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Sample records for standard carbamate drugs

  1. Organic carbamates in drug design and medicinal chemistry.

    Science.gov (United States)

    Ghosh, Arun K; Brindisi, Margherita

    2015-04-09

    The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many derivatives are specifically designed to make drug-target interactions through their carbamate moiety. In this Perspective, we present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of carbamates, and recent applications of carbamates in drug design and medicinal chemistry.

  2. 76 FR 34200 - Land Disposal Restrictions: Revision of the Treatment Standards for Carbamate Wastes

    Science.gov (United States)

    2011-06-13

    ... 2050-AG65 Land Disposal Restrictions: Revision of the Treatment Standards for Carbamate Wastes AGENCY... wastes from the production of carbamates and carbamate commercial chemical products, off-specification or... or intended to be discarded. Currently, under the LDR program, most carbamate wastes must be treated...

  3. Model for High-Throughput Screening of Multitarget Drugs in Chemical Neurosciences: Synthesis, Assay, and Theoretic Study of Rasagiline Carbamates

    Science.gov (United States)

    2013-01-01

    The disappointing results obtained in recent clinical trials renew the interest in experimental/computational techniques for the discovery of neuroprotective drugs. In this context, multitarget or multiplexing QSAR models (mt-QSAR/mx-QSAR) may help to predict neurotoxicity/neuroprotective effects of drugs in multiple assays, on drug targets, and in model organisms. In this work, we study a data set downloaded from CHEMBL; each data point (>8000) contains the values of one out of 37 possible measures of activity, 493 assays, 169 molecular or cellular targets, and 11 different organisms (including human) for a given compound. In this work, we introduce the first mx-QSAR model for neurotoxicity/neuroprotective effects of drugs based on the MARCH-INSIDE (MI) method. First, we used MI to calculate the stochastic spectral moments (structural descriptors) of all compounds. Next, we found a model that classified correctly 2955 out of 3548 total cases in the training and validation series with Accuracy, Sensitivity, and Specificity values > 80%. The model also showed excellent results in Computational-Chemistry simulations of High-Throughput Screening (CCHTS) experiments, with accuracy = 90.6% for 4671 positive cases. Next, we reported the synthesis, characterization, and experimental assays of new rasagiline derivatives. We carried out three different experimental tests: assay (1) in the absence of neurotoxic agents, assay (2) in the presence of glutamate, and assay (3) in the presence of H2O2. Compounds 11 with 27.4%, 8 with 11.6%, and 9 with 15.4% showed the highest neuroprotective effects in assays (1), (2), and (3), respectively. After that, we used the mx-QSAR model to carry out a CCHTS of the new compounds in >400 unique pharmacological tests not carried out experimentally. Consequently, this model may become a promising auxiliary tool for the discovery of new drugs for the treatment of neurodegenerative diseases. PMID:23855599

  4. Qualitative structure-metabolism relationships in the hydrolysis of carbamates.

    Science.gov (United States)

    Vacondio, Federica; Silva, Claudia; Mor, Marco; Testa, Bernard

    2010-11-01

    The aims of this review were 1) to compile a large number of reliable literature data on the metabolic hydrolysis of medicinal carbamates and 2) to extract from such data a qualitative relation between molecular structure and lability to metabolic hydrolysis. The compounds were classified according to the nature of their substituents (R³OCONR¹R²), and a metabolic lability score was calculated for each class. A trend emerged, such that the metabolic lability of carbamates decreased (i.e., their metabolic stability increased), in the following series: Aryl-OCO-NHAlkyl > Alkyl-OCO-NHAlkyl ~ Alkyl-OCO-N(Alkyl)₂ ≥ Alkyl-OCO-N(endocyclic) ≥ Aryl-OCO-N(Alkyl)₂ ~ Aryl-OCO-N(endocyclic) ≥ Alkyl-OCO-NHAryl ~ Alkyl-OCO-NHAcyl > Alkyl-OCO-NH₂ > Cyclic carbamates. This trend should prove useful in the design of carbamates as drugs or prodrugs.

  5. Standardization Study of Antifertility Drug - Pippalyadiyoga

    Directory of Open Access Journals (Sweden)

    D. Shaila

    2005-01-01

    Full Text Available The present paper deals with the standardization study of pippalyadiyoga powder. It is used as a long acting contraceptive. The standardization of compound drug has been achieved by physico-chemical analysis and high performance liquid chromatography (HPLC fingerprint studies. Quantitative evaluation of borax in pippalyadiyoga showed 19.08% as sodium borate. RP-HPLC was performed using methanol and water as mobile phase. The detection and quantification was performed at a wavelength of 345 nm. Linearity of detector response for piperine was between the concentrations 0.005% to 0.1%. The correlation coefficient obtained for the linearity was 0.998. The recovery value of standard piperine was 99.4%. Low value of standard deviation and coefficient of variation are indicative of high precision of the method. Quantitative evaluation of piperine in pippalyadiyoga was found to be 0.339%.

  6. Amino Acid Carbamates As Prodrugs Of Resveratrol.

    Science.gov (United States)

    Mattarei, Andrea; Azzolini, Michele; La Spina, Martina; Zoratti, Mario; Paradisi, Cristina; Biasutto, Lucia

    2015-10-14

    Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene), a plant polyphenol, has important drug-like properties, but its pharmacological exploitation in vivo is hindered by its rapid transformation via phase II conjugative metabolism. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, stability and in vivo pharmacokinetic behaviour of prodrugs of resveratrol in which the OH groups are engaged in an N-monosubstituted carbamate ester (-OC(O)NHR) linkage with a natural amino acid (Leu, Ile, Phe, Thr) to prevent conjugation and modulate the physicochemical properties of the molecule. We also report a convenient, high-yield protocol to obtain derivatives of this type. The new carbamate ester derivatives are stable at pH 1, while they undergo slow hydrolysis at physiological pH and hydrolyse with kinetics suitable for use in prodrugs in whole blood. After administration to rats by oral gavage the isoleucine-containing prodrug was significantly absorbed, and was present in the bloodstream as non-metabolized unaltered or partially deprotected species, demonstrating effective shielding from first-pass metabolism. We conclude that prodrugs based on the N-monosubstituted carbamate ester bond have the appropriate stability profile for the systemic delivery of phenolic compounds.

  7. The survival times of malaria-infected mice are prolonged more by several new two-carbon-linked artemisinin-derived dimer carbamates than by the trioxane antimalarial drug artemether.

    Science.gov (United States)

    Conyers, Ryan C; Mazzone, Jennifer R; Siegler, Maxime A; Tripathi, Abhai K; Sullivan, David J; Mott, Bryan T; Posner, Gary H

    2014-03-01

    Sixteen new artemisinin-derived 2-carbon-linked trioxane dimers were prepared to study chemical structure/antimalarial activity relationships (SAR). Administering a very low single oral dose of only 5mg/kg of dimer secondary alcohol 6a or 6b plus 15 mg/kg of mefloquine hydrochloride prolonged the lives of Plasmodium berghei-infected mice to an average of 25 days after infection. This ACT chemotherapy result is of high medicinal significance because the antimalarial efficacy of the popular trioxane drug artemether (2) plus mefloquine under the same conditions was significantly lower (only 20 day average survival). NH-aryl carbamate derivatives 7e, 7i, and 7j of 2-carbon-linked dimer alcohol 6b also significantly outperformed artemether (2) in prolonging the survival times (25-27 days) of malaria-infected mice. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Suzuki–Miyaura Coupling of Aryl Carbamates, Carbonates, and Sulfamates

    Science.gov (United States)

    Quasdorf, Kyle W.; Riener, Michelle; Petrova, Krastina V.; Garg, Neil K.

    2009-01-01

    The first Suzuki–Miyaura cross-coupling of carbamates, carbonates, and sulfamates is described. The method presented provides a powerful means to use simple derivatives of phenol as precursors to polysubstituted aromatic compounds, as exemplified by a concise synthesis of the anti-inflammatory drug flurbiprofen. PMID:19928764

  9. Considerations on ultra trace analysis of carbamates in water samples.

    Science.gov (United States)

    Nogueira, J M F; Sandra, Tom; Sandra, Pat

    2003-05-09

    A new routine method for the ultra trace analysis of carbamates in water samples is presented, using solid-phase extraction followed by high-performance liquid chromatography coupled to atmospheric pressure electrospray ionisation mass spectrometry (SPE-LC-ESI-MS). Instrumental conditions of LC-ESI-MS in the selected ion monitoring (SIM) mode, showed excellent linear response for the six N-methyl carbamates studied (aldicarb, carbaryl, carbofuran, methomyl, oxamyl and pirimicarb) in the range from 1 to 50 microg/l and a precision having a relative standard deviation below 7.8% was achieved. Instrumental limits of detection of 0.10 microg/l were found for these carbamates, with the exception of methomyl for which 0.50 microg/l was measured. The SPE assays were shown to be easy, fast, very sensitive, requiring a low volume (50 ml) of water sample. For laboratory-spiked water samples having 0.03 and 0.30 microg/l of individual N-methyl carbamates, higher selectivities were achieved in cartridges having octadecylsilica, polystyrene-divinylbenzene and N-vinylpyrrolidane-divinylbenzene as solid phases, for which reasonable average recoveries were obtained. Ten replicates using octadecylsilica SPE cartridges, showed average recoveries between 73.7 and 92.6% with a relative standard deviation lower than 14.7%. The present methodology evidences good robustness, accuracy and precision for monitoring of N-methyl carbamates in water samples, and is shown to be a suitable alternative to replace the currently dedicated analytical systems. The limits of detection for the analysis of N-methyl carbamates in water samples reached in the present methodology (0.5 to 3 ng/l), clearly cover the maximum concentration admissible for pesticides, established by the European Union directive on water quality.

  10. Toxicity of carbamates to insects

    Science.gov (United States)

    Weiden, M. H. J.

    1971-01-01

    The discovery of effective insecticidal materials among the carbamic-acid esters is surveyed to provide insight into some of the factors leading to the development of new control agents. Problems associated with attempts to correlate insecticidal activity with acetylcholinesterase inhibition are outlined. The intoxication syndrome is described and its toxicological significance discussed. Structure—activity profiles are presented for selected compounds to illustrate the biological effects produced by structural variations. Categories of carbamates in which no significant insecticidal activity has been discovered are also listed. PMID:4938022

  11. Nanomaterials potentiating standard chemotherapy drugs' effect

    Science.gov (United States)

    Kazantsev, S. O.; Korovin, M. S.

    2017-09-01

    Application of antitumor chemotherapeutic drugs is hindered by a number of barriers, multidrug resistance that makes effective drug deposition inside cancer cells difficult is among them. Recent research shows that potential efficiency of anticancer drugs can be increased with nanoparticles. This review is devoted to the application of nanoparticles for cancer treatment. Various types of nanoparticles currently used in medicine are reviewed. The nanoparticles that have been used for cancer therapy and targeted drug delivery to damaged sites of organism are described. Also, the possibility of nanoparticles application for cancer diagnosis that could help early detection of tumors is discussed. Our investigations of antitumor activity of low-dimensional nanostructures based on aluminum oxides and hydroxides are briefly reviewed.

  12. Evaluation of NHS carbamates as a potent and selective class of endocannabinoid hydrolase inhibitors.

    Science.gov (United States)

    Niphakis, Micah J; Cognetta, Armand B; Chang, Jae Won; Buczynski, Matthew W; Parsons, Loren H; Byrne, Frederika; Burston, James J; Chapman, Victoria; Cravatt, Benjamin F

    2013-09-18

    Monoacylglycerol lipase (MAGL) is a principal metabolic enzyme responsible for hydrolyzing the endogenous cannabinoid (endocannabinoid) 2-arachidonoylglycerol (2-AG). Selective inhibitors of MAGL offer valuable probes to further understand the enzyme's function in biological systems and may lead to drugs for treating a variety of diseases, including psychiatric disorders, neuroinflammation, and pain. N-Hydroxysuccinimidyl (NHS) carbamates have recently been identified as a promising class of serine hydrolase inhibitors that shows minimal cross-reactivity with other proteins in the proteome. Here, we explore NHS carbamates more broadly and demonstrate their potential as inhibitors of endocannabinoid hydrolases and additional enzymes from the serine hydrolase class. We extensively characterize an NHS carbamate 1a (MJN110) as a potent, selective, and in-vivo-active MAGL inhibitor. Finally, we demonstrate that MJN110 alleviates mechanical allodynia in a rat model of diabetic neuropathy, marking NHS carbamates as a promising class of MAGL inhibitors.

  13. Synthesis, Characterization and Antimicrobial Evaluation of some Thiazole-Derived Carbamates, Semicarbazones, Amides and Carboxamide

    International Nuclear Information System (INIS)

    Balawi, N.A.A.; ALShaikh, M.A.A.; Alafeefy, A.M.; Khan, K.M.

    2016-01-01

    This study comprises the synthesis and characterization of twenty thiazole-derived carbamates (3a-e), N-substituted amides (8a-h) and carboxamide (10) from 2-aminothiazoles (1a, b) via nucleophilic substitution reactions with activated carbonyl compounds including, chloroformates (2a-d), acid chlorides (7a-e) and glutaric anhydride (9), respectively. Sequential hydrazinolysis of carbamate (3e) and condensation with a variety of aldehydes and ketones (5a d) afforded the corresponding semicarbazones (6a-d). Some selected synthesized compounds were subjected to in vitro antimicrobial evaluation against common pathogens including, Gram+ve bacteria Bacillus subtilis (NRRL B-543) and Staphylococcus aureus, Gram-ve bacteria Escherichia coli (NRRLB-21), yeasts-Candida albicans (NRRLY-477) and Saccharomyces cercvisiae (NRRL Y-567) and fungs Asperigillus niger (NRRL 599). Screening results revealed that most of the tested compounds possess good antimicrobial activity compared to standard drugs. The highest inhibitory effects against Gram-ve Escherichia coli, Gram+ve Staphylococcus aureus, yeast Candida albicans and fungus Aspergillus niger was displayed by amide (8g) bearing the thiophene moiety. (author)

  14. Pharmacognostic standardization of Homoeopathic drug: Juniperus virginiana L.

    Directory of Open Access Journals (Sweden)

    P Padma Rao

    2015-01-01

    Full Text Available Background: Juniperus virginiana L., commonly known as ′red cedar′ in English is a well-known evergreen tree belonging to the family Cupressaceae. The leaves and young aerial shoots are used for preparation of medicine in Homoeopathy. Objective: Standardization is the quintessential aspect which ensures purity and quality of drugs. Hence, the pharmacognostic and physico-chemical studies are carried out to facilitate the use of authentic and correct species of raw drug plant material with established parametric standards for manufacturing the drug. Materials and Methods: Pharmacognostic studies on leaves and young aerial parts of authentic samples of J. virginiana L. have been carried out; physico-chemical parameters of raw drug viz., extractive values, ash values, formulation, besides weight per mL, total solids, alcohol content along with High Performance Thin Layer Chromatography (HPTLC and ultraviolet visible studies have been worked out for mother tincture. Results: The leaves are needles, narrow and sharp at tips; stems are round with greyish white to brown bark possessing small lenticels and covered by imbricate leaves. Epidermal cells in the surface have polygonal linear sides with pitted walls containing crystals and starch. Stomata exclusively occur on the adaxial surface in linear rows. Hypodermis of leaf in T.S. is marked with 1-2 layered lignified sclerenchyma. 2-4 secretory canals are present with one conspicuously beneath midvein bundle. The young terminal axis is sheathed by two closely surrounding leaves while the mature stem possess four leaf bases attached. Vascular tissue of stem possesses predominant xylem surrounded by phloem containing sphaeraphides, prismatic crystals and starch grains. Uniseriate rays occur in the xylem. Mature stem possess shrivelled cork, followed by the cortex. Physicochemical properties and HPTLC values of the drug are standardized and presented. Conclusion: The powder microscopic features and

  15. Organophosphorus and carbamate insecticide poisoning.

    Science.gov (United States)

    Vale, Allister; Lotti, Marcello

    2015-01-01

    Both organophosphorus (OP) and carbamate insecticides inhibit acetylcholinesterase (AChE), which results in accumulation of acetylcholine (ACh) at autonomic and some central synapses and at autonomic postganglionic and neuromuscular junctions. As a consequence, ACh binds to, and stimulates, muscarinic and nicotinic receptors, thereby producing characteristic features. With OP insecticides (but not carbamates), "aging" may also occur by partial dealkylation of the serine group at the active site of AChE; recovery of AChE activity requires synthesis of new enzyme in the liver. Relapse after apparent resolution of cholinergic symptoms has been reported with OP insecticides and is termed the intermediate syndrome. This involves the onset of muscle paralysis affecting particularly upper-limb muscles, neck flexors, and cranial nerves some 24-96 hours after OP exposure and is often associated with the development of respiratory failure. OP-induced delayed neuropathy results from phosphorylation and subsequent aging of at least 70% of neuropathy target esterase. Cramping muscle pain in the lower limbs, distal numbness, and paresthesiae are followed by progressive weakness, depression of deep tendon reflexes in the lower limbs and, in severe cases, in the upper limbs. The therapeutic combination of oxime, atropine, and diazepam is well established experimentally in the treatment of OP pesticide poisoning. However, there has been controversy as to whether oximes improve morbidity and mortality in human poisoning. The explanation may be that the solvents in many formulations are primarily responsible for the high morbidity and mortality; oximes would not be expected to reduce toxicity in these circumstances. even if given in appropriate dose. © 2015 Elsevier B.V. All rights reserved.

  16. Pharmacognostic and physicochemical standardization of homoeopathic drug: Rumex crispus L.

    Directory of Open Access Journals (Sweden)

    Subramanian Palani

    2016-01-01

    Full Text Available Background: Rumex crispus L., commonly called as "yellow dock" in English, "patience frisee" in French, and "Ampfer" in German, and ′aceda de culebra′ in Spanish is a well-known herb belonging to Polygonaceae. Roots of the herb are used as medicine in homoeopathy. Objective: The pharmacognostic and physicochemical studies on roots have been carried out to enable the use of correct species and standardize the raw material. Materials and Methods: Pharmacognostic studies on roots of authentic raw drug have been carried out; physicochemical parameters, namely, extractive value, ash values, formulation besides weight per mL, total solids, alcohol content along with high-performance thin layer chromatography (HPTLC and ultraviolet studies for mother tincture have been worked out. Results: Roots are blackish-brown, wiry, rounded with irregular striations, tortuous; internally, it is softwood, light-yellow, and fracture fibrous. Phellem is 8-10 layered, discontinuous, and tanniniferous. Phellogen is two-layered and contains inulin crystals in few. Outer phelloderm is 12-16 layered often containing spherocrystals and associated with stone cells. Secondary phloem is up to 25 layered. Xylem is in the form of strips. The physicochemical properties and HPTLC values of the drug are standardized and presented. Conclusion: The powder microscopic features and organoleptic characters along with anatomical and physicochemical studies are diagnostic to establish standards for the drug.

  17. A new method to characterize the kinetics of cholinesterases inhibited by carbamates.

    Science.gov (United States)

    Xiao, Qiaoling; Zhou, Huimin; Wei, Hong; Du, Huaqiao; Tan, Wen; Zhan, Yiyi; Pistolozzi, Marco

    2017-09-10

    The inhibition of cholinesterases (ChEs) by carbamates includes a carbamylation (inhibition) step, in which the drug transfers its carbamate moiety to the active site of the enzyme and a decarbamylation (activity recovery) step, in which the carbamyl group is hydrolyzed from the enzyme. The carbamylation and decarbamylation kinetics decide the extent and the duration of the inhibition, thus the full characterization of candidate carbamate inhibitors requires the measurement of the kinetic constants describing both steps. Carbamylation and decarbamylation rate constants are traditionally measured by two separate set of experiments, thus making the full characterization of candidate inhibitors time-consuming. In this communication we show that by the analysis of the area under the inhibition-time curve of cholinesterases inhibited by carbamates it is possible to calculate the decarbamylation rate constant from the same data traditionally used to characterize only the carbamylation kinetics, therefore it is possible to obtain a full characterization of the inhibition with a single set of experiments. The characterization of the inhibition kinetics of human and dog plasma butyrylcholinesterase and of human acetylcholinesterase by bambuterol and bambuterol monocarbamate enantiomers was used to demonstrate the validity of the approach. The results showed that the proposed method provides reliable estimations of carbamylation and decarbamylation rate constants thus representing a simple and useful approach to reduce the time required for the characterization of carbamate inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis

    International Nuclear Information System (INIS)

    2016-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  19. Detection of benzimidazole carbamates and amino metabolites in liver by surface plasmon resonance-biosensor

    Science.gov (United States)

    Two surface plasmon resonance (SPR) biosensor screening assays were developed and validated to detect 11 benzimidazole carbamate (BZT) and four amino-benzimidazole veterinary drug residues in liver tissue. The assays used polyclonal antibodies, raised in sheep, to detect BZTs and amino-benzimidazole...

  20. 49 CFR 219.701 - Standards for drug and alcohol testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Standards for drug and alcohol testing. 219.701... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Drug and Alcohol Testing Procedures § 219.701 Standards for drug and alcohol testing. (a) Drug testing required or authorized by subparts B...

  1. Host-guest chemistry of cyclodextrin carbamates and cellulose derivatives in aqueous solution.

    Science.gov (United States)

    Guo, Xin; Jia, Xiangxiang; Du, Jiaojiao; Xiao, Longqiang; Li, Feifei; Liao, Liqiong; Liu, Lijian

    2013-10-15

    Supramolecular polymer micelles were prepared on basis of the inclusion complexation between cyclodextrin carbamates and cellulose derivatives in aqueous media. Cyclodextrin carbamates were synthesized by microwave-assisted method from cyclodextrin and urea. The urea modified cyclodextrin shows the higher yield than the physical mixture of urea/cyclodextrin in the micellization with cellulose derivatives. The supramolecular structure of the core-shell micelles was demonstrated by (1)H NMR spectra, TEM images, and fluorescence spectra. The drug release behavior of the supramolecular polymer micelles was evaluated using prednisone acetate as a model drug. The drug loaded micelles showed steady and long time drug release behavior. With these properties, the supramolecular polymer micelles are attractive as drug carriers for pharmaceutical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. 78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

    Science.gov (United States)

    2013-06-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket Nos. FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and Innovation Act Title VII--Drug Supply Chain; Standards for Admission of Imported Drugs, Registration of...

  3. [Rapid determination of 8 urinary carbamate pesticides by liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Liu, Hualiang; Wang, Yuan; Zhu, Baoli

    2015-11-01

    To establish a method for simultaneously determining the urinary concentrations of 8 carbamate pesticides. After being purified by acetonitrile precipitation, urine samples were transferred to a liquid chromatography-tandem mass spectrometry system, and the concentrations of 8 carbamate pesticides were determined by external standard method. A C18 column was used for ultra-high-performance liquid chromatography; methanol/ammonium acetate solution was used as the mobile phase for gradient elution; the mass spectrometer was operated in a multi-reaction monitoring mode. The calibration curves were linear when the urinary concentrations of these carbamate pesticides were 20~800 µg/L, and the recovery rates were 61.0%~121% at spiked levels of 20, 200 and 800 µg/L, with a relative standard deviation of 1.7%~5.5%. This determination method meets the Guide for establishing occupational health standards-part 5: Determination methods of chemicals in biological materials, and can be used for simultaneous determination of 8 carbamate pesticides in the urine of poisoning patients.

  4. Chalcone-based carbamates for Alzheimer's disease treatment.

    Science.gov (United States)

    Rampa, Angela; Montanari, Serena; Pruccoli, Letizia; Bartolini, Manuela; Falchi, Federico; Feoli, Alessandra; Cavalli, Andrea; Belluti, Federica; Gobbi, Silvia; Tarozzi, Andrea; Bisi, Alessandra

    2017-05-01

    Alzheimer's disease is a still untreatable multifaceted pathology, and drugs able to stop or reverse its progression are urgently needed. In this picture, the recent reformulation of the cholinergic hypothesis renewed the interest for acetylcholinesterase inhibitors. In this paper, a series of naturally inspired chalcone-based carbamates was designed to target cholinesterase enzymes and possibly generate fragments endowed with neuroprotective activity in situ. Results & methodology: All compounds presented in this study showed nanomolar potency for cholinesterase inhibition. Notably, fragment 11d also displayed an interesting neuroprotective profile. These new derivatives are able to simultaneously modulate different key targets involved in Alzheimer's disease, and could be regarded as promising starting points for the development of disease-modifying drug candidates. [Formula: see text].

  5. 75 FR 34452 - Center for Drug Evaluation and Research Data Standards Plan; Availability for Comment

    Science.gov (United States)

    2010-06-17

    ... HUMAN SERVICES Food and Drug Administration Center for Drug Evaluation and Research Data Standards Plan... development of a comprehensive data standards program in the Center for Drug Evaluation and Research (CDER... Administration (FDA) is announcing the availability for public comment of the draft document entitled ``CDER Data...

  6. Chemometrics: A new scenario in herbal drug standardization

    Directory of Open Access Journals (Sweden)

    Ankit Bansal

    2014-08-01

    Full Text Available Chromatography and spectroscopy techniques are the most commonly used methods in standardization of herbal medicines but the herbal system is not easy to analyze because of their complexity of chemical composition. Many cutting-edge analytical technologies have been introduced to evaluate the quality of medicinal plants and significant amount of measurement data has been produced. Chemometric techniques provide a good opportunity for mining more useful chemical information from the original data. Then, the application of chemometrics in the field of medicinal plants is spontaneous and necessary. Comprehensive methods and hyphenated techniques associated with chemometrics used for extracting useful information and supplying various methods of data processing are now more and more widely used in medicinal plants, among which chemometrics resolution methods and principal component analysis (PCA are most commonly used techniques. This review focuses on the recent various important analytical techniques, important chemometrics tools and interpretation of results by PCA, and applications of chemometrics in quality evaluation of medicinal plants in the authenticity, efficacy and consistency. Key words: Chemometrics, HELP, Herbal drugs, PCA, OPA

  7. Investigation of kinetic interactions between approved oximes and human acetylcholinesterase inhibited by pesticide carbamates.

    Science.gov (United States)

    Wille, Timo; Kaltenbach, Lisa; Thiermann, Horst; Worek, Franz

    2013-12-05

    Carbamates are widely used for pest control and act primarily by inhibition of insect and mammalian acetylcholinesterase (AChE). Accidental or intentional uptake of carbamates may result in typical signs and symptoms of cholinergic overstimulation which cannot be discriminated from those of organophosphorus pesticide poisoning. There is an ongoing debate whether standard treatment with atropine and oximes should be recommended for human carbamate poisoning as well, since in vitro and in vivo animal data indicate a deleterious effect of oximes when used in combination with the N-methyl carbamate carbaryl. Therefore, we performed an in vitro kinetic study to investigate the effect of clinically used oximes on carbamoylation and decarbamoylation of human AChE. It became evident that pralidoxime and obidoxime in therapeutic concentrations aggravate the inhibition of AChE by carbaryl and propoxur, with obidoxime being substantially more potent compared to 2-PAM. However, obidoxime had no impact on the decarbamoylation kinetics. Hence, the administration of 2-PAM and especially of obidoxime to severely propoxur and carbaryl poisoned humans cannot be recommended. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. The Use and Effect of Carbamate Insecticide on Animal Health and Products

    Directory of Open Access Journals (Sweden)

    Indraningsih

    2008-06-01

    Full Text Available The use of carbamate in Indonesia is relatively new, in particular after prohibition on the use of most organochlorines (OC. Carbamates that commonly used for agricultural activities are carbofuran (Furadan, aldicarb (Temik and carbaryl (Sevin. When properly used, they will provide benefit, but misuse of insecticides would affect productivity, poisoning, public health problems, environmental contamination and residues in foods. A monitoring result of carbamate used in Java indicates that carbofurans were detected in soils (0,8 – 56,3 ppb; water (0,1 – 5,0 ppb; rice (nd – 5,0 ppb; soybeans (1,2 – 610 ppb; animal feed (12 – 102 ppb; beef (110 – 269 ppb; and sera of beef cattle (167 – 721 ppb. The residue level was above the maximum residue limits (MRL released by Indonesian Standardization Agency (Badan Standardisasi Nasional in some samples. The presence of carbofuran in foods should be taken into account since the carbofuran is regarded highly toxic for public and animal health. This paper describes the toxicity of carbamate, clinical signs of poisoning, residue in foods and environment, handling of poisoning and residue control.

  9. 33 CFR 95.020 - Standard for under the influence of alcohol or a dangerous drug.

    Science.gov (United States)

    2010-07-01

    ... of alcohol or a dangerous drug. 95.020 Section 95.020 Navigation and Navigable Waters COAST GUARD... ALCOHOL OR A DANGEROUS DRUG § 95.020 Standard for under the influence of alcohol or a dangerous drug. An individual is under the influence of alcohol or a dangerous drug when: (a) The individual is operating a...

  10. Proline-Based Carbamates as Cholinesterase Inhibitors

    Czech Academy of Sciences Publication Activity Database

    Pizova, H.; Havelková, M.; Štěpánková, Š.; Bak, A.; Kauerová, T.; Kozik, V.; Oravec, Michal; Imramovský, A.; Kollár, P.; Bobáľ, P.; Jampílek, J.

    2017-01-01

    Roč. 22, č. 11 (2017), č. článku 1969. ISSN 1420-3049 R&D Projects: GA MŠk(CZ) LO1415; GA MŠk(CZ) EF16_013/0001609 Institutional support: RVO:86652079 Keywords : proline * carbamates * in vitro cholinesterase inhibition * in vitro cytotoxicity assay * CoMSA * IVE-PLS * molecular docking study Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 2.861, year: 2016

  11. Reaction engineering of urea alcoholysis: Alkyl carbamates

    OpenAIRE

    Mote, Dhananjay R.; Ranade, Vivek V.

    2017-01-01

    Urea alcoholysis is a reversible reaction generating alkyl carbamate and ammonia as products. The reaction can be performed non-catalytically or in presence of catalyst. The first step in Reaction engineering analysis is to finalize the reactor configuration. In this case it is important to determine the necessity of reactive separation (simultaneous reaction and separation). This has been addressed by first establishing the reversibility of the reaction through theoretical and experimental i...

  12. [Development of analytical methods for residual N-methyl carbamate pesticides in foods].

    Science.gov (United States)

    Goto, Tomomi

    2010-08-01

    One of the major roles of public health agencies is to ensure safe products for consumers through analysis of residual agricultural chemicals and veterinary drugs in foods. The use of agricultural chemicals and veterinary drugs in agriculture is necessary to improve the quality of the food produced. They play a beneficial role in providing a plentiful, low-cost supply of high-quality food. On the other hand, as a consequence of this use, the presence of residues in food that is a critical element of overall public health is unavoidable, and residues in food are of great importance in the evaluation of food quality. N-methyl carbamate pesticides have anticholinesterase activity and are used worldwide. The postcolumn HPLC method is widely used for the detection of N-methyl carbamate pesticides in food. However, this traditional method involves a time-consuming process that requires skillful techniques. Therefore we developed a new analysis method for N-methyl carbamate pesticides as described in detail in this paper. The new method, including sample preparation and determination, is simple and rapid and allows simultaneous determination of pesticides in food within a much shorter analysis time as compared with the traditional method. This should provide high-quality analysis and ensure safe products for consumers.

