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Sample records for cholinesterase

  1. Cholinesterase inhibitors from botanicals

    Directory of Open Access Journals (Sweden)

    Faiyaz Ahmed

    2013-01-01

    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 www.Chemspider.com are also presented and the scope for future research is discussed.

  2. Cholinesterase modulations in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

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

    2011-01-01

    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....

  3. MEASURING CHOLINESTERASE ACTIVITY IN HUMAN SALIVA.

    Science.gov (United States)

    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...

  4. Cholinesterase of skeletal muscle and its subcellular components.

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    Fujii,Masafumi

    1982-06-01

    Full Text Available The cholinesterase activity of skeletal muscle and its subcellular components, including motor endplates, was compared chemically in human, mouse and rat. The total cholinesterase activity of muscle per unit protein was in the descending order of human, mouse and rat. Cholinesterase was present in all subcellular components fractionated by differential centrifugation, and was greatest in the microsome fraction followed, in descending order, by the mitochondria, myofibril, and supernatant fractions. Each of these fractions had greater cholinesterase activity in human muscle than in mouse muscle, and in mouse muscle than in rat muscle. The ratio of the activity of the microsome fraction to the activity of muscle homogenate was 11.1 in human, 4.6 in mouse and 3.4 in rat. Because of its relatively greater proportion, the myofibril fraction seems to contribute most to the total cholinesterase activity of muscle. Muscle membrane contained high cholinesterase activity of motor endplates, and the activity was greater than the activity of the microsome fraction in rat. Cholinesterase activity per motor endplate was in the descending order of rat, human and mouse, and the variation was less than the variation in the total muscle cholinesterase activity among these species.

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

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    Sharan Badiger

    2016-04-01

    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.

  6. [Plasma cholinesterase activity in hepatic diseases].

    Science.gov (United States)

    Araoud, Manel; Mhenni, Hamida; Hellara, Ilhem; Hellara, Olfa; Neffati, Fadoua; Douki, Wahiba; Mili, Marwa; Saffar, Hammouda; Najjar, Mohamed Fadhel

    2013-01-01

    Plasma cholinesterase activity (ChE) may vary in some pathological circumstances. We studied the changes in activity of this enzyme according to the type of liver injury, to assess the interest of this parameter in the diagnosis of liver diseases. Our study was performed on 102 patients with different liver diseases and 53 healthy controls. The ChE activity was lower in patients compared to control group (p < 0.0001), and more pronounced in cirrhotic patients compared to those suffering from hepatitis. Elevated activities of AST, ALT, GGT and ALP and bilirubinemia, and decreased albuminemia were noted in patients compared to controls (p < 0.001). Hypoalbuminemia was significantly important in cirrhotic patients compared to those suffering from cholestasis or hepatitis. A correlation between ChE and bilirubin, albumin and serum protein was found in patients with cirrhosis or those with chronic hepatitis. A significantly lower activity of ChE was found in patients with hepatic insufficiency (HI). In case of suspicion of HI, the prescription of ChE activity could guide or confirm the diagnosis of the impairment. PMID:23747666

  7. Motor endplate cholinesterase in human skeletal muscle.

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    Fujii,Masafumi

    1982-08-01

    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.

  8. Effects of inhaled hexamethylene diisocyanate (HDI) on guinea pig cholinesterases.

    Science.gov (United States)

    Karol, M H; Hansen, G A; Brown, W E

    1984-04-01

    Hexamethylene diisocyanate, HDI, a starting material in the production of many polyurethane products, was found to inhibit stoichiometrically mammalian and electric eel cholinesterases in an in vivo system (W. E. Brown, A. H. Green, M. H. Karol, and Y. Alarie , 1982, Toxicol . Appl. Pharmacol. 62, 45-52). The current study examined in vivo effects on guinea pig cholinesterases resulting from inhalation of HDI. Guinea pigs were exposed to atmospheres of 0.5, 1.8, or 4.0 ppm HDI (ceiling value = 0.02 ppm) for up to 6 hr. Blood samples were drawn prior to exposure and at specified times during exposure. No inhibition of serum cholinesterase was detected following exposure to 0.5 ppm HDI for 6 hr, to 1.8 ppm HDI for 2 hr, or to 4.0 ppm HDI for 3 hr. Similarly, no inhibition was detected when erythrocytes from each blood sample were assayed for acetylcholinesterase activity. Last, animals were sacrificed and cholinesterase activity determined in bronchial lavage fluid. Enzyme levels of HDI-exposed animals were not significantly different (P greater than 0.05) from those of control animals exposed to water vapor. In conclusion, although in vitro experiments had demonstrated potent anticholinesterase activity by HDI, in vivo inhalation exposure of guinea pigs to HDI at concentrations 25-200 times above the recommended (ACGIH) ceiling value did not produce measurable inhibition of cholinesterase activity. PMID:6724200

  9. Structure-Based Search for New Inhibitors of Cholinesterases

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    Barbara Malawska

    2013-03-01

    Full Text Available Cholinesterases are important biological targets responsible for regulation of cholinergic transmission, and their inhibitors are used for the treatment of Alzheimer’s disease. To design new cholinesterase inhibitors, of different structure-based design strategies was followed, including the modification of compounds from a previously developed library and a fragment-based design approach. This led to the selection of heterodimeric structures as potential inhibitors. Synthesis and biological evaluation of selected candidates confirmed that the designed compounds were acetylcholinesterase inhibitors with IC50 values in the mid-nanomolar to low micromolar range, and some of them were also butyrylcholinesterase inhibitors.

  10. Inhibition Mechanism of Cholinesterases by Carbamate: A Theoretical Study

    Institute of Scientific and Technical Information of China (English)

    YAO Yuan; LI Ze-sheng

    2008-01-01

    The density functional theory at the B3LYP/6-311G(d,p) level was applied to exploring the inhibition mechanism of cholinesterases by carbamate.The results indicate that the inhibition reactions with or without the catalytic effect of the catalytic triad in cholinesterases underwent a two-step addition-elimination mechanism,which is in good agreement with the proposed mechanism.The solvent has a strong effect on the inhibition reactions and the reaction with the catalytic triad in the solvent phase is close to the real reaction under biological condition.

  11. Native and tabun-inhibited cholinesterase interactions with oximes

    International Nuclear Information System (INIS)

    The phosphorylation of the serine hydroxyl group in the active site of acetylcholinesterase (AChE) inactivates this essential enzyme in neurotransmission. Its related enzyme butyrylcholinesterase (BChE) also interacts with organophosphorus compounds (OP) scavenging anti-cholinesterase agents and protects synaptic AChE from inhibition. Oximes are reactivators of AChE phosphorylated by OP including insecticides and nerve agents. The effectiveness of oxime-assisted reactivation is primarily attributed to the nucleophilic displacement rate of organophosphate, but efficiency varies with the structure of the bound organophosphate, the structure of the oxime as well as rates of several other cholinesterase's reactions. Besides reactivating cholinesterases, oximes also reversibly inhibit both cholinesterases and protect them from phosphorylation by OP. We tested oximes varying in the type of ring (pyridinium and/or imidazolium), the length and type of the linker between rings, and in the position of the oxime group on the ring to find more effective oximes to reactivate tabun-inhibited human erythrocyte AChE and plasma BChE. Herein we bring an overview of in vitro interactions of native and tabun-inhibited AChE and BChE with oximes together with conformational analysis of the oximes relating molecular properties to their reactivation potency.(author)

  12. The effect of cholinesterase inhibitors of SFEMG in myasthenia gravis.

    Science.gov (United States)

    Massey, J M; Sanders, D B; Howard, J F

    1989-02-01

    We report four patients with myasthenia gravis (MG) in whom single-fiber electromyography (SFEMG) jitter measurements were normal in some muslces while they were taking pyridostigmine and became abnormal 2-14 days after the medication was discontinued. When the abnormality of neuromuscular transmission in MG is mild, cholinesterase inhibitors may mask the findings of increased jitter on SFEMG. PMID:2540433

  13. [Levels of plasma cholinesterase in Colombian working-class populations].

    Science.gov (United States)

    Carmona-Fonseca, Jaime

    2003-12-01

    Levels of plasma cholinesterase in Colombian working-class populations Reference values for plasma cholinesterase (EC 3.1.1.8) are not available for Colombian populations. A representative sample of a working-class population was used to establish these values to provide reference data for use by the social security system. Two working-class populations were sampled from the Aburrá Valley (Aburrá) and eastern Antioquia (Oriente). Cholinesterase activity was measured in 827 workers, with ages spanning 18-49 years, 415 from Aburrá and 412 people from Oriente. Three methods were used to measure cholinesterase: Michel, EQM and Monotest The average values by Michel and EQM were not statistically different between regions (Michel: Aburrá, 1.11, and East, 1.13 deltas pH/hora; EQM: Aburrá, 2.55, and Oriente, 2.48 U/ml). By the Monotest, the enzyme average was statistically higher in Aburra than in Oriente (5,743 and 5,459 U/L respectively; p = 0 .012). By region and technique, men had significantly higher enzymatic levels than women. Within both regions and sexes, no statistically significant difference among the three aged groups was noted. Our obtained Colombian values differed significantly from foreign reference values: Michel and Monotest levels were higher and EQM levels were lower. For making clinical and epidemiologic decisions in Colombia related to these data, the values obtained for the Colombian populations are preferred over values derived from external sources. PMID:14968922

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

    Science.gov (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. Automated conductimetric assay of human serum cholinesterase activity.

    Science.gov (United States)

    Duffy, P; Wallach, J M

    1989-01-01

    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).

  16. A review on cholinesterase inhibitors for Alzheimer's disease.

    Science.gov (United States)

    Anand, Preet; Singh, Baldev

    2013-04-01

    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.

  17. Pharmacoeconomics of cholinesterase inhibitors in the treatment of Alzheimer's disease.

    Science.gov (United States)

    Jönsson, Linus

    2003-01-01

    Cholinesterase inhibitors constitute one of few treatment options available for Alzheimer's disease, the most common cause of dementia. The modest effects and relatively high acquisition costs of these drugs make the health economics of dementia an important subject of study. Simulation models can be used to bring together existing data and make predictions of the long-term cost effectiveness of treatment. Most models have been built around cognitive function as a key parameter based on the observed relationship between cognitive function and costs of care. Patients with more severe disease attain higher total costs of care. Also, these patients have a higher share of formal care costs than do patients with mild disease, who are usually looked after by informal caregivers. The valuation of unpaid care is controversial, and the choice of method may affect results considerably. Another important issue is the measurement of health-related QOL in patients with Alzheimer's disease. The few existing studies have used proxy respondents to elicit utility weights in different disease states; however, this methodology has not been validated. It is likely that the increased drug costs incurred by the use of cholinesterase inhibitors will be offset (at least partly) by savings in other healthcare costs. However, these results should be viewed as preliminary, since we are still awaiting data from long-term follow-up studies. Also, the value of treatment for patients and caregivers in terms of QOL improvements has yet to be established. PMID:13129415

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

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    II-Sei Watanabe

    1986-12-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Carla eFalugi

    2012-04-01

    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. 3.1.1.7 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.

  20. Electrochemical sensor based on Arthrobacter globiformis for cholinesterase activity determination.

    Science.gov (United States)

    Stoytcheva, Margarita; Zlatev, Roumen; Valdez, Benjamin; Magnin, Jean-Pierre; Velkova, Zdravka

    2006-07-15

    The sensors applied recently for determination of cholinesterase activity are mostly enzymatic amperometric sensors, in spite of their disadvantages: short life-time at ambient temperature, instability of the response, interferences, as well as passivation of the electrode surface. In the present paper a new approach for determination of cholinesterase activity was proposed, overcoming the main drawbacks of the analysis performed with amperometric enzymatic sensors. Instead of the immobilization of enzymes on a conducting electrode surface, whole cells of Arthrobacter globiformis, containing choline oxidase were fixed on a Clark type oxygen probe. Current proportional to bacteria respiration is registered as a sensor response. The application of whole cells of bacteria as a sensing element permits to achieve high stability of the response and long life-time of the sensor at ambient temperature, due to the conservation of the enzyme in its natural micro-environment inside the immobilized cells. The proposed sensor keeps its functionality more than 7 weeks stored in deionized water at ambient temperature. For the first 2 weeks the amplitude of the response decreases with only 10% and at the end of the studied 7 weeks period the response was 50% of the initial. The other advantages of the proposed sensor are: the dissolved oxygen is used as a mediator which concentration can be reliably and interferences free measured by the aim of a Clark type oxygen probe applied as a transducer; reproducible bacterial membranes can be elaborated by filtration of resuspended bacterial culture after preliminary determination of its activity; application of membranes containing lyophilized bacteria capable to be conserved infinitely long time and activated just before their application; negligible cost compared with the sensors based on immobilized enzymes. The steady-state response of the proposed bacterial sensor to choline obtained in 200 s is linear in the investigated

  1. Cholinesterase inhibitors from the roots of Harpagophytum procumbens.

    Science.gov (United States)

    Bae, Yoon Ho; Cuong, To Dao; Hung, Tran Manh; Kim, Jeong Ah; Woo, Mi Hee; Byeon, Jeong Su; Choi, Jae Sue; Min, Byung Sun

    2014-01-01

    Inhibition of cholinesterase has been proposed to be a therapeutic target for the treatment of Alzheimer's diseases. In our preliminary screening study on the acetylcholinesterase (AChE) inhibitory activity, an ethyl acetate soluble fraction of the roots of Harpagophytum procumbens (Pedaliaceae) was found to inhibit AChE activity at the concentration of 100 μg/mL. Ten compounds (1-10) were isolated from the active fraction and evaluated for their inhibitory effect on AChE and butyrylcholinesterase (BChE). Among the isolates, verbascosides (5, 6, and 8) containing a caffeoyl and a 3,4-dihydroxyphenethyl groups in their structures, showed effective AChE inhibitory activity and also possessed BChE inhibitory activity. The findings suggest that verbascoside derivatives may be partially related to the anti-Alzheimer effect of this medicinal plant. PMID:24374905

  2. REPEATED INHIBITION OF CHOLINESTERASE BY CHLORPYRIFOS IN RATS: BEHAVIORAL, NEUROCHEMICAL AND PHARMACOLOGICAL INDICES OF TOLERANCE

    Science.gov (United States)

    Daily sc injections of the organophosphate (OP) diisopropylfluorophosphate (DFP) caused prolonged inhibition of cholinesterase (ChE) activity in whole blood and brain and downregulation of muscarinic receptors in the CNS; these changes were accompanied by progressive, persistent ...

  3. Cholinesterase activity in rat liver and serum during experimentally induced inflammation.

    Science.gov (United States)

    Simon, G; Budavári, I

    1977-01-01

    Cholinesterase activity of albino rats with acute local oedematous inflammation induced by turpentine, croton oil or Freund's adjuvant was elevated in the liver homogenate but decreased in the serum. Aprotinin administration prevented the decrease of serum activity. In the oedema fluid of rats treated with croton oil an enzyme with cholinester splitting activity was detected and it was shown to be identical with serum cholinesterase (EC 3. 1. 1. 8.). PMID:311577

  4. [Study of the interaction of main potato glycoalkaloids in inhibition of immobilized butyryl cholinesterase].

    Science.gov (United States)

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

    2006-01-01

    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.

  5. The Correlative Study of Serum Pseudo-cholinesterase, Biological Parameters and Symptoms Among Occupational Workers

    OpenAIRE

    Tunsaringkarn, Tanasorn; Zapuang, Kalaya; Rungsiyothin, Anusorn

    2013-01-01

    Cholinesterase is one of many important enzymes needed for acetylcholine hydrolysis. This study aimed to evaluate the serum pseudo-cholinesterase (BuChE) level and its relation to biological parameters (hematological and biochemical parameters) and symptoms among occupational workers, gasoline station worker in Bangkok, Thailand. Our results revealed that the average BuChE level was in normal range, but it had strong relation to hemoglobin (Hb), hematocrit (Hct), blood urea nitrogen (BUN), cr...

  6. Characterizations of cholinesterases in golden apple snail (Pomacea canaliculata).

    Science.gov (United States)

    Zou, Xiang-Hui; Xie, Heidi Qun-Hui; Zha, Guang-Cai; Chen, Vicky Ping; Sun, Yan-Jie; Zheng, Yu-Zhong; Tsim, Karl Wah-Keung; Dong, Tina Ting-Xia; Choi, Roy Chi-Yan; Luk, Wilson Kin-Wai

    2014-07-01

    Cholinesterases (ChEs) have been identified in vertebrates and invertebrates. Inhibition of ChE activity in invertebrates, such as bivalve molluscs, has been used to evaluate the exposure of organophosphates, carbamate pesticides, and heavy metals in the marine system. The golden apple snail (Pomacea canaliculata) is considered as one of the worst invasive alien species harmful to rice and other crops. The ChE(s) in this animal, which has been found recently, but poorly characterized thus far, could serve as biomarker(s) for environmental surveillance as well as a potential target for the pest control. In this study, the tissue distribution, substrate preference, sensitivity to ChE inhibitors, and molecular species of ChEs in P. canaliculata were investigated. It was found that the activities of both AChE and BChE were present in all test tissues. The intestine had the most abundant ChE activities. Both enzymes had fair activities in the head, kidney, and gills. The BChE activity was more sensitive to tetra-isopropylpyrophosphoramide (iso-OMPA) than the AChE. Only one BChE molecular species, 5.8S, was found in the intestine and head, whereas two AChE species, 5.8S and 11.6S, were found there. We propose that intestine ChEs of this snail may be potential biomarkers for manipulating pollutions. PMID:24217797

  7. Purification and studies on characteristics of cholinesterases from Daphnia magna

    Institute of Scientific and Technical Information of China (English)

    Yan-xia YANG; Li-zhi NIU; Shao-nan LI

    2013-01-01

    Due to their significant value in both economy and ecology,Daphnia had long been employed to investigate in vivo response of cholinesterase (ChE) in anticholinesterase exposures,whereas the type constitution and property of the enzyme remained unclear.A type of ChE was purified from Daphnia magna using a three-step procedure,i.e.,Triton X-100 extraction,ammonium sulfate precipitation,and diethylaminoethyl (DEAE)-SepharoseTM-Fast-Flow chromatography.According to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE),molecular mass of the purified ChE was estimated to be 84 kDa.Based on substrate studies,the purified enzyme preferred butyrylthiocholine iodide (BTCh) [with maximum velocity (Vmax)/Michaelis constant (Km)=8.428 L/(min·mg protein)] to acetylthiocholine iodide (ATCh) [with Vmax/Km=5.346 L/(min·mg protein)] as its substrate.Activity of the purified enzyme was suppressed by high concentrations of either ATCh or BTCh.Inhibitor studies showed that the purified enzyme was more sensitive towards inhibition by tetraisopropylpyrophosphoramide (iso-OMPA) than by 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide (BW284C51).Result of the study suggested that the purified ChE was more like a type of pseudocholinesterase,and it also suggested that Daphnia magna contained multiple types of ChE in their bodies.

  8. Diethyl 2-(Phenylcarbamoylphenyl Phosphorothioates: Synthesis, Antimycobacterial Activity and Cholinesterase Inhibition

    Directory of Open Access Journals (Sweden)

    Jarmila Vinšová

    2014-05-01

    Full Text Available A new series of 27 diethyl 2-(phenylcarbamoylphenyl phosphorothioates (thiophosphates was synthesized, characterized by NMR, IR and CHN analyses and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium avium and two strains of Mycobacterium kansasii. The best activity against M. tuberculosis was found for O-{4-bromo-2-[(3,4-dichlorophenylcarbamoyl]phenyl} O,O-diethyl phosphorothioate (minimum inhibitory concentration of 4 µM. The highest activity against nontuberculous mycobacteria was exhibited by O-(5-chloro-2-{[4-(trifluoromethylphenyl]carbamoyl}-phenyl O,O-diethyl phosphorothioate with MIC values from 16 µM. Prepared thiophosphates were also evaluated against acetylcholinesterase from electric eel and butyrylcholinesterase from equine serum. Their inhibitory activity was compared to that of the known cholinesterases inhibitors galanthamine and rivastigmine. All tested compounds showed a higher (for AChE inhibition and comparable (for BChE inhibition activity to that of rivastigmine, with IC50s within the 8.04 to 20.2 µM range.

  9. Recovery of cholinesterase activity in mallard ducklings administered organophosphorus pesticides

    Science.gov (United States)

    Fleming, W.J.; Bradbury, S.P.

    1981-01-01

    Oral doses of the organophosphorus pesticides acephate, dicrotophos, fensulfothion, fonofos, malathion, and parathion were administered to mallard ducklings (Anas platyrhynchos), and brain and plasma cholinesterase (ChE) activities were determined for up to 77 d after dosing. In vivo recovery of brain ChE activity to within 2 standard deviations of the mean activity of undosed birds occurred within 8 d, after being depressed an average of 25-58% at 24 h after dosing. In vivo recovery of plasma ChE appeared as fast as or faster than that of brain, but the pattern of recovery was more erratic and therefore statistical comparison with brain ChE recovery was not attempted. In vitro tests indicated that the potential for dephosphorylation to contribute to in vivo recovery of inhibited brain ChE differed among chemical treatments. Some ducklings died as a result of organophosphate dosing. In an experiment in which ducklings within each treatment group received the same dose (mg/kg), the brain ChE activity in birds that died was less than that in birds that survived. Brain ChE activities in ducklings that died were significantly different among pesticide treatments: fensulfothion > parathion> acephate > malathion (p < 0.05).

  10. Behavioral changes and cholinesterase activity of rats acutely treated with propoxur.

    Science.gov (United States)

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

    1999-01-01

    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.

  11. Potential association of reduced cholinesterase activity with Trypanosoma evansi pathogenesis in buffaloes.

    Science.gov (United States)

    Singh, Shanker K; Singh, Vivek K; Yadav, Brajesh K; Nakade, Udayraj P; Kumari, Priyambada; Srivastava, Mukesh K; Sharma, Abhishek; Choudhary, Soumen; Swain, Dilip; Garg, Satish K

    2016-07-30

    The present study aimed to investigate the association of cholinesterase activity with trypanosomosis in buffaloes. Thirty-three clinical cases of trypanosomosis in water buffaloes, found positive for trypomastigotes of T. evansi on blood smear examination, were divided into two groups based on clinical manifestations. Twenty diseased buffaloes revealing only common clinical signs were allocated to Group I, while the remaining 13 buffaloes showing common clinical manifestations along with neurological disturbances were allocated to Group II. Twelve clinically healthy buffaloes, free from any haemoprotozoa infection, were kept as healthy control (Group III). Blood samples were collected from buffaloes of all three groups to determine serum cholinesterase activity. Compared to buffaloes of healthy control group, cholinesterase activity in T. evansi-infected buffaloes of Group I and II was significantly (Pbuffaloes exhibiting neurological disorders and no neurological disorders. Summing up, reduced cholinesterase activity seems to be associated with the pathogenesis of natural T. evansi infection and its clinical manifestations in buffaloes possibly by evading immune response. Further studies are warranted on association of cholinesterase activity in T. evansi-infected buffaloes with neurological disorders. PMID:27369572

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

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    S Austin Richard

    2013-08-01

    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.

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

    Science.gov (United States)

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

    2008-10-01

    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.

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

    Science.gov (United States)

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

    2008-10-01

    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. PMID:18514898

  15. Cholinesterase inhibitors and hospitalization for bradycardia: a population-based study.

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    Laura Y Park-Wyllie

    2009-09-01

    Full Text Available BACKGROUND: Cholinesterase inhibitors are commonly used to treat dementia. These drugs enhance the effects of acetylcholine, and reports suggest they may precipitate bradycardia in some patients. We aimed to examine the association between use of cholinesterase inhibitors and hospitalization for bradycardia. METHODS AND FINDINGS: We examined the health care records of more than 1.4 million older adults using a case-time-control design, allowing each individual to serve as his or her own control. Case patients were residents of Ontario, Canada, aged 67 y or older hospitalized for bradycardia between January 1, 2003 and March 31, 2008. Control patients (3:1 were not hospitalized for bradycardia, and were matched to the corresponding case on age, sex, and a disease risk index. All patients had received cholinesterase inhibitor therapy in the 9 mo preceding the index hospitalization. We identified 1,009 community-dwelling older persons hospitalized for bradycardia within 9 mo of using a cholinesterase inhibitor. Of these, 161 cases informed the matched analysis of discordant pairs. Of these, 17 (11% required a pacemaker during hospitalization, and six (4% died prior to discharge. After adjusting for temporal changes in drug utilization, hospitalization for bradycardia was associated with recent initiation of a cholinesterase inhibitor (adjusted odds ratio [OR] 2.13, 95% confidence interval [CI] 1.29-3.51. The risk was similar among individuals with pre-existing cardiac disease (adjusted OR 2.25, 95% CI 1.18-4.28 and those receiving negative chronotropic drugs (adjusted OR 2.34, 95% CI 1.16-4.71. We found no such association when we replicated the analysis using proton pump inhibitors as a neutral exposure. Despite hospitalization for bradycardia, more than half of the patients (78 of 138 cases [57%] who survived to discharge subsequently resumed cholinesterase inhibitor therapy. CONCLUSIONS: Among older patients, initiation of cholinesterase

  16. [Change of cholinesterase relative activity under modulated ultra high frequency electromagnetic radiation in experiments in vitro].

    Science.gov (United States)

    Pashovkina, M S; Pashovkin, T N

    2011-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-01-01

    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.

  18. Caregiver Acceptance of Adverse Effects and Use of Cholinesterase Inhibitors in Alzheimer's Disease

    Science.gov (United States)

    Oremus, Mark; Wolfson, Christina; Vandal, Alain C.; Bergman, Howard; Xie, Qihao

    2007-01-01

    Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire…

  19. Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice

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    Andrea R. Durrant

    2012-06-01

    Full Text Available The cholinesterases, acetylcholinesterase and butyrylcholinesterase (pseudocholinesterase, are abundant in the nervous system and in other tissues. The role of acetylcholinesterase in terminating transmitter action in the peripheral and central nervous system is well understood. However, both knowledge of the function(s of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited. This study investigates acetylcholinesterase and butyrylcholinesterase in sera of dystrophin-deficient mdx mutant mice, an animal model for the human Duchenne muscular dystrophy and in control healthy mice. The data show systematic and differential variations in the concentrations of both enzymes in the sera, and specific changes dictated by alteration of hormonal balance in both healthy and dystrophic mice. While acetylcholinesterase in mdx-sera is elevated, butyrylcholinesterase is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls. The androgen testosterone (T is a negative modulator of butyrylcholinesterase, but not of acetylcholinesterase, in male mouse sera. T-removal elevated both butyrylcholinesterase activity and the butyrylcholinesterase/acetylcholinesterase ratio in mdx male sera to values resembling those in healthy control male mice. Mechanisms of regulation of the circulating cholinesterases and their impairment in the dystrophic mice are suggested, and clinical implications for diagnosis and treatment are considered.

  20. Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease.

    Science.gov (United States)

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

    2011-12-01

    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.

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

    OpenAIRE

    Ros-Moreno R.M.; Armas-Serra C.De.; Gimenez-Pardo C.; Rodriguez-Caabeiro F.

    2002-01-01

    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 ...

  2. PREDICTING OUTCOME AND SEVERITY IN ACUTE ORGANOPHOSPHOROUS POISONING WITH CLINICAL SCORING AND SERUM CHOLINESTERASE LEVELS

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    Basavaraj R

    2014-11-01

    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

  3. [Role of hormonal and seasonal factors in the effect of vitamin E on cholinesterase activity in the nervous system].

    Science.gov (United States)

    Teplyĭ, D L; Savich, V F

    1975-01-01

    Tests were set up on 73 Citellus fulvus to study the influence exerted by different doses of vitamin E (4 and 8 mg) introduced per os on the activity of the total cholinesterase in various divisions of the central nervous system and also the part played by the hormonal and seasonal factors in this effect. Each test series lasted 30 days (in spring, summer and autumn). The cholinesterase activity was determined after Vensen and Segonzak (1968). The results of the experiments revealed some characteristic trends in the change of the cholinesterase activity occurring under the effect of vitamin E that depended upon a number of factors, such as: the dose of tocopherol, the sex of the animal, time of the year, the brain division under study and the seasonal dynamics of the initial activity. It is shown that in the brain sectors where a material difference existed in the cholinesterase activity between the control males and females it vanished under the effect of tocopherol. On the other hand, in the brain sectors where no such difference existed, it appeared under the effect of tocopherol. The regular character of changes in the cholinesterase activity of the brain and spinal cord produced by different doses of vitamin E suggest the possibility of the brain cholinesterase activity disorders to a play a part in the development of neuro-muscular pathology in cases of the E vitamin deficiency. PMID:1210181

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

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    Samuel Botião Nerilo

    2014-12-01

    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.

  5. Identification of 4-aminoquinoline core for the design of new cholinesterase inhibitors.

    Science.gov (United States)

    Chen, Yao; Bian, Yaoyao; Sun, Yuan; Kang, Chen; Yu, Sheng; Fu, Tingming; Li, Wei; Pei, Yuqiong; Sun, Haopeng

    2016-01-01

    Inhibition of acetylcholinesterase (AChE) using small molecules is still one of the most successful therapeutic strategies in the treatment of Alzheimer's disease (AD). Previously we reported compound T5369186 with a core of quinolone as a new cholinesterase inhibitor. In the present study, in order to identify new cores for the designing of AChE inhibitors, we screened different derivatives of this core with the aim to identify the best core as the starting point for further optimization. Based on the results, we confirmed that only 4-aminoquinoline (compound 04 and 07) had cholinesterase inhibitory effects. Considering the simple structure and high inhibitory potency against AChE, 4-aminoquinoline provides a good starting core for further designing novel multifunctional AChEIs. PMID:27441112

  6. Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of)

    2013-11-15

    A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC{sub 50} = 2.3 ± 0.7 μM) and AChE (IC{sub 50} = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K{sub i}) value to BuChE is 2.91 ± 0.15 μM.

  7. Impact of geriatric comorbidity and polypharmacy on cholinesterase inhibitors prescribing in dementia

    OpenAIRE

    Hoffmann Falk; van den Bussche Hendrik; Wiese Birgitt; Schön Gerhard; Koller Daniela; Eisele Marion; Glaeske Gerd; Scherer Martin; Kaduszkiewicz Hanna

    2011-01-01

    Abstract Background Although most guidelines recommend the use of cholinesterase inhibitors (ChEIs) for mild to moderate Alzheimer's Disease, only a small proportion of affected patients receive these drugs. We aimed to study if geriatric comorbidity and polypharmacy influence the prescription of ChEIs in patients with dementia in Germany. Methods We used claims data of 1,848 incident patients with dementia aged 65 years and older. Inclusion criteria were first outpatient diagnoses for dement...

  8. Anti-cholinesterase activity of the standardized extract of Syzygium aromaticum L.

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    Manoj K. Dalai

    2014-01-01

    Full Text Available Background: Clove (Syzygium aromaticum is a well-known culinary spice with strong aroma; contains a high amount of oil known as clove oil. The major phyto-constituent of the clove oil is eugenol. Clove and its oil possess various medicinal uses in indigenous medicine as an antiseptic, anti-oxidant, analgesic and neuroprotective properties. Thus, it draws much attention among researchers from pharmaceutical, food and cosmetic industries. Objective: The aim of the present study was to determine the anti-cholinesterase activity of the methanol extract of clove, its oil and eugenol. Materials and Methods: In vitro anti-cholinesterase activity of S. aromaticum was performed by a thin layer chromatography bio autography, 96 well micro titer plate and kinetic methods. Reverse phase high performance liquid chromatography (RP-HPLC analysis was carried out to identify the biomarker compound eugenol in clove oil. Results: Acetylcholinesterase (AChE and butyrylcholinesterase (BChE inhibition study revealed that eugenol possess better inhibition of the enzymes than extract and oil. Clove extract, its oil and eugenol showed better inhibition of AChE than BChE. Polyphenolic compound eugenol was detected through RP-HPLC analysis. The content of eugenol in essential oil was found to be 0.5 μg/ml. Kinetic analysis of the cholinesterase inhibition study of the extract; clove oil and eugenol have shown that they possess mixed type of inhibition for AChE and non-competitive type of inhibition for BChE. Conclusion: These results might be useful in explaining the effect of clove as anti-cholinesterase agent for the management of cognitive ailments like Alzheimer′s disease.

  9. PON1 Status Does Not Influence Cholinesterase Activity in Egyptian Agricultural Workers Exposed to Chlorpyrifos

    OpenAIRE

    Ellison, Corie A.; Crane, Alice L.; Bonner, Matthew R; Knaak, James B.; Browne, Richard W; Lein, Pamela J; Olson, James R.

    2012-01-01

    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 ...

  10. 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

    2013-03-01

    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

  11. The Activity of Cholinesterases in Diapausing and Flying Red Mason Bees Osmia bicornis (Megachilidae).

    Science.gov (United States)

    Dmochowska-Slezak, Kamila; Zaobidna, Ewa; Domeracka, Joanna; Swiatkowska, Marta; Rusznica, Małgorzata; Zółtowska, Krystyna

    2015-01-01

    The red mason bee (Osmia bicornis) is a highly effective pollinator that is exposed to various xenobiotics. The organism's potential resistance to the toxic effects of xenobiotics can be determined based on cholinesterase activity. The activity of cholinesterases (ChEs) towards acetylcholine (ACh) and butyrylcholine (BCh) was determined in extracts of diapausing (between October and late March) and flying bees (May). In both males and females, enzyme activity was higher towards ACh than towards BCh. The ratio of ACh/BCh activity was determined in the range of 1.43 to 4.15 in diapausing females and 3.00 to 7.18 in diapausing males. No significant changes in ChE activity towards ACh were observed in females before December and in males before February. Enzyme activity towards ACh increased dynamically in the second half of March. Enzyme activity towards BCh remained stable in both sexes until mid-March, after which it increased significantly. Excluding mid-March, enzyme BCh activity was significantly higher in females than in males. The activity of carboxylesterase towards 4-p-nitrophenyl butyrate was determined in females to assess the involvement of non-specific esterases in the hydrolysis of choline esters. Carboxylesterase activity was low in comparison with cholinesterase activity, and it remained practically unchanged throughout diapause, suggesting that choline esters in female O. bicornis extracts were hydrolyzed mainly by acetylcholinesterases. PMID:26975137

  12. Serum and Plasma Cholinesterase Activity in the Cape Griffon Vulture (Gyps coprotheres).

    Science.gov (United States)

    Naidoo, Vinny; Wolter, Kerri

    2016-04-28

    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.

  13. Serum and Plasma Cholinesterase Activity in the Cape Griffon Vulture (Gyps coprotheres).

    Science.gov (United States)

    Naidoo, Vinny; Wolter, Kerri

    2016-04-28

    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. PMID:26981685

  14. Cholinesterase-inhibiting and genotoxic effects of acute carbofuran intoxication in man: a case report.

    Science.gov (United States)

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

    2008-10-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Himanshu Madaan

    2011-04-01

    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.

  16. New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity

    Directory of Open Access Journals (Sweden)

    Mehran Fadaeinasab

    2015-11-01

    Full Text Available Background/Aims: Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1 and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2, along with five known, macusine B (3, vinorine (4, undulifoline (5, isoresrpiline (6 and rescinnamine (7 were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE and butyrylcholinesterase (BChE. Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Conclusion: Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations.

  17. 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

    2008-01-01

    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...

  18. Recovery of cholinesterase activity in five avian species exposed to dicrotophos, an organophosphorus pesticide

    Science.gov (United States)

    Fleming, W.J.; Grue, C.E.

    1981-01-01

    The responses of brain and plasma cholinesterase (ChE) activities were examined in mallard ducks, bobwhite quail, barn owls, starlings, and common grackles given oral doses of dicrotophos, an organophosphorus insecticide. Up to an eightfold difference in response of brain ChE activity to dicrotophos was found among these species. Brain ChE activity recovered to within 2 SD of normal within 26 days after being depressed 55 to 64%. Recovery of brain ChE activity was similar among species and followed the model Y = a + b (log10X).

  19. Arylesterase Phenotype-Specific Positive Association Between Arylesterase Activity and Cholinesterase Specific Activity in Human Serum

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    Yutaka Aoki

    2014-01-01

    Full Text Available Context: Cholinesterase (ChE specific activity is the ratio of ChE activity to ChE mass and, as a biomarker of exposure to cholinesterase inhibitors, has a potential advantage over simple ChE activity. Objective: To examine the association of several potential correlates (serum arylesterase/paraoxonase activity, serum albumin, sex, age, month of blood collection, and smoking with plasma ChE specific activity. Methods: We analyzed data from 195 cancer-free controls from a nested case-control study, accounting for potential confounding. Results: Arylesterase activity had an independent, statistically significant positive association with ChE specific activity, and its magnitude was the greatest for the arylesterase phenotype corresponding to the QQ PON1192 genotype followed by phenotypes corresponding to QR and RR genotypes. Serum albumin was positively associated with ChE specific activity. Conclusions: Plasma arylesterase activity was positively associated with plasma ChE specific activity. This observation is consistent with protection conferred by a metabolic phenotype resulting in reduced internal dose.

  20. Variation of Cholinesterase-Based Biosensor Sensitivity to Inhibition by Organophosphate Due To Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Miroslav Pohanka

    2009-07-01

    Full Text Available A cholinesterase based biosensor was constructed in order to assess the effects of ionizing radiation on exposed AChE. Although the primary objective of the experiment was to investigate the effect of ionizing radiation on the activity of the biosensor, no changes in cholinesterase activity were observed. Current provided by oxidation of thiocholine previously created from acetylthiocholine by enzyme catalyzed reaction was in a range 395–455 nA. No significant influence of radiation on AChE activity was found, despite the current variation. However, a surprising phenomenon was observed when a model organophosphate paraoxon was assayed. Irradiated biosensors seem to be more susceptible to the inhibitory effects of paraoxon. Control biosensors provided a 94 ± 5 nA current after exposure to 1 ppm paraoxon. The biosensors irradiated by a 5 kGy radiation dose and exposed to paraoxon provided a current of 49 ± 6 nA. Irradiation by doses ranging from 5 mGy to 100 kGy were investigated and the mentioned effect was confirmed at doses above 50 Gy. After the first promising experiments, biosensors irradiated by 5 kGy were used for calibration on paraoxon and compared with the control biosensors. Limits of detection 2.5 and 3.8 ppb were achieved for irradiated and non-irradiated biosensors respectively. The overall impact of this effect is discussed.

  1. Chemical and molecular aspects on interactions of galanthamine and its derivatives with cholinesterases.

    Science.gov (United States)

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

    2015-01-01

    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.

  2. Sesquiterpene Lactones from Cynara cornigera: Acetyl Cholinesterase Inhibition and In Silico Ligand Docking.

    Science.gov (United States)

    Hegazy, Mohamed-Elamir F; Ibrahim, Abeer Y; Mohamed, Tarik A; Shahat, Abdelaaty A; El Halawany, Ali M; Abdel-Azim, Nahla S; Alsaid, Mansour S; Paré, Paul W

    2016-01-01

    Wild artichoke (Cynara cornigera), a thistle-like perennial belonging to the Asteraceae family, is native to the Mediterranean region, northwestern Africa, and the Canary Islands. While the pleasant, albeit bitter, taste of the leaves and flowers is attributed to the sesquiterpene lactones cynaropicrin and cynarin, a comprehensive phytochemical investigation still needs to be reported. In this study seven sesquiterpene lactones were isolated from an aqueous methanol plant extract, including a new halogenated metabolite (1), the naturally isolated compound sibthorpine (2), and five metabolites isolated for the first time from C. cornigera. Structures were established by spectroscopic methods, including HREIMS, (1 )H, (13 )C, DEPT, (1 )H-(1 )H COSY, HMQC, and HMBC-NMR experiments as well as by X-ray analysis. The isolated bioactive nutrients were analyzed for their antioxidant and metal chelating activity. Compound 1 exhibited a potent metal chelating activity as well as a high antioxidant capacity. Moreover, select compounds were effective as acetyl cholinesterase inhibitors presenting the possibility for such compounds to be examined for anti-neurodegenerative activity. A computational pharmacophore elucidation and docking study was performed to estimate the pharmacophoric features and binding conformation of isolated compounds in the acetyl cholinesterase active site. PMID:26441064

  3. Effect of acute and chronic cholinesterase inhibition on biogenic amines in rat brain.

    Science.gov (United States)

    Soininen, H; Unni, L; Shillcutt, S

    1990-12-01

    The effects of five cholinesterase inhibitors on forebrain monoamine and their metabolite levels, and on forebrain and plasma cholinesterase (ChE) activity in rat were studied in acute and chronic conditions. Acute tetrahydroaminoacridine (THA) dosing caused lower brain (68%) and higher plasma (90%) ChE inhibition than the other drugs studied and increased levels of brain dihydroxyphenylacetic acid (DOPAC) (236%), homovanillic acid (HVA) (197%) and 5-hydroxyindoleacetic acid (5-HIAA) (130%). Acute physostigmine (PHY) administration caused a 215% increase in brain DOPAC content. Despite high brain ChE inhibition induced by metrifonate (MTF), dichlorvos (DDVP) or naled no changes in brain noradrenaline (NA), dopamine (DA) or serotonin (5-HT) occurred due to treatment with the study drugs in the acute study. In the chronic 10-day study THA or PHY caused no substantial ChE inhibition in brain when measured 18 hours after the last dose, whereas MTF induced 74% ChE inhibition. Long-term treatment with THA or MTF caused no changes in monoamine levels, but PHY treatment resulted in slightly increased 5-HT values. These results suggest that MTF, DDVP and naled seem to act solely by cholinergic mechanisms. However, the central neuropharmacological mechanism of action of THA and PHY may involve changes in cholinergic as well as dopaminergic and serotoninergic systems. PMID:1711162

  4. Synthesis, cholinesterase inhibition and molecular modelling studies of coumarin linked thiourea derivatives.

    Science.gov (United States)

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

    2015-12-01

    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.

  5. A step toward the reactivation of aged cholinesterases-crystal structure of ligands binding to aged human butyrylcholinesterase

    NARCIS (Netherlands)

    Wandhammer, M.; Koning, M. de; Grol, M. van; Loiodice, M.; Saurel, L.; Noort, D.; Goeldner, M.; Nachon, F.

    2013-01-01

    Organophosphorus nerve agents irreversibly inhibit cholinesterases. Phosphylation of the catalytic serine can be reversed by the mean of powerful nucleophiles like oximes. But the phosphyl adduct can undergo a rapid spontaneous reaction leading to an aged enzyme, i.e., a conjugated enzyme that is no

  6. TIME COURSE OF CHOLINESTERASE INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL CARBOFURAN, FORMETANATE, METHOMYL, METHIOCARB, OXAMYL ON PROPOXUR.

    Science.gov (United States)

    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); ...

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

    Directory of Open Access Journals (Sweden)

    Márcio M. Costa

    2012-12-01

    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

  8. Cholinesterase - blood

    Science.gov (United States)

    ... Fenichel GM, Jankovic J, Mazziotta JC, eds. Bradley's Neurology in Clinical Practice . 6th ed. Philadelphia, PA: Elsevier ... 1/2015 Updated by: Daniel Kantor, MD, Kantor Neurology, Coconut Creek, FL and Immediate Past President of ...

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

    Directory of Open Access Journals (Sweden)

    Nelson Jeng-Yeou Chear

    2016-04-01

    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.

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

    Science.gov (United States)

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

    2009-03-01

    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.

