissue from the same fish was assayed for the physiological endpoints, cholinesterase (ChE) activity, muscarinic cholinergic receptor (MChR) number (B(max)), and MChR affinity (K(D)). Cholinesterase activity decreased significantly with increasing concentrations of both diazinon and malathion and differed significantly among exposure durations, with 24- and 96-h means less than 48-h recovery means. Decreases in B(max) with OP concentration were not significant for either chemical, and K(D) was unaffected. Changes in swimming speed and distance were significantly correlated with changes in ChE activity for both chemicals; rate of turning was significantly correlated with ChE activity in malathion exposures. These results suggest that correlations between physiological and behavioral changes previously seen in mammals also occur in fish.

  5. Selective reversal of muscle relaxation in general anesthesia: focus on sugammadex

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    Sorin J Brull


    Full Text Available Sorin J Brull1, Mohamed Naguib21Department of Anesthesiology, Mayo Clinic College of Medicine, Mayo Clinic Hospital, Jacksonville, FL, USA; 2Department of Anesthesiology and Pain Medicine, The University of Texas M D Anderson Cancer Center,  Houston, TX, USAAbstract: Despite the significant improvements in the pharmacology of muscle relaxants in the past six decades, the search for the ideal muscle relaxant continues, mainly because of the incomplete efficacy and persistent side effects associated with their antagonism. Clinical concerns remain about the residual paralysis and hemodynamic side effects associated with the classic pharmacologic reversal agents, the acetylcholinesterase inhibitors. Although the development of the “ideal muscle relaxant” remains illusory, pharmacologic advancements hold promise for improved clinical care and patient safety. Recent clinical advances include the development of short-acting nondepolarizing muscle relaxant agents that have fast onset and a very rapid metabolism that allows reliable and complete recovery; and the development of selective, “designer” reversal agents that are specific for a single drug or class of drugs. This article reviews recent developments in the pharmacology of these selective reversal agents: plasma cholinesterases, cysteine, and sugammadex. Although each of the selective reversal agents is specific in its substrate, the clinical use of the combination of muscle relaxant with its specific reversal agent will allow much greater intraoperative titrating ability, decreased side effect profile, and may result in a decreased incidence of postoperative residual paralysis and improved patient safety.Keywords: selective reversal agents, cysteine, plasma cholinesterases, sugammadex

  6. Occupational pesticide intoxications among farmers in Bolivia: a cross-sectional study

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    Huici Omar


    Full Text Available Abstract Background Pesticide use and its consequences are of concern in Bolivia due to an intensive and increasing use. Methods To assess the magnitude and reasons for occupational pesticide intoxication, a cross-sectional study with interviews and blood-tests was performed among 201 volunteer farmers from 48 villages in the temperate and subtropical valleys in the eastern part of the Andes Mountains in Bolivia. Of these 171 male farmers using pesticides in their agricultural production were used in the statistical analysis, including linear- and logistic regression analysis. Results This study documented a frequent use of the most toxic pesticides among farmers who have had almost no instructions in how to use pesticides and protect themselves against the dangers of intoxication, reflected in the hazardous practices used when handling pesticides. Symptoms of intoxications were common in connection with spraying operations. The risk of experiencing symptoms and the serum cholinesterase activity were influenced by whether or not organophosphates were used and the number of times sprayed. The experience of symptoms was moreover influenced by the hygienic and personal protective measures taken during spraying operations while this had no influence on the serum cholinesterase level. Conclusion The study showed that occupational pesticide intoxications were common among farmers and did depend on multiple factors. Pesticide use is probably one of the largest toxicological problems in Bolivia, and a coordinated action by authorities, society and international bodies is needed to limit the number of intoxications and the environmental pollution.

  7. ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer's Disease Therapy (United States)

    Marco-Contelles, José; Unzeta, Mercedes; Bolea, Irene; Esteban, Gerard; Ramsay, Rona R.; Romero, Alejandro; Martínez-Murillo, Ricard; Carreiras, M. Carmo; Ismaili, Lhassane


    Highlights: ASS2324 is a hybrid compound resulting from the juxtaposition of donepezil and the propargylamine PF9601NASS2324 is a multi-target directed propargylamine able to bind to all the AChE/BuChE and MAO A/B enzymesASS2324 shows antioxidant, neuroprotective and suitable permeability propertiesASS2324 restores the scopolamine-induced cognitive impairment to the same extent as donepezil, and is less toxicASS2324 prevents β-amyloid induced aggregation in the cortex of double transgenic miceASS2324 is the most advanced anti-Alzheimer agent for pre-clinical studies that we have identified in our laboratories The complex nature of Alzheimer's disease (AD) has prompted the design of Multi-Target-Directed Ligands (MTDL) able to bind to diverse biochemical targets involved in the progress and development of the disease. In this context, we have designed a number of MTD propargylamines (MTDP) showing antioxidant, anti-beta-amyloid, anti-inflammatory, as well as cholinesterase and monoamine oxidase (MAO) inhibition capacities. Here, we describe these properties in the MTDL ASS234, our lead-compound ready to enter in pre-clinical studies for AD, as a new multipotent, permeable cholinesterase/monoamine oxidase inhibitor, able to inhibit Aβ-aggregation, and possessing antioxidant and neuroprotective properties. PMID:27445665

  8. Studies on the Purification and Characterization of Soybean Esterase,and Its Sensitivity to Organophosphate and Carbamate Pesticides

    Institute of Scientific and Technical Information of China (English)

    LI Jian-ke; ZHOU Yan-li; WEN Yan-xia; WANG Jian-hua; HU Qiu-hui


    Soybean esterase,a cholinesterase-like enzyme,was purified by differential centrifugation firstly,then,ammonium sulfate precipitation,dialysis,and finally,DEAE-cellulose-32 ion-exchange chromatography after extracting it from soybean seeds with phosphate buffer(0.3 mol L-1,pH 7.0).The extract recovery rate of the purified enzyme was 8.18% and purification fold was 91.58.The soybean esterase appeared as two bands on the denaturing SDS-PAGE with molecular weights of 24 and 37.2 kDa,respectively,which proved that it is a dimer protein consisting of two subunits.The result of nondenaturing PAGE revealed that the soybean esterase is a single band with cholinesterase-like activity using α-naphthyl acetate as the substrate and fast blue B salt as coloring agent.The esterase showed very high sensitivity to 18 kinds of organophosphate pesticides and 6 kinds of carbamate pesticides with the lowest detective limits of 0.03125-0.0625 and 0.03 125-0.25 mg kg-1,respectively,and can meet the demands of MRL specified by the most countries.

  9. 2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase. (United States)

    Leong, Sze Wei; Abas, Faridah; Lam, Kok Wai; Shaari, Khozirah; Lajis, Nordin H


    In the present study, a series of 2-benzoyl-6-benzylidenecyclohexanone analogs have been synthesized and evaluated for their anti-cholinesterase activity. Among the forty-one analogs, four compounds (38, 39, 40 and 41) have been identified as lead compounds due to their highest inhibition on both AChE and BChE activities. Compounds 39 and 40 in particular exhibited highest inhibition on both AChE and BChE with IC50 values of 1.6μM and 0.6μM, respectively. Further structure-activity relationship study suggested that presence of a long-chain heterocyclic in one of the rings played a critical role in the dual enzymes' inhibition. The Lineweaver-Burk plots and docking results suggest that both compounds could simultaneously bind to the PAS and CAS regions of the enzyme. ADMET analysis further confirmed the therapeutic potential of both compounds based upon their high BBB-penetrating. Thus, 2-benzoyl-6-benzylidenecyclohexanone containing long-chain heterocyclic amine analogs represent a new class of cholinesterase inhibitor, which deserve further investigation for their development into therapeutic agents for cognitive diseases such as Alzheimer.