  13. O-(Triazolyl)methyl carbamates as a novel and potent class of FAAH inhibitors

    Science.gov (United States)

    Colombano, Giampiero; Albani, Clara; Ottonello, Giuliana; Ribeiro, Alison; Scarpelli, Rita; Tarozzo, Glauco; Daglian, Jennifer; Jung, Kwang-Mook; Piomelli, Daniele; Bandiera, Tiziano

    2015-01-01

    Inhibition of fatty acid amide hydrolase (FAAH) activity is under investigation as a valuable strategy for the treatment of several disorders, including pain and drug addiction. A number of potent FAAH inhibitors belonging to different chemical classes have been disclosed. O-aryl carbamates are one of the most representative families. In the search for novel FAAH inhibitors, we synthesized a series of O-(1,2,3-triazol-4-yl)methyl carbamate derivatives exploiting the copper-catalyzed [3 + 2] cycloaddition reaction between azides and alkynes (click chemistry). We explored structure-activity relationships within this new class of compounds and identified potent inhibitors of both rat and human FAAH with IC50 values in the single-digit nanomolar range. PMID:25338703

  14. Ethynylphenyl carbonates and carbamates as dual-action acetylcholinesterase inhibitors and anti-inflammatory agents.

    Science.gov (United States)

    Saxena, Jaya; Meloni, David; Huang, Mou-Tuan; Heck, Diane E; Laskin, Jeffrey D; Heindel, Ned D; Young, Sherri C

    2015-12-01

    Novel ethynylphenyl carbonates and carbamates containing carbon- and silicon-based choline mimics were synthesized from their respective phenol and aniline precursors and screened for anticholinesterase and anti-inflammatory activities. All molecules were micromolar inhibitors of acetylcholinesterase (AChE), with IC50s of 28-86 μM; the carbamates were two-fold more potent than the carbonates. Two of the most potent AChE inhibitors suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation by 40%. Furthermore, these molecules have physicochemical properties in the range of other CNS drugs. These molecules have the potential to treat inflammation; they could also dually target Alzheimer's disease through restoration of cholinergic balance and inflammation suppression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. 40 CFR 721.2025 - Substituted phenylimino carbamate derivative.

    Science.gov (United States)

    2010-07-01

    ... derivative. 721.2025 Section 721.2025 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.2025 Substituted phenylimino carbamate derivative. (a) Chemical... as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject to reporting under this...

  16. 21 CFR 70.10 - Color additives in standardized foods and new drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Color additives in standardized foods and new... SERVICES GENERAL COLOR ADDITIVES General Provisions § 70.10 Color additives in standardized foods and new... proposes the inclusion of a color additive in the standardized food, the provisions of the regulations in...

  17. Select Small Core Structure Carbamates Exhibit High Contact Toxicity to “Carbamate-Resistant” Strain Malaria Mosquitoes, Anopheles gambiae (Akron)

    Science.gov (United States)

    Wong, Dawn M.; Li, Jianyong; Chen, Qiao-Hong; Han, Qian; Mutunga, James M.; Wysinski, Ania; Anderson, Troy D.; Ding, Haizhen; Carpenetti, Tiffany L.; Verma, Astha; Islam, Rafique; Paulson, Sally L.; Lam, Polo C.-H.; Totrov, Maxim; Bloomquist, Jeffrey R.; Carlier, Paul R.

    2012-01-01

    Acetylcholinesterase (AChE) is a proven target for control of the malaria mosquito (Anopheles gambiae). Unfortunately, a single amino acid mutation (G119S) in An. gambiae AChE-1 (AgAChE) confers resistance to the AChE inhibitors currently approved by the World Health Organization for indoor residual spraying. In this report, we describe several carbamate inhibitors that potently inhibit G119S AgAChE and that are contact-toxic to carbamate-resistant An. gambiae. PCR-RFLP analysis was used to confirm that carbamate-susceptible G3 and carbamate-resistant Akron strains of An. gambiae carry wild-type (WT) and G119S AChE, respectively. G119S AgAChE was expressed and purified for the first time, and was shown to have only 3% of the turnover number (k cat) of the WT enzyme. Twelve carbamates were then assayed for inhibition of these enzymes. High resistance ratios (>2,500-fold) were observed for carbamates bearing a benzene ring core, consistent with the carbamate-resistant phenotype of the G119S enzyme. Interestingly, resistance ratios for two oxime methylcarbamates, and for five pyrazol-4-yl methylcarbamates were found to be much lower (4- to 65-fold). The toxicities of these carbamates to live G3 and Akron strain An. gambiae were determined. As expected from the enzyme resistance ratios, carbamates bearing a benzene ring core showed low toxicity to Akron strain An. gambiae (LC50>5,000 μg/mL). However, one oxime methylcarbamate (aldicarb) and five pyrazol-4-yl methylcarbamates (4a–e) showed good to excellent toxicity to the Akron strain (LC50 = 32–650 μg/mL). These results suggest that appropriately functionalized “small-core” carbamates could function as a resistance-breaking anticholinesterase insecticides against the malaria mosquito. PMID:23049714

  18. Select small core structure carbamates exhibit high contact toxicity to "carbamate-resistant" strain malaria mosquitoes, Anopheles gambiae (Akron).

    Science.gov (United States)

    Wong, Dawn M; Li, Jianyong; Chen, Qiao-Hong; Han, Qian; Mutunga, James M; Wysinski, Ania; Anderson, Troy D; Ding, Haizhen; Carpenetti, Tiffany L; Verma, Astha; Islam, Rafique; Paulson, Sally L; Lam, Polo C-H; Totrov, Maxim; Bloomquist, Jeffrey R; Carlier, Paul R

    2012-01-01

    Acetylcholinesterase (AChE) is a proven target for control of the malaria mosquito (Anopheles gambiae). Unfortunately, a single amino acid mutation (G119S) in An. gambiae AChE-1 (AgAChE) confers resistance to the AChE inhibitors currently approved by the World Health Organization for indoor residual spraying. In this report, we describe several carbamate inhibitors that potently inhibit G119S AgAChE and that are contact-toxic to carbamate-resistant An. gambiae. PCR-RFLP analysis was used to confirm that carbamate-susceptible G3 and carbamate-resistant Akron strains of An. gambiae carry wild-type (WT) and G119S AChE, respectively. G119S AgAChE was expressed and purified for the first time, and was shown to have only 3% of the turnover number (k(cat)) of the WT enzyme. Twelve carbamates were then assayed for inhibition of these enzymes. High resistance ratios (>2,500-fold) were observed for carbamates bearing a benzene ring core, consistent with the carbamate-resistant phenotype of the G119S enzyme. Interestingly, resistance ratios for two oxime methylcarbamates, and for five pyrazol-4-yl methylcarbamates were found to be much lower (4- to 65-fold). The toxicities of these carbamates to live G3 and Akron strain An. gambiae were determined. As expected from the enzyme resistance ratios, carbamates bearing a benzene ring core showed low toxicity to Akron strain An. gambiae (LC(50)>5,000 μg/mL). However, one oxime methylcarbamate (aldicarb) and five pyrazol-4-yl methylcarbamates (4a-e) showed good to excellent toxicity to the Akron strain (LC(50) = 32-650 μg/mL). These results suggest that appropriately functionalized "small-core" carbamates could function as a resistance-breaking anticholinesterase insecticides against the malaria mosquito.

  19. Synthesis and biological activity of new salicylanilide N,N-disubstituted carbamates and thiocarbamates.

    Science.gov (United States)

    Krátký, Martin; Volková, Marie; Novotná, Eva; Trejtnar, František; Stolaříková, Jiřina; Vinšová, Jarmila

    2014-08-01

    The development of novel antimicrobial drugs represents a cutting edge research topic. In this study, 20 salicylanilide N,N-disubstituted carbamates and thiocarbamates were designed, synthesised and characterised by IR, (1)H NMR and (13)C NMR. The compounds were evaluated in vitro as potential antimicrobial agents against Mycobacterium tuberculosis and nontuberculous mycobacteria (Mycobacterium avium and Mycobacterium kansasii) as well as against eight bacterial and fungal strains. Additionally, we investigated the inhibitory effect of these compounds on mycobacterial isocitrate lyase and cellular toxicity. The minimum inhibitory concentrations (MICs) against mycobacteria were from 4 μM for thiocarbamates and from 16 μM for carbamates. Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, were inhibited with MICs from 0.49 μM by thiocarbamates, whilst Gram-negative bacteria and most of the fungi did not display any significant susceptibility. All (thio)carbamates mildly inhibited isocitrate lyase (up to 22%) at a concentration of 10 μM. The (thio)carbamoylation of the parent salicylanilides led to considerably decreased cytotoxicity and thus improved the selectivity indices (up to 175). These values indicate that some derivatives are attractive candidates for future research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Salicylanilide N-monosubstituted carbamates: Synthesis and in vitro antimicrobial activity.

    Science.gov (United States)

    Krátký, Martin; Vinšová, Jarmila

    2016-03-15

    The research of innovative antimicrobial agents represents a cutting edge topic. Hence, we synthesized and characterised novel salicylanilide N-monosubstituted carbamates. Twenty compounds were evaluated in vitro against eight bacterial strains and eight fungal species. The lowest minimum inhibitory concentrations (MICs) were found to be ⩽0.49 μM. Genus Staphylococcus, including methicillin-resistant Staphylococcus aureus, and fungus Trichophyton mentagrophytes showed uniformly the highest rate of susceptibility, whilst Gram-negative bacteria and most of the fungi were less susceptible. A wide range of carbamates provided comparable or superior in vitro antimicrobial activity in comparison to established drugs. Interestingly, extended-spectrum β-lactamase producing strain of Klebsiella pneumoniae was inhibited with MICs starting from 31.25 μM. With respect to Staphylococci, 2-[(4-bromophenyl)carbamoyl]-4-chlorophenyl phenylcarbamate exhibited the lowest MIC values (⩽0.98 μM). 2-[(4-Bromophenyl)carbamoyl]-4-chlorophenyl benzylcarbamate showed the widest spectrum of antifungal action. The results indicate that some salicylanilide carbamates can be considered to be promising candidates for future investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Discovery of Aromatic Carbamates that Confer Neuroprotective Activity by Enhancing Autophagy and Inducing the Anti-Apoptotic Protein B-Cell Lymphoma 2 (Bcl-2).

    Science.gov (United States)

    Kinarivala, Nihar; Patel, Ronak; Boustany, Rose-Mary; Al-Ahmad, Abraham; Trippier, Paul C

    2017-12-14

    Neurodegenerative diseases share certain pathophysiological hallmarks that represent common targets for drug discovery. In particular, dysfunction of proteostasis and the resultant apoptotic death of neurons represent common pathways for pharmacological intervention. A library of aromatic carbamate derivatives based on the clinically available drug flupirtine was synthesized to determine a structure-activity relationship for neuroprotective activity. Several derivatives were identified that possess greater protective effect in human induced pluripotent stem cell-derived neurons, protecting up to 80% of neurons against etoposide-induced apoptosis at concentrations as low as 100 nM. The developed aromatic carbamates possess physicochemical properties desirable for CNS therapeutics. The primary known mechanisms of action of the parent scaffold are not responsible for the observed neuroprotective activity. Herein, we demonstrate that neuroprotective aromatic carbamates function to increase the Bcl-2/Bax ratio to an antiapoptotic state and activate autophagy through induction of beclin 1.

  2. Drug Combinations as the New Standard for Melanoma Treatment.

    Science.gov (United States)

    Polkowska, Marta; Czepielewska, Edyta; Kozłowska-Wojciechowska, Małgorzata

    2016-12-01

    Advanced melanoma is related to a very grim prognosis and fast progression. Until recently, there has been no indicated treatment that would affect the disease's outcome. However, the progress in immunotherapy and molecular therapy has significantly changed the unfavourable prognosis of melanoma progression and its short survival rate. Both approaches have improved patients' outcomes and provided renewed hope for successful treatment. Moreover, in order to further enhance patients' outcomes and to avoid mechanisms of tumour resistance, investigators attempted a combined approach. Targeted therapy combinations allowed a better response rate and progression-free survival than monotherapy with one of the agents. Another promising combination, but with limiting toxicities, is a concurrent immuno- and molecular-targeted therapy. It is suspected that complimentary usage of these drugs may lead to synergism, providing robust and quick tumour responses as well as long-lasting effects. Results of currently ongoing clinical trials that investigate combination strategies in melanoma are expected to provide more mature data about the effectiveness and the safety profile of those therapies. Until more robust results of these studies occur, the best management of advanced and metastatic melanoma is immunotherapy with anti-PD1 drugs or targeted therapy with concomitant BRAF and MEK inhibitor. However, which of these two options should be used first is still under discussion.

  3. Synthesis and Antimicrobial Evaluation of 1-[(2-Substituted phenyl)carbamoyl]naphthalen-2-yl Carbamates.

    Science.gov (United States)

    Gonec, Tomas; Pospisilova, Sarka; Holanova, Lucie; Stranik, Josef; Cernikova, Aneta; Pudelkova, Valeria; Kos, Jiri; Oravec, Michal; Kollar, Peter; Cizek, Alois; Jampilek, Josef

    2016-09-07

    Series of thirteen 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl carbamates and thirteen 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl carbamates with alkyl/cycloalkyl/arylalkyl chains were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, two methicillin-resistant S. aureus strains, Mycobacterium marinum, and M. kansasii. 1-[(2-Chlorophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate and 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate showed antistaphylococcal (MICs = 42 µM against MRSA) and antimycobacterial (MICs = 21 µM) activity against the tested strains comparable with or higher than that of the standards ampicillin and isoniazid. In the case of bulkier carbamate tails (R > propyl/isopropyl), the activity was similar (MICs ca. 70 µM). Screening of the cytotoxicity of both of the most effective compounds was performed using THP-1 cells, and no significant lethal effect was observed (LD50 >30 µM). The structure-activity relationships are discussed.

  4. Synthesis and Antimicrobial Evaluation of 1-[(2-Substituted phenylcarbamoyl]naphthalen-2-yl Carbamates

    Directory of Open Access Journals (Sweden)

    Tomas Gonec

    2016-09-01

    Full Text Available Series of thirteen 1-[(2-chlorophenylcarbamoyl]naphthalen-2-yl carbamates and thirteen 1-[(2-nitrophenylcarbamoyl]naphthalen-2-yl carbamates with alkyl/cycloalkyl/arylalkyl chains were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, two methicillin-resistant S. aureus strains, Mycobacterium marinum, and M. kansasii. 1-[(2-Chlorophenylcarbamoyl]naphthalen-2-yl ethylcarbamate and 1-[(2-nitrophenylcarbamoyl]naphthalen-2-yl ethylcarbamate showed antistaphylococcal (MICs = 42 µM against MRSA and antimycobacterial (MICs = 21 µM activity against the tested strains comparable with or higher than that of the standards ampicillin and isoniazid. In the case of bulkier carbamate tails (R > propyl/isopropyl, the activity was similar (MICs ca. 70 µM. Screening of the cytotoxicity of both of the most effective compounds was performed using THP-1 cells, and no significant lethal effect was observed (LD50 >30 µM. The structure-activity relationships are discussed.

  5. Chemometrics: A new scenario in herbal drug standardization.

    Science.gov (United States)

    Bansal, Ankit; Chhabra, Vikas; Rawal, Ravindra K; Sharma, Simant

    2014-08-01

    Chromatography and spectroscopy techniques are the most commonly used methods in standardization of herbal medicines but the herbal system is not easy to analyze because of their complexity of chemical composition. Many cutting-edge analytical technologies have been introduced to evaluate the quality of medicinal plants and significant amount of measurement data has been produced. Chemometric techniques provide a good opportunity for mining more useful chemical information from the original data. Then, the application of chemometrics in the field of medicinal plants is spontaneous and necessary. Comprehensive methods and hyphenated techniques associated with chemometrics used for extracting useful information and supplying various methods of data processing are now more and more widely used in medicinal plants, among which chemometrics resolution methods and principal component analysis (PCA) are most commonly used techniques. This review focuses on the recent various important analytical techniques, important chemometrics tools and interpretation of results by PCA, and applications of chemometrics in quality evaluation of medicinal plants in the authenticity, efficacy and consistency.

  6. Synthesis, characterization and in vitro evaluation of substituted N-(2-phenylcyclopropyl)carbamates as acetyl- and butyrylcholinesterase inhibitors.

    Science.gov (United States)

    Horáková, Eva; Drabina, Pavel; Brož, Břetislav; Štěpánková, Šárka; Vorčáková, Katarína; Královec, Karel; Havelek, Radim; Sedlák, Miloš

    2016-01-01

    A serie of O-substituted N-2-phenylcyclopropylcarbamates was prepared and characterized. These carbamates were tested as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). It was found, that these compounds exhibit moderate inhibition activity with values of IC 50 in the range of 54.8-94.4 μM (for AChE) and up to 5.8 μM (for BChE). The AChE/BChE selectivity for each carbamate was calculated. These values varied from 0.50 to 9.46, two carbamate derivatives inhibited only AChE selectively. The most promising derivative was prepared in all optically pure forms (four isomers). It was found that individual stereoisomers differed only slightly in the inhibition ability. The cytotoxicity of all carbamates was evaluated using the standard in vitro test with Jurkat cells. With regard to their inhibition activity and cytotoxicity as well as easy preparation, O-substituted N-2-phenylcyclopropylcarbamates can be considered as promising compounds for potential medicinal applications.

  7. Diazeniumdiolated carbamates: a novel class of nitric oxide donors.

    Science.gov (United States)

    Nandurdikar, Rahul S; Maciag, Anna E; Cao, Zhao; Keefer, Larry K; Saavedra, Joseph E

    2012-03-15

    We report an indirect method for synthesis of previously inaccessible diazeniumdiolated carbamates. Synthesis involves use of previously reported triisopropylsilyloxymethylated isopropylamine diazeniumdiolate (TOM-ylated IPA/NO). These novel diazeniumdiolated carbamate prodrugs upon activation release nitric oxide (NO) similar to their secondary amine counterparts. They are also efficient sources of intracellular NO. These prodrugs may have potential applications as therapeutic NO-donors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Palladium-Catalyzed Synthesis of N-Aryl Carbamates

    Science.gov (United States)

    Vinogradova, Ekaterina V.; Park, Nathaniel H.; Fors, Brett P.; Buchwald, Stephen L.

    2013-01-01

    An efficient synthesis of aryl carbamates was achieved by introducing alcohols into the reaction of palladium-catalyzed cross-coupling of ArX (X = Cl, OTf) with sodium cyanate. The use of aryl triflates as electrophilic components in this transformation allowed for an expanded substrate scope for direct synthesis of aryl isocyanates. This methodology provides direct access to major carbamate protecting groups, S-thiocarbamates, and diisocyanate precursors to polyurethane materials. PMID:23441814

  9. Iron-Catalyzed Alkylations of Aryl Sulfamates and Carbamates

    Science.gov (United States)

    Silberstein, Amanda L.; Ramgren, Stephen D.; Garg, Neil K.

    2012-01-01

    The alkylation of aryl sulfamates and carbamates using iron catalysis is reported. The method constructs sp2–sp3 carbon–carbon bonds and provides synthetically useful yields across a range of substrates (>35 examples). The directing group ability of sulfamates and carbamates, accompanied by their low reactivity toward conventional cross-couplings, render these substrates useful for the synthesis of polyfunctionalized arenes. PMID:22758657

  10. Chemoselective Synthesis of Carbamates using CO2 as Carbon Source.

    Science.gov (United States)

    Riemer, Daniel; Hirapara, Pradipbhai; Das, Shoubhik

    2016-08-09

    Synthesis of carbamates directly from amines using CO2 as the carbon source is a straightforward and sustainable approach. Herein, we describe a highly effective and chemoselective methodology for the synthesis of carbamates at room temperature and atmospheric pressure. This methodology can also be applied to protect the amino group in amino acids and peptides, and also to synthesize important pharmaceuticals. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Discovery of carbamate degrading enzymes by functional metagenomics

    OpenAIRE

    Ufarté, Lisa; Laville, Elisabeth; Duquesne, Sophie; Morgavi, Diego; Robe, Patrick; Klopp, Christophe; Rizzo, Angeline; Pizzut-Serin, Sandra; Potocki-Veronese, Gabrielle

    2017-01-01

    Bioremediation of pollutants is a major concern worldwide, leading to the research of new processes to break down and recycle xenobiotics and environment contaminating polymers. Among them, carbamates have a very broad spectrum of uses, such as toxinogenic pesticides or elastomers. In this study, we mined the bovine rumen microbiome for carbamate degrading enzymes. We isolated 26 hit clones exhibiting esterase activity, and were able to degrade at least one of the targeted polyurethane and pe...

  12. Physicochemical studies of the carbamate-CO2-solvent system

    International Nuclear Information System (INIS)

    Prencipe, M.; Ishida, T.

    1977-08-01

    The formation of carbamate from CO 2 and the various amine solutions has been investigated for the purpose of elucidating the structure of the species generated in the reaction. The amine solutions used were 1 and 2 molar solutions of di-n-butylamine (DNBA) in triethylamine (TEA), pure DNBA and pure TEA. It has been found that the nonaqueous solvent participates in the formation of carbamate in 1 and 2M-DNBA/TEA solutions as a proton acceptor in DNBA-carbamate formation. However, due to the high concentration of the solutions and the basicities of the amines, a significant amount of DNBA which does not form the DNBA-carbamate anion is also found to be participating as a proton acceptor. Pure TEA absorbs only 1 / 60 of the absorption by pure DNBA. The extent of TEA participation in the CO 2 -absorption process other than as a proton acceptor in DNBA-carbamate is negligible. The formation of carbamic acid and zwitterion have been found unlikely. 7 tables, 15 figs

  13. Systematic derivation of an Australian standard for Tall Man lettering to distinguish similar drug names.

    Science.gov (United States)

    Emmerton, Lynne; Rizk, Mariam F S; Bedford, Graham; Lalor, Daniel

    2015-02-01

    Confusion between similar drug names can cause harmful medication errors. Similar drug names can be visually differentiated using a typographical technique known as Tall Man lettering. While international conventions exist to derive Tall Man representation for drug names, there has been no national standard developed in Australia. This paper describes the derivation of a risk-based, standardized approach for use of Tall Man lettering in Australia, and known as National Tall Man Lettering. A three-stage approach was applied. An Australian list of similar drug names was systematically compiled from the literature and clinical error reports. Secondly, drug name pairs were prioritized using a risk matrix based on the likelihood of name confusion (a four-component score) vs. consensus ratings of the potential severity of the confusion by 31 expert reviewers. The mid-type Tall Man convention was then applied to derive the typography for the highest priority drug pair names. Of 250 pairs of confusable Australian drug names, comprising 341 discrete names, 35 pairs were identified by the matrix as an 'extreme' risk if confused. The mid-type Tall Man convention was successfully applied to the majority of the prioritized drugs; some adaption of the convention was required. This systematic process for identification of confusable drug names and associated risk, followed by application of a convention for Tall Man lettering, has produced a standard now endorsed for use in clinical settings in Australia. Periodic updating is recommended to accommodate new drug names and error reports. © 2014 John Wiley & Sons, Ltd.

  14. Synthesis, structural characterization, docking, lipophilicity and cytotoxicity of 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-alkyl carbamates, novel acetylcholinesterase and butyrylcholinesterase pseudo-irreversible inhibitors.

    Science.gov (United States)

    Pejchal, Vladimír; Štěpánková, Šárka; Pejchalová, Marcela; Královec, Karel; Havelek, Radim; Růžičková, Zdeňka; Ajani, Haresh; Lo, Rabindranath; Lepšík, Martin

    2016-04-01

    In the current study, sixteen novel derivatives of (R)-1-(6-fluorobenzo[d]thiazol-2-yl)ethanamine were synthesized as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. Chemical structures together with purity of the synthesized compounds were substantiated by IR, (1)H, (13)C, (19)F NMR, high resolution mass spectrometry and elemental analysis. The optical activities were confirmed by optical rotation measurements. The synthesized compounds were evaluated for their AChE and BChE inhibitory activities. In addition, the cytotoxicity of the most active compounds was investigated against human cell lines employing XTT tetrazolium salt reduction assay and xCELLigence system allowing a label-free assessment of the cells proliferation. Our results demonstrated that the inhibitory mechanism was confirmed to be pseudo-irreversible, in line with previous studies on carbamates. Compounds indicated as 3b, 3d, 3l and 3n showed the best AChE inhibitory activity of all the evaluated compounds and were up to tenfold more potent than standard drug rivastigmine. The binding mode was determined using state-of-the-art covalent docking and scoring methodology. The obtained data clearly demonstrated that 3b, 3d, 3l and 3n benzothiazole carbamates possess high inhibitory activity against AChE and BChE and concurrently negligible cytotoxicity. In conclusion, our results indicate, that these derivatives could be promising in an effective therapeutic intervention for Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Synthesis of Sulfoximine Carbamates by Rhodium-Catalyzed Nitrene Transfer of Carbamates to Sulfoxides.

    Science.gov (United States)

    Zenzola, Marina; Doran, Robert; Luisi, Renzo; Bull, James A

    2015-06-19

    Sulfoximines are of considerable interest for incorporation into medicinal compounds. A convenient synthesis of N-protected sulfoximines is achieved, under mild conditions, by rhodium-catalyzed transfer of carbamates to sulfoxides. The first examples of 4-membered thietane-oximines are prepared. Sulfoximines bearing Boc and Cbz groups are stable to further cross coupling reactions, and readily deprotected. This method may facilitate the preparation of NH-sulfoximines providing improved (global) deprotection strategies, which is illustrated in the synthesis of methionine sulfoxide (MSO).

  16. A fast, simple and green method for the extraction of carbamate pesticides from rice by microwave assisted steam extraction coupled with solid phase extraction.

    Science.gov (United States)

    Song, Weitao; Zhang, Yiqun; Li, Guijie; Chen, Haiyan; Wang, Hui; Zhao, Qi; He, Dong; Zhao, Chun; Ding, Lan

    2014-01-15

    This paper presented a fast, simple and green sample pretreatment method for the extraction of 8 carbamate pesticides in rice. The carbamate pesticides were extracted by microwave assisted water steam extraction method, and the extract obtained was immediately applied on a C18 solid phase extraction cartridge for clean-up and concentration. The eluate containing target compounds was finally analysed by high performance liquid chromatography with mass spectrometry. The parameters affecting extraction efficiency were investigated and optimised. The limits of detection ranging from 1.1 to 4.2ngg(-1) were obtained. The recoveries of 8 carbamate pesticides ranged from 66% to 117% at three spiked levels, and the inter- and intra-day relative standard deviation values were less than 9.1%. Compared with traditional methods, the proposed method cost less extraction time and organic solvent. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Carbamate Insecticides Target Human Melatonin Receptors.

    Science.gov (United States)

    Popovska-Gorevski, Marina; Dubocovich, Margarita L; Rajnarayanan, Rajendram V

    2017-02-20

    Carbaryl (1-naphthyl methylcarbamate) and carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate) are among the most toxic insecticides, implicated in a variety of diseases including diabetes and cancer among others. Using an integrated pharmacoinformatics based screening approach, we have identified these insecticides to be structural mimics of the neurohormone melatonin and were able to bind to the putative melatonin binding sites in MT 1 and MT 2 melatonin receptors in silico. Carbaryl and carbofuran then were tested for competition with 2-[ 125 I]-iodomelatonin (300 pM) binding to hMT 1 or hMT 2 receptors stably expressed in CHO cells. Carbaryl and carbofuran showed higher affinity for competition with 2-[ 125 I]-iodomelatonin binding to the hMT 2 compared to the hMT 1 melatonin receptor (33 and 35-fold difference, respectively) as predicted by the molecular modeling. In the presence of GTP (100 μM), which decouples the G-protein linked receptors to modulate signaling, the apparent efficacy of carbaryl and carbofuran for 2-[ 125 I]-iodomelatonin binding for the hMT 1 melatonin receptor was not affected but significantly decreased for the hMT 2 melatonin receptor compatible with receptor antagonist/inverse agonist and agonist efficacy, respectively. Altogether, our data points to a potentially new mechanism through which carbamate insecticides carbaryl and carbofuran could impact human health by altering the homeostatic balance of key regulatory processes by directly binding to melatonin receptors.

  18. Effect of carbamates on mRNA encoding lipid enzymes in hamster flank organs.

    Science.gov (United States)

    López-Lezama, Juan C; Cabeza, Marisa; Mayorga, Israel; Soriano, Juan; Sainz, Teresita; Bratoeff, Eugene

    2014-05-01

    Flank organs are an androgen-dependent pilosebaceous complex present in male and female hamsters. These organs have been used for the evaluation of antiandrogenic drugs, which could be used for the treatment of androgen-dependent afflictions. This study demonstrated the role of four different steroidal carbamates 7-10 in the expression of mRNAs coding for different enzymes involved in the lipid metabolism in flank organs. To determine the biological effects of compounds 7-10 on the expression of mRNA coding for lipid enzymes, steroids 7-10, testosterone (T), progesterone (P), and/or 7-10 were applied on the flank organs. Later, the mRNA expression for the enzymes was determined by polymerase chain reaction. The binding of 8 and 9 to the progesterone receptor (PR) as well as their effects on the activity of 5α-reductase were also evaluated. Treatments with T, P, and 7-10 increased the mRNA expression for glycerol 3-phosphate acyl transferase (GPAT), β-hydroxy-β-methylglutaryl-CoA synthase (HMG-CoA-S), β-hydroxy-β-methylglutaryl-CoA reductase (HMG-CoA-R), phosphatidylinositol synthase (PI-S), and squalene-synthase (SQ-S). However, the combined treatments with P + 7-10 decreased the expression of GPAT, HMG-CoA-S, and HMG-CoA-R. Expression of mRNA for all enzymes was variable under treatment with T + 7-10. Data showed that these carbamates did not bind to the PR, but inhibited the activity of 5α-reductase. Carbamates 7-10 changed the mRNA expression model induced by T and P in flank organs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Discovery of carbamate degrading enzymes by functional metagenomics.