  11. Cholinesterase inhibitors in Alzheimer's disease and Lewy body spectrum disorders: the emerging pharmacogenetic story

    Directory of Open Access Journals (Sweden)

    Lam Benjamin

    2009-12-01

    Full Text Available Abstract This review provides an update on the current state of pharmacogenetic research in the treatment of Alzheimer's disease (AD and Lewy body disease (LBD as it pertains to the use of cholinesterase inhibitors (ChEI. AD and LBD are first reviewed from clinical and pathophysiological perspectives. This is followed by a discussion of ChEIs used in the symptomatic treatment of these conditions, focusing on their unique and overlapping pharmacokinetic and pharmacodynamic profiles, which can be used to identify candidate genes for pharmacogenetics studies. The literature published to date is then reviewed and limitations are discussed. This is followed by a discussion of potential endophenotypes which may help to refine future pharmacogenetic studies of response and adverse effects to ChEIs.

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

    Science.gov (United States)

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

    2009-03-01

    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. PMID:19054558

  13. The Arabidopsis thaliana ortholog of a purported maize cholinesterase gene encodes a GDSL-lipase.

    Science.gov (United States)

    Muralidharan, Mrinalini; Buss, Kristina; Larrimore, Katherine E; Segerson, Nicholas A; Kannan, Latha; Mor, Tsafrir S

    2013-04-01

    Acetylcholinesterase is an enzyme that is intimately associated with regulation of synaptic transmission in the cholinergic nervous system and in neuromuscular junctions of animals. However the presence of cholinesterase activity has been described also in non-metazoan organisms such as slime molds, fungi and plants. More recently, a gene purportedly encoding for acetylcholinesterase was cloned from maize. We have cloned the Arabidopsis thaliana homolog of the Zea mays gene, At3g26430, and studied its biochemical properties. Our results indicate that the protein encoded by the gene exhibited lipase activity with preference to long chain substrates but did not hydrolyze choline esters. The At3g26430 protein belongs to the SGNH clan of serine hydrolases, and more specifically to the GDS(L) lipase family. PMID:23430565

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

    Directory of Open Access Journals (Sweden)

    Lucie Cahlíková

    2011-08-01

    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.

  15. Diagnosis of anticholinesterase poisoning in birds: Effects of environmental temperature and underfeeding on cholinesterase activity

    Science.gov (United States)

    Rattner, B.A.

    1982-01-01

    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.

  16. Cholinesterases inhibitory and antioxidant activities of Harpagophytum procumbens from in vitro systems.

    Science.gov (United States)

    Georgiev, Milen I; Alipieva, Kalina; Orhan, Ilkay Erdogan

    2012-02-01

    A previous report showed that extracts of cell suspension and transformed root cultures of Harpagophytum procumbens (commonly known as Devil's claw), an African plant with high medicinal value, exhibit strong antiinflammatory characteristics. The present work tests the ability of extracts, phenylethanoid-containing fractions and the major phenylethanoid glycoside isolated from the Devil's claw cultures, to inhibit acetylcholinesterase and butyrylcholinesterase, and the antioxidant activity in iron-related systems (e.g. ferric-reducing antioxidant power and ferrous ion-chelating capacity). The results indicated that the phenylethanoid fractions may be attractive for various commercial purposes since they displayed significant cholinesterase inhibitory activity (even higher than that of pure galanthamine in the case of butyrylcholinesterase inhibition assay). Crude methanolic extracts from cell and hairy root cultures of Devil's claw exhibited strong ferrous ion-chelating capacity (1.5-2 times higher than pure butylated hydroxyanisole, used as positive standard). PMID:21721061

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

    Science.gov (United States)

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

    1996-11-01

    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.

  18. Temperature: a prolonged confounding factor on cholinesterase activity in the tropical reef fish Acanthochromis polyacanthus.

    Science.gov (United States)

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

    2013-09-15

    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.

  19. Hepatic cholinesterase of laying hens naturally infected by Salmonella Gallinarum (fowl typhoid).

    Science.gov (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

    2016-09-01

    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.

  20. Do cholinesterase inhibitors act primarily on attention deficit? A naturalistic study in Alzheimer's disease patients.

    Science.gov (United States)

    Bracco, Laura; Bessi, Valentina; Padiglioni, Sonia; Marini, Sandro; Pepeu, Giancarlo

    2014-01-01

    Attention is the first non-memory domain affected in Alzheimer's disease (AD), before deficits in language and visuo-spatial function, and it is claimed that attention deficits are responsible for the difficulties with daily living in early demented patients. The aim of this longitudinal study in a group of 121 Caucasian, community-dwelling, mild-to-moderate AD patients (Mini-Mental State Examination (MMSE) score >17) was to detect which cognitive domains were most affected by the disease and whether one year treatment with cholinesterase inhibitors was more effective in preserving attention than memory. All subjects were evaluated by a neuropsychological battery including global measurements (MMSE, Information-Memory-Concentration Test) and tasks exploring verbal long-term memory, language, attention, and executive functions. The comparison between two evaluations, made 12 months apart, shows statistically significant differences, indicating deterioration compared to baseline, in the following tests: MMSE (with no gender differences), Composite Memory Score, Short Story Delayed Recall, Trail-Making Test A, Semantic Fluency Test, and Token Test. Conversely, there were no differences in the two evaluations of the Digit Span, Corsi Tapping Test, Short Story Immediate Recall, and Phonemic Fluency Tests. It appears that the treatment specifically attenuated the decline in tests assessing attention and executive functions. A stabilization of the ability to pay attention, with the ensuing positive effects on executive functions, recent memory, and information acquisition which depend on attention, appears to be the main neuropsychological mechanism through which the activation of the cholinergic system, resulting from cholinesterase inhibition, exerts its effect on cognition. PMID:24577458

  1. Cholinesterase inhibition and behavioral toxicity of carbofuran on Oreochromis niloticus early life stages.

    Science.gov (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

    2011-10-01

    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.

  2. Secondary metabolites of Seseli rigidum: Chemical composition plus antioxidant, antimicrobial and cholinesterase inhibition activity.

    Science.gov (United States)

    Stankov-Jovanović, V P; Ilić, M D; Mitić, V D; Mihajilov-Krstev, T M; Simonović, S R; Nikolić Mandić, S D; Tabet, J C; Cole, R B

    2015-01-01

    Extracts of different polarity obtained from various plant parts (root, leaf, flower and fruit) of Seseli rigidum were studied by different antioxidant assays: DPPH and ABTS radical scavenging activity, by total reducing power method as well as via total content of flavonoids and polyphenols. Essential oils of all plant parts showed weak antioxidant characteristics. The inhibitory concentration range of the tested extracts, against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus, and fungi Candida albicans and Aspergillus niger was 0.01-1.50 mg/mL and of a microbicidal 0.02-3.00 mg/mL. In the interaction with cholinesterase, all essential oils proved effective as inhibitors. The highest percentage of inhibition versus human and horse cholinesterase was shown by root essential oil (38.20% and 48.30%, respectively) among oils, and root hexane extract (40.56% and 50.65% respectively). Essential oils and volatile components of all plant parts were identified by GC, GC-MS and headspace/GC-MS. Statistical analysis of the ensemble of results showed that the root essential oil composition differed significantly from essential oils of other parts of the plant. Taking into account all of the studied activities, the root hexane extract showed the best overall properties. By means of high performance liquid chromatography coupled to high resolution mass spectrometry, the 30 most abundant constituents were identified in extracts of different polarity. The presence of identified constituents was linked to observed specific biological activities, thus designating compounds potentially responsible for each exhibited activity. PMID:25863020

  3. 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

    2015-01-01

    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.

  4. 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

    2015-01-01

    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 butyrylcholinesterasc(BChE)inhibitory activity at 100μg/mL.Antioxidant activity of the extracts was tested using 2,2-diphenyl-1-picrylhydrazyl(DPPH)and N,N-dimethyl-p-phenylendiamine(DMPD)radical scavenging,nietal-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 metalchelation 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.

  5. Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase

    Science.gov (United States)

    Legler, Patricia; Boisvert, Susanne; Compton, Jaimee; Millard, Charles

    2014-07-01

    We applied a combination of rational design and directed evolution (DE) to Bacillus subtilis p-nitrobenzyl esterase (pNBE) with the goal of enhancing organophosphorus acid anhydride hydrolase (OPAAH) activity. DE started with a designed variant, pNBE A107H, carrying a histidine homologous with human butyrylcholinesterase G117H to find complementary mutations that further enhance its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400) within a 6.7 Å radius of the nucleophilic serine O?. All 95 variants were screened for esterase activity with a set of five substrates: pNP-acetate, pNP-butyrate, acetylthiocholine, butyrylthiocholine, or benzoylthiocholine. A microscale assay for OPAAH activity was developed for screening DE libraries. Reductions in esterase activity were generally concomitant with enhancements in OPAAH activity. One variant, A107K, showed an unexpected 7-fold increase in its kcat/Km for benzoylthiocholine, demonstrating that it is also possible to enhance the cholinesterase activity of pNBE. Moreover, DE resulted in at least three variants with modestly enhanced OPAAH activity compared to wild type pNBE. A107H/A190C showed a 50-fold increase in paraoxonase activity and underwent a slow time- and temperature-dependent change affecting the hydrolysis of OPAA and ester substrates. Structural analysis suggests that pNBE may represent a precursor leading to human cholinesterase and carboxylesterase 1 through extension of two vestigial specificity loops; a preliminary attempt to transfer the Ω-loop of BChE into pNBE is described. pNBE was tested as a surrogate scaffold for mammalian esterases. Unlike butyrylcholinesterase and pNBE, introducing a G143H mutation (equivalent to G117H) did not confer detectable OP hydrolase activity on human carboxylesterase 1. We discuss the importance of the oxyanion-hole residues for enhancing the OPAAH activity of selected serine hydrolases.

  6. Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase

    Directory of Open Access Journals (Sweden)

    Patricia Marie Legler

    2014-07-01

    Full Text Available We applied a combination of rational design and directed evolution (DE to Bacillus subtilis p-nitrobenzyl esterase (pNBE with the goal of enhancing organophosphorus acid anhydride hydrolase (OPAAH activity. DE started with a designed variant, pNBE A107H, carrying a histidine homologous with human butyrylcholinesterase G117H to find complementary mutations that further enhance its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400 within a 6.7 Å radius of the nucleophilic serine O. All 95 variants were screened for esterase activity with a set of five substrates: pNP-acetate, pNP-butyrate, acetylthiocholine, butyrylthiocholine, or benzoylthiocholine. A microscale assay for OPAAH activity was developed for screening DE libraries. Reductions in esterase activity were generally concomitant with enhancements in OPAAH activity. One variant, A107K, showed an unexpected 7-fold increase in its kcat/Km for benzoylthiocholine, demonstrating that it is also possible to enhance the cholinesterase activity of pNBE. Moreover, DE resulted in at least three variants with modestly enhanced OPAAH activity compared to wild type pNBE. A107H/A190C showed a 50-fold increase in paraoxonase activity and underwent a slow time- and temperature-dependent change affecting the hydrolysis of OPAA and ester substrates. Structural analysis suggests that pNBE may represent a precursor leading to human cholinesterase and carboxylesterase 1 through extension of two vestigial specificity loops; a preliminary attempt to transfer the Ω-loop of BChE into pNBE is described. pNBE was tested as a surrogate scaffold for mammalian esterases. Unlike butyrylcholinesterase and pNBE, introducing a G143H mutation (equivalent to G117H did not confer detectable OP hydrolase activity on human carboxylesterase 1. We discuss the importance of the oxyanion-hole residues for enhancing the OPAAH activity of selected serine hydrolases.

  7. Recovery of plasmatic cholinesterase activity in a neotropical fish Prochilodus lineatus (Pisces, Curimatidae) exposed to organophosphorous pesticides.

    Science.gov (United States)

    Loteste, Alicia; Cazenave, Jimena; Parma de Croux, M Julieta

    2002-07-01

    The objective was to determine the plasmatic enzyme cholinesterase recovery, after being inhibited by an organophosphorous in juveniles of Prochilodus lineatus. Fish were exposed 12 h to a sublethal concentration of 1 mg/l of monocrotophos, and immediately placing in clean water during 12, 24, 48 and 96 h to detoxification. After this period, blood was extracted and plasma were used for the quantification of cholinesterase. The results showed a enzymatic inhibition of 91.9%, 55.1%, 50.4% and 33.4% with 12, 24, 48 and 96 h of recovery, respectively. The enzymatic activity spreads to be normalized with the course of hours and the degree of inhibition obtained initially was very high and sustained in the first 48 h. PMID:12597563

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

    Directory of Open Access Journals (Sweden)

    Abdulrahman I. Almansour

    2015-01-01

    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.

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

    International Nuclear Information System (INIS)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ellison, Corie A., E-mail: cellison@buffalo.edu [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: alcrane@buffalo.edu [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: mrbonner@buffalo.edu [Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Knaak, James B., E-mail: jbknaak@aol.com [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: rwbrowne@buffalo.edu [Department of Biotechnical and Clinical Laboratory Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, University of California School of Veterinary Medicine, Davis, CA 95618 (United States); Olson, James R., E-mail: jolson@buffalo.edu [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)

    2012-12-15

    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.

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

    Directory of Open Access Journals (Sweden)

    F. Rahimi Anbarkeh

    2015-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Dimitrov Mitko

    2009-08-01

    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.

  14. Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta

    Directory of Open Access Journals (Sweden)

    Michalina Hebda

    2016-03-01

    Full Text Available Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer’s disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention—compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM. Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE (EeAChE IC50 = 0.76 μM, EqBuChE IC50 = 0.618 μM, and it inhibits amyloid beta aggregation (35.8% at 10 μM. Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase. Their ability to cross the blood-brain barrier (BBB was confirmed in vitro in the parallel artificial membrane permeability BBB assay. These compounds can be used as a solid starting point for further development of novel multifunctional ligands as potential anti-Alzheimer’s agents.

  15. Co-opting functions of cholinesterases in neural, limb and stem cell development.

    Science.gov (United States)

    Vogel-Hopker, Astrid; Sperling, Laura E; Layer, Paul G

    2012-02-01

    Acetylcholinesterase (AChE) is a most remarkable protein, not only because it is one of the fastest enzymes in nature, but also since it appears in many molecular forms and is regulated by elaborate genetic networks. As revealed by sensitive histochemical procedures, AChE is expressed specifically in many tissues during development and in many mature organisms, as well as in healthy and diseased states. Therefore it is not surprising that there has been a long-standing search for additional, "non-classical" functions of cholinesterases (ChEs). In principle, AChE could either act nonenzymatically, e.g. exerting cell adhesive roles, or, alternatively, it could work within the frame of classic cholinergic systems, but in non-neural tissues. AChE might be considered a highly co-opting protein, since possibly it combines such various functions within one molecule. By presenting four different developmental cases, we here review i) the expression of ChEs in the neural tube and their close relation to cell proliferation and differentiation, ii) that AChE expression reflects a polycentric brain development, iii) the retina as a model for AChE functioning in neural network formation, and iv) nonneural ChEs in limb development and mature bones. Also, possible roles of AChE in neuritic growth and of cholinergic regulations in stem cells are briefly outlined. PMID:21933123

  16. Simulating the impact of cholinesterase-inhibiting pesticides on non-target wildlife in irrigated crops

    Science.gov (United States)

    Pisani, J.M.; Grant, W.E.; Mora, M.A.

    2008-01-01

    We present a simulation model for risk assessment of the impact of insecticide inhibitors of cholinesterase (ChE) applied in irrigated agricultural fields on non-target wildlife. The model, which we developed as a compartment model based on difference equations (??t = 1 h), consists of six submodels describing the dynamics of (1) insecticide application, (2) insecticide movement into floodable soil, (3) irrigation and rain, (4) insecticide dissolution in water, (5) foraging and insecticide intake from water, and (6) ChE inhibition and recovery. To demonstrate application of the model, we simulated historical and "worst-case" scenarios of the impact of ChE-inhibiting insecticides on white-winged doves (Zenaida asiatica) inhabiting natural brushland adjacent to cotton and sugarcane fields in the Lower Rio Grande Valley of Texas, USA. Only when a rain event occurred just after insecticide application did predicted levels of ChE inhibition surpass the diagnostic level of 20% exposure. The present model should aid in assessing the effect of ChE-inhibiting insecticides on ChE activity of different species that drink contaminated water from irrigated agricultural fields, and in identifying specific situations in which the juxtaposition of environmental conditions and management schemes could result in a high risk to non-target wildlife. ?? 2007 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

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

    1999-01-01

    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.

  19. Bird predation on cutworms (Lepidoptera: Noctuidae) in wheat fields and chlorpyrifos effects on brain cholinesterase activity

    Science.gov (United States)

    McEwen, L.C.; DeWeese, L.R.; Schladweiler, P.

    1986-01-01

    Horned larks, Eremophila alpestris (L.), and McCown's longspurs, Calcarius mccownii (Lawrence), were collected at intervals from two winter wheat fields in Montana [USA] after aerial application of chlorpyrifos to control cutworms. Both bird species had a high (95-100%) incidence of Lepidoptera, mostly pale western cutworms, Agrotis orthogonia Morrison, in their stomachs at 3 days postspray. Incidence of cutworms and other insects in stomachs of birds from sprayed fields was lower at 9 and 16 days postspray than in control birds, presumably due to insecticide-caused reduction of insects. Effects of birds on population dynamics of insect pests in wheat are unknown, but birds do contribute to cutworm mortality. Predation is one of the limiting factors to cutworm increase and can supplement insecticidal control. Brain cholinesterase activity in horned larks collected from the sprayed fields at 3 and 9 days postspray was significantly lower than in unexposed larks, but at 16 days the difference was not significant. Although nontarget birds clearly were exposed to chlorpyrifos and manifested a sublethal physiological response, toxic effects were less severe than those resulting from endrin application for cutworm control in wheat. More study is needed of larger chlorpyrifos-treated fields under a variety of conditions to fully assess effects on nontarget life.

  20. Evaluation of Antioxidant and Acetyl Cholinesterase inhibitory activity of Peltophorum pterocarpum in Scopolamine treated Rats

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    N. B. Sridharamurthy

    2012-09-01

    Full Text Available To evaluate the antioxidant and Acetyl cholinesterase activity of Methanol extract of Peltophorum pterocarpum (MEPP in scopolamine treated rats. The methanol extract was subjected for phytochemical analysis to identify different phytochemical constituents. Neuroprotective activity of methanol extract was studied against accelerated ageing with D-galactose followed by scopolamine to induce memory. Behavioral studies, AChE activity, antioxidant parameters of brain homogenate, serum biochemical parameters and histopathological changes of brain were assessed in Control / Scopolamine / Standard / Extract treated animals. Phytochemical investigation of methanol revealed the presence of carbohydrates, proteins, aminoacids, glycosides, triterpinoids, flavonoids and total phenolic content. D-galactose induced oxidative stress and scopolamine induced memory impairment in rats were significantly prevented by treatment with methanol extract of Peltophorum pterocarpum bark. Methanol extract treated group improved memory in elevated plus maze and Y maze tests, reduction in AChE activity, increased activity of brain antioxidant enzymes such as catalase, super oxide dismutase, glutathione and reducing the increased activity of lipid peroxidation and also reduction in serum biochemical parameter glucose, total cholesterol and reverse in the degenerative changes in the histopathological study of the rat brain. Hence methanol extract of Peltophorum pterocarpum treated animals confirmed the protection of brain against oxidative stress, neurodegeneration and behavioral (learning, memory changes of extract under study.

  1. The relationship between total cholinesterase activity and mortality in four butterfly species.

    Science.gov (United States)

    Bargar, Timothy A

    2012-09-01

    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. PMID:22740147

  2. The relationship between total cholinesterase activity and mortality in four butterfly species

    Science.gov (United States)

    Bargar, Timothy A.

    2012-01-01

    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.

  3. Recovery of brain and plasma cholinesterase activities in ducklings exposed to organophosphorus pesticides

    Science.gov (United States)

    Fleming, W.J.

    1981-01-01

    Brain and plasma cholinesterase (ChE) activities were determined for mallard ducklings (Anas platyrhynchos) exposed to dicrotophos and fenthion. Recovery rates of brain ChE did not differ between ducklings administered a single oral dose vs. a 2-week dietary dose of these organophosphates. Exposure to the organophosphates, followed by recovery of brain ChE, did not significantly affect the degree of brain ChE inhibition or the recovery of ChE activity at a subsequent exposure. Recovery of brain ChE activity followed the general model Y = a + b(logX) with rapid recovery to about 50% of normal, followed by a slower rate of recovery until normal ChE activity levels were attained. Fenthion and dicrotophos-inhibited brain ChE were only slightly reactivated in vitro by pyridine-2-aldoxime methiodide, which suggested that spontaneous reactivation was not a primary method of recovery of ChE activity. Recovery of brain ChE activity can be modeled for interpretation of sublethal inhibition of brain ChE activities in wild birds following environmental applications of organophosphates. Plasma ChE activity is inferior to brain ChE activity for environmental monitoring, because of its rapid recovery and large degree of variation among individuals.

  4. Characterization of catalytic efficiency parameters of brain cholinesterases in tropical fish.

    Science.gov (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

    2014-12-01

    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.

  5. Antioxidant, cholinesterase inhibition activities and essential oil analysis of Nelumbo nucifera seeds.

    Science.gov (United States)

    Khan, Shahnaz; Khan, Hidayatullah; Ali, Farman; Ali, Nayab; Khan, Fahim Ullah; Khan, Sami Ullah

    2016-06-01

    Nelumbo nucifera seeds' essential oil (EO), crude extract and subsequent fractions were evaluated for their DPPH, ABTS and superoxide anion-free radical scavenging and cholinesterase inhibitory activities. The ethyl acetate fraction and EO showed outstanding antioxidant activities with IC50 values of 191, 450 μg/mL (DPPH), 123, 221 μg/mL (ABTS) and 69, 370 μg/mL (superoxide anion). The ethyl acetate fraction and EO also caused significant inhibition of acetylcholinesterase and butyrylcholinesterase with IC50 values of 70 ± 0.6, 64 ± 0.8 and 75 ± 0.3, 58 ± 0.2, in dose-dependent manner. The first ever gas chromatography-mass spectrometry analysis of the EO obtained from N. nucifera seeds resulted in identification of 19 constituents, mainly comprised of oxygenated sesquiterpenes responsible for their promising bioactivity. The crude and fractions revealed the presence of saponins, flavonoids, steroids, alkaloids, terpenoids and cardiac glycosides in phytochemical investigation. PMID:26212099

  6. 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

    Science.gov (United States)

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

    1978-01-01

    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.

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

    Science.gov (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

    2011-01-01

    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

  8. 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

    2011-01-01

    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.

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

    Science.gov (United States)

    Li, Shaonan; Tan, Yajun

    2011-01-01

    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 microg/L and 0.01 to 2.00 microg/L, respectively. For exposure to triazophos, ChE was induced up to 176.5% at 1.5 microg/L and day 10 when measured by acetylthiocholine (ATCh), whereas it was induced up to 174.2% at 0.5 microg/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, respectively, with both maximal inductions detected at 0.1 microg/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. PMID:21790060

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

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    Martin Krátký

    2016-02-01

    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.

  11. Brain cholinesterases: III. Future perspectives of AD research and clinical practice.

    Science.gov (United States)

    Shen, Z-X

    2004-01-01

    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.

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

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    Radosław Świercz

    2013-08-01

    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.

  13. Cholinesterases in development: AChE as a firewall to inhibit cell proliferation and support differentiation.

    Science.gov (United States)

    Layer, Paul G; Klaczinski, Janine; Salfelder, Anika; Sperling, Laura E; Thangaraj, Gopenath; Tuschl, Corina; Vogel-Höpker, Astrid

    2013-03-25

    Acetylcholinesterase (AChE) is a most remarkable protein, not only because it is one of the fastest enzymes in nature, but also since it appears in many molecular forms and is regulated by elaborate genetic networks. AChE is expressed in many tissues during development and in mature organisms, as well as in healthy and diseased states. In search for alternative, "non-classical" functions of cholinesterases (ChEs), AChE could either work within the frame of classic cholinergic systems, but in non-neural tissues ("non-synaptic function"), or act non-enzymatically. Here, we review briefly some of the major ideas and advances of this field, and report on some recent progress from our own experimental work, e.g. that (i) non-neural ChEs have pronounced, predominantly enzymatic effects on early embryonic (limb) development in chick and mouse, that (ii) retinal R28 cells of the rat overexpressing synaptic AChE present a significantly decreased cell proliferation, and that (iii) in developing chick retina ACh-synthesizing and ACh-degrading cells originate from the same postmitotic precursor cells, which later form two locally opposing cell populations. We suggest that such distinct distributions of ChAT(+) vs. AChE(+) cells in the inner half retina provide graded distributions of ACh, which can direct cell differentiation and network formation. Thus, as corroborated by works from many labs, AChE can be considered a highly co-opting protein, which can combine enzymatic and non-enzymatic functions within one molecule. PMID:23047026

  14. Pharmacokinetics and effects on serum cholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric mice transplanted with human hepatocytes.

    Science.gov (United States)

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

    2014-11-01

    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.

  15. Regional inhibition of cholinesterase in free-ranging western pond turtles (Emys marmorata) occupying California mountain streams.

    Science.gov (United States)

    Meyer, Erik; Sparling, Donald; Blumenshine, Steve

    2013-03-01

    The present study investigated the potential effects of cholinesterase (ChE)-inhibiting pesticides on western pond turtles (Emys marmorata) occupying streams in two regions of California, USA. The southern region was suspected of having increased exposure to atmospheric deposition of contaminants originating from Central Valley agriculture. The northern region represented reference ChE activities because this area was located outside of the prominent wind patterns that deposit pesticides into the southern region. Total ChE activity was measured in plasma from a total of 81 turtles from both regions. Cholinesterase activity of turtles was significantly depressed by 31% (p = 0.005) in the southern region after accounting for additional sources of variation in ChE activity. Male turtles had significantly increased ChE activity compared with females (p = 0.054). Cloaca temperature, length, mass, handling time, body condition, and lymph presence were not significant predictors of turtle ChE activity. In the southern region, 6.3% of the turtles were below the diagnostic threshold of two standard deviations less than the reference site mean ChE activity. Another diagnostic threshold determined that 75% of the turtles from the southern region had ChE activities depressed by 20% of the reference mean. The decrease in ChE activity in the southern region suggests sublethal effects of pesticide exposure, potentially altering neurotransmission, which can result in various deleterious behaviors. PMID:23341143

  16. 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.

    2002-06-01

    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.

  17. Phytochemical profile of a blend of black chokeberry and lemon juice with cholinesterase inhibitory effect and antioxidant potential.

    Science.gov (United States)

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

    2012-10-15

    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.

  18. Impact of geriatric comorbidity and polypharmacy on cholinesterase inhibitors prescribing in dementia

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    Hoffmann Falk

    2011-12-01

    Full Text Available Abstract Background Although most guidelines recommend the use of cholinesterase inhibitors (ChEIs for mild to moderate Alzheimer's Disease, only a small proportion of affected patients receive these drugs. We aimed to study if geriatric comorbidity and polypharmacy influence the prescription of ChEIs in patients with dementia in Germany. Methods We used claims data of 1,848 incident patients with dementia aged 65 years and older. Inclusion criteria were first outpatient diagnoses for dementia in at least three of four consecutive quarters (incidence year. Our dependent variable was the prescription of at least one ChEI in the incidence year. Main independent variables were polypharmacy (defined as the number of prescribed medications categorized into quartiles and measures of geriatric comorbidity (levels of care dependency and 14 symptom complexes characterizing geriatric patients. Data were analyzed by multivariate logistic regression. Results On average, patients were 78.7 years old (47.6% female and received 9.7 different medications (interquartile range: 6-13. 44.4% were assigned to one of three care levels and virtually all patients (92.0% had at least one symptom complex characterizing geriatric patients. 13.0% received at least one ChEI within the incidence year. Patients not assigned to the highest care level were more likely to receive a prescription (e.g., no level of care dependency vs. level 3: adjusted Odds Ratio [OR]: 5.35; 95% CI: 1.61-17.81. The chance decreased with increasing numbers of symptoms characterizing geriatric patients (e.g., 0 vs. 5+ geriatric complexes: OR: 4.23; 95% CI: 2.06-8.69. The overall number of prescribed medications had no influence on ChEI prescription and a significant effect of age could only be found in the univariate analysis. Living in a rural compared to an urban environment and contacts to neurologists or psychiatrists were associated with a significant increase in the likelihood of receiving Ch

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

    Directory of Open Access Journals (Sweden)

    Roberto Raschetti

    2007-11-01

    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 ClinicalTrials.gov. 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

  20. 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

    Science.gov (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...

  1. DEPRESSION OF THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS BY PHYSOSTIGMINE, CARBARYL AND PROPOXUR AND THE RELATIONSHIP TO INHIBITION OF BRAIN CHOLINESTERASE

    Science.gov (United States)

    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...

  2. 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

    2015-01-01

    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

  3. Effect of temperature and pH on carbamoylation and phosphorylation of serum cholinesterases. Theoretical interpretation of activation energies in complex reactions

    Science.gov (United States)

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

    1972-01-01

    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

  4. Effects of Agricultural Management Policies on the Exposure of Black-Winged Stilts (Himantopus himantopus Chicks to Cholinesterase-Inhibiting Pesticides in Rice Fields.

    Directory of Open Access Journals (Sweden)

    Gregorio M Toral

    Full Text Available Levels of exposure to pesticides in rice fields can be significant depending on the environmental policies practiced. The aim of European Union integrated management policy is to reduce pesticide use and impact on environment. Rice fields provide an alternative breeding habitat for many waterbirds that are exposed to the pesticides used and therefore can be valuable indicators of their risk for wildlife. To evaluate integrated management success we examined exposure of Black-winged Stilts (Himantopus himantopus to cholinesterase-inhibiting pesticides in rice fields under different types of management by measuring plasma cholinesterase activity. Cholinesterase activity was lower in birds sampled in (a 2008 after a period of intense pesticide application, than in (b 2005-2007 and 2011 in rice fields subject to integrated management in Doñana (SW Spain and (c in control natural wetlands in Spain and Morocco. During 2009 and 2010, cholinesterase activity was lower in rice fields in Doñana than in rice fields in Larache and Sidi Allal Tazi (NW Morocco. Our results suggest that integrated management successfully reduced the exposure of Black-winged Stilts to pesticides in most of the years. Care should be taken to implement mosquito and pest crop controls on time and with environmentally friendly products in order to reduce its impact on wildlife.

  5. 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)

    2010-10-19

    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.

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

    Science.gov (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

    2009-08-01

    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. PMID:19769001

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

    Directory of Open Access Journals (Sweden)

    Noll Campbell

    2008-12-01

    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

  8. 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

    2011-01-01

    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

  9. 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;

    2010-01-01

    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...

  10. Ferulic acid-carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents.

    Science.gov (United States)

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

    2016-02-15

    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.

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

    Science.gov (United States)

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

    2013-11-01

    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.

  12. 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

    2010-01-01

    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

  13. Long Term Outcome and Prediction Models of Cognition, Activities of Daily Living and Nursing Home Placement in Alzheimer’s Disease with Cholinesterase Inhibitor Treatment

    OpenAIRE

    Wattmo, Carina

    2011-01-01

    Background Prospective longitudinal studies in Alzheimer's disease (AD) that include cholinesterase inhibitor (ChEI) treatment in routine clinical settings are scarce. The patients vary in severity of the disease, clinical course, rate of progression and response to treatment. Knowledge about the predicted course of the disease, sociodemographic and clinical factors affecting the outcome and the impact of ChEI therapy, could be valuable for clinicians and the social services. This info...

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

    OpenAIRE

    Wattmo, Carina

    2013-01-01

    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 ...

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

    OpenAIRE

    Wattmo C; Paulsson E; Minthon L; Londos E

    2013-01-01

    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 ...

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

    OpenAIRE

    Mariane Gonçalves Santos; Ricardo Vilela Vitor; Maurício Gustavo Nakamura; Luana de Souza Morelini; Rafaela Scalco Ferreira; Alexandre Giusti Paiva; Luciana Azevedo; Vanessa Bergamin Boralli Marques; Isarita Martins; Eduardo Costa Figueiredo

    2013-01-01

    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 thiop...

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

    Science.gov (United States)

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

    2006-01-01

    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.

  18. Studies on combined effects of organophosphates and heavy metals in birds. I. Plasma and brain cholinesterase in Coturnix quail fed methyl mercury and orally dosed with parathion

    Science.gov (United States)

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

    1975-01-01

    We found that mercury potentiated the toxicity and biochemical effects of parathion. Male Coturnix quail (Coturnix coturnix japonica) were fed a sublethal concentration of morsodren (4 ppm as methyl mercury) for 18 weeks. This resulted in an accumulation of 21.0 ppm of mercury in the liver and 8.4 ppm in the carcass. Birds fed clean feed and those fed morsodren-treated feed were orally dosed with 2, 4, 6, 8,and 10 mg/kg parathion, and their 48-h survival times compared. The computed LD50 was 5.86mg/kg in birds not fed morsodren and 4.24 in those fed the heavy metal. When challenged with a sublethal, oral dose of parathion (1.0 mg/kg), morsodren-fed birds exhibited significantly greater inhibition of plasma and brain cholinesterase activity than controls dosed with parathion. Brain cholinesterase activity was inhibited 41% in morsodren-fed birds and 26in clean-fed birds dosed with parathion, which suggested that the increase in parathion toxicity in the presence of morsodren was directly related to the inhibitation of brain cholinesterase.

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

    Science.gov (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

    2013-06-01

    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.

  20. Effects of stress pretreatment on the dynamics of blood cholinesterase activity after exposure to an organophosphorus pesticide in the rat.

    Science.gov (United States)

    Gralewicz, Slawomir; Swiercz, Radoslaw; Lutz, Piotr; Wiaderna, Dorota; Wasowicz, Wojciech

    2010-01-01

    A single i.p. administration of 1.0 mg/kg of chlorphenvinphos (CVP), an organophosphorus pesticide, results in an acute stress response, evidenced by a marked (6-7 fold) rise in plasma corticosterone (CORT) concentration, and a diminished behavioural sensitivity to amphetamine (AMPH) three weeks postexposure. Surprisingly, in rats subjected to a single series of inescapable electric footshocks (60 10 msec triplets of 3.0 mA, 2 msec, square pulses during 20 min - IF ) two weeks prior to the CVP exposure, these effects are not observed. It has been assumed that the reduced effectiveness of CVP might be related to some persisting alterations in the functional state of the cholinergic system. The aim of the present work was to discover whether and in what way the IF pretreatment affects i) the cholinesterase activity in blood, and ii) the dynamics of the alterations in the cholinesterase (ChE) activity following the CVP exposure. The experiments were performed on 3 mo. old, male Wistar rats. In the first experiment, the blood samples were taken from the tail vein 15, 60 and 180 min after the IF. In the second experiment, the rats were pretreated with IF and 14 days later given 1.0 mg/kg of CVP i.p. Blood samples were taken 15 min, 60 min, 180 min, 24 h, 7 days, and 14 days after the CVP exposure. In the first experiment no differences in the ChE activity in plasma (pChE) and erythrocytes (rbcChE) were found between the shocked and control rats. In the second experiment, however, in rats pretreated with IF the rbcChE activity of was reduced by CVP less and pChE activity returned to normal faster than in rats not pretreated with IF. The results confirm that exposure to IF, a nonchemical stressor, induces some long-lasting adaptive changes which render the cholinergic system less susceptible to the harmful action of ChE inhibitors. It has been hypothesized that the changes consist in an increase of the antioxidant potential in blood and possibly other tissues. PMID

  1. Recombinant butyryl-cholinesterase (RBuChe) therapy following VX poisoning by the percutaneous route: preliminary studies

    International Nuclear Information System (INIS)

    Medical countermeasures to prevent or mitigate the effects of nerve agent poisoning are part of the UK MoD's integrated approach to CBRN defence. Protexia is currently in advanced development as a pretreatment for nerve agent poisoning by PharmAthene in collaboration with US DoD. The principle of its use in this context has been demonstrated in a model of inhalation exposure. Nerve agent poisoning by the percutaneous route poses additional challenges for medical countermeasures. The present study investigates the effects of non-pegylated rBuChE administered following poisoning by VX in an animal model of percutaneous exposure. This investigation is part of an ongoing programme of work assessing the potential of candidate medical interventions. Male guinea pigs implanted with dermal and blood microdialysis probes were maintained under anaesthesia. VX (296 micro g/kg or 740 micro g/kg) was applied to the dorsal skin and non-pegylated rBuChE or placebo was administered (i.v.) 30 minutes later. Dialysate fractions were collected for 8 hours and VX was analysed by LC-MS-MS. Cholinesterase levels were measured in selected tissues post mortem. Following VX (296 micro g/kg), non-pegylated rBuChE significantly reduced the concentration of VX in the blood but had no effect on dermal concentrations; additionally following VX (740 micro g/kg), non-pegylated rBuChE prevented lethality. Tissue cholinesterase activity was inhibited following VX exposure but in those animals treated with rhBuChE, activities were similar to control values. To our knowledge these results provide the first evidence of the mechanism of therapeutic intervention with rBuChE. Further work is necessary to increase confidence in these preliminary observations by conducting confirmatory studies. Crown Copyright 2008. This work was carried out as part of the UK MoD NBC Research Programme. Non-pegylated rBuChE was supplied by PharmAthene under a materials transfer and non-disclosure agreement. (author)

  2. The Glutathione-S-Transferase, Cytochrome P450 and Carboxyl/Cholinesterase Gene Superfamilies in Predatory Mite Metaseiulus occidentalis

    Science.gov (United States)

    Hoy, Marjorie A.

    2016-01-01

    Pesticide-resistant populations of the predatory mite Metaseiulus (= Typhlodromus or Galendromus) occidentalis (Arthropoda: Chelicerata: Acari: Phytoseiidae) have been used in the biological control of pest mites such as phytophagous Tetranychus urticae. However, the pesticide resistance mechanisms in M. occidentalis remain largely unknown. In other arthropods, members of the glutathione-S-transferase (GST), cytochrome P450 (CYP) and carboxyl/cholinesterase (CCE) gene superfamilies are involved in the diverse biological pathways such as the metabolism of xenobiotics (e.g. pesticides) in addition to hormonal and chemosensory processes. In the current study, we report the identification and initial characterization of 123 genes in the GST, CYP and CCE superfamilies in the recently sequenced M. occidentalis genome. The gene count represents a reduction of 35% compared to T. urticae. The distribution of genes in the GST and CCE superfamilies in M. occidentalis differs significantly from those of insects and resembles that of T. urticae. Specifically, we report the presence of the Mu class GSTs, and the J’ and J” clade CCEs that, within the Arthropoda, appear unique to Acari. Interestingly, the majority of CCEs in the J’ and J” clades contain a catalytic triad, suggesting that they are catalytically active. They likely represent two Acari-specific CCE clades that may participate in detoxification of xenobiotics. The current study of genes in these superfamilies provides preliminary insights into the potential molecular components that may be involved in pesticide metabolism as well as hormonal/chemosensory processes in the agriculturally important M. occidentalis. PMID:27467523

  3. Organophosphate and carbamate insecticides in agricultural waters and cholinesterase (ChE) inhibition in common carp (Cyprinus carpio)

    Science.gov (United States)

    Gruber, S.J.; Munn, M.D.

    1998-01-01

    Cholinesterase (ChE) activity was used as a biomarker for assessing exposure of common carp (Cyprinus carpio) to organophosphate and carbamate insecticides from irrigated agricultural waters. Carp were collected from a lake (Royal Lake) that receives most of its water from irrigation return flows and from a reference lake (Billy Clapp Lake) outside of the irrigation system. Results indicated that the mean whole-brain ChE activity of carp from Royal Lake (3.47 μmol/min/g tissue) was 34.2% less than that of carp from Billy Clapp Lake (5.27 μmol/min/g tissue) (p = 0.003). The depressed ChE activity in brain tissue of Royal Lake carp was in response to ChE-inhibiting insecticides detected in water samples in the weeks prior to tissue sampling; the most frequently detected insecticides included chlorpyrifos, azinphos-methyl, carbaryl, and ethoprop. Neither sex nor size appears to be a covariable in the analysis; ChE activity was not correlated with fish length or weight in either lake and there was no significant difference in ChE activity between the two sexes within each lake. Although organophosphate and carbamate insecticides can break down rapidly in the environment, this study suggests that in agricultural regions where insecticides are applied for extended periods of the year, nontarget aquatic biota may be exposed to high levels of ChE-inhibiting insecticides for a period of several months.

  4. Altered quantities and in vivo activities of cholinesterase from Daphnia magna in sub-lethal exposure to organophosphorus insecticides.

    Science.gov (United States)

    Liu, Hongcui; Yuan, Bingqiang; Li, Shaonan

    2012-06-01

    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.

  5. Inhibition pathways of the potent organophosphate CBDP with cholinesterases revealed by X-ray crystallographic snapshots and mass spectrometry

    International Nuclear Information System (INIS)

    Tri-o-cresyl-phosphate (TOCP) is a common additive in jet engine lubricants and hydraulic fluids suspected to have a role in aero-toxic syndrome in humans. TOCP is metabolized to cresyl saligenin phosphate (CBDP), a potent irreversible inhibitor of butyrylcholinesterase (BChE), a natural bio-scavenger present in the bloodstream, and acetylcholinesterase (AChE), the off-switch at cholinergic synapses. Mechanistic details of cholinesterase (ChE) inhibition have, however, remained elusive. Also, the inhibition of AChE by CBDP is unexpected, from a structural standpoint, i.e., considering the narrowness of AChE active site and the bulkiness of CBDP. In the following, we report on kinetic X-ray crystallography experiments that provided 2.7-3.3 Angstroms snapshots of the reaction of CBDP with mouse AChE and human BChE. The series of crystallographic snapshots reveals that AChE and BChE react with the opposite enantiomers and that an induced-fit rearrangement of Phe297 enlarges the active site of AChE upon CBDP binding. Mass spectrometry analysis of aging in either H2 16O or H2 18O furthermore allowed us to identify the inhibition steps, in which water molecules are involved, thus providing insights into the mechanistic details of inhibition. X-ray crystallography and mass spectrometry show the formation of an aged end product formed in both AChE and BChE that cannot be reactivated by current oxime-based therapeutics. Our study thus shows that only prophylactic and symptomatic treatments are viable to counter the inhibition of AChE and BChE by CBDP. (authors)

  6. Transferable residues from dog fur and plasma cholinesterase inhibition in dogs treated with a flea control dip containing chlorpyrifos.

    Science.gov (United States)

    Boone, J S; Tyler, J W; Chambers, J E

    2001-11-01

    We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a commercial, nonprescription chlorpyrifos flea dip for 4 consecutive treatments at 3-week intervals (nonshampoo protocol) and another 12 dogs were dipped with shampooing between dips (shampoo protocol). The samples collected at 4 hr and 7, 14, and 21 days after treatment in the nonshampoo protocol averaged 971, 157, 70, and 26 microg chlorpyrifos, respectively; in the shampoo protocol the samples averaged 459, 49, 15, and 10 microg, respectively. The highest single sample was about 7,000 microg collected at 4 hr. The pretreatment specific activities in the plasma of the dogs were about 75 nmol/min/mg protein for butyrylcholinesterase (BChE), and 9 nmol/min/mg protein for acetylcholinesterase (AChE). BChE was inhibited 50-75% throughout the study, and AChE was inhibited 11-18% in the nonshampoo protocol; inhibition was not as great in the shampoo protocol. There was no correlation (pdogs. Transferable residues had largely dissipated during the three weeks after treatment, with the largest decrease occurring during the first week. Greater plasma ChE inhibition was observed at 7 days than at 4 hr, probably reflecting the bioactivation of chlorpyrifos to chlorpyrifos-oxon. Plasma cholinesterase activity did not return to control levels during the 3-week period. The differences between the shampoo and nonshampoo protocols were explained by differences in the techniques of the dip applicators.