  10. Contaminant studies in the Sierra Nevadas (United States)

    Sparling, D.W.; Fellers, G.


    full text: Several species of anuran amphibians (frogs and toads) are experiencing severe population declines in even seemingly pristine areas of the Sierra Mountains of California. Among the most severely depressed species are the redlegged frog, the foothill and mountain yellow-legged frogs, the Yosemite toad, and the Cascades frog. Several factors, such as habitat fragmentation, introduced predators (especially fish), and disease, have been linked to these declines. But recent evidence from a USGS-led study shows that contaminants are a primary factor. During the past three years, researchers from the USGS Patuxent Wildlife Research Center, the Western Ecology Research Center, the USDA Beltsville Agriculture Research Center, and the Texas A&M University have teamed up to conduct an extensive study on airborne pesticides and their effects on amphibian populations in the Sierra Nevada Mountains. Previous work on environmental chemistry demonstrated that pesticides from the intensely agricultural Central Valley of California are being blown into the more pristine Sierra Nevada Mountains, especially around Sequoia and Yosemite National Parks. Several pesticides, including diazinon, chlorpyrifos, malathion and endosulfan, can be measured in snow, rainfall, and pond waters in these national parks. With the exception of endosulfan, these pesticides affect and even kill both invertebrates and vertebrate species by inhibiting cholinesterase, an enzyme essential to proper nervous system functioning. In the summer of 2001, we published a paper showing that these same pesticides are now found in adults and the tadpoles of Pacific treefrogs. The results of this landmark study showed that more than 50 percent of the tadpoles and adults sampled in Yosemite and Sequoia National Parks had detectable levels of diazinon or chlorpyrifos and that 86 percent of the Pacific treefrogs sampled in the Lake Tahoe region had detectable levels of endosulfan. In contrast, frogs that were


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    Sukati S.


    Full Text Available The Relationship Between Cholinesterase Enzym and Iodine Status of Child Bearing Age Woman (CBAW In The Endemic Goitre Area.Background: Pesticide as a pollutant substance is a goitrogenic agent. It can form a strong complex bound with iodine in the body. Women who ive in the endemic goiter, area where the iodine source in the nature is limited and frequently exposed by pesticide, can increase the prevalence of iodine deficiency disorder (IDD.Objectives: To find out the relationship between cholinesterase enzyme concentration (as an indicator of pesticide exposure in the body and iodine status of women in the endemic goiter area.Methods: The study was conducted in Pakis sub district, Magelang Regency, Central Java on July to November 2005. The design of the research was "cross-sectional" study. Samples were 265 women of child bearing age (17-35 years old. The data collected were concentration of free T4 (FT4 , cholinesterase enzyme in plasma, intake of cyanide originated from food, concentration of urine iodine excretion (UIE, type of contraception used and nutritional status. The concentration of serum FT4 were divided into two group (< 0.79 ng/gL = low > nonnal. These data were analyzed by using chi-square test with odd ratio at 95% CL. Association between independent and dependent variables by controlling other variable were analyzed by multiple logistic regression.Results: Pesticides that frequently used in the area of study was Organophosphate and Carbamat The pesticide residue on raw vegetables was Carbofuran. Its concentration was 0.056 to 55.65 mg/kg. The highest residues was found in cabbage and it had exceeded the maximum limit of permitted residue. The pesticide residue of cooked vegetables was very low. Low concentration of cholinesterase enzyme (< 3600 U/L was found in 3.8% women. More than 29% had low iodine status. Logistic regression analysis showed that women exposed to pesticide had 33 fold greater risk for IDD than that of

  12. Repeated exposure to neurotoxic levels of chlorpyrifos alters hippocampal expression of neurotrophins and neuropeptides. (United States)

    Lee, Young S; Lewis, John A; Ippolito, Danielle L; Hussainzada, Naissan; Lein, Pamela J; Jackson, David A; Stallings, Jonathan D


    Chlorpyrifos (CPF), an organophosphorus pesticide (OP), is one of the most widely used pesticides in the world. Subchronic exposures to CPF that do not cause cholinergic crisis are associated with problems in cognitive function (i.e., learning and memory deficits), but the biological mechanism(s) underlying this association remain speculative. To identify potential mechanisms of subchronic CPF neurotoxicity, adult male Long Evans (LE) rats were administered CPF at 3 or 10mg/kg/d (s.c.) for 21 days. We quantified mRNA and non-coding RNA (ncRNA) expression profiles by RNA-seq, microarray analysis and small ncRNA sequencing technology in the CA1 region of the hippocampus. Hippocampal slice immunohistochemistry was used to determine CPF-induced changes in protein expression and localization patterns. Neither dose of CPF caused overt clinical signs of cholinergic toxicity, although after 21 days of exposure, cholinesterase activity was decreased to 58% or 13% of control levels in the hippocampus of rats in the 3 or 10mg/kg/d groups, respectively. Differential gene expression in the CA1 region of the hippocampus was observed only in the 10mg/kg/d dose group relative to controls. Of the 1382 differentially expressed genes identified by RNA-seq and microarray analysis, 67 were common to both approaches. Differential expression of six of these genes (Bdnf, Cort, Crhbp, Nptx2, Npy and Pnoc) was verified in an independent CPF exposure study; immunohistochemistry demonstrated that CRHBP and NPY were elevated in the CA1 region of the hippocampus at 10mg/kg/d CPF. Gene ontology enrichment analysis suggested association of these genes with receptor-mediated cell survival signaling pathways. miR132/212 was also elevated in the CA1 hippocampal region, which may play a role in the disruption of neurotrophin-mediated cognitive processes after CPF administration. These findings identify potential mediators of CPF-induced neurobehavioral deficits following subchronic exposure to CPF at

  13. Clinical Effect Compare of Patients with Acute Organophosphate Poisoning Treated by Pralidoxime Chloride Using Intravenous Injection and Micro Pump%微量泵输注与静脉注射氯解磷定抢救急性有机磷农药中毒的疗效观察

    Institute of Scientific and Technical Information of China (English)

    张小青; 卢绍禹


    目的:比较微量泵输注与静脉注射氯解磷定抢救有机磷农药中毒患者的临床效果。方法回顾性分析84例急性有机磷农药中毒病例,按照随机对照原则分为A、B两组。 A组患者采用常规间断静脉注射氯解磷定;B组在首次静脉注射氯解磷定后给予持续微量泵静脉维持给药。观察比较两组患者的胆碱酯酶恢复情况、住院时间、不良反应发生率、及死亡率。结果 B组患者的胆碱酯酶恢复时间(P<0.001)、住院时间(P<0.01)、不良反应发生率及死亡率(P<0.005)均低于A组。结论微量泵输注氯解磷定抢救有机磷中毒死亡率及不良反应发生率低,并且操作简便,值得临床推广。%Objettive To compare The clinical ef ect of patients with acute Organophosphate poisoning treated by pralidoxime Chloride using intravenous injection and micro pump. Methods 84 patients with acute Organophosphate poisoning were retrospectively analyzed. The patients were divided into group A and group B. Each group has 42 cases. patients in group A were treated with intermit ent intravenous injection of Pralidoxime Chloride. patients in group B were treated with continuous intravenous injection of Pralidoxime Chloride by micro pump. The recovery of cholinesterase, average length of stay in hospital ,the incidence of adverse reactions, mortality rate were compared between the two groups. Rusults The recovery time of cholinesterase ( P<0.001), average length of stay ( P<0.01), incidence of adverse reactions and mortality rate ( P<0.005).in group B were significantly less than those in group A. Conclusion Mortality rate and incidence of adverse reactions of patients with acute Organophosphate poisoning treated by cholinesterase Chloride using micro pump is less, and it is easy to control, it is worthy of clinical application.

  14. Much caution does no harm! Organophosphate poisoning often causes pancreatitis. (United States)

    Yoshida, Shozo; Okada, Hideshi; Nakano, Shiho; Shirai, Kunihiro; Yuhara, Toshiyuki; Kojima, Hiromasa; Doi, Tomoaki; Kato, Hisaaki; Suzuki, Kodai; Morishita, Kentaro; Murakami, Eiji; Ushikoshi, Hiroaki; Toyoda, Izumi; Ogura, Shinji