    Science.gov (United States)

    Ufarté, Lisa; Laville, Elisabeth; Duquesne, Sophie; Morgavi, Diego; Robe, Patrick; Klopp, Christophe; Rizzo, Angeline; Pizzut-Serin, Sandra; Potocki-Veronese, Gabrielle

    2017-01-01

    Bioremediation of pollutants is a major concern worldwide, leading to the research of new processes to break down and recycle xenobiotics and environment contaminating polymers. Among them, carbamates have a very broad spectrum of uses, such as toxinogenic pesticides or elastomers. In this study, we mined the bovine rumen microbiome for carbamate degrading enzymes. We isolated 26 hit clones exhibiting esterase activity, and were able to degrade at least one of the targeted polyurethane and pesticide carbamate compounds. The most active clone was deeply characterized. In addition to Impranil, this clone was active on Tween 20, pNP-acetate, butyrate and palmitate, and on the insecticide fenobucarb. Sequencing and sub-cloning of the best target revealed a novel carboxyl-ester hydrolase belonging to the lipolytic family IV, named CE_Ubrb. This study highlights the potential of highly diverse microbiota such as the ruminal one for the discovery of promiscuous enzymes, whose versatility could be exploited for industrial uses.

  20. Drug evaluation and the permissive principle: continuities and contradictions between standards and practices in antidepressant regulation.

    Science.gov (United States)

    Abraham, John; Davis, Courtney

    2009-08-01

    Pharmaceuticals are not permitted on to the market unless they are granted regulatory approval. The regulatory process is, therefore, crucial in whether or not a drug is widely prescribed. Regulatory agencies have developed standards of performance that pharmaceuticals are supposed to meet before entering the market. Regulation of technologies is often discussed by reference to the precautionary principle. In contrast, this paper develops the concept of the 'permissive principle' as a way of understanding the departure of regulators' practices from standards of drug efficacy to which regulatory agencies themselves subscribe. By taking a case study of antidepressant regulation in the UK and the USA, the mechanisms of permissive regulatory practices are examined. An STS methodology of both spatial (international) and temporal comparisons of regulatory practices with regulatory standards is employed to identify the nature and extent of the permissive regulation. It is found that the permissive principle was adopted by drug regulators in the UK and the USA, but more so by the former than the latter. Evidently, permissive regulation, which favours the commercial interests of the drug manufacturer, but is contrary to the interests of patients, may penetrate to the heart of regulatory science. On the other hand, permissive regulation of specific drugs should not be regarded as an inevitable result of marketing strategies and concomitant networks deployed by powerful pharmaceutical companies, because the extent of permissive regulation may vary according to the intra-institutional normative commitments of regulators to uphold their technical standards against the commercial interests of the manufacturer. Likely sociological factors that can account for such permissive regulatory practices are 'corporate bias', secrecy and excessive regulatory trust in the pharmaceutical industry in the UK, political expediency and ideological capture in the USA, combined in both countries

  1. Hydrophobic coating of polyaniline-poly(propylene oxide) copolymer for direct immersion solid phase microextraction of carbamate pesticides.

    Science.gov (United States)

    Ai, Youhong; Zhang, Jingqiang; Zhao, Faqiong; Zeng, Baizhao

    2015-08-14

    A nanostructural polyaniline-poly(propylene oxide) (PANI-PPO) composite coating was electrochemically synthesized on a stainless steel wire, by using acidic ionic liquid 1-sulfobutyl-3-methylimidazolium hydrosulfate as supporting electrolyte. The coating showed strong hydrophobicity and allowed for the direct immersion solid-phase microextraction of carbamate pesticides (i.e. 2-(1-methylethoxy) phenyl methylcarbamate, m-tolyl-n-methylcarbamate, 2-(1-methylethyl) phenyl methylcarbamate, 2-(1-methylpropyl) phenol methylcarbamate and 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate) in complex matrices. Moreover, this coating could be used for at least 120 times of extraction. When it was coupled with gas chromatography for the determination of these carbamate pesticides the linear ranges were about 0.1-100 μg L(-1) and the detection limits were 0.012-0.048 μg L(-1). It also displayed acceptable repeatability and reproducibility. When a fiber was used for five successive measurements the relative standard deviations (RSDs) were smaller than 8.7%, and the RSDs for fiber-to-fiber were 5.7-12.9% (n=5). The practical feasibility of the proposed method was evaluated by determining carbamate pesticides in vegetable samples and the recoveries for standards added were 79.8-108.8%. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Accuracy and completeness of drug information in Wikipedia: a comparison with standard textbooks of pharmacology.

    Directory of Open Access Journals (Sweden)

    Jona Kräenbring

    Full Text Available The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7% ± 0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8 ± 1.5% (p < 0.001. Completeness varied in-between categories, and was lowest in the category "pharmacokinetics" (68.0% ± 4.2%; p < 0.001 and highest in the category "indication" (91.3% ± 2.0% when compared to the textbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6 ± 1.6 references and 262.8 ± 37.4 edits performed by 142.7 ± 17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education.

  3. Accuracy and Completeness of Drug Information in Wikipedia: A Comparison with Standard Textbooks of Pharmacology

    Science.gov (United States)

    Gutmann, Joanna; Muehlich, Susanne; Zolk, Oliver; Wojnowski, Leszek; Maas, Renke; Engelhardt, Stefan; Sarikas, Antonio

    2014-01-01

    The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7%±0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8±1.5% (ptextbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6±1.6 references and 262.8±37.4 edits performed by 142.7±17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education. PMID:25250889

  4. Detection of systemic hypersensitivity to drugs using standard guinea pig assays.

    Science.gov (United States)

    Weaver, James L; Staten, David; Swann, Joslyn; Armstrong, George; Bates, Melissa; Hastings, Kenneth L

    2003-12-01

    The most commonly used assays designed to detect either skin or systemic immune-based hypersensitivity reactions are those using guinea pigs (GP). We obtained data from various FDA records to evaluate the correlation between GP assay results and reported post-marketing systemic hypersensitivity reactions. We examined the new drug application (NDA) reviews of approved drugs for the results of GP assays. Post-marketing human data were extracted from the FDA adverse event reporting system (AERS). Drug usage data were obtained from a commercial database maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between 1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were found to have positive results in at least one GP assay. Simple reporting index (RI) values for systemic hypersensitivity reactions were calculated from AERS data and usage to produce the index of adverse event reports per million shipping units of drug. A variety of definitions of positive human response were examined. A statistically significant association was seen for rash between post-marketing and clinical trials adverse event reports. No statistically significant associations between human data and GP test results were observed. These data suggest that standard GP assays have limited ability to predict human systemic hypersensitivity potential for pharmaceuticals.

  5. ERK-dependent phosphorylation of HSF1 mediates chemotherapeutic resistance to benzimidazole carbamates in colorectal cancer cells.

    Science.gov (United States)

    Wales, Christina T K; Taylor, Frederick R; Higa, Allan T; McAllister, Harvey A; Jacobs, Aaron T

    2015-07-01

    Drugs containing the benzimidazole carbamate scaffold include anthelmintic and antifungal agents, and they are now also recognized as having potential applications in the treatment of colorectal and other cancers. These agents act by binding to β-tubulin, and in doing so they disrupt microtubules, arrest cell division, and promote apoptotic cell death in malignant cells. We have evaluated several commercially available benzimidazole carbamates for cytotoxic activity in colorectal cancer cells. In addition to cytotoxicity, we also observe activation of the transcription factor, heat shock factor-1 (HSF1). HSF1 is well known to mediate a cytoprotective response that promotes tumor cell survival and drug resistance. Here, we show that biochemical inhibition with the HSF1 inhibitor KRIBB11 or siRNA-based silencing of HSF1 results in a significant enhancement of drug potency, causing an approximately two-fold decrease in IC50 values of parbendazole and nocodazole. We also define a mechanism for drug-induced HSF1 activation, which results from a phosphorylation event at Ser326 that is dependent on the activation of the extracellular regulated protein kinase-1/2 (ERK-1/2) mitogen-activated protein kinase pathway. Inhibition of the upstream kinase MEK-1/2 with U0126 attenuates the phosphorylation of both ERK-1/2 and HSF1, and significantly enhances drug cytotoxicity. From these data we propose a unique model whereby the ERK-1/2-dependent activation of HSF1 promotes chemotherapeutic resistance to benzimidazole carbamates. Therefore, targeting the ERK-1/2 signaling cascade is a potential strategy for HSF1 inhibition and a means of enhancing the cytotoxicity of these agents.

  6. Crystal structures of carbamate kinase from Giardia lamblia bound with citric acid and AMP-PNP.

    Directory of Open Access Journals (Sweden)

    Kap Lim

    Full Text Available The parasite Giardia lamblia utilizes the L-arginine dihydrolase pathway to generate ATP from L-arginine. Carbamate kinase (CK catalyzes the last step in this pathway, converting ADP and carbamoyl phosphate to ATP and ammonium carbamate. Because the L-arginine pathway is essential for G. lamblia survival and absent in high eukaryotes including humans, the enzyme is a potential target for drug development. We have determined two crystal structures of G. lamblia CK (glCK with bound ligands. One structure, in complex with a nonhydrolyzable ATP analog, adenosine 5'-adenylyl-β,γ-imidodiphosphate (AMP-PNP, was determined at 2.6 Å resolution. The second structure, in complex with citric acid bound in the postulated carbamoyl phosphate binding site, was determined in two slightly different states at 2.1 and 2.4 Å resolution. These structures reveal conformational flexibility of an auxiliary domain (amino acid residues 123-170, which exhibits open or closed conformations or structural disorder, depending on the bound ligand. The structures also reveal a smaller conformational change in a region associated the AMP-PNP adenine binding site. The protein residues involved in binding, together with a model of the transition state, suggest that catalysis follows an in-line, predominantly dissociative, phosphotransfer reaction mechanism, and that closure of the flexible auxiliary domain is required to protect the transition state from bulk solvent.

  7. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  8. Assessment of Sexual Dysfunction Symptoms in Female Drug Users: Standardized vs. Unstandardized Methods.

    Science.gov (United States)

    Diehl, Alessandra; Rassool, G Hussein; dos Santos, Manoel Antônio; Pillon, Sandra Cristina; Laranjeira, Ronaldo

    2016-01-01

    The aim of this study is to evaluate whether there is a difference in the identified prevalence between the assessment of symptoms of sexual dysfunction in female drug users using a standardized scale and by means of a nonstandardized set of questions about sexual dysfunctions. A cross-sectional study was conducted with two groups of substance-dependent women using the Drug Abuse Screening Test, the Short Alcohol Dependence Data questionnaire, the Fagerström Test for Nicotine Dependence for the evaluation of the severity of dependence, and the Arizona Sexual Experience Scale. In both groups, the severity of dependence and the prevalence of symptoms of sexual dysfunctions in women were similar. The use of standardized and nonstandardized instruments to assess sexual dysfunction symptoms is an essential resource for the provision of good-quality care to this clientele.

  9. Determine equilibrium dissociation constant of drug-membrane receptor affinity using the cell membrane chromatography relative standard method.

    Science.gov (United States)

    Ma, Weina; Yang, Liu; Lv, Yanni; Fu, Jia; Zhang, Yanmin; He, Langchong

    2017-06-23

    The equilibrium dissociation constant (K D ) of drug-membrane receptor affinity is the basic parameter that reflects the strength of interaction. The cell membrane chromatography (CMC) method is an effective technique to study the characteristics of drug-membrane receptor affinity. In this study, the K D value of CMC relative standard method for the determination of drug-membrane receptor affinity was established to analyze the relative K D values of drugs binding to the membrane receptors (Epidermal growth factor receptor and angiotensin II receptor). The K D values obtained by the CMC relative standard method had a strong correlation with those obtained by the frontal analysis method. Additionally, the K D values obtained by CMC relative standard method correlated with pharmacological activity of the drug being evaluated. The CMC relative standard method is a convenient and effective method to evaluate drug-membrane receptor affinity. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Methodological Study to Develop Standard Operational Protocol on Oral Drug Administration for Children.

    Science.gov (United States)

    Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder

    2017-05-01

    To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.

  11. Effect of carbamate molluscicide on African giant land snail ...

    African Journals Online (AJOL)

    The effect of 50, 100, 200, 300, 400 and 500mg/ml of carbamate molluscicide on the behavioural and macroscopic changes of Limicolaria aurora were investigated in the laboratory using Carica papaya as bait for 120h. The data showed that 48h after dosing the organism with furadan, 60% mortality was recorded.

  12. The effects of carbamate pesticide on fish in freshwater ecosystems ...

    African Journals Online (AJOL)

    Other effects include rupture of the columnar epithelium of fish stomach. Carbamate insecticides are generally neurotoxic, inhibiting activity of cholinesterase. High concentration of carbaryl in water leads to fish and fish-food mortality. Keywords: Carbaryl; fish; freshwater ecosystems; pesticide. International Journal of Natural ...

  13. 21 CFR 520.434 - Chlorphenesin carbamate tablets.

    Science.gov (United States)

    2010-04-01

    ... carbamate. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1...) Indications for use. For use as an adjunct to therapy of acute inflammatory and traumatic conditions of... beginning of treatment, the diagnosis should be redetermined and appropriate therapy instituted. Not...

  14. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (French Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  15. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (Spanish Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  16. A review on the status of quality control and standardization of herbal drugs in India

    Directory of Open Access Journals (Sweden)

    Anju Dhiman

    2016-01-01

    Full Text Available Background: Most of the herbal medicines in the world originate from the developing countries. There are ample opportunities for these countries to expand their global export. The world market for botanical medicines including drug products and raw materials has been estimated to have an annual growth rate between 5% and 15%. Total global botanical drug market is estimated at US$62 billion and is expected to grow to the tune of US$5 trillion by the year 2050. In the USA alone, the usage of botanicals has been increased by 380% between the years 1990 and 1997. Materials and Methods: Ayurveda, the Indian system of medicine, is one of the ancient, yet living traditions that face a typical Western bias. Widespread and growing use of botanicals has created public health challenges globally in terms of quality, safety, and efficacy. Results and Discussion: The development of parameters for standardization and quality control of botanicals is a challenging task. Various regulatory authorities, research organizations, and botanical drug manufacturers have contributed in developing guiding principles and addressing issues related to the quality, safety, and efficacy. Conclusions: The present review describes the regulatory aspects of herbal drugs in India and various other countries.

  17. Approaches to Increasing Ethical Compliance in China with Drug Trial Standards of Practice

    DEFF Research Database (Denmark)

    Rosenberg, Jacob

    2016-01-01

    researchers, and strong reinforcement by Chinese journal editors not to publish studies with these flaws, then research ethics and publication standards will probably improve. Other solutions to foster ethical practice of drug trials are discussed including Chinese initiatives directed at managing conflict......Zeng et al.'s Ethics Review highlights some of the challenges associated with clinical research in China. They found that only a minority of published clinical trials of anti-dementia drugs reported that they fulfilled the basic ethical principles as outlined in the Declaration of Helsinki....... With recent reports of scientific misconduct from China, there is an urgent need to find approaches to compel researchers to adhere to ethical research practices. This problem does not call for a simple solution, but if forces are joined with governmental regulations, education in ethics issues for medical...

  18. Carbamates of 4'-demethyl-4-deoxypodophyllotoxin: synthesis, cytotoxicity and cell cycle effects.

    Science.gov (United States)

    Chen, Shi-Wu; Gao, Yuan-Yu; Zhou, Ni-Ni; Liu, Jie; Huang, Wen-Ting; Hui, Ling; Jin, Yan; Jin, Yong-Xin

    2011-12-15

    In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4'-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4'-demethyl- 4-deoxypodophyllic)-α-amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities against four cell lines (A-549, HeLa, SiHa, and HL-60) compared with either parent DPT or anti-cancer drug VP-16. Furthermore, flow cytometric analysis exhibited that N-(1-oxyl-4'-demethyl-4-deoxypodophyllic)-d-α-methine amide (15f) induced cell cycle arrest in the G2/M phase in A-549 cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Iron-Catalyzed Reaction of Urea with Alcohols and Amines: A Safe Alternative for the Synthesis of Primary Carbamates.

    Science.gov (United States)

    Peña-López, Miguel; Neumann, Helfried; Beller, Matthias

    2016-08-23

    A general study of the iron-catalyzed reaction of urea with nucleophiles is here presented. The carbamoylation of alcohols allows for the synthesis of N-unsubstituted (primary) carbamates, including present drugs (Felbamate and Meprobamate), without the necessity to apply phosgene and related derivatives. Using amines as nucleophiles gave rise to the respective mono- and disubstituted ureas via selective transamidation reaction. These atom-economical transformations provide a direct and selective access to valuable compounds from cheap and readily available urea using a simple Lewis-acidic iron(II) catalyst. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Food and drug administration. Radiation protection standards and recommendations for electronic products: the development process

    International Nuclear Information System (INIS)

    Little, M.S.

    1980-01-01

    The Food and Drug Administration is responsible for maintaining a national program to protect the public health from unnecessary and harmful radiation emitted by radiation products. This program involves the promulgation and implementation of mandatory and voluntary standards to promote safe and effective design and use of such products. This paper describes the process by which electronic product radiation safety standards and recommendations are developed. To assist the agency in the development effort and to achieve a sound technological and scientific basis and risk/benefit assessment, it is important that knowledgeable professionals, industrial representatives, and consumers participate in that process. This paper is designed to provide useful information to aid anyone wishing to participate more effectively. (author)

  1. An Integrated Chemical Reactor-Heat Exchanger Based on Ammonium Carbamate (POSTPRINT)

    Science.gov (United States)

    2012-10-01

    AFRL-RQ-WP-TP-2013-0237 AN INTEGRATED CHEMICAL REACTOR-HEAT EXCHANGER BASED ON AMMONIUM CARBAMATE (POSTPRINT) Douglas Johnson and Jamie...4. TITLE AND SUBTITLE AN INTEGRATED CHEMICAL REACTOR-HEAT EXCHANGER BASED ON AMMONIUM CARBAMATE (POSTPRINT) 5a. CONTRACT NUMBER In-house 5b...Ammonium carbamate (AC) which has a decomposition enthalpy of 1.8 MJ/kg is suspended in propylene glycol and used as the heat exchanger working fluid

  2. The toxicity of carbamates to adult Anopheles stephensi*

    Science.gov (United States)

    Hadaway, A. B.; Barlow, F.

    1963-01-01

    Experiments to evaluate the residual contact toxicity of five carbamates to adult Anopheles stephensi have shown that four of the compounds (Hercules 7522, UC 10854, Bayer 39007 and RE-5305) were effective as contact insecticides for at least three months when applied as wettable powders on plywood at a dosage of 1 g/m2. They were rapidly sorbed, however, on dried mud bricks stored at 25°C and 50%-55% relative humidity, and were unstable on fresh limewash. The authors conclude that, although these compounds show promise as residual insecticides, their residual properties may be expected to vary according to the properties of the building materials to which they are applied. A fifth carbamate, Sevin, was much less effective as a contact insecticide. PMID:14166987

  3. The IR spectra, hydrogen bonding and conformations of aliphatic and aromatic epoxy carbamates

    Science.gov (United States)

    Furer, V. L.

    1999-12-01

    The IR spectra of hexamethylene-bis (methyl) glycidyl carbamate, toluene-2,4-bis (methyl) glycidyl carbamate in the crystalline state and in the melt were studied. The absorption curves for the most stable molecular conformations were compared with experimental IR spectra. The IR spectra of toluene-2,4-bis (methyl) glycidyl carbamate and methyl- N-methyl carbamate clusters were calculated. The spectral features of the different molecular structures were revealed. The results obtained can be used for the analysis of the chemical and physical transformations in polyurethanes.

  4. Integrity, standards, and QC-related issues with big data in pre-clinical drug discovery.

    Science.gov (United States)

    Brothers, John F; Ung, Matthew; Escalante-Chong, Renan; Ross, Jermaine; Zhang, Jenny; Cha, Yoonjeong; Lysaght, Andrew; Funt, Jason; Kusko, Rebecca

    2018-03-15

    The tremendous expansion of data analytics and public and private big datasets presents an important opportunity for pre-clinical drug discovery and development. In the field of life sciences, the growth of genetic, genomic, transcriptomic and proteomic data is partly driven by a rapid decline in experimental costs as biotechnology improves throughput, scalability, and speed. Yet far too many researchers tend to underestimate the challenges and consequences involving data integrity and quality standards. Given the effect of data integrity on scientific interpretation, these issues have significant implications during preclinical drug development. We describe standardized approaches for maximizing the utility of publicly available or privately generated biological data and address some of the common pitfalls. We also discuss the increasing interest to integrate and interpret cross-platform data. Principles outlined here should serve as a useful broad guide for existing analytical practices and pipelines and as a tool for developing additional insights into therapeutics using big data. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Efficient synthesis of readily water-soluble sulfonic Acid carbamates.

    Science.gov (United States)

    Idzik, Krzysztof R; Nödler, Karsten; Licha, Tobias

    2015-04-16

    A series of various readily water-soluble carbamates were synthesized with good yields. These compounds are useful chemical tracers for assessing the cooling progress in a georeservoir during geothermal power plant operation. Acylation of primary amines was carried out as well as using a solution of sodium bicarbonate and without the presence of salt. Products were characterized by 1H-NMR and 13C-NMR. Purity was confirmed through elemental analysis.

  6. On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

    Science.gov (United States)

    Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza

    2015-08-01

    The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Carbamate Pesticide-Induced Apoptosis in Human T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Qing Li

    2015-04-01

    Full Text Available We previously found that carbamate pesticides induced significant apoptosis in human natural killer cells. To investigate whether carbamate pesticides also induce apoptosis in human T lymphocytes, in the present study Jurkat human T cells were treated in vitro with thiram, maneb, carbaryl or ziram. Apoptosis was determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspase 3 and mitochondrial cytochrome-c release were determined by flow cytometry. We found that thiram, ziram, maneb and carbaryl also induced apoptosis in a time- and dose-dependent manner in the human T cells. However, the strength of the apoptosis-inducing effect differed among the pesticides, with the: thiram > ziram > maneb > carbaryl. Moreover, thiram significantly increased the intracellular level of active caspase 3 and caspase inhibitors significantly inhibited apoptosis. Thiram also significantly caused mitochondrial cytochrome-c release. These findings indicate that carbamate pesticides can induce apoptosis in human T cells, and the apoptosis is mediated by the activation of caspases and the release of mitochondrial cytochrome-c.

  8. Carbonic anhydrase and acetylcholinesterase inhibitory effects of carbamates and sulfamoylcarbamates.

    Science.gov (United States)

    Göçer, Hülya; Akincioğlu, Akın; Göksu, Süleyman; Gülçin, İlhami; Supuran, Claudiu T

    2015-04-01

    Carbonic anhydrases (CA), as a family of metalloenzymes, are found in almost every type of tissue and play an important role in catalyzing the equilibration of carbon dioxide and carbonic acid. In this study, a series of carbamate derivative was synthesized, and their inhibition effects on hCA I, hCA II and acetylcholinesterase (AChE) enzymes were investigated. They were determined to be very good inhibitor against for both isoenzymes (hCA I and hCA II) and AChE. The hCA I and hCA II were effectively inhibited by the carbamate derivatives, with inhibition constants (Ki) in the range of 194.4-893.5 nM (for hCA I) and 103.9-835.7 nM (for hCA II). On the other hand, Ki parameters of these compounds for AChE enzyme inhibition were determined in the range of 12.0-61.3 nM. The results clearly showed that both CA isoenzymes and AChE were inhibited by carbamate derivatives at the nM levels.

  9. Discovery of carbamate degrading enzymes by functional metagenomics.

    Directory of Open Access Journals (Sweden)

    Lisa Ufarté

    Full Text Available Bioremediation of pollutants is a major concern worldwide, leading to the research of new processes to break down and recycle xenobiotics and environment contaminating polymers. Among them, carbamates have a very broad spectrum of uses, such as toxinogenic pesticides or elastomers. In this study, we mined the bovine rumen microbiome for carbamate degrading enzymes. We isolated 26 hit clones exhibiting esterase activity, and were able to degrade at least one of the targeted polyurethane and pesticide carbamate compounds. The most active clone was deeply characterized. In addition to Impranil, this clone was active on Tween 20, pNP-acetate, butyrate and palmitate, and on the insecticide fenobucarb. Sequencing and sub-cloning of the best target revealed a novel carboxyl-ester hydrolase belonging to the lipolytic family IV, named CE_Ubrb. This study highlights the potential of highly diverse microbiota such as the ruminal one for the discovery of promiscuous enzymes, whose versatility could be exploited for industrial uses.

  10. Detection of organophosphate and carbamate pesticides in vegetable samples by a photothermal biosensor.

    Science.gov (United States)

    Pogacnik, Lea; Franko, Mladen

    2003-01-01

    Previously developed photothermal biosensor was optimised by determining the most suitable enzyme substrate (acetylthiocholine iodide) and the optimal carrier buffer (0.05 M phosphate buffer, pH 8.0). Excitation laser operating at 488 nm and 120 mW power provided the highest biosensor sensitivity. The biosensor was tested for detection of toxic organophosphate and carbamate compounds present in samples of salad, iceberg lettuce, and onion. Sufficient sensitivities to different pesticides (carbofuran, propamocarb, oxydemeton-methyl and parathion-ethyl) were achieved without time-consuming sample preparation procedures. The results show good agreement with the concentrations of pesticides determined with standard GC-MS detection method. The developed photothermal biosensor offers new low cost means to detect low concentrations of pesticides in vegetable samples with high throughput and little or no sample pretreatment.

  11. DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PESTICIDES

    Science.gov (United States)

    The US EPAs N-Methyl Carbamate Cumulative Risk Assessment (NMCRA) assesses the effect on acetylcholine esterase (AChE) activity of exposure to 10 N-methyl carbamate (NMC) pesticides through dietary, drinking water, and residential exposures.

  12. Standards of the Network of Colleges and Universities Committed to the Elimination of Drug and Alcohol Abuse.

    Science.gov (United States)

    Office of Educational Research and Improvement (ED), Washington, DC.

    The background, goals and standards of the Network of Colleges and Universities Committed to the Elimination of Drug and Alcohol Abuse are described. The network was formed in 1987 at the instigation of the Office of Educational Research and Improvement, U.S. Department of Education. A planning group met to establish the standards for…

  13. Human pregnane X receptor is activated by dibenzazepine carbamate-based inhibitors of constitutive androstane receptor.

    Science.gov (United States)

    Jeske, Judith; Windshügel, Björn; Thasler, Wolfgang E; Schwab, Matthias; Burk, Oliver

    2017-06-01

    Unintentional activation of xenosensing nuclear receptors pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR) by clinical drug use is known to produce severe side effects in patients, which may be overcome by co-administering antagonists. However, especially antagonizing CAR is hampered by the lack of specific inhibitors, which do not activate PXR. Recently, compounds based on a dibenzazepine carbamate scaffold were identified as potent CAR inhibitors. However, their potential to activate PXR was not thoroughly investigated, even if the lead compound was named "CAR inhibitor not PXR activator 1" (CINPA1). Thus, we performed a comprehensive analysis of the interaction of CINPA1 and four analogs with PXR. Cellular assays were used to investigate intra- and intermolecular interactions and transactivation activity of PXR as a function of the compounds. Modulation of PXR target gene expression was analyzed in primary human hepatocytes. Ligand binding to PXR was investigated by molecular docking and limited proteolytic digestion. We show here that CINPA1 induced the assembly of the PXR ligand-binding domain, released co-repressors from and recruited co-activators to the receptor. CINPA1 and its analogs induced the PXR-dependent activation of a CYP3A4 reporter gene and CINPA1 induced the expression of endogenous cytochrome P450 genes in primary hepatocytes, while not consistently inhibiting CAR-mediated induction. Molecular docking revealed favorable binding of CINPA1 and analogs to the PXR ligand-binding pocket, which was confirmed in vitro. Altogether, our data provide consistent evidence that compounds with a dibenzazepine carbamate scaffold, such as CINPA1 and its four analogs, bind to and activate PXR.

  14. NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice

    International Nuclear Information System (INIS)

    Dekundy, Andrzej; Kaminski, Rafal M.; Zielinska, Elzbieta; Turski, Waldemar A.

    2007-01-01

    Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.8 mg/kg), on convulsant and lethal properties of an OP pesticide dichlorvos or a carbamate drug physostigmine, were studied in mice. Both dichlorvos and physostigmine induced dose-dependent seizure activity and lethality. Atropine did not prevent the occurrence of convulsions but decreased the lethal effects of both dichlorvos and physostigmine. MK-801 or CPP blocked or attenuated, respectively, dichlorvos-induced convulsions. Contrariwise, NMDA antagonists had no effect in physostigmine-induced seizures or lethality produced by dichlorvos or physostigmine. Concurrent pretreatment with atropine and either MK-801 or CPP blocked or alleviated seizures produced by dichlorvos, but not by physostigmine. Both MK-801 and CPP co-administered with atropine enhanced its antilethal effects in both dichlorvos and physostigmine poisoning. In both saline- and AChE inhibitor-treated mice, no interaction of the investigated antidotes with brain cholinesterase was found. The data indicate that both muscarinic ACh and NMDA receptor-mediated mechanisms contribute to the acute toxicity of AChE inhibitors, and NMDA receptors seem critical to OP-induced seizures

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

    Directory of Open Access Journals (Sweden)

    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.

  16. O-(triazolyl)methyl carbamates as a novel and potent class of fatty acid amide hydrolase (FAAH) inhibitors.

    Science.gov (United States)

    Colombano, Giampiero; Albani, Clara; Ottonello, Giuliana; Ribeiro, Alison; Scarpelli, Rita; Tarozzo, Glauco; Daglian, Jennifer; Jung, Kwang-Mook; Piomelli, Daniele; Bandiera, Tiziano

    2015-02-01

    Inhibition of fatty acid amide hydrolase (FAAH) activity is under investigation as a valuable strategy for the treatment of several disorders, including pain and drug addiction. A number of potent FAAH inhibitors belonging to different chemical classes have been disclosed to date; O-aryl carbamates are one of the most representative families. In the search for novel FAAH inhibitors, a series of O-(1,2,3-triazol-4-yl)methyl carbamate derivatives were designed and synthesized exploiting a copper- catalyzed [3+2] cycloaddition reaction between azides and alkynes (click chemistry). Exploration of the structure-activity relationships within this new class of compounds identified potent inhibitors of both rat and human FAAH with IC50 values in the single-digit nanomolar range. In addition, these derivatives showed improved stability in rat plasma and kinetic solubility in buffer with respect to the lead compound. Based on the results of the study, the novel analogues identified can be considered to be promising starting point for the development of new FAAH inhibitors with improved drug-like properties. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Copper-catalyzed one-pot synthesis of N-aryl oxazolidinones from amino alcohol carbamates.

    Science.gov (United States)

    Mahy, William; Plucinski, Pawel K; Frost, Christopher G

    2014-10-03

    An efficient sequential intramolecular cyclization of amino alcohol carbamates followed by Cu-catalyzed cross-coupling with aryl iodides under mild conditions has been developed. The reaction occurred in good yields and tolerated aryl iodides containing functionalities such as nitriles, ketones, ethers, and halogens. Heteroaryl iodides and substituted amino alcohol carbamates were also well tolerated.

  18. 40 CFR 268.39 - Waste specific prohibitions-spent aluminum potliners; reactive; and carbamate wastes.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Waste specific prohibitions-spent aluminum potliners; reactive; and carbamate wastes. 268.39 Section 268.39 Protection of Environment... Land Disposal § 268.39 Waste specific prohibitions—spent aluminum potliners; reactive; and carbamate...