  7. 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

    2012-02-08

    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.

  8. Design, synthesis and evaluation of novel dual monoamine-cholinesterase inhibitors as potential treatment for Alzheimer's disease.

    Science.gov (United States)

    Liu, Wei; Lang, Ming; Youdim, Moussa B H; Amit, Tamar; Sun, Yewei; Zhang, Zaijun; Wang, Yuqiang; Weinreb, Orly

    2016-10-01

    Current novel therapeutic approach suggests that multifunctional compounds with diverse biological properties and a single bioavailability and pharmacokinetic metabolism, will produce higher significant advantages in treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). Based on this rational, a new class of cholinesterase (ChE)-monoamine oxidase (MAO) inhibitors were designed and synthesized by amalgamating the propargyl moiety of the irreversible selective MAO-B inhibitor, neuroprotective/neurorestorative anti-Parkinsonian drug, rasagiline, into the "N-methyl" position of the ChE inhibitor, anti-AD drug rivastigmine. Initially, we examined the MAO and ChE inhibitory effect of these novel compounds, MT series in vitro and in vivo. Among MT series, MT-031 exhibited higher potency as a dual MAO-A and ChE inhibitor compared to other compounds in acute-treated mice. Additionally, MT-031 was found to increase the striatal levels of dopamine (DA), serotonin (5-HT) and norepinephrine (NE), and prevent the metabolism of DA and 5-HT. Finally, we have demonstrated that MT-031 exerted neuroprotective effect against H2O2-induced neurotoxicity and reactive oxygen species generation in human neuroblastoma SH-SY5Y cells. These findings provide evidence that MT-031 is a potent brain permeable novel multifunctional, neuroprotective and MAO-A/ChE inhibitor, preserves in one molecule entity some of the beneficial properties of its parent drugs, rasagiline and rivastigmine, and thus may be indicated as novel therapeutic approach for AD. PMID:27318273

  9. Transferable residues from dog fur and plasma cholinesterase inhibition in dogs treated with a flea control dip containing chlorpyrifos.

    Science.gov (United States)

    Boone, J S; Tyler, J W; Chambers, J E

    2001-11-01

    We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a commercial, nonprescription chlorpyrifos flea dip for 4 consecutive treatments at 3-week intervals (nonshampoo protocol) and another 12 dogs were dipped with shampooing between dips (shampoo protocol). The samples collected at 4 hr and 7, 14, and 21 days after treatment in the nonshampoo protocol averaged 971, 157, 70, and 26 microg chlorpyrifos, respectively; in the shampoo protocol the samples averaged 459, 49, 15, and 10 microg, respectively. The highest single sample was about 7,000 microg collected at 4 hr. The pretreatment specific activities in the plasma of the dogs were about 75 nmol/min/mg protein for butyrylcholinesterase (BChE), and 9 nmol/min/mg protein for acetylcholinesterase (AChE). BChE was inhibited 50-75% throughout the study, and AChE was inhibited 11-18% in the nonshampoo protocol; inhibition was not as great in the shampoo protocol. There was no correlation (pdogs. Transferable residues had largely dissipated during the three weeks after treatment, with the largest decrease occurring during the first week. Greater plasma ChE inhibition was observed at 7 days than at 4 hr, probably reflecting the bioactivation of chlorpyrifos to chlorpyrifos-oxon. Plasma cholinesterase activity did not return to control levels during the 3-week period. The differences between the shampoo and nonshampoo protocols were explained by differences in the techniques of the dip applicators. PMID:11712994

  10. Recovery study of cholinesterases and neurotoxic signs in the non-target freshwater invertebrate Chilina gibbosa after an acute exposure to an environmental concentration of azinphos-methyl.

    Science.gov (United States)

    Cossi, Paula Fanny; Beverly, Boburg; Carlos, Luquet; Kristoff, Gisela

    2015-10-01

    Azinphos-methyl belongs to the class of organophosphate insecticides which are recognized for their anticholinesterase action. It is one of the most frequently used insecticides in the Upper Valley of Río Negro and Río Neuquén in Argentina, where agriculture represents the second most important economic activity. It has been detected in water from this North Patagonian region throughout the year and the maximum concentration found was 22.48 μg L(-1) during the application period. Chilina gibbosa is a freshwater gastropod widely distributed in South America, particularly in Patagonia, Argentina and in Southern Chile. Toxicological studies performed with C. gibbosa in our laboratory have reported neurotoxicity signs and cholinesterase inhibition after exposure to azinphos-methyl for 48 h. Recovery studies together with characterization of the enzyme and sensitivity of the enzyme to pesticides can improve the toxicological evaluation. However, little is known about recovery patterns in organisms exposed to organophosphates. The aim of the present work was to evaluate the recovery capacity (during 21 days in pesticide-free water) of cholinesterase activity and neurotoxicity in C. gibbosa after 48 h of exposure to azinphos-methyl. Also, lethality and carboxylesterase activity were registered during the recovery period. Regarding enzyme activities, after a 48-h exposure to 20 μg L(-1) of azinphos-methyl, cholinesterases showed an inhibition of 85% with respect to control, while carboxylesterases were not affected. After 21 days in pesticide-free water, cholinesterases continued to be inhibited (70%). Severe neurotoxicity signs were observed after exposure: 82% of the snails presented lack of adherence to vessels, 11% showed weak adherence, and 96% exhibited an abnormal protrusion of the head-foot region from shell. After 21 days in pesticide-free water, only 15% of the snails presented severe signs of neurotoxicity. However, during the recovery period significant

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

    Science.gov (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

    2016-04-01

    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.

  12. PATTERN AND SEVERITY OF DIASTOLIC DYSFUNCTION IN ORGANOPHOSPHORUS COMPOUND POISONING PATIENTS IN RELATION TO PLASMA CHOLINESTERASE (PC h E LEVEL IN RURAL POPULATION IN SOUTH INDIA

    Directory of Open Access Journals (Sweden)

    Prashant S

    2015-07-01

    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

  13. Scale Alpha and Beta of Quantitative Convergence and Chemical Reactivity Analysis in Dual Cholinesterase/Monoamine Oxidase Inhibitors for the Alzheimer Disease Treatment Using Density Functional Theory (DFT

    Directory of Open Access Journals (Sweden)

    Alejandro Morales-Bayuelo

    2013-01-01

    Full Text Available Molecular quantum similarity descriptors and Density Functional Theory (DFT based reactivity descriptors were studied for a series of cholinesterase/monoamine oxidase inhibitors used for the Alzheimer's disease treatment (AD. This theoretical study is expected to shed some light onto some molecular aspects that could contribute to the knowledge of the molecular mechanics behind interactions of these molecules with acetylcholinesterase (AChE and butyrylcholinesterase (BuChE, as well as with monoamine oxidase (MAO A and B. The Topogeometrical Superposition Algorithm to handle flexible molecules (TGSA-Flex alignment method was used to solve the problem of the relative orientation in the quantum similarity (QS field. Using the molecular quantum similarity (MQS field and reactivity descriptors supported in the DFT was possible the quantification of the steric and electrostatic effects through of the Coulomb and Overlap quantitative convergence scales (alpha and beta. In addition, an analysis of reactivity indexes is development, using global and local descriptors, identifying the binding sites and selectivity in the (cholinesterase/monoamine oxidase inhibitors, understanding the retrodonor process, and showing new insight for drugs design in a disease of difficult control as Alzheimer.

  14. Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur.

    Science.gov (United States)

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

    2007-03-01

    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.

  15. Biochemical characterization of cholinesterases in Enchytraeus albidus and assessment of in vivo and in vitro effects of different soil properties, copper and phenmedipham.

    Science.gov (United States)

    Howcroft, C F; Gravato, C; Amorim, M J B; Novais, S C; Soares, A M V M; Guilhermino, L

    2011-01-01

    Enchytraeus albidus are important organisms of the soil biocenosis, used as standard test species in environmental risk assessment. The inhibition of cholinesterases (ChE) activity of several species has been widely used to assess the exposure and effects of anti-cholinesterase environmental contaminants. Several studies have shown the association between ChE activity inhibition and adverse effects on behaviour and survival. Extensive studies addressing survival and behavioural endpoints, as well as other biomarkers, have been done in E. albidus with different types of soil contaminants. The main objectives of this study were: (1) to characterize biochemically the ChE present in the soluble post-mitochondrial fraction of E. albidus whole body homogenates, using different substrates and selective inhibitors; (2) to assess the in vivo effects of copper, phenmedipham and different soil properties (pH, organic matter, clay) on the ChE activity; (3) to assess the in vitro effects of copper and phenmedipham on the ChE activity. The results suggest the presence of one ChE in the soluble post-mitochondrial fraction of E. albidus whole body homogenates, which displays properties of both acetylcholinesterase and pseudocholinesterase considering the typical mammalian enzymes. It is also shown that ChE activity is not inhibited by exposure to different soil properties and that copper and phenmedipham inhibited ChE activity both in in vivo and in in vitro conditions and therefore ChE inhibition seems to be a robust biomarker for this herbicide and this heavy metal. This study showed that ChE activity in E. albidus might be correlated to previously determined higher level effects like survival and reproduction, as well as avoidance behaviour. PMID:21080225

  16. 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

    2015-01-01

    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.

  17. Antiaggregation Potential of Padina gymnospora against the Toxic Alzheimer's Beta-Amyloid Peptide 25-35 and Cholinesterase Inhibitory Property of Its Bioactive Compounds.

    Directory of Open Access Journals (Sweden)

    Balakrishnan Shanmuganathan

    Full Text Available Inhibition of β-amyloid (Aβ aggregation in the cerebral cortex of the brain is a promising therapeutic and defensive strategy in identification of disease modifying agents for Alzheimer's disease (AD. Since natural products are considered as the current alternative trend for the discovery of AD drugs, the present study aims at the evaluation of anti-amyloidogenic potential of the marine seaweed Padina gymnospora. Prevention of aggregation and disaggregation of the mature fibril formation of Aβ 25-35 by acetone extracts of P. gymnospora (ACTPG was evaluated in two phases by Thioflavin T assay. The results were further confirmed by confocal laser scanning microscopy (CLSM analysis and Fourier transform infrared (FTIR spectroscopic analysis. The results of antiaggregation and disaggregation assay showed that the increase in fluorescence intensity of aggregated Aβ and the co-treatment of ACTPG (250 μg/ml with Aβ 25-35, an extensive decrease in the fluorescence intensity was observed in both phases, which suggests that ACTPG prevents the oligomers formation and disaggregation of mature fibrils. In addition, ACTPG was subjected to column chromatography and the bioactivity was screened based on the cholinesterase inhibitory activity. Finally, the active fraction was subjected to LC-MS/MS analysis for the identification of bioactive compounds. Overall, the results suggest that the bioactive compound alpha bisabolol present in the alga might be responsible for the observed cholinesterase inhibition with the IC50 value < 10 μg/ml for both AChE and BuChE when compared to standard drug donepezil (IC50 value < 6 μg/ml and support its use for the treatment of neurological disorders.

  18. Effect of APOE and CHRNA7 genotypes on the cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease.

    Science.gov (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

    2015-03-01

    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.

  19. Biomonitoring of Organophosphorus Agent Exposure by Reactivation of Cholinesterase Enzyme Based on Carbon Nanotube-Enhanced Flow-Injection Amperometric Detection

    Energy Technology Data Exchange (ETDEWEB)

    Du, Dan; Wang, Jun; Smith, Jordan N.; Timchalk, Charles; Lin, Yuehe

    2009-11-15

    A portable, rapid, and sensitive assessment of sub-clinical organophosphorus (OPs) agent exposure based on reactivation of cholinesterase (ChE) from OP-inhibited ChE using rat saliva (in vitro) was developed using an electrochemical sensor coupled with a microflow-injection system. The sensor was based on a carbon nanotube (CNT)-modified screen printed carbon electrode (SPE), which was integrated into a flow cell. Due to the extent of inter-individual ChE activity variability, ChE biomonitoring often requires an initial base-line determination (non-inhibited) of enzyme activity which is then directly compared with activity after OP exposure. This manuscript described an alternative strategy where reactivation of the phosphorylated enzyme was exploited to enable measurement of both inhibited and baseline ChE activity (i.e. after reactivation) in the same sample. The use of CNT makes the electrochemical detection of the products from enzymatic reactions more feasible with extremely high sensitivity and at low potentials. Paraoxon was selected as a model OP compound for in vitro inhibition studies. Some experiment parameters, (e.g. inhibition and reactivation times), have been optimized such that, 92 - 95% ChE reactivation can be achieved over a broad range of ChE inhibition (5 - 94 %) with paraoxon. The extent of enzyme inhibition using this electrochemical sensor correlates well with conventional enzyme activity measurements.

  20. Effects of sublethal fenitrothion ingestion on cholinesterase inhibition, standard metabolism, thermal preference, and prey-capture ability in the Australian central bearded dragon (Pogona vitticeps, Agamidae).

    Science.gov (United States)

    Bain, David; Buttemer, William A; Astheimer, Lee; Fildes, Karen; Hooper, Michael J

    2004-01-01

    The central bearded dragon (Pogona vitticeps) is a medium-sized lizard that is common in semiarid habitats in Australia and that potentially is at risk of fenitrothion exposure from use of the chemical in plague locust control. We examined the effects of single sublethal doses of this organophosphate (OP; low dose = 2.0 mg/kg; high dose = 20 mg/kg; control = vehicle alone) on lizard thermal preference, standard metabolic rate, and prey-capture ability. We also measured activities of plasma total cholinesterase (ChE) and acetylcholinesterase before and at 0, 2, 8, 24, 120, and 504 h after OP dosing. Predose plasma total ChE activity differed significantly between sexes and averaged 0.66 +/- 0.06 and 0.45 +/- 0.06 micromol/min/ml for males and females, respectively. Approximately 75% of total ChE activity was attributable to butyrylcholinesterase. Peak ChE inhibition reached 19% 2 h after OP ingestion in the low-dose group, and 68% 8 h after ingestion in high-dose animals. Neither OP doses significantly affected diurnal body temperature, standard metabolic rate, or feeding rate. Plasma total ChE levels remained substantially depressed up to 21 d after dosing in the high-dose group, making this species a useful long-term biomonitor of OP exposure in its habitat. PMID:14768874

  1. Synthesis and crystal structure of new temephos analogues as cholinesterase inhibitor: molecular docking, QSAR study, and hydrogen bonding analysis of solid state.

    Science.gov (United States)

    Gholivand, Khodayar; Ebrahimi Valmoozi, Ali Asghar; Bonsaii, Mahyar

    2014-06-25

    A series of temephos (Tem) derivatives were synthesized and characterized by 31P, 13C, and 1H NMR and FT-IR spectral techniques. Also, the crystal structure of compound 9 was investigated. The hydrogen bonding energies (E2) were calculated by NBO analysis of the crystal cluster. The activities and the mixed-type mechanism of Tem derivatives were evaluated using the modified Ellman's and Lineweaver-Burk's methods on cholinesterase (ChE) enzymes. The inhibitory activities of Tem derivatives with a P═S moiety were higher than those with a P═O moiety. Docking analysis disclosed that the hydrogen bonds occurred between the OR (R=CH3 and C2H5) oxygen and N-H nitrogen atoms of the selected compounds and the receptor site (GLN and GLU) of ChEs. PCA-QSAR indicated that the correlation coefficients of the electronic variables were dominant compared to the structural descriptors. MLR-QSAR models clarified that the net charges of nitrogen and phosphorus atoms contribute important electronic function in the inhibition of ChEs. The validity of the QSAR model was confirmed by a LOO cross-validation method with q2=0.965 between the training and testing sets. PMID:24893121

  2. DEVELOPMENT OF REFERENCE RANGES FOR PLASMA TOTAL CHOLINESTERASE AND BRAIN ACETYLCHOLINESTERASE ACTIVITY IN FREE-RANGING CARNABY'S BLACK-COCKATOOS (CALYPTORHYNCHUS LATIROSTRIS).

    Science.gov (United States)

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

    2016-07-01

    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.

  3. Absence of effects of different types of detergents on the cholinesterasic activity and histological markers of mosquitofish (Gambusia holbrooki) after a sub-lethal chronic exposure.

    Science.gov (United States)

    Nunes, B; Miranda, M T; Correia, A T

    2016-08-01

    The release of anthropogenic compounds into the aquatic environment has been a particular concern, since some of these substances exhibit biologic activity of different types in non-target species. Among anthropogenic compounds present in the aquatic compartment, detergents are commonly found and may be responsible for physiological modifications in exposed organisms. The impairment of key physiological functions, such as neurotransmission, and tissue damage in some important organs, has been used to assess the effects of several classes of xenobiotics, including detergents, in aquatic organisms. The present study intended to assess the effect of three types of detersive compounds (sodium dodecylsulfate (SDS), benzalkonium chloride (BZC), and Triton X-100 (TX100)) in the acetylcholinesterase activity (AChE) and tissue damage (gills and liver) of Gambusia holbrooki after a chronic exposure to realistic levels of these compounds. SDS, BZC, and TX100 did not cause any significant alteration in AChE. Furthermore, no specific gross morphological changes were also observed in the gills and liver of the exposed individuals. It is possible to conclude that, under ecologically relevant conditions of exposure, both tissue damage and cholinesterasic impairment are not toxicological pathways affected by detergents in G. holbrooki. PMID:27074930

  4. Cholinesterase inhibitors, donepezil and rivastigmine, attenuate spatial memory and cognitive flexibility impairment induced by acute ethanol in the Barnes maze task in rats.

    Science.gov (United States)

    Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Filarowska, Joanna; Silberring, Jerzy; Kotlinska, Jolanta H

    2016-10-01

    Central cholinergic dysfunction contributes to acute spatial memory deficits produced by ethanol administration. Donepezil and rivastigmine elevate acetylcholine levels in the synaptic cleft through the inhibition of cholinesterases-enzymes involved in acetylcholine degradation. The aim of our study was to reveal whether donepezil (acetylcholinesterase inhibitor) and rivastigmine (also butyrylcholinesterase inhibitor) attenuate spatial memory impairment as induced by acute ethanol administration in the Barnes maze task (primary latency and number of errors in finding the escape box) in rats. Additionally, we compared the influence of these drugs on ethanol-disturbed memory. In the first experiment, the dose of ethanol (1.75 g/kg, i.p.) was selected that impaired spatial memory, but did not induce motor impairment. Next, we studied the influence of donepezil (1 and 3 mg/kg, i.p.), as well as rivastigmine (0.5 and 1 mg/kg, i.p.), given either before the probe trial or the reversal learning on ethanol-induced memory impairment. Our study demonstrated that these drugs, when given before the probe trial, were equally effective in attenuating ethanol-induced impairment in both test situations, whereas rivastigmine, at both doses (0.5 and 1 mg/kg, i.p.), and donepezil only at a higher dose (3 mg/kg, i.p.) given prior the reversal learning, attenuated the ethanol-induced impairment in cognitive flexibility. Thus, rivastigmine appears to exert more beneficial effect than donepezil in reversing ethanol-induced cognitive impairments-probably due to its wider spectrum of activity. In conclusion, the ethanol-induced spatial memory impairment may be attenuated by pharmacological manipulation of central cholinergic neurotransmission. PMID:27376896

  5. 类黄酮化合物作为胆碱酯酶抑制剂的研究进展%Research Progress on Flavonoids as Cholinesterase Inhibitors

    Institute of Scientific and Technical Information of China (English)

    孙莉莉; 崔璀; 赵永梅

    2015-01-01

    类黄酮是一类广泛分布于自然界的天然化合物,具有抗肿瘤、抗氧化、抗炎、血管舒张、神经元保护、保肝等多种生理活性,尤其是具有低毒的优势,使其在预防和治疗慢性疾病方面,如阿尔茨海默症( Alzheimer’s disease, AD)引起人们广泛关注。然而,类黄酮化合物与胆碱酯酶作用的研究报道还不是很多,因此,本文总结了近几年类黄酮化合物作为胆碱酯酶抑制剂的研究进展,期望为今后开发抗AD药物提供参考。%Flavonoids are a large class of compounds widely distributed in nature. Many of them expressed a wide range of biological activities such as anti-tumor, antioxidant, anti-inflammatory, vasodilator, neuron protection, hepatoprotective, and so on, espcially they show so low toxicity that they could be potential to treatment for chronic disease, such as Alzheimer’s disease ( AD) . In recent years, many research groups choose flavonoids to develop new drug for treatment of AD. Herein, current researches in flavonoids as cholinesterase inhibitors were systematically summarized, which can serve as a reference for designing new anti-AD drugs.

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

    Science.gov (United States)

    Mroczek, Tomasz

    2016-09-10

    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.

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

    Directory of Open Access Journals (Sweden)

    Wattmo C

    2013-03-01

    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

  8. Sensitivity of brain cholinesterase activity to diazinon (BASUDIN 50EC) and fenobucarb (BASSA 50EC) insecticides in the air-breathing fish Channa striata (Bloch, 1793).

    Science.gov (United States)

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

    2006-05-01

    With the expansion of agricultural areas within the Mekong River Delta in Vietnam, a concurrent, dramatic increase has occurred in agrochemical usage. To date, little consideration has been given to the negative impacts of this agricultural activity on the aquatic resources of the region. Both acute toxicity and subacute effects on brain cholinesterase (ChE) of two of the most commonly used insecticides, diazinon and fenobucarb, on adult native snakehead (Channa striata) were evaluated in a static, nonrenewable system, the environmental parameters of which, such as dissolved oxygen, water temperature, and pH, fluctuated similarly to field conditions. Four levels of insecticides, from 0.008 to 0.52 mg/L (for diazinon) and from 0.11 to 9.35 mg/L (for fenobucarb), were tested to assess the effects on the brain ChE activity of the snakehead up to 30 and 10 d for diazinon and fenobucarb, respectively. Diazinon was highly toxic to this fish species, with a 96-h median lethal concentration (LC50) of only 0.79 mg/L, and it also caused long-term ChE inhibition, with activity still significantly inhibited by 30% after 30 d for the three highest concentrations. Fenobucarb was less toxic to this species, with a 96-h LC50 of 11.4 mg/L. Fenobucarb caused more rapid ChE inhibition but also rapid recovery. The results of the present study indicate an urgent need to regulate the usage of these pesticides in the Mekong River Delta. PMID:16704077

  9. 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.

    Science.gov (United States)

    Perić, Lorena; Ribarić, Luka; Nerlović, Vedrana

    2013-08-01

    Cholinesterase (ChE, EC 3.1.1.7) 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.

  10. Systematic Review and Meta-Analysis of Combination Therapy with Cholinesterase Inhibitors and Memantine in Alzheimer’s Disease and Other Dementias

    Directory of Open Access Journals (Sweden)

    Taim Muayqil

    2012-11-01

    Full Text Available Background:N-methyl-D-aspartic acid antagonists (memantine and cholinesterase inhibitors (ChEIs are the only two approved classes of drugs to treat dementia; this paper explores the evidence for using these two treatments in combination. Objective: To determine the efficacy and safety of using combination therapy with memantine and a ChEI to treat dementia in comparison to monotherapy with either memantine or a ChEI. Methods: In March 2012, we systematically searched MEDLINE/PubMed, EMBASE, Cochrane library, and grey literature databases. All study types were included, except for case series or reports, which looked at combination therapy versus monotherapy in various dementing disorders. Data was pooled for blinded randomized controlled trials (RCTs only; mean differences and standardized mean differences were used to determine effect sizes. Results: Thirteen studies were included in this review; 3 were blinded RCTs, with a total of 971 Alzheimer’s disease (AD patients, which were included into the meta-analysis. No papers were found that primarily addressed combination therapy in other dementias. In the meta-analysis, small but statistically significant effect sizes were seen in favor of combination therapy among patients with moderate to severe AD on the scales of cognition (0.45–0.52; p Conclusion: Although there were statistically significant changes in favor of combination therapy in moderate to severe AD, heterogeneity in scales and patient characteristics exists. However, it is unclear if clinically significant outcomes can be achieved using the combination therapy. More studies are required before a recommendation for combination therapy can be made.

  11. 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

    2014-01-01

    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

  12. Depression of the photic after discharge of flash evoked potentials by physostigmine, carbaryl and propoxur, and the relationship to inhibition of brain cholinesterase.

    Science.gov (United States)

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

    2008-01-01

    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

  13. 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

    2001-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Mariane Gonçalves Santos

    2013-03-01

    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

  15. 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

    2002-01-01

    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

  16. 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

    Directory of Open Access Journals (Sweden)

    Jaqueline Pérola de Souza

    2006-04-01

    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.

  17. 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

    2006-01-01

    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

  18. 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.

    Science.gov (United States)

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

    2016-01-01

    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.

  19. 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

    2009-01-01

    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).

  20. 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

    Directory of Open Access Journals (Sweden)

    Ricardo Barcelos

    2007-01-01

    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.

  1. 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

    2012-01-01

    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.

  2. Changes of plasma cholinesterase and erythrocyte acetylcholinesterase activity of banked blood%库存血液中血浆胆碱酯酶、红细胞乙酰胆碱酯酶水平变化

    Institute of Scientific and Technical Information of China (English)

    钟沛霖; 马升弟; 金振良; 徐瑞龙; 王苏华; 盛慧球; 王秀芹; 邹和建

    2005-01-01

    目的观察库血保存天数与血浆胆碱酯酶(cholinesterase,ChE)、红细胞乙酰胆碱酯酶(EAChE)活力水平变化的关系.方法库存血标本资料选取健康志愿供血者全血200ml加ACD-B 50ml,按库血条件保存,按时逐日每份抽取1 ml,测定E-AChE.当时留取血浆2ml,存入-40℃冰箱,第21天后同时测定血浆ChE.以抽取标本后,即刻测定结果为对照组资料.E-AChE测定采用便携式胆碱酯酶测定仪(SB-YY)及其配套试剂板;ChE采用Roch公司的胆碱酯酶试剂盒,Beck Man CX9全自动分析仪测定.结果库血保存天数为9 d以内的血浆ChE值与对照组比较,差异无显著性(P>0.05);而保存10~12 d以后的各组均显著低于对照组(P<0.05),保存天数与血浆ChE值呈负相关(r=-0.988 8,P<0.01)、直线回归,y=-67.321x+4255,R2=0.9778;但E-AChE水平无显著下降,各组间方差分析差异均无显著性(P>0.05),库血保存时间与E-AChE直线回归方程无显著意义(P>0.05).结论本研究表明库血中血浆内含一定量ChE、红细胞E-AChE;E-AChE随保存天数延长,21 d内无明显下降,为重症AOPP抢救中选用少浆红细胞提供一定的实验依据.

  3. New Cholinesterase Inhibitory Constituents from Lonicera quinquelocularis

    Science.gov (United States)

    Khan, Dilfaraz; Khan, Hidayat Ullah; Khan, Farmanullah; Khan, Shafiullah; Badshah, Syed; Khan, Abdul Samad; Samad, Abdul; Ali, Farman; Khan, Ihsanullah; Muhammad, Nawshad

    2014-01-01

    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. PMID:24733024

  4. 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

    2008-01-01

    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

  5. Quantitative analysis of cholinesterase from Daphnia magna by indirect and non-competitive enzyme-linked immunosorbent assay%大型溞胆碱酯酶间接非竞争酶联免疫吸附定量分析法的建立

    Institute of Scientific and Technical Information of China (English)

    刘洪翠; 杨艳霞; 李少南

    2012-01-01

    用达到电泳纯的大型溞(Daphnia magna)胆碱酯酶(cholinesterase,ChE)免疫BALB/c小鼠,得到效价达1∶8000的鼠抗大型溞ChE多克隆抗血清;通过优化抗原抗体反应条件,建立定量分析大型溞ChE含量的间接非竞争酶联免疫吸附法(indirect and non-competitive enzyme-linked immunosorbent assay).结果表明:此方法检测灵敏度为24 ng·mL-1;经免疫交叉反应鉴定,所获抗血清与5、10 μg·mL-1标准蛋白质和其他生物如花翅摇蚊、尖额溞、斑马鱼(脑、脑除外的整体)、家蚕、意大利蜜蜂、赤子爱胜蚯蚓、非洲爪蟾(蝌蚪)等来源的ChE交叉反应率分别为:<0.25%、<0.25%、2.13%、10.19%、3.88%、3.56%、2.81%、3.93%、5.00%和2.75%,具较高的特异性.说明用本试验得到的抗血清建立的间接非竞争酶联免疫吸附法可用于大型溞体内ChE含量的测定,以利于在农药暴露环境下大型溞体内ChE活性的精确检测.%Polyclonal anti-serum of cholinesteiase with dilution ratio of 1 :8 000 was obtained by immunizing BALB/c mice with purified cholinesterase (ChE) from Daphnia magna. An indirect and non-competitive enzyme-linked immunosorbent assay (ELISA), which used mice anti-Daphnia ChE as antibodies to react with the Daphnia ChE, was established to quantify immunoreactive content of ChE in D. magna. The minimal detection limit of the method was estimated to be 24 ng-mL"'. Specificity of anti-serum was high, with cross reaction of <0. 25%, <0. 25%, 2.13%, 10.19%, 3.88%, 3.56%, 2.81%, 3.93%, 5.00% and 2.75% towards non-ChE marker (5. 10 μg·mL-1), Chironomus kiinensis, Alona sp. , Brachydanio rerio (the brain, the whole body without brain), Bombyx mori, Apis mellifera L., Eisenia foetida , and tadpoles of Xenopus laevis, respectively. It is indicated that the established method can be used to quantify immunoreactive content of ChE in D. magna so as to measureme accurately in vivo activity of the ChE in pesticide

  6. The Study of the Ester Deriviatives of Florescent Substances Used as the Substrate of Cholinesterase in Human Blood%荧光物质的酯类衍生物用作人血胆 碱酯酶底物的研究

    Institute of Scientific and Technical Information of China (English)

    杨梅; 张素玢; 冯立娟

    2001-01-01

    合成了几种荧光物质4-甲基伞形酮、荧光素、二溴荧光素的乙酸酯及丁酸酯 ,研究了它们用作人血胆碱酯酶(ChE)底物进行活性测定的各种条件,通过米氏常数(Km )和人血ChE稀释比曲线的测定系统地比较了六种物质作为底物与ChE作用的特异性和灵敏度 .结果表明荧光物质量子产率越高、发射波长越长、酯基的烃基链越长的物质,用作人血Ch E活性测定底物的选择性和灵敏度越好.%In this paper,we choose several qualified fluorescent subtances:4-meth y lumbelliferyl, fluorescein,3,7-dibromo-fluorescein,synthetised their acetate a nd butyrate,studied the feasibility of them used as substrates for the determinati on of cholinesterase(ChE).Meanwhile,by Km and ChE's diluted ratio curve, the sensitivity and selectivity of these substrates are evalutated and compared .The result s show that the esters of those fluorescent substance possess higher quantiu m yield and longer emission wavelength with better substrate of ChE.

  7. 碳酸氢钠联合乌司他丁治疗急性辛硫磷农药中毒胆碱酯酶活力的变化%The influence of sodium bicarbonate combined with ulinastatin on cholinesterase activity for patients with acute phoxim pesticide poisoning

    Institute of Scientific and Technical Information of China (English)

    赵波; 杨兰菊; 肖磊; 孙宝泉; 邹宪宝; 高冬梅; 菅向东

    2016-01-01

    Objective To observe the effect of sodium bicarbonate combined with ulinastatin on cholinesterase activity for patients with acute phoxim pesticide poisoning.Methods A total of 67 eligible patients with acute phoxim pesticide poisoning,Who were admitted to the emeryency department of hospital from March 2011 to February 2014,Acording to different treatments au patients were randomly divided into the conventional treatment group (n=34) and the sodium bicarbonate+ulinastatin group (n=35).The conventional treatment group were given thorough gastric lavage with water,the sodium bicarbonate + ulinastatin group were given gastric lavage with 2% sodium bicarbonate solution.Both groups were given such treatments as catharsis,administration of oxygen,fluid infusion,diuresis,and antidotes such as atropine and pralidoxime methylchloride.On the basis of comprehensive treatment,people in the sodium bicarbonate+ulinastatin group were given 5% sodium bicarbonate injection and ulinastatin.The clinical effect of the two groups were compared.Results The serum cholinesterase activity of the sodium bicarbonate +ulinastatin group was significantly higher than the conventional treatment group from the 5th day,and the difference was statistically significant(P<0.05).The total atropine dosage,total pralidoxime methylchloride dosage and hospitalization days were better than the conventional treatment group,and the differences were statistically significant (P<0.05).The difference in the time of atropinization between the two groups was not statistically significant (P>0.05).The results of arterial blood pH,HCO3-of the sodium bicarbonate + ulinastatin group were higher than the conventional treatment group,and the difference of HCO3-at the 10th day was statistically significant (P<0.05).Conclusions Sodium bicarbonate combined with ulinastatin can improve the therapeutic effect and reduce complications in the treatment of acute phoxim pesticide poisoning,and have beneficial

  8. Functional and morphological structure changes in the gut harrier during cholinesterase inhibitor intoxication and therapeutic effect of benthiactzine in rats%胆碱酯酶抑制剂中毒大鼠肠屏障功能和形态结构变化及宾赛克嗪治疗作用的研究

    Institute of Scientific and Technical Information of China (English)

    潘志远; 龙超良; 汪海

    2010-01-01

    目的 观察胆碱酯酶抑制剂类神经性毒剂中毒后大鼠肠屏障功能和组织形态结构的变化以及宾赛克嚷的治疗作用.方法 40只雄性Wistar大鼠按随机数字表法均分为对照组、维埃克斯染毒模型组及宾赛克嗪1、3、9 mg/kg治疗组.皮下注射维埃克斯13μg/kg染毒;宾赛克嗪组在染毒后5 min腹腔注射相应剂量药物.各组于染毒后3 h取血,检测血浆D-乳酸浓度及二胺氧化酶(DAO)活性;同时取小肠组织,观察肠黏膜形态和超微结构变化.结果 与对照组比较.模型组血浆D-乳酸浓度和DAO活性均明显升高[D-乳酸:(87.752±22.906)mg/L比(29.072±6.546)mg/L,DAO:(6.72±0.93)U/L比(2.99±0.43)U/L,均P<0.01];宾赛克嗪1、3、9 mg/kg组呈现剂量依赖性降低血浆D-乳酸浓度和DAO活性,其中宾赛克嗪9 mg/kg组可逆转染毒后血浆D-乳酸浓度[(45.290±11.141)mg/L]和DAO活性C(3.17±0.68)U/L]增高(均P<0.01).光镜下观察模型组大鼠空肠和回肠肠壁变薄,皱壁变短,结构紊乱,固有层毛细血管扩张充血,黏膜间质水肿等病理变化;电镜下观察模型组大鼠回肠上皮细胞发生坏死,细胞器损伤,紧密连接破坏等变化.宾赛克嗪1、3、9 mg/kg组呈现剂量依赖性抑制小肠的病理变化.结论 胆碱酯酶抑制剂中毒时出现肠黏膜上皮细胞损伤,肠黏膜屏障功能破坏,通透性增加;宾赛克嗪能抑制中毒肠黏膜屏障结构和功能的损伤.%Objective To investigate the functional and morphological structure changes in the gut barrier of rats induced by cholinesterase inhibitor VX poisoning, and the therapeutic effect of benthiactzine. Methods Forty male Wistar rats were randomly divided into five groups: normal saline control group, VX poisoning (model) group, benthiactzine 1, 3, 9 mg/kg treatment groups, with 8 rats in each group. In the benthiactzine treatment groups, different dosages of the drug were respectively given (intraperitoneal injection) 5 minutes after

  9. Alzheimer's disease and Type 2 diabetes mellitus: the cholinesterase connection?

    Directory of Open Access Journals (Sweden)

    Siva Prasad Akula

    2006-11-01

    Full Text Available Abstract Alzheimer's disease and type 2 diabetes mellitus tend to occur together. We sought to identify protein(s common to both conditions that could suggest a possible unifying pathogenic role. Using human neuronal butyrylcholinesterase (AAH08396.1 as the reference protein we used BLAST Tool for protein to protein comparison in humans. We found three groups of sequences among a series of 12, with an E-value between 0–12, common to both Alzheimer's disease and diabetes: butyrylcholinesterase precursor K allele (NP_000046.1, acetylcholinesterase isoform E4-E6 precursor (NP_000656.1, and apoptosis-related acetylcholinesterase (1B41|A. Butyrylcholinesterase and acetylcholinesterase related proteins were found common to both Alzheimer's disease and diabetes; they may play an etiological role via influencing insulin resistance and lipid metabolism.

  10. [Ligands of cholinesterases of ephedrine and pseudoephedrine structure].

    Science.gov (United States)

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

    2013-01-01

    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.

  11. [Ligands of cholinesterases of ephedrine and pseudoephedrine structure].

    Science.gov (United States)

    2013-01-01

    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. PMID:25509044

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

    Directory of Open Access Journals (Sweden)

    Magda Lúcia Félix de Oliveira

    2009-12-01

    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.

  14. Protection of benthiactzine on mixed type acidosis of concomitant respiratory failure and circulatory failure induced by intoxication of cholinesterase inhibitor%宾赛克嗪对胆碱酯酶抑制剂中毒所致呼吸衰竭和循环衰竭时混合型酸中毒的影响

    Institute of Scientific and Technical Information of China (English)

    宋丽雪; 唐渊; 龙超良; 王汝欢; 张津津; 汪海

    2012-01-01

    new antidote benthiactzine on mixed type acidosis of concomitant respiratory failure and circulatory failure induced by intoxication of cholinesterase inhibitor ( ChEI) . Methods Seven male dogs,weighing(12 - 15)kg,were injected intermuscularly 1/3 LD soman(l LD = 10 μg/kg)per ten minutes. The mean the pressure of carbondioxide decreased to 60 mmHg and the pressure of oxygen increased to 50 mmHg was defined as respirato ry failure. The mean the blood pressure decreased to (40-45) mmHg was defined as circulatory failure . The changes of arterial blood were evaluated by an eight-channel direct -writing oscillograph, and were observed before and after soman injection. Statistical analysis of the data wag performed using the self control t test with the SAS 6.12 Software Program. Results The results indicated that PaCO2 and PO2 were (45. 5 ±12.3) mmHg and (87. 8 ±14. 3) mmHg with significant difference (P<0.01,n=7); and BE,BB, SB and CH+ were ( -6.7 ±1.7) mmol/L, (41.1 ±1.8) mmol/L, (18.8 ±1.2) mmol/L, and (50.4 ± 10. 5) mmol/L, respectively. When it be continually treated above 6 h, the life feature be recovered in the acidosis dog. When the acidosis induced 2 h by the soman(4 LD) in dog, the blood pressure decreased , MAP was below 45 mmHg, and caused respiratory failure and circulatory failure. After treatment with benthiactzine 1 h, PaCO2, CH+ and PO2 changed to (40. 2 ±7. 9) mmHg, (61.3 ±5.4) mmol/L, (114.5 ±27.1) mmHg,respectively, The other symptoms has not been continuously worsened , and acid poisoning was partially controlled . Conclusion Intoxiciation of cholinest erase inhibitors could lead to compensated primary acute respiratory acidosis complicating continuous metabolic aci -dosis. After treatment with benthiactzine , the symptoms of acidosis will be relieved , and broken away from the acidosis state.

  15. Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds from Allanblackia monticola and Symphonia globulifera.

    Science.gov (United States)

    Lenta, Bruno Ndjakou; Vonthron-Sénécheau, Catherine; Weniger, Bernard; Devkota, Krishna Prasad; Ngoupayo, Joseph; Kaiser, Marcel; Naz, Qamar; Choudhary, Muhammad Iqbal; Tsamo, Etienne; Sewald, Norbert

    2007-01-01

    In a preliminary antiprotozoal screening of several Clusiaceae species, the methanolic extracts of Allanblackia monticola and Symphonia globulifera showed high in vitro leishmanicidal activity. Further bioguided phytochemical investigation led to the isolation of four benzophenones: guttiferone A (1), garcinol (2), cambogin (3) and guttiferone F (4), along with three xanthones: allanxanthone A (5), xanthone V1 (6) and globulixanthone C (7) as active constituents. Compounds 1 and 6 were isolated from S. globulifera leaves, while compounds 2-5 were obtained from A. monticola fruits. Guttiferone A (1) and F (4) showed particulary strong leishmanicidal activity in vitro, with IC50 values (0.2 microM and 0.16 microM, respectively) comparable to that of the reference compound, miltefosine (0.46 microM). Although the leishmanicidal activity is promising, the cytotoxicity profile of these compounds prevent at this state further in vivo biological evaluation. In addition, all the isolated compounds were tested in vitro for their anticholinesterase properties. The four benzophenones showed potent anticholinesterase properties towards acetylcholinesterase (AChE) and butylcholinesterase (AChE). For AChE, the IC50 value (0.66 microM) of garcinol (2) was almost equal to that of the reference compound galanthamine (0.50 microM). Furthermore, guttiferone A (1) and guttiferone F (4) (IC50 = 2.77 and 3.50 microM, respectively) were more active than galanthamine (IC50 = 8.5) against BChE. PMID:17960072

  16. Leishmanicidal and Cholinesterase Inhibiting Activities of Phenolic Compounds from Allanblackia monticola and Symphonia globulifera

    Directory of Open Access Journals (Sweden)

    Norbert Sewald

    2007-07-01

    Full Text Available In a preliminary antiprotozoal screening of several Clusiaceae species, the methanolic extracts of Allanblackia monticola and Symphonia globulifera showed high in vitro leishmanicidal activity. Further bioguided phytochemical investigation led to the isolation of four benzophenones: guttiferone A (1, garcinol (2, cambogin (3 and guttiferone F (4, along with three xanthones: allanxanthone A (5, xanthone V1 (6 and globulixanthone C (7 as active constituents. Compounds 1 and 6 were isolated from S. globulifera leaves, while compounds 2-5 were obtained from A. monticola fruits. Guttiferone A (1 and F (4 showed particulary strong leishmanicidal activity in vitro, with IC50 values (0.2 μM and 0.16 μM, respectively comparable to that of the reference compound, miltefosine (0.46 μM. Although the leishmanicidal activity is promising, the cytotoxicity profile of these compounds prevent at this state further in vivo biological evaluation. In addition, all the isolated compounds were tested in vitro for their anticholinesterase properties. The four benzophenones showed potent anticholinesterase properties towards acetylcholinesterase (AChE and butylcholinesterase (AChE. For AChE, the IC50 value (0.66 μM of garcinol (2 was almost equal to that of the reference compound galanthamine (0.50 μM. Furthermore, guttiferone A (1 and guttiferone F (4 (IC50 = 2.77 and 3.50 μM, respectively were more active than galanthamine (IC50 = 8.5 against BChE.

  17. Leishmanicidal and Cholinesterase Inhibiting Activities of Phenolic Compounds from Allanblackia monticola and Symphonia globulifera

    OpenAIRE

    Norbert Sewald; Etienne Tsamo; Muhammad Iqbal Choudhary; Qamar Naz; Marcel Kaiser; Joseph Ngoupayo; Krishna Prasad Devkota; Bernard Weniger; Catherine Vonthron-Sénécheau; Bruno Ndjakou Lenta

    2007-01-01

    In a preliminary antiprotozoal screening of several Clusiaceae species, the methanolic extracts of Allanblackia monticola and Symphonia globulifera showed high in vitro leishmanicidal activity. Further bioguided phytochemical investigation led to the isolation of four benzophenones: guttiferone A (1), garcinol (2), cambogin (3) and guttiferone F (4), along with three xanthones: allanxanthone A (5), xanthone V1 (6) and globulixanthone C (7) as active constituents. Compounds 1 and 6 were isolat...

  18. Effect of Different Administration Paradigms on Cholinesterase Inhibition following Repeated Chlorpyrifos Exposure in Late Preweanling Rats

    OpenAIRE

    Carr, Russell L.; Nail, Carole A.