    Organophosphate poisoning (OP) results in various poisoning symptoms due to its strong inhibitory effect on cholinesterase. One of the occasional complications of OP is pancreatitis. A 62-year-old woman drank alcohol and went home at midnight. After she quarreled with her husband and drank 100 ml of malathion, a parasympathomimetic organophosphate that binds irreversibly to cholinesterase, she was transported to our hospital in an ambulance. On admission, activated charcoal, magnesium citrate, and pralidoxime methiodide (PAM) were used for decontamination after gastric lavage. Abdominal computed tomography detected edema of the small intestine and colon with doubtful bowel ischemia, and acute pancreatitis was suspected. Arterial blood gas analysis revealed severe lactic acidosis. The Ranson score was 6 and the APACHE II (Acute Physiology and Chronic Health Evaluation) score was 14. Based on these findings, severe acute pancreatitis was diagnosed. One day after admission, hemodiafiltration (HDF) was started for the treatment of acute pancreatitis. On the third hospital day, OP symptoms were exacerbated, with muscarinic manifestations including bradycardia and hypersalivation and decreased plasma cholinesterase activity. Atropine was given and the symptoms improved. The patient's general condition including hemodynamic status improved. Pancreatitis was attenuated by 5 days of HDF. Ultimately, it took 14 days for acute pancreatitis to improve, and the patient discharged on hospital day 32. Generally, acute pancreatitis associated with OP is mild. In fact, one previous report showed that the influence of organophosphates on the pancreas disappears in approximately 72 hours, and complicated acute pancreatitis often improves in 4-5 days. However, it was necessary to treat pancreatitis for more than 2 weeks in this case. Therefore, organophosphate-associated pancreatitis due to malathion is more severe. Although OP sometime causes severe necrotic pancreatitis or

  15. Butyrylcholinesterase in guinea pig lung lavage: a novel biomarker to assess lung injury following inhalation exposure to nerve agent VX. (United States)

    Graham, Jacob R; Wright, Benjamin S; Rezk, Peter E; Gordon, Richard K; Sciuto, Alfred M; Nambiar, Madhusoodana P


    Respiratory disturbances play a central role in chemical warfare nerve agent (CWNA) induced toxicity; they are the starting point of mass casualty and the major cause of death. We developed a microinstillation technique of inhalation exposure to nerve agent VX and assessed lung injury by biochemical analysis of the bronchoalveolar lavage fluid (BALF). Here we demonstrate that normal guinea pig BALF has a significant amount of cholinesterase activity. Treatment with Huperzine A, a specific inhibitor of acetylcholinesterase (AChE), showed that a minor fraction of BALF cholinesterase is AChE. Furthermore, treatment with tetraisopropyl pyrophosphoramide (iso-OMPA), a specific inhibitor of butyrylcholinesterase (BChE), inhibited more than 90% of BChE activity, indicating the predominance of BChE in BALF. A predominance of BChE expression in the lung lavage was seen in both genders. Substrate specific inhibition indicated that nearly 30% of the cholinesterase in lung tissue homogenate is AChE. BALF and lung tissue AChE and BChE activities were strongly inhibited in guinea pigs exposed for 5 min to 70.4 and 90.4 microg/m3 VX and allowed to recover for 15 min. In contrast, BALF AChE activity was increased 63% and 128% and BChE activity was increased 77% and 88% after 24 h of recovery following 5 min inhalation exposure to 70.4 microg/m3 and 90.4 mg/m3 VX, respectively. The increase in BALF AChE and BChE activity was dose dependent. Since BChE is synthesized in the liver and present in the plasma, an increase in BALF indicates endothelial barrier injury and leakage of plasma into lung interstitium. Therefore, a measure of increased levels of AChE and BChE in the lung lavage can be used to determine the chronology of barrier damage as well as the extent of lung injury following exposure to chemical warfare nerve agents.

  16. Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina)

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    Cazenave, Jimena, E-mail: [Laboratorio de Ictiologia, Instituto Nacional de Limnologia (INALI-CONICET-UNL), Paraje El Pozo, Ciudad Universitaria UNL, 3000 Santa Fe (Argentina); Bacchetta, Carla; Parma, Maria J.; Scarabotti, Pablo A. [Laboratorio de Ictiologia, Instituto Nacional de Limnologia (INALI-CONICET-UNL), Paraje El Pozo, Ciudad Universitaria UNL, 3000 Santa Fe (Argentina); Wunderlin, Daniel A. [Dto. Bioquimica Clinica-CIBICI-CONICET, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre esq Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina)


    This field study assessed water quality of Salado River basin by using a set of biomarkers in the fish Prochilodus lineatus. Multiple biomarkers were measured, including morphological indexes (condition factor, liver somatic index), hematological (red and white blood cells) and biochemical (glucose, total protein and cholinesterase activity) parameters. Besides, detoxication and oxidative stress markers (antioxidant enzymes, lipid peroxidation) were measured in liver, gills and kidney. Despite water quality assessment did not show marked differences among sites, biomarkers responses indicate that fish are living under stressful environmental conditions. According to multivariate analysis glucose, glutathione S-transferase activity, lipid peroxidation levels and the count of white blood cells are key biomarkers to contribute to discrimination of sites. So, we suggest use those biomarkers in future monitoring of freshwater aquatic systems. - A battery of biomarkers was successfully applied to assess the health of the fish Prochilodus lineatus from Salado River basin.

  17. ¬Enzyme Inhibition Studies on N-Substituted Sulfonamides Derived from m-phenetidine

    Directory of Open Access Journals (Sweden)



    Full Text Available Organic synthesis of various compounds followed by biological activities is the going on methodology in the world for pharmacological evaluation. The undertaken research is the synthesis of N-(3-ethoxyphenyl-4-methylbenzenesulfonamide (3 through condensation reaction of m-phenetidine (1 and 4-methylbenzenesulfonyl chloride (2 using basic aqueous media of sodium carbonate. Further, the synthesized compound 3 was reacted with different alkyl/aralkyl halides (4a-j using DMF as aprotic polar solvent and NaH as a base to yield 5a-j compounds. The synthesized molecules were characterized from their spectral data. The synthesized compounds were evaluated against cholinesterase (AChE and BChE, lipoxygenase (LOX, urease, chymotrypsin and tyrosinase enzymes; and found to be the moderate inhibitor against tyrosinase enzyme.

  18. ¬Enzyme Inhibition Studies on N-Substituted Sulfonamides Derived from m-phenetidine

    Directory of Open Access Journals (Sweden)



    Full Text Available Organic synthesis of various compounds followed by biological activities is the going on methodology in the world for pharmacological evaluation. The undertaken research is the synthesis of N-(3-ethoxyphenyl-4-methylbenzenesulfonamide (3 through condensation reaction of m-phenetidine (1 and 4-methylbenzenesulfonyl chloride (2 using basic aqueous media of sodium carbonate. Further, the synthesized compound 3 was reacted with different alkyl/aralkyl halides (4a-j using DMF as aprotic polar solvent and NaH as a base to yield 5a-j compounds. The synthesized molecules were characterized from their spectral data. The synthesized compounds were evaluated against cholinesterase (AChE and BChE, lipoxygenase (LOX, urease, chymotrypsin and tyrosinase enzymes; and found to be the moderate inhibitor against tyrosinase enzyme.

  19. Assessment of landfill leachate toxicity reduction after biological treatment. (United States)

    Jemec, Anita; Tišler, Tatjana; Zgajnar-Gotvajn, Andreja


    In the present article, the efficiency of biological treatment of landfill leachates was evaluated by implementation of physicochemical characterisation and a complex toxicity assessment. An array of toxicity tests using bacterium Vibrio fischeri, alga Desmodesmus subspicatus, crustacean Daphnia magna, and embryo of fish Danio rerio, as well as unconventional methods using biochemical biomarkers (protein content, enzymes cholinesterase, and glutathione-S-transferase), were employed. Toxicity of leachates varied depending on the season of collection in relation to their different physicochemical characteristics. Uncommon effects of leachates on organisms, such as hormetic-like increases of algal growth and reproduction of daphnids, were identified. New approaches using the activities of enzymes were found unsuitable for routine hazard assessment of leachates. Although physicochemical parameters and toxicity decreased significantly after biological treatment, the effluents did not meet the demands of the current Slovenian legislation; thus, the existing biological treatment was found inappropriate. The development of advanced treatment techniques for landfill leachates is thus encouraged.

  20. Lipid malnutrition of patients with liver cirrhosis: effect of low intake of dietary lipid on plasma fatty acid composition.

    Directory of Open Access Journals (Sweden)



    Full Text Available The plasma fatty acid composition of cirrhotic patients and their dietary intake of fatty acids were determined. Significantly lower plasma arachidonic, docosahexaenoic, dihomo-gamma-linolenic and eicosapentaenoic acid levels were observed in cirrhotic patients than in healthy controls. A remarkably low dietary intake of polyunsaturated fatty acids supplied from fish, vegetable oil and pulses was shown in cirrhotic patients. Positive correlations were observed between plasma arachidonic acid concentrations and clearance rate of indocyanine green (KICG (r = 0.826, p less than 0.05 and between dihomo-gamma-linolenic acid levels and cholinesterase activities (r = 0.841, p less than 0.05. From these results, we conclude that a supply of polyunsaturated fatty acids is necessary for the nutritional treatment of patients with liver cirrhosis.