  19. Subchronic Toxicity Study in Rats of Two New Ethyl-Carbamates with Ixodicidal Activity

    Directory of Open Access Journals (Sweden)

    María Guadalupe Prado-Ochoa

    2014-01-01

    Full Text Available Female and male Wistar rats were used to determine the subchronic oral toxicities of two new ethyl-carbamates with ixodicidal activities (ethyl-4-bromphenyl-carbamate and ethyl-4-chlorphenyl-carbamate. The evaluated carbamates were administered in the drinking water (12.5, 25 and 50 mg/kg/day for 90 days. Exposure to the evaluated carbamates did not cause mortality or clinical signs and did not affect food consumption or weight gain. However, exposure to these carbamates produced alterations in water consumption, hematocrit, percentages of reticulocytes, plasma proteins, some biochemical parameters (aspartate aminotransferase, gamma-glutamyl transpeptidase, cholinesterase, and creatinine activities, thiobarbituric acid reactive substances, and the relative weight of the spleen. Histologically, slight pathological alterations were found in the liver that were consistent with the observed biochemical alterations. The nonobserved adverse effect levels (NOAELs of the evaluated carbamates were 12.5 mg/kg/day for both the female and male rats. The low severity and reversibility of the majority of the observed alterations suggest that the evaluated carbamates have low subchronic toxicity.

  20. Drug: D08442 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available icine acetylcholinesterase (AChE) [KO:K01049] ... CAS: 114-26-1 PubChem: 96025128 ChEBI: 34938 ChEMBL: CHEMBL446060 LigandBox: D08442 NIKKAJI: J2.893B ... ... D08442 Drug Propoxur (BAN); Bolfo (TN) ... C11H15NO3 D08442.gif ... Same as: C14334 ... Carbamate veterinary med

  1. Synthesis and decreasing Aβ content evaluation of arctigenin-4-yl carbamate derivatives.

    Science.gov (United States)

    Xu, Xingyu; Li, Cong; Lei, Min; Zhu, Zhiyuan; Yan, Jianming; Shen, Xu; Hu, Lihong

    2016-07-01

    A series of arctigenin-4-yl carbamate derivatives were synthesized and evaluated for potency in reducing β-amyloid (Aβ) content in HEK293-APPswe cells. Most of the arctigenin-4-yl aralkyl or aryl carbamate derivatives showed improved potency in reducing Aβ content. Among the synthesized compounds, arctigenin-4-yl (3-chlorophenyl)carbamate (20) exhibited the strongest potency with 78.7% Aβ content reduction at 20μM. Furthermore, the effect of arctigenin-4-yl (4-chlorophenyl)carbamate (19) and arctigenin-4-yl (3-chlorophenyl)carbamate (20) on lowing Aβ content was better than arctigenin under the concentrations of 1, 10 and 20μM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Piezoelectric Biosensors for Organophosphate and Carbamate Pesticides: A Review

    Directory of Open Access Journals (Sweden)

    Giovanna Marrazza

    2014-09-01

    Full Text Available Due to the great amount of pesticides currently being used, there is an increased interest for developing biosensors for their detection. Among all the physical transducers, piezoelectric systems have emerged as the most attractive due to their simplicity, low instrumentation costs, possibility for real-time and label-free detection and generally high sensitivity. This paper presents an overview of biosensors based on the quartz crystal microbalance, which have been reported in the literature for organophosphate and carbamate pesticide analysis.

  3. Brazilian vodkas have undetectable levels of ethyl carbamate

    Directory of Open Access Journals (Sweden)

    Elainy V. S. Pereira

    2013-01-01

    Full Text Available While in Europe vodka is mainly derived from potatoes or cereals, a large proportion of Brazilian vodka is likely obtained from sugarcane, which contains ethyl carbamate (EC precursors. EC, in addition to several other contaminants and congeners, were investigated in 32 samples of Brazilian vodka. All samples complied with the Brazilian regulations for congeners and contaminants, having EC content below 0.01 mg/L (detection limit. These results are probably related to the processing of vodka, in particular the use of extractive and rectifying stainless steel distillation columns, which allow the production of high strength spirits with low levels of congeners and contaminants.

  4. Vortex-assisted surfactant-enhanced emulsification liquid-liquid microextraction for the determination of carbamates in juices by micellar electrokinetic chromatography tandem mass spectrometry.

    Science.gov (United States)

    Moreno-González, David; Huertas-Pérez, José F; García-Campaña, Ana M; Gámiz-Gracia, Laura

    2015-07-01

    A new method based on vortex-assisted surfactant-enhanced-emulsification liquid-liquid microextraction has been developed for the extraction of carbamate pesticides in juice samples prior to their determination by micellar electrokinetic chromatography coupled to tandem mass spectrometry. This sample treatment allowed the satisfactory extraction and the extract clean-up of 25 carbamates from different fruit and vegetal juices (banana, tomato, and peach). In this study, the addition of ammonium perfluorooctanoate in the aqueous sample in combination with vortex agitation, provided very clean extracts with short extraction times. Under optimized conditions, recoveries of the proposed method for these pesticides from fortified juice samples ranged from 81% to 104%, with relative standard deviations lower than 15%. Limits of quantification were between 2.3µgkg(-)(1) and 4.7µgkg(-)(1), showing the high sensitivity of this fast and simple method. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. An evaluation of liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization for the rapid and simultaneous measurement of carbamate pesticides and organophorus pesticides

    International Nuclear Information System (INIS)

    Kim, Byung Joo; So, Hun Young

    2000-01-01

    Liquid chromatography/mass spectrometry with an atmospheric pressure chemical ionization interface (LC/APCI/MS) is evaluated for the simultaneous determination of carbamate pesticides and organophosphorus pesticides in a single chromatographic analysis. APCI mass spectra of those compounds were obtained to study their ionization characteristics. APCI provided abundant ions such as protonated molecules and characteristic fragment ions for carbamate pesticides and organophosphorus pesticides. To evaluate the feasibility of the LC/APCI/MS for a routine quantitative analysis, the linearity and repeatability of LC/APCI/MS were examined by measuring standard solution mixtures of five carbamate pesticides and four organophosphorus pesticides over the range of 1 to 100 μg/mL. The peak areas in chromatograms of characteristic ions for those compounds showed less than 3% of variation from run to tun. The standard calibration curves for the nine pesticides show good linearity in the concentration range. The detection limits of the LC/APCI/MS system for those compounds range from 0.006 to 0.2 ng

  6. An evaluation of liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization for the rapid and simultaneous measurement of carbamate pesticides and organophorus pesticides

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byung Joo; So, Hun Young [Korea Research Institute of Standards and Sceince, Taejon (Korea, Republic of)

    2000-05-01

    Liquid chromatography/mass spectrometry with an atmospheric pressure chemical ionization interface (LC/APCI/MS) is evaluated for the simultaneous determination of carbamate pesticides and organophosphorus pesticides in a single chromatographic analysis. APCI mass spectra of those compounds were obtained to study their ionization characteristics. APCI provided abundant ions such as protonated molecules and characteristic fragment ions for carbamate pesticides and organophosphorus pesticides. To evaluate the feasibility of the LC/APCI/MS for a routine quantitative analysis, the linearity and repeatability of LC/APCI/MS were examined by measuring standard solution mixtures of five carbamate pesticides and four organophosphorus pesticides over the range of 1 to 100 {mu}g/mL. The peak areas in chromatograms of characteristic ions for those compounds showed less than 3% of variation from run to tun. The standard calibration curves for the nine pesticides show good linearity in the concentration range. The detection limits of the LC/APCI/MS system for those compounds range from 0.006 to 0.2 ng.

  7. Using standardized methods for research on HIV and injecting drug use in developing/transitional countries: case study from the WHO Drug Injection Study Phase II

    Directory of Open Access Journals (Sweden)

    Stimson Gerry V

    2006-03-01

    Full Text Available Abstract Background Successful cross-national research requires methods that are both standardized across sites and adaptable to local conditions. We report on the development and implementation of the methodology underlying the survey component of the WHO Drug Injection Study Phase II – a multi-site study of risk behavior and HIV seroprevalence among Injecting Drug Users (IDUs. Methods Standardized operational guidelines were developed by the Survey Coordinating Center in collaboration with the WHO Project Officer and participating site Investigators. Throughout the duration of the study, survey implementation at the local level was monitored by the Coordinating Center. Surveys were conducted in 12 different cities. Prior rapid assessment conducted in 10 cities provided insight into local context and guided survey implementation. Where possible, subjects were recruited both from drug abuse treatment centers and via street outreach. While emphasis was on IDUs, non-injectors were also recruited in cities with substantial non-injecting use of injectable drugs. A structured interview and HIV counseling/testing were administered. Results Over 5,000 subjects were recruited. Subjects were recruited from both drug treatment and street outreach in 10 cities. Non-injectors were recruited in nine cities. Prior rapid assessment identified suitable recruitment areas, reduced drug users' distrust of survey staff, and revealed site-specific risk behaviors. Centralized survey coordination facilitated local questionnaire modification within a core structure, standardized data collection protocols, uniform database structure, and cross-site analyses. Major site-specific problems included: questionnaire translation difficulties; locating affordable HIV-testing facilities; recruitment from drug treatment due to limited/selective treatment infrastructure; access to specific sub-groups of drug users in the community, particularly females or higher income groups

  8. Graphene based solid phase extraction combined with ultra high performance liquid chromatography-tandem mass spectrometry for carbamate pesticides analysis in environmental water samples.

    Science.gov (United States)

    Shi, Zhihong; Hu, Junda; Li, Qi; Zhang, Shulan; Liang, Yuhuan; Zhang, Hongyi

    2014-08-15

    In this paper, graphene, a new sorbent material, was synthesized and used for solid-phase extraction (SPE) of the six carbamate pesticides (pirimicarb, baygon, carbaryl, isoprocarb, baycarb and diethofencarb) in environmental water samples. The target analytes can be extracted on the graphene-packed SPE cartridge, and then eluted with acetone. The eluate was collected and dried by high purity nitrogen gas at room temperature. 1mL of 20% (v/v) acetonitrile aqueous solution was used to redissolve the residue. The final sample solution was analyzed by ultra performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) system. Under optimum conditions, good linearity was obtained for the carbamates with correlation coefficient in the range of 0.9992-0.9998. The limits of detection (S/N=3) for the six carbamate pesticides were in the range of 0.5-6.9ngL(-1). Relative standard deviations (RSD) for five replicate determinations were below 5.54%. RSD values for cartridge-to-cartridge precision (n=7) were in the range of 1.27-8.13%. After proper regeneration, the graphene-packed SPE cartridge could be re-used over 100 times for standard solution without significant loss of performance. The enrichment factors for the target analytes were in the range of 34.2-51.7. The established method has been successfully applied to the determination of carbamate pesticide residues in environmental water samples such as river water, well water and lake water. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Lead optimization studies towards the discovery of novel carbamates as potent AChE inhibitors for the potential treatment of Alzheimer's disease.

    Science.gov (United States)

    Roy, Kuldeep K; Tota, Santoshkumar; Tripathi, Tusha; Chander, Subhash; Nath, Chandishwar; Saxena, Anil K

    2012-11-01

    The optimization of our previous lead compound 1 (AChE IC(50)=3.31 μM) through synthesis and pharmacology of a series of novel carbamates is reported. The synthesized compounds were evaluated against mouse brain AChE enzyme using the colorimetric method described by Ellman et al. The three compounds 6a (IC(50)=2.57μM), 6b (IC(50)=0.70 μM) and 6i (IC(50)=2.56 μM) exhibited potent in vitro AChE inhibitory activities comparable to the drug rivastigmine (IC(50)=1.11 μM). Among them, the compound 6b has been selected as possible optimized lead for further neuropharmacological studies. In addition, the AChE-carbamate Michaelis complexes of these potent compounds including rivastigmine and ganstigmine have been modeled using covalent docking protocol of GOLD and important direct/indirect interactions contributing to stabilization of the AChE-carbamate Michaelis complexes have been investigated. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Direct, Intermolecular, Enantioselective, Iridium-Catalyzed Allylation of Carbamates to Form Carbamate-Protected, Branched Allylic Amines

    Science.gov (United States)

    Weix, Daniel J.; Marković, Dean; Ueda, Mitsuhiro; Hartwig, John F.

    2009-01-01

    The direct reaction between carbamates and achiral allylic carbonates to form branched, conveniently protected primary allylic amines with high regioselectivity and enantioselectivity is reported. This process occurs without base or with 0.5 equiv K3PO4 in the presence of a metalacyclic iridium catalyst containing a labile ethylene ligand. The reactions of aryl, heteroaryl and alkyl-substituted allylic carbonates with BocNH2, FmocNH2, CbzNH2, TrocNH2, TeocNH2, and 2-oxazolidinone occur in good yields, with high selectivity for the branched isomer, and high enantioselectivities (98% average ee). PMID:19552468

  11. Human experimental pain models: A review of standardized methods in drug development

    Directory of Open Access Journals (Sweden)

    K. Sunil kumar Reddy

    2012-01-01

    Full Text Available Human experimental pain models are essential in understanding the pain mechanisms and appear to be ideally suited to test analgesic compounds. The challenge that confronts both the clinician and the scientist is to match specific treatments to different pain-generating mechanisms and hence reach a pain treatment tailored to each individual patient. Experimental pain models offer the possibility to explore the pain system under controlled settings. Standardized stimuli of different modalities (i.e., mechanical, thermal, electrical, or chemical can be applied to the skin, muscles, and viscera for a differentiated and comprehensive assessment of various pain pathways and mechanisms. Using a multimodel-multistructure testing, the nociception arising from different body structures can be explored and modulation of specific biomarkers by new and existing analgesic drugs can be profiled. The value of human experimental pain models is to link animal and clinical pain studies, providing new possibilities for designing successful clinical trials. Spontaneous pain, the main compliant of the neuropathic patients, but currently there is no human model available that would mimic chronic pain. Therefore, current human pain models cannot replace patient studies for studying efficacy of analgesic compounds, although being helpful for proof-of-concept studies and dose finding.

  12. New Water-Soluble Carbamate Ester Derivatives of Resveratrol

    Directory of Open Access Journals (Sweden)

    Andrea Mattarei

    2014-10-01

    Full Text Available Low bioavailability severely hinders exploitation of the biomedical potential of resveratrol. Extensive phase-II metabolism and poor water solubility contribute to lowering the concentrations of resveratrol in the bloodstream after oral administration. Prodrugs may provide a solution—protection of the phenolic functions hinders conjugative metabolism and can be exploited to modulate the physicochemical properties of the compound. We report here the synthesis and characterization of carbamate ester derivatives of resveratrol bearing on each nitrogen atom a methyl group and either a methoxy-poly(ethylene glycol-350 (mPEG-350 or a butyl-glucosyl promoiety conferring high water solubility. Ex vivo absorption studies revealed that the butyl-glucosyl conjugate, unlike the mPEG-350 one, is able to permeate the intestinal wall. In vivo pharmacokinetics confirmed absorption after oral administration and showed that no hydrolysis of the carbamate groups takes place. Thus, sugar groups can be attached to resveratrol to obtain soluble derivatives maintaining to some degree the ability to permeate biomembranes, perhaps by facilitated or active transport.

  13. Mosquitocidal carbamates with low toxicity to agricultural pests: an advantageous property for insecticide resistance management.

    Science.gov (United States)

    Swale, Daniel R; Carlier, Paul R; Hartsel, Joshua A; Ma, Ming; Bloomquist, Jeffrey R

    2015-08-01

    Insecticide resistance in the malaria mosquito Anopheles gambiae is well documented, and widespread agricultural use of pyrethroids may exacerbate development of resistance when pyrethroids are used in vector control. We have developed carbamate anticholinesterases that possess a high degree of An. gambiae:human selectivity for enzyme inhibition. The purpose of this study was to assess the spectrum of activity of these carbamates against other mosquitoes and agricultural pests. Experimental carbamates were potent inhibitors of mosquito acetylcholinesterases, with IC50 values in the nanomolar range. Similar potencies were observed for Musca domestica and Drosophila melanogaster enzymes. Although meta-substituted carbamates were potent inhibitors, two ortho-substituted carbamates displayed poor enzyme inhibition (IC50 ≥ 10(-6)  M) in honey bee (Apis mellifera), Asian citrus psyllid (Diaphorina citri) and lepidopteran agricultural pests (Plutella xylostella and Ostrinia nubilalis). Enzyme inhibition results were confirmed by toxicity studies in caterpillars, where the new carbamates were 2-3-fold less toxic than propoxur and up to tenfold less active than bendiocarb, indicating little utility of these compounds for crop protection. The experimental carbamates were broadly active against mosquito species but not agricultural pests, which should mitigate selection for mosquito insecticide resistance by reducing agricultural uses of these compounds. © 2014 Society of Chemical Industry. © 2014 Society of Chemical Industry.

  14. Genotoxicity and cytotoxicity assessment of new ethyl-carbamates with ixodicidal activity.

    Science.gov (United States)

    Prado-Ochoa, María Guadalupe; Muñoz-Guzmán, Marco Antonio; Vázquez-Valadez, Víctor Hugo; Velázquez-Sánchez, Ana María; Salazar, Ana María; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2016-09-01

    The mammalian erythrocyte micronucleus test was used on the peripheral blood of Wistar rats exposed to two new ethyl-carbamates: ethyl-4-bromophenyl-carbamate (LQM 919) and ethyl-4-chlorophenyl-carbamate (LQM 996) to analyze their genotoxic potential. The mitotic index and cell proliferation kinetics in human lymphocyte cultures in the presence of these ethyl-carbamates were used to evaluate cytotoxicity and cytostaticity respectively. Exposure to greater acute doses (300mg/kg) and to all of the subchronic doses (12.5, 25 and 50mg/kg daily for 90 days) of these ethyl-carbamates induced an increased frequency (pcarbamates. Increases in MN-PCE was higher in males than in females exposed to LQM 996 50mg/Kg (pcarbamate exposure. The highest concentration (0.3mM) of both ethyl-carbamates in lymphocyte cultures increased the percentage of cells in first division metaphase and decreased the percentage of cells in third division metaphase, indicating an increase in cell cycle length or a possible cell cycle arrest in metaphase (cytostatic effect). The results of this study show that the evaluated ethyl-carbamates may induce genotoxic damage in rats and alterations in the human lymphocyte cell cycle. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Syntheses and evaluation of anticonvulsant activity of novel branched alkyl carbamates.

    Science.gov (United States)

    Hen, Naama; Bialer, Meir; Yagen, Boris

    2012-03-22

    A novel class of 19 carbamates was synthesized, and their anticonvulsant activity was comparatively evaluated in the rat maximal electroshock (MES) and subcutaneous metrazol (scMet) seizure tests and pilocarpine-induced status epilepticus (SE) model. In spite of the alkyl-carbamates' close structural features, only compounds 34, 38, and 40 were active at the MES test. The analogues 2-ethyl-3-methyl-butyl-carbamate (34) and 2-ethyl-3-methyl-pentyl-carbamate (38) also exhibited potent activity in the pilocarpine-SE model 30 min postseizure onset. Extending the aliphatic side chains of homologous carbamates from 7 to 8 (34 to 35) and from 8 to 9 carbons in the homologues 38 and 43 decreased the activity in the pilocarpine-SE model from ED(50) = 81 mg/kg (34) to 94 mg/kg (35) and from 96 mg/kg (38) to 114 mg/kg (43), respectively. The most potent carbamate, phenyl-ethyl-carbamate (47) (MES ED(50) = 16 mg/kg) contains an aromatic moiety in its structure. Compounds 34, 38, 40, and 47 offer the optimal efficacy-safety profile and, consequently, are promising candidates for development as new antiepileptics.

  16. 78 FR 6762 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

    Science.gov (United States)

    2013-01-31

    ... AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meeting. SUMMARY: The Food and Drug Administration (FDA) is announcing a public meeting to discuss the proposed rules to establish... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110...

  17. 78 FR 10107 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

    Science.gov (United States)

    2013-02-13

    ... AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meeting. SUMMARY: The Food and Drug Administration (FDA) is providing public meeting registration information for two FSMA related... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110...

  18. 77 FR 57055 - Regulatory New Drug Review: Solutions for Study Data Exchange Standards; Notice of Meeting...

    Science.gov (United States)

    2012-09-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I Regulatory New Drug Review: Solutions for..., 2012 (77 FR 48491). The document announced a meeting entitled ``Regulatory New Drug Review: Solutions...

  19. Everolimus treatment for patients with autoimmune hepatitis and poor response to standard therapy and drug alternatives in use

    DEFF Research Database (Denmark)

    Ytting, Henriette; Larsen, Fin Stolze

    2015-01-01

    here report the efficacy of everolimus treatment of patients with AIH. MATERIALS AND METHODS: Seven patients (six female, mean age 47 years, range 22-62 years) in whom disease control could not be achieved with standard therapy or the alternative drugs in use were included. RESULTS: Treatment...

  20. Standard drug concentrations and smart-pump technology reduce continuous-medication-infusion errors in pediatric patients.

    Science.gov (United States)

    Larsen, Gitte Y; Parker, Howard B; Cash, Jared; O'Connell, Mary; Grant, MaryJo C

    2005-07-01

    To determine if combining standard drug concentrations with "smart-pump" technology reduces reported medication-infusion errors. Preintervention and postintervention comparison of reported medication errors related to infusion therapies during the calendar years 2002 and 2003. A 242-bed university-affiliated tertiary pediatric hospital. Change in continuous-medication-infusion process, comprising the adoption of (1) standard drug concentrations, (2) "smart" syringe pumps, and (3) human-engineered medication labels. Comparison of reported continuous-medication-infusion errors before and after the intervention. The number of reported errors dropped by 73% for an absolute risk reduction of 3.1 to 0.8 per 1000 doses. Preparation errors that occurred in the pharmacy decreased from 0.66 to 0.16 per 1000 doses; the number of 10-fold errors in dosage decreased from 0.41 to 0.08 per 1000 doses. The use of standard drug concentrations, smart syringe pumps, and user-friendly labels reduces reported errors associated with continuous medication infusions. Standard drug concentrations can be chosen to allow most neonates to receive needed medications without concerns related to excess fluid administration.

  1. Paclitaxel C-10 carbamates: potential candidates for the treatment of neurodegenerative tauopathies

    Science.gov (United States)

    Hyde, Edward; Deiches, Robert F.; –Y. Lee, Virginia M.; Trojanowski, John Q.; Huryn, Donna

    2009-01-01

    A series of paclitaxel C-10 carbamates were synthesized and evaluated in a bi-directional permeability assay in comparison with paclitaxel and the blood-brain barrier-permeable C-10 ester derivative, TX-67. A number of the carbamates were found not to be substrates for Pgp. Moreover, when tested for Pgp-inhibitory potential, representative compounds proved to be devoid of Pgp interactions. Side–by–side comparison between TX-67 and the corresponding C-10 carbamate, CNDR-3, revealed a significantly longer half–life for CNDR-3 in both mouse and human plasma, suggesting that this class of derivatives is appropriate for further in vivo evaluation. PMID:17485207

  2. Factorial design optimization of experimental variables in preconcentration of carbamates pesticides in water samples using solid phase extraction and liquid chromatography-electrospray-mass spectrometry determination.

    Science.gov (United States)

    Latrous El Atrache, Latifa; Ben Sghaier, Rafika; Bejaoui Kefi, Bochra; Haldys, Violette; Dachraoui, Mohamed; Tortajada, Jeanine

    2013-12-15

    An experimental design was applied for the optimization of extraction process of carbamates pesticides from surface water samples. Solid phase extraction (SPE) of carbamates compounds and their determination by liquid chromatography coupled to electrospray mass spectrometry detector were considered. A two level full factorial design 2(k) was used for selecting the variables which affected the extraction procedure. Eluent and sample volumes were statistically the most significant parameters. These significant variables were optimized using Doehlert matrix. The developed SPE method included 200mg of C-18 sorbent, 143.5 mL of water sample and 5.5 mL of acetonitrile in the elution step. For validation of the technique, accuracy, precision, detection and quantification limits, linearity, sensibility and selectivity were evaluated. Extraction recovery percentages of all the carbamates were above 90% with relative standard deviations (R.S.D.) in the range of 3-11%. The extraction method was selective and the detection and quantification limits were between 0.1 and 0.5 µg L(-1), and 1 and 3 µg L(-1), respectively. © 2013 Elsevier B.V. All rights reserved.

  3. Dispersive solid-phase extraction cleanup combined with accelerated solvent extraction for the determination of carbamate pesticide residues in Radix Glycyrrhizae samples by UPLC-MS-MS.

    Science.gov (United States)

    Yang, Ru-zhen; Wang, Jin-hua; Wang, Ming-lin; Zhang, Rong; Lu, Xiao-yu; Liu, Wei-hua

    2011-10-01

    Dispersive solid-phase extraction (DSPE) cleanup combined with accelerated solvent extraction (ASE) is described here as a new approach for the extraction of carbamate pesticides in Radix Glycyrrhizae samples prior to UPLC-MS-MS. In the DSPE-ASE method, 15 carbamate pesticides were extracted from Radix Glycyrrhizae samples with acetonitrile by the ASE method at 60 °C with a 5 min heating time and two static cycles. Cleanup of a 1 mL aliquot of the extract by the DSPE method used 20 mg PSA (primary secondary amine), 50 mg Al(2)O(3)-N, and 20 mg GCB (graphitized carbon black) (as cleanup sorbents) under the determined optimum conditions. The linearity of the method was in the range of 10 to 200 ng/mL with correlation coefficients (r(2)) of more than 0.996. The limits of detection were approximately 0.2 to 5.0 µg/kg. The method was successfully used for the analysis of target pesticides in Radix Glycyrrhizae samples. The recoveries of the carbamate pesticides at the spiking levels of 50, 100, and 200 µg/kg ranged from 79.7% to 99.3% with relative standard deviations lower than 10%. This multi-residue analytical method allows for a rapid, efficient, sensitive and reliable determination of target pesticides in Radix Glycyrrhizae and other medicinal herbs.

  4. Activation of electrophilicity of stable Y-delocalized carbamate cations in intramolecular aromatic substitution reaction: evidence for formation of diprotonated carbamates leading to generation of isocyanates.

    Science.gov (United States)

    Kurouchi, Hiroaki; Kawamoto, Kyoko; Sugimoto, Hiromichi; Nakamura, Satoshi; Otani, Yuko; Ohwada, Tomohiko

    2012-10-19

    Although cations with three heteroatoms, such as monoprotonated guanidine and urea, are stabilized by Y-shaped conjugation and such Y-conjugated cations are sufficiently basic to be further protonated (or protosolvated) to dications in strongly acid media, only O-monoprotonated species have been detected in the case of carbamates even in magic acid. We found that the trifluoromethanesulfonic acid-catalyzed cyclization of arylethylcarbamates proceeds to afford dihydroisoquinolones in high yield. In strong acids, methyl carbamates are fully O-monoprotonated, and these monocations do not undergo cyclization even under heating. But, as the acidity of the reaction medium is further increased, the cyclization reaction of methyl phenethylcarbamates starts to proceed as a first-order reaction, with a linear relationship between rate and acidity. The sign and magnitude of the entropy of activation ΔS(‡) were found to be similar to those of other A(Ac)1 reactions. These results strongly support the idea that further protonation of the O-protonated carbamates is involved in the cyclization, but the concentration of the dications is very low and suggests that the rate-determining step is dissociation of methanol from the diprotonated carbamate to generate protonated isocyanate, which reacts with the aromatic ring. Therefore, O-protonated carbamates are weak bases in sharp contrast to other Y-shaped monocations.

  5. Carbamates as Potential Prodrugs and a New Warhead for HDAC Inhibition

    Directory of Open Access Journals (Sweden)

    Kristina King

    2018-02-01

    Full Text Available We designed and synthesized carbamates of the clinically-approved HDAC (histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA in order to validate our previously-proposed hypothesis that these carbamates might serve as prodrugs for hydroxamic acid containing HDAC inhibitors. Biochemical assays proved our new compounds to be potent inhibitors of histone deacetylases in vitro, and they also showed antiproliferative effects in leukemic cells. These results, as well as stability analysis led to the suggestion that the intact carbamates are inhibitors of histone deacetylases themselves, representing a new zinc-binding warhead in HDAC inhibitor design. This suggestion was further supported by the synthesis and evaluation of a carbamate derivative of the HDAC6-selective inhibitor bufexamac.

  6. Mercaptobenzothiazole on gold biosensor systems for organophosphate and carbamate pesticide compounds

    CSIR Research Space (South Africa)

    Somerset, VS

    2010-05-01

    Full Text Available Organophosphate and carbamate pesticides are powerful neurotoxins that impede the activity of cholinesterase enzyme leading to severe health effects. This study firstly reports the development, characterisation, and application of thick...

  7. Comparative voltammetric study and determination of carbamate pesticide residues in soil at carbon nanotubes paste electrodes

    Directory of Open Access Journals (Sweden)

    THOMMANDRU RAVEENDRANATH BAB

    2014-02-01

    Full Text Available In this investigation, the persistence of carbamate pesticides in soil samples was investigated. A simple and selective differential pulse adsorptive stripping voltammetry was selected for this investigation. Carbon nanotubes paste electrodes were used as working electrodes for differential pulse adsorptive stripping voltammetry and cyclic voltammetry. A symmetric study of the various operational parameters that affect the stripping response was carried out by differential pulse voltammetry. Peak currents were linear over the concentration range of 10-5 to 10-10 M with an accumulation potential of -0.6 V and a 70 s accumulation time with lower detection limits of 1.09 x 10-7 M, 1.07 × 10-7M, 1.09×10-7 M for chlorphropham, thiodicarb, aldicarb. The relative standard deviation (n=10 and correlation coefficient values were 1.15 %, 0.988; 1.13 %, 0.978; and 1.14 %, 0.987, respectively. Universal buffer with pH range 2.0 - 6.0 was used as sup­porting electrolyte. The solutions with uniform concentration (10-5 M were used in all deter­minations. Calculations were made by standard addition method.

  8. Conformation analysis and computation of energy barrier to rotation about Csbnd N bond in para-methylphenyl carbamate and its solvent dependence in comparison with tertiary carbamates and tertiary amides

    Science.gov (United States)

    Modarresi-Alam, Ali Reza; Nowroozi, Alireza; Najafi, Parisa; Movahedifar, Fahimeh; Hajiabadi, Hossein

    2014-11-01

    Barrier to rotation about conjugated Csbnd N bond in p-Methyl phenyl carbamate (PMPC) was computed 14-16 kcal/mol at three levels of HF, B3LYP and MP2 using 6-311++G∗∗ basis set. The solvent effect and energy barriers about Csbnd N bond in PMPC were compared to the case of tertiary carbamates and tertiary amides. Moreover, it is shown that in primary carbamates such as PMPC and tertiary amides isomerisation process passes through TS2 and TS1 respectively, while in tertiary carbamates goes through a combination of both TSs. Furthermore, X-ray analysis which is reported for the first time for primary aryl carbamates demonstrated that the inclusive plane of carbamate functional group is perpendicular to the plane of phenyl ring. The results of computations are completely in agreement with the X-ray data.