    2008-01-01

    Chlorpyrifos (CPS) is widely used in agricultural settings and residue analysis has suggested that children in agricultural communities are at risk of exposure. This has resulted in a large amount of literature investigating the potential for CPS-induced developmental neurotoxic effects. Two developmental routes of administration of CPS are orally in corn oil at a rate of 0.5 ml/kg and subcutaneously in dimethyl sulfoxide (DMSO) at a rate of 1.0 ml/kg. For comparison between these methods, ra...

  19. 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

    2006-01-01

    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.

  20. Effects of X-irradiation on acetyl cholinesterase activity in the frog Rana hexadactyla

    International Nuclear Information System (INIS)

    Changes in acetylchloinesterase (AChE) activity in brain, muscle and liver tissues of normal and X-irradiated frogs were studied. Low doses of radiation produced an increase in enzyme activity while high doses produced decrement. Post-irradiation studies with sublethal dose showed an early increase followed by reversible decrement in enzyme activity while lethal dose exhibited an early increase followed by irreversible inhibition of enzyme activity. (author)

  1. Higher sensitivity to cadmium induced cell death of basal forebrain cholinergic neurons: A cholinesterase dependent mechanism

    International Nuclear Information System (INIS)

    Cadmium is an environmental pollutant, which is a cause of concern because it can be greatly concentrated in the organism causing severe damage to a variety of organs including the nervous system which is one of the most affected. Cadmium has been reported to produce learning and memory dysfunctions and Alzheimer like symptoms, though the mechanism is unknown. On the other hand, cholinergic system in central nervous system (CNS) is implicated on learning and memory regulation, and it has been reported that cadmium can affect cholinergic transmission and it can also induce selective toxicity on cholinergic system at peripheral level, producing cholinergic neurons loss, which may explain cadmium effects on learning and memory processes if produced on central level. The present study is aimed at researching the selective neurotoxicity induced by cadmium on cholinergic system in CNS. For this purpose we evaluated, in basal forebrain region, the cadmium toxic effects on neuronal viability and the cholinergic mechanisms related to it on NS56 cholinergic mourine septal cell line. This study proves that cadmium induces a more pronounced, but not selective, cell death on acetylcholinesterase (AChE) on cholinergic neurons. Moreover, MTT and LDH assays showed a dose dependent decrease of cell viability in NS56 cells. The ACh treatment of SN56 cells did not revert cell viability reduction induced by cadmium, but siRNA transfection against AChE partially reduced it. Our present results provide new understanding of the mechanisms contributing to the harmful effects of cadmium on the function and viability of neurons, and the possible relevance of cadmium in the pathogenesis of neurodegenerative diseases

  2. Synthesis and biological evaluation of a series of dithiocarbamates as new cholinesterase inhibitors.

    Science.gov (United States)

    Altıntop, Mehlika D; Gurkan-Alp, A Selen; Ozkay, Yusuf; Kaplancıklı, Zafer A

    2013-08-01

    In the present paper, a novel series of dithiocarbamates was synthesized via the treatment of 4-(trifluoromethyl)benzyl chloride with appropriate sodium salts of N,N-disubstituted dithiocarbamic acids. The chemical structures of the compounds were elucidated by (1) H NMR, mass spectral data, and elemental analyses. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman's spectrophotometric method. The most potent AChE inhibitor was found as compound 2g (IC50  = 0.53 ± 0.001 µM) followed by compounds 2f (IC50  = 0.74 ± 0.001 µM) and 2j (IC50  = 0.89 ± 0.002 µM) when compared with donepezil (IC50  = 0.048 ± 0.001 µM). Compounds 2f and 2g were more effective than donepezil (IC50  = 7.88 ± 0.52 µM) on BuChE inhibition. Compounds 2f and 2g exhibited the inhibitory effect on BuChE with IC50 values of 1.39 ± 0.041 and 3.64 ± 0.072 µM, respectively. PMID:23881696

  3. Cholinesterase activity as a device for biomonitoring pesticide exposure in the freshwater mussel Elliptio complanata

    Data.gov (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...

  4. Anti-cholinesterase activity of the standardized extract of Syzygium aromaticum L.

    OpenAIRE

    Manoj K. Dalai; Santanu Bhadra; Sushil K Chaudhary; Arun Bandyopadhyay; Mukherjee, Pulok K.

    2014-01-01

    Background: Clove (Syzygium aromaticum) is a well-known culinary spice with strong aroma; contains a high amount of oil known as clove oil. The major phyto-constituent of the clove oil is eugenol. Clove and its oil possess various medicinal uses in indigenous medicine as an antiseptic, anti-oxidant, analgesic and neuroprotective properties. Thus, it draws much attention among researchers from pharmaceutical, food and cosmetic industries. Objective: The aim of the present study was to determin...

  5. Serum cholinesterase activities distinguish between stroke patients and controls and predict 12-month mortality

    DEFF Research Database (Denmark)

    Ben Assayag, Einor; Shenhar-Tsarfaty, Shani; Ofek, Keren;

    2010-01-01

    To date there is no diagnostic biomarker for mild stroke, although elevation of inflammatory biomarkers has been reported at early stages. Previous studies implicated acetylcholinesterase (AChE) involvement in stroke, and circulating AChE activity reflects inflammatory response, since acetylcholi...

  6. ACUTE PHARMACOLOGICAL INHIBITION OF CHOLINESTERASE RESULTS IN MINIMAL NEUROMUSCULAR JITTER CHANGES.

    Science.gov (United States)

    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...

  7. Multifunctional cholinesterase and amyloid Beta fibrillization modulators. Synthesis and biological investigation.

    Science.gov (United States)

    Butini, Stefania; Brindisi, Margherita; Brogi, Simone; Maramai, Samuele; Guarino, Egeria; Panico, Alessandro; Saxena, Ashima; Chauhan, Ved; Colombo, Raffaella; Verga, Laura; De Lorenzi, Ersilia; Bartolini, Manuela; Andrisano, Vincenza; Novellino, Ettore; Campiani, Giuseppe; Gemma, Sandra

    2013-12-12

    In order to identify novel Alzheimer's modifying pharmacological tools, we developed bis-tacrines bearing a peptide moiety for specific interference with surface sites of human acetylcholinesterase (hAChE) binding amyloid-beta (Aβ). Accordingly, compounds 2a-c proved to be inhibitors of hAChE catalytic and noncatalytic functions, binding the catalytic and peripheral sites, interfering with Aβ aggregation and with the Aβ self-oligomerization process (2a). Compounds 2a-c in complex with TcAChE span the gorge with the bis-tacrine system, and the peptide moieties bulge outside the gorge in proximity of the peripheral site. These moieties are likely responsible for the observed reduction of hAChE-induced Aβ aggregation since they physically hamper Aβ binding to the enzyme surface. Moreover, 2a was able to significantly interfere with Aβ self-oligomerization, while 2b,c showed improved inhibition of hAChE-induced Aβ aggregation. PMID:24900626

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

    Directory of Open Access Journals (Sweden)

    Luís Miguel Fonseca Alves

    2014-06-01

    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.

  9. Regulation of Gastric Electrical and Mechanical Activity by Cholinesterases in Mice

    OpenAIRE

    Worth, Amy A; Forrest, Abigail S.; Peri, Lauren E.; Ward, Sean M; Hennig, Grant W; Sanders, Kenton M

    2015-01-01

    Background/Aims Gastric peristalsis begins in the orad corpus and propagates to the pylorus. Directionality of peristalsis depends upon orderly generation and propagation of electrical slow waves and a frequency gradient between proximal and distal pacemakers. We sought to understand how chronotropic agonists affect coupling between corpus and antrum. Methods Electrophysiological and imaging techniques were used to investigate regulation of gastric slow wave frequency by muscarinic agonists i...

  10. Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase

    OpenAIRE

    Patricia Marie Legler; Susanne eBoisvert; Compton, Jaimee R.; Millard, Charles B.

    2014-01-01

    We applied a combination of rational design and directed evolution (DE) to Bacillus subtilis p-nitrobenzyl esterase (pNBE) with the goal of enhancing organophosphorus acid anhydride hydrolase (OPAAH) activity. DE started with a designed variant, pNBE A107H, carrying a histidine homologous with human butyrylcholinesterase G117H to find complementary mutations that further enhance its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400) within a 6.7 Å radius of the nucl...

  11. Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase

    OpenAIRE

    Legler, Patricia M.; Boisvert, Susanne M.; Compton, Jaimee R.; Millard, Charles B.

    2014-01-01

    We applied a combination of rational design and directed evolution (DE) to Bacillus subtilis p-nitrobenzyl esterase (pNBE) with the goal of enhancing organophosphorus acid anhydride hydrolase (OPAAH) activity. DE started with a designed variant, pNBE A107H, carrying a histidine homologous with human butyrylcholinesterase G117H to find complementary mutations that further enhance its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400) within a 6.7 Å radius of the nucleo...

  12. QSAR for cholinesterase inhibition by organophosphorus esters and CNDO/2 calculations for organophosphorus ester hydrolysis

    Science.gov (United States)

    Johnson, H.; Kenley, R. A.; Rynard, C.; Golub, M. A.

    1985-01-01

    Quantitative structure-activity relationships were derived for acetyl- and butyrylcholinesterase inhibition by various organophosphorus esters. Bimolecular inhibition rate constants correlate well with hydrophobic substituent constants, and with the presence or absence of catonic groups on the inhibitor, but not with steric substituent constants. CNDO/2 calculations were performed on a separate set of organophosphorus esters, RR'P(O)X, where R and R' are alkyl and/or alkoxy groups and X is fluorine, chlorine or a phenoxy group. For each subset with the same X, the CNDO-derived net atomic charge at the central phosphorus atom in the ester correlates well with the alkaline hydrolysis rate constant. For the whole set of esters with different X, two equations were derived that relate either charge and leaving group steric bulk, or orbital energy and bond order to the hydrogen hydrolysis rate constant.

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

    Directory of Open Access Journals (Sweden)

    Saurabh Kumar Sinha

    2015-09-01

    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.

  14. Isolation of cholinesterase and β-secretase 1 inhibiting compounds from Lycopodiella cernua.

    Science.gov (United States)

    Nguyen, Van Thu; To, Dao Cuong; Tran, Manh Hung; Oh, Sang Ho; Kim, Jeong Ah; Ali, Md Yousof; Woo, Mi-Hee; Choi, Jae Sue; Min, Byung Sun

    2015-07-01

    Three new serratene-type triterpenoids (1-3) and a new hydroxy unsaturated fatty acid (13) together with nine known compounds (4-12) were isolated from Lycopodiella cernua. The chemical structures were established using NMR, MS, and Mosher's method. Compound 13 showed the most potent inhibitory activity against acetylcholinesterase (AChE) with an IC50 value of 0.22μM. For butyrylcholinesterase (BChE) inhibitory activity, 5 showed the most potent activity with an IC50 value of 0.42μM. Compound 2 showed the most potent activity with an IC50 of 0.23μM for BACE-1 inhibitory activity. The kinetic activities were investigated to determine the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 4, 5, and 13 were mixed; BChE inhibition by 5 was competitive, while 2 and 6 showed mixed-types. In addition, molecular docking studies were performed to investigate the interaction of these compounds with the pocket sites of AChE. The docking results revealed that the tested inhibitors 3, 4, and 13 were stably present in several pocket domains of the AChE residue. PMID:26003344

  15. Application of a cholinesterase biosensor to screen for organophosphorus pesticides extracted from soil.

    Science.gov (United States)

    Kumaran, S; Morita, M

    1995-04-01

    Based on the principle of enzyme inactivation, a butyrylcholinesterase (EC 3.1.1.8.) biosensor, to determine some organophosphorus (ORP) pesticides (Fenitrothion, Diazinon, Parathion ethyl, Mevinphos and Heptenophos) in soil extracts, is presented. The enzyme was immobilized on pre-activated Pall Biodyne(TM) transfer membranes, which were physically attached to the sensitive ends of glass pH electrodes. Contact of the enzyme with pesticide samples results in specific inhibition of enzyme activity. Sensor calibration was possible by correlating the inhibition of enzyme activity (monitored by observing reduction in electrode potential changes with substrate additions) with varying concentrations of pesticide compounds in a buffer solution. A simple procedure was designed to extract ORP pesticides from spiked soil samples using a mixture of dichloromethane and acetone as the extraction solvent mixture. The sensor was successfully used to determine pesticide concentrations ranging from a low of 35 ppb (Diazinon) to 21 ppm (Fenitrothion) in soil, with resultant relative standard deviations of percentage enzyme inactivation less than 12%. The complete extraction and analytical procedure is simple, inexpensive and rapid. Mass production of the enzyme membranes and their easy attachment to the electrodes, render them disposable after a single use. The biosensor is seen as a potential analytical instrument for early warning against pesticide contaminations in soil. PMID:18966276

  16. Susceptibility of the aging Brown Norway rat to carbaryl, an anti-cholinesterase-based insecticide: Thermoregulatory and cardiovascular responses.

    Science.gov (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...

  17. Species-specific patterns of swimming escape performance and cholinesterase activity in a guild of aquatic insects exposed to endosulfan

    International Nuclear Information System (INIS)

    Next to imposing direct lethal effects, pollutants may also indirectly impose mortality by making prey organisms more vulnerable to predation. We report that four water boatmen species differed strongly in direct endosulfan-imposed mortality, and only the species that suffered highest mortality, Sigara iactans, also showed a reduction in escape swimming speed. While head AChE activity was inhibited in all four species, body ChE was only inhibited in S. iactans where it covaried with escape swimming speed, indicating a mechanistic link between body ChE and swimming speed. Our study underscores the need for risk assessment to consider sublethal pollutant effects, which may considerably affect survival rates under natural conditions, also when testing concentrations of a pesticide that cause direct mortality. Such sublethal effects may generate discrepancies between laboratory and field studies and should be considered when designing safety factors for toxicants where the risk assessment is solely based on LC50 values. - Highlights: ► Endosulfan, even at lethal levels, did not affect swimming propensity when attacked. ► Endosulfan reduced escape swimming in one out of four tested corixid species. ► Lower body ChE levels were associated with a slower escape speed in one species. ► Head AChE activity was more sensitive to endosulfan than body ChE. ► Endosulfan had strongly different effects on the closely related species. - Endosulfan only detectably reduced escape swimming speed in one of the four studied water boatmen species and this was associated with an inhibition of body ChE.

  18. Anti-oxidative and cholinesterase inhibitory effects of leaf extracts and their isolated compounds from two closely related Croton species.

    Science.gov (United States)

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

    2013-01-01

    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. PMID:23377133

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

    OpenAIRE

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

    2013-01-01

    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...

  20. Anti-oxidative and cholinesterase inhibitory effects of leaf extracts and their isolated compounds from two closely related Croton species.

    Science.gov (United States)

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

    2013-02-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Johannes Van Staden

    2013-02-01

    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.

  2. New cholinesterase inhibitors for Alzheimer's disease: Structure Activity Studies (SARs) and molecular docking of isoquinolone and azepanone derivatives.

    Science.gov (United States)

    Bacalhau, Patrícia; San Juan, Amor A; Marques, Carolina S; Peixoto, Daniela; Goth, Albertino; Guarda, Cátia; Silva, Mara; Arantes, Sílvia; Caldeira, A Teresa; Martins, Rosário; Burke, Anthony J

    2016-08-01

    A library of isoquinolinone and azepanone derivatives were screened for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. The strategy adopted included (a) in vitro biological assays, against eel AChE (EeAChE) and equine serum BuChE (EqBuChE) in order to determine the compounds IC50 and their dose-response activity, consolidated by (b) molecular docking studies to evaluate the docking poses and interatomic interactions in the case of the hit compounds, validated by STD-NMR studies. Compound (1f) was identified as one of these hits with an IC50 of 89.5μM for EeAChE and 153.8μM for EqBuChE, (2a) was identified as a second hit with an IC50 of 108.4μM (EeAChE) and 277.8μM (EqBuChE). In order to gain insights into the binding mode and principle active site interactions of these molecules, (R)-(1f) along with 3 other analogues (also as the R-enantiomer) were docked into both RhAChE and hBuChE models. Galantamine was used as the benchmark. The docking study was validated by performing an STD-NMR study of (1f) with EeAChE using galantamine as the benchmark. PMID:27231829

  3. Comparative Effects of Oral Chlorpyrifos Exposure on Cholinesterase Activity and Muscarinic Receptor Binding in Neonatal and Adult Rat Heart

    OpenAIRE

    Howard, Marcia D.; Mirajkar, Nikita; Karanth, Subramanya; Pope, Carey N.

    2007-01-01

    Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M2 muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M2 receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus...

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

    Directory of Open Access Journals (Sweden)

    Abdulselam Ertaş

    2014-09-01

    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.

  5. Effects of structural modifications on the metal binding, anti-amyloid activity, and cholinesterase inhibitory activity of chalcones.

    Science.gov (United States)

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

    2015-09-28

    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.

  6. Novel series of tacrine-tianeptine hybrids: Synthesis, cholinesterase inhibitory activity, S100B secretion and a molecular modeling approach.

    Science.gov (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

    2016-10-01

    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.

  7. Transferable residues from dog fur and plasma cholinesterase inhibition in dogs treated with a flea control dip containing chlorpyrifos.

    OpenAIRE

    Boone, J S; Tyler, J. W.; Chambers, J. E.

    2001-01-01

    We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a...

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

    Science.gov (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

    2015-10-01

    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. PMID:26297990

  9. Cholinesterase inhibitors and add-on nutritional supplements in Alzheimer's disease: A systematic review of randomized controlled trials

    NARCIS (Netherlands)

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

    2014-01-01

    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

  10. Tyrosinase, Acetyl- and Butyryl-Cholinesterase Inhibitory Activity of Stachys lavandulifolia Vahl (Lamiaceae and Its Major Constituents

    Directory of Open Access Journals (Sweden)

    Rosa Tundis

    2014-09-01

    Full Text Available The n-hexane (HE, dichloromethane (DC, methanol (ME, ethanol 70% (ET, and methanol with Soxlhet apparatus (MS extracts of Stachys lavandulifolia aerial parts were screened for their potential tyrosinase, acetylcholinesterase (AChE and butyrylcholinesterase (BChE inhibitory activity. ET and MS inhibited tyrosinase with IC 50 values of 33.4 and 42.8 m g/mL, respectively. The phytochemical investigation of these extracts resulted in the isolation of the known compounds monomelittoside (1, melittoside (2, 5-allosyloxy-aucubin (3, acteoside (4 and arbutin (5. The HE extract, characterized by germacrene D, b -pinene, b -myrcene, and trans-caryophyllene as main constituents, showed the highest AChE inhibitory activity with an IC 50 value of 13.7 m g/mL while DC extract was the most active against BChE (IC 50 value of 143.9 m g/mL. The diterpene stachysolone (6 was isolated from this extract. The antioxidant properties were also investigated by four in vitro methods (DPPH, ABTS, FRAP and b -carotene bleaching tests.

  11. Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors.

    Science.gov (United States)

    Lockridge, Oksana; Norgren, Robert B; Johnson, Rudolph C; Blake, Thomas A

    2016-09-19

    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

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

    Directory of Open Access Journals (Sweden)

    C.E. Lamien

    2013-05-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Ali Gorzi

    2013-10-01

    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.

  14. Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors

    Science.gov (United States)

    2016-01-01

    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

  15. TRANSFERABLE RESIDUES FROM DOG FUR AND PLASMA CHOLINESTERASE INHIBITION IN DOGS TREATED WITH A FLEA CONTROL DIP CONTAINING CHLORPYRIFOS. (R825170)

    Science.gov (United States)

    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...

  16. 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.

    Science.gov (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

    2012-06-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Borbón Javier F.

    2012-03-01

    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.

  18. IN VITRO SENSITIVITY OF CHOLINESTERASES AND [3H]OXOTREMORINE-M BINDING IN HEART AND BRAIN OF ADULT AND AGING RATS TO ORGANOPHOSPHORUS ANTICHOLINESTERASES

    OpenAIRE

    Mirajkar, Nikita; Pope, Carey N.

    2008-01-01

    Organophosphorus (OP) insecticides elicit toxicity via acetylcholinesterase inhibition, allowing acetylcholine accumulation and excessive stimulation of cholinergic receptors. Some OP insecticides bind to additional macromolecules including butyrylcholinesterase and cholinergic receptors. While neurotoxicity from OP anticholinesterases has been extensively studied, effects on cardiac function have received less attention. We compared the in vitro sensitivity of acetylcholinesterase, butyrylch...

  19. Plasma cholinesterase activity as a biomarker for quantifying exposure of green sturgeon to carbaryl following applications to control burrowing shrimp in Washington State.

    Science.gov (United States)

    Troiano, Alexandra T; Grue, Christian E

    2016-08-01

    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 recovery by 48 h. Plasma samples were collected from free-living green sturgeon before and 4 d to 5 d after application of carbaryl in Willapa Bay. Activity of BChE after application was reduced 28% (p < 0.001), indicating exposure to the pesticide. However, the lack of congruence between BChE and AChE activity in captive 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. PMID:26678014

  20. Design, synthesis and evaluation of novel indandione derivatives as multifunctional agents with cholinesterase inhibition, anti-β-amyloid aggregation, antioxidant and neuroprotection properties against Alzheimer's disease.

    Science.gov (United States)

    Mishra, Chandra Bhushan; Manral, Apra; Kumari, Shikha; Saini, Vikas; Tiwari, Manisha

    2016-08-15

    A series of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)-1H-indene-1,3(2H)-diones were designed, synthesized and appraised as multifunctional anti-Alzheimer agents. In vitro studies of compounds 27-38 showed that these compounds exhibit moderate to excellent AChE, BuChE and Aβ aggregation inhibitory activity. Notably, compounds 34 and 38 appeared as most active multifunctional agents in the entire series and exhibited excellent inhibition against AChE (IC50=0.048μM: 34; 0.036μM: 38), Aβ aggregation (max% inhibition 82.2%, IC50=9.2μM: 34; max% inhibition 80.9%, IC50=10.11μM: 38) and displayed significant antioxidant potential in ORAC-FL assay. Both compounds also successfully diminished H2O2 induced oxidative stress in SH-SY5Y cells. Fascinatingly, compounds 34 and 38 showed admirable neuroprotective effects against H2O2 and Aβ induced toxicity in SH-SY5Y cells. Additionally, both derivatives showed no considerable toxicity in neuronal cell viability assay and represented drug likeness properties in the primarily pharmacokinetics study. All these results together, propelled out that compounds 34 and 38 might serve as promising multi-functional lead candidates for treatment of AD in the future. PMID:27353888

  1. QSAR for cholinesterase inhibition by organophosphorus esters and CNDO/2 calculations for organophosphorus ester hydrolysis. [quantitative structure-activity relationship, complete neglect of differential overlap

    Science.gov (United States)

    Johnson, H.; Kenley, R. A.; Rynard, C.; Golub, M. A.

    1985-01-01

    Quantitative structure-activity relationships were derived for acetyl- and butyrylcholinesterase inhibition by various organophosphorus esters. Bimolecular inhibition rate constants correlate well with hydrophobic substituent constants, and with the presence or absence of cationic groups on the inhibitor, but not with steric substituent constants. CNDO/2 calculations were performed on a separate set of organophosphorus esters, RR-primeP(O)X, where R and R-prime are alkyl and/or alkoxy groups and X is fluorine, chlorine or a phenoxy group. For each subset with the same X, the CNDO-derived net atomic charge at the central phosphorus atom in the ester correlates well with the alkaline hydrolysis rate constant. For the whole set of esters with different X, two equations were derived that relate either charge and leaving group steric bulk, or orbital energy and bond order to the hydrolysis rate constant.

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

    Directory of Open Access Journals (Sweden)

    Marzhan Myrzakhanova

    2013-01-01

    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.

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

    Science.gov (United States)

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

    2015-01-01

    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.

  4. 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.

    Science.gov (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

    2015-11-01

    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.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    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...

  6. 二溴磷亚慢性暴露对大鼠血液胆碱酯酶活性的影响%Effect of Subchronic Exposure to Naled on Activity of Blood Cholinesterase in Rats

    Institute of Scientific and Technical Information of China (English)

    李羡筠; 陈晓琴; 梁少华; 郑艳艳

    2008-01-01

    [目的]了解二溴磷亚慢性暴露对大鼠血液胆碱酯酶(Chg)活性的影响.[方法]取4~6周龄SD大鼠80只,随机分为4组.剂量组分别以23.2、2.32、0.232 mg/kg二澳磷原药喂饲,连续90 d,自由摄食;对照组饲喂不含受试物的基础饲料.染毒结束时测定大鼠血清ChE活性.[结果]高剂量组大鼠ChE活性低于对照组,中剂量组和低剂量组大鼠ChE活性与对照组类似.[结论]二溴磷亚慢性暴露对大鼠ChE活性的抑制,呈现明显的剂量一反应关系.

  7. Kinetics of Acetylcholinesterase Inhibition by an Aqueous Extract of Mentha longifolia Leaves

    OpenAIRE

    Chandra Shekhar; Suresh Kumar

    2014-01-01

    Cholinesterase inhibitors are the class of compounds which inhibit cholinesterase enzyme. These are used as drugs for symptomatic treatment of Alzheimer’s disease (AD). The present study, evaluate anti-cholinesterase property of an aqueous extract of Mentha longifolia leaves, which is an aromatic plant traditionally used for several medicinal properties. Ellman’s method was used to determine the acetylcholinesterase (AChE) enzyme inhibitory activity of an aqueous extracts of Mentha longifolia...

  8. Nano-Intercalated Organophosphorus-Hydrolyzing Enzymes in Organophosphorus Antagonism

    OpenAIRE

    Petrikovics Ilona; Wales, Melinda E.; Budai Marianna; Yu, Jorn C. C.; Szilasi Mária

    2011-01-01

    A dendritic poly(2-alkyloxazoline)-based polymer was studied as a new carrier system for the organophosphorus-hydrolyzing recombinant enzymes, organophosphorus acid anhydrolase and organophosphorus hydrolase. Paraoxon (PO) and diisopropylfluorophosphate (DFP) were used as model organophosphorus compounds. Changes in plasma cholinesterase activity were monitored. The cholinesterase activity was proportional to the concentrations of DFP or PO. Plasma cholinesterase activity was higher in animal...

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

    DEFF Research Database (Denmark)

    Kirkeby, S

    1976-01-01

    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...

  10. 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

    2009-01-01

    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

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

    NARCIS (Netherlands)

    Asperen, K. van

    1959-01-01

    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

  12. 21 CFR 520.600 - Dichlorvos.

    Science.gov (United States)

    2010-04-01

    ... a few days before or after treatment with or exposure to cholinesterase inhibiting drugs, pesticides... medication. Resume normal feeding schedule afterwards. Swine may be retreated in 4 to 5 weeks. (f) Conditions... exposure to cholinesterase-inhibiting drugs, pesticides, or chemicals. (7) Federal law restricts this...

  13. Age-related behavioral effects of methomyI in Brown Norway rats.

    Science.gov (United States)

    Methomyl is a cholinesterase-inhibiting carbamate pesticide that is used in the field on cotton and a variety of fruits and vegetables. Concerns have been raised generally about age-related differences in susceptibility to cholinesterase-inhibiting pesticides, especially for chil...

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

    Directory of Open Access Journals (Sweden)

    Jiří Bajgal

    2016-03-01

    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.

  15. Effect of induced epilepsy on some biochemical parameters in female rats

    Directory of Open Access Journals (Sweden)

    J.S. H. Ali

    2012-01-01

    Full Text Available The activity of cholinesterase and some biochemical parameters of blood such as glucose, cholesterol and phospholipids were estimated in 52 epilepsy induced females of Wister albino rats. Animals of this experiment were divided into two groups, group (I regarded as control and group (II administrated subcutaneously by pentylenetetrazole 100mg/kg and divided in to three sub-groups according to the time of samples collection 3 hrs, 24 hrs and 1 week. The results revealed that epilepsy induction caused a significant inhibition of serum cholinesterase activity 3 hrs after induction while in the brain, the activity of cholinesterase was significantly increased after 24 hrs Serum glucose level was significantly elevated after 3 hrs and 24 hrs of induction, total cholesterol and phospholipids were not changed. From the results obtained in this study, it can be concluded that epilepsy caused significant changes in cholinesterase activity in brain and serum in addition to the glucose level in the serum.

  16. SwissProt search result: AK107259 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107259 002-125-G11 (P32752) Cholinesterase (EC 3.1.1.8) (Acylcholine acylhydrolase) (Choli...ne esterase II) (Butyrylcholine esterase) (Pseudocholinesterase) (Fragment) CHLE_PIG 5e-18 ...

  17. 77 FR 8856 - FIFRA Scientific Advisory Panel; Notice of Public Meeting

    Science.gov (United States)

    2012-02-15

    ... more of the following areas: Cholinergic and non-cholinergic mechanisms, cholinesterase inhibition... established from ChE inhibition that are used for regulatory purposes. At this time, the Agency is...

  18. Rivastigmine Transdermal Patch

    Science.gov (United States)

    ... class of medications called cholinesterase inhibitors. It improves mental function (such as memory and thinking) by increasing ... Be sure the skin is free of powders, oil, and lotions. Select a patch in a sealed ...

  19. 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

  20. 21 CFR 524.900 - Famphur.

    Science.gov (United States)

    2010-04-01

    ... good condition. Brahman and Brahman crossbreeds are less tolerant of cholinesterase-inhibiting insecticides than other breeds. Do not treat Brahman bulls. (3) Do not slaughter within 35 days after...

  1. A Method for Fast Assessment of OP/CB Exposure in the Japanese Quail (Coturnix coturnix japonica Using Combined Esterases Enzyme Activity as Biomarkers

    Directory of Open Access Journals (Sweden)

    Kasim Sakran Abass

    2014-01-01

    Full Text Available The aims of this study were to investigate the presence of different esterase activities in plasma and liver for Japanese quail and to combine determination of both carboxylesterase and cholinesterase as biochemical biomarker in order to identify the effects of carbamate and organophosphate compounds exposure. Carboxylesterase exhibits larger sensitivity to carbamate and organophosphate compounds than to cholinesterase and is present at higher levels. This permitted nature and distribution of carboxylesterase or cholinesterase to be measured. One predominant toxicological form of enzyme level constant in its patterns of motivation and inhibition with cholinesterase was identified in plasma with an apparent Michaelis constant for butyrylthiocholine iodide of 0.394 mM. Carboxylesterase activity in liver was considered by its preferential hydrolysis of the S-phenyl thioacetate. A concentration dependent decrease of carboxylesterase and cholinesterase has demonstrated during in vitro incubation of malathion, parathion, and trichlorfon in the range 0.125–2 mM, while with methomyl was in the range 0.25–4 mM. When quail (n=15 was exposed orally for 48 h to concentrations of carbamate or organophosphate compounds of 3–200 mg/kg, the percentage inhibition of cholinesterase was in each case larger than that of carboxylesterase and reached statistical significance (P<0.05 at lower concentrations.

  2. Is plasma β-glucuronidase a novel human biomarker for monitoring anticholinesterase pesticides exposure? A Malaysian experience

    International Nuclear Information System (INIS)

    A cross-sectional study was conducted to investigate the effects of acute and chronic pesticide exposure on the plasma β-glucuronidase enzyme activity among five patients of acute pesticide poisoning in Tengku Ampuan Rahimah Hospital, Klang, 230 farmers in the MADA area, Kedah and 49 fishermen in Setiu, Terengganu. The duration of pesticide exposure among the patients was unknown, but the plasma samples from patients were collected on day one in the hospital. The duration of pesticide exposure among the farmers was between 1 and 45 years. The β-glucuronidase activity was compared with plasma cholinesterase activity in the same individual. The plasma cholinesterase activity was measured using Cholinesterase (PTC) Reagent set kit (Teco Diagnostics, UK) based on colorimetric method, while the plasma β-glucuronidase activity was measured fluorometrically based on β-glucuronidase assay. The plasma cholinesterase activity was significantly reduced (p 0.05). The plasma β-glucuronidase activity among the farmers was significantly elevated (p 0.05). The plasma cholinesterase activity was positively correlated with the plasma β-glucuronidase activity among the farmers (r = 0.205, p 0.05). Thus, plasma β-glucuronidase enzyme activity can be measured as a biomarker for the chronic exposure of pesticide. However, further studies need to be performed to confirm whether plasma β-glucuronidase can be a sensitive biomarker for anticholinesterase pesticide poisoning

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

    Directory of Open Access Journals (Sweden)

    V Dhananjayan

    2012-01-01

    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.

  4. Acute behavioral toxicity of carbaryl and propoxur in adult rats.

    Science.gov (United States)

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

    1983-04-01

    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.

  5. 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

    2005-01-01

    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.

  6. Effects of age on behavioral and physiological responses to carbaryl in rats.

    Science.gov (United States)

    Takahashi, R N; Poli, A; Morato, G S; Lima, T C; Zanin, M

    1991-01-01

    Motor, sensory and thermoregulatory functions were examined in young (3 months) and mature (12 months) rats following PO administration of single low doses (10 and 50 mg/kg) of carbaryl, a carbamate insecticide, and these effects were related to blood cholinesterase activity. Carbaryl 50 mg/kg decreased the frequency of ambulation in the open-field arena within 30 min while it enhanced the duration of haloperidol-induced catalepsy in both young and mature rats. Administration of carbaryl also resulted in an increased nociceptive threshold to thermic stimuli mainly in mature rats. An age-related reduction in body temperature was observed at 30, 60 and 90 min after injection. Activity of blood cholinesterase was reduced in young and mature rats at 30 and 60 min following carbaryl exposure. These results indicate that carbaryl can induce an age-related impairment on some behavioral and autonomic functions in rats correlated to the inhibition of cholinesterase activity. PMID:1904531

  7. Responses of the iguanid lizard Anolis carolinensis to four organophosphorus pesticides

    Science.gov (United States)

    Hall, R.J.; Clark, D.R., Jr.

    1982-01-01

    Dose related mortality and cholinesterase effects of parathion, methyl parathion, azinphos-methyl and malathion on Anolis carolinensis were investigated. The comparative effects of the four compounds on fish, birds and mammals are well known, but the effects of organophosphates on reptiles have not been studied critically. Sensitivity and patterns of mortality from exposure to the pesticides resemble those of birds and mammals rather than those of other poikilothermic vertebrates. Possible symptoms of epinephrine accumulation were observed in exposed animals; this side effect is consistent with the known mechanisms of the pesticides. Our findings indicate that brain cholinesterase activity is related to dose, that 50% inhibition of cholinesterase is associated with death and that 40% inhibition indicates sublethal exposure. Anolis lizards are frequently exposed to pesticides in the field and they may be useful in monitoring the hazards posed to a variety of wildlife species.

  8. Molecular basis of neural function

    International Nuclear Information System (INIS)

    The conference proceedings contain abstracts of plenary lectures, of young neurochemists' ESN honorary lectures, lectures at symposia and workshops and poster communications. Twenty abstracts were inputted in INIS. The subject of these were the use of autoradiography for the determination of receptors, cholecystokinin, nicotine, adrenaline, glutamate, aspartate, tranquilizers, for distribution and pharmacokinetics of obidoxime-chloride, for cell proliferation, mitosis of brain cells, DNA repair; radioimmunoassay of cholinesterase, tyrosinase; positron computed tomography of the brain; biological radiation effects on cholinesterase activity; tracer techniques for determination of adrenaline; and studies of the biological repair of nerves. (J.P.)

  9. 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

    2016-10-01

    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.

  10. [Effects of repeated sevoflurane anesthesia on hepatic and renal function in a pediatric patient].

    Science.gov (United States)

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

    1994-10-01

    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.

  11. Persistent symptoms in agricultural workers exposed to organophosphate pesticides

    Directory of Open Access Journals (Sweden)

    Martha E. Palacios N

    2011-07-01

    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.

  12. 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

    2015-08-01

    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

  13. A Novel Approach for Evaluating Carbamate Mixtures for Dose Additivity

    Science.gov (United States)

    Two mathematical approaches were used to test the hypothesis ofdose-addition for a binary and a seven-chemical mixture ofN-methyl carbamates, toxicologically similar chemicals that inhibit cholinesterase (ChE). In the more novel approach, mixture data were not included in the ana...

  14. 21 CFR 558.185 - Coumaphos.

    Science.gov (United States)

    2010-04-01

    ... in paragraph (e)(1) of this section. (c) Related tolerances. See 40 CFR 180.189. (d) Special... treatment with or exposure to cholinesterase-inhibiting drugs, pesticides, or chemicals.” Also, see § 500.25... normal grain ration to which the animals are accustomed, but not in rations containing more than...

  15. AN ENVIRONMENTAL TECHNOLOGY VERIFICATION (ETV) TESTING OF ENZYMATIC TEST KITS FOR WARFARE AGENTS AND PESTICIDES IN DRINKING WATER

    Science.gov (United States)

    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...

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

    OpenAIRE

    Slotkin, Theodore A.

    2010-01-01

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Navrotzky, V.K.

    1959-01-01

    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.

  18. Toxic action of organophosphorus compounds and esterase inhibition in houseflies

    NARCIS (Netherlands)

    Asperen, K. van

    1960-01-01

    The paper deals with investigations on the inhibition in vivo of the cholin-esterase and the aliesterase in houseflies poisoned by treatment with organophosphorus insecticides. The kinetics of the inhibition of esterases by DDVP, paraoxon and diazoxon in the presence and in the absence of substrate

  19. 77 FR 54402 - Dichlorvos (DDVP); Order Denying NRDC's Objections on Remand

    Science.gov (United States)

    2012-09-05

    ... cholinergic effects.'' (Ref. 27 at 25; see 73 FR 42688-42689). Inhibition of blood cholinesterase ``is not an... order, (72 FR 68662, December 5, 2007), denying a petition to revoke all tolerances established for the... this objection, (73 FR 42683, July 23, 2008), but that order was vacated, in part, by the United...

  20. Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease

    OpenAIRE

    Smith, Gwenn S.; Kramer, Elisse; Ma, Yilong; Hermann, Carol R.; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David

    2009-01-01

    Pre-clinical and human neuropharmacological evidence suggests a role of cholinergic modulation of monoamines as a pathophysiological and therapeutic mechanism in Alzheimer's disease. The present study measured the effects of treatment with the cholinesterase inhibitor and nicotinic receptor modulator, galantamine, on the cerebral metabolic response to the selective serotonin reuptake inhibitor, citalopram. Seven probable Alzheimer's disease patients and seven demographically comparable contro...

  1. Possible Overlapping Time Frames of Acquisition and Consolidation Phases in Object Memory Processes: A Pharmacological Approach

    Science.gov (United States)

    Akkerman, Sven; Blokland, Arjan; Prickaerts, Jos

    2016-01-01

    In previous studies, we have shown that acetylcholinesterase inhibitors and phosphodiesterase inhibitors (PDE-Is) are able to improve object memory by enhancing acquisition processes. On the other hand, only PDE-Is improve consolidation processes. Here we show that the cholinesterase inhibitor donepezil also improves memory performance when…

  2. 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

  3. CARBARYL EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF ADOLESCENT AND SENESCENT BROWN NORWAY RATS

    Science.gov (United States)

    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...

  4. Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology.

    Science.gov (United States)

    Burns, Alistair; O'Brien, John; Auriacombe, Sophie; Ballard, Clive; Broich, Karl; Bullock, Roger; Feldman, Howard; Ford, Gary; Knapp, Martin; McCaddon, Andrew; Iliffe, Steve; Jacova, Claudia; Jones, Roy; Lennon, Sean; McKeith, Ian; Orgogozo, Jean-Marc; Purandare, Nitin; Richardson, Mervyn; Ritchie, Craig; Thomas, Alan; Warner, James; Wilcock, Gordon; Wilkinson, David

    2006-11-01

    The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review the evidence on the drug treatment for dementia. The level of evidence (types) was rated using a standard system: Types 1a and 1b (evidence from meta-analysis of randomised controlled trials or at least one controlled trial respectively); types 2a and 2b (one well-designed study or one other type of quasi experimental study respectively); type 3 (non-experimental descriptive studies); and type 4 (expert opinion). There is type 1a evidence for cholinesterase inhibitors (donepezil, rivastigmine and galantamine) for mild to moderate Alzheimer's disease; memantine for moderate to severe Alzheimer's disease; and for the use of bright light therapy and aromatherapy. There is type 1a evidence of no effect of anti inflammatory drugs or statins. There is conflicting evidence regarding oestrogens, with type 2a evidence of a protective effect of oestrogens but 1b evidence of a harmful effect. Type 1a evidence for any effect of B12 and folate will be forthcoming when current trials report. There is type 1b evidence for gingko biloba in producing a modest benefit of cognitive function; cholinesterase inhibitors for the treatment of people with Lewy body disease (particularly neuropsychiatric symptoms); cholinesterase inhibitors and memantine in treatment cognitive impairment associated with vascular dementia; and the effect of metal collating agents (although these should not be prescribed until more data on safety and efficacy are available). There is type 1b evidence to show that neither cholinesterase inhibitors nor vitamin E reduce the risk of developing Alzheimer's disease in people with mild cognitive impairment; and there is no evidence that there is any intervention that can prevent the onset of dementia. There is type 1b evidence for the beneficial effects of adding memantine to cholinesterase inhibitors, and type 2b evidence of positive switching outcomes from one

  5. 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

    2016-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Seyed Ali Johari

    2016-05-01

    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.

  7. Occupational pesticide intoxications among farmers in Bolivia: a cross-sectional study

    DEFF Research Database (Denmark)

    Jørs, Erik; Morant, Rafael Cervantes; Aguilar, Guido Condarco;

    2006-01-01

    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 ......, and a coordinated action by authorities, society and international bodies is needed to limit the number of intoxications and the environmental pollution....... 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...

  8. Fatty Acid Amide Hydrolase (FAAH), Acetylcholinesterase (AChE), and Butyrylcholinesterase (BuChE): Networked Targets for the Development of Carbamates as Potential Anti-Alzheimer's Disease Agents.

    Science.gov (United States)

    Montanari, Serena; Scalvini, Laura; Bartolini, Manuela; Belluti, Federica; Gobbi, Silvia; Andrisano, Vincenza; Ligresti, Alessia; Di Marzo, Vincenzo; Rivara, Silvia; Mor, Marco; Bisi, Alessandra; Rampa, Angela

    2016-07-14

    The modulation of the endocannabinoid system is emerging as a viable avenue for the treatment of neurodegeneration, being involved in neuroprotective and anti-inflammatory processes. In particular, indirectly enhancing endocannabinoid signaling to therapeutic levels through FAAH inhibition might be beneficial for neurodegenerative disorders such as Alzheimer's disease, effectively preventing or slowing the progression of the disease. Hence, in the search for a more effective treatment for Alzheimer's disease, in this paper, the multitarget-directed ligand paradigm was applied to the design of carbamates able to simultaneously target the recently proposed endocannabinoid system and the classic cholinesterase system, and achieve effective dual FAAH/cholinesterase inhibitors. Among the two series of synthesized compounds, while some derivatives proved to be extremely potent on a single target, compounds 9 and 19 were identified as effective dual FAAH/ChE inhibitors, with well-balanced nanomolar activities. Thus, 9 and 19 might be considered as new promising candidates for Alzheimer's disease treatment. PMID:27309570

  9. Kindling: a pharmacological approach.

    Science.gov (United States)

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

    1982-01-01

    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.

  10. 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

    2003-01-01

    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.

  11. 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.

    1994-12-31

    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.

  12. 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

    2015-12-01

    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.