  1. Identification by CI-mass spectrometry of an unexpected benzodiazepine degradation product (United States)

    Buret, D.; Breton, D.; Clair, P.; Lafosse, M.


    The French Military Health Service (SSA) has developed an innovative drug product, as a treatment against neurotoxic organophosphate poisoning (NOP). It contains three drug substances: an anticholinergic, an anticonvulsant and a cholinesterase reactivator. Testing stability study, in normal conditions, over 18 months, for this speciality, has given unexpected results. Indeed, one of the drug substances, avizafone (pro-drug of diazepam), breaks down partially into a compound which migrates into the plastic container where this degradation product is demethylated after absorption. Mass spectrometry with negative chemical ionisation (negative CI-MS) was used, to monitor decomposition of the drug substance. This method first showed migration of the degradation product and has been used to monitor its evolution during the stability testing study. The demethylation seems to be due to an additive product present in the plastic. The degradation products remain trapped in the container holding the pharmaceutical formulation.

  2. New Acetylcholinesterase Inhibitors for Alzheimer's Disease

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    Mona Mehta


    Full Text Available Acetylcholinesterase (AChE remains a highly viable target for the symptomatic improvement in Alzheimer's disease (AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AchE for myasthenia gravis had effectively proven that AchE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEI continue to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs in development and their respective mechanisms of actions. This pharmacological approach continues to be active with many promising compounds.

  3. Application of enzyme multibiosensor for toxicity analysis of real water samples of different origin

    Directory of Open Access Journals (Sweden)

    Soldatkin A. P.


    Full Text Available Aim. The analysis of toxicity of different water samples with the multibiosensor developed earlier. Methods. The potentiometric multibiosensor with several immobilized enzymes as bioselective elements and the matrix of pH-sensitive field effect transistors as transducers of the biochemical signal into the electric one was applied for the analysis. Results. The bioselective elements of the multibiosensor were developed using acetylcholinesterase, butyryl- cholinesterase, urease, glucose oxidase, and three-enzyme system (invertase, mutarotase, glucose oxidase. The measurement of toxic compounds in water samples of different origin was performed using the constructed sensor. The results obtained were compared with those obtained by the conventional methods of toxic agent’s analysis (atomic absorption spectrometry, thin-film chroma- tography, and atomic absorbic analyser of mercury. Conclusion. A strong conformity between the results obtained with the multibiosensor and traditional methods has been shown.

  4. Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina). (United States)

    Cazenave, Jimena; Bacchetta, Carla; Parma, María J; Scarabotti, Pablo A; Wunderlin, Daniel A


    This field study assessed water quality of Salado River basin by using a set of biomarkers in the fish Prochilodus lineatus. Multiple biomarkers were measured, including morphological indexes (condition factor, liver somatic index), hematological (red and white blood cells) and biochemical (glucose, total protein and cholinesterase activity) parameters. Besides, detoxication and oxidative stress markers (antioxidant enzymes, lipid peroxidation) were measured in liver, gills and kidney. Despite water quality assessment did not show marked differences among sites, biomarkers responses indicate that fish are living under stressful environmental conditions. According to multivariate analysis glucose, glutathione S-transferase activity, lipid peroxidation levels and the count of white blood cells are key biomarkers to contribute to discrimination of sites. So, we suggest use those biomarkers in future monitoring of freshwater aquatic systems.

  5. Anti-diabetic related health food properties of traditional rice (Oryza sativa L.) in Sri Lanka

    Institute of Scientific and Technical Information of China (English)

    Wanigasekara Daya Ratnasooriya; Muhammad Iqbal Choudhary; Kourosh Dalvandi


    Objective:To evaluate a range of anti-diabetic related properties and some consumer preferred physicochemical properties of selected Sri Lankan traditional rice varieties. Methods: Sudu Heeneti, Goda Heeneti, Masuran and Dik Wee varieties were used in this study. Anti-diabetic related properties of bran extracts of selected varieties were studied for methylglyoxal mediated protein glycation inhibition, acetyl and butyryl-cholinesterase inhibitionin vitro and anti-hyperglycemic activityin vivo. Further, selected varieties were studied for starch hydrolysis ratein vitro. Physicochemical properties including grain color, size, shape, crude protein, crude fat, ash, dietary fiber and total carbohydrate contents were studied. Results: Brans of selected varieties had significant (P Conclusions: It is concluded that selected varieties could be promoted as physicochemically sound rices with a range of anti-diabetic related properties in the management of diabetes and its complications.

  6. Effects of pesticides on songbird productivity in conjunction with pecan cultivation in southern Georgia: A multiple-exposure experimental design (United States)

    Patnode, K.A.; White, D.H.


    A prototypic experimental design was used to assess sublethal effects of multiple and varied organophosphates and carbamates on reproduction in birds. The design allowed for classification of pesticide exposure according to toxicity of applied compounds and type and frequency of applications. Daily survival rates (DSRs) of nests, eggs, and nestlings were determined for northern mockingbirds (Mimus polyglottos), brown thrashers (Toxostoma rufum), and northern cardinals (Cardinalis cardinalis) nesting along edges of pecan orchards and row crops in southern Georgia [USA]. Egg and nestling DSRs for all species combined varied inversely (P 0.05) among three exposure levels. Brain cholinesterase activities were age-dependent and substantiated adult, but not nestling, exposure. Results suggest that increasing exposure to pesticides may reduce songbird productivity.

  7. Studies on the effect of fenbendazole and mebendazole on some enzymes of swine kidney worm Stephanurus dentatus. (United States)

    Singh, K; Kaushal, P


    The effect of fenbendazole and mebendazole on the activity of some enzymes of the homogenates of swine kidney worm Stephanurus dentatus was investigated. Fenbendazole at 10(-5) M inhibited malate oxidation by 49% and 51% and oxaloacetate reduction by 33% and 40% whereas, mebendazole at 10(-5) M diminished malate oxidation by 25% and 35% and oxaloacetate reduction by 12% and 14% in male and female S. dentatus, respectively. Lactate dehydrogenase activity was inhibited by 45% and 50% in male and female worm respectively by 10(-5) M fenbendazole. Aldolase activity in both male and female S. dentatus was inhibited by 10(-5) M fenbendazole and mebendazole. Fenbendazole at 10(-5) M caused moderate inhibition of acid and alkaline phosphomonoesterases but mebendazole did not show a significant effect on these enzymes. Cholinesterase activity was not affected significantly with either compound. The possible mode of action of the two compounds is compared.

  8. Synthesis of Novel Biologically Active s-Triazolo[3,4-b]-1,3,4-thiadiazole Derivatives

    Institute of Scientific and Technical Information of China (English)



    @@ Heterocycles bearing a symmetrical triazole or 1,3,4-thiadiazole ring system are reported to show a broad spectrum of biological activities.[1,2] The 1,2,4-triazole nucleus has been recently incorporated into a wide variety of therapeutically interesting drugs including H1/H2 histamine receptor blockers, cholinesterase active agents, CNS stimulants, antianxiety and sedatives[3] Coumarins are nowadays an important group of organic compounds that used as bactericides, fungicides,anti-inflammatory, anticoagulant, anti-HIV and antitumour agents.[4,5] Keeping in view the biological importance of the above mentioned heterocyclic compounds and in continuation of our search for biologically active nitrogen and sulphur heterocycles, a series of s-triazolo[3,4-b]-1,3,4-thiadiazole derivatives was synthesized.

  9. Nootropic candidates inhibit head-twitches induced by mescaline in mice. (United States)

    Yamamoto, T; Ohno, M; Yatsugi, S; Fujikawa, Y; Ueki, S


    The effects of various nootropic candidates on mescaline-induced head-twitches were studied in mice. The number of head-twitches induced by mescaline (100 mg/kg, s.c.) was significantly reduced by idebenone (32 and 100 mg/kg, i.p.), minaprine (0.32-10 mg/kg, p.o.) and nebracetam (100 mg/kg, p.o.). Cholinesterase inhibitors such as tetrahydroaminoacridine (1 and 10 mg/kg, p.o.), NIK-247 (10 and 18 mg/kg, p.o.) and physostigmine (0.32 mg/kg, i.p.) also suppressed the head-twitch response to mescaline. These results suggest that the direct or indirect cholinergic-activating effects of these drugs may be involved in inhibiting mescaline-induced head-twitches.