  9. Purely in silico BCS classification: science based quality standards for the world's drugs.

    Science.gov (United States)

    Dahan, Arik; Wolk, Omri; Kim, Young Hoon; Ramachandran, Chandrasekharan; Crippen, Gordon M; Takagi, Toshihide; Bermejo, Marival; Amidon, Gordon L

    2013-11-04

    BCS classification is a vital tool in the development of both generic and innovative drug products. The purpose of this work was to provisionally classify the world's top selling oral drugs according to the BCS, using in silico methods. Three different in silico methods were examined: the well-established group contribution (CLogP) and atom contribution (ALogP) methods, and a new method based solely on the molecular formula and element contribution (KLogP). Metoprolol was used as the benchmark for the low/high permeability class boundary. Solubility was estimated in silico using a thermodynamic equation that relies on the partition coefficient and melting point. The validity of each method was affirmed by comparison to reference data and literature. We then used each method to provisionally classify the orally administered, IR drug products found in the WHO Model list of Essential Medicines, and the top-selling oral drug products in the United States (US), Great Britain (GB), Spain (ES), Israel (IL), Japan (JP), and South Korea (KR). A combined list of 363 drugs was compiled from the various lists, and 257 drugs were classified using the different in silico permeability methods and literature solubility data, as well as BDDCS classification. Lastly, we calculated the solubility values for 185 drugs from the combined set using in silico approach. Permeability classification with the different in silico methods was correct for 69-72.4% of the 29 reference drugs with known human jejunal permeability, and for 84.6-92.9% of the 14 FDA reference drugs in the set. The correlations (r(2)) between experimental log P values of 154 drugs and their CLogP, ALogP and KLogP were 0.97, 0.82 and 0.71, respectively. The different in silico permeability methods produced comparable results: 30-34% of the US, GB, ES and IL top selling drugs were class 1, 27-36.4% were class 2, 22-25.5% were class 3, and 5.46-14% were class 4 drugs, while ∼8% could not be classified. The WHO list

  10. Methodological Study to Develop Standard Operational Protocol on Intramuscular (IM, Intradermal (ID and Subcutaneous Drug Administration for Children

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Bijarania

    2017-10-01

    Full Text Available Introduction: Medicine administration is a major role played by registered nurses. Medicines are prescribed by the physician and dispensed by the pharmacist but responsibility for meticulous administration rests with the registered nurse. It becomes even more important when drugs are to be administered to children. Drug administration via Intramuscular (IM, Intradermal (ID and Subcutaneous route is a complex process. Errors are associated with medicine administration. Aim: The objective of this study was to develop Standard Operational Protocol (SOP for IM, ID and Subcutaneous drug administration and checklist to assess the implementation of the developed SOP. Materials and Methods: A methodological research design adapted to carry out the present study to develop standard operational protocol for IM, ID and subcutaneous drug administration for children, admitted in Advanced Paediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. The study included 58 bedside nurses and 90 observations of medicine administration procedure. Results: The Content Validity Index (CVI was prepared to assess the validity of content (items of SOPs and checklists. Over all Cronbach's-alpha values was calculated to assess the internal consistency of Items in SOPs and checklists. CVI of SOP and checklists were 98.51%, 97.83% and 99.03%. Over all Cronbach'salpha values were calculated 0.96, 0.82 and 0.95. All the nurses felt that SOPs are useful. Conclusion: Valid and feasible SOPs for drug administration in children along with valid and reliable checklists were developed. It is recommended to use this document for drug administration in children to prevent any possible error during drug administration to children.

  11. Synthesis of propargylic and allenic carbamates via the C-H amination of alkynes.

    Science.gov (United States)

    Grigg, R David; Rigoli, Jared W; Pearce, Simon D; Schomaker, Jennifer M

    2012-01-06

    Propargylic amines are important intermediates for the synthesis of nitrogen-containing heterocycles. The insertion of a nitrene into a propargylic C-H bond has not been explored, despite the attention directed toward the Rh-catalyzed amination of other types of C-H bonds. In this communication, the conversion of a series of homopropargylic carbamates to propargylic carbamates and aminated allenes is described. © 2011 American Chemical Society

  12. Synthesis, characterization, and self-assembly of bicarbamates and tri-carbamates

    Science.gov (United States)

    Singh, Rajiv Kumar

    Recent decades have witnessed the discovery of a wide variety of nanomaterials. These nanomaterials vary from zero-dimensional nanodots to three-dimensional nanoflowers. However the properties of these nanomaterials have not been fully explored. A majority of the nonmaterials discovered so far are inorganic. There is little information about nanomaterials which are entirely based on organic compounds. Therefore this thesis focuses on the synthesis of two-dimensional nanosheets based on organic frameworks. In this study, a number of two-armed and three-armed carboxamides and carbamates have been synthesized, characterized and self-assembly process was studied. The self-assembly of these amides and carbamates were studied in a large number of single solvents as well as combination of solvents. Two-armed amides and carbamates having aromatic cores are found to have poor solubility in all but DMF and DMSO. The two-armed amides and carbamates having linker alkyl chain are found to have good solubility and crystal formation in a few solvents, but the quality of the crystal is not good enough for the XRD analysis. The polar solvents along with a trace amount of water are found to be more effective in getting perfect crystals of three-armed carbamates for X-ray crystallography. Carbamates with side-arms of three carbons and a cyclohexyl ring form perfect quality crystals in EtOAc, MeCN, and THF:H2O. In the process of growing single crystal several crystallization techniques were used. Slow evaporation process is found to be more efficient in getting good quality crystal. The crystal structures of carbamates have been determined as a part of the project. The morphology of the nanosheets was also studied by the transmission electron microscope (TEM). The TEM image of the carbamates reveals that its morphology is two-dimensional sheet. Additionally, data from powdered XRD have also revealed the formation of same or similar crystalline isoform from a variety of conditions.

  13. Management of exogenous intoxication by carbamates and organophosphates at an emergency unit

    OpenAIRE

    Sydney Correia Leão; José Fernandes de Araújo; Alessandro Rodrigues Silveira; Alex André Ferreira Queiroz; Maria Júlia Silveira Souto; Rodrigo Oliveira Almeida; Diego Carvalho Maciel; Tânia Maria de Andrade Rodrigues

    2015-01-01

    Summary Objectives: to evaluate and indicate the procedure to be followed in the health unit, both for diagnosis and the treatment of acute exogenous intoxications by carbamates or organophosphates. Methods: a descriptive study based on retrospective analysis of the clinical history of patients diagnosed with intoxication by carbamates or organophosphates admitted at the emergency unit of the Hospital de Urgências de Sergipe Governador João Alves (HUSE) between January and December of 2012....

  14. Insecticidal carbamates exhibiting species-selective inhibition of acetylcholinesterase (AChE)

    OpenAIRE

    2008-01-01

    The present invention includes insecticidal carbamates that are useful, for example, for the control of insects, such as mosquitoes, which can be used in applications where exposure to and/or contact with humans is likely. The insecticides of the present invention include phenyl N-methyl carbamates and compositions comprising them that exhibit species-selective inhibition of acetylcholinesterase (AChE) and are preferably toxic to mosquitoes but not humans. Of particular interest are compounds...

  15. Synthesis and biological evaluation of carbamates derived from aminocombretastatin A-4 as vascular disrupting agents.

    Science.gov (United States)

    Conesa-Milián, Laura; Falomir, Eva; Murga, Juan; Carda, Miguel; Meyen, Eef; Liekens, Sandra; Alberto Marco, J

    2018-03-10

    A series of twenty-six carbamates derived from aminocombretastatin A-4 (AmCA-4) were synthesized and evaluated for their capacity to affect cell proliferation, tubulin polymerization, mitotic cell arrest, microtubule network organization, apoptosis and endothelial tubular structures in vitro. The anti-proliferative activity of the synthetic carbamates was measured on several human tumor cell lines (i.e. HT-29, MCF-7, HeLa, A-549, MDA-MB-231, HL-60) as well as on the endothelial cell line HMEC-1 and the non-tumor cell line HEK-293. The compounds showed anti-proliferative activity in the nanomolar range thereby exceeding by far the activity of combretastatin A-4 (CA-4) and, in some cases, the activity of AmCA-4. The most active compounds proved to be the carbamates bearing chloro, bromo or methoxy groups in the meta position of the phenyl ring. Moreover, all carbamates inhibited in vitro tubulin polymerization, in a similar manner to that of CA-4 and AmCA-4 by interacting with the colchicine binding site in tubulin. The synthetic carbamates proved as active as AmCA-4 in causing mitotic arrest, as assessed in A549 human lung cancer cells, and disruption of the microtubule cellular network. Some selected carbamates induced apoptosis at concentrations as low as 10 nM, being more active than AmCA-4. Finally, these selected carbamates displayed a vascular disrupting activity on endothelial cells in a dose-dependent manner. In conclusion, our data indicate that carbamates derived from aminocombretastatin A-4 represent interesting lead compounds for the design of vascular disrupting agents. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. N-Methylimidazole-catalyzed synthesis of carbamates from hydroxamic acids via the Lossen rearrangement.

    Science.gov (United States)

    Yoganathan, Sabesan; Miller, Scott J

    2013-02-01

    An efficient, one-pot, N-methylimidazole (NMI) accelerated synthesis of aromatic and aliphatic carbamates via the Lossen rearrangement is reported. NMI is a catalyst for the conversion of isocyanate intermediates to the carbamates. Moreover, the utility of arylsulfonyl chloride in combination with NMI minimizes the formation of often-observed hydroxamate-isocyanate dimers during the sequence. Under the present conditions, lowering of temperatures is also possible, enabling a mild protocol.

  17. Microplate assay analysis of the distribution of organophosphate and carbamate resistance in Guatemalan Anopheles albimanus

    OpenAIRE

    Brogdon, W. G.; Beach, R. F.; Stewart, J. M.; Castanaza, L.

    1988-01-01

    Simple microplate assay methods for determining the frequency of insecticide resistance in single mosquitos were used to study the distribution and localization of organophosphate and carbamate resistance in field populations of Anopheles albimanus Weidemann in Guatemala, where such resistance, caused by heavy use of agricultural pesticides, has long been assumed to be widespread. Areas of complete susceptibility to organophosphates and carbamates were observed, as well as areas where the res...

  18. 78 FR 42084 - Electronic Study Data Submission; Data Standard Support; Availability of the Center for Drug...

    Science.gov (United States)

    2013-07-15

    ... commitment to the development, implementation, and maintenance of a comprehensive data standards program to facilitate the efficient and effective review of regulatory submissions so that safe and effective products... Innovation Act. The CDER Data Standards Strategy supersedes version 1.1 of the CDER Data Standards Plan...

  19. Physicochemical studies of the carbamate-CO/sub 2/-solvent system

    Energy Technology Data Exchange (ETDEWEB)

    Prencipe, M.; Ishida, T.

    1977-08-01

    The formation of carbamate from CO/sub 2/ and the various amine solutions has been investigated for the purpose of elucidating the structure of the species generated in the reaction. The amine solutions used were 1 and 2 molar solutions of di-n-butylamine (DNBA) in triethylamine (TEA), pure DNBA and pure TEA. It has been found that the nonaqueous solvent participates in the formation of carbamate in 1 and 2M-DNBA/TEA solutions as a proton acceptor in DNBA-carbamate formation. However, due to the high concentration of the solutions and the basicities of the amines, a significant amount of DNBA which does not form the DNBA-carbamate anion is also found to be participating as a proton acceptor. Pure TEA absorbs only /sup 1///sub 60/ of the absorption by pure DNBA. The extent of TEA participation in the CO/sub 2/-absorption process other than as a proton acceptor in DNBA-carbamate is negligible. The formation of carbamic acid and zwitterion have been found unlikely. 7 tables, 15 figs.

  20. Synthesis of Novel Cellulose Carbamates Possessing Terminal Amino Groups and Their Bioactivity.

    Science.gov (United States)

    Ganske, Kristin; Wiegand, Cornelia; Hipler, Uta-Christina; Heinze, Thomas

    2016-03-01

    Cellulose phenyl carbonates are an excellent platform to synthesize a broad variety of soluble and functional cellulose carbamates. In this study, the synthesis of cellulose carbamates with terminal amino groups, namely ω-aminoethylcellulose- and ω-aminoethyl-p-aminobenzyl-cellulose carbamate, is discussed. The products are well soluble and their structures can be clearly described by NMR spectroscopy. The cellulose carbamates exhibit a bactericide and fungicide activity in vitro. The ω-aminoethylcellulose carbamate possesses a strong activity against Candida albicans and Staphylococcus aureus (IC50 of 0.02 mg mL(-1) and 0.05 mg mL(-1)). The antimicrobial activity and cytotoxicity can be improved by p-amino-benzylamine (ABA) as an additional substituent. The mixed cellulose carbamate exhibits a high biocompatibility (LC50 of 3.18 mg mL(-1)) and forms films on cotton and PES, which exhibit a strong activity against S. aureus and Klebsiella pneumoniae. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Chemistry and Chemical Equilibrium Dynamics of BMAA and Its Carbamate Adducts.

    Science.gov (United States)

    Diaz-Parga, Pedro; Goto, Joy J; Krishnan, V V

    2018-01-01

    Beta-N-methylamino-L-alanine (BMAA) has been demonstrated to contribute to the onset of the ALS/Parkinsonism-dementia complex (ALS/PDC) and is implicated in the progression of other neurodegenerative diseases. While the role of BMAA in these diseases is still debated, one of the suggested mechanisms involves the activation of excitatory glutamate receptors. In particular, the excitatory effects of BMAA are shown to be dependent on the presence of bicarbonate ions, which in turn forms carbamate adducts in physiological conditions. The formation of carbamate adducts from BMAA and bicarbonate is similar to the formation of carbamate adducts from non-proteinogenic amino acids. Structural, chemical, and biological information related to non-proteinogenic amino acids provide insight into the formation of and possible neurological action of BMAA. This article reviews the carbamate formation of BMAA in the presence of bicarbonate ions, with a particular focus on how the chemical equilibrium of BMAA carbamate adducts may affect the molecular mechanism of its function. Highlights of nuclear magnetic resonance (NMR)-based studies on the equilibrium process between free BMAA and its adducts are presented. The role of divalent metals on the equilibrium process is also explored. The formation and the equilibrium process of carbamate adducts of BMAA may answer questions on their neuroactive potency and provide strong motivation for further investigations into other toxic mechanisms.

  2. N-Monosubstituted Methoxy-oligo(ethylene glycol Carbamate Ester Prodrugs of Resveratrol

    Directory of Open Access Journals (Sweden)

    Andrea Mattarei

    2015-09-01

    Full Text Available Resveratrol is a natural polyphenol with many interesting biological activities. Its pharmacological exploitation in vivo is, however, hindered by its rapid elimination via phase II conjugative metabolism at the intestinal and, most importantly, hepatic levels. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, hydrolysis, and in vivo pharmacokinetic behavior of resveratrol prodrugs in which the OH groups are engaged in an N-monosubstituted carbamate ester linkage. As promoiety, methoxy-oligo(ethylene glycol groups (m-OEG (CH3–[OCH2CH2]n– of defined chain length (n = 3, 4, 6 were used. These are expected to modulate the chemico-physical properties of the resulting derivatives, much like longer poly(ethylene glycol (PEG chains, while retaining a relatively low MW and, thus, a favorable drug loading capacity. Intragastric administration to rats resulted in the appearance in the bloodstream of the prodrug and of the products of its partial hydrolysis, confirming protection from first-pass metabolism during absorption.

  3. Physicochemical and elemental studies of Hydrocotyle javanica Thunb. for standardization as herbal drug

    Directory of Open Access Journals (Sweden)

    Manab Mandal

    2017-11-01

    Conclusions: Hence the present physicochemical and elements studies reveals that the plant Hydrocotyle javanica Thunb. could be a potent source of herbal preparation as well as a safe and novel synthetic antibacterial drug.

  4. Standard-based comprehensive detection of adverse drug reaction signals from nursing statements and laboratory results in electronic health records.

    Science.gov (United States)

    Lee, Suehyun; Choi, Jiyeob; Kim, Hun-Sung; Kim, Grace Juyun; Lee, Kye Hwa; Park, Chan Hee; Han, Jongsoo; Yoon, Dukyong; Park, Man Young; Park, Rae Woong; Kang, Hye-Ryun; Kim, Ju Han

    2017-07-01

    We propose 2 Medical Dictionary for Regulatory Activities-enabled pharmacovigilance algorithms, MetaLAB and MetaNurse, powered by a per-year meta-analysis technique and improved subject sampling strategy. This study developed 2 novel algorithms, MetaLAB for laboratory abnormalities and MetaNurse for standard nursing statements, as significantly improved versions of our previous electronic health record (EHR)-based pharmacovigilance method, called CLEAR. Adverse drug reaction (ADR) signals from 117 laboratory abnormalities and 1357 standard nursing statements for all precautionary drugs ( n   = 101) were comprehensively detected and validated against SIDER (Side Effect Resource) by MetaLAB and MetaNurse against 11 817 and 76 457 drug-ADR pairs, respectively. We demonstrate that MetaLAB (area under the curve, AUC = 0.61 ± 0.18) outperformed CLEAR (AUC = 0.55 ± 0.06) when we applied the same 470 drug-event pairs as the gold standard, as in our previous research. Receiver operating characteristic curves for 101 precautionary terms in the Medical Dictionary for Regulatory Activities Preferred Terms were obtained for MetaLAB and MetaNurse (0.69 ± 0.11; 0.62 ± 0.07), which complemented each other in terms of ADR signal coverage. Novel ADR signals discovered by MetaLAB and MetaNurse were successfully validated against spontaneous reports in the US Food and Drug Administration Adverse Event Reporting System database. The present study demonstrates the symbiosis of laboratory test results and nursing statements for ADR signal detection in terms of their system organ class coverage and performance profiles. Systematic discovery and evaluation of the wide spectrum of ADR signals using standard-based observational electronic health record data across many institutions will affect drug development and use, as well as postmarketing surveillance and regulation. © The Author 2017. Published by Oxford University Press on behalf of the American

  5. Electrochemical Biosensor Based on Optimized Biocomposite for Organophosphorus and Carbamates Pesticides Detection

    Directory of Open Access Journals (Sweden)

    R. Montes

    2018-01-01

    Full Text Available This paper presents the characterization and optimization of biosensors based on graphite-epoxy which incorporates the enzyme acetylcholinesterase (AChE. By means of advanced electrochemical techniques, such as electrochemical impedance spectroscopy (EIS and cyclic voltammetry (CV, the characterization and optimization of graphite-epoxy-AChE biosensors have been performed. In order to obtain sensitive electrodes, the optimal composition of the transducer material (graphite-epoxy-enzyme ratio was studied. The optimization of the conductive particles distribution inside the biomaterial has allowed an improvement of the electrochemical properties. Optimal composition guarantees improving electrochemical properties required, such as high electron-transfer rate, high signal-to-noise ratio, and suitable sensitivity. The optimal biocomposite composition range was obtained between 16% and 17% of graphite and 0.12% of AChE. The biosensors were applied to the analysis of different pesticides, organophosphorus and carbamates, using indirect measurements based on enzymatic inhibition process. These optimized biosensors present detection limit one order of magnitude lower compared to the standard composition (nonoptimized and allow achieving concentrations lower than the established ones by the pesticides regulation. Finally, spiked tap water samples with pesticides were analyzed with the optimized biosensors.

  6. Effect of carbaryl (carbamate insecticide) on acetylcholinesterase activity of two strains of Daphnia magna (Crustacea, Cladocera).

    Science.gov (United States)

    Toumi, Hela; Bejaoui, Mustapha; Touaylia, Samir; Burga Perez, Karen F; Ferard, Jean François

    2016-11-01

    The present study was designed to investigate the effect of carbaryl (carbamate insecticide) on the acetylcholinesterase activity in two strains (same clone A) of the crustacean cladoceran Daphnia magna. Four carbaryl concentrations (0.4, 0.9, 1.8 and 3.7 µg L(-1)) were compared against control AChE activity. Our results showed that after 48 h of carbaryl exposure, all treatments induced a significant decrease of AChE activities whatever the two considered strains. However, different responses were registered in terms of lowest observed effect concentrations (LOEC: 0.4 µg L(-1) for strain 1 and 0.9 µg L(-1) for strains 2) revealing differences in sensitivity among the two tested strains of D. magna. These results suggest that after carbaryl exposure, the AChE activity responses can be also used as a biomarker of susceptibility. Moreover, our results show that strain1 is less sensitive than strain 2 in terms of IC50-48 h of AChE activity. Comparing the EC50-48 h of standard ecotoxicity test and IC50-48 h of AChE inhibition, there is the same order of sensitivity with both strains.

  7. [Survey and analysis of ethyl carbamate in commercial fermented foods in Hangzhou in 2010].

    Science.gov (United States)

    Wu, Ping-Gu; Yang, Da-Jin; Shen, Xiang-Hong; Wang, Li-Yuan; Pan, Xiao-Dong; Zhang, Jing; Zhao, Yong-Xin; Tan, Ying

    2011-07-01

    To observe the ethyl carbamate concentrations in different commercial fermented foods in Hangzhou in 2010. In 2010, 237 commercial fermented food samples of eight categories, including yellow wine, white spirit, wine, beer, cooking wine, sauce, vinegar and fermented bean curd, were purchased from 3 different size markets respectively in Hangzhou. The ethyl carbamate was measured by gas chromatography-mass spectrometry in selection ion mode, after the samples were coupled with D5-ethyl carbamate, and purified by diatomite solid phase extraction column. The results showed that ethyl carbamate was detected in all samples analyzed (100%) with the range from 2.0 µg/kg to 515.0 µg/kg. The ethyl carbamate average (median) levels in 8 food categories were descending with fermented red bean curd (182.2 µg/kg (161.2 µg/kg)), yellow wine (159.6 µg/kg (121.0 µg/kg)), cooking wine (86.8 µg/kg (95.6 µg/kg)), white spirit (72.0 µg/kg (60.5 µg/kg)), soy sauce (47.2 µg/kg (40.7µg/kg)), vinegar (26.7 µg/kg (31.8 µg/kg)), wine (15.7 µg/kg (16.8 µg/kg)) and beer (2.2 µg/kg (2.3 µg/kg)). The ethyl carbamate was detected in all fermented foods in Hangzhou in 2010, and the levels of ethyl carbamate in red bean curd and yellow wine were higher than others.

  8. Clinical trials information in drug development and regulation : existing systems and standards

    NARCIS (Netherlands)

    Valkenhoef, Gert van; Tervonen, Tommi; Brock, Bert de; Hillege, Hans

    2012-01-01

    Clinical trials provide pivotal evidence on drug efficacy and safety. The evidence, information from clinical trials, is currently used by regulatory decision makers in marketing authorization decisions, but only in an implicit manner. For clinical trials information to be used in a transparent and

  9. 77 FR 48491 - Regulatory New Drug Review: Solutions for Study Data Exchange Standards; Notice of Meeting...

    Science.gov (United States)

    2012-08-14

    ... many years, it is not an extensible modern technology. Moreover, it is not supported and maintained by..., structured documents and Clinical Data Architecture) be a viable study data exchange standard? Please explain...

  10. [Actuality investigation on general crude drugs and its quality standard of Tibetan medicine].

    Science.gov (United States)

    Zhong, Guoyue; Zhou, Fucheng; Shi, Shangmei; Zhou, Huarong; Yu, Jiangyong; Ping, A; Liu, Haiqing; Dawa, Zhuoma

    2012-08-01

    To provide a reference for the standardization of Tibetan medicine. Investigating the hospital preparations , Tibetan formulated products, and the literature recorded preparations in the Tibetan, Qinghai, Gansu, Sichuan and Yunnan Provinces. Moreover, the varieties, original bases and standard conditions of these preparations were analyzed. According to Chinese Pharmacopoeia, Tibetan medicine part of ministerial standard, Tibetan medicine standards and related monographs and literatures of Tibetan medicine. About 502 various of herbs were used in 711 hospital preparations from 40 medical institutions, Tibetan formulated products from Tibetan pharmaceutical factories, and 439 literature recorded preparations. About 154 herbs were used in more than 10 preparations, while most of them were Tibetan endemic species. About 416 medicinal varieties have the original documented basis, including 287 botanicals, 78 animal medicines, 51 mineral medicines, involving a total of 94 families, 261 genus and 643 species of botanical origin (including species of the next grade), 35 families, 52 genera and 61 species of the animal origin (including species of the next grade). About 122 varieties of herbs were cross-used in the traditional Chinese medicine and Tibetan medicine, about 80% of Tibetan medicinal varieties are produced in the Tibetan Areas of Tibet Plateau. About 293 medicinal varieties were contained in the above standards. Most of the herb's standards only contains character, indentification, and examination, except for 8 varieties which were recorded in the Chinese Pharmacopoeia (2010) as Tibetan medicine. This study of quality standard of Tibetan medicine should have an emphasis on the general varieties, especially the study on the arrangement research and the efficacious material basis of the varieties and the original, as well as term standardization of the National Medicine.

  11. Determination of the residues of 18 carbamate pesticides in chestnut and pine nut by GPC cleanup and UPLC-MS-MS.

    Science.gov (United States)

    Lin, Qin-Bao; Xue, Yuan-Yuan; Song, Huan

    2010-01-01

    A new method using gel permeation chromatography (GPC) cleanup followed by ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS-MS) has been established for simultaneous determination of 18 carbamate pesticides in nuts (chestnut and pine nut). Recoveries obtained by fortifying nut (spiking at 0.02 mg/kg) range from 70.21% to 89.56%. The proposed method features good sensitivity. Its limits of quantification are low enough to allow pesticide residues to be determined at concentrations below the maximum residue levels legally accepted. The precision, expressed as relative standard deviation, ranges from 2.26% to 4.07%.

  12. Synthesis and inhibitory properties of some carbamates on carbonic anhydrase and acetylcholine esterase.

    Science.gov (United States)

    Yılmaz, Süleyman; Akbaba, Yusuf; Özgeriş, Bünyamin; Köse, Leyla Polat; Göksu, Süleyman; Gülçin, İlhami; Alwasel, Saleh H; Supuran, Claudiu T

    2016-12-01

    A series of carbamate derivatives were synthesized and their carbonic anhydrase I and II isoenzymes and acetylcholinesterase enzyme (AChE) inhibitory effects were investigated. All carbamates were synthesized from the corresponding carboxylic acids via the Curtius reactions of the acids with diphenyl phosphoryl azide followed by addition of benzyl alcohol. The carbamates were determined to be very good inhibitors against for AChE and hCA I, and II isoenzymes. AChE inhibition was determined in the range 0.209-0.291 nM. On the other hand, tacrine, which is used in the treatment of Alzheimer's disease possessed lower inhibition effect (Ki: 0.398 nM). Also, hCA I and II isoenzymes were effectively inhibited by the carbamates, with inhibition constants (Ki) in the range of 4.49-5.61 nM for hCA I, and 4.94-7.66 nM for hCA II, respectively. Acetazolamide, which was clinically used carbonic anhydrase (CA) inhibitor demonstrated Ki values of 281.33 nM for hCA I and 9.07 nM for hCA II. The results clearly showed that AChE and both CA isoenzymes were effectively inhibited by carbamates at the low nanomolar levels.

  13. Trace determination of carbamate pesticides in medicinal plants by a fluorescent technique.

    Science.gov (United States)

    Wei, Jin-Chao; Wei, Bin; Yang, Wu; He, Cheng-Wei; Su, Huan-Xing; Wan, Jian-Bo; Li, Peng; Wang, Yi-Tao

    2017-12-18

    The safety issue of using carbamate pesticides in medicinal plants (MPs) has been a global concern and hence attracted attention of many researchers to develop analytical tools for trace pesticides detection. Derived from the fluorescence-based techniques, a rapid, convenient and efficient method for the detection of three carbamate pesticides, including carbofuran, aldicarb and methomyl has been developed by using core-shell QDs. By optimizing experimental parameters, the system demonstrated high detection sensitivities for the investigated carbamates, with the lowest detectable concentrations less than 0.05 μM. The molecular docking study indicated that the selected carbamate pesticides bound to the catalytic active site of acetylcholinesterase via π-π or H-π interactions, which also revealed the potential mechanism of the differences in inhibition strength among the three pesticides on AChE. Moreover, in order to investigate the applicability and reliability of the proposed method for the pesticide analysis in real sample with complex matrix, the matrix effects of eight common MPs have been systematically explored. These findings suggested that this technique was a simple, sensitive and reliable method for rapid determination of carbamate pesticides in real samples, especially those with complex matrices like MPs, vegetables, fruits, and other agricultural crops. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Synergism studies with binary mixtures of pyrethroid, carbamate and organophosphate insecticides on Frankliniella occidentalis (Pergande).

    Science.gov (United States)

    Bielza, Pablo; Espinosa, Pedro J; Quinto, Vicente; Abellán, Jaime; Contreras, Josefina

    2007-01-01

    The major mechanism of resistance to most insecticides in Frankliniella occidentalis (Pergande) is metabolic, piperonyl butoxide (PBO) suppressible, mediated by cytochrome-P450 monooxygenases and conferring cross-resistance among insecticide classes. The efficacy of insecticide mixtures of acrinathrin, methiocarb, formetanate and chlorpyrifos was studied by topical exposure in strains of F. occidentalis selected for resistance to each insecticide. The method consisted in combining increasing concentrations of one insecticide with a constant low rate of the second one as synergist. Acrinathrin activity against F. occidentalis was enhanced by carbamate insecticides, methiocarb being a much better synergist than formetanate. Monooxygenase action on the carbamates would prevent degradation of the pyrethroid, hence providing a level of synergism by competitive substrate inhibition. However, the number of insecticides registered for control of F. occidentalis is very limited, and they are needed for antiresistance strategies such as mosaics and rotations. Therefore, a study was made of the synergist effect of other carbamates not used against thrips, such as carbofuran and carbosulfan, against a susceptible strain and a field strain. Neither carbamate showed synergism to acrinathrin in the susceptible strain, but both did in the field strain, carbosulfan being a better synergist than carbofuran. The data obtained indicate that low rates of carbamates could be used as synergists to restore some pyrethroid susceptibility in F. occidentalis. Copyright (c) 2006 Society of Chemical Industry.

  15. [Determination of 51 carbamate pesticide residues in vegetables by liquid chromatography-tandem mass spectrometry based on optimization of QuEChERS sample preparation method].