  13. Progress in drug development for Alzheimer's disease: An overview in relation to mitochondrial energy metabolism.

    Science.gov (United States)

    Hroudová, Jana; Singh, Namrata; Fišar, Zdeněk; Ghosh, Kallol K

    2016-10-01

    Current possibilities of Alzheimer's disease (AD) treatment are very limited and are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or N-methyl-d-aspartate receptor antagonist, memantine. Newly synthesized drugs affect multiple AD pathophysiological pathways and can act as inhibitors of cholinesterases (AChE, BuChE), inhibitors of monoamine oxidases (MAO-A, MAO-B), modulators of mitochondrial permeability transition pores, modulators of amyloid-beta binding alcohol dehydrogenase and antioxidants. Effects of clinically used as well as newly developed AD drugs were studied in relation to energy metabolism and mitochondrial functions, including oxidative phosphorylation, activities of enzymes of citric acid cycle or electron transfer system, mitochondrial membrane potential, calcium homeostasis, production of reactive oxygen species and MAO activity. PMID:27094132

  14. 転移性骨腫瘍で発症した細小肝細胞癌の1例

    OpenAIRE

    西本, 和央; 西野, 俊彦; 椎木, 英夫; 金内, 雅夫; 土肥, 和紘; 夏目, 由美子; 廣橋, 伸治; 市島, 國雄

    1997-01-01

    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...

  15. Sviluppo e studio di biosensori sostenibili e performanti dedicati alla determinazione di composti nutraceutici e contaminanti di interesse agroalimentare

    OpenAIRE

    MONTI, Patrizia

    2016-01-01

    The ability of a biosensor to respond to an analyte lies in the nature of the biological component. Based on the evidence that aflatoxin is able to inhibit the enzymatic activity of the acetyl cholinesterase enzyme (ACE) (Arduini et al., 2007), an amperometric biosensor based on enzymes ACE and choline oxidase has been developed. The biosensor was tested with different mixtures of mycotoxins (aflatoxin, patulin, type B trichothecene and ochratoxin) and reported the presence of aflatoxins and ...

  16. Study of effects of donepezil and aspirin on working memory in rats using electroconvulsive shock model

    OpenAIRE

    Rahul M. Manjare; Abhijit V. Tilak; Bhalchandra T. Rane; Sanjay A. Dabhade; Rahul R. Bhalsinge; Harshal P. Patil

    2014-01-01

    Background: Memory is the most common cognitive ability lost with dementia commonly seen in Alzheimer's disease (AD). Donepezil was the first cholinesterase inhibitor to be licensed in UK for AD. There is preliminary evidence that aspirin decreases the risk and delays the onset of AD. Low dose aspirin users had numerically lower prevalence of Alzheimer's dementia and had better cognitive function than non-users. Methods: Retention of conditioned avoidance response (CAR) was assessed by usi...

  17. Neonatal Exposure to Parathion Alters Lipid Metabolism in Adulthood: Interactions with Dietary Fat Intake and Implications for Neurodevelopmental Deficits

    OpenAIRE

    Lassiter, T. Leon; Ryde, Ian T.; Levin, Edward D.; Seidler, Frederic J; Slotkin, Theodore A.

    2010-01-01

    Organophosphates are developmental neurotoxicants but recent evidence also points to metabolic dysfunction. We determined whether neonatal parathion exposure in rats has long-term effects on regulation of adipokines and lipid peroxidation. We also assessed the interaction of these effects with increased fat intake. Rats were given parathion on postnatal days 1–4 using doses (0.1 or 0.2 mg/kg/day) that straddle the threshold for barely detectable cholinesterase inhibition and the first signs o...

  18. Galantamine treatment in Alzheimer's disease: response and long-term outcome in a routine clinical setting

    OpenAIRE

    Wallin, Åsa

    2011-01-01

    Åsa K Wallin, Carina Wattmo, Lennart MinthonClinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, SwedenBackground: In the absence of long-term, placebo-controlled studies of cholinesterase inhibitors in Alzheimer's disease (AD), analysis of the results of open-label trials becomes crucial. This study aimed to explore the three-year effects of galantamine treatment, as well as subgroups of response and adherence to treatment.Methods...

  19. Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

    OpenAIRE

    Shin-Ichi Yokota; Kaai Nakamura; Midori Ando; Hiroyasu Kamei; Fumihiko Hakuno; Shin-Ichiro Takahashi; Shigenobu Shibata

    2014-01-01

    Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepa...

  20. Polyketides from the plant endophytic fungus Cladosporium sp. IFB3lp-2.

    Science.gov (United States)

    Wuringege; Guo, Zhi-Kai; Wei, Wei; Jiao, Rui-Hua; Yan, Tong; Zang, Le-Yun; Jiang, Rong; Tan, Ren-Xiang; Ge, Hui-Ming

    2013-09-01

    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.

  1. Neuroprotective Potential of Novel Multi-Targeted Isoalloxazine Derivatives in Rodent Models of Alzheimer's Disease Through Activation of Canonical Wnt/β-Catenin Signalling Pathway.

    Science.gov (United States)

    Machhi, Jatin; Sinha, Anshuman; Patel, Pratik; Kanhed, Ashish M; Upadhyay, Pragnesh; Tripathi, Ashutosh; Parikh, Zalak S; Chruvattil, Ragitha; Pillai, Prakash P; Gupta, Sarita; Patel, Kirti; Giridhar, Rajani; Yadav, Mange Ram

    2016-05-01

    Previous reports suggest that Alzheimer's disease is protected by cholinesterase inhibitors. We synthesized some isoalloxazine derivatives and evaluated them using in vitro cholinesterase inhibition assay. Two of the compounds (7m and 7q) were figured out as potent cholinesterase inhibitors. They further showed anti-Aβ aggregatory activity in the in vitro assay. The current study deals with the evaluation of neuroprotective potentials of the potent compounds (7m and 7q) using different in vitro and in vivo experiments. The compounds were first assessed for their tendency to cross blood-brain barrier using in vitro permeation assay. They were evaluated using scopolamine-induced amnesic mice model. Additionally, ROS scavenging and anti-apoptotic properties of 7m and 7q were established against Aβ1-42-induced toxicity in rat hippocampal neuronal cells. 7m and 7q were also evaluated using Aβ1-42-induced Alzheimer's rat model. Lastly, their involvement in Wnt/β-catenin pathway was also demonstrated. The results indicated good CNS penetration for 7m and 7q. The neuroprotective effects of 7m and 7q were evidenced by improved cognitive ability in both scopolamine and Aβ1-42-induced Alzheimer's-like condition in rodents. The in vivo results also confirmed their anti-cholinesterase and anti-oxidant potential. Immunoblot results showed that treatment with 7m and 7q decreased Aβ1-42, p-tau, cleaved caspase-3, and cleaved PARP levels in Aβ1-42-induced Alzheimer's rat brain. Additionally, immunoblot results demonstrated that 7m and 7q activated the Wnt/β-catenin pathway as evidenced by increased p-GSK-3, β-catenin, and neuroD1 levels in Aβ1-42-induced Alzheimer's rat brain. These findings have shown that isoalloxazine derivatives (7m and 7q) could be the potential leads for developing effective drugs for the treatment of AD. PMID:26797524

  2. Treating Patients With Moderate to Severe Alzheimer's Disease: Implications of Recent Pharmacologic Studies

    OpenAIRE

    Forchetti, Concetta M.

    2005-01-01

    Background and Objective: As the prevalence of Alzheimer's disease (AD) continues to rise, physicians will be challenged to manage increasing numbers of patients with moderate to severe AD. Despite the need for active treatment and management, the growing AD population has been overlooked in the primary care setting. Currently, the approved treatments for AD are the cholinesterase inhibitors donepezil, riva-stigmine, and galantamine and the N-methyl-d-aspartate receptor antagonist memantine. ...

  3. 全科医生处方集

    Institute of Scientific and Technical Information of China (English)

    方玉婷

    2011-01-01

    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。

  4. An Atypical Cutaneous Reaction to Rivastigmine Transdermal Patch

    Directory of Open Access Journals (Sweden)

    T. Grieco

    2011-01-01

    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.

  5. TARGETING OF NEUROTROPHIC FACTORS, THEIR RECEPTORS, AND SIGNALING PATHWAYS IN THE DEVELOPMENTAL NEUROTOXICITY OF ORGANOPHOSPHATES IN VIVO AND IN VITRO

    OpenAIRE

    Slotkin, Theodore A.; Seidler, Frederic J; Fumagalli, Fabio

    2008-01-01

    Neurotrophic factors control neural cell differentiation and assembly of neural circuits. We previously showed that organophosphate pesticides differentially regulate members of the fibroblast growth factor (fgf) gene family. We administered chlorpyrifos and diazinon to neonatal rats on postnatal days 1–4 at doses devoid of systemic toxicity or growth impairment, and spanning the threshold for barely-detectable cholinesterase inhibition. We evaluated the impact on gene families for different ...

  6. Comparative Developmental Neurotoxicity of Organophosphates In Vivo: Transcriptional Responses of Pathways for Brain Cell Development, Cell Signaling, Cytotoxicity and Neurotransmitter Systems

    OpenAIRE

    Slotkin, Theodore A.; Seidler, Frederic J

    2007-01-01

    Organophosphates affect mammalian brain development through a variety of mechanisms beyond their shared property of cholinesterase inhibition. We used microarrays to characterize similarities and differences in transcriptional responses to chlorpyrifos and diazinon, assessing defined gene groupings for the pathways known to be associated with the mechanisms and/or outcomes of chlorpyrifos-induced developmental neurotoxicity. We exposed neonatal rats to daily doses of chlorpyrifos (1 mg/kg) or...

  7. COMPARATIVE EFFECTS OF CHLOPYRIFOS IN WILD TYPE AND CANNABINIOID CB1 RECEPTOR KNOCKOUT MICE

    OpenAIRE

    Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey

    2011-01-01

    Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55,212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in ti...

  8. Exposure to Organophosphates Reduces the Expression of Neurotrophic Factors in Neonatal Rat Brain Regions: Similarities and Differences in the Effects of Chlorpyrifos and Diazinon on the Fibroblast Growth Factor Superfamily

    OpenAIRE

    Slotkin, Theodore A.; Seidler, Frederic J; Fumagalli, Fabio

    2007-01-01

    Background The fibroblast growth factor (FGF) superfamily of neurotrophic factors plays critical roles in neural cell development, brain assembly, and recovery from neuronal injury. Objectives We administered two organophosphate pesticides, chlorpyrifos and diazinon, to neonatal rats on postnatal days 1–4, using doses below the threshold for systemic toxicity or growth impairment, and spanning the threshold for barely detectable cholinesterase inhibition: 1 mg/kg/day chlorpyrifos and 1 or 2 m...

  9. Human exposure and risk from indoor use of chlorpyrifos.

    OpenAIRE

    Gibson, J.E.; Peterson, R K; Shurdut, B A

    1998-01-01

    The toxicity, exposure, and risk from chlorpyrifos are briefly discussed in juxtaposition with two recent articles in Environmental Health Perspectives concerning potential exposures to children. In studies conducted according to EPA guidelines, chlorpyrifos has been shown not to be mutagenic, carcinogenic, or teratogenic, nor does it adversely affect reproduction. Chlorpyrifos toxicity does not occur in the absence of significant cholinesterase inhibition. If exposures are less than those th...

  10. Anticholinesterase activities of cold and hot aqueous extracts of F. racemosa stem bark

    OpenAIRE

    Faiyaz Ahmed; Asna Urooj

    2010-01-01

    The present study evaluated the anticholinesterase activity of cold and hot aqueous extracts of Ficus racemosa stem bark against rat brain acetylcholinesterase in vitro. Both the cold aqueous extract (FRC) and the hot aqueous extract (FRH) exhibited a dose dependent inhibition of rat brain acetylcholinesterase. FRH showed significantly higher ( p ≤ 0.001) cholinesterase inhibitory activity compared to FRC; however, both the extracts did not show 50% inhibition of AChE at the doses tested (200...

  11. Mineralization of Paraoxon and Its Use as a Sole C and P Source by a Rationally Designed Catabolic Pathway in Pseudomonas putida

    OpenAIRE

    de la Peña Mattozzi, Matthew; Tehara, Sundiep K.; Hong, Thomas; Keasling, Jay D.

    2006-01-01

    Organophosphate compounds, which are widely used as pesticides and chemical warfare agents, are cholinesterase inhibitors. These synthetic compounds are resistant to natural degradation and threaten the environment. We constructed a strain of Pseudomonas putida that can efficiently degrade a model organophosphate, paraoxon, and use it as a carbon, energy, and phosphorus source. This strain was engineered with the pnp operon from Pseudomonas sp. strain ENV2030, which encodes enzymes that trans...

  12. Effectiveness of Donepezil, Rivastigmine, and (±)Huperzine A in Counteracting the Acute Toxicity of Organophosphorus Nerve Agents: Comparison with Galantamine

    OpenAIRE

    Aracava, Yasco; Pereira, Edna F. R.; Akkerman, Miriam; Adler, Michael; Albuquerque, Edson X.

    2009-01-01

    Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (±)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepub...

  13. Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity

    OpenAIRE

    Miroslav Pohanka

    2014-01-01

    Acetylcholinesterase (AChE) inhibitors are widely used for the symptomatic treatment of Alzheimer’s disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE). Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a “cholinergic anti-inflammatory pathway” which raises questions about the role of these inhibitors in the immune system. Thi...

  14. Efficacy study of Prunus amygdalus (almond) nuts in scopolamine-induced amnesia in rats

    OpenAIRE

    Kulkarni, Kirti S.; Kasture, S.B.; Mengi, S.A.

    2010-01-01

    Objective: Cognitive disorders such as amnesia, attention deficit and Alzheimer’s disease are emerging nightmares in the field of medicine because no exact cure exists for them, as existing nootropic agents (piractam, tacrine, metrifonate) have several limitations. The present study was undertaken to investigate the effect of Prunus amygdalus (PA) nuts on cognitive functions, total cholesterol levels and cholinesterase (ChE) activity in scopolamine-induced amnesia in rats. Materials and Metho...

  15. Morbidity in newborns exposed to organophosphorus pesticides

    OpenAIRE

    Đorđević Momčilo; Sazdanović Predrag; Đorđević Gordana; Jovanović Božidar

    2010-01-01

    Introduction. Insecticides are toxines by which we destroy harmful insects. The most frequent insecticides which are used today are organophosphorus pesticides. This group of compounds make substances whose activity mechanism is based on the inhibition of acetylcho­linesterase in nerve synapsis, thus producing holynergic syndrome, resulting from the accumulation of acetylcholine which developed due to the absence of decomposition under the influence of cholinesterase. In the clinical pi...

  16. Progress update: Pharmacological treatment of Alzheimer’s disease

    OpenAIRE

    Hogan, David B.

    2007-01-01

    A number of drugs have been approved for the treatment of Alzheimer’s disease (AD) and a larger number are being studied as possible therapies. The current mainstays of the pharmacotherapy of AD are the cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine. They collectively have acceptable tolerability and proven but modest efficacy. The agents being studied include dietary supplements (eg, vitamin E), herbal preparations (eg, Ginkgo biloba), medications approved for...

  17. Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain

    OpenAIRE

    Creeley, Catherine E.; Wozniak, David F.; Nardi, Anthony; Farber, Nuri B.; Olney, John W.

    2006-01-01

    The NMDA antagonist, memantine (Namenda), and the cholinesterase inhibitor, donepezil (Aricept), are currently being used widely, either individually or in combination, for treatment of Alzheimer’s disease (AD). NMDA antagonists have both neuroprotective and neurotoxic properties; the latter is augmented by drugs, such as pilocarpine, that increase cholinergic activity. Whether donepezil, by increasing cholinergic activity, might augment memantine’s neurotoxic potential has not been investiga...

  18. Characteristics of patients with Alzheimer’s disease who switch to rivastigmine transdermal patches in routine clinical practice

    OpenAIRE

    López-Pousa S; Arranz FJ

    2013-01-01

    Secundino López-Pousa,1 Francisco Javier Arranz21Unit for Assessment of Memory and Dementia, Institut d’Assistència Sanitària de Girona, Salt, Girona, 2CNS Area, Medical Department and Health Innovation, Esteve, Barcelona, SpainBackground: The aim of this study was to assess the sociodemographic and clinical characteristics of patients with Alzheimer’s disease who switched from any oral cholinesterase inhibitor to rivastigmine patches.Metho...

  19. Environmental impacts of the control with organophosphate pesticides and explosions of the red-billed quelea bird Quelea quelea in Africa

    OpenAIRE

    Cheke, R.A.; E. van der Walt; Mbereki, C.; Mtobesya, B.N.; Magoma, R.N.; Farman, D.I.; Adranyi, E.; McWilliam, A

    2011-01-01

    Both spraying with pesticides and using explosions to kill red-billed quelea (Quelea quelea) may affect non-target organisms and leave hazardous contaminants in the environment. Results of monitoring such effects in Botswana and Tanzania showed that although few non-target mortalities were noted, indirect effects in terms of depressed cholinesterases in birds and small mammals were marked and pesticides and contaminants from products used for the explosions persisted at controlled sites at un...

  20. Characterization of an Antennal Carboxylesterase from the Pest Moth Spodoptera littoralis Degrading a Host Plant Odorant

    OpenAIRE

    Nicolas Durand; Gerard Carot-Sans; Thomas Chertemps; Françoise Bozzolan; Virginie Party; Michel Renou; Stéphane Debernard; Gloria Rosell; Martine Maïbèche-Coisne

    2010-01-01

    Background: Carboxyl/cholinesterases (CCEs) are highly diversified in insects. These enzymes have a broad range of proposed functions, in neuro/developmental processes, dietary detoxification, insecticide resistance or hormone/ pheromone degradation. As few functional data are available on purified or recombinant CCEs, the physiological role of most of these enzymes is unknown. Concerning their role in olfaction, only two CCEs able to metabolize sex pheromones have been functionally character...

  1. Biochemical and cytochemical evidence indicates that coated vesicles in chick embryo myotubes contain newly synthesized acetylcholinesterase

    OpenAIRE

    1985-01-01

    We have isolated highly purified coated vesicles from 17-d-old chick embryo skeletal muscle. These isolated coated vesicles contain acetylcholinesterase (AChE) in a latent, membrane-protected form as demonstrated enzymatically and morphologically using the Karnovsky and Roots histochemical procedure (J. Histochem. Cytochem., 1964, 12:219- 221). By the use of appropriate inhibitors the cholinesterase activity can be shown to be specific for acetylcholine. It also can be concluded that most of ...

  2. Effects of Long-Term Administration of Lithium and Hydrochlorothiazide in Rats

    OpenAIRE

    LOGHIN, FELICIA; Olinic, Adriana; Popa, Daniela-Saveta; Socaciu, Carmen; Leucuta, Sorin E.

    1999-01-01

    The biochemical and histological changes following 60 days administration of daily doses equivalent to 1/20 LD50 of lithium lactate and hydrochlorothiazide, as such and in association, were studied in male Wistar rats. No mortality or overt signs of toxicity were observed during the experiment and the serum activities of transaminases, alkaline phosphatase and cholinesterase were not significantly modified compared to controls. The histopathological examination of all the investigated organs:...

  3. Pesticide exposure, risk factors and health problems among cutflower farmers: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Del Prado-Lu Jinky

    2007-09-01

    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. Postponed effect of neostigmine on oxidative homeostasis

    Directory of Open Access Journals (Sweden)

    Pohanka Miroslav

    2014-09-01

    Full Text Available Cholinesterases are enzymes able to hydrolyze the neurotransmitter acetylcholine and thus to terminate transmission. Once the enzymes are inhibited, excitotoxicity can appear in the adjacent cells. It is well known that oxidative stress is involved in the toxicity of cholinesterase inhibitors. Commonly, stress follows inhibition of cholinesterases and disappears shortly afterwards. In the present experiment, it was decided to test the impact of an inhibitor, neostigmine, on oxidative stress in BALB/c mice after a longer interval. The animals were sacrificed three days after onset of the experiment and spleens and livers were collected. Reduced glutathione (GSH, glutathione reductase (GR, glutathione S-transferase (GST, thiobarbituric acid reactive substances (TBARS, ferric reducing antioxidant power (FRAP, caspase-3 and activity of acetylcholinesterase (AChE were assayed. The tested markers were not altered with exceptions of FRAP. The FRAP values indicate accumulation of low molecular weight antioxidants in the examined organs. The role of low molecular weight antioxidants in the toxicity of AChE inhibitors is discussed.

  5. Postponed effect of neostigmine on oxidative homeostasis.

    Science.gov (United States)

    Pohanka, Miroslav

    2014-09-01

    Cholinesterases are enzymes able to hydrolyze the neurotransmitter acetylcholine and thus to terminate transmission. Once the enzymes are inhibited, excitotoxicity can appear in the adjacent cells. It is well known that oxidative stress is involved in the toxicity of cholinesterase inhibitors. Commonly, stress follows inhibition of cholinesterases and disappears shortly afterwards. In the present experiment, it was decided to test the impact of an inhibitor, neostigmine, on oxidative stress in BALB/c mice after a longer interval. The animals were sacrificed three days after onset of the experiment and spleens and livers were collected. Reduced glutathione (GSH), glutathione reductase (GR), glutathione S-transferase (GST), thiobarbituric acid reactive substances (TBARS), ferric reducing antioxidant power (FRAP), caspase-3 and activity of acetylcholinesterase (AChE) were assayed. The tested markers were not altered with exceptions of FRAP. The FRAP values indicate accumulation of low molecular weight antioxidants in the examined organs. The role of low molecular weight antioxidants in the toxicity of AChE inhibitors is discussed. PMID:26109890

  6. Sensitivity of the sea snail Gibbula umbilicalis to mercury exposure--linking endpoints from different biological organization levels.

    Science.gov (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

    2015-01-01

    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.

  7. Sublethal responses of wolf spiders (Lycosidae) to organophosphorous insecticides.

    Science.gov (United States)

    Van Erp, S; Booth, L; Gooneratne, R; O'Halloran, K

    2002-10-01

    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.

  8. Changes of learning and memory ability and brain nicotinic receptors of rat offspring with coal burning fluorosis

    Energy Technology Data Exchange (ETDEWEB)

    Gui, C.Z.; Ran, L.Y.; Li, J.P.; Guan, Z.Z. [Guiyang Medical College, Guiyang (China). Dept. of Pathology

    2010-09-15

    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.

  9. Clinical evaluation of the measurement of hepatosplenic volume ratio by computed tomography

    International Nuclear Information System (INIS)

    The liver and spleen ratio (S/L ratio) was estimated with X-ray computed tomography. Clinical usefulness of S/L ratio was evaluated by comparison with other liver functions (retention rate of ICG, total bilirubin, serum albumin, and cholinesterase activity) in 42 hepatocellular carcinoma patients with liver cirrhosis. The correlation between S/L ratio and retention rate of ICG, total bilirubin, serum albumin or cholinesterase activity was good (r=0.870, r=0.719, r=-0.691, or r=0.606, respectively p<0.001). Positive correlation was observed between S/L ratio and retention rate of ICG or total bilirubin. Negative correlation was observed between S/L ratio and serum albumin or cholinesterase activity. In conclusion, the measurement of S/L ratio on computed tomography was considered to be useful as an evaluation for the degree of severity in liver cirrhosis by considering both effective hepatic blood flow and portal hypertension. (author)

  10. Health Aspects of Organophosphorous Pesticides in Asian Countries

    Directory of Open Access Journals (Sweden)

    B Balali-Mood

    2012-10-01

    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.

  11. [Cholinergic system of the heart].

    Science.gov (United States)

    Kučera, Matej; Hrabovská, Anna

    2015-12-01

    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.

  12. Galantamine improves sleep quality in patients with dementia.

    Science.gov (United States)

    Naharci, Mehmet Ilkin; Ozturk, Ahmet; Yasar, Halit; Cintosun, Umit; Kocak, Necmettin; Bozoglu, Ergun; Tasci, Ilker; Doruk, Huseyin

    2015-12-01

    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.

  13. Hydrogen peroxide potentiates organophosphate toxicosis in chicks

    Directory of Open Access Journals (Sweden)

    Banan K. Al-Baggou

    2011-11-01

    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

  14. Crocin Restores Hypotensive Effect of Subchronic Administration of Diazinon in Rats

    Directory of Open Access Journals (Sweden)

    Marjan Razavi

    2013-01-01

    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. Behavioral swimming effects and acetylcholinesterase activity changes in Jenynsia multidentata exposed to chlorpyrifos and cypermethrin individually and in mixtures.

    Science.gov (United States)

    Bonansea, Rocío Inés; Wunderlin, Daniel Alberto; Amé, María Valeria

    2016-07-01

    The pesticides cypermethrin (CYP) and chlorpyrifos (CPF) were found together in water bodies located in agricultural and urban areas. However, the impact to non-target biota from exposure to mixtures has received little attention. In the current study, we evaluated changes in swimming behavior and cholinesterase enzymes activity in Jenynsia multidentata, to investigate the possible effects of these insecticides individually and in mixtures. Moreover, differences between technical and commercial mixtures of the pesticides were evaluated. Females of J. multidentata were exposed over 96-h to CYP (0.04 and 0.4µgL(-1)), CPF (0.4 and 4µgL(-1)), individually and in a technical and commercial mixtures. Swimming behavior was recorded after 24h and 96h of exposure. Also, we measured cholinesterase enzymes activity in brain and muscle after 96h of exposure. Exposure to CYP increased the exploratory activity of J. multidentata in the upper area of the aquarium. Fish exposed to CPF (4µg L(-1)) showed a decrease in swimming activity and an increase in the time spent at the bottom of the aquarium. Interestingly, fish exposed to the technical and commercial mixture of CYP and CPF displayed a different behavior based on the concentration of exposure. Low concentration of pesticides elicited an increase in J. multidentata swimming activity with preference for the upper area of the aquarium, and high concentrations caused decrease in swimming activity with preference for the bottom area of the aquarium. Based on the response of cholinesterase enzymes, acetylcholinesterase in muscle was more sensitive to exposure to CYP, CPF and their mixtures than in brain. A decrease in swimming behavior correlates significantly with the inhibition of acetylcholinesterase activity in muscle of J. multidentata exposed to high concentrations of pesticides. These results draw attention to the need of more studies on the potential ecotoxicological impact of pesticides and its mixtures at

  16. Effect of Acetylcholinesterase and Butyrylcholinesterase on Intrauterine Insemination, Contribution to Inflammations, Oxidative Stress and Antioxidant Status; A Preliminary Report

    Science.gov (United States)

    Haghnazari, Lida; Vaisi-Raygani, Asad; Keshvarzi, Farahnaz; Ferdowsi, Farivar; Goodarzi, Massoud; Rahimi, Zohreh; Baniamerian, Hossin; Tavilani, Haidar; Vaisi-Raygani, Hadis; Vaisi-Raygani, Hessam; Pourmotabbed, Tayehbeh

    2016-01-01

    Background: Oxidative stress affects women fertility and influences on the sperm quality by alterating activities of cholinesterases, a molecular marker of stress-related infertility. The aim of the present study was to investigate the role of acetyl-cholinesterase (AChE), butyrylcholinesterase (BuChE) activities and phenotypes in patients with unexplained infertility (idiopathic). It’s possible association with inflammation marker C-reactive protein (CRP) and other oxidative stress markers, i.e. before and after intra uterine insemination (IUI). Methods: In this study, blood samples of 60 patients with unexplained infertility were collected the day before and 24 hr after IUI (between 8 AM and 9 AM after the overnight fasting) and activities of BuChE, AChE, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GpX) and serum levels of thiol proteins (TP), C-reactive protein (CRP), total antioxidant capacity (TAC) were measured. Statistical significance was assumed at pCAT activity between various BuChE (UU and non-UU) phenotypes. However, after IUI, a significant negative correlation between the AChE activity and BuChE activity was found (p=0.045) and the level of RBC AChE activity was significantly reduced (382.4± 163.19 vs. 586.7±384 IU/grHb, p=0.025). Meanwhile, after IUI, the activities of SOD (1568±847.5 IU/grHb vs. 1126±229.3, p=0.031) and CAT (310±53.4 IU/grHb vs. 338±73, p=0.025) were increased. Conclusion: This study suggests that decline in cholinesterases activities may be responsible for stimulation of oxidative stress and inflammation and reduction in fertility rates by IUI. PMID:27478769

  17. Biosensor based on Butyrylcholinesterase for Detection of Carbofuran

    Science.gov (United States)

    Dey, Mousumi; Bhuvanagayathri, R.; Daniel, David K.

    2015-04-01

    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

  18. Neuroprotective Role of Novel Triazine Derivatives by Activating Wnt/β Catenin Signaling Pathway in Rodent Models of Alzheimer's Disease.

    Science.gov (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

    2015-08-01

    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.

  19. Acetylcholinesterase assay for cerebrospinal fluid using bupivacaine to inhibit butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Anders Jens

    2001-12-01

    Full Text Available Abstract Background Most test systems for acetylcholinesterase activity (E.C.3.1.1.7. are using toxic inhibitors (BW284c51 and iso-OMPA to distinguish the enzyme from butyrylcholinesterase (E.C.3.1.1.8. 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.

  20. Acetylcholinesterase activities in marine snail (Cronia contracta) as a biomarker of neurotoxic contaminants along the Goa coast, West coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Gaitonde, D.; Sarkar, A.; Kaisary, S.; DeSilva, C.; Dias, C.F.M.; Rao, P.V.S.S.D.P.; Ray, D.; Nagarajan, R.; DeSousa, S.N.; Sarkar, S.; Patill, D.

    of muscle tissue (Cajaraville et al. 2000). AChE is the enzyme that is usually located in membranes of vertebrates and non-vertebrates animals (Bocquene´ et al, 1997). Cholinesterase enzymes (ChE) are often highly polymorphic enzymes in inverte- brates.... According to the mechanism of action, the AChE is released at the myoneutral junction in organisms if an action potential is developed at the nerve ending and diffuses through the gap between the nerve and the muscle (the gap is about 100 A ˚ wide...

  1. 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.

    2009-07-01

    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)

  2. Polyneuropathy due to n-hexane.

    Science.gov (United States)

    Paulson, G W; Waylonis, G W

    1976-08-01

    In 25 years, at least eight of 50 total exposed employees in a small plant developed a mild neuropathy. Studies of urine or blood for lead, arsenic, mercury, cadmium, thallium, and antimony revealed no sign of toxic agents, but the atmosphere in one room contained toxic levels of n-hexane. The sourse was the glue used in the plant. Serum cholinesterase levels were reduced, offering a possible laboratory tests to alert clinicians to the possibility of n-hexane exposure. All patients recovered completely. Mechanical and administrative adjustments should prevent such industrial accidents. PMID:182098

  3. Mortality of passerines adjacent to a North Carolina corn field treated with granular carbofuran.

    Science.gov (United States)

    Augspurger, Tom; Smith, Milton R.; Meteyer, Carol U.; Converse, Kathryn A.

    1996-01-01

    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.

  4. 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;

    1995-01-01

    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....

  5. 白アリ防除剤に関する実験的研究 第2編 クロルピリホスのラットにおけるコリンエステラーゼ活性におよぼす影響

    OpenAIRE

    酒井, 律江

    1990-01-01

    Inhibition of cholinesterase (ChE) activity was examined by experiments on enzyme activity of ChE of rat administered intraperitoneally chlorpyrifos and enzyme kinetic study of ChE in plasma. Plasma ChE activity was inhibited more highly than erythrocyte ChE activity in rat 12 hrs after administration. Plasma ChE activity was recovered 1 month after administration but erythrocyte ChE activity was not recovered. No difference between frontal cortex and striatum ChE activity was recognized. Cha...

  6. Anticholinesterase activities of cold and hot aqueous extracts of F. racemosa stem bark.

    Science.gov (United States)

    Ahmed, Faiyaz; Urooj, Asna

    2010-04-01

    The present study evaluated the anticholinesterase activity of cold and hot aqueous extracts of Ficus racemosa stem bark against rat brain acetylcholinesterase in vitro. Both the cold aqueous extract (FRC) and the hot aqueous extract (FRH) exhibited a dose dependent inhibition of rat brain acetylcholinesterase. FRH showed significantly higher (P cholinesterase inhibitory activity compared to FRC; however, both the extracts did not show 50% inhibition of AChE at the doses tested (200-1000 mug ml(-1)). The IC(50) values of 1813 and 1331 mug ml(-1) were deduced for FRC and FRH, respectively (calculated by extrapolation using Boltzmann's dose response analysis).

  7. 有机磷杀虫药中毒

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    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.

  8. [Neurochemical characteristics of rats during flight on the Kosmos-782 artificial satellite and after returning to earth].

    Science.gov (United States)

    Gazenko, O G; Demin, N N; Panov, A N; Rashevskaia, D A; Rubinskaia, N L

    1979-01-01

    The brain of rats flown aboard the biosatellite Cosmos-782 was sampled immediately postflight and taken under neurochemical study. It was shown cytospectrophotometrically that the absolute content of RNA decreased by 20% in the cytoplasm of cerebellar Purkinje cells and remained unaltered in glial cells-satellites, and that the protein content did not change. In the frontal cortex (homogenates) the concentration of sulfhydryl groups decreased by 26%, activity of nonspecific cholinesterase by 33%. The activity of the latter in the cerebellum also diminished.

  9. Safety profile of Cerebrolysin: clinical experience from dementia and stroke trials.

    Science.gov (United States)

    Thome, J; Doppler, E

    2012-04-01

    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.

  10. Eye-related visual hallucinations: Consider ′Charles Bonnet syndrome′

    Directory of Open Access Journals (Sweden)

    Nilgun Cinar

    2011-01-01

    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.

  11. Eye-related visual hallucinations: consider 'Charles Bonnet syndrome'.

    Science.gov (United States)

    Cinar, Nilgun; Sahin, Sevki; Karsidag, Sibel

    2011-01-01

    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.

  12. Utilização de técnicas eletroanalíticas na determinação de pesticidas em alimentos

    Directory of Open Access Journals (Sweden)

    Galli Andressa

    2006-01-01

    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.

  13. Cognitive dysfunction and its determinants in patients with neurocysticercosis

    Directory of Open Access Journals (Sweden)

    Vinod Varghese

    2016-01-01

    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.

  14. Cognitive Dysfunction and its Determinants in Patients with Neurocysticercosis

    Science.gov (United States)

    Varghese, Vinod; Chandra, Sadanandavalli Retnaswami; Christopher, Rita; Rajeswaran, Jamuna; Prasad, Chandrajit; Subasree, R.; Issac, Thomas Gregor

    2016-01-01

    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

  15. Alzheimer's disease: early diagnosis and treatment.

    Science.gov (United States)

    Chu, L W

    2012-06-01

    With ageing of populations, the worldwide population of persons with dementia will reach over 81 million by 2040, of which the most common cause is Alzheimer's disease. In recent years, there have been major advances in the understanding of its pathogenesis, methods to diagnose it, and treatment. Magnetic resonance brain imaging, cerebrospinal fluid biomarkers, and Pittsburgh compound B and fluorodeoxyglucose positron emission tomography of the brain can facilitate an accurate diagnosis of Alzheimer's disease in its early stage, and diagnose the mild cognitive impairment stage of Alzheimer's disease. At present, only symptomatic but not disease-modifying drug treatments are available. Donepezil, rivastigmine and galantamine are the currently approved cholinesterase inhibitors for the treatment of mild, moderate, and severe Alzheimer's disease. Overall, cholinesterase inhibitors show beneficial effects on cognition, activity of daily living, behaviour, and overall clinical rating. Memantine is another symptomatic treatment for moderate-to-severe Alzheimer's disease patients. It has a small beneficial effect on cognition, activity of daily living, behaviour, and overall clinical rating. Vitamin E has antioxidant properties, and may be used in some Alzheimer's disease patients without vascular risk factors. Concurrent non-pharmacological and psychosocial management of patients and their caregivers have a very important role. Disease-modifying therapies are still under development, whilst immunotherapy may be a viable option in the near future. PMID:22665688

  16. Studies on the In Vitro Antiproliferative, Antimicrobial, Antioxidant, and Acetylcholinesterase Inhibition Activities Associated with Chrysanthemum coronarium Essential Oil

    Directory of Open Access Journals (Sweden)

    Sanaa K. Bardaweel

    2015-01-01

    Full Text Available The essential oil of the Jordanian Chrysanthemum coronarium L. (garland was isolated by hydrodistillation from dried flowerheads material. The oil was essayed for its in vitro scavenging activity using the 1,1-diphenyl-2-picrylhydrazyl (DPPH method. The results demonstrate that the oil exhibits moderate radical scavenging activity relative to the strong antioxidant ascorbic acid. In addition, cholinesterase inhibitory activity of C. coronarium essential oil was evaluated for the first time. Applying Ellman’s colorimetric method, interesting cholinesterase inhibitory activity, which is not dose dependent, was evident for the oil. Furthermore, antimicrobial activities of the oil against both Gram-negative and Gram-positive bacteria were evaluated. While it fails to inhibit Gram-negative bacteria growth, the antibacterial effects demonstrated by the oil were more pronounced against the Gram-positive strains. Moreover, the examined oil was assessed for its in vitro antiproliferative properties where it demonstrated variable activities towards different human cancer cell lines, of which the colon cancer was the most sensitive to the oil treatment.

  17. Population genetic studies of the Aka pygmies (Central Africa): a survey of red cell and serum enzymes.

    Science.gov (United States)

    Vergnes, H; Sevin, A; Sevin, J; Jaeger, G

    1979-05-10

    Blood samples collected in a single Pygmy tribe, the Aka, living in Bokoka district (Central African Empire) were investigated with respect to the phenotype and gene frequencies of the following 12 enzyme systems: acid phosphatase, adenosine deaminase, adenylate kinase, carbonic anhydrase, esterase D, glucose-6-phosphate dehydrogenase, malate dehydrogenase, phosphoglucomutase 1, phosphoglucomutase 2, phosphogluconate dehydrogenase, superoxide dismutase and serum cholinesterase variants (locus E1 and E2). The data obtained in the study of genetic polymorphisms of this isolated and inbred population show a specific pattern with the following characteristics: the very low frequency of PGDB and pa alleles; the existence of two rare PGM variants at the PGM2 locus, typical PGM26Pyg (4.2%) and PGM29 (0.2%); the high frequency of the pr allele (10.8%) and CAII2 (8.22%) and ESD2 genes (18.4%). Furthermore, at the G6PD locus four distinct alleles have been found: the negroid GdA- (4%) and GdA+ (16%), the common GdB+ (79.2%)--, and the rare Gd+Ibadan Austin (0.7%). Cholinesterase typings disclosed the presence of the uncommon E1f and E1s genes distributed within a single breeding unit. The results are compared with other data previously reported on South African Khoisan and some Negroid populations; the particular genetic background of Pygmies is discussed.

  18. Methyl parathion and fenvalerate toxicity in American kestrels: Acute physiological responses and effects of cold

    Science.gov (United States)

    Rattner, B.A.; Franson, J.C.

    1984-01-01

    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.

  19. Pesticides and amphibian population declines in California, USA

    Science.gov (United States)

    Sparling, D.W.; Fellers, G.M.; McConnell, L.L.

    2001-01-01

    Several species of anuran amphibians have undergone drastic population declines in the western United States over the last 10 to 15 years. In California, the most severe declines are in the Sierra Mountains east of the Central Valley and downwind of the intensely agricultural San Joaquin Valley. In contrast, coastal and more northern populations across from the less agrarian Sacramento Valley are stable or declining less precipitously. In this article, we provide evidence that pesticides are instrumental in declines of these species. Using Hyla regilla as a sentinel species, we found that cholinesterase (ChE) activity in tadpoles was depressed in mountainous areas east of the Central Valley compared with sites along the coast or north of the Valley. Cholinesterase was also lower in areas where ranid population status was poor or moderate compared with areas with good ranid status. Up to 50% of the sampled population in areas with reduced ChE had detectable organophosphorus residues, with concentrations as high as 190 ppb wet weight. In addition, up to 86% of some populations had measurable endosulfan concentrations and 40% had detectable 4,4'- dichlorodiphenyldichloroethylene, 4,4'-DDT, and 2,4'-DDT residues.

  20. Health effects related to pesticide use among rice farmers of the MUDA area

    International Nuclear Information System (INIS)

    The objectives of this study were to assess the knowledge and practices related to pesticide handling and use among rice farmers; the types of pesticides most often associated with exposure symptoms; the types of exposure symptoms experienced by the farmers; and the neurological effect among farmers as shown by serum cholinesterase inhibition, as a result of exposure to carbarnate and organophosphate pesticides. Results indicate that farmers knowledge is still inadequate with respect to the need for proper storage of pesticides, the danger of pesticide exposure during mixing, proper disposal of pesticide containers, early symptoms of pesticide poisoning, and the possibility of pesticide absorption through the skin. Both farmers' knowledge and practices on the use of personal protective equipment (PPE) are unsatisfactory. Improper practices include the use of increased dosages and mixing of pesticides. The prevalence of pesticide exposure symptoms increased from 1991 to 1993. A majority of the health effects are due to exposure to herbicides. Among the farmers examined, 29% had below normal serum cholinesterase level. In conclusion, indiscriminate use of pesticides in rice farming has resulted in recognisable impact on the farmers' state of health even though the situation is not alarming. (Author)

  1. Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by Soman. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Sparenborg, S.; Brennecke, L.H.; Jaax, N.K.; Braitman, D.J.

    1992-12-31

    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.

  2. 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

    2009-01-01

    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.

  3. Altitude acclimatization improves submaximal cognitive performance in mice and involves an imbalance of the cholinergic system.

    Science.gov (United States)

    Guerra-Narbona, R; Delgado-García, J M; López-Ramos, J C

    2013-06-15

    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. PMID:23599398

  4. Environmental exposure to organophosphate pesticides: assessment of endocrine disruption and hepatotoxicity in pregnant women.

    Science.gov (United States)

    Cecchi, A; Rovedatti, M G; Sabino, G; Magnarelli, G G

    2012-06-01

    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.

  5. Cholinergic enzymes and inflammatory markers in rats infected by Sporothrix schenckii.

    Science.gov (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

    2016-08-01

    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.

  6. Evaluation of the effect of Ferula asafoetida Linn. gum extract on learning and memory in Wistar rats

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    Vijayalakshmi

    2012-01-01

    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.

  7. Enhancement of parathion toxicity to quail by heat and cold exposure

    Science.gov (United States)

    Rattner, B.A.; Becker, J.M.; Nakatsugawa, T.

    1987-01-01

    Effects of ambient temperature on the acute oral toxicity of parathion were investigated in Japanese quail (Coturnix japonica) maintained at thermoneutral temperature (26.degree. C) or exposed to elevated (37.degree. C) or reduced (4.degree. 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 26.degree. 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., 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.

  8. Inhibition of acetylcholinesterase in guppies (Poecilia reticulata) by chlorpyrifos at sublethal concentrations: Methodological aspects

    Energy Technology Data Exchange (ETDEWEB)

    van der Wel, H.; Welling, W.

    1989-04-01

    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.

  9. Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii

    Energy Technology Data Exchange (ETDEWEB)

    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: dsparl@siu.edu; Fellers, G. [Western Ecology Research Center, U.S. Geological Survey, Point Reyes National Seashore, Point Reyes, CA 94956 (United States)

    2007-06-15

    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.