  10. Anticholinesterases and antioxidant alkamides from Piper nigrum fruits. (United States)

    Tu, Yanbei; Zhong, Yujiao; Du, Hongjian; Luo, Wei; Wen, Yaya; Li, Qin; Zhu, Chao; Li, Yanfang


    The anticholinesterase and antioxidant effects of five different extracts of Piper nigrum were evaluated. Twenty-one known alkamides were isolated from active ethyl acetate extract and investigated for their cholinesterase inhibitory and antioxidant effects. Among them, piperine (2), piperettine (5) and piperettyline (20) exhibited dual inhibition against AChE and BChE, and feruperine (18) was the most potent selective inhibitor of BChE. Molecular docking simulation was performed to get insight into the binding interactions of the ligands and enzymes. In addition, N-trans-feruloyltyramine (3) contributed to the strongest DPPH radical-scavenging activity. The self-induced Aβ aggregation inhibition of 2, 5 and 18 was further evaluated. Results indicated that some alkamides could be multifunctional lead candidates for Alzheimer's disease therapy.

  11. 急性有机磷农药中毒致呼吸衰竭的影响因素分析%Study on correlated clinical factors of respiratory failure induced by acute organophosphorus pesticide poisoning

    Institute of Scientific and Technical Information of China (English)

    陶贤洲; 王佐


    目的:分析急性有机磷农药中毒( AOPP)致呼吸衰竭的相关临床因素,为制订有效的预防及干预措施提供科学依据。方法回顾分析94例重性AOPP患者临床资料,根据血气分析结果将患者分为呼吸衰竭组(41例)和非呼吸衰竭组(53例),观察患者的APACHEⅡ评分、胆碱酯酶、血糖、血清淀粉酶、肝肾功能及心肌酶谱等指标。结果胆碱酯酶水平呼吸衰竭组患者低于非呼吸衰竭组患者(P<0.05);APACHEⅡ评分、血清淀粉酶、肝肾功能及心肌酶谱等,呼吸衰竭组患者高于非呼吸衰竭组患者(P<0.05);Logistic回归分析显示APACHEⅡ评分、胆碱酯酶及血清淀粉酶与呼吸衰竭相关。结论 APACHEⅡ评分、胆碱酯酶及血清淀粉酶水平可作为AOPP引起呼吸衰竭的预测指标。%Objective To investigate the correlated clinical factors of respiratory failure induced by acute organophosphorus pesticide poisoning ( AOPP) ,and to provide relevant data for prevention and intervention of respiratory failure .Methods This retrospective study in-cluded 94 patients with severe AOPP ,and all patients were divided into respiratory failure group ( n=41 ) and non-respiratory failure group (n=53) according to arterial blood gas analysis .We observed APACHEⅡscores,cholinesterase,blood glucose,serum amylase,hepatic func-tion,renal function and myocardial enzyme between the two groups .Results Cholinesterase level in the respiratory failure group was lower than that in non-respiratory failure group (P<0.05);APACHEⅡ scores,serum amylase,hepatic function,renal function and myocardial enzyme in the respiratory failure group were higher than those of non-respiratory failure group (P<0.05).Spearman correlation analysis and Logistic regression analyses showed APACHEⅡscores,cholinesterase and serum amylase were related to respiratory failure ,and they had sig-nificant predictive effects on respiratory failure

  12. Contaminant concentrations, biochemical and hematological biomarkers in blood of West Indian manatees Trichechus manatus from Brazil. (United States)

    Anzolin, D G; Sarkis, J E S; Diaz, E; Soares, D G; Serrano, I L; Borges, J C G; Souto, A S; Taniguchi, S; Montone, R C; Bainy, A C D; Carvalho, P S M


    The West Indian manatee Trichechus manatus is threatened with extinction in Brazil, and this study focused on nondestructive blood samples analyzed for metals, polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), as well as biochemical and hematological biomarkers. Studied manatees were kept at Projeto Peixe-Boi headquarters in Pernambuco State, and at two natural areas in estuaries where they are released to the wild. Manatees kept at the natural estuary in Paraiba State have blood concentrations of Al, Pb, Cd, Sn that are 11, 7, 8 and 23 times greater, respectively, than the concentrations found in blood of animals from the same species in Florida, USA. An inhibition of butyrylcholinesterase in manatees kept at the two reintroduction sites in Alagoas and Paraiba States indicated possible exposure of the animals to cholinesterase inhibitor insecticides. PCBs and OCPs were not detected. Results from this study will help delineate conservation efforts in the region.

  13. 呆聪液对老年痴呆大鼠血清酶及LPO的影响%The effect of Daicong solution on the serum enzymes and LPO in aged rats dementia model

    Institute of Scientific and Technical Information of China (English)

    赵淑梅; 张太国; 岳启安; 左凤英; 李光宗; 高敬宗; 尤敏; 管福来


    Objective To explore the effect of Daicong solution (DCS) on aged rats dementia model.Method The experiment used 22 month old rats whose basal nuclei was destroyed by bilateral electrolytic method as model for aged rats dementia.They were treated with DCS for a month.Then the level of superoxide dismutase (SOD),lipid peroxide(LPO),monoamine oxidase (MAO) and cholinesterase(CHE) in the serum was measured. Result Compared with the control,the activity of SOD increased markedly(P< 0.01), the content of LOP and activity MAO and CHE were decreased(P< 0.01).Conclusion DCS is effective in treating the aged dementia.

  14. Oleanolic acid and related derivatives as medicinally important compounds. (United States)

    Sultana, Nighat; Ata, Athar


    Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle after removal of organic bases and free acids. The literature survey revealed it to be biologically very important. In this review the biological significance of oleanolic acid and its derivatives has been discussed. The aim of this review is to update current knowledge on oleanolic acid and its natural and semisynthetic analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory, anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial, hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti-angiogenic, antiallergic, antiviral and immunomodulatory activities. We present in this review, for the first time, a compilation of the most relevant scientific papers and technical reports of the chemical, pre-clinical and clinical research on the properties of oleanolic acid and its derivatives.

  15. Special Issue: “Molecules against Alzheimer”

    Directory of Open Access Journals (Sweden)

    Michael Decker


    Full Text Available This Special Issue, entitled “Molecules against Alzheimer”, gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer’s disease (AD, the most prevalent neurodegenerative disorder and a leading cause of death worldwide. This Special Issue contains many interesting examples describing the design, synthesis, and pharmacological profiling of novel compounds that hit one or several key biological targets, such as cholinesterases, β-amyloid formation or aggregation, monoamine oxidase B, oxidative stress, biometal dyshomeostasis, mitochondrial dysfunction, serotonin and/or melatonin systems, the Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase, or nuclear erythroid 2-related factor. The development of novel AD diagnostic agents based on tau protein imaging and the use of lithium or intranasal insulin for the prevention or the symptomatic treatment of AD is also covered in some articles of the Special Issue.

  16. Molecular modeling and anticholinesterasic activity of novel 2-arylaminocyclohexyl N,N-dimethylcarbamates

    Energy Technology Data Exchange (ETDEWEB)

    Bagatin, Mariane C.; Candido, Augusto A.; Basso, Ernani A.; Gauze, Gisele F., E-mail: [Universidade Estadual de Maringa (UEM), PR (Brazil). Departamento de Quimica; Pinheiro, Glaucia M. S.; Hoeehr, Nelci F. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Departamento de Patologia Clinica; Machinski Junior, Miguel; Mossini, Simone A.G. [Universidade Estadual de Maringa (UEM), PR (Brazil). Departamento de Ciencias Basicas da Saude


    This work reports a detailed theoretical and experimental study of the novel isomer series cis- and trans-2-arylaminocyclohexyl N,N-dimethylcarbamates as potential inhibitors of cholinesterases. In vitro inhibition assay by Ellman's method with human blood samples showed that the new carbamates are selective to the inhibition of enzyme butyrylcholinesterase (BuChE) with maximum inhibition of 90% and IC{sub 50} of 6 and 8 mmol L{sup -1} for the more actives compounds of the series. Molecular modeling studies point to significant differences for the conformations of the compounds in the active sites of enzymes BuChE and acetylcholinesterase (AChE). The results show that the compounds interact more effectively with the active site of enzyme BuChE since the carbamate group is close to the key residues of the catalytic triad. (author)