    Science.gov (United States)

    Wang, Lianzhu; Zhou, Yu; Huang, Xiaoyan; Wang, Ruilong; Lin, Zixu; Chen, Yong; Wang, Dengfei; Lin, Dejuan; Xu, Dunming

    2013-12-01

    The raw extracts of six vegetables (tomato, green bean, shallot, broccoli, ginger and carrot) were analyzed using gas chromatography-mass spectrometry (GC-MS) in full scan mode combined with NIST library search to confirm main matrix compounds. The effects of cleanup and adsorption mechanisms of primary secondary amine (PSA) , octadecylsilane (C18) and PSA + C18 on co-extractives were studied by the weight of evaporation residue for extracts before and after cleanup. The suitability of the two versions of QuEChERS method for sample preparation was evaluated for the extraction of 51 carbamate pesticides in the six vegetables. One of the QuEChERS methods was the original un-buffered method published in 2003, and the other was AOAC Official Method 2007.01 using acetate buffer. As a result, the best effects were obtained from using the combination of C18 and PSA for extract cleanup in vegetables. The acetate-buffered version was suitable for the determination of all pesticides except dioxacarb. Un-buffered QuEChERS method gave satisfactory results for determining dioxacarb. Based on these results, the suitable QuEChERS sample preparation method and liquid chromatography-positive electrospray ionization-tandem mass spectrometry under the optimized conditions were applied to determine the 51 carbamate pesticide residues in six vegetables. The analytes were quantified by matrix-matched standard solution. The recoveries at three levels of 10, 20 and 100 microg/kg spiked in six vegetables ranged from 58.4% to 126% with the relative standard deviations of 3.3%-26%. The limits of quantification (LOQ, S/N > or = 10) were 0.2-10 microg/kg except that the LOQs of cartap and thiofanox were 50 microg/kg. The method is highly efficient, sensitive and suitable for monitoring the 51 carbamate pesticide residues in vegetables.

  16. Assessment of Acute Oral and Dermal Toxicity of 2 Ethyl-Carbamates with Activity against Rhipicephalus microplus in Rats

    Directory of Open Access Journals (Sweden)

    María Guadalupe Prado-Ochoa

    2014-01-01

    Full Text Available The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P<0.05 and had slight nervous system manifestations. These clinical signs were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity.

  17. Time-course, dose-response, and age comparative sensitivity of N-methyl carbamates in rats

    Science.gov (United States)

    N-Methyl carbamate insecticides are reversible inhibitors of central and peripheral acetylcholinesterease (ChE). Despite their widespread use, there are few studies of neurotoxicity in young animals. To study potential age-related differences, we evaluated seven carbamates (carba...

  18. New synthesis of carbamate, thiocarbamate and urea type herbicides: preparation of 14C-labelled diuron and EPTC

    International Nuclear Information System (INIS)

    Volford, J.; Horvath, L.

    1981-01-01

    N,N-dialkyl-carbamic acid-trimethylsilyl-esters were synthesized starting with 14 CO 2 . The new synthesis route is simple and provides good radiochemical yield. Silyl-carbaminates directly or through carbamoyl-halogenides may be used for preparation of labelled herbicides: carbamates, thiocarbamates and ureas. (author)

  19. Exposure assessment and risk characterisation of ethyl carbamate from Korean traditional fermented rice wine, Takju and Yakju.

    Science.gov (United States)

    Lee, Joon-Goo; Park, Sung-Kug; Yoon, Hae-Jung; Kang, Dong-Hyun; Kim, Meehye

    2016-01-01

    Ethyl carbamate is one of the most hazardous chemicals naturally occurring in food, and is present in alcoholic beverages. Korean traditional rice wine, Takju and Yakju, is frequently consumed in Korea, but there have been no studies characterising the risks of ethyl carbamate in these products. In order to assess and characterise the exposure risk of ethyl carbamate in Korean traditional rice wines, ethyl carbamate was investigated by means of GC-MS. The analytical methods were optimised and validated through determining linearity, detection limit, quantification limit, recovery and precision. A total of 283 traditional Korean rice wines, including 175 Takju and 108 Yakju samples, were analysed. Exposure assessment was performed by factoring in ethyl carbamate content, daily consumption and body weight. Daily exposures of ethyl carbamate were estimated for adults in four age groups, and risks of ethyl carbamate were characterised by the margin of exposure, which is more than 10 000. Based on this study, the risks of ethyl carbamate in Korean traditional rice wine were shown to be of low concern.

  20. Hydroxycarbamine: from an Old Drug Used in Malignant Hemopathies to a Current Standard in Sickle Cell Disease

    Science.gov (United States)

    Cannas, Giovanna; Poutrel, Solène; Thomas, Xavier

    2017-01-01

    While hydroxycarbamide (hydroxyurea, HU) has less and fewer indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support for safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. No increased incidence of leukemia and teratogenicity was demonstrated. HU has become the standard-of-care for sickle cell anemia but remains underused. Barriers to its use should be identified and overcome. PMID:28293403

  1. HYDROXYCARBAMINE: FROM AN OLD DRUG USED IN MALIGNANT HEMOPATHIES TO A CURRENT STANDARD IN SICKLE CELL DISEASE

    Directory of Open Access Journals (Sweden)

    Giovanna Cannas

    2017-02-01

    Full Text Available While hydroxycarbamine (hydroxyurea, HU has less and less indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support of safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. HU has become the standard-of-care for sickle cell anemia, but remains underused. Barriers to its use should be identified and overcome.

  2. Effect of new ethyl and methyl carbamates on Rhipicephalus microplus larvae and adult ticks resistant to conventional ixodicides.

    Science.gov (United States)

    Pérez-González, I E; Prado-Ochoa, M G; Muñoz-Guzmán, M A; Vázquez-Valadez, V H; Velázquez-Sánchez, A M; Avila-Suárez, B L; Cuenca-Verde, C; Angeles, E; Alba-Hurtado, F

    2014-01-31

    The effects of six new synthetic carbamates on fully engorged females of four Rhipicephalus microplus strains (one reference strain susceptible to conventional ixodicides, two strains multiresistant to ixodicides and one tick field isolate) were compared. In addition, the effect of two other new synthetic carbamates was tested on larvae from the same strains. The first six tested carbamates reduced egg laying and inhibited egg hatching in the four studied strains (Pcarbamates induced larval mortality in all of the evaluated strains. The three studied R. microplus strains displayed 50% resistance ratios (RR50) of less than 2 when compared to the susceptible reference strain. These results demonstrate that both carbamates with a larvicidal effect and carbamates that inhibit egg laying and embryo development are efficacious against tick strains that are resistant to commercial ixodicides, no cross resistance was observed. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Predicting a single HIV drug resistance measure from three international interpretation gold standards.

    Science.gov (United States)

    Yashik, Singh; Maurice, Mars

    2012-07-01

    To investigate the possibility of combining the interpretation of three gold standard interpretation algorithms using weighted heuristics in order to produce a single resistance measure. The outputs of HIVdb, Rega, ANRS were combined to obtain a single resistance profile using the equally weighted voting algorithm, accuracy based weighing voting algorithm and the Bayesian based weighted voting algorithm techniques. The Bayesian based voting combination increased the accuracy of the resistance profile prediction compared to phenotype, from 58% to 69%. The equal weighted voting algorithm and the accuracy based algorithm both increased the prediction accuracy to 60%. From the result obtained it is evident that combining the gold standard interpretation algorithms may increase the predictive ability of the individual interpretation algorithms. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  4. Dissociation or cyclization: options for a triad of radicals released from oxime carbamates.

    Science.gov (United States)

    McBurney, Roy T; Walton, John C

    2013-05-15

    A set of oxime carbamates having N-alkyl and N,N-dialkyl substituents were prepared via carbonyldiimidazole intermediates. It was shown by EPR spectroscopy that they underwent clean homolysis of their N-O bonds upon UV photolysis. During photolysis of acetophenone O-allylcarbamoyl oxime, the corresponding oxazolidin-2-onylmethyl radical was detected by EPR spectroscopy, providing the first evidence that N-monosubstituted carbamoyloxyl radicals can hold their structural integrity. N,N-Disubstituted carbamoyloxyl radicals dissociated rapidly at the lowest accessible temperatures. Above room temperature, both types of oxime carbamate acted as selective new precursors for aminyl and iminyl radicals. Rate parameters were measured for 5-exo cyclization of N-benzyl-N-pent-4-enylaminyl radicals; the rate constant was smaller than for C-centered and O-centered analogues. Oxime carbamates derived from the volatile diethylamine afforded aryliminyl radicals that proved convenient for phenanthridine preparations.

  5. Presenting a New Standard Drug Model for Turmeric and Its Prized Extract, Curcumin

    Directory of Open Access Journals (Sweden)

    Franco Cavaleri

    2018-01-01

    Full Text Available Various parts of the turmeric plant have been used as medicinal treatment for various conditions from ulcers and arthritis to cardiovascular disease and neuroinflammation. The rhizome’s curcumin extract is the most studied active constituent, which exhibits an expansive polypharmacology with influence on many key inflammatory markers. Despite the expansive reports of curcucmin’s therapeutic value, clinical reliability and research repeatability with curcumin treatment are still poor. The pharmacology must be better understood and reliably mapped if curcumin is to be accepted and used in modern medical applications. Although the polypharmacology of this extract has been considered, in mainstream medicine, to be a drawback, a perspective change reveals a comprehensive and even synergistic shaping of the NF-kB pathway, including transactivation. Much of the inconsistent research data and unreliable clinical outcomes may be due to a lack of standardization which also pervades research standard samples. The possibility of other well-known curcumin by-products contributing in the polypharmacology is also discussed. A new flowchart of crosstalk in transduction pathways that lead to shaping of nuclear NF-kB transactivation is generated and a new calibration or standardization protocol for the extract is proposed which could lead to more consistent data extraction and improved reliability in therapy.

  6. Presenting a New Standard Drug Model for Turmeric and Its Prized Extract, Curcumin.

    Science.gov (United States)

    Cavaleri, Franco

    2018-01-01

    Various parts of the turmeric plant have been used as medicinal treatment for various conditions from ulcers and arthritis to cardiovascular disease and neuroinflammation. The rhizome's curcumin extract is the most studied active constituent, which exhibits an expansive polypharmacology with influence on many key inflammatory markers. Despite the expansive reports of curcucmin's therapeutic value, clinical reliability and research repeatability with curcumin treatment are still poor. The pharmacology must be better understood and reliably mapped if curcumin is to be accepted and used in modern medical applications. Although the polypharmacology of this extract has been considered, in mainstream medicine, to be a drawback, a perspective change reveals a comprehensive and even synergistic shaping of the NF-kB pathway, including transactivation. Much of the inconsistent research data and unreliable clinical outcomes may be due to a lack of standardization which also pervades research standard samples. The possibility of other well-known curcumin by-products contributing in the polypharmacology is also discussed. A new flowchart of crosstalk in transduction pathways that lead to shaping of nuclear NF-kB transactivation is generated and a new calibration or standardization protocol for the extract is proposed which could lead to more consistent data extraction and improved reliability in therapy.

  7. HPLC Fingerprinting of Sennosides in Laxative Drugs with Isolation of Standard Substances from Some Senna Leaves

    Directory of Open Access Journals (Sweden)

    L. Omur Demirezer

    2011-01-01

    Full Text Available Senna leaves are one of the oldest medicinal herbs and they are used as laxative. Herbal teas which contain senna leaves are most commonly used to promote weight loss. The quality control of slimming teas which contain Senna leaves and also pharmaceutical preparations including Senna extract enriched by sennoside B was achieved by HPLC fingerprinting method. While the presence of sennoside A and B in laxative drugs was proved, it was seen to be devoid of sennosides in slimming teas. Kaempferol 3-O-β-D-gentiobioside (1, aloe-emodine 8-O-β-D-glucopyranoside (2, rhein 8-O-β-D-glucopyranoside (3, torachrysone 8-O-β-D-glucopyranoside (4, isorhamnetine 3-O-β-D-gentiobioside (5 were also isolated from Senna leaves.

  8. Industry Perspective on Standardizing Food-Effect Studies for New Drug Development.

    Science.gov (United States)

    Marroum, Patrick J; Nuthalapati, Silpa; Parikh, Apurvasena; Shebley, Mohamad; Hoffman, David; Zha, Jiuhong; Khatri, Amit; Awni, Walid M

    2018-02-19

    Investigating the effect of food on bioavailability during the development of an oral drug product is of prime importance because it has major implications on the study design of the clinical trials and dosing and administration recommendations. For modified-release formulations that exhibit dose dumping when administered with food, this may result in clinical concerns around safety and efficacy. In this article, we provide an overview of the various considerations in our opinion that impact the design and conduct of food-effect studies. We summarize the various recommendations from the different regulatory agencies and provide specific suggestions on study conduct in terms of statistical design, timing of studies, subject selection, and type and caloric content of the meal. We also discuss the role of modeling and simulation. Finally, we present an interpretation of the results of food-effect studies in addition to dosing and labeling recommendations in relation to regulatory guidance documents.

  9. Automated identification of drug and food allergies entered using non-standard terminology.

    Science.gov (United States)

    Epstein, Richard H; St Jacques, Paul; Stockin, Michael; Rothman, Brian; Ehrenfeld, Jesse M; Denny, Joshua C

    2013-01-01

    An accurate computable representation of food and drug allergy is essential for safe healthcare. Our goal was to develop a high-performance, easily maintained algorithm to identify medication and food allergies and sensitivities from unstructured allergy entries in electronic health record (EHR) systems. An algorithm was developed in Transact-SQL to identify ingredients to which patients had allergies in a perioperative information management system. The algorithm used RxNorm and natural language processing techniques developed on a training set of 24 599 entries from 9445 records. Accuracy, specificity, precision, recall, and F-measure were determined for the training dataset and repeated for the testing dataset (24 857 entries from 9430 records). Accuracy, precision, recall, and F-measure for medication allergy matches were all above 98% in the training dataset and above 97% in the testing dataset for all allergy entries. Corresponding values for food allergy matches were above 97% and above 93%, respectively. Specificities of the algorithm were 90.3% and 85.0% for drug matches and 100% and 88.9% for food matches in the training and testing datasets, respectively. The algorithm had high performance for identification of medication and food allergies. Maintenance is practical, as updates are managed through upload of new RxNorm versions and additions to companion database tables. However, direct entry of codified allergy information by providers (through autocompleters or drop lists) is still preferred to post-hoc encoding of the data. Data tables used in the algorithm are available for download. A high performing, easily maintained algorithm can successfully identify medication and food allergies from free text entries in EHR systems.

  10. Infrared spectra of aliphatic amine carbamates and the solution of the inverse spectroscopic problem. Part II

    Science.gov (United States)

    Stepanyan, S. A.; Gribov, L. A.; Ribnikar, S. V.; Mioč, U. B.

    1992-03-01

    For two carbamates of primary and secondary amines, taken to have structures of ionic pairs, EtHNCOO -+H 3NEt and Me 2NCOO -+H 2NMe, force fields were formed and vibrational frequencies calculated. A detailed assignment of the observed band frequencies was obtained. A parallel calculation was done for molecules with 13C-substituted COO --group carbon atoms. Separation factors for the isotope exchange between gaseous CO 2 and the two carbamate types were calculated. Their values vary 2 from 1.03 at 293 K to 1.01 at 573 K.

  11. pHP-Tethered N-Acyl Carbamate: A Photocage for Nicotinamide.

    Science.gov (United States)

    Salahi, Farbod; Purohit, Vatsal; Ferraudi, Guillermo; Stauffacher, Cynthia; Wiest, Olaf; Helquist, Paul

    2018-04-13

    The synthesis of a new photocaged nicotinamide having an N-acyl carbamate linker and a p-hydroxyphenacyl (pHP) chromophore is described. The photophysical and photochemical studies showed an absorption maximum at λ = 330 nm and a quantum yield for release of 11% that are dependent upon both pH and solvent. While the acyl carbamate releases nicotinamide efficiently, a simpler amide linker was inert to photocleavage. This photocaged nicotinamide has significant advantages with respect to quantum yield, absorbance wavelength, rate of release, and solubility that make it the first practical example of a photocaged amide.

  12. Film formation of ω-aminoalkylcellulose carbamates--a quartz crystal microbalance (QCM) study.

    Science.gov (United States)

    Elschner, Thomas; Doliška, Aleš; Bračič, Matej; Stana-Kleinschek, Karin; Heinze, Thomas

    2015-02-13

    The film formation of novel ω-aminoalkylcellulose carbamates on gold surface was studied by means of quartz crystal microbalance with dissipation monitoring (QCM-D) and atomic force microscopy (AFM). The influence of the pH value of the buffer solution, the concentration, the degree of polymerization, and the structure (spacer length) of the polymers on the coating was investigated. The layer formation was explained based on the pKa value and the degree of substitution of the ω-aminoalkylcellulose carbamates determined by potentiometric titration. This work provides novel supporting materials that might be applied in field of immobilization of biomolecules. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Impact of antiepileptic drugs on thrombocytopenia in glioblastoma patients treated with standard chemoradiotherapy.

    Science.gov (United States)

    Simó, Marta; Velasco, Roser; Graus, Francesc; Verger, Eugenia; Gil, Miguel; Pineda, Estela; Blasco, Jaume; Bruna, Jordi

    2012-07-01

    Epilepsy in glioblastoma multiforme (GBM) patients is common. Hematological toxicity is a potential side effect of antiepileptic drugs (AEDs) and a frequent limiting-dose effect of temozolomide (TMZ). The aim of the study was to investigate the impact of AEDs on thrombocytopenia in GBM patients treated with radiotherapy and TMZ. A cohort of 101 newly diagnosed GBM patients treated with radiotherapy and TMZ was reviewed. Clinical data, presence of seizures, AEDs use, platelet count, and accumulated TMZ dose were analyzed at each cycle. Thrombocytopenia was operationalized as a continuous platelet count and a dichotomic variable (cut-off <100.000/mm(3)). This cut-off represents the threshold beyond which TMZ treatment is modified. A linear and a probit pooled cross-sectional regression analysis were used to study the impact of age, gender, AEDs, and accumulated TMZ on thrombocytopenia. Impact of AEDs on survival was also analyzed. Thirty-five patients (35%) presented seizures at onset and 18 (27%) during follow-up. Seven (13%) needed two or more AEDs for seizure control. Grade 3-4 thrombocytopenia was found in 8%. Decrease in platelet count was related to accumulated TMZ (p < 0.001), age (p < 0.001), and valproate (p = 0.004). Platelet count <100.000/mm(3) was only associated with accumulated TMZ (p = 0.001). Recursive Partitioning Analysis prognostic class was the only variable with significant impact on survival. Valproate and age had an independent negative effect on total platelet count, although neither had an effect on critical thrombocytopenia (<100.000/mm(3)). Therefore, the systematic withhold of valproate in GBM patients might not be justified. Nevertheless, this negative effect may be taken into account especially in elderly patients.

  14. In vitro Evaluation of Benzimidazole Carbamates on Cystic Larvae of ...

    African Journals Online (AJOL)

    polyvinylpyrrolidone-drug solutions and dimethylsulfoxide-drug suspensions) of mebendazole, albendazole and ricobendazole (albendazole sulphoxide) by analyzing their in vitro efficacy on Echinococcus granulosus, Mesocestoides corti and Taenia ...

  15. Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

    Directory of Open Access Journals (Sweden)

    Benito Alcaide

    2013-04-01

    Full Text Available A combined experimental and computational study on regioselective gold-catalyzed synthetic routes to 1,3-oxazinan-2-ones (kinetically controlled products and 1,3-oxazin-2-one derivatives (thermodynamically favored from easily accessible allenic carbamates has been carried out.

  16. Suzuki–Miyaura Cross-Coupling of Aryl Carbamates and Sulfamates: Experimental and Computational Studies

    Science.gov (United States)

    Quasdorf, Kyle W.; Antoft-Finch, Aurora; Liu, Peng; Silberstein, Amanda L.; Komaromi, Anna; Blackburn, Tom; Ramgren, Stephen D.; Houk, K. N.; Snieckus, Victor; Garg, Neil K.

    2011-01-01

    The first Suzuki–Miyaura cross-coupling reactions of the synthetically versatile O-aryl carbamate and O-sulfamate groups is described. The transformations utilize the inexpensive, bench-stable catalyst NiCl2(PCy3)2 to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups (EDGs, EWGs) are tolerated, in addition to those that possess ortho substitutents. Furthermore, heteroaryl substrates may be employed as coupling partners. A computational study providing the full catalytic cycles for these cross-coupling reactions is described. The oxidative additions with carbamates and sulfamates occur via a five-centered transition state, resulting in the exclusive cleavage of the Ar–O bond. Water is found to stabilize the Ni–carbamate catalyst resting state, and thus provides rationalization of the relative decreased rate of coupling of carbamates. Several synthetic applications are presented to showcase the utility of the methodology in the synthesis of polysubstituted aromatic compounds of natural product and bioactive molecule interest. PMID:21456551

  17. The preparation and study of cellulose carbamates and their regenerated membranes.

    Science.gov (United States)

    Yu, Guomin; Teng, Yun; Lai, Weidong; Yin, Cuiyu

    2016-12-01

    Using wood pulps with the average degree of polymerization 300-350 and urea as raw materials, cellulose carbamates were successfully synthesized by esterification reaction in N, N-dimethylacetamide(DMAc), an inexpensive, high boiling aprotic and polar solvent, for the purpose of improving the solubility of cellulose, reducing costs and environmental pollution. The products were dissolved in 9% sodium hydroxide solution at a low temperature after washing and drying and the cellulose carbamates solutions were obtained. The solutions were uniformly casted on a glass support after degassing. The regenerated cellulose membranes (CMs) were prepared by immersing the support in coagulation bath for some minutes. The structures of cellulose carbamates were characterized by Fourier transform infrared spectroscopy (FT-IR), 13 C solid state nuclear magnetic resonance spectrometry ( 13 C NMR), Thermal gravimetric analysis(TG), Scanning electron microscopy (SEM) and X-ray diffractometry(XRD). The filtration performances of CMs were tested. The results reveal that part groups of cellulose were substituted by amino in the medium, the cellulose carbamates were prepared with the reducing crystallinity and thermal decomposition temperature. The CMs have good separation performance for methylene blue. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Quantum calculations of the electro-optical parameters of haloid ethers, esters, amides and carbamates

    Science.gov (United States)

    Furer, V. L.

    1992-03-01

    Force and electro-optical parameters of haloid ethers, esters, amides and carbamates were calculated using the MINDO/3 method. The obtained values of parameters, frequencies and intensities of bands in IR spectra are in good accordance with experiment. The changes of molecular parameters due to the electronic interactions and conformational transitions are discussed.

  19. VALUE OF ED50 TESTING IN ASSESSING HAZARDS OF ACUTE POISONING BY CARBAMATES AND ORGANOPHOSPHATES

    Science.gov (United States)

    Vandekar, M.; Reiner, E.; Svetličić, B.; Fajdetić, T.

    1965-01-01

    It is shown from the kinetics of inhibition of cholinesterase by N-methylcarbamates and organophosphates that the LD50 dose is likely to be a much greater multiple of the dose causing signs of poisoning in 50% of the animals (the ED50) for the carbamates than for the organophosphates. The expected difference was demonstrated by a comparison of the LD50s and ED50s, intravenous and intramuscular, of five carbamates (2-isopropoxyphenyl N-methylcarbamate, 3-isopropylphenyl N-methylcarbamate, 6-chloro-3,4-xylyl N-methylcarbamate, 3,4,5-trimethylphenyl N-methylcarbamate, and 3-methyl-5-isopropylphenyl N-methylcarbamate) and two organophosphorus compounds (diethyl 4-nitrophenyl phosphate and dimethyl 4-nitrophenyl phosphate). The slightest evoked tremor was chosen as the most reliable sign of poisoning from which to estimate the ED50 values. Carbamates gave much greater LD50/ED50 ratios than organophosphorus compounds. It is likely that occupational exposure to carbamates will produce incapacitating symptoms at doses well below lethal levels. PMID:5836574

  20. Pharmacophore-based design and discovery of (-)-meptazinol carbamates as dual modulators of cholinesterase and amyloidogenesis.

    Science.gov (United States)

    Xie, Qiong; Zheng, Zhaoxi; Shao, Biyun; Fu, Wei; Xia, Zheng; Li, Wei; Sun, Jian; Zheng, Wei; Zhang, Weiwei; Sheng, Wei; Zhang, Qihong; Chen, Hongzhuan; Wang, Hao; Qiu, Zhuibai

    2017-12-01

    Multifunctional carbamate-type acetylcholinesterase (AChE) inhibitors with anti-amyloidogenic properties like phenserine are potential therapeutic agents for Alzheimer's disease (AD). We reported here the design of new carbamates using pharmacophore model strategy to modulate both cholinesterase and amyloidogenesis. A five-feature pharmacophore model was generated based on 25 carbamate-type training set compounds. (-)-Meptazinol carbamates that superimposed well upon the model were designed and synthesized, which exhibited nanomolar AChE inhibitory potency and good anti-amyloidogenic properties in in vitro test. The phenylcarbamate 43 was highly potent (IC 50 31.6 nM) and slightly selective for AChE, and showed low acute toxicity. In enzyme kinetics assay, 43 exhibited uncompetitive inhibition and reacted by pseudo-irreversible mechanism. 43 also showed amyloid-β (Aβ) lowering effects (51.9% decrease of Aβ 42 ) superior to phenserine (31% decrease of total Aβ) in SH-SY5Y-APP 695 cells at 50 µM. The dual actions of 43 on cholinergic and amyloidogenic pathways indicated potential uses as symptomatic and disease-modifying agents.

  1. COMPARISON OF ACUTE NEUROBEHAVIORAL AND CHOLINESTERASE INHIBITORY EFFECTS OF N-METHYL CARBAMATES IN RAT

    Science.gov (United States)

    There are few studies evaluating direct functional and biochemical consequences of exposure. In the present study of the acute toxicity of seven N-methyl carbamate pesticides, we evaluated the dose-response profiles of cholinesterase (ChE) inhibition in brain and erythrocytes (R...

  2. Impact of Chemical Proportions on the Acute Neurotoxicity of a Mixture of Seven Carbamates in Rats

    Science.gov (United States)

    Environmental exposures generally involve multiple chemicals and pathways, and statistical methodologies now exist to evaluate interactions among any number of chemicals in defined mixtures. N-methyl carbamate pesticides are presumed to act through a common mode of action, that i...

  3. Management of exogenous intoxication by carbamates and organophosphates at an emergency unit.

    Science.gov (United States)

    Leão, Sydney Correia; Araújo, José Fernandes de; Silveira, Alessandro Rodrigues; Queiroz, Alex André Ferreira; Souto, Maria Júlia Silveira; Almeida, Rodrigo Oliveira; Maciel, Diego Carvalho; Rodrigues, Tânia Maria de Andrade

    2015-01-01

    to evaluate and indicate the procedure to be followed in the health unit, both for diagnosis and the treatment of acute exogenous intoxications by carbamates or organophosphates. a descriptive study based on retrospective analysis of the clinical history of patients diagnosed with intoxication by carbamates or organophosphates admitted at the emergency unit of the Hospital de Urgências de Sergipe Governador João Alves (HUSE) between January and December of 2012. Some criteria were evaluated, such as: intoxicating agent; patient's age and gender; place of event, cause, circumstances and severity of the intoxication; as well as signs and symptoms of the muscarinic, nicotinic and neurological effects. seventy patients (average age: 25 ± 19.97) formed the study's population. It was observed that 77.14% of them suffered carbamate intoxication. However, organophosphate intoxications were more severe, with 68.75% of patients presenting moderate to severe forms. Suicide attempt was the leading cause of poisoning, with 62 cases (88.57% of total). Atropine administration was an effective therapeutic approach for treating signs and symptoms, which included sialorrhea (p = 0.0006), nausea (p = 0. 0029) and emesis (p carbamates or organophosphates.

  4. Mechanism-Based Analysis of Acetylcholinesterase Inhibitory Potency of Organophosphates, Carbamates, and Their Analogs

    Science.gov (United States)

    Acetylcholinesterase (AChE) is a key enzyme in the nervous system of animals, terminating impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine. Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a s...

  5. TIME-COURSE OF ACUTE NEUROTOXICITY PRODUCED BY N-METHYL CARBAMATES IN PREWEANLING RATS.

    Science.gov (United States)

    N-methyl carbamate insecticides are reversible inhibitors of central and peripheral acetylcholinesterease (ChE). Despite their widespread and long-term use, we could find no studies of a systematic comparison of neurotoxicity in young animals across this group of chemicals. To ...

  6. Acetylcholinesterase inhibition as an indicator of organophosphate and carbamate poisoning in Kenyan agricultural workers.

    NARCIS (Netherlands)

    Ohayo-Mitoko, G.J.A.; Heederik, D.; Kromhout, H.; Omondi, B.E.O.; Boleij, J.S.M.

    1997-01-01

    Acetylcholinesterase inhibition was determined for 666 Kenyan agricultural workers; 390 (58.6%) mainly pesticide applicators exposed to organophosphate and carbamate pesticides and 276 (41.4%) unexposed controls from four rural agricultural areas during 1993 and 1994. Baseline levels were depressed

  7. Dietary cumulative acute risk assessment of organophosphorus, carbamates and pyrethroids insecticides for the Brazilian population.

    NARCIS (Netherlands)

    Jardim, Andreia Nunes Oliveira; Brito, Alessandra Page; van Donkersgoed, Gerda; Boon, Polly E; Caldas, Eloisa Dutra

    Cumulative acute dietary risk assessments of organophosphorus (OPs), carbamates (CBs) and pyrethroids (PYs) were conducted for the Brazilian population. Residue data for 30786 samples of 30 foods were obtained from two national monitoring programs and one University laboratory, and consumption data

  8. Cumulative risk assessment of the exposure to organophosphorus and carbamate insecticides in the dutch diet

    NARCIS (Netherlands)

    Boon, P.E.; Voet, van der H.; Raaij, van M.T.M.; Klaveren, van J.D.

    2008-01-01

    We report the acute cumulative exposure to organophosphorus insecticides (OPs) and carbamates in the Dutch population and young children (1-6 years) via the diet. Residue data were derived from Dutch monitoring programmes performed during 2003-2005, and food consumption levels from the Dutch

  9. Trifluoroacetic acid-promoted Michael addition-cyclization reactions of vinylogous carbamates.

    Science.gov (United States)

    Naganaboina, Ram Tilak; Nayak, Amrita; Peddinti, Rama Krishna

    2014-06-07

    A simple and efficient methodology has been developed for the synthesis of pyrrolobenzoxazine and 3-arylamino coumarin derivatives promoted by trifluoroacetic acid. The initial step in the current protocol involves a Michael addition of the 1,4-benzoxazinone derivatives, a novel class of vinylogous carbamates to the Michael acceptors and subsequent cyclization.