  10. Vascular action as the primary mechanism of cognitive effects of cholinergic, CNS-acting drugs, a rat phMRI BOLD study

    Science.gov (United States)

    Kocsis, Pál; Gyertyán, István; Éles, János; Laszy, Judit; Hegedűs, Nikolett; Gajári, Dávid; Deli, Levente; Pozsgay, Zsófia; Dávid, Szabolcs; Tihanyi, Károly

    2014-01-01

    Concordant results of functional magnetic resonance imaging (fMRI) and behavioral tests prove that some non-blood–brain barrier-penetrating drugs produce robust central nervous system (CNS) effects. The anticholinergic scopolamine interferes with learning when tested in rats, which coincides with a negative blood-oxygen-level-dependent (BOLD) change in the prefrontal cortex (PFC) as demonstrated by fMRI. The peripherally acting butylscopolamine also evokes a learning deficit in a water-labyrinth test and provokes a negative BOLD signal in the PFC. Donepezil—a highly CNS-penetrating cholinesterase inhibitor—prevents the negative BOLD and cognitive deficits regardless whether the provoking agent is scopolamine or butylscopolamine. Interestingly, the non-BBB-penetrating cholinesterase inhibitor neostigmine also prevents or substantially inhibits those cognitive and fMRI changes. Intact cerebral blood flow and optimal metabolism are crucial for the normal functioning of neurons and other cells in the brain. Drugs that are not BBB penetrating yet act on the CNS highlight the importance of unimpaired circulation, and point to the cerebral vasculature as a primary target for drug action in diseases where impaired circulation and consequently suboptimal energy metabolism are followed by upstream pathologic events. PMID:24643080

  11. Determination of 3,5,6-trichloro-2-pyridinol levels in the urine of termite control workers using chlorpyrifos.

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    Jitsunari,Fumihiko

    1989-10-01

    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.

  12. Evaluation of the antiamnesic effects of Phyllanthus amarus in mice.

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    Hanumanthachar Joshi

    2009-11-01

    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.

  13. ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer's Disease Therapy

    Science.gov (United States)

    Marco-Contelles, José; Unzeta, Mercedes; Bolea, Irene; Esteban, Gerard; Ramsay, Rona R.; Romero, Alejandro; Martínez-Murillo, Ricard; Carreiras, M. Carmo; Ismaili, Lhassane

    2016-01-01

    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

  14. Synthesis and evaluation of multi-target-directed ligands against Alzheimer's disease based on the fusion of donepezil and ebselen.

    Science.gov (United States)

    Luo, Zonghua; Sheng, Jianfei; Sun, Yang; Lu, Chuanjun; Yan, Jun; Liu, Anqiu; Luo, Hai-Bin; Huang, Ling; Li, Xingshu

    2013-11-27

    A novel series of compounds obtained by fusing the cholinesterase inhibitor donepezil and the antioxidant ebselen were designed as multi-target-directed ligands against Alzheimer's disease. An in vitro assay showed that some of these molecules did not exhibit highly potent cholinesterase inhibitory activity but did have various other ebselen-related pharmacological effects. Among the molecules, compound 7d, one of the most potent acetylcholinesterase inhibitors (IC50 values of 0.042 μM for Electrophorus electricus acetylcholinesterase and 0.097 μM for human acetylcholinesterase), was found to be a strong butyrylcholinesterase inhibitor (IC50 = 1.586 μM), to possess rapid H2O2 and peroxynitrite scavenging activity and glutathione peroxidase-like activity (ν0 = 123.5 μM min(-1)), and to be a substrate of mammalian TrxR. A toxicity test in mice showed no acute toxicity at doses of up to 2000 mg/kg. According to an in vitro blood-brain barrier model, 7d is able to penetrate the central nervous system. PMID:24160297

  15. 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

    2013-01-01

    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.

  16. Apathy in Alzheimer’s Disease: Any Effective Treatment?

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    Raffaele Rea

    2014-01-01

    Full Text Available Objective. This review has evaluated the effectiveness of pharmacological treatment of apathy in patients with Alzheimer’s disease (AD. Methods. A systematic literature search was conducted on published clinical trials assessing the effects of pharmacological treatment on apathy in AD over the last 10 years. Results. Fourteen studies considered of good quality were included in the analysis (4 randomized controlled trials, 9 open-label studies, and 1 retrospective analysis. Cholinesterase inhibitors were investigated in 9 studies, monoaminergic compounds such as methylphenidate and modafinil in two trials and one trial, respectively, and Ginkgo biloba (EGb 761 extract and citalopram in one study each. Cholinesterase inhibitors did not show statistical significant effect in 1 RCT study but were associated to improvement in 3 open-label studies. Methylphenidate elicited a small but significant activity accompanied by relevant side effects such as high blood pressure, cough, and osteoarticular pain. EGb 761 was well tolerated and countered apathy. Other treatments induced modest improvements or were ineffective. Conclusions. Apathy treatment remains a challenge and there is no evident advantage of any specific pharmacotherapy tested so far. The development of controlled studies according to updated guidelines for the diagnosis of apathy in patients with AD is desirable.

  17. EVALUATION OF MEMORY ENHANCING ACTIVITY OF SR-105 IN EXPERIMENTAL ANIMALS

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    Ladde Shivakumar

    2011-03-01

    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.

  18. Evaluation of the antiamnesic effects of Phyllanthus amarus in mice

    Directory of Open Access Journals (Sweden)

    Hanumanthachar Joshi

    2007-06-01

    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.

  19. EVIDENCE BASED ANTI-DEMENTING ACTIVITY OF SARASWATA GHRITA “A NOOTROPIC COMPOUND FROM AYURVEDA

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    Obed Ahmed Ansari, J.S. Tripathi and Sayema Ansari

    2013-11-01

    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.

  20. Biochemical Studies On The Effect Of Sodium Nitrite And/Or Glutathione Treatment On Male Rats

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    Eman Helal; *Zahkok, S; **Ghada Z A Soliman; * Al-Kassas, M;

    2008-03-01

    Full Text Available Introduction: Using food preservatives as sodium nitrite are increased in industrial food productions. Teratogenic, mutagenic and carcinogenic effects have been related to using of some food preservatives. Purpose: To study the effect of sodium nitrite (food additives and treated with glutathione (nature antitoxic on rats. Material And Methods: Certain parameters were measured as percentage of body weight change, body temperature, heart rates, Red & white blood cells count (RBCs & WBCs, hemoglobin (Hb level, hematocrite (Hct value, serum total lipids, serum cholesterol, serum total protein, serum albumin, serum glucose, serum alanine transaminase and aspartate transaminase (ALT & AST activity and serum total cholinesterase. The organs, body weight were detected. Organs were prepared for biochemical analysis. Results: Body weight, respiration rate, hepatosomatic index, RBCs & WBCs count, Hb, Hct, serum total lipids, protein, albumin, A/G ratio, liver and muscle total lipids and cholesterol were significantly reduced while serum cholesterol, kidney total lipids and cholesterol, serum ALT & AST was significantly increased. Supplementation of sodium nitrite to rats had no effect on serum glucose level or cholinesterase activity Conclusion: Due to the hazardous effect of food additives as sodium nitrite, it is recommended that the use of sodium nitrite as food additives must be limited and gluathione has the ability to prevent its toxic effect

  1. Anticholinesterase activity of 7-methoxyflavones isolated from Kaempferia parviflora.

    Science.gov (United States)

    Sawasdee, Pattara; Sabphon, Chalisa; Sitthiwongwanit, Duangporn; Kokpol, Udom

    2009-12-01

    The rhizome of Kaempferia parviflora or kra-chai-dum (in Thai) is used traditionally as a folk medicine. The preliminary cholinesterase inhibitory screening of this plant extract exhibited significant acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Thirteen known methoxyflavones (1-13) were isolated and their structures were completely elucidated based on NMR analysis and compared with literature reports. Minor compounds 12-13 were reported for the first time from this species. The cholinesterase inhibitory test results showed that the highest potential inhibitors toward AChE and BChE were 5,7,4'-trimethoxyflavone (6) and 5,7-dimethoxyflavone (7), respectively, with the percentage inhibitory activity varying over 43-85%. The structure-activity relationship study led to the conclusion that compounds bearing 5,7-dimethoxy groups and a free substituent at C-3 had a significant inhibitory effect at a concentration of 0.1 mg/mL, but those bearing a 5-hydroxyl group reduced the inhibitory potency. On the other hand, flavones bearing a 3'- or 5'-methoxy group did not influence the inhibitory effect. Interestingly, 5,7-dimethoxyflavone (7) exhibited strong selectivity for BChE over AChE which may be of great interest to modify as a treatment agent for Alzheimer's disease. PMID:19548291

  2. A bioactive cycloartane triterpene from Garcinia hombroniana.

    Science.gov (United States)

    Jamila, Nargis; Khan, Naeem; Khan, Imran; Khan, Amir Atlas; Khan, Sadiq Noor

    2016-06-01

    The dichloromethane bark extract of Garcinia hombroniana yielded one new cycloartane triterpene; (22Z,24E)-3β-hydroxycycloart-14,22,24-trien-26-oic acid (1) together with five known compounds: garcihombronane G (2), garcihombronane J (3), 3β acetoxy-9α-hydroxy-17,14-friedolanostan-14,24-dien-26-oic acid (4), (22Z, 24E)-3β, 9α-dihydroxy-17,14-friedolanostan-14,22,24-trien-26-oic acid (5) and 3β, 23α-dihydroxy-17,14-friedolanostan-8,14,24-trien-26-oic acid (6). Their structures were established by the spectral techniques of NMR and ESI-MS. These compounds together with some previously isolated compounds; garcihombronane B (7), garcihombronane D (8) 2,3',4,5'-tetrahydroxy-6-methoxybenzophenone (9), volkensiflavone (10), 4''-O-methyll-volkensiflavone (11), volkensiflavone-7-O-glucopyranoside (12), volkensiflavone-7-O-rhamnopyranoside (13), Morelloflavone (14), 3''-O-methyl-morelloflavone (15) and morelloflavone-7-O-glucopyranoside (16) were evaluated for cholinesterase enzymes inhibitory activities using acetylcholinesterase and butyrylcholinesterase. In these activities, compounds 1-9 showed good dual inhibition on both the enzymes while compounds 10-16 did not reasonably contribute to both the cholinesterases inhibitory effects. PMID:26158779

  3. PROGNOSTIC VALUE OF GLASGOW COMA SCALE

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    Shashank

    2014-03-01

    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.

  4. Lycopene modulates cholinergic dysfunction, Bcl-2/Bax balance, and antioxidant enzymes gene transcripts in monosodium glutamate (E621) induced neurotoxicity in a rat model.

    Science.gov (United States)

    Sadek, Kadry; Abouzed, Tarek; Nasr, Sherif

    2016-04-01

    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. PMID:26900785

  5. Toxicity of metal oxide nanoparticles in immune cells of the sea urchin.

    Science.gov (United States)

    Falugi, C; Aluigi, M G; Chiantore, M C; Privitera, D; Ramoino, P; Gatti, M A; Fabrizi, A; Pinsino, A; Matranga, V

    2012-05-01

    The potential toxicity of stannum dioxide (SnO₂), cerium dioxide (CeO₂) and iron oxide (Fe₃O₄) nanoparticles (NPs) in the marine environment was investigated using the sea urchin, Paracentrotus lividus, as an in vivo model. We found that 5 days after force-feeding of NPs in aqueous solutions, the three NPs presented different toxicity degrees, depending on the considered biomarkers. We examined: 1) the presence of the NPs in the coelomic fluid and the uptake into the immune cells (coelomocytes); 2) the cholinesterase activity and the expression of the stress-related proteins HSC70 and GRP78; 3) the morphological changes affecting cellular compartments, such as the endoplasmic reticulum (ER) and lysosomes. By Environmental Scanning Electron Microscope (ESEM) analysis, coupled with Energy Dispersive X-ray Spectroscopy (EDS) we found that NPs were uptaken inside coelomocytes. The cholinesterases activity, a well known marker of blood intoxication in vertebrates, was greatly reduced in specimens exposed to NPs. We found that levels of stress proteins were down-regulated, matching the observed ER and lysosomes morphological alterations. In conclusion, this is the first study which utilizes the sea urchin as a model organism for biomonitoring the biological impact of NPs and supports the efficacy of the selected biomarkers. PMID:22104963

  6. HUBUNGAN KADAR ENZYM KHOLINESTERASE DENGAN KADAR HORMON THYROID PADA WUS DI DAERAH GONDOK ENDEMIK

    Directory of Open Access Journals (Sweden)

    Sukati S.

    2012-11-01

    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

  7. Contaminant studies in the Sierra Nevadas

    Science.gov (United States)

    Sparling, D.W.; Fellers, G.

    2002-01-01

    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

  8. Five oximes (K-27, K-33, K-48, BI-6 and methoxime) in comparison with pralidoxime: in vitro reactivation of red blood cell acetylcholinesterase inhibited by paraoxon.

    Science.gov (United States)

    Petroianu, G A; Arafat, K; Kuca, K; Kassa, J

    2006-01-01

    Oximes are cholinesterase reactivators of use in poisoning with organophosphorus compounds. Pralidoxime (PRX) is used clinically as an adjunct to atropine in such exposure. Clinical experience with PRX (and other oximes) is, however, disappointing and routine use has been questioned. In addition it is known that oximes are not equally effective against all existing organophosphorus compounds. There is a clear demand for 'broad spectrum' cholinesterase reactivators with a higher efficacy than PRX. Over the years new reactivators of cholinesterase of potential clinical utility have been developed. Their chemical structures were derived from those of existing esterase reactivators, especially pralidoxime, obidoxime and HI-6. The purpose of the study was to quantify in vitro the extent of oxime (pralidoxime, K-27, K-33, K-48, methoxime and BI-6) conferred protection, using paraoxon as an inhibitor. Paraoxon (POX), the active metabolite of parathion (O,O-diethyl-O-p-nitro-phenyl phosphorothioate) is a non-neuropathic organophosphate. Red blood cell (RBC) acetylcholinesterase (AChE) activities in whole blood were measured photometrically in the presence of different POX concentrations and the IC50 was calculated. Determinations were repeated in the presence of increasing oxime concentrations. The IC50 of POX increases with the oxime concentration in a linear manner. The calculated IC50 values were plotted against the oxime concentrations to obtain an IC50 shift curve. The slope of the shift curve (tg alpha) was used to quantify the magnitude of the protective effect (nm IC50 increase per microm reactivator). Based on our determinations the new K series of reactivators is far superior to pralidoxime, methoxime and BI-6, K-27 being the outstanding compound with a tg alpha value of 3.7 (nm IC50 increase per microm reactivator) which is approximately 13 times the reactivator ability of PRX. In general there is an (expected) inverse relationship between the binding constant K

  9. In vitro oxime reactivation of red blood cell acetylcholinesterase inhibited by methyl-paraoxon.

    Science.gov (United States)

    Petroianu, G A; Arafat, K; Nurulain, S M; Kuca, K; Kassa, J

    2007-01-01

    Oximes are cholinesterase reactivators of use in poisoning with organophosphorus ester enzyme inhibitors. Pralidoxime (PRX) is the oxime used in the United States. Clinical experience with pralidoxime (and other oximes) is disappointing and the routine use has been questioned. Furthermore oximes are not equally effective against all existent enzyme inhibitors. There is a clear demand for 'broad spectrum' cholinesterase reactivators with a higher efficacy than those clinically available. To meet this need over the years new reactivators of cholinesterase of potential clinical utility have been developed. The purpose of the study was to quantify 'in vitro' the extent of protection conferred by available (pralidoxime and methoxime) and experimental (K-27, K-33 and K-48) oximes, using methyl-paraoxon (methyl-POX) as an esterase inhibitor and to compare the results with those previously obtained using paraoxon (POX) as an inhibitor. Red blood cell (RBC) acetylcholinesterase (AChE) activities in whole blood were measured photometrically in the presence of different methyl-POX concentrations and IC(50) values calculated. Determinations were repeated in the presence of increasing oxime concentrations. The IC(50) of methyl-POX (59 nm) increased with the oxime concentration in a linear manner. The calculated IC(50) values were plotted against the oxime concentrations to obtain an IC(50) shift curve. The slope of the shift curve (tg alpha) was used to quantify the magnitude of the protective effect (nm IC(50) increase per microm reactivator). Based on our determinations the new K-series of reactivators is superior to pralidoxime (tg alpha = 1.9) and methoxime (tg alpha = 0.7), K-27 and K-48 being the outstanding compounds with a tg alpha value of 10 (nm IC(50) increase per microm reactivator), which is approximately five times the reactivator ability of PRX. The tg alpha value determined for K-33 was 6.3. The ranking of reactivator potencies of the examined oximes determined

  10. Repeated exposure to neurotoxic levels of chlorpyrifos alters hippocampal expression of neurotrophins and neuropeptides.

    Science.gov (United States)

    Lee, Young S; Lewis, John A; Ippolito, Danielle L; Hussainzada, Naissan; Lein, Pamela J; Jackson, David A; Stallings, Jonathan D

    2016-01-18

    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

  11. Radiotracer Approaches to Carbamate Insecticide Toxicology

    International Nuclear Information System (INIS)

    Methylcarbamates constitute one of the major groups of insecticides. Many unresolved problems in their toxicology may be readily approached with radiotracer studies. Dimethylcarbamates have been prepared with carbonyl-C14-labelling and methylcarbamates withmethyl-, carbonyl-and ring-labelling utilizing carbon-14. The pharmacological action of these.compounds presumably results from acetylcholinesterase inhibition and may involve carbamylation. Reaction of carbonyl- or methyl-labelled carbamates with purified cholinesterase or other esterases would allow a critical examination of this carbamylation reaction and the ease of spontaneous and induced reactivation or decarbamylation. The physiological significance of cholinesterase inhibition might be examined by administering acetate-C14 and analysis for radiolabelled acetylcholine accumulation in nervous tissue, or by utilizing acetyl-C14-choline as the substrate for in vitro determination of the degree of cholinesterase inhibition in tissues of poisoned animals with minimal dilution of the inhibitors and enzymes during analysis. Some progress has been made with radiolabelled materials in investigating the metabolism of carbamate insecticides. Sevin (1-naphthyl methylcarbamate) has been most extensively studied along with its potential hydrolysis products. The assumption that the metabolism of Sevin involves an initial hydrolysis and then further decomposition of the fragments was not supported by carbon-14 studies. The major detoxification mechanism in mammals, and probably also in insects, results from initial oxidative attack on the carbamate by the microsomes in the presence of reduced nicotinamide-adenine dinucleotide phosphate. Sevin is rapidly metabolized in mammals, but the fate of certain of the fragments has not been resolved. Some of the metabolites appear in the milk of lactating animals. One step in the metabolism appears to be formation of the N-methylol derivative. Preliminary studies on the metabolism

  12. New cinnamic - N-benzylpiperidine and cinnamic - N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties.

    Science.gov (United States)

    Estrada, Martín; Herrera-Arozamena, Clara; Pérez, Concepción; Viña, Dolores; Romero, Alejandro; Morales-García, José A; Pérez-Castillo, Ana; Rodríguez-Franco, María Isabel

    2016-10-01

    Here we describe new families of multi-target directed ligands obtained by linking antioxidant cinnamic-related structures with N-benzylpiperidine (NBP) or N,N-dibenzyl(N-methyl)amine (DBMA) fragments. Resulting hybrids, in addition to their antioxidant and neuroprotective properties against mitochondrial oxidative stress, are active at relevant molecular targets in Alzheimer's disease, such as cholinesterases (hAChE and hBuChE) and monoamine oxidases (hMAO-A and hMAO-B). Hybrids derived from umbellic - NBP (8), caffeic - NBP (9), and ferulic - DBMA (12) displayed balanced biological profiles, with IC50s in the low-micromolar and submicromolar range for hChEs and hMAOs, and an antioxidant potency comparable to vitamin E. Moreover, the caffeic - NBP hybrid 9 is able to improve the differentiation of adult SGZ-derived neural stem cells into a neuronal phenotype in vitro. PMID:27267007

  13. [Today's threat of use of organophosphorus compounds].

    Science.gov (United States)

    Sokołowski, Rafał; Płusa, Tadeusz

    2015-09-01

    Organophosphates are stable cholinesterases inhibitors (AChE). Inhibition of AChE activity leads to the accumulation of large amounts of acetylcholine and hyperactivity of the cholinergic system by stimulating acetylcholine receptors - muscarinic and nicotinic. This group included tabun, sarin, soman and VX gases. Exposure to gaseous form causes symptoms within a few seconds of exposure. This depends on the gas concentration in the atmosphere. The most sensitive organ is the eyes and the respiratory system. Severe poisoning are characterized by the immediate loss of consciousness with convulsions. Therapeutic management of acute poisoning organophosphorus compounds boils down to treating symptomatic and supportive vital functions. Monitoring of cardiovascular, respiratory and renal failure in intensive care gives only guarantee the effective treatment of poisoning. Properties toxic organophosphorus compounds also are of interest to terrorist groups. PMID:26449583

  14. Safety profile of Cerebrolysin: clinical experience from dementia and stroke trials.

    Science.gov (United States)

    Thome, J; Doppler, E

    2012-04-01

    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. PMID:22514795

  15. Effects of 60Co gamma radiations on the conduction properties of frog sciatic nerve

    International Nuclear Information System (INIS)

    The effect of Co60 gamma radiations on the amplitude, detection period and duration of the action potential of sciatic nerves of Rana tigrina frogs have been studied. Dose levels of upto 120 kR were employed. Irradiation of the nerves with dose levels upto 30 kR does not seem to affect the action of potential profiles. The amplitude falls rapidly thereafter, registering less than 5% of the original value after irradiation by a dose of 120 kR. Qualitatively similar behaviour is seen in the case of detection period and duration of action potential. These results are examined in the light of data already collected through experiments on the effect of Co60 gamma rays on the enzyme acetyl-cholinesterase (AchE). (author)

  16. Hologram QSAR models of 4-[(diethylamino)methyl]-phenol inhibitors of acetyl/butyrylcholinesterase enzymes as potential anti-Alzheimer agents.

    Science.gov (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

    2012-01-01

    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.

  17. Multibiomarker assessment of three Brazilian estuaries using oysters as bioindicators

    International Nuclear Information System (INIS)

    Oysters have been largely employed as bioindicators of environmental quality in biomonitoring studies. Crassostrea rhizophorae was selected to evaluate the health status of three estuarine areas impacted by anthropogenic activities along the Brazilian coast, in three estuarine complexes, ranging in latitude from 7 to 25 deg. S. In each estuary three sites were sampled in Winter and in Summer: a site considered as reference, and two sites next to contamination sources. Condition index was similar at all sites and estuaries, with the highest values found for Itamaraca oysters in Summer. Necrosis, hyperplasia, mucocyte hypertrophy and fusion of ordinary filaments were the main histopathological lesions observed. Muscle cholinesterase activity was overall similar, but with a strong seasonal effect. Inhibition or activation of branchial total ATPase and Na,K-ATPase activities at the contaminated sites was observed. The health status of these estuarine areas is quite similar, and the combined use of biomarkers is recommended

  18. ¬Enzyme Inhibition Studies on N-Substituted Sulfonamides Derived from m-phenetidine

    Directory of Open Access Journals (Sweden)

    *Aziz-ur-Rehman

    2013-06-01

    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. 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

    2015-01-01

    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.

  20. Relationship between biomarker responses and contaminant concentration in selected tissues of flounder (Platichthys flesus from the Polish coastal area of the Baltic Sea

    Directory of Open Access Journals (Sweden)

    Magdalena Podolska

    2008-09-01

    Full Text Available Previous studies in the Gulf of Gdańsk discussed the responses of selected enzymatic biomarkers to the contaminant gradient in fish and mussels. In the present study, flounder muscle and liver tissues were analyzed for polychlorinated biphenyls (PCB congeners: 28, 52, 101, 118, 138, 153 and 180, organochlorine pesticides (HCHs, HCB and DDTs, and trace metals (Pb, Cd, Zn, Cu, Hg, Cr. An attempt was made to identify the relationship between the measured enzymatic biomarker responses (cholinesterases, malic enzyme, isocitrate dehydrogenase, glutathione S-transferase and contaminant concentrations in selected flounder tissues. The observed differences in enzymatic biomarker levels suggest that chronic exposure to low-concentration mixtures of contaminants may be occurring in the studied area. However, no conclusive evidence was found of a clear link between the biomarker responses and contaminant concentrations in flounder tissues.

  1. Toxicity of phosphor esters: Willy Lange (1900-1976) and Gerda von Krueger (1907-after 1970).

    Science.gov (United States)

    Petroianu, G A

    2010-10-01

    In 1851 Williamson serendipitously discovered a new and efficient way to produce ethers using ethyl iodide and potassium salts. Based on this new synthetic approach, the Frenchman Philippe de Clermont and the Muscovite Wladimir Moschnin, both élèves of Adolphe Wurtz in his Paris School of Chemistry, achieved the synthesis of the first ester of pyrophosphoric acid (TEPP). de Clermont "tasted" the new compound and although TEPP is a potent cholinesterase inhibitor he failed to recognize its toxicity. Almost a century later, in 1932, Willy Lange (1900-1976) and his graduate student Gerda v. Krueger (1907-after 1970) described the toxicity of organophosphonates. While the classic paper of the two "Uber Ester der Monofluorphosphorsäure." is cited by almost everybody working in the field, little is known about Lange and almost nothing about v. Krueger. This brief communication attempts to shed some light on the life of both. PMID:21105582

  2. Case histories of bald eagles and other raptors killed by organophosphorus insecticides topically applied to livestock

    Science.gov (United States)

    Henny, C.J.; Kolbe, E.J.; Hill, E.F.; Blus, L.J.

    1987-01-01

    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.

  3. Novel tacrine-8-hydroxyquinoline hybrids as multifunctional agents for the treatment of Alzheimer's disease, with neuroprotective, cholinergic, antioxidant, and copper-complexing properties.

    Science.gov (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

    2010-07-01

    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.

  4. Contaminant concentrations, biochemical and hematological biomarkers in blood of West Indian manatees Trichechus manatus from Brazil.

    Science.gov (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

    2012-07-01

    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. PMID:22626623

  5. Chemical composition and biological activity of leaves and fruits of Triphasia trifolia; Composicao quimica e atividade biologica das folhas e frutos de Triphasia trifolia

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Renata P. dos; Trevisan, Maria Teresa Salles; Silveira, Edilberto R.; Pessoa, Otilia Deusdenia L. [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica]. E-mail: opessoa@ufc.br; Melo, Vania Maria M. [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Biologia

    2008-07-01

    The chemical composition of the essential oils from leaves and fruits of Triphasia trifolia was analyzed by GC-FID and GC-MS. The major constituents of oil obtained from leaves were sabinene (35.4%) and myrcene (34.1%), while the prevalent compounds in oil from fruits were sabinene (37.2%), {beta}-pinene (23.95) and {gamma}g-terpinene (16.3%). Both oils showed moderate antimicrobial activity. The fruit decoction was also investigated leading to the isolation of the coumarins isopimpinelin, (R)-byakangelicin and (S)-mexoticin. From leaves were isolated the coumarins (R)-byakangelicin, aurapten, (S)-mexoticin, isosibiricin, isomerazin and coumurrayin and the flavonoid vitexin. All coumarins showed cholinesterase inhibition on TLC tests. (author)

  6. Composição química e atividade biológica das folhas e frutos de Triphasia trifolia Chemical composition and biological activity of leaves and fruits of Triphasia trifolia

    Directory of Open Access Journals (Sweden)

    Renata P. dos Santos

    2008-01-01

    Full Text Available The chemical composition of the essential oils from leaves and fruits of Triphasia trifolia was analyzed by GC-FID and GC-MS. The major constituents of oil obtained from leaves were sabinene (35.4% and myrcene (34.1%, while the prevalent compounds in oil from fruits were sabinene (37.2%, beta-pinene (23.95 and gamma-terpinene (16.3%. Both oils showed moderate antimicrobial activity. The fruit decoction was also investigated leading to the isolation of the coumarins isopimpinelin, (R-byakangelicin and (S-mexoticin. From leaves were isolated the coumarins (R-byakangelicin, aurapten, (S-mexoticin, isosibiricin, isomerazin and coumurrayin and the flavonoid vitexin. All coumarins showed cholinesterase inhibition on TLC tests.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    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...... data to provide advice for management strategies and gathering information for resistance risk assessment on the organophosphates azamethiphos and dimethoate and the carbamate methomyl, which have been the primary insecticides used against adult houseflies in Denmark. Cluster analysis was performed...... and > 2000 houseflies were assigned to one of three phenotypes based on total acetylcholinesterase activity as well as inhibition by azamethiphos, methomyl or omethoate. A cluster, i.e. a phenotype, with high total AChE activity and high sensitivity to azamethiphos and less sensitivity to inhibition...

  8. Anticholinesterases and antioxidant alkamides from Piper nigrum fruits.

    Science.gov (United States)

    Tu, Yanbei; Zhong, Yujiao; Du, Hongjian; Luo, Wei; Wen, Yaya; Li, Qin; Zhu, Chao; Li, Yanfang

    2016-09-01

    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. PMID:26407107

  9. Cyolane residues in milk of lactating goats

    International Nuclear Information System (INIS)

    Consecutive feeding of lactating goats with 14C-alkyl labelled cyolane for 5 days at dietary levels 8 and 16 ppm resulted in the appearance of measurable insecticide residues in milk (0.02-0.04 mg/kg). The residue levels were markedly reduced after a withdrawal period of 7 days. Analysis of urine and milk residues showed the presence of similar metabolites in addition to the parent compound. The major part of the residue consisted of mono-, diethyl phosphate and 2 hydrophilic unknown metabolites. The erythrocyte cholinesterase activity was reduced to about 50% after 24 hours whereas the plasma enzyme was only slightly affected. The animals remained symptom-free during the experimental period. (author)

  10. Molecular interaction of acetylcholinesterase with carnosic acid derivatives: a neuroinformatics study.

    Science.gov (United States)

    Merad, M; Soufi, W; Ghalem, S; Boukli, F; Baig, M H; Ahmad, K; Kamal, Mohammad A

    2014-04-01

    Alzheimer's disease is a progressive degenerative disease of the brain marked by gradual and irreversible declines in cognitive functions. Acetylcholinesterase (AChE) plays a biological role in the termination of nerve impulse transmissions at cholinergic synapses by rapid hydrolysis of its substrate, "acetylcholine". The deficit level of acetylcholine leads to deprived nerve impulse transmission. Thus the cholinesterase inhibitors would reverse the deficit in acetylcholine level and consequently may reverse the memory impairments, which is characteristic of the Alzheimer's disease. The molecular interactions between AChE and Carnosic acid, a well known antioxidant substance found in the leaves of the rosemary plant has always been an area of interest. Here in this study we have performed in silico approach to identify carnosic acid derivatives having the potential of being a possible drug candidate against AChE. The best candidates were selected on the basis of the results of different scoring functions. PMID:24059305

  11. Studies on the effect of fenbendazole and mebendazole on some enzymes of swine kidney worm Stephanurus dentatus.

    Science.gov (United States)

    Singh, K; Kaushal, P

    1996-09-01

    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.

  12. Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina)

    Energy Technology Data Exchange (ETDEWEB)

    Cazenave, Jimena, E-mail: jcazenave@inali.unl.edu.a [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)

    2009-11-15

    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.

  13. Nootropic candidates inhibit head-twitches induced by mescaline in mice.

    Science.gov (United States)

    Yamamoto, T; Ohno, M; Yatsugi, S; Fujikawa, Y; Ueki, S

    1992-07-01

    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.

  14. Oleanolic acid and related derivatives as medicinally important compounds.

    Science.gov (United States)

    Sultana, Nighat; Ata, Athar

    2008-12-01

    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. Contaminant concentrations, biochemical and hematological biomarkers in blood of West Indian manatees Trichechus manatus from Brazil.

    Science.gov (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

    2012-07-01

    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.

  16. Genotoxicity of paracetamol on the germ cells of Drosophilla melanogaster

    Directory of Open Access Journals (Sweden)

    Saleha Y. M. alakilli

    2007-12-01

    Full Text Available Paracetamol is a common analgesic and antipyretic drug. The aim of the present study is to determine the potential genetic effects of Paracetamol in Drosophilla melanogaster using two methods: Sex Linked Recessive Lethals (SLRL test and effect of Paracetamol on enzyme activity using spectrophotometric analysis. Three concentrations of drug were used (5, 10, and 20 mM. The results reveal significant differences in S.L.R.L, except spermatozoa stages showed insignificant increases when the data of the four broods were considered all together in three treatments. Meanwhile, Paracetamol showed a genotoxic effects in the three categories of the two generations of S.L.R.L, F1 heterozygous females, F2 bar eye females and F2 wild type males on the genetic back ground of Cholinesterase in all treatments.

  17. Combined effect of gamma irradiation and plant oils on the potato tuber moth, Phthorimaea operculella (Z)

    International Nuclear Information System (INIS)

    1- Susceptibility of Phthorimaea operculella to plant oil and gamma- irradiation. 2- Susceptibility of Phthorimaea operculella to powder of some plants and gamma irradiation.-selection of the suitable concentration of plant oils. - effect on male fertility. -effect on female fecundity. -effect on adult survival. 3- Separate and combined effects of radiation and plant oil on the male mating competitiveness using the sterile dose. 4- Separate and combined effects of radiation and plant oil on the male mating competitiveness using the sub sterile dose. 5- The effects of gamma- irradiation and plant oil on the pest when the potato tubers store for different periods. 6- Some biochemical studies. o Determine the adult total protein content of treated pupae. Determine the effect of plant oils and gamma- irradiation on the activity of some enzymes as proteinase, ATPase, keitenase cholinesterase.

  18. TREATMENTS FOR ALZHEIMER’S DISEASE: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Nandagopan G.L

    2013-06-01

    Full Text Available Several diagnostic procedures have been carried out for implementing a successful treatment procedure for Alzheimer’s disease. Most of the researches went in vain and many other scientists continued their researches for the same. Recent researches in Neurological areas have found an innovative diagnostic procedure for detecting the primary stages of Alzheimer’s disease. As only symptomatic treatments are now available for Alzheimer’s disease (AD, safe and effective mechanism-based therapies remain a great unmet need for patients with this neurodegenerative disease. Biochemical derivatives of complex molecules have been derived for the treatment of Alzheimer’s disease in its primary stage. Thus we propose that targeting cholinesterase and Beta-secretase (BACE1 may be an effective and safe treatment strategy for AD. Nanotechnology and Disease modifying drugs has delivered significant developments in the early detection of Alzheimer’s disease, has also been depicted here.

  19. Biodegradation of a carbamate pesticide, Propoxur, in rat tissues.

    Science.gov (United States)

    Kumar, R; Madhavi, N B; Sharma, C B

    1993-01-01

    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.

  20. [Fatal poisonings with propoxur].

    Science.gov (United States)

    Pfordt, J; Magerl, H; Vock, R

    1987-01-01

    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.

  1. Chemical Characterization and Acetylcholinesterase Inhibition Potential of Volatile Components of Aerial Parts of Pluchea lanceolata (DC. Oliv. & Hiern

    Directory of Open Access Journals (Sweden)

    Pooja Srivastava

    2015-06-01

    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.

  2. Mini Review: Anticholinergic Activity as a Behavioral Pathology of Lewy Body Disease and Proposal of the Concept of “Anticholinergic Spectrum Disorders”

    Science.gov (United States)

    Tomioka, Hiroi; Hachisu, Mitsugu

    2016-01-01

    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.

  3. Anticholinesterase activities of cold and hot aqueous extracts of F. racemosa stem bark

    Directory of Open Access Journals (Sweden)

    Faiyaz Ahmed

    2010-01-01

    Full Text Available The present study evaluated the anticholinesterase activity of cold and hot aqueous extracts of Ficus racemosa stem bark against rat brain acetylcholinesterase in vitro. Both the cold aqueous extract (FRC and the hot aqueous extract (FRH exhibited a dose dependent inhibition of rat brain acetylcholinesterase. FRH showed significantly higher ( p ≤ 0.001 cholinesterase inhibitory activity compared to FRC; however, both the extracts did not show 50% inhibition of AChE at the doses tested (200-1000 μg ml -1 . The IC 50 values of 1813 and 1331 μg ml -1 were deduced for FRC and FRH, respectively (calculated by extrapolation using Boltzmann′s dose response analysis.

  4. Fate and persistence of carbaryl residues in milk, fat and meat of lactating goats

    International Nuclear Information System (INIS)

    Residues in milk, fat and meat of goats exposed to dietary 14C-carbaryl (5 and 15 ppm) for one week were determined. Good correlation between dietary intake and milk residues was observed. The highest residues were observed in milk samples collected 10 hours following feeding. Determination of 14C-residues in tissues after a 7-day intoxication period revealed that liver, kidney, omental and subcutaneous fat contained the highest residues (0.184, 0.166, 0.120 and 0.164 ppm respectively). After 7 days the levels in liver and kidney decreased considerably. Inhibition of plasma and erythrocyte cholinesterase was not observed in blood samples collected 24 hours after the last dose. (author)

  5. Fate of 14C-monocrotophos in lactating goats

    International Nuclear Information System (INIS)

    14C-monocrotophos was fed daily to two groups of lactating goats for five days at 5 and 10 mg per goat per day. The radioactivity in urine and faeces accounted for 50% and 7%, respectively, 24 hours after the first dose. About 25% of the radiocarbon was found in various organs. About 1-2% of the administered radiocarbon was secreted in milk. It was concluded that monocrotophos was rapidly eliminated through urine and faeces of teddy goats. 14C-residues in milk and urine were tentatively identified as monocrotophos, dimethylphosphate and N-desmethyl monocrotophos. The erythrocyte cholinesterase activity was reduced to 50% 24 hours after treatment, but no toxic symptoms were observed. (author)

  6. Fate and metabolism of radiolabelled monocrotophos in Egyptian lactating goats

    International Nuclear Information System (INIS)

    Lactating goats receiving two dermal applications of 14C-monocrotophos sprayings did not show any adverse effects related to pesticide applications. Under conditions simulating those of agricultural practice, residues were secreted in milk at a concentration of 0.13 ppm after the first day; declining to 0.02 ppm on the fifth day and to non-detectable levels on the 7th day. The hair and skin contained the highest concentration. In most edible organs, residue levels were generally low following the second application and declined rapidly after a 14-day withdrawal period to levels ranging from trace to 0.04 ppm. The insecticide inhibited both plasma erythrocyte cholinesterase activity significantly one day after application. Slow recovery could be observed during the 14-day withdrawal period. (author)

  7. Design, synthesis and evaluation of tacrine-flurbiprofen-nitrate trihybrids as novel anti-Alzheimer's disease agents.

    Science.gov (United States)

    Chen, Yao; Sun, Jianfei; Huang, Zhangjian; Liao, Hong; Peng, Sixun; Lehmann, Jochen; Zhang, Yihua

    2013-05-01

    To search for multifunctional anti-Alzheimer's disease (AD) agents with good safety, the previously synthesized tacrine-flurbiprofen hybrids 1a and 1b were modified into tacrine-flurbiprofen-nitrate trihybrids 3a-h. These compounds displayed comparable or higher cholinesterase inhibitory activity relative to the bivalent hybrids. Compound 3a was the most potent, which released moderate NO, exerted blood vessel relaxative activity, and showed significant Aβ inhibitory effects whereas tacrine and flurbiprofen did not exhibit any Aβ inhibitory activity at the same dose. In addition, 3a was active in improving memory impairment in vivo. More importantly, the hepatotoxicity study showed that 3a was much safer than tacrine, suggesting it might be a promising anti-AD agent for further investigation.

  8. Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity

    Directory of Open Access Journals (Sweden)

    Miroslav Pohanka

    2014-06-01

    Full Text Available Acetylcholinesterase (AChE inhibitors are widely used for the symptomatic treatment of Alzheimer’s disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE. Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a “cholinergic anti-inflammatory pathway” which raises questions about the role of these inhibitors in the immune system. This review covers research and discussion of the role of the inhibitors in modulating the immune response using as examples the commonly available drugs, donepezil, galantamine, huperzine, neostigmine and pyridostigmine. Major attention is given to the cholinergic anti-inflammatory pathway, a well-described link between the central nervous system and terminal effector cells in the immune system.

  9. Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity.

    Science.gov (United States)

    Pohanka, Miroslav

    2014-01-01

    Acetylcholinesterase (AChE) inhibitors are widely used for the symptomatic treatment of Alzheimer's disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE). Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a "cholinergic anti-inflammatory pathway" which raises questions about the role of these inhibitors in the immune system. This review covers research and discussion of the role of the inhibitors in modulating the immune response using as examples the commonly available drugs, donepezil, galantamine, huperzine, neostigmine and pyridostigmine. Major attention is given to the cholinergic anti-inflammatory pathway, a well-described link between the central nervous system and terminal effector cells in the immune system. PMID:24893223

  10. Cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Ransmayr, Gerhard

    2015-12-01

    Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy. PMID:26609664

  11. Biosensors for the determination of environmental inhibitors of enzymes

    International Nuclear Information System (INIS)

    Characteristic features of functioning and practical application of enzyme-based biosensors for the determination of environmental pollutants as enzyme inhibitors are considered with special emphasis on the influence of the methods used for the measurement of the rates of enzymic reactions, of enzyme immobilisation procedure and of the composition of the reaction medium on the analytical characteristics of inhibitor assays. The published data on the development of biosensors for detecting pesticides and heavy metals are surveyed. Special attention is given to the use of cholinesterase-based biosensors in environmental and analytical monitoring. The approaches to the estimation of kinetic parameters of inhibition are reviewed and the factors determining the selectivity and sensitivity of inhibitor assays in environmental objects are analysed. The bibliography includes 195 references.

  12. Radioisotope studies of some effects and interactions of trace contaminants

    International Nuclear Information System (INIS)

    The coordinated programme of ''isotopic tracer-aided studies of the biological side-effects of foreign chemical residues in food and agriculture'', initiated in 1973, had involved the participation of 12 scientists from 10 countries. Pesticide residues, toxic metals, atmospheric sulphur dioxide were studied, and the use of radiotracer techniques as monitoring tools for existing contaminant levels or for their biological effects. The programme had been successful in the development and application of selected labelled substrate techniques. Specific aspects studied were the effects of environmental contaminants at the molecular level of the cell nucleus, the development and significance of radioimmunoassay procedure for trace contaminants, action and joint action of toxic elements, and the radiometric analysis of cholinesterase as an index of exposure to organophosphorus and carbamate pesticides. Ten papers were presented and 12 coordinated investigations discussed. A number of recommendations were made

  13. Cholinergic basis of memory improving effect of Ocimum tenuiflorum linn

    Directory of Open Access Journals (Sweden)

    Joshi H

    2006-01-01

    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.

  14. 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

    2014-01-01

    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

  15. Six different plasma enzymes in bald eagles (Haliaeetus leucocephalus) and their usefulness in pathological diagnosis

    Science.gov (United States)

    Dieter, M.P.; Wiemeyer, Stanley N.

    1978-01-01

    1. Activities of creatine phosphokinase, glutamic oxalacetic transaminase, glutamic pyruvic transaminase, lactate dehydrogenase, fructose diphosphate aldolase and cholinesterase were measured in plasma of bald eagles. 2. There were no sex differences in the plasma enzyme activities. 3. An acute dieldrin dosage (10 mg/kg) of a female bald eagle resulted in 400% increases in activities of plasma creatine phosphokinase and glutamic oxalacetic transaminase and 250% increases in activities of lactate dehydrogenase and glutamic pyruvic transaminase. 4. At 11 days post-dosage all but one of the plasma enzyme activities had returned to normal; glutamic oxalacetic transaminase activity remained 100% above pre-dosage values. 5. Plasma enzyme assays constitute a non-destrcutive procedure that can be used in valuable wildlife species to screen for the presence and prevalence of environmental contaminants.

  16. Synthesis of Novel Biologically Active s-Triazolo[3,4-b]-1,3,4-thiadiazole Derivatives

    Institute of Scientific and Technical Information of China (English)

    SUN,Yi-Feng

    2004-01-01

    @@ 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.

  17. Oleanolic acid and related derivatives as medicinally important compounds.

    Science.gov (United States)

    Sultana, Nighat; Ata, Athar

    2008-12-01

    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. PMID:18618318

  18. Application of enzyme multibiosensor for toxicity analysis of real water samples of different origin

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    Soldatkin A. P.