  17. Hologram QSAR models of 4-[(diethylamino)methyl]-phenol inhibitors of acetyl/butyrylcholinesterase enzymes as potential anti-Alzheimer agents. (United States)

    de Souza, Simone Decembrino; de Souza, Alessandra Mendonça Teles; de Sousa, Ana Carolina Corrêa; Sodero, Ana Carolina Rennó; Cabral, Lúcio Mendes; Albuquerque, Magaly Girão; Castro, Helena Carla; Rodrigues, Carlos Rangel


    Hologram QSAR models were developed for a series of 36 inhibitors (29 training set and seven test set compounds) of acetyl/butyrylcholinesterase (AChE/BChE) enzymes, an attractive molecular target for Alzheimer's disease (AD) treatment. The HQSAR models (N = 29) exhibited significant cross-validated (AChE, q2 = 0.787; BChE, q2 = 0. 904) and non-cross-validated (AChE, r2 = 0.965; BChE, r2= 0.952) correlation coefficients. The models were used to predict the inhibitory potencies of the test set compounds, and agreement between the experimental and predicted values was verified, exhibiting a powerful predictive capability. Contribution maps show that structural fragments containing aromatic moieties and long side chains increase potency. Both the HQSAR models and the contribution maps should be useful for the further design of novel, structurally related cholinesterase inhibitors.

  18. Possible Role of Common Spices as a Preventive and Therapeutic Agent for Alzheimer's Disease (United States)

    Mirmosayyeb, Omid; Tanhaei, Amirpouya; Sohrabi, Hamid R.; Martins, Ralph N.; Tanhaei, Mana; Najafi, Mohammad Amin; Safaei, Ali; Meamar, Rokhsareh


    For centuries, spices have been consumed as food additives or medicinal agents. However, there is increasing evidence indicating the plant-based foods in regular diet may lower the risk of neurodegenerative diseases including Alzheimer disease. Spices, as one of the most commonly used plant-based food additives may provide more than just flavors, but as agents that may prevent or even halt neurodegenerative processes associated with aging. In this article, we review the role and application of five commonly used dietary spices including saffron turmeric, pepper family, zingiber, and cinnamon. Besides suppressing inflammatory pathways, these spices may act as antioxidant and inhibit acetyl cholinesterase and amyloid β aggregation. We summarized how spice-derived nutraceuticals mediate such different effects and what their molecular targets might be. Finally, some directions for future research are briefly discussed. PMID:28250905

  19. Pharmacological treatments of behavioral and psychological symptoms of dementia in Alzheimer's disease: role of acetylcholinesterase inhibitors and memantine. (United States)

    Desmidt, Thomas; Hommet, Caroline; Camus, Vincent


    Behavioral and psychological symptoms of dementia (BPSD) are frequent in Alzheimer's disease (AD). They are associated with disability and suffering for both the patients and their caregivers. Even if BPSD are now well diagnosed and characterized by standardized tools, their treatment remains often challenging in clinical setting because of the frequent and severe side effects of the psychotropic drugs when used in this indication. Evidence-based data confirm that antipsychotics and antidepressants are efficient for the treatment of BPSD but have a poor tolerance profile and their use is problematic. Use of cholinesterase inhibitors and memantine, whom French authorities have questioned the relevance in 2008, also have a significant efficacy on non-cognitive symptoms of AD. Therefore, and although their tolerance profile is considered unsatisfying, they keep an indication in patients with AD and BPSD.

  20. [Pesticide pollution in water systems in a small rural community in Southeast Brazil]. (United States)

    Veiga, Marcelo Motta; Silva, Dalton Marcondes; Veiga, Lilian Bechara Elabras; Faria, Mauro Velho de Castro


    Recent advances in analytical techniques allow identifying pesticide pollution in water systems. In small rural communities, the negative effects of pesticide pollution can be aggravated by the lack of infrastructure and adverse socioeconomic conditions. This study investigated pesticide pollution in potential water supply sources in a tomato growing area in Paty do Alferes, Rio de Janeiro State, Brazil. The study selected 27 points where five monthly samples were collected. Pesticide pollution was determined by analyzing acetyl-cholinesterase inhibition. In 19 of the 27 sample points, some pesticide pollution was detected, and in two points the pesticide pollution was above the permitted limits. The results thus proved the incidence of pesticide pollution in water sources in Paty do Alferes that could jeopardize the local population's health.

  1. Diferencias en la salud de jornaleras y jornaleros agrícolas migrantes en Sinaloa, México Health differences between male and female migrant agricultural workers in Sinaloa, Mexico

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    Martha Edilia Palacios-Nava


    Full Text Available OBJETIVO: Evaluar las diferencias en la prevalencia de síntomas de origen muscarínico y nicotínico, y el nivel de colinesterasa eritrocítica de jornaleras y jornaleros agrícolas, antes de la exposición a plaguicidas. MATERIAL Y MÉTODOS: Entre enero y febrero de 2001 se realizó un estudio transversal con 488 trabajadores migrantes en el estado de Sinaloa, México. Se aplicó un cuestionario y se midió colinesterasa eritrocítica antes del inicio de sus labores en la temporada agrícola. Las diferencias por sexo se analizaron utilizando prueba t para variables cuantitativas, ji2 para cualitativas y razón de momios para la prevalencia. Se consideraron alfa=0.05 e intervalos de confianza de 95% como niveles de significancia. RESULTADOS: Se encontraron diferencias significativas en edad, forma de migración, lugar de procedencia, nivel de escolaridad y antigüedad migratoria (p=0.000. Las mujeres presentaron seis veces más posibilidad de enfermar de anemia y asma, dos veces más parásitos, el doble de infecciones respiratorias y estomacales, y 38% más en enfermedades del corazón. También se encontró entre ellas una mayor posibilidad de presentar 13 de 19 síntomas interrogados. El promedio del nivel de colinesterasa se encontró en límites de normalidad (4.22 U/ml±0.77 y fue semejante a los reportados por el método Magnotti. CONCLUSIONES: La prevalencia de síntomas, enfermedades y el nivel de colinesterasa encontrados en este estudio pueden ser un referente basal para la comparación posterior de alteraciones producidas por exposición a plaguicidas.OBJECTIVE: To assess the differences in the prevalence of muscarinic and nicotinic type symptoms and the level of erythrocytic cholinesterase, prior to pesticide exposure, in male and female migrant agricultural workers. MATERIAL AND METHODS: A cross-sectional study was carried out in 2001 in Sinaloa State, Mexico, among 488 migrant workers. A questionnaire was applied and erythrocytic

  2. [Pharmacological treatment of dementia: when, how and for how long. Recommendations of the Working Group on Dementia of the Catalan Society of Geriatrics and Gerontology]. (United States)

    Rodríguez, Daniel; Formiga, Francesc; Fort, Isabel; Robles, María José; Barranco, Elena; Cubí, Dolors


    Dementia in general--and Alzheimer's disease (AD) in particular--are bound to loom large among the most acute healthcare, social, and public health problems of the 21st century. AD shows a degenerative progression that can be slowed down--yet not halted--by today's most widely accepted specific treatments (those based on cholinesterase inhibitors as well as those using memantine). There is enough evidence to consider these treatments advisable for the mild, moderate and severe phases of the illness. However, in the final stage of the disease, a decision has to be made on whether to withdraw such treatment or not. In this paper, the Working Group on Dementia for the Catalan Society of Geriatrics and Gerontology reviews the use of these specific pharmacological treatments for AD, and, drawing on the scientific evidence thus gathered, makes a series of recommendations on when, how, and for how long, the currently existing specific pharmacological treatments should be used.

  3. Case histories of bald eagles and other raptors killed by organophosphorus insecticides topically applied to livestock. (United States)

    Henny, C J; Kolbe, E J; Hill, E F; Blus, L J


    Since 1982 when secondary poisoning of a red-tailed hawk (Buteo jamaicensis) was documented following the recommended use of famphur applied topically to cattle, the Patuxent Wildlife Research Center has tested dead birds of prey for poisoning by famphur and other pour-on organophosphorus (OP) insecticides. Brain cholinesterase (ChE) activity was first determined, then if ChE was depressed greater than or equal to 50%, stomach and/or crop contents were evaluated for anti-ChE compounds. This report presents the circumstances surrounding the OP-caused deaths of eight bald eagles (Haliaeetus leucocephalus), two red-tailed hawks, and one great horned owl (Bubo virginianus) between March 1984 and March 1985. OP poisoning of raptors by pour-on insecticides in the United States is widespread, but its magnitude is unknown.