  10. Ultrasound-assisted surfactant-enhanced emulsification microextraction for the determination of carbamates in wines by ultra-high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Moreno-González, David; Huertas-Pérez, José F; García-Campaña, Ana M; Bosque-Sendra, Juan M; Gámiz-Gracia, Laura

    2013-11-08

    A new sensitive multiresidue method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed for the detection, confirmation and quantification of twenty five carbamates in wine samples. The separation was achieved in 5.5 min, using a Zorbax Eclipse plus RRHD C18 column (50 mm×2.1 mm, 1.8 μm), with a mobile phase of water and methanol, both of them with 0.01% formic acid. The analytes were detected in positive mode with multiple reaction monitoring mode. Ultrasound-assisted surfactant-enhanced emulsification microextraction (UASEME), using a low-density extraction solvent has been optimized for the satisfactory extraction of carbamates and clean-up of extracts. The matrix effect was studied, showing that the proposed procedure provides very clean extracts. Under optimum conditions, recoveries for fortified wine samples ranged from 74 to 102%, with relative standard deviations lower than 6%. Limits of quantification ranged from 0.15 to 0.92 μgl(-1), showing the high sensitivity of this fast and simple method and its compliance with current requirements. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Fully automated dynamic in-syringe liquid-phase microextraction and on-column derivatization of carbamate pesticides with gas chromatography/mass spectrometric analysis.

    Science.gov (United States)

    Lee, Jingyi; Lee, Hian Kee

    2011-09-01

    A new fully automated dynamic in-syringe liquid-phase microextraction (LPME) and on-column derivatization approach, with gas chromatography/mass spectrometric (GC/MS) analysis, was developed to determine carbamate pesticides from water samples. With the use of a CTC CombiPal autosampler and its associated Cycle Composer software, a sample preparation-GC/MS method was enabled that allowed sample extraction, extract injection, and analyte derivatization to be carried out completely automatically. Optimization of extraction parameters was carried out by orthogonal array design which required a minimum of 16 experiments; the entire set of experiments was performed completely automatically and consecutively without any human intervention. Low limits of detection ranging from 0.05 to 0.1 μg/L were achieved for the carbamates. Effective enrichment of the analytes at a low concentration of 0.01 mg/L was also achieved (enrichment factors of between 57 and 138). The precision of the optimized method was satisfactory, with relative standard deviations of <6.0% (n = 6). High relative recoveries of between 81 and 125% were obtained when the method was applied to the analysis of real water samples, indicating that the sample matrix had little effect on the developed method. This automated dynamic in-syringe LPME approach demonstrated the feasibility of a complete analytical system comprising sample preparation and GC/MS that might be operated onsite, fully automatically without human intervention.

  12. Intermolecular Hydroamination of Allenes with N-Unsubstituted Carbamates Catalyzed by a Gold(I) N-Heterocyclic Carbene Complex

    Science.gov (United States)

    Kinder, Robert E.; Zhang, Zhibin; Widenhoefer, Ross A.

    2009-01-01

    Reaction of 2,3-pentadienyl benzoate and benzyl carbamate with a catalytic 1:1 mixture of (NHC)AuCl and AgOTf in dioxane at 23 °C for 5 h led to isolation of (E)-4-(benzyloxycarbonylamino)-2-pentenyl benzoate in 84% yield as a single regio- and diastereomer. Gold(I)-catalyzed hydroamination was effective for a number of N-unsubstituted carbamates and a range of substituted allenes. PMID:18570376

  13. Copper-catalyzed oxidative coupling of formamides with salicylaldehydes: synthesis of carbamates in the presence of a sensitive aldehyde group.

    Science.gov (United States)

    Barve, Balaji D; Wu, Yang-Chang; El-Shazly, Mohamed; Chuang, Da-Wei; Cheng, Yuan-Bin; Wang, Jeh-Jeng; Chang, Fang-Rong

    2014-04-04

    A diverse library of novel carbamates was synthesized utilizing copper-catalyzed oxidative C-O coupling of formamides and salicylaldehydes. Sensitive aldehyde groups remained intact in the presence of an oxidant and a transition-metal salt. Salicylaldehydes bearing electron-donating, electron-withdrawing, and halogen groups as well as 1-hydroxy-2-naphthaldehydes provided the desired carbamates in good to excellent yields.

  14. Evidence based herbal drug standardization approach in coping with challenges of holistic management of diabetes: a dreadful lifestyle disorder of 21st century.

    Science.gov (United States)

    Chawla, Raman; Thakur, Pallavi; Chowdhry, Ayush; Jaiswal, Sarita; Sharma, Anamika; Goel, Rajeev; Sharma, Jyoti; Priyadarshi, Smruti Sagar; Kumar, Vinod; Sharma, Rakesh Kumar; Arora, Rajesh

    2013-07-04

    Plants by virtue of its composition of containing multiple constituents developed during its growth under various environmental stresses providing a plethora of chemical families with medicinal utility. Researchers are exploring this wealth and trying to decode its utility for enhancing health standards of human beings. Diabetes is dreadful lifestyle disorder of 21st century caused due to lack of insulin production or insulin physiological unresponsiveness. The chronic impact of untreated diabetes significantly affects vital organs. The allopathic medicines have five classes of drugs, or otherwise insulin in Type I diabetes, targeting insulin secretion, decreasing effect of glucagon, sensitization of receptors for enhanced glucose uptake etc. In addition, diet management, increased food fiber intake, Resistant Starch intake and routine exercise aid in managing such dangerous metabolic disorder. One of the key factors that limit commercial utility of herbal drugs is standardization. Standardization poses numerous challenges related to marker identification, active principle(s), lack of defined regulations, non-availability of universally acceptable technical standards for testing and implementation of quality control/safety standard (toxicological testing). The present study proposed an integrated herbal drug development & standardization model which is an amalgamation of Classical Approach of Ayurvedic Therapeutics, Reverse Pharmacological Approach based on Observational Therapeutics, Technical Standards for complete product cycle, Chemi-informatics, Herbal Qualitative Structure Activity Relationship and Pharmacophore modeling and, Post-Launch Market Analysis. Further studies are warranted to ensure that an effective herbal drug standardization methodology will be developed, backed by a regulatory standard guide the future research endeavors in more focused manner.

  15. BRAF plus MEK-targeted drugs: a new standard of treatment for BRAF-mutant advanced melanoma.

    Science.gov (United States)

    Queirolo, Paola; Spagnolo, Francesco

    2017-03-01

    BRAF plus MEK-targeted drugs have out-performed BRAF inhibitor monotherapy in three randomized phase 3 studies, and such combinations have become a new standard of treatment for BRAF-mutant advanced melanoma. With an overall response rate of about 70%, no other therapy in melanoma has shown a better response rate in late-phase clinical trials than combined BRAF and MEK inhibitors; the rapid kinetics of response make them the ideal front-line treatment for symptomatic, BRAF-mutant advanced melanoma patients. Nevertheless, the development of mechanisms of resistance limits the duration of response to such treatment in the majority of cases, with only about 20% of patients treated with the combination being progression-free at 3 years. The aim of this review is to report the efficacy and safety outcomes of the combination of BRAF plus MEK inhibitors compared with BRAF inhibitor monotherapy and immunotherapy, as well as to discuss future perspectives to improve outcomes based on current clinical and translational research studies.

  16. The Most Prevalnet Organism in Diabetic Foot Ulcers and Its Drug Sensitivity and Resistance to Different Standard Antibiotics

    International Nuclear Information System (INIS)

    Nageen, A.

    2016-01-01

    Objective: To find the most prevalent organism in diabetic foot ulcers and its drug sensitivity and resistance to different standard antibiotics. Study Design: Adescriptive and cross-sectional study. Place and Duration of Study: Ward 7, Jinnah Postgraduate Medical Center, Karachi, from December 2010 to December 2012. Methodology: Ninety-five diabetic patients with infected foot wounds of Wegener grade 2 - 5 who had not received any previous antibiotics were included in the study by consecutive sampling. Pus culture specimen from wounds was taken and the organism isolated was identified. Also the most sensitive group of antibiotics and the most resistant one to that organism was noted. Results: Staphylococcus aureus was the most prevalent organism constituting 23.16% (n=22) of the organisms isolated; Escherichia coli with 17.89% (n=17) and Klebsiella with 12.63% (n=12) followed. Males presented more with diabetic foot (n=52) out of 95 patients. The most common age group affected was 41 - 60 years (73 patients). The organisms were most sensitive to Meropenem, effective in 90 (95%) patients and most resistant to Cotrimoxazole (80, 84% patients). Out of the 95 patients, 39 (41%) patients were hypertensive, 30 (31.5%) were obese and 14 (15%) were smokers. Staphylococcus aureus was the most prevalent organism overall irrespective to gender, age groups and co-morbidity of the patients. Conclusion: Staphylococcus aureus was the most frequent organism in diabetic foot ulcers; the most effective antibiotic is Meropenem and least effective is Cotrimoxazole. (author)

  17. Individualized versus standardized risk assessment in patients at high risk for adverse drug reactions (IDrug) - study protocol for a pragmatic randomized controlled trial.

    Science.gov (United States)

    Stingl, Julia Carolin; Kaumanns, Katharina Luise; Claus, Katrin; Lehmann, Marie-Louise; Kastenmüller, Kathrin; Bleckwenn, Markus; Hartmann, Gunther; Steffens, Michael; Wirtz, Dorothee; Leuchs, Ann-Kristin; Benda, Norbert; Meier, Florian; Schöffski, Oliver; Holdenrieder, Stefan; Coch, Christoph; Weckbecker, Klaus

    2016-04-26

    Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of drugs with high risk potential. Apart from these clinical parameters, drug safety and efficacy can be influenced by pharmacogenetic factors. Evidence-based recommendations concerning drug-gene-combinations have been issued by international consortia and in drug labels. However, clinical benefit of providing information on individual patient factors in a comprehensive risk assessment aiming to reduce the occurrence and severity of adverse drug reactions is not evident. Purpose of this randomized controlled trial is to compare the effect of a concise individual risk information leaflet with standard information on risk factors for side effects. The trial was designed as a prospective, two-arm, randomized, controlled, multicenter, pragmatic study. 960 elderly, multimorbid outpatients in general medicine are included if they take at least one high risk and one other long-term drug (polymedication). As high risk "index drugs" oral anticoagulants and antiplatelets were chosen because of their specific, objectively assessable side effects. Following randomization, test group patients receive an individualized risk assessment leaflet evaluating their personal data concerning bleeding- and thromboembolic-risk-scores, potential drug-drug-interactions, age, renal function and pharmacogenetic factors. Control group patients obtain a standardized leaflet only containing general information on these criteria. Follow-up period is 9 months for each patient. Primary endpoint is the occurrence of a thromboembolic/bleeding event or death. Secondary endpoints are other adverse drug reactions, hospital admissions, specialist referrals and medication changes due to adverse drug reactions, the patients' adherence to medication regimen as well as health related quality of life

  18. Electrochemical release of amine molecules from carbamate-based, electroactive self-assembled monolayers.

    Science.gov (United States)

    Hong, Daewha; Kang, Kyungtae; Hong, Seok-Pyo; Shon, Hyun Kyong; Son, Jin Gyeong; Lee, Tae Geol; Choi, Insung S

    2012-01-10

    In this paper, carbamate-based self-assembled monolayers (SAMs) of alkanethiolates on gold were suggested as a versatile platform for release of amine-bearing molecules in response to the electrical signal. The designed SAMs underwent the electrochemical oxidation on the gold surface with simultaneous release of the amine molecules. The synthesis of the thiol compounds was achieved by coupling isocyanate-containing compounds with hydroquinone. The electroactive thiol was mixed with 11-mercaptoundecanol [HS(CH(2))(11)OH] to form a mixed monolayer, and cyclic votammetry was used for the characterization of the release behaviors. The mixed SAMs showed a first oxidation peak at +540 mV (versus Ag/AgCl reference electrode), indicating the irreversible conversion from carbamate to hydroquinone groups with simultaneous release of the amine molecules. The analysis of ToF-SIMS further indicated that the electrochemical reaction on the gold surface successfully released amine molecules.

  19. Optimization of 1,2,5-Thiadiazole Carbamates as Potent and Selective ABHD6 Inhibitors #

    Science.gov (United States)

    Patel, Jayendra Z.; Nevalainen, Tapio J.; Savinainen, Juha R.; Adams, Yahaya; Laitinen, Tuomo; Runyon, Robert S.; Vaara, Miia; Ahenkorah, Stephen; Kaczor, Agnieszka A.; Navia-Paldanius, Dina; Gynther, Mikko; Aaltonen, Niina; Joharapurkar, Amit A.; Jain, Mukul R.; Haka, Abigail S.; Maxfield, Frederick R.; Laitinen, Jarmo T.; Parkkari, Teija

    2015-01-01

    At present, inhibitors of α/β-hydrolase domain 6 (ABHD6) are viewed as a promising approach to treat inflammation and metabolic disorders. This article describes the optimization of 1,2,5-thiadiazole carbamates as ABHD6 inhibitors. Altogether, 34 compounds were synthesized and their inhibitory activity was tested using lysates of HEK293 cells transiently expressing human ABHD6 (hABHD6). Among the compound series, 4-morpholino-1,2,5-thiadiazol-3-yl cyclooctyl(methyl)carbamate (JZP-430, 55) potently and irreversibly inhibited hABHD6 (IC50 44 nM) and showed good selectivity (∼230 fold) over fatty acid amide hydrolase (FAAH) and lysosomal acid lipase (LAL), the main off-targets of related compounds. Additionally, activity-based protein profiling (ABPP) indicated that compound 55 (JZP-430) displayed good selectivity among the serine hydrolases of mouse brain membrane proteome. PMID:25504894

  20. Fenugreek hydrogel-agarose composite entrapped gold nanoparticles for acetylcholinesterase based biosensor for carbamates detection.

    Science.gov (United States)

    Kestwal, Rakesh Mohan; Bagal-Kestwal, Dipali; Chiang, Been-Huang

    2015-07-30

    A biosensor was fabricated to detect pesticides in food samples. Acetylcholinesterase was immobilized in a novel fenugreek hydrogel-agarose matrix with gold nanoparticles. Transparent thin films with superior mechanical strength and stability were obtained with 2% fenugreek hydrogel and 2% agarose. Immobilization of acetylcholinesterase on the membrane resulted in high enzyme retention efficiency (92%) and a significantly prolonged shelf life of the enzyme (half-life, 55 days). Transmission electron microscopy revealed that, gold nanoparticles (10-20 nm in diameter) were uniformly dispersed in the fenugreek hydrogel-agarose-acetylcholinesterase membrane. This immobilized enzyme-gold nanoparticle dip-strip system detected various carbamates, including carbofuran, oxamyl, methomyl, and carbaryl, with limits of detection of 2, 21, 113, and 236 nM (S/N = 3), respectively. Furthermore, the fabricated biosensor exhibited good testing capabilities when used to detect carbamates added to various fruit and vegetable samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Azetidine and Piperidine Carbamates as Efficient, Covalent Inhibitors of Monoacylglycerol Lipase.

    Science.gov (United States)

    Butler, Christopher R; Beck, Elizabeth M; Harris, Anthony; Huang, Zhen; McAllister, Laura A; Am Ende, Christopher W; Fennell, Kimberly; Foley, Timothy L; Fonseca, Kari; Hawrylik, Steven J; Johnson, Douglas S; Knafels, John D; Mente, Scot; Noell, G Stephen; Pandit, Jayvardhan; Phillips, Tracy B; Piro, Justin R; Rogers, Bruce N; Samad, Tarek A; Wang, Jane; Wan, Shuangyi; Brodney, Michael A

    2017-12-14

    Monoacylglycerol lipase (MAGL) is the main enzyme responsible for degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the CNS. MAGL catalyzes the conversion of 2-AG to arachidonic acid (AA), a precursor to the proinflammatory eicosannoids such as prostaglandins. Herein we describe highly efficient MAGL inhibitors, identified through a parallel medicinal chemistry approach that highlighted the improved efficiency of azetidine and piperidine-derived carbamates. The discovery and optimization of 3-substituted azetidine carbamate irreversible inhibitors of MAGL were aided by the generation of inhibitor-bound MAGL crystal structures. Compound 6, a highly efficient and selective MAGL inhibitor against recombinant enzyme and in a cellular context, was tested in vivo and shown to elevate central 2-AG levels at a 10 mg/kg dose.

  2. Cumulative risk assessment of the intake of organophosphorus and carbamate pesticides in the Danish diet

    DEFF Research Database (Denmark)

    Jensen, A. F.; Petersen, Annette; Granby, Kit

    2003-01-01

    Reference Dose (ARfD) nor ADI was exceeded for any of the compounds studied. The results indicate that the Danish population is neither exposed to any cumulative chronic risk, nor at risk of acute exposure, from consumption of organophosphorus and carbamate pesticides from fruit, vegetables and cereals....... in the Danish nation-wide food consumption survey in 1995. The pesticide data are based on the Danish pesticide residue-monitoring programme from 1996-2001. The amount of 35 organophosphorus pesticides and carbamates were included in the cumulative risk assessment. Processing factors, such as reduction...... fruit, vegetables and cereals is for adults 0.8-2% of the Acceptable Daily Intake (ADI) in chlorpyrifos equivalents, and 0.03-11% of the ADI in methamidophos equivalents; and for children 2-5% of the ADI in the chlorpyrifos equivalents, and 0.07-27% of the ADI in methamidophos equivalents. Neither Acute...

  3. Irradiation degradation of carbamate and organophosphorous pesticides in Chinese herbal medicines

    International Nuclear Information System (INIS)

    Chen Qiyong; Chang Chunyan; Xiao Yabing; Wu Ruoxin

    2013-01-01

    In order to put forward new method and basis to remove pesticide residues in Chinese herbs, the influence factors such as irradiation doses and water content of electron beam irradiation on degradation efficiency of carbamate and organophosphorous pesticides in ginseng are investigated. Additionally, the irradiation degradation of two pesticides treated with the same dose in several traditional Chinese herbal medicines like Baifuling is also studied. The irradiation can effectively degrade these pesticide residues in herbal medicines; the efficiency of lower doses are inferior to higher doses. The degradation rate rises when dose increases, and varies among 4 ∼ 10 kGy in different Chinese herbal medicines. The degradation efficiency of organophosphorous pesticides is better than those of carbamate pesticides. (authors)

  4. 76 FR 34147 - Land Disposal Restrictions: Revision of the Treatment Standards for Carbamate Wastes

    Science.gov (United States)

    2011-06-13

    ..., selenium, sulfides, vanadium, and zinc, which can reasonably be expected to be present at the point of...-02-0 3.98 11.0 mg/L TCLP Selenium 7782-49-2 0.82 5.7 mg/L TCLP * * * * * * * P127 Carbofuran \\10...

  5. Synthesis and Antimicrobial Evaluation of 1-[(2-Substituted phenyl)carbamoyl]naphthalen-2-yl Carbamate

    Czech Academy of Sciences Publication Activity Database

    Goněc, T.; Pospíšilová, Š.; Holanová, L.; Straník, J.; Černíková, A.; Pudelkova, V.; Kos, J.; Oravec, Michal; Kollár, P.; Čížek, A.; Jampílek, J.

    2016-01-01

    Roč. 21, č. 9 (2016), č. článku 1189. ISSN 1420-3049 R&D Projects: GA MŠk(CZ) LM2015061; GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : carbamates * hydroxynaphthalene-carboxamides * in vitro antibacterial activity * in vitro cytotoxicity assay * structure-activity relationships Subject RIV: EH - Ecology, Behaviour Impact factor: 2.861, year: 2016

  6. Management of exogenous intoxication by carbamates and organophosphates at an emergency unit

    Directory of Open Access Journals (Sweden)

    Sydney Correia Leão

    2015-10-01

    Full Text Available Summary Objectives: to evaluate and indicate the procedure to be followed in the health unit, both for diagnosis and the treatment of acute exogenous intoxications by carbamates or organophosphates. Methods: a descriptive study based on retrospective analysis of the clinical history of patients diagnosed with intoxication by carbamates or organophosphates admitted at the emergency unit of the Hospital de Urgências de Sergipe Governador João Alves (HUSE between January and December of 2012. Some criteria were evaluated, such as: intoxicating agent; patient's age and gender; place of event, cause, circumstances and severity of the intoxication; as well as signs and symptoms of the muscarinic, nicotinic and neurological effects. Results: seventy patients (average age: 25±19.97 formed the study's population. It was observed that 77.14% of them suffered carbamate intoxication. However, organophosphate intoxications were more severe, with 68.75% of patients presenting moderate to severe forms. Suicide attempt was the leading cause of poisoning, with 62 cases (88.57% of total. Atropine administration was an effective therapeutic approach for treating signs and symptoms, which included sialorrhea (p=0.0006, nausea (p=0. 0029 and emesis (p lt0.0001. The use of activated charcoal was shown effective, both in combating the signs and symptoms presented by both patient groups (p <0.0001. Conclusion: it is concluded that the use of atropine and activated charcoal is highly effective to treat the signs and symptoms developed by patients presenting acute exogenous intoxication by carbamates or organophosphates.

  7. Nickel-Catalyzed Amination of Aryl Sulfamates and Carbamates Using an Air-Stable Precatalyst

    Science.gov (United States)

    Hie, Liana; Ramgren, Stephen D.; Mesganaw, Tehetena; Garg, Neil K.

    2012-01-01

    A facile nickel-catalyzed method to achieve the amination of synthetically useful aryl sulfamates and carbamates is reported. Contrary to most Ni-catalyzed amination reactions, this user-friendly approach relies on an air-stable Ni(II) precatalyst, which, when employed with a mild reducing agent, efficiently delivers aminated products in good to excellent yields. The scope of the method is broad with respect to both coupling partners and includes heterocyclic substrates. PMID:22849697

  8. Organophosphorus and carbamates residues in milk and feedstuff supplied to dairy cattle

    OpenAIRE

    Rafael Fagnani; Vanerli Beloti; Ana Paula P. Battaglini; Karen da S. Dunga; Ronaldo Tamanini

    2011-01-01

    Considering acute and chronic toxicity effects on human and animal health caused by pesticide residues in food, this study aimed to analyze organophosphorate (OP) and carbamate (CB) in feedstuff and water destined for dairy cattle, as well as in the milk produced by these animals, through gas chromatography (GC). In the Agreste region of Pernambuco, Brazil, 30 raw milk samples and all components of the animals' diet were collected from several farms. Out of the 30 milk of milk analyzed, six (...

  9. Synthesis of dimethyl carbonate from methyl carbamate and methanol over lanthanum compounds

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Dengfeng; Zhang, Xuelan; Gao, Yangyan [State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan, 030001 (China); Graduate university of Chinese, Academy of Sciences, Beijing, 100049 (China); Xiao, Fukui; Wei, Wei; Sun, Yuhan [State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan, 030001 (China)

    2010-09-15

    Various lanthanum compounds were used as the catalyst for the synthesis of dimethyl carbonate (DMC) from methyl carbamate and methanol. Among them, La(NO{sub 3}){sub 3} presented the best catalytic performance with the DMC yield of 53.7% under suitable reaction conditions. Based on the results of X-ray diffraction, Fourier transform infrared spectroscopy and element analysis, a possible reaction mechanism over lanthanum nitrate was proposed for this reaction. (author)

  10. The toxicologic effects of the carbamate insecticide aldicarb in mammals: a review.

    OpenAIRE

    Risher, J F; Mink, F L; Stara, J F

    1987-01-01

    Aldicarb, 2-methyl-2-(methylthio)propionaldehyde-O-methylcarbamoyloxime, is an oxime carbamate insecticide manufactured by the Union Carbide Corporation and sold under the trade name Temik. It is a soil-applied systemic pesticide used against certain insects, mites, and nematodes, and is applied below the soil surface for absorption by plant roots. It is generally applied to the soil in the form of 5, 10, or 15% granules, and soil moisture is essential for the release of the toxicant. Uptake ...

  11. Surface Display of Recombinant Drosophila melanogaster Acetylcholinesterase for Detection of Organic Phosphorus and Carbamate Pesticides

    OpenAIRE

    Li, Jingquan; Qian Ba,; Yin, Jun; Wu, Songjie; Zhuan, Fangfang; Xu, Songci; Li, Junyang; Salazar, Joelle K.; Zhang, Wei; Wang, Hui

    2013-01-01

    Acetylcholinesterase (AChE) is commonly used for the detection of organophosphate (OP) and carbamate (CB) insecticides. However, the cost of this commercially available enzyme is high, making high-throughput insecticide detection improbable. In this study we constructed a new AChE yeast expression system in Saccharomyces cerevisiae for the expression of a highly reactive recombinant AChE originating from Drosophila melanogaster (DmAChE). Specifically, the coding sequence of DmAChE was fused w...

  12. Removal of carbamates and detoxification potential in a biomixture: Fungal bioaugmentation versus traditional use.

    Science.gov (United States)

    Rodríguez-Rodríguez, Carlos E; Madrigal-León, Karina; Masís-Mora, Mario; Pérez-Villanueva, Marta; Chin-Pampillo, Juan Salvador

    2017-01-01

    The use of fungal bioaugmentation represents a promising way to improve the performance of biomixtures for the elimination of pesticides. The ligninolyitc fungus Trametes versicolor was employed for the removal of three carbamates (aldicarb, ALD; methomyl, MTM; and methiocarb, MTC) in defined liquid medium; in this matrix ALD and MTM showed similar half-lives (14d), nonetheless MTC exhibited a faster removal, with a half-life of 6.5d. Then the fungus was employed in the bioaugmentation of an optimized biomixture to remove the aforementioned carbamates plus carbofuran (CFN). Bioaugmented and non-bioaugmented systems removed over 99% ALD and MTM after 8d of treatment, nonetheless a slight initial delay in the removal was observed in the bioaugmented biomixtures (removal after 3d: ALD 87%/97%; MTM 86%/99%, in bioaugmented/non-bioaugmented systems). The elimination of the other carbamates was slower, but independent of the presence of the fungus: >98% for MTM after 35d and >99.5% for CFN after 22d. Though the bioaugmentation did not improve the removal capacity of the biomixture, it favored a lower production of transformation products at the first stages of the treatment, and in both cases, a marked decrease in the toxicity of the matrix was swiftly achieved along the process (from 435 to 448 TU to values <1TU in 16d). Copyright © 2016 Elsevier Inc. All rights reserved.

  13. O-hydroxyacetamide carbamates as a highly potent and selective class of endocannabinoid hydrolase inhibitors.

    Science.gov (United States)

    Niphakis, Micah J; Johnson, Douglas S; Ballard, T Eric; Stiff, Cory; Cravatt, Benjamin F

    2012-05-16

    The two major endocannabinoid transmitters, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are degraded by distinct enzymes in the nervous system, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. FAAH and MAGL inhibitors cause elevations in brain AEA and 2-AG levels, respectively, and reduce pain, anxiety, and depression in rodents without causing the full spectrum of psychotropic behavioral effects observed with direct cannabinoid receptor-1 (CB1) agonists. These findings have inspired the development of several classes of endocannabinoid hydrolase inhibitors, most of which have been optimized to show specificity for either FAAH or MAGL or, in certain cases, equipotent activity for both enzymes. Here, we investigate an unusual class of O-hydroxyacetamide carbamate inhibitors and find that individual compounds from this class can serve as selective FAAH or dual FAAH/MAGL inhibitors in vivo across a dose range (0.125-12.5 mg kg(-1)) suitable for behavioral studies. Competitive and click chemistry activity-based protein profiling confirmed that the O-hydroxyacetamide carbamate SA-57 is remarkably selective for FAAH and MAGL in vivo, targeting only one other enzyme in brain, the additional 2-AG hydrolase ABHD6. These data designate O-hydroxyacetamide carbamates as a versatile chemotype for creating endocannabinoid hydrolase inhibitors that display excellent in vivo activity and tunable selectivity for FAAH-anandamide versus MAGL (and ABHD6)-2-AG pathways.

  14. Characterization of tunable piperidine and piperazine carbamates as inhibitors of endocannabinoid hydrolases

    Science.gov (United States)

    Long, Jonathan Z.; Jin, Xin; Adibekian, Alexander; Li, Weiwei; Cravatt, Benjamin F.

    2010-01-01

    Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are two enzymes from the serine hydrolase superfamily that degrade the endocannabinoids 2-arachidonoylglycerol and anandamide, respectively. We have recently discovered that MAGL and FAAH are both inhibited by carbamates bearing an N-piperidine/piperazine group. Piperidine/piperazine carbamates show excellent in vivo activity, raising brain endocannabinoid levels and producing CB1-dependent behavioral effects in mice, suggesting that they represent a promising class of inhibitors for studying the endogenous functions of MAGL and FAAH. Herein, we disclose a full account of the syntheses, structure-activity relationships, and inhibitory activities of piperidine/piperazine carbamates against members of the serine hydrolase family. These scaffolds can be tuned for MAGL-selective or dual MAGL-FAAH inhibition by the attachment of an appropriately substituted bisarylcarbinol or aryloxybenzyl moiety, respectively, on the piperidine/piperazine ring. Modifications to the piperidine/piperazine ring ablated inhibitory activity, suggesting a strict requirement for a six-member ring to maintain potency. PMID:20099888

  15. Determination of Ethyl Carbamate in Chinese Yellow Rice Wine by Diatomaceous Earth Extraction and GC/MS Method.

    Science.gov (United States)

    Wu, Pinggu; Zhang, Liqun; Shen, Xianghong; Wang, Liyuan; Zou, Yan; Zhang, Jing; Tan, Ying; Tang, Jun; Ma, Bingjie; Pan, Xiaodong; Jiang, Wei

    2015-01-01

    A sensitive and rapid analytical method based on alkaline diatomaceous earth extraction followed by GC/MS was developed for the quantitative determination of the toxic contaminant ethyl carbamate (EC) in yellow rice wines. The optimal extraction conditions were investigated. With the application of diatomaceous earth extraction, the damage of organic acids to the capillary column was greatly reduced. By using d5-EC as an internal standard for quantitative analysis of EC, the linearity of the calibration curves was good between 10 and 1000 ng/mL. The LOD and LOQ were 1.7 and 5.0 μg/kg, respectively. The spiked level of EC was 5.0-300 μg/kg, and the average recovery of the spikes was between 78.4 and 98.2%, with an RSD between 4.3 and 8.3%. Upon validation by five laboratories when spiked with 50, 100, and 300 μg/kg, the average respective recoveries were 102.9, 102.2, and 98.7% with a RSD between 0.7 and 8.1%. The validation results demonstrated that the method is fast, simple, selective, and suitable for the determination of EC in yellow rice wines.

  16. Covalent Inhibition of Recombinant Human Carboxylesterase 1 and 2 and Monoacylglycerol Lipase by the Carbamates JZL184 and URB597

    Science.gov (United States)

    Crow, J. Allen; Bittles, Victoria; Borazjani, Abdolsamad; Potter, Philip M.; Ross, Matthew K.