    2009-06-01

    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.

  19. Cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Ransmayr, Gerhard

    2015-12-01

    Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy.

  20. Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheimer agents

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    Xin Zhang

    2015-01-01

    Full Text Available A series of genistein-polyamine conjugates (4a–4h were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases (ChEs inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase (AChE with an IC50 value of 2.75 μmol/L, which was better than that of rivastigmine (5.60 μmol/L. Lineweaver–Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site (CAS and the peripheral anionic site (PAS of AChE. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a–4h did not affect HepG-2 cell viability at the concentration of 10 μmol/L.

  1. Report: screening of selected medicinal plants for their enzyme inhibitory potential - a validation of their ethnopharmacological uses.

    Science.gov (United States)

    Khuda, Fazli; Iqbal, Zafar; Khan, Ayub; Zakiullah; Shah, Yasar; Khan, Abad

    2014-05-01

    In present study four medicinal plants namely Valeriana wallichii, Xanthium strumarium, Achyranthes aspera and Duchesnea indica belonging to different families were collected in Khyber Pakhtunkhwa province and crude extract and subsequent fractions were analyzed for their inhibitory potential against acetylcholinesterase, butyrylcholinesterase and α-glucosidase enzymes. Valeriana wallichii, Xanthium strumarium and Achyranthes aspera were significantly active against cholinesterases. Chloroform and ethylacetate fractions of Valeriana wallichii exhibited significant activity against acetylcholinesterase (IC50: 61μg/ml) and butyrylcholinesterase enzymes (IC50: 58μg/ml), respectively. Similarly ethylacetate fraction of Achyranthes aspera showed significant activity against acetylcholinesterase (IC50: 61 μg/ml) and butyrylcholinesterase enzymes (IC50: 61 μg/ml), respectively. In case of α-glucosidase enzyme, the chloroform fraction of Xanthium strumarium exhibited significant inhibitory activity (IC50: 72 μg/ml) as compared to the standard compound acarbose (IC50: 483 μg/ml). Duchesnea indica showed no such activities. PMID:24811822

  2. REVIEW ARTICLE: Environmental applications of analytical biosensors

    Science.gov (United States)

    Marco, María-Pilar; Barceló, Damià

    1996-11-01

    A review of the fundamental aspects and environmental applications of biosensors is presented. The bases of different transducer principles such as electrochemical, optical and piezoelectric are discussed. Various examples are given of the applications of such principles to develop immunosensor devices to determine common environmental contaminants. Attention is also paid to catalytic biosensors, using enzymes as sensing elements. Biosensor devices based on the use of cholinesterase and various oxidase enzymes such as tyrosinase, laccase, peroxidase and aldehyde dehydrogenase are reported. Some examples are given of the applications of other biomolecules such as whole cells, DNA or proteins, to determine pollution. Validation studies are presented comparing biosensors with chromatographic techniques to determine organophosphorus pesticides and phenolic compounds in environmental samples.

  3. 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: gfgbandoch@uem.br [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

    2013-11-15

    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)

  4. Dementia in Down's syndrome.

    Science.gov (United States)

    Ballard, Clive; Mobley, William; Hardy, John; Williams, Gareth; Corbett, Anne

    2016-05-01

    Down's syndrome is the most common genetic cause of learning difficulties, and individuals with this condition represent the largest group of people with dementia under the age of 50 years. Genetic drivers result in a high frequency of Alzheimer's pathology in these individuals, evident from neuroimaging, biomarker, and neuropathological findings, and a high incidence of cognitive decline and dementia. However, cognitive assessment is challenging, and diagnostic methods have not been fully validated for use in these patients; hence, early diagnosis remains difficult. Evidence regarding the benefits of cholinesterase inhibitors and other therapeutic options to treat or delay progressive cognitive decline or dementia is very scarce. Despite close similarities with late-onset Alzheimer's disease, individuals with Down's syndrome respond differently to treatment, and a targeted approach to drug development is thus necessary. Genetic and preclinical studies offer opportunities for treatment development, and potential therapies have been identified using these approaches. PMID:27302127

  5. Influence of clitoria ternatea extracts on memory and central cholinergic activity in rats.

    Science.gov (United States)

    Taranalli, A D; Cheeramkuzhy, T C

    2000-01-01

    Clitoria ternatea , commonly known as Shankpushpi, is widely used in the traditional Indian system of medicine as a brain tonic and is believed to promote memory and intelligence. We examined the effectiveness of alcoholic extracts of aerial and root parts of C. ternatea at 300 and 500 mg/kg doses orally in rats in attenuating electroshock-induced amnesia. Extracts at 300 mg/kg dose produced significant memory retention, and the root parts were found to be more effective. In order to delineate the possible mechanism through which C. ternatea elicits the anti-amnesic effects, we studied its influence on central cholinergic activity by estimating the acetylcholine content of the whole brain and acetylcholinesterase activity at different regions of the rat brain, viz., cerebral cortex, midbrain, medulla oblongata and cerebellum. Our results suggest that C. ternatea extracts increase rat brain acetylcholine content and acetyl cholinesterase a ctivity in a similar fashion to the standard cerebro protective drug Pyritinol. PMID:21214440

  6. The Sarin-like Organophosphorus Agent bis (isopropyl methyl)phosphonate Induces Apoptotic Cell Death and COX-2 Expression in SK-N-SH Cells.

    Science.gov (United States)

    Arima, Yosuke; Yoshimoto, Kanji; Namera, Akira; Makita, Ryosuke; Murata, Kazuhiro; Nagao, Masataka

    2016-03-01

    Organophosphorus compounds, such as sarin, are highly toxic nerve agents that inhibit acetylcholinesterase (AChE), but not cholinesterase, via multiple mechanisms. Recent studies have shown that organophosphorus compounds increase cyclooxygenase-2 (COX-2) expression and induce neurotoxicity. In this study, we examined the toxicity of the sarin-like organophosphorus agent bis(isopropyl methyl)phosphonate (BIMP) and the effects of BIMP on COX-2 expression in SK-N-SH human neuroblastoma cells. Exposure to BIMP changed cell morphology and induced caspase-dependent apoptotic cell death accompanied by cleavage of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). It also increased COX-2 expression, while pretreatment with a COX inhibitor, ibuprofen, decreased BIMP-dependent cell death and COX-2 expression in SK-N-SH cells. Thus, our findings suggest that BIMP induces apoptotic cell death and upregulates COX-2 expression. PMID:27348899

  7. 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

    Directory of Open Access Journals (Sweden)

    Martha Edilia Palacios-Nava

    2004-08-01

    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

  8. Bedside point of care toxicology screens in the ED: Utility and pitfalls.

    Science.gov (United States)

    Bhalla, Ashish

    2014-07-01

    Exposure to drugs and toxins is a major cause for patients' visits to the emergency department (ED). For most drugs-of-abuse intoxication, ED physicians are skeptical to rely on results of urine drug testing for emergent management decisions. This is partially because immunoassays, although rapid, have limitations in sensitivity and specificity and chromatographic assays, which are more definitive, are more labor intensive. Testing for toxic alcohols is needed, but rapid commercial assays are not available. ED physicians need stat assays for acetaminophen, salicylates, co-oximetry, cholinesterase, iron, and some therapeutic drugs that could be used as agents of self-harm. In this review, we look at the potential limitations of these screening tests and suggest improvements and innovations needed for better clinical utilization. New drugs of abuse should be sought and assays should be developed to meet changing abuse patterns. PMID:25337490

  9. Adverse respiratory health and hematological alterations among agricultural workers occupationally exposed to organophosphate pesticides: a cross-sectional study in North India.

    Directory of Open Access Journals (Sweden)

    Mohd Fareed

    Full Text Available BACKGROUND: Non-protective work practices followed by farm workers during spraying of pesticides lead to occupational exposure among them. OBJECTIVE: This study is designed to explore the respiratory health and hematological profile of agricultural workers occupationally exposed to OP pesticides. MATERIALS AND METHODS: A cross sectional study was undertaken among 166 pesticide sprayers working in mango orchards of Lucknow district in North India compared with 77 controls to assess the respiratory illness, lung functions, cholinesterase levels and hematological profile. A questionnaire based survey and clinical examination for respiratory health were conducted among study subjects. Lung function test was conducted among study subjects by using spirometer. Cholinesterase level as biomarker of OP pesticides and hematological profile of study subjects were investigated in the laboratory by following the standard protocols. RESULTS: Overall respiratory morbidity observed among exposed subjects was 36.75%. Symptoms for respiratory illness like dry cough, productive cough, wheezing, irritation of throat and blood stained sputum were found to be significantly more (p<0.05 among pesticide sprayers than controls. Lung function parameters viz. PEFR, FEV1, %PEFR predicted, %FEV1 predicted and FEV1/FVC were found to be significantly decreased (p<0.05 among pesticide sprayers as compared to controls. Exposure wise distribution of respiratory illness and lung functions among pesticide sprayers show that the exposure duration significantly elevates (p<0.05 the respiratory problems and significantly decreases (p<0.001 lung functions among pesticide sprayers. Activities of acetylcholinesterase and butyrylcholinesterase were found to be significantly depleted (p<0.001 among pesticide sprayers as compared to controls which show the exposure of OP pesticides among them. The hematological profile viz. RBC, WBC, monocytes, neutrophils, MCV, MCH, MCHC and platelet

  10. Genomic resources for the brown planthopper, Nilaparvata lugens: Transcriptome pyrosequencing and microarray design

    Institute of Scientific and Technical Information of China (English)

    Chris Bass; Martin Bay Hebsgaard; Joseph Hughes

    2012-01-01

    The brown planthopper,Nilaparvata lugens is a pest of cultivated rice throughout Asia and is controlled using insecticides and/or resistant rice varieties.This species has developed resistance to many classes of insecticide and biotypes have developed that are virulent against formerly resistant rice cultivars.Insects use a suite of detoxification enzymes,including cytochrome P450s,glutathione S-transferases and carboxyl/cholinesterases to defend themselves against plant secondary metabolites and pesticides.Pyrosequencing on the Roche 454-FLX platform was used to produce a substantial expressed sequence tag (EST) dataset to complement the existing Sanger sequenced ESTs in GenBank.A total of 78 959 reads were combined with the 37 392 publically available Sanger ESTs; these assembled into 8 911 contigs and 10 620 singletons.Analysis of the distribution of tentative unique genes (TUGs) with the gene ontology for biological processes and molecular functions suggests that the 454 and Sanger EST assembly is broadly representative of the N.lugens transcriptome.The brown planthopper transcriptome was found to contain 31 TUGs encoding P450s,nine encoding glutathione S-transferases and 26 encoding carboxyl/cholinesterases and many of these are putatively involved in the detoxification of xenobiotics.The Agilent eArray platform was used to construct an oligonucleotide microarray populated with probes for ~ 19 000 unigene sequences,including all those known to encode detoxification enzymes.The genomic resources developed in this study will be useful to the community studying this crop pest and will help elucidate the molecular mechanism underlying insecticide resistance and planthopper adaptation to resistant rice cultivars.

  11. An Increased Ratio of Glycated Albumin to HbA1c Is Associated with the Degree of Liver Fibrosis in Hepatitis B Virus-Positive Patients

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    Hirayuki Enomoto

    2014-01-01

    Full Text Available Background. In hepatitis B virus- (HBV- positive patients, the relationship between the metabolic variables and histological degree of liver fibrosis has been poorly investigated. Methods. A total of 176 HBV-positive patients were assessed in whom the ratios of glycated albumin-to-glycated hemoglobin (GA/HbA1c were calculated in order to investigate the relationship with the degree of liver fibrosis. Results. The GA/HbA1c ratio increased in association with the severity of fibrosis (METAVIR scores: F0-1: 2.61 ± 0.24, F2: 2.65 ± 0.24, F3: 2.74 ± 0.38, and F4: 2.91 ± 0.63. The GA/HbA1c ratios were inversely correlated with four variables of liver function: the prothrombin time (PT percentage (P<0.0001, platelet count (P<0.0001, albumin value (P<0.0001, and cholinesterase value (P<0.0001. The GA/HbA1c ratio was positively correlated with two well-known markers of liver fibrosis, FIB-4 (P<0.0001 and the AST-to-platelet ratio index (APRI (P<0.0001. Furthermore, the GA/HbA1c showed better correlations with two variables of liver function (PT percentage and cholinesterase value than did FIB-4 and with all four variables than did the APRI. Conclusion. The GA/HbA1c ratio is associated with the degree of liver fibrosis in HBV-positive patients.

  12. Dengue in the South-eastern region of Brazil: historical analysis and epidemiology

    Directory of Open Access Journals (Sweden)

    Serufo José Carlos

    1993-01-01

    Full Text Available The aim of the study is an historical analysis of the work undertaken by the Public Health organizations dedicated to the combat of the Aedes aegypti, as well as an epidemiolocal study of persons with unexplained fever, with a view to evaluating the ocurrence of dengue within the population. The Mac-Elisa, Gac-Elisa, hemaglutination inhibition, isolation and typage tests were used. Organophosphate intoxication in agricultural workers was also assessed by measuring concentrations of serie cholinesterase. A sera samples of 2,094 were collected in 23 towns, and the type 1 dengue virus was detected in 17 towns and autochthony was confirmed in 12 of them. The cholinesterase was measured in 2,391 sera samples of which 53 cases had abnormal levels. Poisoning was confirmed in 3 cases. Results reveal an epidemic the gravity of which was not officially know. The relationshipe between levels of IgM and IgG antibodies indicates the outbreak tendency. The widespread distribution of the vector is troubling because of the possibility of the urbanization of wild yellow fever, whereas the absence of A. aegypti in 2 towns with autochthony suggests the existence of another vector. Since there is no vaccine against dengue, the combat of the vector is the most efficient measure for preventing outbreaks. The eradication of the vector depends on government decisions which depend, for their execution, on the organization of the Health System and the propagation of information concerning the prevention of the disease using all possible means because short and long term results depend on the education and the active participation of the entire population.

  13. The neuropsychiatry of Parkinson's disease.

    Science.gov (United States)

    Lauterbach, E C

    2005-06-01

    The neuropsychiatry of Parkinson's disease (PD) and its correlates are reviewed. Dementia occurs in up to 30% and can be treated with cholinesterase inhibitors. Cognitive impairments involve executive, visuospatial, attentional, and memory dysfunctions. Apathy may respond to dopamine agonists or cholines-terase inhibitors. Cognitive impairment, psychosis, and depression predict quality of life. Visual hallucinations and paranoia are common, and respond to low dose clozapine. Depression is common and predicts caregiver burden and depression. The best data suggest the efficacy of nortriptyline and the safety of SSRIs. Anxiety disorders occur in 40% of patients, especially off-period panic attacks and specific phobias. Bromazepam has proven useful for anxiety in PD, but buspirone has only diminished drug-induced dyskinesias to date. Sleep disorders occur in up to 94% of patients. Insomnia is common and is treated by dopaminergic agent dose reduction, nocturnal dosing, treatment of depression, or use of short half-lived hypnotics, depending on etiology. Parasomnias include REM behavior disorder and vivid dreams and nightmares. Excessive daytime somnolence occurs in at least 15% of patients. Sleep attacks are common and patients should be warned about driving when taking dopamine agonists. Sexual disorders occur in most patients. Paraphilias are associated with dopamine agonists, and clozapine may be useful in their treatment. Surgical therapies are associated with a wide variety of neuropsychiatric features, and vigilance for suicide attempts with subthalamic nucleus stimulation seems warranted. Neuropsychiatric disorders are important determinants of quality of life and caregiver burden in PD. More clinical research is needed to establish effective treatments. PMID:16175159

  14. Effects of temephos (Abate? 4E) on fiddler crabs (Uca pugnax and Uca minax) on a Delaware salt marsh

    Science.gov (United States)

    Pinkney, A.E.; McGowan, P.C.; Murphy, D.R.; Lowe, T.P.; Sparling, D.W.; Meredith, W.H.

    1999-01-01

    The non-target effects of temephos (as Abate 4E, 44.6% active ingredient) on fiddler crabs were examined on the salt marsh at Bombay Hook National Wildlife Refuge (NWR), near Dover, DE. Six 170 x 170 m plots were established; 3 were sprayed on 4 occasions at a rate of 1.5 fl oz/acre (0.054 kg active ingredient/ha) and 3 were controls. On each plot, marsh fiddler crab (Uca pugnax) populations were monitored by repeatedly counting the number of burrow holes in 2 counting areas marked out along tidal guts. One half of each counting area was covered with bird netting to evaluate sublethal toxic effects, which, if present, could result in increased susceptibility to bird predation. A statistically significant linear association was established between the number of holes and the number of crabs. No significant differences were found in the numbers of holes (or crabs) in the sprayed vs. control plots and in the covered vs. uncovered sections. However, survival of juvenile crabs in in situ bioassays was significantly reduced (16% lower) by the spraying. Median acetylcholinesterase activity in claw muscle of red-jointed fiddler crabs (U. minax) collected 2 days after an operational spray with Abate 4E was significantly reduced (28% lower) compared to unsprayed crabs. In view of the toxicity to juvenile crabs and the cholinesterase inhibition, we recommend continued monitoring and research for non-target impacts of Abate 4E on fiddler crabs to establish whether the reported level of cholinesterase inhibition results in acute or chronic toxicity.

  15. Toxicological studies for some agricultural waste extracts on mosquito larvae and experimental animals

    Institute of Scientific and Technical Information of China (English)

    Somia El-Maghraby; Galal A Nawwar; Reda FA Bakr; Nadia Helmy; Omnia MHM Kamel

    2012-01-01

    Objective: To evaluate some agricultural waste extracts as insecticide and their effects on enzyme activities in liver and kidney of male mice. Methods: The insecticidal activity of five tested compounds (one crude extract and 4 waste compounds) was bioassay against the 3rd instars of the Culex pipiens (Cx. pipiens) larvae in the laboratory. The LC50 values of eucalyptol, apricot kernel, Rice bran, corn, black liquor and white liquor are 91.45, 1 166.1, 1 203.3, 21 449.65, 4 025.78 and 6 343.18 ppm, respectively. Selection of the compounds for the subsequent studies was not only dependent on LC50 values but also on the persistence of these wastes products on large scale. Results:White and black liquor did not produce any gross effect at 200 mg/Kg body weight. No apparent toxic symptoms were observed in tested animals during the whole period of the experiment which run out for 14 days. No statistically significance was observed in the enzyme cholinesterase activity, the activities of liver enzymes and kidney function in treated mice with black and white liquors. While, no and slight inhibition was observed after the 2 weeks of treatment period with deltamethrin and fenitrothion reached to about 24%in plasma cholinesterase enzyme activity. Significantly increase in the activities of liver enzymes and kidney function in treated mice with deltamethrin and fenitrothion. Conclusions:Black liquor can be used efficiently to control Cx. pipiens larvae under laboratory condition. Environmental problem caused by rice straw can be solved by converting the waste material to beneficial natural selective insecticide.

  16. Dengue in the South-eastern region of Brazil: historical analysis and epidemiology

    Directory of Open Access Journals (Sweden)

    José Carlos Serufo

    1993-06-01

    Full Text Available The aim of the study is an historical analysis of the work undertaken by the Public Health organizations dedicated to the combat of the Aedes aegypti, as well as an epidemiolocal study of persons with unexplained fever, with a view to evaluating the ocurrence of dengue within the population. The Mac-Elisa, Gac-Elisa, hemaglutination inhibition, isolation and typage tests were used. Organophosphate intoxication in agricultural workers was also assessed by measuring concentrations of serie cholinesterase. A sera samples of 2,094 were collected in 23 towns, and the type 1 dengue virus was detected in 17 towns and autochthony was confirmed in 12 of them. The cholinesterase was measured in 2,391 sera samples of which 53 cases had abnormal levels. Poisoning was confirmed in 3 cases. Results reveal an epidemic the gravity of which was not officially know. The relationshipe between levels of IgM and IgG antibodies indicates the outbreak tendency. The widespread distribution of the vector is troubling because of the possibility of the urbanization of wild yellow fever, whereas the absence of A. aegypti in 2 towns with autochthony suggests the existence of another vector. Since there is no vaccine against dengue, the combat of the vector is the most efficient measure for preventing outbreaks. The eradication of the vector depends on government decisions which depend, for their execution, on the organization of the Health System and the propagation of information concerning the prevention of the disease using all possible means because short and long term results depend on the education and the active participation of the entire population.

  17. Pharmacological management of anticholinergic delirium - theory, evidence and practice.

    Science.gov (United States)

    Dawson, Andrew H; Buckley, Nicholas A

    2016-03-01

    The spectrum of anticholinergic delirium is a common complication following drug overdose. Patients with severe toxicity can have significant distress and behavioural problems that often require pharmacological management. Cholinesterase inhibitors, such as physostigmine, are effective but widespread use has been limited by concerns about safety, optimal dosing and variable supply. Case series support efficacy in reversal of anticholinergic delirium. However doses vary widely and higher doses commonly lead to cholinergic toxicity. Seizures are reported in up to 2.5% of patients and occasional cardiotoxic effects are also recorded. This article reviews the serendipitous path whereby physostigmine evolved into the preferred anticholinesterase antidote largely without any research to indicate the optimal dosing strategy. Adverse events observed in case series should be considered in the context of pharmacokinetic/pharmacodynamic studies of physostigmine which suggest a much longer latency before the maximal increase in brain acetylcholine than had been previously assumed. This would favour protocols that use lower doses and longer re-dosing intervals. We propose based on the evidence reviewed that the use of cholinesterase inhibitors should be considered in anticholinergic delirium that has not responded to non-pharmacological delirium management. The optimal risk/benefit would be with a titrated dose of 0.5 to 1 mg physostigmine (0.01-0.02 mg kg(-1) in children) with a minimum delay of 10-15 min before re-dosing. Slower onset and longer acting agents such as rivastigmine would also be logical but more research is needed to guide the appropriate dose in this setting.

  18. In situ effects of pesticides on amphibians in the Sierra Nevada

    Science.gov (United States)

    Sparling, Donald W.; Bickham, John W.; Cowman, Deborah; Fellers, Gary M.; Lacher, Thomas E.; Matson, Cole W.; McConnell, Laura

    2015-01-01

    For more than 20 years, conservationists have agreed that amphibian populations around the world are declining. Results obtained through laboratory or mesocosm studies and measurement of contaminant concentrations in areas experiencing declines have supported a role of contaminants in these declines. The current study examines the effects of contaminant exposure to amphibians in situ in areas actually experiencing declines. Early larval Pseudacris regilla were translocated among Lassen Volcanic, Yosemite and Sequoia National Parks, California, USA and caged in wetlands in 2001 and 2002 until metamorphosis. Twenty contaminants were identified in tadpoles with an average of 1.3–5.9 (maximum = 10) contaminants per animal. Sequoia National Park, which had the greatest variety and concentrations of contaminants in 2001, also had tadpoles that experienced the greatest mortality, slowest developmental rates and lowest cholinesterase activities. Yosemite and Sequoia tadpoles and metamorphs had greater genotoxicity than those in Lassen during 2001, as determined by flow cytometry. In 2001 tadpoles at Yosemite had a significantly higher rate of malformations, characterized as hemimelia (shortened femurs), than those at the other two parks but no significant differences were observed in 2002. Fewer differences in contaminant types and concentrations existed among parks during 2002 compared to 2001. In 2002 Sequoia tadpoles had higher mortality and slower developmental rates but there was no difference among parks in cholinesterase activities. Although concentrations of most contaminants were below known lethal concentrations, simultaneous exposure to multiple chemicals and other stressors may have resulted in lethal and sublethal effects.

  19. In vitro evaluation of anti-Alzheimer effects of dry ginger (Zingiber officinale Roscoe) extract.

    Science.gov (United States)

    Mathew, Maya; Subramanian, Sarada

    2014-06-01

    As the disease modifying therapies against Alzheimer's disease (AD) continue to exist as a major challenge of this century, the search for newer drug leads with lesser side effects is on the rise. A large number of plant extracts and phytocompounds are being actively pursued for their anti-Alzheimer effects. In the present study, the antioxidant activity, cholinesterase inhibition, anti-amyloidogenic potential and neuroprotective properties of methanolic extract of dry ginger (GE) have been evaluated. The extract contained 18 +/- 0.6 mg/g gallic acid equivalents of total phenolic content and 4.18 +/- 0.69 mg quercetin equivalents/g of dry material. GE expressed high antioxidant activity with an IC50 value of 70 +/- 0.304 microg/mL in DPPH assay and 845.4 +/- 56.62 microM Fe(II) equivalents/g dry weight in FRAP assay respectively. In Ellman's assay for the cholinesterase inhibitory activity, GE had an IC50 value of 41 +/- 1.2 microg/mL and 52 +/- 2 microg/mL for inhibition of acetyl- and butyrylcholinesterase respectively. Also, GE increased the cell survival against amyloid beta (Abeta) induced toxicity in primary adult rat hippocampal cell culture. Aggregation experiments with the thioflavin T binding studies showed that GE effectively prevented the formation of Abeta oligomers and dissociated the preformed oligomers. These findings suggest that methanolic GE influences multiple therapeutic molecular targets of AD and can be considered as an effective nontoxic neutraceutical supplement for AD. PMID:24956891

  20. Organophosphorus agent induced delayed neuropathy: a case report

    Directory of Open Access Journals (Sweden)

    Harshit Acharya

    2016-02-01

    Full Text Available A 40-year old male, was presented with complaint of difficulty in walking with inability to flex foot and toes in bilateral feet ( and ldquo;foot drop and rdquo;, which was acute at the onset and gradually progressive since the past 7 days. The patient's wife and their 2 children had similar complaint with the same period of onset. At home, his family used cottonseed oil as cooking oil with wheat grain mixed with castor oil. On neurological examination, he was found to have lower motor neuron weakness with spasticity. After ruling out other common causes of polyneuropathy and lower motor weakness; due to high suspicion of poisoning by food adulterant, RBC acetyl cholinesterase (AChE and plasma cholinesterase (BuChE were tested at National Institute of Occupational Health (NIOH, which came low and confirmed diagnosis of Organophosphorus (OP poisoning. Nerve conduction study was done; which showed decreased amplitude of conduction in bilateral peroneal and right tibial nerve along with decreased mean nerve conduction velocity of bilateral median nerve. Thus patient was diagnosed with organophosphorus agent induced delayed axonal type of polyneuropathy and physiotherapy was started as treatment. OP compounds are a diverse group of chemicals which are principally used as insecticides in agriculture. Following organophosphate poisoning (OPP, 3 well-defined neurological syndromes are recognised: cholinergic crisis, intermediate syndrome and delayed polyneuropathy. Some organophosphates, particularly triorthocresyl phosphate (TOCP and tricresyl phosphate (TCP, produce delayed neuropathy. On ingestion, they do not produce significant cholinergic crisis, but 7 to 20 days later it leads to a pure motor axonal neuropathy with wrist and foot drop. The mechanism may involve inhibition of neuropathy target esterase (NTE, which is found in the brain, peripheral nerves, and lymphocytes. This form of toxicity has been seen occasionally in small epidemics in

  1. Effects of a lyophilized aqueous extract of Feretia apodanthera Del. (Rubiaceae) on pentylenetetrazole-induced kindling, oxidative stress, and cognitive impairment in mice.

    Science.gov (United States)

    Taiwe, G S; Moto, F C O; Ayissi, E R M; Ngoupaye, G T; Njapdounke, J S K; Nkantchoua, G C N; Kouemou, N; Omam, J P O; Kandeda, A K; Pale, S; Pahaye, D; Ngo Bum, E

    2015-02-01

    Feretia apodanthera Del. (Rubiaceae) is extensively used in ethnomedicine in Cameroon and Nigeria for epilepsy, febrile convulsions, and rheumatic pains and for enhancing cognitive performance. The aim of the present study was to examine the effects of a lyophilized aqueous extract of F. apodanthera on the course of kindling development, kindling-induced learning deficit, oxidative stress markers, and cholinesterase activity in pentylenetetrazole (PTZ)-kindled mice. Pentylenetetrazole, 30mg/kg, induced kindling in mice after 30.00±1.67days. The aqueous extract of F. apodanthera showed dose-dependent antiseizure effects. Feretia apodanthera (150-200mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures, and generalized tonic-clonic seizures. The extract also improved the seizure score and decreased the number of myoclonic jerks. Pentylenetetrazole kindling induced significant oxidative stress and cognitive impairment which were reversed by pretreatment with F. apodanthera in a dose-dependent manner. The significant decrease in cholinesterase activity observed in the PTZ-kindled mice was reversed by pretreatment with the F. apodanthera extract. The results indicated that pretreatment with the aqueous extract of F. apodanthera antagonizes seizures, oxidative stress, and cognitive impairment in PTZ-kindled mice. The aqueous extract of F. apodanthera also showed anxiolytic activities, but the inhibition of memory impairment was not attributed to the anxiolytic activities of the plant. These results thus suggest the potential of F. apodanthera as an adjuvant in epilepsy both to prevent seizures as well as to protect against seizure-induced oxidative stress and memory impairment.

  2. The timing of drug funding announcements relative to elections: a case study involving dementia medications.

    Directory of Open Access Journals (Sweden)

    Sudeep S Gill

    Full Text Available BACKGROUND: Following initial regulatory approval of prescription drugs, many factors may influence insurers and health systems when they decide whether to add these drugs to their formularies. The role of political pressures on drug funding announcements has received relatively little attention, and elections represent an especially powerful form of political pressure. We examined the temporal relationship between decisions to add one class of drugs to publicly funded formularies in Canada's ten provinces and elections in these jurisdictions. METHODS: Dates of provincial formulary listings for cholinesterase inhibitors, which are drugs used to treat Alzheimer's disease and related dementias, were compared to the dates of provincial elections. Medical journal articles, media reports, and proceedings from provincial legislatures were reviewed to assemble information on the chronology of events. We tested whether there was a statistically significant increase in the probability of drug funding announcements within the 60-day intervals preceding provincial elections. RESULTS: Decisions to fund the cholinesterase inhibitors were made over a nine-year span from 1999 to 2007 in the ten provinces. In four of ten provinces, the drugs were added to formularies in a time period closely preceding a provincial election (P = 0.032; funding announcements in these provinces were made between 2 and 47 days prior to elections. Statements made in provincial legislatures highlight the key role of political pressures in these funding announcements. CONCLUSIONS: Impending elections appeared to affect the timing of drug funding announcements in this case study. Despite an established structure for evidence-based decision-making, drug funding remains a complex process open to influence from many sources. Awareness of such influences is critical to maintain effective drug policy and public health decision-making.

  3. In vitro and in vivo metabolism and inhibitory activities of vasicine, a potent acetylcholinesterase and butyrylcholinesterase inhibitor.

    Directory of Open Access Journals (Sweden)

    Wei Liu

    Full Text Available Vasicine (VAS, a potential natural cholinesterase inhibitor, exhibited promising anticholinesterase activity in preclinical models and has been in development for treatment of Alzheimer's disease. This study systematically investigated the in vitro and in vivo metabolism of VAS in rat using ultra performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. A total of 72 metabolites were found based on a detailed analysis of their 1H- NMR and 13C NMR data. Six key metabolites were isolated from rat urine and elucidated as vasicinone, vasicinol, vasicinolone, 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, 9-oxo-1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, and 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-β-D-glucuronide. The metabolic pathway of VAS in vivo and in vitro mainly involved monohydroxylation, dihydroxylation, trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. The main metabolic soft spots in the chemical structure of VAS were the 3-hydroxyl group and the C-9 site. All 72 metabolites were found in the urine sample, and 15, 25, 45, 18, and 11 metabolites were identified from rat feces, plasma, bile, rat liver microsomes, and rat primary hepatocyte incubations, respectively. Results indicated that renal clearance was the major excretion pathway of VAS. The acetylcholinesterase (AChE and butyrylcholinesterase (BChE inhibitory activities of VAS and its main metabolites were also evaluated. The results indicated that although most metabolites maintained potential inhibitory activity against AChE and BChE, but weaker than that of VAS. VAS undergoes metabolic inactivation process in vivo in respect to cholinesterase inhibitory activity.

  4. Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer’s Disorders Using Molecular Docking and Molecular Dynamics Simulation

    Directory of Open Access Journals (Sweden)

    Chandrabhan Seniya

    2014-01-01

    Full Text Available Cholinesterase inhibitors (ChE-Is are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA. Additionally, acetylcholinesterase (AChE is the target for many Alzheimer’s dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6 to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential.

  5. Morbidity in newborns exposed to organophosphorus pesticides

    Directory of Open Access Journals (Sweden)

    Đorđević Momčilo

    2010-01-01

    Full Text Available Introduction. Insecticides are toxines by which we destroy harmful insects. The most frequent insecticides which are used today are organophosphorus pesticides. This group of compounds make substances whose activity mechanism is based on the inhibition of acetylcho­linesterase in nerve synapsis, thus producing holynergic syndrome, resulting from the accumulation of acetylcholine which developed due to the absence of decomposition under the influence of cholinesterase. In the clinical picture of acute toxication by cholinesterase inhibitors there is a clear difference between muscarinic and nicotine effects. The basic aim of the study was to establish the effects of organophosphorus pesticides present in blood and breast milk of mothers on newborns morbidity. Material and methods. The study group consisted of 18 newborns whose mothers had isolated organophosphorus pesticides in their blood and breast­milk on the third day after delivery, and the control group consisted of 84 newborns whose mothers did not have isolated organophosphorus pesticides in their blood and breastmilk. Results. Morbidity is three times greater, often in combination with some disorders of the central nervous system, and the relative risk for its appearance is eight time greater in newborns exposed to organophosphorus pesticides. Disscusion. Disorders that appear in newborns exposed to pesticides are mutagenic, cancerogenic and neurotoxic and some agenses could disturb the immune system which is reflected in morbidity increase, primarly of the central nervous system. Conclusion. The presence of organophosphorus pesticides in blood and breast milk has negative effects on newborns. In addition to acetylcho­linesterase inhibition, organophosphorus pesticides react by means of other mechanisms as well.

  6. A Human Life-Stage Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Chlorpyrifos: Development and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles; Bartels, M. J.; Poet, Torka S.

    2014-08-01

    Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Blood flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.

  7. Biological Activities and Composition of Ferulago carduchorum Essential Oil

    Science.gov (United States)

    Golfakhrabadi, Fereshteh; Khanavi, Mahnaz; Ostad, Seyed Nasser; Saeidnia, Soodabeh; Vatandoost, Hassan; Abai, Mohammad Reza; Hafizi, Mitra; Yousefbeyk, Fatemeh; Rad, Yaghoob Razzaghi; Baghenegadian, Ameneh; Ardekani, Mohammad Reza Shams

    2015-01-01

    Background: Ferulago carduchorum Boiss and Hausskn belongs to the Apiaceae family. This plant grows in west part of Iran that local people added it to dairy and oil ghee to delay expiration date and give them a pleasant taste. The aim of this study was to investigate the antioxidant, antimicrobial, acetyl cholinesterase inhibition, cytotoxic, larvicidal activities and composition of essential oil of F. carduchorum. Methods: Acetyl cholinesterase (AChE) inhibitory, larvicidal activities and chemical composition of essential oil of F. carduchorum were investigated. Besides, antioxidant, antimicrobial and cytotoxic activities of essential oil were tested using DPPH, microdilution method and MTT assay, respectively. Results: The major components of essential oil were (z)-β-ocimene (43.3%), α-pinene (18.23%) and bornyl acetate (3.98%). Among 43 identified components, monoterpenes were the most compounds (84.63%). The essential oil had noticeable efficiency against Candida albicans (MIC= 2340 μg ml−1) and it was effective against Anopheles stephensi with LC50 and LC90 values of 12.78 and 47.43 ppm, respectively. The essential oil could inhibit AChE (IC50= 23.6 μl ml−1). The essential oil showed high cytotoxicity on T47D, HEP-G2 and HT-29 cell lines (IC50< 2 μg ml−1). Conclusion: The essential oil of F. carduchorum collected from west of Iran had anti-Candida, larvicidal and cytotoxicity effects and should be further investigated in others in vitro and in vivo experimental models. PMID:26114148

  8. Anti-diabetic related health food properties of traditional rice (Oryza sativa L. in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Walimuni Kanchana Subhashini Mendis Abeysekera

    2015-10-01

    Full Text Available 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 inhibition in vitro and anti-hyperglycemic activity in vivo. Further, selected varieties were studied for starch hydrolysis rate in 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 < 0.05 and dose dependent methylglyoxal mediated protein glycation inhibition [IC50: (174.77 ± 6.65 to (342.87 ± 0.43 µg/mL] and acetyl [(IC50: (37.00 ± 0.68 to (291.00 ± 3.54 µg/mL] and butyryl-cholinesterase [IC50: (18.50 ± 0.60 to (96.60 ± 0.56 µg/mL] inhibitory activities. Further, Sudu Heeneti, Masuran and Dik Wee had low starch digestion rate (52.40 ± 1.44 to 53.76 ± 1.19 indicating that these varieties may be low glycemic index rices. Brans of Masuran tested in rat model showed anti-hyperglycemic activity. Physicochemical properties studied showed that selected varieties were red in color and grain size and shape were mostly medium and bold respectively. Moisture, crude protein, crude fat, ash and total carbohydrate contents varied significantly (P < 0.05 among the varieties. 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.

  9. Effects of hyperprolactinemia on toxicological parameters and proliferation of islet cells in male rats.

    Science.gov (United States)

    Ose, Keiko; Miyata, Kaori; Yoshioka, Kaoru; Okuno, Yasuyoshi

    2009-04-01

    Prolactin has a wide variety of biological effects. Consequences of hyperprolactinemia on islet B cell proliferation as well as general toxicological parameters were here examined using anterior pituitary-grafted rats. Three or six anterior pituitary glands were implanted under single renal capsules of F344 male rats and left there for 13 weeks afterward. Clinical observation along with measurement of body weight and food consumption was conducted during the observation period, and subsequently hematology, blood biochemistry, gross pathology, organ weights and histopathology were examined. In addition, the proliferation rate of islet B cells was measured by a 5-bromo-2'-deoxy-uridine (BrdU) labeling technique. Serum prolactin concentrations at week 13 were 36, 70, 75 and 105 ng/ml in the sham-operated, 3-pituitary-grafted groups from male or female donors, and 6-pituitary-grafted group from male donors, respectively. Higher cholinesterase and total cholesterol values, lower trigriceride and leutenizing hormones (LH) values, and higher adrenal weights compared to those in the sham-operated group were apparent in the 3- and/or 6-pituitary-grafted groups. Also, the study revealed that mammary gland structure was transformed with change of differentiation from a male to a female acinar pattern. Furthermore a specific increase of islet cell proliferation rate was found, positively correlated with serum prolactin concentration. These findings suggest that elevation of serum prolactin level over 13 weeks induces islet cell proliferation and changes in toxicological parameters, including cholinesterase activity, elements of lipid metabolism and histopathology/morphology of the adrenals and mammary glands in male rats. PMID:19336972

  10. Increased dopamine D1 receptor binding in the human mesocortical system following central cholinergic activation

    International Nuclear Information System (INIS)

    Full text: The interaction between the cholinergic and dopaminergic system has been implicated in many pathological processes including, Alzheimer's disease, schizophrenia and drug addiction. Little is known about the control of dopamine (DA) release following central cholinergic activation in humans, but experimental studies suggest that endogenously released Acetylcholine (ACh) achieved by the administration of cholinesterase inhibitors, can increase dopamine efflux in different regions of the brain. This leads to the activation of different types of post-synaptic dopaminergic receptors which belong to the family of G-protein coupled receptors (GPCRs). A common paradigm of the GPCRs desensitization is that agonist-induced receptor signaling is rapidly attenuated by receptor internalisation. Several experiments have shown that the activation of Dl receptors in acute conditions leads, within minutes, to translocation of the receptor from the surface of the neurons to the endosomal compartment in the cytoplasm and increased receptor turnover. To assess changes in Dl receptor density following an intravenous infusion of the selective cholinesterase inhibitor physostigmine salicylate (PHY), we studied eleven normal subjects (10 male and 1 female, mean age 36.1 and 61617; 9.9) using [11C]-SCH23390 and PET The binding potential (BP) for SCH23390 was significantly (p0.05). There was no statistically significant difference between baseline and physostigmine Kl ratio (p>0.05) suggesting that BP changes observed were not secondary to regional blood flow changes or to an order effect of the scans. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  11. Kinetic model of ethopropazine interaction with horse serum butyrylcholinesterase and its docking into the active site.

    Science.gov (United States)

    Golicnik, Marko; Sinko, Goran; Simeon-Rudolf, Vera; Grubic, Zoran; Stojan, Jure

    2002-02-01

    The action of a potent tricyclic cholinesterase inhibitor ethopropazine on the hydrolysis of acetylthiocholine and butyrylthiocholine by purified horse serum butyrylcholinesterase (EC 3.1.1.8) was investigated at 25 and 37 degrees C. The enzyme activities were measured on a stopped-flow apparatus and the analysis of experimental data was done by applying a six-parameter model for substrate hydrolysis. The model, which was introduced to explain the kinetics of Drosophila melanogaster acetylcholinesterase [Stojan et al. (1998) FEBS Lett. 440, 85-88], is defined with two dissociation constants and four rate constants and can describe both cooperative phenomena, apparent activation at low substrate concentrations and substrate inhibition by excess of substrate. For the analysis of the data in the presence of ethopropazine at two temperatures, we have enlarged the reaction scheme to allow primarily its competition with the substrate at the peripheral site, but the competition at the acylation site was not excluded. The proposed reaction scheme revealed, upon analysis, competitive effects of ethopropazine at both sites; at 25 degrees C, three enzyme-inhibitor dissociation constants could be evaluated; at 37 degrees C, only two constants could be evaluated. Although the model considers both cooperative phenomena, it appears that decreased enzyme sensitivity at higher temperature, predominantly for the ligands at the peripheral binding site, makes the determination of some expected enzyme substrate and/or inhibitor complexes technically impossible. The same reason might also account for one of the paradoxes in cholinesterases: activities at 25 degrees C at low substrate concentrations are higher than at 37 degrees C. Positioning of ethopropazine in the active-site gorge by molecular dynamics simulations shows that A328, W82, D70, and Y332 amino acid residues stabilize binding of the inhibitor. PMID:11811945

  12. Methyl Parathion Masks Withdrawal from Physical Dependence on Morphine

    Directory of Open Access Journals (Sweden)

    Robin W. Rockhold

    2002-10-01

    Full Text Available Abstract: The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP, an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced by continuous intracerebroventricular (i.c.v. infusion of morphine (26 nmol/μl/h for 3 days in adult male Sprague-Dawley rats. Each rat received two doses of MP, 12.5 mg/kg, dermally, initially, 3 days prior to initiation of i.c.v. morphine infusion and again on the first day of infusion. Withdrawal was precipitated after 3 days of infusion by administering an opioid antagonist, naloxone (48 nmol/5 μl, i.c.v.. Twelve of 23 MP-treated rats exhibited signs of acetylcholinesterase inhibitor intoxication (mild tremors and showed reduced spontaneous locomotor activity (tested by an open field test, prior to naloxone. The brain cholinesterase activity in these 12 rats was 13% of levels in control rats. Eleven rats that did not show toxic signs, exhibited cholinesterase activities that were 20% of control (not significant versus toxic group. The group that showed signs of MP intoxication exhibited a significantly lower incidence of opioid withdrawal jumping, rearing and wet dog shakes compared with the non-toxic group. No differences between quantal withdrawal signs (ptosis, penis-licking, and vocalization were noted between the two groups. The results suggest that toxic inhibition of acetylcholinesterase non-specifically reduces locomotor activity and may obscure certain behavioral signs of withdrawal from opioid dependence. This indicates that caution should be used in interpreting a direct involvement of acetylcholinesterase inhibition in preventing opioid dependence.