  4. Mini Review: Anticholinergic Activity as a Behavioral Pathology of Lewy Body Disease and Proposal of the Concept of “Anticholinergic Spectrum Disorders” (United States)

    Tomioka, Hiroi; Hachisu, Mitsugu


    Given the relationship between anticholinergic activity (AA) and Alzheimer's disease (AD), we rereview our hypothesis of the endogenous appearance of AA in AD. Briefly, because acetylcholine (ACh) regulates not only cognitive function but also the inflammatory system, when ACh downregulation reaches a critical level, inflammation increases, triggering the appearance of cytokines with AA. Moreover, based on a case report of a patient with mild AD and slightly deteriorated ACh, we also speculate that AA can appear endogenously in Lewy body disease due to the dual action of the downregulation of ACh and hyperactivity of the hypothalamic-pituitary-adrenal axis. Based on these hypotheses, we consider AA to be a behavioral pathology of Lewy body disease. We also propose the concept of “anticholinergic spectrum disorders,” which encompass a variety of conditions, including AD, Lewy body disease, and delirium. Finally, we suggest the prescription of cholinesterase inhibitors to patients in this spectrum of disorders to abolish AA by upregulating ACh.

  5. Mini review on blood-brain barrier penetration of pyridinium aldoximes. (United States)

    Kalász, H; Nurulain, S M; Veress, G; Antus, S; Darvas, F; Adeghate, E; Adem, A; Hashemi, F; Tekes, K


    This paper reviews the blood-brain barrier (BBB) penetration of newly developed pyridinium aldoximes. Pyridinium aldoximes are highly charged hydrophilic compounds used in the treatment of subjects exposed to organophosphonates because they are effective as acetylcholinesterase reactivators. Pyridinium aldoximes have antidotal effects against poisoning with cholinesterase inhibitors, a frequent problem affecting people working with organophosphate-based insecticides and pesticides. Toxic organophosphonate products such as sarin and tabun can be used by terrorists as chemical warfare agents. This poses a severe challenge to all innocent and peace-loving people worldwide. This review gives a brief summary of BBB transporters and description of the current in vitro and in vivo methods for the characterization of BBB penetration of established and novel pyridinium aldoximes. The authors provide a putative mechanism of penetration, outline some future ways of formulation and discuss the possible advantages and disadvantages of increasing BBB penetration.

  6. Cholinergic basis of memory improving effect of Ocimum tenuiflorum linn

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    Joshi H


    Full Text Available Dementia is one of the age-related mental problems and a characteristic symptom of Alzheimer′s disease. Nootropic agents are used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of Ocimum tenuiflorum Linn. as a nootropic and anticholinesterase agent in mice. Ethanol extract of dried whole plant of O. tenuiflorum Linn. ameliorated the amnesic effect of scopolamine (0.4 mg/kg and aging-induced memory deficits in mice. Passive avoidance paradigm served as the exteroceptive behavioural model. O. tenuiflorum extract increased step-down latency and acetyl cholinesterase inhibition significantly. Hence, O. tenuiflorum can be employed in the treatment of cognitive disorders such as dementia and Alzheimer′s disease.

  7. Novel tacrine-8-hydroxyquinoline hybrids as multifunctional agents for the treatment of Alzheimer's disease, with neuroprotective, cholinergic, antioxidant, and copper-complexing properties. (United States)

    Fernández-Bachiller, María Isabel; Pérez, Concepción; González-Muñoz, Gema C; Conde, Santiago; López, Manuela G; Villarroya, Mercedes; García, Antonio G; Rodríguez-Franco, María Isabel


    Tacrine and PBT2 (an 8-hydroxyquinoline derivative) are well-known drugs that inhibit cholinesterases and decrease beta-amyloid (Abeta) levels by complexation of redox-active metals, respectively. In this work, novel tacrine-8-hydroxyquinoline hybrids have been designed, synthesized, and evaluated as potential multifunctional drugs for the treatment of Alzheimer's disease. At nano- and subnanomolar concentrations they inhibit human acetyl- and butyrylcholinesterase (AChE and BuChE), being more potent than tacrine. They also displace propidium iodide from the peripheral anionic site of AChE and thus could be able to inhibit Abeta aggregation promoted by AChE. They show better antioxidant properties than Trolox, the aromatic portion of vitamin E responsible for radical capture, and display neuroprotective properties against mitochondrial free radicals. In addition, they selectively complex Cu(II), show low cell toxicity, and could be able to penetrate the CNS, according to an in vitro blood-brain barrier model.

  8. A review study on medicinal plants affecting amnesia through cholinergic system

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    Baradaran Azar


    Full Text Available Neurotransmitter modification is an important method for the treatment of memory loss or amnesia. Cholinomimetic drugs, particularly, acetylcholine esterase inhibitors are the mainstream in pharmacotherapy of amnesia. Donepezil, tacrine, galantamine, and rivastigmine are cholinesterase inhibitors which are widely used in the treatment of amnesia, however, their therapeutic effects are not significant. Therefore, other possibilities including herbal medicine sources have been considered for memory loss therapy. There are some Medicinal plants with cholinomimetic property which mostly possess antioxidant activity, too. These plants may not only ameliorate amnesia but also can be a good source for drug discovery. In this paper other than introducing the medicinal plants and their components affective on cholinergic system and effective on memory loss, their probable advantages over synthetic drugs are discussed.

  9. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas (United States)

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.


    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  10. Survey of phytochemical composition and biological effects of three extracts from a wild plant (Cotoneaster nummularia Fisch. et Mey.: a potential source for functional food ingredients and drug formulations.

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    Gokhan Zengin

    Full Text Available This study was focused on the analysis of the phenolic content, antioxidant, antibacterial, anti-cholinesterase, anti-tyrosinase, anti-amylase and anti-glucosidase activity of three solvent extracts from Cotoneaster nummularia. Moreover, water extract was tested in terms of mutagenic/anti-mutagenic effects. The antioxidant activities of these extracts were evaluated by DPPH, ABTS, O2, metal chelating, phosphomolybdenum, β-carotene/linoleic acid, ferric and cupric reducing power assays. Enzyme inhibitory activities were also examined with colorimetric methods. Generally, methanol and water extracts exhibited excellent biological activities. These extracts were rich in phenolic and flavonoid content. Furthermore, Cotoneaster extracts indicated appreciable antibacterial properties against human pathogen strains. HPLC analysis showed that ferulic acid, chlorogenic acid, (- - epicatechin and (+-catechin were the major phenolics in extracts tested. These data offer that these extracts from C. nummularia may be considered as a potential source of biological agents for developing functional foods or drug formulations.

  11. Chemical Characterization and Acetylcholinesterase Inhibition Potential of Volatile Components of Aerial Parts of Pluchea lanceolata (DC. Oliv. & Hiern

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    Pooja Srivastava


    Full Text Available Pluchea lanceolata (DC. Oliv. & Hiern (Rasana is an important medicinal plant due to its usage in number of Ayurvedic formulations. First time, chemical composition of essential oil from the aerial part of P. lanceolata was analyzed by gas chromatography-mass spectrometry (GC-MS and NMR spectroscopy. Ex-vivo cholinesterase inhibitory activity of the essential oil was also evaluated using mouse brain homogenate. The major components were linalool (32.2%, β-caryophyllene (8.5%, α-terpineol (8.0%, spathulenol (7.4%, linalylacetate (5.6%, naphthalene, 1,6-dimethyl-4-(1-methylethyl- (4.3%, α-copaene (3.6%, epi-cubebol (3.6% and trans-α-bergamontene (3.1%. The experimental results showed that hydrodistilate of P. lanceolata significantly inhibited acetylcholinesterase activity (IC 50 value 2.54 ± 0.03 µg/mL.

  12. Research progress of posterior cortical atrophy

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    Li-jun PENG


    Full Text Available Posterior cotical atrophy (PCA is a kind of progressive dementia with main clinical manifestations of visual dysfunction as the starting symptom and associated with progressive cognitive disorder. The histopathology and imaging of PCA show visual dysfunction, neuritic plaques (NPs and neurofibrillary tangles (NFTs, which are the same as those in Alzheimer's disease (AD. Researches also showed that mutation of presenilin-1 (PS-1 gene and apolipoprotein E (ApoE genotype may participate in the occurrence and development of PCA. Parieto-occipital lobe atrophy, hypoperfusion and/or glucose metabolism reduction in the right posterior cerebrum can be seen in PCA. Cholinesterase inhibitors (ChEIs may improve the symptoms and postpone the progression of illness. No unified diagnostic criteria will reduce the comparability between different studies. Reasonable usage of the diagnostic criteria of PCA will be helpful in classifying and differentiating this disease. DOI: 10.3969/j.issn.1672-6731.2016.06.011

  13. Thyrotoxic Dysphagia in an 82-Year-Old Male

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    Konstantinos Parperis


    Full Text Available Dysphagia is a common problem in elderly patients and a rare manifestation of Graves' disease. We report a case of an 82-year-old male who presented with a 4-week history of dysphagia and weight loss. Workup for his dysphagia with upper endoscopy, MRI brain, electromyography, acetyl-cholinesterase receptor antibodies, and voltage-gated calcium channel antibodies were negative. Modified Barium swallow test showed oropharyngeal dysphagia. Thyroid function tests that revealed hyperthyroidism and antibodies to TSH-receptor were positive. Based on the above findings, we considered Graves' disease as the most likely diagnosis. Patient was treated with methimazole and beta-blockers and subsequently his dysphagia resolved. This paper highlights the importance to clinicians of considering thyrotoxicosis as possible diagnosis in an elderly patient presenting with unexplained dysphagia.

  14. Organophosphate insecticide poisoning of Canada geese in the Texas panhandle (United States)

    White, D.H.; Mitchell, C.A.; Wynn, L.D.; Flickinger, Edward L.; Kolbe, E.J.


    Sixteen hundred waterfowl, mostly Canada Geese, died near Etter, Texas, in late January 1981 from anticholinesterase poisoning. Winter wheat in the area of the die-off had been treated with organophosphate insecticides to control greenbugs. Cholinesterase (ChE) levels in brains of a sample of geese found dead were 75% below normal, enough to account for death (Ludke et al. 1975). The gastrointestinal (G I) tracts of geese found dead were packed with winter wheat; gas chromatography techniques identified parathion and methyl parathion in the GI tract contents. Residues of both chemicals were confirmed by mass spectrometry. We recommend that less toxic materials, such as malathion, be used on grain crops when waterfowl are in the vicinity of treatment.

  15. Amitraz: a mimicker of organophosphate poisoning. (United States)

    Dhooria, Sahajal; Behera, Digambar; Agarwal, Ritesh


    Amitraz is used as an ectoparasiticide for dogs and cattle. Human poisoning due to amitraz may be misdiagnosed as organophosphate/carbamate (OPC) toxicity, since amitraz poisoning shares several clinical features (miosis, bradycardia and hypotension) encountered with OPC poisoning. A 19-year-old man with an alleged history of suicidal ingestion of a pesticide presented with drowsiness and was found to have constricted pupils, hypotension and bradycardia. He was diagnosed as a case of OPC poisoning and was treated with atropine and pralidoxime prior to presentation to our centre. Absence of a hypersecretory state, and the presence of hyperglycaemia and hypothermia along with a normal serum cholinesterase level suggested an alternate possibility. Retrieval of the poison container confirmed the diagnosis of amitraz poisoning. The patient made a rapid recovery with supportive management. Clinician awareness is key to successful management of this poisoning, which carries a good prognosis.

  16. The use of self-reported symptoms as a proxy for acute organophosphate poisoning after exposure to chlorpyrifos 50 % plus cypermethrin 5 % among Nepali farmers

    DEFF Research Database (Denmark)

    Kofod, Dea Haagensen; Jørs, Erik; Varma, Anshu


    cholinesterase (PchE) activity, in addition to the symptoms, when assessing occupational acute pesticide poisoning. This study evaluated self-reported symptoms as a proxy for acute organophosphate poisoning among Nepali farmers by examining self-reported acute organophosphate poisoning symptoms and PchE activity......%: moderately hazardous) spray session or a 2-h placebo spray session, and after 7 days' washout, the farmers were assigned to the other spray session. Before and after each spray session farmers were interviewed about acute organophosphate poisoning symptoms and PchE activity was measured. Analyses were...... symptoms among the farmers regardless of organophosphate exposure or poisoning. Thus, self-reported acute organophosphate symptoms seem to be a poor proxy for acute organophosphate poisoning as the occurrence of these symptoms is not necessarily associated with acute organophosphate poisoning. TRIAL...

  17. [Gender difference of clinical features in Japanese patients with alcoholic liver cirrhosis]. (United States)

    Kawashima, Osamu; Ohata, Mitsuru; Sakamoto, Kazuhiko; Hashimoto, Kenichi; Nakajima, Hisato; Yamauchi, Masayoshi


    Gender difference of alcohol intake and laboratory data was investigated in 165 Japanese patients with alcoholic liver cirrhosis. Mean age of first drinking and habitual drinking were higher in female. Duration of drinking was shorter in female. Although cumulative alcohol intake was larger in male, mean daily alcohol intake did not differ in both gender. Moreover, daily alcohol intake adjusted to body weight was significantly larger in female. Body mass index, serum levels of total protein, albumin and cholinesterase were significantly decreased in female. Platelet counts on admission did not differ in both gender. However, it was significantly increased in female after one month abstinence. C reactive protein, ammonia and serum levels of total bilirubin were significantly higher in female as compared to male. In conclusion, female alcoholics seems to progress to liver cirrhosis earlier because of high daily alcohol intake adjusted to body weight, poor nutritional condition and inflammation caused by endotoxin.

  18. Biodegradation of a carbamate pesticide, Propoxur, in rat tissues. (United States)

    Kumar, R; Madhavi, N B; Sharma, C B


    Propoxur (Baygon, 2-isopropoxyphenyl N-methylcarbamate) is a carbamate pesticide commonly used against house insects. When the insecticide was administered intramuscularly in rats it was converted to a new metabolite which was found to be present in the serum, liver, kidney and brain 6 h after the administration of the pesticide. The metabolite was purified by high performance liquid to chromatography and comparison of the infrared spectra of Propoxur and the metabolite showed that a deamination reaction was responsible for the formation of the metabolite from the parent pesticide. The pesticide also induced haematological changes such as an increased level of total bilubrin, amylase and glutamic-oxalacetic transaminase and decrease of cholinesterase activity, indicating damage of the liver and nervous system in rats.

  19. [Fatal poisonings with propoxur]. (United States)

    Pfordt, J; Magerl, H; Vock, R


    The insecticide propoxur (2-isopropoxyphenyl-N-methylcarbamate) acts by blocking cholinesterase. This inhibition is fast and, unlike that brought about by organophosphorus compounds, reversible. The toxicity of propoxur to man is stated to be low compared with that of parathion. Only a small number of fatal intoxications have been published; at the Würzburg University Institute of Legal Medicine eight cases have been observed since 1978. In seven cases death occurred after deliberate oral ingestion of solutions of propoxur with suicidal intent, while in the other, intoxication was accidental, following inhalation of an aerosol containing propoxur. Organs and body fluids were investigated toxicologically and histologically. The results are presented and discussed. Special attention is paid to the combination of propoxur and alcohol.

  20. Rapid enzymatic response to compensate UV radiation in copepods.

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    María Sol Souza

    Full Text Available Ultraviolet radiation (UVR causes physical damage to DNA, carboxylation of proteins and peroxidation of lipids in copepod crustaceans, ubiquitous and abundant secondary producers in most aquatic ecosystems. Copepod adaptations for long duration exposures include changes in behaviour, changes in pigmentation and ultimately changes in morphology. Adaptations to short-term exposures are little studied. Here we show that short-duration exposure to UVR causes the freshwater calanoid copepod, Eudiaptomus gracilis, to rapidly activate production of enzymes that prevent widespread collateral peroxidation (glutathione S-transferase, GST, that regulate apoptosis cell death (Caspase-3, Casp-3, and that facilitate neurotransmissions (cholinesterase-ChE. None of these enzyme systems is alone sufficient, but they act in concert to reduce the stress level of the organism. The interplay among enzymatic responses provides useful information on how organisms respond to environmental stressors acting on short time scales.