  13. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Richard A Hansen

    2008-06-01

    Full Text Available Richard A Hansen1, Gerald Gartlehner2, Aaron P Webb1, Laura C Morgan3, Charity G Moore4, Daniel E Jonas31School of Pharmacy, 3Cecil G Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, NC, USA; 2Department for Evidence-based Medicine and Clinical Epidemiology, Danube University, Krems, Austria; 4Center for Research on Health Care Data Center; University of Pittsburgh, Pittsburgh, PA, USAAbstract: Pharmacologic treatments for Alzheimer’s disease include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine. We reviewed their evidence by searching MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 through 2007 (July for placebo-controlled and comparative trials assessing cognition, function, behavior, global change, and safety. Thirty-three articles on 26 studies were included in the review. Meta-analyses of placebo-controlled data support the drugs’ modest overall benefits for stabilizing or slowing decline in cognition, function, behavior, and clinical global change. Three open-label trials and one double-blind randomized trial directly compared donepezil with galantamine and rivastigmine. Results are conflicting; two studies suggest no differences in efficacy between compared drugs, while one study found donepezil to be more efficacious than galantamine, and one study found rivastigmine to be more efficacious than donepezil. Adjusted indirect comparison of placebo-controlled data did not find statistically significant differences among drugs with regard to cognition, but found the relative risk of global response to be better with donepezil and rivastigmine compared with galantamine (relative risk = 1.63 and 1.42, respectively. Indirect comparisons also favored donepezil over galantamine with regard to behavior. Across trials, the incidence of adverse events was generally lowest for donepezil and highest for rivastigmine.Keywords: Alzheimer

  14. Biological Activities and Composition of Ferulago carduchorum Essential Oil

    Directory of Open Access Journals (Sweden)

    Fereshteh Golfakhrabadi

    2015-10-01

    Full Text Available Background: Ferulago carduchorum Boiss and Hausskn belongs to the Apiaceae family. This plant grows in west part of Iran that local people added it to dairy and oil ghee to delay expiration date and give them a pleasant taste. The aim of this study was to investigate the antioxidant, antimicrobial, acetyl cholinesterase inhibition, cytotoxic, larvicidal activities and composition of essential oil of F. carduchorum.Methods: Acetyl cholinesterase (AChE inhibitory, larvicidal activities and chemical composition of essential oil of F. carduchorum were investigated. Besides, antioxidant, antimicrobial and cytotoxic activities of essential oil were tested using DPPH, microdilution method and MTT assay, respectively.Results: The major components of essential oil were (z-β-ocimene (43.3%, α-pinene (18.23% and bornyl acetate (3.98%. Among 43 identified components, monoterpenes were the most compounds (84.63%. The essential oil had noticeable efficiency against Candida albicans (MIC= 2340 μg ml-1 and it was effective against Anophelesstephensi with LC50 and LC90 values of 12.78 and 47.43 ppm, respectively. The essential oil could inhibit AChE (IC50= 23.6 μl ml-1. The essential oil showed high cytotoxicity on T47D, HEP-G2 and HT-29 cell lines (IC50< 2 μg ml-1.Conclusion: The essential oil of F. carduchorum collected from west of Iran had anti-Candida, larvicidal and cytotoxicity effects and should be further investigated in others in vitro and in vivo experimental models.

  15. AN ANALYSIS OF RELATED RISK FACTORS OF SECONDARY PULMONARY INFECTION IN PATIENTS WITH ORGANOPHOSPHORUS POISONING COMPLICATED BY RESPIRTORY FAILURE%有机磷中毒合并呼吸衰竭患者继发肺部感染的相关因素分析

    Institute of Scientific and Technical Information of China (English)

    赖军华

    2012-01-01

    Objective To study the related factors of secondary pulmonary infection in patients with organophosphorus poisoning complicated by respiratory failure, and provide scientific basis for early preventing and controlling of infection. Methods The clinical data of 112 cases with acute organophosphorus poisoning complicated by respiratory failure were analyzed retrospectively, and correlation of pulmonary infection and patients' age, complicated aspiration, using ventilator and blood glucose etc were analyzed by Logistic stepwise regression analysis. Results Univariate analysis showed that pulmonary infection was associated with age, combined aspiration, ventilator, blood glucose, acute physiology and chronic health evaluation M ( APACHE M ), cholinesterase activity, hand hygiene, sensitivity C - reactive protein, disturbance of consciousness and the use of sedatives after ventilator support,ICU days and so on. Multivariate Logistic regression analysis showed that combined aspiration, use of breathing machines, hand hygiene, the degree of cholinesterase activity reduction had significant effects on secondary pulmonary infection. Conclusion The combined aspiration, the use of breathing machines, hand hygiene, the level of cholinesterase activity reduction are risk factors of secondary pulmonary infection in patients with organophorus poisoning complicated by respiratory failure.%目的 探讨有机磷中毒合并呼吸衰竭患者继发肺部感染的相关因素,为及早有效预防并控制感染提供科学依据.方法 回顾分析重症有机磷中毒合并呼吸衰竭患者112例的临床资料,用Logistic逐步回归法分析患者年龄、合并误吸、使用呼吸机、血糖等因素与肺部感染的相关性.结果 单因素分析提示,年龄、合并误吸、使用呼吸机、血糖、急性生理学和慢性健康状况评分Ⅲ时间、胆碱酯酶活性、手卫生、超敏C反应蛋白、意识障碍或呼吸机支持后镇静剂

  16. Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion.

    Science.gov (United States)

    Camp, Shelley; Zhang, Limin; Marquez, Michael; de la Torre, Brian; Long, Jeffery M; Bucht, Goran; Taylor, Palmer

    2005-12-15

    AChE is an alternatively spliced gene. Exons 2, 3 and 4 are invariantly spliced, and this sequence is responsible for catalytic function. The 3' alternatively spliced exons, 5 and 6, are responsible for AChE disposition in tissue [J. Massoulie, The origin of the molecular diversity and functional anchoring of cholinesterases. Neurosignals 11 (3) (2002) 130-143; Y. Li, S. Camp, P. Taylor, Tissue-specific expression and alternative mRNA processing of the mammalian acetylcholinesterase gene. J. Biol. Chem. 268 (8) (1993) 5790-5797]. The splice to exon 5 produces the GPI anchored form of AChE found in the hematopoietic system, whereas the splice to exon 6 produces a sequence that binds to the structural subunits PRiMA and ColQ, producing AChE expression in brain and muscle. A third alternative RNA species is present that is not spliced at the 3' end; the intron 3' of exon 4 is used as coding sequence and produces the read-through, unanchored form of AChE. In order to further understand the role of alternative splicing in the expression of the AChE gene, we have used homologous recombination in stem cells to produce gene specific deletions in mice. Alternatively and together exon 5 and exon 6 were deleted. A cassette containing the neomycin gene flanked by loxP sites was used to replace the exon(s) of interest. Tissue analysis of mice with exon 5 deleted and the neomycin cassette retained showed very low levels of AChE expression, far less than would have been anticipated. Only the read-through species of the enzyme was produced; clearly the inclusion of the selection cassette disrupted splicing of exon 4 to exon 6. The selection cassette was then deleted in exon 5, exon 6 and exons 5 + 6 deleted mice by breeding to Ella-cre transgenic mice. AChE expression in serum, brain and muscle has been analyzed. Another AChE gene targeted mouse strain involving a region in the first intron, found to be critical for AChE expression in muscle cells [S. Camp, L. Zhang, M. Marquez, B

  17. Pesticides and brain cancer linked in orchard farmers of Kashmir

    Directory of Open Access Journals (Sweden)

    Bhat Abdul

    2010-12-01

    Full Text Available Background: The atmosphere of valley of Kashmir is ideal for fresh and dry fruit production. Millions of tons of pesticides, insecticides and fungicides (chemicals like chlorpyriphos, mancozeb, captan, dimethoate, phosalone, etc. are being used by the orchard farmers to spray the plants, fruits and the leaves every year. The increasing trend in the incidence of primary malignant brain tumors in orchard farmers of Kashmir is alarming. Aim: To determine the relationship between the patients of primary malignant brain tumors and their occupation. Materials and Methods: Retrospectively case files along with death certificates of 432 patients of primary malignant brain tumors and 457 controls (non-tumor neurologic diseases, admitted for treatment simultaneously over a period of 4 years from January 2005 to December 2008, to the Department of Neurosurgery, Sher-I-Kashmir Institute of Medical Sciences (SKIMS, Kashmir, were studied. Follow-up and family contact was established. The serum cholinesterase activity was measured by kinetic/DGKC calorimetric method and ethylenediaminetetraacetic acid (EDTA samples were sent to the laboratory. The results are expressed in U/l which is U/l×1000. The laboratory at SKIMS, Srinagar, and Dr Lal PathLabs at New Delhi used a reference range for serum cholinesterase as 3167-6333 U/l. Results: Analysis revealed that 90.04% (389 out of 432 patients were orchard-farm workers, orchard residents and orchard playing children exposed to the high levels of multiple types of neurotoxic and carcinogenic (chlorpyriphos, dimethoate, mancozeb and captan chemicals for more than 10-20 years. About 31.9% (124 out of 389 of these from both sexes were younger than 40 years beginning exposure at an early age and had higher (<6334 U/l serum cholinesterase (SCE levels. The 9.96% (43 out of 432 patients were not exposed to pesticides. On the other hand, only 119 patients out of 457 controls had recorded history of pesticide exposure and

  18. Amyloid-β peptides act as allosteric modulators of cholinergic signalling through formation of soluble BAβACs.

    Science.gov (United States)

    Kumar, Rajnish; Nordberg, Agneta; Darreh-Shori, Taher

    2016-01-01

    -β interacts readily in an apolipoprotein-facilitated manner with butyrylcholinesterase, forming highly stable and soluble complexes, BAβACs, which can be separated in their native states by sucrose density gradient technique. Enzymological analyses further evinced that amyloid-β concentration dependently increased the acetylcholine-hydrolyzing capacity of cholinesterases. In silico biomolecular analysis further deciphered the allosteric amino acid fingerprint of the amyloid-β-cholinesterase molecular interaction in formation of BAβACs. In the case of butyrylcholinesterase, the results indicated that amyloid-β interacts with a putative activation site at the mouth of its catalytic tunnel, most likely leading to increased acetylcholine influx into the catalytic site, and thereby increasing the intrinsic catalytic rate of butyrylcholinesterase. In conclusion, at least one of the native physiological functions of amyloid-β is allosteric modulation of the intrinsic catalytic efficiency of cholinesterases, and thereby regulation of synaptic and extrasynaptic cholinergic signalling. High apolipoprotein-E may pathologically alter the biodynamics of this amyloid-β function.

  19. Effects of Suanzaoren Decoction on cognitive function and cholinergic system in sleep deprived rats%酸枣仁汤对睡眠剥夺大鼠认知功能和胆碱能系统的影响

    Institute of Scientific and Technical Information of China (English)

    张斌; 张晓双; 白黎明

    2015-01-01

    目的:考察酸枣仁汤(SZRT )对睡眠剥夺大鼠认知功能和胆碱能系统的影响。方法雄性大鼠随机分为5组即大平台对照组、睡眠剥夺组及SZRT高、中、低剂量组,釆用改良多平台法建立大鼠睡眠剥夺模型、Y型电迷宫测定学习记忆、HE染色观察大鼠海马组织形态学、比色法测定海马Ach含量及AChE与ChA T的活性。结果与睡眠剥夺组相比,Y‐迷宫,SZRT 高剂量组错误次数减少,主动回避率增多。SZRT可减轻睡眠剥夺大鼠海马锥体细胞损伤,酸枣仁汤高、中剂量组可提高海马Ach含量,降低AChE活性,提高ChAT活性。结论 SZRT能改善睡眠剥夺大鼠所致的学习记忆下降,可能与保护胆碱能系统有关。%Objective To investigate the effects of Suanzaoren Decoction (SZRT ) on cognitive function and cholinergic system in sleep deprived rats .Methods Rats were randomly divided into 5 groups ,big platform control group ,sleep deprived group ,high ,medium and low dose group of SZRT .The rat model of sleep deprived was established with modified multiple platform method .Learning and memory of rats were tested by Y‐type maze .The histomorphology in hippocampal was observed by HE staining .The contents of acetylcholine ,activity of choline acetyltransferase and cholinesterase of rat hippocampal were determined by colorimetry .Results Compared with sleep deprived group ,high‐dose group can significantly decrease the error number and increase the active avoid‐ance .SZRT can reduce the hippocampal pyramidal cells injury .High and medium‐dose group can obviously increase the content of acetylcholine ,increase cholinesterase and decrease choline acetyltransferase activity in hippocampal .Conclusion SZRT can im‐prove the learning and memory in rats after sleep deprivation ,which probably was related to the protection of cholinergic system .

  20. Combotherapy and current concepts as well as future strategies for the treatment of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Fan LY

    2014-03-01

    Full Text Available Ling-Yun Fan,1,2 Ming-Jang Chiu2–4 1Department of Neurology, En Chu Kong Hospital, 2Department of Neurology, College of Medicine, Graduate Institute of Brain and Mind Sciences, 3Graduate Institute of Psychology, 4Graduate Institute of Biomedical Engineering and Bioinformatics, National Taiwan University Hospital, Taipei, Taiwan Abstract: It has been estimated that 35.6 million people globally had dementia in 2010 and the prevalence of dementia has been predicted to double every 20 years. Thus, 115.4 million people may be living with dementia in 2050. Alzheimer's disease (AD is the leading cause of dementia and is present in 60%–70% of people with dementia. Unfortunately, there are few approved drugs that can alleviate the cognitive or behavioral symptoms of AD dementia. Recent studies have revealed that pathophysiological changes related to AD occur decades before the appearance of clinical symptoms of dementia. This extended preclinical phase of AD provides a critical chance for disease-modifying agents to halt or delay the relentless process of AD. Although several trials targeting various pathological processes are ongoing, the examination of the combined use of different approaches to combat AD seems warranted. In this article, we will review current therapies, future strategies, and ongoing clinical trials for the treatment of AD with a special focus on combination therapies. Furthermore, preventive strategies for cognitively normal subjects in the presymptomatic stages of AD will also be addressed. In this review, we discuss current hypotheses of the disease process. In the decades since the approval of cholinesterase inhibitors, no new drug has ultimately demonstrated clear success in clinical trials. Given the difficulties that have been encountered in attempts to identify a single drug that can treat AD, we must pursue effective multi-target strategies, ie, combination therapies. The combination of cholinesterase inhibitors and

  1. Solitary living in Alzheimer’s disease over 3 years: association between cognitive and functional impairment and community-based services

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    Wattmo C

    2014-11-01

    Full Text Available Carina Wattmo, Elisabet Londos, Lennart Minthon Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Malmö, SwedenIntroduction: Many individuals with Alzheimer’s disease (AD live alone, and this figure is expected to increase. This study aimed to describe the cognitive and functional abilities of solitary-living AD patients, and the potential predictors of their usage of community-based services.Methods: This 3-year, prospective, multicenter study included 1,021 participants with mild-to-moderate AD (Mini-Mental State Examination score, 10–26 treated with a cholinesterase inhibitor in a routine clinical setting. At baseline and every 6 months, patients were assessed using cognitive, instrumental, and basic activities of daily living (ADL scales, and service utilization was recorded. Logistic regression models were used to predict the usage of community-based services.Results: At the start of cholinesterase inhibitor therapy (time of AD diagnosis, 355 individuals (35% were living alone. They were mainly female, older, had more impaired basic ADL capacity, and had a larger number of concomitant medications when compared with those living with family. Regarding the solitary-living patients, lower instrumental ADL (IADL ability and more medications were independent predictors of usage of home-help services, whereas more impaired IADL at baseline and faster IADL deterioration were predictors of nursing home admission. For those living with family, older age, lower basic ADL, and a greater number of medications predicted home-help services, whereas a larger amount of home help predicted nursing home placement. In addition, female sex was a risk factor for both the utilization of home-help services and nursing home placement. Cognitive ability was not significantly associated with the usage of community-based services.Conclusion: A large number of AD patients, predominantly females, live alone with severe

  2. Galantamine treatment in Alzheimer's disease: response and long-term outcome in a routine clinical setting

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    Wallin ÅK

    2011-09-01

    Full Text Available Åsa K Wallin, Carina Wattmo, Lennart MinthonClinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, SwedenBackground: In the absence of long-term, placebo-controlled studies of cholinesterase inhibitors in Alzheimer's disease (AD, analysis of the results of open-label trials becomes crucial. This study aimed to explore the three-year effects of galantamine treatment, as well as subgroups of response and adherence to treatment.Methods: Two hundred and eighty patients with a clinical diagnosis of AD were included in the prospective, open-label, multicenter Swedish Alzheimer Treatment Study, and received galantamine treatment. Efficacy measures included cognitive tests, ie, the Mini-Mental State Examination (MMSE and Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog, functional rating (Instrumental Activities of Daily Living Scale [IADL], and global rating. Assessments were carried out before treatment and every six months for a period of three years. K-means cluster analysis was used to identify response subgroups.Results: After three years of treatment, the mean change from baseline was 2.6 points in MMSE and 5.6 points in ADAS-cog scores. Globally, half of the patients improved or remained unchanged for two years. Cluster analysis identified two response clusters. Cluster 1 included patients with low ability in ADAS-cog and IADL scores at baseline. Even though the patients in cluster 1 were older and less educated, they responded better at six months compared with patients in cluster 2. Cluster 2 included patients with better ADAS-cog and IADL scores at baseline. Patients in cluster 2 had a higher frequency of the APOE ε4 allele, a slower pretreatment progression rate, and remained in the study longer than those in cluster 1. Three-year completers (n = 129, 46% received higher doses of galantamine compared with dropouts.Conclusion: AD patients who received long-term galantamine treatment were

  3. Real-world evaluation of compliance and preference in Alzheimer’s disease treatment

    Directory of Open Access Journals (Sweden)

    Pai MC

    2015-11-01

    Full Text Available Ming-Chyi Pai,1,2 Hany Aref,3 Nazem Bassil,4 Nagaendran Kandiah,5 Jae-Hong Lee,6 AV Srinivasan,7 Shelley diTommaso,8 Ozgur Yuksel81Division of Behavioral Neurology, Department of Neurology, 2Alzheimer’s Disease Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 3Department of Neurology, Ain Shams University, Cairo, Egypt; 4Saint Georges Hospital Medical Center, Balamand University, Beirut, Lebanon; 5Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore; 6Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, South Korea; 7The Tamil Nadu Dr MGR Medical University, Chennai, Tamil Nadu, India; 8Novartis Pharma AG, Postfach, Basel, SwitzerlandPurpose: Rivastigmine transdermal patch has shown higher caregiver satisfaction and greater preference than oral formulation in patients with Alzheimer’s disease. However, there is limited literature available related to caregiver preference or treatment compliance in real-world clinical settings. To date, no such data are available from Asia and the Middle East, which account for a sizeable proportion of patients with Alzheimer’s disease. The objective of this study was to evaluate treatment preference and compliance with oral and transdermal medications in daily clinical practice in an ethnically diverse patient population from Asia and the Middle East with mild-to-moderate Alzheimer’s disease.Patients and methods: RECAP (Real-world Evaluation of Compliance And Preference in the treatment of Alzheimer’s disease was a 24-week, multicenter, prospective, noninterventional study. Two treatment cohorts were observed during the study: oral (cholinesterase inhibitors or memantine and transdermal (rivastigmine patch. Caregiver preference, physician preference, and patient compliance were evaluated at week 24.Results: A total of 978 of 1

  4. Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation.

    Science.gov (United States)

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Yan, Yu-Hui; Li, Shao-Heng; Wang, Yue; Meng, Ya-Kun; Yang, Jing-Xian; Kang, Ting-Guo

    2016-09-01

    Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-κB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-α and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKα and IKKβ) expression and inhibit NF-κB signaling pathway activity; moreover, the increased miRNA-199a suppresses

  5. Retrospective ecotoxicological data and current information needs for terrestrial vertebrates residing in coastal habitat of the United States

    Science.gov (United States)

    Rattner, B.A.; Eisenreich, K.M.; Golden, N.H.; McKernan, M.A.; Hothem, R.L.; Custer, T.W.

    2005-01-01

    The Contaminant Exposure and Effects?Terrestrial Vertebrates (CEE-TV) database was developed to conduct simple searches for ecotoxicological information, examine exposure trends, and identify significant data gaps. The CEE-TV database contains 16,696 data records on free-ranging amphibians, reptiles, birds, and mammals residing in estuarine and coastal habitats of the Atlantic, Gulf, and Pacific coasts, Alaska, Hawaii, and the Great Lakes. Information in the database was derived from over 1800 source documents, representing 483 unique species (about 252,000 individuals), with sample collection dates spanning from 1884 to 2003. The majority of the records contain exposure data (generally contaminant concentrations) on a limited number (n=209) of chlorinated and brominated compounds, cholinesterase-inhibiting pesticides, economic poisons, metals, and petroleum hydrocarbons, whereas only 9.3% of the records contain biomarker or bioindicator effects data. Temporal examination of exposure data provides evidence of declining concentrations of certain organochlorine pesticides in some avian species (e.g., ospreys, Pandion haliaetus), and an apparent increase in the detection and possibly the incidence of avian die-offs related to cholinesterase-inhibiting pesticides. To identify spatial data gaps, 11,360 database records with specific sampling locations were combined with the boundaries of coastal watersheds, and National Wildlife Refuge and National Park units. Terrestrial vertebrate ecotoxicological data were lacking in 41.9% of 464 coastal watersheds in the continental United States. Recent (1990?2003) terrestrial vertebrate contaminant exposure or effects data were available for only about half of the National Wildlife Refuge and National Park units in the geographic area encompassed by the database. When these data gaps were overlaid on watersheds exhibiting serious water quality problems and/or high vulnerability to pollution, 72 coastal watersheds, and 76 National

  6. Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation.

    Science.gov (United States)

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Yan, Yu-Hui; Li, Shao-Heng; Wang, Yue; Meng, Ya-Kun; Yang, Jing-Xian; Kang, Ting-Guo

    2016-09-01

    Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-κB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-α and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKα and IKKβ) expression and inhibit NF-κB signaling pathway activity; moreover, the increased miRNA-199a suppresses

  7. Acute toxicity of high doses of the glycoalkaloids, alpha-solanine and alpha-chaconine, in the Syrian Golden hamster.

    Science.gov (United States)

    Langkilde, Søren; Schrøder, Malene; Stewart, Derek; Meyer, Otto; Conner, Sean; Davies, Howard; Poulsen, Morten

    2008-09-24

    Sprouted, stressed, or spoiled potato tubers have reportedly led to human acute intoxication, coma, and death when consumed in high amounts. These effects have been attributed to glycoalkaloids (GAs), primarily alpha-solanine and alpha-chaconine, naturally present in all potatoes. The level of GAs in potato tubers has previously been shown to increase substantially as a result of improper handling and postharvest storage. A short-term study was performed to investigate the dose-response profile of alpha-solanine and alpha-chaconine alone or in combination, administered daily by oral gavage to Syrian Golden hamsters. Daily doses of 100 mg of alpha-solanine [kg body weight (BW)] (-1) induced death in two of four hamsters within 4 days, when administered by gavage to female Syrian hamsters. Doses of 100 mg of alpha-chaconine alone or alpha-solanine and alpha-chaconine combined in a ratio of 1:2.5, in doses of 75 or 100 mg (kg BW) (-1), induced death in one of four hamsters within the same period. Animals dosed with alpha-solanine alone or in combination with alpha-chaconine suffered from fluid-filled and dilated small intestines. The GA administration had no effect on acetyl cholinesterase (AChE) or butyryl cholinesterase (BuChE) activity in plasma or brain. Liquid chromatography-mass spectrometry-based metabolomics showed that there was a specific accumulation of alpha-chaconine in the liver tissues. In addition, metabolomics gave direct evidence of glycolytic metabolism of the GA with the beta 1, beta 2, and gamma-GAs detected in the urine and, to a lesser extent, the feces. Doses from 75 mg (kg BW) (-1) of alpha-chaconine, alpha-solanine, or the two compounds combined were potentially lethal within 4-5 days in the Syrian Golden hamster. However, the cause of death in these studies could not be established. No synergistic effects of alpha-solanine combined with alpha-chaconine were evident.

  8. Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Arne Dettmer; Susanne Krusche; Sonja Merkesdal; Michael Galanski; Michael P Manns; Joerg S Bleck; Timm D Kirchhoff; Michael Gebel; Lars Zender; Nisar P Malek; Bernhard Panning; Ajay Chavan; Herbert Rosenthal; Stefan Kubicka

    2006-01-01

    AIM: To evaluate the treatment effect of percutaneous ethanol injection (PEI) for patients with advanced,non-resectable HCC compared with combination of transarterial chemoembolisation (TACE) and repeated single-session PEI, repeated single-session PEI alone,repeated TACE alone, or best supportive care.METHODS: All patients who received PEI treatment during the study period were included and stratified to one of the following treatment modalities according to physical status and tumor extent: combination of TACE and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. Prognostic value of clinical parameters including Okuda-classification, presence of portal vein thrombosis,presence of ascites, number of tumors, maximum tumor diameter, and serum cholinesterase (CHE), as well as Child-Pugh stage, α-fetoprotein (AFP), fever, incidence of complications were assessed and compared between the groups. Survival was determined using Kaplan-Meier and multivariate regression analyses.RESULTS: The 1- and 3-year survival of all patients was 73% and 47%. In the subgroup analyses, the combination of TACE and PEI (1) was associated with a longer survival (1-, 3-, 5-year survival: 90%, 52%,and 43%) compared to PEI treatment alone (2) (1-, 3-,5-year survival:65%, 50%, and 37%). Secondary PEI after initial stratification to TACE (3) yielded comparable results (1-, 3-, 5-year survival: 91%, 40%, and 30%)while PEI after stratification to best supportive care (4)was associated with decreased survival (1-, 3-, 5-year survival: 50%, 23%, 12%). Apart from the chosen treatment modalities, predictors for better survival were tumor number (n<5), tumor size (<5cm), no ascites before PEI, and stable serum cholinesterase after PEI (P<0.05). The mortality within 2 wk after PEI was 2.8%(n=3). There were 24 (8.9%) major complications after PEI including segmental liver infarction, focal liver necrosis, and liver abscess. All

  9. Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jing [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States); Parsons, Loren [Committee on Neurobiology of Affective Disorders, The Scripps Research Institute, La Jolla, CA (United States); Pope, Carey, E-mail: carey.pope@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States)

    2013-11-01

    Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were

  10. Antiamnesic potentiality of Argyreia speciosa (Burm.f Boj. in mice

    Directory of Open Access Journals (Sweden)

    Habbu P

    2010-01-01

    Full Text Available Several ′rasayana′ herbs that are enlisted in Indian system of medicine have been in use for the treatment of age-related neurodegenerative disorders including Alzheimer′s disease (AD. Roots of Argyreia speciosa are used in several Ayurvedic preparations as brain tonic and nervine tonic. The present work was undertaken to justify the traditional claim of the plant as nootropic and antiamnesic agent in mice. The ethyl acetate and ethanolic fractions (EtAS of roots were selected for the study. Exteroceptive behavioural models such as elevated plus maze and Water maze were used to assess the short-term memory, whereas, scopolamine and natural ageing- induced amnesia served as interoceptive models. The whole brain acetyl cholinesterase activity was measured to assess the effect of A. speciosa on the central cholinergic system. Scopolamine (0.4 mg/kg, i.p. increased the transfer latency significantly ( P< 0.01 in young mice on the first and second day as compared to control indicating the impairment of memory. Pretreatment with EAAS (100 and 200 mg/kg, p.o. significantly ( P< 0.01 attenuated scopolamine and ageing-induced amnesia. Escape latency time was recorded in the water maze model as an index of acquisition, and trials were conducted for 4 days. The mean time spent in target quadrant (TSTQ during retrieval trial on fifth day was taken as the index of retrieval (memory. EAAS (100 and 200 mg/kg, p.o. administered before the training trial (from day 1 to day 4, significantly ( P< 0.01 attenuated scopolamine and ageing-induced decrease in TSTQ during the retrieval test on the fifth day. EAAS (100 and 200 mg/kg, p.o. significantly produced reduction in whole brain acetyl cholinesterase (AChE activity of both young and aged mice thus exhibiting anti-AChE activity in whole brain homogenate compared to Piracetam, scopolamine and control groups of mice. The results indicate that A. speciosa has significant nootropic and antiamnesic activity

  11. Anticholinesterase effect of eserine (physostigmine in fish and crustacean species

    Directory of Open Access Journals (Sweden)

    José M. Monserrat

    2001-03-01

    Full Text Available The kinetic characteristic (Km of cholinesterase from the crab Chasmagnathus granulata, the shrimp Farfantepenaeus paulensis and the fish Odontesthes bonaeriensis were compared and correlated with the anticholinesterasic effect of eserine (physostigmine. For the crustaceans, the estimated Km values were about 5-8 times higher than that estimated for the fish (0.04 mM. In the crab and the shrimp, the concentration of eserine which inhibited 50% of cholinesterase activity (IC50 was estimated as 5.33x10-4 and 4.33x10-4 mM, respectively. In both cases, it was significantly higher (P As caraterísticas cinéticas (Km de colinesterases do caranguejo Chasmagnathus granulata, o camarão Farfantepenaeus paulensis e o peixe Odontesthes bonaeriensis foram comparadas e correlacionadas com os efeitos anticolinesterásicos da eserina (fisostigmina. Nos crustáceos, o valores estimados de Km foram aproximadamente 5-8 vezes maiores do que aquele estimado para a espécie de peixe (0.04 mM. No caranguejo e camarão, a concentração de eserina que inibiu 50% da atividade colinesterásica (CI50 foi estimada em 5.33x10-4 e 4.33x10-4 mM, respectivamente. Estes valores foram significativamente maiores (P < 0.05 que aquele estimado para as larvas de peixes (7.43x10-5 mM. Um valor de Km mais elevado poderia refletir uma menor afinidade da colinesterase pelo seu substrato natural, acetilcolina, ou análogos tais como inseticidas carbamatos e fosforados. Se a CI50 para eserina é considerada como um índice da susceptibilidade da enzima a inibição por inseticidas, logo a colinesterase de larvas de peixes poderiam ser uma ferramenta mais útil no monitoramento de inseticidas do que aquelas das espécies de crustáceos.

  12. Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

    Energy Technology Data Exchange (ETDEWEB)

    Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey, E-mail: carey.pope@okstate.edu

    2011-11-15

    Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and

  13. Comparison of four prognostic models and a new Logistic regression model to predict short-term prognosis of acute-on-chronic hepatitis B liver failure

    Institute of Scientific and Technical Information of China (English)

    HE Wei-ping; HU Jin-hua; ZHAO Jun; TONG Jing-jing; DING Jin-biao; LIN Fang; WANG Hui-fen

    2012-01-01

    Background Acute-on-chronic hepatitis B liver failure (ACLF-HBV) is a clinically severe disease associated with major life-threatening complications including hepatic encephalopathy and hepatorenal syndrome.The aim of this study was to evaluate the short-term prognostic predictability of the model for end-stage liver disease (MELD),MELD-based indices,and their dynamic changes in patients with ACLF-HBV,and to establish a new model for predicting the prognosis of ACLF-HBV.Methods A total of 172 patients with ACLF-HBV who stayed in the hospital for more than 2 weeks were retrospectively recruited.The predictive accuracy of MELD,MELD-based indices,and their dynamic change (△) were compared using the area under the receiver operating characteristic curve method.The associations between mortality and patient characteristics were studied by univariate and multivariate analyses.Results The 3-month mortality was 43.6%.The largest concordance (c) statistic predicting 3-month mortality was the MELD score at the end of 2 weeks of admission (0.8),followed by the MELD:sodium ratio (MESO) (0.796) and integrated MELD (iMELD) (0.758) scores,△MELD (0.752),△MESO (0.729),and MELD plus sodium (MELD-Na) (0.728) scores.In multivariate Logistic regression analysis,the independent factors predicting prognosis were hepatic encephalopathy (OR=-3.466),serum creatinine,international normalized ratio (INR),and total bilirubin at the end of 2 weeks of admission (OR=10.302,6.063,5.208,respectively),and cholinesterase on admission (OR=0.255).This regression model had a greater prognostic value (c=0.85,95% Cl 0.791-0.909) compared to the MELD score at the end of 2 weeks of admission (Z=4.9851,P=-0.0256).Conclusions MELD score at the end of 2 weeks of admission is a useful predictor for 3-month mortality in ACLF-HBV patients.Hepatic encephalopathy,serum creatinine,international normalized ratio,and total bilirubin at the end of 2 weeks of admission and cholinesterase on admission are

  14. 有机磷中毒合并呼吸衰竭患者继发肺部感染的相关危险因素分析%The analysis of associated risk factor on patients with organophosphorus poisoning combine with respiratory failure secondary pulmonary infection

    Institute of Scientific and Technical Information of China (English)

    李奕冰; 张国秀; 李洁; 赵鑫

    2014-01-01

    Objective To explore the associated risk factors on patients with organophosphorus poisoning combine with respiratory failure secondary pulmonary infection.Methods Two hundred and twenty-four clinical data of organophosphorus poisoning combine with respiratory failure were collected from January 2009 to May 2013.Retrospectively analyzed the situation of pulmonary infection and Logistic regression model were used to analyzed the relative risk of organophosphorus poisoning combine with respiratory failure secondary pulmonary infection.Results The secondary pulmonary infection rate of organophosphorus poisoning combine with respiratory failure was 68.75% (154/224).Logistic regression analysis showed that combined with aspiration,hand hygiene,breathing machine,the decrease of cholinesterase activity were the relative risk factors (P < 0.05).Conclusions The secondary pulmonary infection rate of organophosphorus poisoning combine with respiratory failure is higher.Combined with aspiration,hand hygiene,breathing machine,the decrease of cholinesterase activity may be the relative risk factors.%目的 探讨有机磷中毒合并呼吸衰竭患者继发肺部感染的相关危险因素.方法 收集2009年1月至2013年5月收治的有机磷中毒合并呼吸衰竭患者224例临床资料,回顾性分析继发肺部感染情况并运用Logistic回归模型探讨其相关危险因素.结果 有机磷中毒合并呼吸衰竭患者继发肺部感染率为68.75%(154/224),Logistic回归分析结果显示合并误吸、手卫生、使用呼吸机、胆碱酯酶活性的降低可能是其发生的相关危险因素,差异有统计学意义(P<0.05).结论 有机磷中毒合并呼吸衰竭患者继发肺部感染率高,合并误吸、手卫生、呼吸机的使用、胆碱酯酶活性的降低为其相关危险因素.

  15. Apathy: a practical guide for neurologists.

    Science.gov (United States)

    Stanton, Biba R; Carson, Alan

    2016-02-01

    Apathy is an under-recognised and underestimated problem for people with chronic neurological disorders. Despite being common and disabling, it is seldom volunteered as a symptom by patients or even their caregivers. Yet apathy undoubtedly has an important impact on caregiver stress, functional disability and quality of life. A detailed clinical assessment can distinguish apathy from depression and allow clinicians to make practical suggestions to reduce the impact of symptoms on individual patients and their families. Pharmacological approaches to treatment include cholinesterase inhibitors, dopamine agonists and stimulants. CASE 1A 66-year-old man with progressive supranuclear palsy returned to clinic for review. His wife was upset and finding it difficult to cope. She described him as 'completely lazy', as he just sat in his chair all day watching television, even though he could still do things for himself. She felt that he could not be bothered to speak to her anymore because he was 'obsessed with TV'. He did not seem to engage with the visits to the grandchildren that she arranged. He said that he felt fine apart from the problems with his walking.The neurologist was confident that the patient was not depressed, and that the wife's concerns reflected the apathy that is often very pronounced in progressive supranuclear palsy. By explaining to the man's wife that these problems were due to his disease, their relationship improved and she felt more able to cope with caring for him. CASE 2A 75-year-old man attended clinic with his wife. She had worried about him for over a year, as he had become increasingly withdrawn. He used to enjoy going to the local pub but now stayed at home all day. He seemed less concerned about his personal appearance, about which he used to be meticulous. More recently, she had noticed that he had become forgetful. On examination, he had a mild episodic memory deficit but no impairments in other domains.He was diagnosed with mild

  16. Characteristics of patients with Alzheimer’s disease who switch to rivastigmine transdermal patches in routine clinical practice

    Directory of Open Access Journals (Sweden)

    López-Pousa S

    2013-01-01

    Full Text Available Secundino López-Pousa,1 Francisco Javier Arranz21Unit for Assessment of Memory and Dementia, Institut d’Assistència Sanitària de Girona, Salt, Girona, 2CNS Area, Medical Department and Health Innovation, Esteve, Barcelona, SpainBackground: The aim of this study was to assess the sociodemographic and clinical characteristics of patients with Alzheimer’s disease who switched from any oral cholinesterase inhibitor to rivastigmine patches.Methods: An observational, retrospective, multicenter study was conducted in patients with a diagnosis of Alzheimer’s disease who had switched to rivastigmine patches within the previous year in the routine clinical practice of 150 neurologists. Sociodemographic, clinical, and therapeutic data were collected in one office visit. Stepwise logistic regression models were used to find associations.Results: Data were obtained from a total of 1022 patients and their caregivers, and showed a mean age of 78.4 ± 6.62 years, 62.61% being women, and mostly having a family caregiver. The switch to rivastigmine patches was mainly instigated on the initiative of the physician (82.39% or on request of the caregiver (21.23% or patient (10.37%. Reasons for the switch included improving ease of administration (56.65%, tolerability (36.79%, efficacy (31.60%, and adherence (18.59%. Prior treatment with oral rivastigmine versus donepezil or galantamine increased the probability of switching in order to improve ease of administration (odds ratio, oral rivastigmine versus donepezil 4.20, P < 0.0001; odds ratio, oral rivastigmine versus galantamine 3.55, P < 0.0001. Conversely, previous treatment with donepezil or galantamine produced an approximate four-fold increase in the odds of switching due to lack of efficacy. A higher level of education as well as more concomitant diseases increased the probability of switching because of intolerance.Conclusion: Improved ease of administration was the main reason for switching to

  17. A comprehensive evaluation of the efficacy of leading oxime therapies in guinea pigs exposed to organophosphorus chemical warfare agents or pesticides

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelm, Christina M., E-mail: wilhelmc@battelle.org [Battelle, 505 King Avenue, JM-7, Columbus, OH 43201-2693 (United States); Snider, Thomas H., E-mail: snidert@battelle.org [Battelle, 505 King Avenue, JM-7, Columbus, OH 43201-2693 (United States); Babin, Michael C., E-mail: babinm@battelle.org [Battelle, 505 King Avenue, JM-7, Columbus, OH 43201-2693 (United States); Jett, David A., E-mail: jettd@ninds.nih.gov [National Institutes of Health/National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892 (United States); Platoff, Gennady E., E-mail: platoffg@niaid.nih.gov [National Institutes of Health/National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892 (United States); Yeung, David T., E-mail: dy70v@nih.gov [National Institutes of Health/National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892 (United States)

    2014-12-15

    The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection at the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl{sub 2}, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 h post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman's method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes. - Highlights: • First comprehensive evaluation of leading AChE oxime reactivators • All oximes are compared against current U.S. therapy 2-PAM Cl. • Relative therapeutic oxime efficacies against OP CWNA and pesticides • Contribution to more effective

  18. Poisoning of raptors with organophosphorus and carbamate pesticides with emphasis on Canada, U.S. and U.K.

    Science.gov (United States)

    Mineau, P.; Fletcher, M.R.; Glaser, L.C.; Thomas, N.J.; Brassard, C.; Wilson, L.K.; Elliott, J.E.; Lyon, L.A.; Henny, C.J.; Bollinger, T.; Porter, S.L.

    1999-01-01

    We reviewed cases of raptor mortality resulting from cholinesterase-inhibiting pesticides. We compiled records from the U.S., U.K. and Canada for the period 1985-95 (520 incidents) and surveyed the relevant literature to identify the main routes of exposure and those products that led to the greatest number of poisoning cases. A high proportion of cases in the U.K. resulted from abusive uses of pesticides (willful poisoning). The proportion was smaller in North America where problems with labeled uses of pesticides were as frequent as abuse cases. Poisoning resulting from labeled use was possible with a large number of granular pesticides and some seed treatments through secondary poisoning or through the ingestion of contaminated invertebrates, notably earthworms. With the more toxic products, residue levels in freshly-sprayed insects were high enough to cause mortality. The use of organophosphorus products as avicides and for the topical treatment of livestock appeared to be common routes of intoxication. The use of insecticides in dormant oils also gave rise to exposure that can be lethal or which can debilitate birds and increase their vulnerability. A few pesticides of high toxicity were responsible for the bulk of poisoning cases. Based on limited information, raptors appeared to be more sensitive than other bird species to organophosphorus and carbamate pesticides. Some of the more significant risk factors that resulted in raptor poisonings were: insectivory and vermivory; opportunistic taking of debilitated prey; scavenging, especially if the gastrointestinal tracts are consumed; presence in agricultural areas; perceived status as pest species; and flocking or other gregarious behavior at some part of their life cycle. Lethal or sublethal poisoning should always be considered in the diagnosis of dead or debilitated raptors even when another diagnosis (e.g., electrocution, car or building strike) is apparent. Many cases of poisoning are not currently

  19. Deprescribing: An Application to Medication Management in Older Adults.

    Science.gov (United States)

    Bemben, Nina M

    2016-07-01

    Polypharmacy has been found to have potentially negative consequences for patients due to use of potentially inappropriate medications, as well as increased risk of drug interactions and adverse effects. Deprescribing has been proposed as a method of improving medication use throughout a patient's course of care. This article reviews the process of deprescribing and applies the process to medication classes commonly encountered by clinical pharmacists. This review of therapeutics included studies identified through a PubMed search and by review of the reference list of included studies. Relevant studies known to the author were also included. Previous studies have identified several classes of medications as a high priority for construction of evidence-based deprescribing guidelines. In the absence of currently available evidence-based clinical practice guidelines, this articles reviews applicable evidence and applies the deprescribing process to three high-priority medication classes: statins, cholinesterase inhibitors and bisphosphonates. Available evidence can be used to apply the deprescribing process to preventive medications for chronic diseases commonly encountered by clinical pharmacists. PMID:27263530

  20. Effects of oral tetrachlorvinphos fly control (Equitrol) administration in horses: physiological and behavioural findings.

    Science.gov (United States)

    Berger, J; Valdez, S; Puschner, B; Leutenegger, C M; Gardner, I A; Madigan, J E

    2008-01-01

    Highly reactive horses may pose risks to humans involved in equestrian activities. Among the factors that may affect horses' reactivity to external stimuli are pesticides used for fly control in equine facilities. The organophosphorus (OP) insecticide tetrachlorvinphos (TCVP) is used as a feed-through larvicide to prevent completion of the fly larval life cycle in horse manure. TCVP exerts its effect by inhibiting the enzyme cholinesterase (ChE) leading to the accumulation of the neurotransmitter acetylcholine (AChE) in synapses of the central and peripheral nervous systems. The aim of the present study was to investigate alterations of whole-blood ChE levels associated with feeding a commercially available product (Equitrol, Farnam Companies, Inc.) to horses for fly control. A second aim was to report neurological, physiological and behavioural findings in addition to profiles of selected immune markers (IFN-gamma, IL-12p40 and COX-2) and serum thyroid hormones during and after a 30-day treatment period of TCVP feeding. The results indicated significant decreases in whole-blood ChE activity and concomitant behavioural alterations, manifested as increased reactivity and decreased controllability in treated horses. No changes were detected in physiological or neurological parameters, immune markers or thyroid hormones in treated (n=6) or control (n=4) horses during the course of the study.