    2012-01-01

    Carboxylesterase type 1 (CES1) and CES2 are serine hydrolases located in the liver and small intestine. CES1 and CES2 actively participate in the metabolism of several pharmaceuticals. Recently, carbamate compounds were developed to inhibit members of the serine hydrolase family via covalent modification of the active site serine. URB597 and JZL184 inhibit fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively; however, carboxylesterases in liver have been identified as a major off-target. We report the kinetic rate constants for inhibition of human recombinant CES1 and CES2 by URB597 and JZL184. Bimolecular rate constants (kinact/Ki) for inhibition of CES1 by JZL184 and URB597 were similar [3.9 (±0.2) × 103 M-1 s-1 and 4.5 (±1.3) × 103 M-1 s-1, respectively]. However, kinact/Ki for inhibition of CES2 by JZL184 and URB597 were significantly different [2.3 (±1.3) × 102 M-1 s-1 and 3.9 (±1.0) × 103 M-1 s-1, respectively]. Rates of inhibition of CES1 and CES2 by URB597 were similar; however, CES1 and MAGL were more potently inhibited by JZL184 than CES2. We also determined kinetic constants for spontaneous reactivation of CES1 carbamoylated by either JZL184 or URB597 and CES1 diethylphosphorylated by paraoxon. The reactivation rate was significantly slower (4.5x) for CES1 inhibited by JZL184 than CES1 inhibited by URB597. Half life of reactivation for CES1 carbamoylated by JZL184 was 49 ± 15 h, which is faster than carboxylesterase turnover in HepG2 cells. Together, the results define the kinetics of inhibition for a class of drugs that target hydrolytic enzymes involved in drug and lipid metabolism. PMID:22943979

  17. Thiadiazole Carbamates: Potent Inhibitors of Lysosomal Acid Lipase and Potential Niemann-Pick Type C Disease Therapeuticsa

    Science.gov (United States)

    Rosenbaum, Anton I.; Cosner, Casey C.; Mariani, Christopher J.; Maxfield, Frederick R.; Wiest, Olaf; Helquist, Paul

    2010-01-01

    Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized at the cellular level by abnormal accumulation of cholesterol and other lipids in lysosomal storage organelles. Lysosomal acid lipase (LAL) has been recently identified as a potential therapeutic target for NPC. LAL can be specifically inhibited by a variety of 3,4-disubstituted thiadiazole carbamates. An efficient synthesis of the C(3) oxygenated/C(4) aminated analogues has been developed that furnishes the products in high yields and high degrees of purity. Common intermediates can also be used for the synthesis of the C(3) carbon substituted derivatives. Herein we tested various thiadiazole carbamates, amides, esters, and ketones for inhibition of LAL. In addition, we tested a diverse selection of commercially available non-thiadiazole carbamates. Our studies show that, among the compounds examined herein, only thiadiazole carbamates are effective inhibitors of LAL. We present a mechanism for LAL inhibition by these compounds whereby LAL transiently carbamoylates the enzyme similarly to previously described inhibition of acetylcholinesterase by rivastigmine and other carbamates as well as acylation of various lipases by orlistat. PMID:20557099

  18. Effect of new ethyl and methyl carbamates on biological parameters and reproduction of the cattle tick Rhipicephalus microplus.

    Science.gov (United States)

    Prado-Ochoa, M G; Muñoz-Guzmán, M A; Abrego-Reyes, V H; Velázquez-Sánchez, A M; Lara-Rocha, M; Cuenca-Verde, C; Angeles, E; Alba-Hurtado, F

    2013-05-01

    The effect of carbamates on engorged female Rhipicephalus microplus ticks and larvae was evaluated using the adult immersion test (AIT) and the larval packet test (LPT), respectively. Seventeen synthetic carbamates different from current commercial acaricides were synthesised at the National Autonomous University of Mexico. None of the carbamates had an effect on the percentage of females laying eggs. Six of the compounds inhibited egg laying up to 65.4% and inhibited egg hatching by up to 100% (pCarbamates LQM 934 and LQM 938 had an effect on larval mortality (pCarbamate LQM 934 showed lethal concentrations (LC) of LC90=0.76% and LC99=0.87%, while LQM 938 showed concentrations of LC90=0.267% and LC99=0.305%. The compounds were distributed into three classes of acaricidal activity using the AIT or the LPT. These three classes were as follows: (1) compounds having no apparent effect; (2) compounds that inhibit egg laying and embryo development or (3) compounds that exhibit acaricidal activity to larval ticks. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Thiadiazole carbamates: potent inhibitors of lysosomal acid lipase and potential Niemann-Pick type C disease therapeutics.

    Science.gov (United States)

    Rosenbaum, Anton I; Cosner, Casey C; Mariani, Christopher J; Maxfield, Frederick R; Wiest, Olaf; Helquist, Paul

    2010-07-22

    Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized at the cellular level by abnormal accumulation of cholesterol and other lipids in lysosomal storage organelles. Lysosomal acid lipase (LAL) has been recently identified as a potential therapeutic target for NPC. LAL can be specifically inhibited by a variety of 3,4-disubstituted thiadiazole carbamates. An efficient synthesis of the C(3) oxygenated/C(4) aminated analogues has been developed that furnishes the products in high yields and high degrees of purity. Common intermediates can also be used for the synthesis of the C(3) carbon substituted derivatives. Herein we tested various thiadiazole carbamates, amides, esters, and ketones for inhibition of LAL. In addition, we tested a diverse selection of commercially available non-thiadiazole carbamates. Our studies show that, among the compounds examined herein, only thiadiazole carbamates are effective inhibitors of LAL. We present a mechanism for LAL inhibition by these compounds whereby LAL transiently carbamoylates the enzyme similarly to previously described inhibition of acetylcholinesterase by rivastigmine and other carbamates as well as acylation of various lipases by orlistat.

  20. Kinetic and thermodynamic analysis for lipase-catalyzed hydrolytic resolution of (R,S)-alcohols though their azolyl carbamates.

    Science.gov (United States)

    Cheng, Ya-Ling; Wu, An-Chi; Wang, Pei-Yun; Tsai, Shau-Wei

    2012-08-01

    A new approach to the lipase-catalyzed hydrolytic resolution of (R,S)-azolyl carbamates for obtaining chiral azolyl carbamates and alcohol is described. With (R,S)-1-phenylethyl azolyl carbamates as the model substrates, the best reaction condition of using (R,S)-1-phenylethyl 4-bromopyrazole carbamate (1) as the substrate in water-saturated diisopropyl ether at 45 °C is selected. The kinetic constants, and hence enantiomeric ratio of 124, are then estimated from the kinetic analysis by considering the alcohol inhibition effect, with which theoretical time-course conversions for both enantiomers are numerically solved and agree with the experimental data. The thermodynamic parameters -ΔΔH and -ΔΔS satisfying a linear enthalpy-entropy compensation relationship of -ΔΔS = -38.84 + 3.29(-ΔΔH) are further estimated. An extension of the resolution platform to (R,S)-4-bromopyrazole carbamates derived from other (R,S)-alcohols (4, 5, 7) is also addressed.

  1. Absorption of carbon dioxide and isotope exchange rate of carbon in a reaction system between carbon dioxide and carbamic acid

    International Nuclear Information System (INIS)

    Takeshita, Kenji; Kitamoto, Asashi

    1985-01-01

    The performance of isotope separation of carbon-13 by chemical exchange between carbon dioxide and carbamic acid was studied. The working fluid used in the study was a solution of DNBA, (C 4 H 9 ) 2 NH and n-octane mixture. Factors related to the isotope exchange rate were measured, such as the absorption rate of carbon dioxide into the solution of DNBA and n-octane, the isotope exchange rate and the separation factor in the reaction between CO 2 and carbamic acid. The absorption of CO 2 into the working fluid was the sum of chemical absorption by DNBA and physical absorption by n-octane. The absorption of carbon dioxide into the working fluid was negligible at temperatures over 90 0 C, but increased gradually at lower temperatures. Carbon dioxide was absorbed into DNBA by chemical absorption, and DNBA was converted to carbamic acid by the reaction. The reaction for synthesis and decomposition of carbamic acid was reversible. The separation factor in equilibrium reached a large value at lower temperatures. The isotope exchange rate between gas and liquid was proportional to the product of the concentration of carbamic acid and the concentration of CO 2 by physical absorption. The isotope separation of carbon by chemical exchange reaction is better operated under the conditions of lower temperature and higher pressure. (author)

  2. The IR spectra and hydrogen bonding of toluene-2,6-bis(methyl) and 4,4'-diphenylmethane-bis(methyl) carbamates

    Science.gov (United States)

    Furer, V. L.

    2000-03-01

    The IR spectroscopy has been used to study models of polyurethanes containing different hard segments. The spectra of toluene-2,6-bis(methyl) and 4,4'-diphenylmethane-bis(methyl) carbamates at different temperatures were studied. The absorption curves of the free and associated carbamate molecules were compared with experimental IR spectra. The characteristic features of toluene-2,6-bis(methyl) carbamate and methyl- N-methyl carbamate clusters were revealed. The IR spectra for the two most stable toluene-2,6-bis(methyl) carbamate conformations were compared. The origin of the multiplet structure of bands in the experimental IR spectra of polyurethanes was discussed. The results obtained can be used for the analysis of the chemical and physical transformations in urethanes and polyurethanes.

  3. Synthesis and Preclinical Evaluation of Sulfonamido-based [(11)C-Carbonyl]-Carbamates and Ureas for Imaging Monoacylglycerol Lipase.

    Science.gov (United States)

    Wang, Lu; Mori, Wakana; Cheng, Ran; Yui, Joji; Hatori, Akiko; Ma, Longle; Zhang, Yiding; Rotstein, Benjamin H; Fujinaga, Masayuki; Shimoda, Yoko; Yamasaki, Tomoteru; Xie, Lin; Nagai, Yuji; Minamimoto, Takafumi; Higuchi, Makoto; Vasdev, Neil; Zhang, Ming-Rong; Liang, Steven H

    2016-01-01

    Monoacylglycerol lipase (MAGL) is a 33 kDa member of the serine hydrolase superfamily that preferentially degrades 2-arachidonoylglycerol (2-AG) to arachidonic acid in the endocannabinoid system. Inhibition of MAGL is not only of interest for probing the cannabinoid pathway but also as a therapeutic and diagnostic target for neuroinflammation. Limited attempts have been made to image MAGL in vivo and a suitable PET ligand for this target has yet to be identified and is urgently sought to guide small molecule drug development in this pathway. Herein we synthesized and evaluated the physiochemical properties of an array of eleven sulfonamido-based carbamates and ureas with a series of terminal aryl moieties, linkers and leaving groups. The most potent compounds were a novel MAGL inhibitor, N-((1-(1H-1,2,4-triazole-1-carbonyl)piperidin-4-yl) methyl)-4-chlorobenzenesulfonamide (TZPU; IC50 = 35.9 nM), and the known inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(((4-chlorophenyl)sulfonamido) methyl)piperidine-1-carboxylate (SAR127303; IC50 = 39.3 nM), which were also shown to be selective for MAGL over fatty acid amide hydrolase (FAAH), and cannabinoid receptors (CB1 & CB2). Both of these compounds were radiolabeled with carbon-11 via [(11)C]COCl2, followed by comprehensive ex vivo biodistribution and in vivo PET imaging studies in normal rats to determine their brain permeability, specificity, clearance and metabolism. Whereas TZPU did not show adequate specificity to warrant further evaluation, [(11)C]SAR127303 was advanced for preliminary PET neuroimaging studies in nonhuman primate. The tracer showed good brain permeability (ca. 1 SUV) and heterogeneous regional brain distribution which is consistent with the distribution of MAGL.

  4. Synthesis and Preclinical Evaluation of Sulfonamido-based [11C-Carbonyl]-Carbamates and Ureas for Imaging Monoacylglycerol Lipase

    Science.gov (United States)

    Wang, Lu; Mori, Wakana; Cheng, Ran; Yui, Joji; Hatori, Akiko; Ma, Longle; Zhang, Yiding; Rotstein, Benjamin H.; Fujinaga, Masayuki; Shimoda, Yoko; Yamasaki, Tomoteru; Xie, Lin; Nagai, Yuji; Minamimoto, Takafumi; Higuchi, Makoto; Vasdev, Neil; Zhang, Ming-Rong; Liang, Steven H.

    2016-01-01

    Monoacylglycerol lipase (MAGL) is a 33 kDa member of the serine hydrolase superfamily that preferentially degrades 2-arachidonoylglycerol (2-AG) to arachidonic acid in the endocannabinoid system. Inhibition of MAGL is not only of interest for probing the cannabinoid pathway but also as a therapeutic and diagnostic target for neuroinflammation. Limited attempts have been made to image MAGL in vivo and a suitable PET ligand for this target has yet to be identified and is urgently sought to guide small molecule drug development in this pathway. Herein we synthesized and evaluated the physiochemical properties of an array of eleven sulfonamido-based carbamates and ureas with a series of terminal aryl moieties, linkers and leaving groups. The most potent compounds were a novel MAGL inhibitor, N-((1-(1H-1,2,4-triazole-1-carbonyl)piperidin-4-yl) methyl)-4-chlorobenzenesulfonamide (TZPU; IC50 = 35.9 nM), and the known inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(((4-chlorophenyl)sulfonamido) methyl)piperidine-1-carboxylate (SAR127303; IC50 = 39.3 nM), which were also shown to be selective for MAGL over fatty acid amide hydrolase (FAAH), and cannabinoid receptors (CB1 & CB2). Both of these compounds were radiolabeled with carbon-11 via [11C]COCl2, followed by comprehensive ex vivo biodistribution and in vivo PET imaging studies in normal rats to determine their brain permeability, specificity, clearance and metabolism. Whereas TZPU did not show adequate specificity to warrant further evaluation, [11C]SAR127303 was advanced for preliminary PET neuroimaging studies in nonhuman primate. The tracer showed good brain permeability (ca. 1 SUV) and heterogeneous regional brain distribution which is consistent with the distribution of MAGL. PMID:27279908

  5. Age dependence of organophosphate and carbamate neurotoxicity in the postnatal rat: extrapolation to the human

    International Nuclear Information System (INIS)

    Vidair, Charles A.

    2004-01-01

    One important aspect of risk assessment for the organophosphate and carbamate pesticides is to determine whether their neurotoxicity occurs at lower dose levels in human infants compared to adults. Because these compounds probably exert their neurotoxic effects through the inhibition of acetylcholinesterase (AChE), the above question can be narrowed to whether the cholinesterase inhibition and neurotoxicity they produce is age-dependent, both in terms of the effects produced and potency. The rat is the animal model system most commonly used to address these issues. This paper first discusses the adequacy of the postnatal rat to serve as a model for neurodevelopment in the postnatal human, concluding that the two species share numerous pathways of postnatal neurodevelopment, and that the rat in the third postnatal week is the neurodevelopmental equivalent of the newborn human. Then, studies are discussed in which young and adult rats were dosed by identical routes with organophosphates or carbamates. Four pesticides were tested in rat pups in their third postnatal week: aldicarb, chlorpyrifos, malathion, and methamidophos. The first three, but not methamidophos, caused neurotoxicity at dose levels that ranged from 1.8- to 5.1-fold lower (mean 2.6-fold lower) in the 2- to 3-week-old rat compared to the adult. This estimate in the rat, based on a limited data set of three organophosphates and a single carbamate, probably represents the minimum difference in the neurotoxicity of an untested cholinesterase-inhibiting pesticide that should be expected between the human neonate and adult. For the organophosphates, the greater sensitivity of postnatal rats, and, by analogy, that expected for human neonates, is correlated with generally lower levels of the enzymes involved in organophosphate deactivation

  6. Synthesis of acyl carbamates via four component Pd-catalyzed carbonylative coupling of aryl halides, potassium cyanate, and alcohols.

    Science.gov (United States)

    Yin, Hongfei; de Almeida, Angelina M; de Almeida, Mauro V; Lindhardt, Anders T; Skrydstrup, Troels

    2015-03-06

    A simple and mild method is demonstrated for assembling acyl carbamates through a base-free four-component Pd-catalyzed carbonylation of aryl halides in the presence of potassium cyanate and alcohols in a two-chamber system. This approach produces a wide range of aryl acyl carbamates in good to excellent yields from the corresponding aryl bromides or iodides with near-stoichiometric carbon monoxide. In addition, the method can be extended to the synthesis of primary amides thereby expanding the usefulness of cyanate as an ammonia equivalent.

  7. Nonracemic, chiral homoenolate reagents derived from (cycloalk-1-enyl)methyl carbamates and evaluation of their configurational stabilities

    DEFF Research Database (Denmark)

    Özlügedik, M.; Kristensen, Jesper Langgaard; Wibbeling, B.

    2002-01-01

    the products 19/ent-19. Lithiated 2-unsubstituted (cyclopent-1-enyl) methyl carbamates, such as 11a or 11h, epimerise rapidly at -78 °C and the thermodynamically controlled ratio is opposite to the kinetically achieved ratio. High configurational stability was found for the 2-methylcycloalk-1-enyl derivatives......-methylcyclopentenyl)methyl and (2-methyl-cyclohexenyl)methyl reagents, established the (1S) configuration of the major lithium compound. Thus, the kinetically controlled deprotonation of the corresponding allyl carbamates removes the (pro-S) proton. Overall, a simple method for the enantioselective synthesis...

  8. Probabilistic assessment of the cumulative dietary acute exposure of the population of Denmark to organophosphorus and carbamate pesticides

    DEFF Research Database (Denmark)

    Jensen, Bodil Hamborg; Petersen, Annette; Christensen, Tue

    2009-01-01

    and cereals. The probabilistic approach was used in the assessments. Residue data obtained from the Danish monitoring programme carried out in the period 2004-2007, which included 6704 samples of fruit, vegetables and cereals, were used in the calculations. Food consumption data were obtained from......Organophosphorus and carbamate pesticides are acetylcholinesterase-inhibiting pesticides and as such have a common mode of action. We assessed the cumulative acute exposure of the population of Denmark to 25 organophosphorus and carbamate pesticide residues from the consumption of fruit, vegetables...

  9. Combating highly resistant emerging pathogen Mycobacterium abscessus and Mycobacterium tuberculosis with novel salicylanilide esters and carbamates.

    Science.gov (United States)

    Baranyai, Zsuzsa; Krátký, Martin; Vinšová, Jarmila; Szabó, Nóra; Senoner, Zsuzsanna; Horváti, Kata; Stolaříková, Jiřina; Dávid, Sándor; Bősze, Szilvia

    2015-08-28

    In the Mycobacterium genus over one hundred species are already described and new ones are periodically reported. Species that form colonies in a week are classified as rapid growers, those requiring longer periods (up to three months) are the mostly pathogenic slow growers. More recently, new emerging species have been identified to lengthen the list, all rapid growers. Of these, Mycobacterium abscessus is also an intracellular pathogen and it is the most chemotherapy-resistant rapid-growing mycobacterium. In addition, the cases of multidrug-resistant Mycobacterium tuberculosis infection are also increasing. Therefore there is an urgent need to find new active molecules against these threatening strains. Based on previous results, a series of salicylanilides, salicylanilide 5-chloropyrazinoates and carbamates was designed, synthesized and characterised. The compounds were evaluated for their in vitro activity on M. abscessus, susceptible M. tuberculosis H37Rv, multidrug-resistant (MDR) M. tuberculosis MDR A8, M. tuberculosis MDR 9449/2006 and on the extremely-resistant Praha 131 (XDR) strains. All derivatives exhibited a significant activity with minimum inhibitory concentrations (MICs) in the low micromolar range. Eight salicylanilide carbamates and two salicylanilide esters exhibited an excellent in vitro activity on M. abscessus with MICs from 0.2 to 2.1 μM, thus being more effective than ciprofloxacin and gentamicin. This finding is potentially promising, particularly, as M. abscessus is a threateningly chemotherapy-resistant species. M. tuberculosis H37Rv was inhibited with MICs from 0.2 μM, and eleven compounds have lower MICs than isoniazid. Salicylanilide esters and carbamates were found that they were effective also on MDR and XDR M. tuberculosis strains with MICs ≥1.0 μM. The in vitro cytotoxicity (IC50) was also determined on human MonoMac-6 cells, and selectivity index (SI) of the compounds was established. In general, salicylanilide

  10. Simple, specific analysis of organophosphorus and carbamate pesticides in sediments using column extraction and gas chromatography

    Science.gov (United States)

    Belisle, A.A.; Swineford, D.M.

    1988-01-01

    A simple, specific procedure was developed for the analysis of organophosphorus and carbamate pesticides in sediment. The wet soil was mixed with anhydrous sodium sulfate to bind water and the residues were column extracted in acetone:methylene chloride (1:l,v/v). Coextracted water was removed by additional sodium sulfate packed below the sample mixture. The eluate was concentrated and analyzed directly by capillary gas chromatography using phosphorus and nitrogen specific detectors. Recoveries averaged 93 % for sediments extracted shortly after spiking, but decreased significantly as the samples aged.

  11. Radioiodinated 2-nitrobenzyl carbamates as bioreductive alkylating agents for tissue hypoxia

    International Nuclear Information System (INIS)

    Culbert, P.A.; Hunter, D.H.; Wearring, A.V.; Chamberlain, M.J.

    1993-01-01

    Three N-methylcarbamates of iodonitrobenzyl alcohols (4-iodo-2-nitrobenzyl alcohol 2, 5-iodo-2-nitrobenzyl alcohol 3 and 4-iodo-2,6-dinitrobenzyl alcohol 4) bearing [ 125 I] have been prepared and characterized for their lipophilicity, their reduction potentials and the in vivo lability of the radioiodine in healthy mice. Based upon these results, 2 and 4 were tested in tumour-bearing mice showing limited uptake of radioactivity in tumours and a tumour-to-blood ratio of less than 1. Consequently these particular carbamates are not satisfactory as hypoxia imaging agents. (Author)

  12. Radioiodinated 2-nitrobenzyl carbamates as bioreductive alkylating agents for tissue hypoxia

    International Nuclear Information System (INIS)

    Cuthbert, P.A.; Wearring, A.V.; Chamberlain, M.J.; Hunter, D.H.

    1993-01-01

    Three N-methylcarbamates of iodonitrobenzyl alcohols (4-iodo-2-nitrobenzyl alcohol 2, 5-iodo-2-nitrobenzyl alcohol 3 and 4-iodo-2,6-dinitrobenzyl alcohol 4) bearing [ 125 I] have been prepared and characterized for their lipophilicity, their reduction potentials and the in vivo lability of the radioiodine in healthy mice. Based upon these results, 2 and 4 were tested in tumor-bearing mice showing limited uptake of radioactivity in tumours and a tumor-to-blood ratio of less than 1. Consequently these particular carbamates are not satisfactory as hypoxia imaging agents. (author)

  13. Who benefits from additional drug counseling among prescription opioid-dependent patients receiving buprenorphine-naloxone and standard medical management?

    Science.gov (United States)

    Weiss, Roger D; Griffin, Margaret L; Potter, Jennifer Sharpe; Dodd, Dorian R; Dreifuss, Jessica A; Connery, Hilary S; Carroll, Kathleen M

    2014-07-01

    In the multi-site Prescription Opioid Addiction Treatment Study (POATS), conducted within the National Drug Abuse Clinical Trials Network, participants randomly assigned to receive individual drug counseling in addition to buprenorphine-naloxone and medical management did not have superior opioid use outcomes. However, research with other substance-dependent populations shows that subgroups of participants may benefit from a treatment although the entire population does not. We conducted a secondary analysis of POATS data to determine whether a subgroup of participants benefited from drug counseling in addition to buprenorphine-naloxone and medical management, either due to greater problem severity or more exposure to counseling as a result of greater treatment adherence. Problem severity was measured by a history of heroin use, higher Addiction Severity Index drug composite score, and chronic pain. Adequate treatment adherence was defined a priori as attending at least 60% of all offered sessions. Patients who had ever used heroin and received drug counseling were more likely to be successful (i.e., abstinent or nearly abstinent from opioids) than heroin users who received medical management alone, but only if they were adherent to treatment and thus received adequate exposure to counseling (OR=3.7, 95% CI=1.1-11.8, p=0.03). The association between severity and outcome did not vary by treatment condition for chronic pain or ASI drug severity score. These findings emphasize the importance of treatment adherence, and suggest that patients with prescription opioid dependence are a heterogeneous group, with different optimal treatment strategies for different subgroups. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Synthesis and anticancer activity of novel water soluble benzimidazole carbamates.

    Science.gov (United States)

    Cheong, Jae Eun; Zaffagni, Michela; Chung, Ivy; Xu, Yingjie; Wang, Yiqiang; Jernigan, Finith E; Zetter, Bruce R; Sun, Lijun

    2018-01-20

    Metastases account for more than 90% of all cancer deaths and respond poorly to most therapies. There remains an urgent need for new therapeutic modalities for the treatment of advanced metastatic cancers. The benzimidazole methylcarbamate drugs, commonly used as anti-helmitics, have been suggested to have anticancer activity, but progress has been stalled by their poor water solubility and poor suitability for systemic delivery to disseminated cancers. We synthesized and characterized the anticancer activity of novel benzimidazoles containing an oxetane or an amine group to enhance solubility. Among them, the novel oxetanyl substituted compound 18 demonstrated significant cytotoxicity toward a variety of cancer cell types including prostate, lung, and ovarian cancers with strong activity toward highly aggressive cancer lines (IC 50 : 0.9-3.8 μM). Compound 18 achieved aqueous solubility of 361 μM. In a mouse xenograft model of a highly metastatic human prostate cancer, compound 18 (30 mg/kg) significantly inhibited the growth of established tumors (T/C: 0.36) without noticeable toxicity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. [Developing and standardizing experimental protocols using human iPS-derived cells to predict adverse drug reactions in pre-clinical safety studies].

    Science.gov (United States)

    Sekino, Yuko; Sato, Kaoru; Kanda, Yasunari; Ishida, Seiichi

    2013-01-01

    In this study, we have standardized experimental protocols to evaluate the possibility of using cells differentiated from human induced pluripotent stem cells (hiPSCs) in the pre-clinical studies for the drug approval processes. Cells differentiated from hiPSC, especially cardiomyocytes, neurons and hepatocytes, are expected to be used as new pharmacological and toxicological assay tools. Current preclinical test methods have limitations for predicting clinical adverse drug reactions. This is because of the so-called 'problem of species difference'. Drug-induced arrhythmia, cognitive impairment and hepatotoxicity which can't be predicted in pre-clinical studies are major causes of the high rate attrition of new-drug candidates in clinical studies and of withdrawal of products from the market. The development of new pre-clinical test methods using cells differentiated from hiPSCs would resolve these problems, in addition to solving the issue of "the replacement, refinement and reduction (3Rs)" of animal experiments. From 2010 to 2011, we surveyed companies belonging to the Japan Pharmaceutical Manufacturers Association (JPMA) and academic researchers about the usage of differentiated cells in their laboratories. We found that studies were performed using differentiated cells from different cell lines of hiPSC with laboratory-specific differentiation methods. The cells were cultured in various conditions and their activities were measured using different methods. This resulted in a variety of pharmacological responses of the cells. It is therefore impossible to compare reproducibility and ensure reliability of experiments using these cells. To utilize the cells in the drug approval processes, we need robust, standardized test methods to accurately reproduce these methods in all laboratories. We will then be able to compare and analyze the obtained results. Based on the survey, the Ministry of Health, Labor and Welfare funded our study. In our study, we standardize

  16. Bivalent Carbamates as Novel Control Agents of the Malaria Mosquito, Anopheles gambiae.

    Science.gov (United States)

    Mutunga, James M; Chen, Qiao-Hong; Wong, Dawn M; Lam, Polo C-H; Li, Jianyong; Totrov, Maxim M; Gross, Aaron D; Carlier, Paul R; Bloomquist, Jeffrey R

    2016-10-01

    Widespread pyrethroid resistance has caused an urgent need to develop new insecticides for control of the malaria mosquito, Anopheles gambiae. Insecticide discovery efforts were directed towards the construction of bivalent inhibitors that occupy both the peripheral and catalytic sites of the mosquito acetylcholinesterase (AChE). It was hypothesized that this approach would yield a selective, high potency inhibitor that would also circumvent known catalytic site mutations (e.g. G119S) causing target site resistance. Accordingly, a series of bivalent phthalimide-pyrazole carbamates were prepared having an alkyl chain linker of varying length, along with other modifications. The most active compound was (1-(3-(1,3-dioxoisoindolin-2-yl)propyl)-1H-pyrazol-4-yl methylcarbamate, 8a), which has a chain length of three carbons, good mosquito anticholinesterase activity, and ca. 5-fold selectivity compared to human AChE. Moreover, this compound was toxic to mosquitoes by topical application (LD 50 = 63 ng/female) with only 6-fold cross resistance in the Akron strain of Anopheles gambiae that showed 50- to 60-fold resistance to conventional carbamate insecticides. However, contact lethality in the WHO paper assay was disappointing. The implications of these results for design of new mosquitocides are discussed.

  17. Carbamate and Pyrethroid Resistance in the Akron Strain of Anopheles gambiae

    Science.gov (United States)

    Mutunga, James M.; Anderson, Troy D.; Craft, Derek T.; Gross, Aaron D.; Swale, Daniel R.; Tong, Fan; Wong, Dawn M.; Carlier, Paul R.; Bloomquist, Jeffrey R.

    2015-01-01

    Insecticide resistance in the malaria vector, Anopheles gambiae is a serious problem, epitomized by the multi-resistant Akron strain, originally isolated in the country of Benin. Here we report resistance in this strain to pyrethroids and DDT (13-fold to 35-fold compared to the susceptible G3 strain), but surprisingly little resistance to etofenprox, a compound sometimes described as a “pseudo-pyrethroid.” There was also strong resistance to topically-applied commercial carbamates (45-fold to 81-fold), except for the oximes aldicarb and methomyl. Biochemical assays showed enhanced cytochrome P450 monooxygenase and carboxylesterase activity, but not that of glutathione-S-transferase. A series of substituted α,α,α,-trifluoroacetophenone oxime methylcarbamates were evaluated for enzyme inhibition potency and toxicity against G3 and Akron mosquitoes. The compound bearing an unsubstituted phenyl ring showed the greatest toxicity to mosquitoes of both strains. Low cross resistance in Akron was retained by all analogs in the series. Kinetic analysis of acetylcholinesterase activity and its inhibition by insecticides in the G3 strain showed inactivation rate constants greater than that of propoxur, and against Akron enzyme inactivation rate constants similar to that of aldicarb. However, inactivation rate constants against recombinant human AChE were essentially identical to that of the G3 strain. Thus, the acetophenone oxime carbamates described here, though potent insecticides that control resistant Akron mosquitoes, require further structural modification to attain acceptable selectivity and human safety. PMID:26047119

  18. Optimization of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors.

    Science.gov (United States)

    Patel, Jayendra Z; Nevalainen, Tapio J; Savinainen, Juha R; Adams, Yahaya; Laitinen, Tuomo; Runyon, Robert S; Vaara, Miia; Ahenkorah, Stephen; Kaczor, Agnieszka A; Navia-Paldanius, Dina; Gynther, Mikko; Aaltonen, Niina; Joharapurkar, Amit A; Jain, Mukul R; Haka, Abigail S; Maxfield, Frederick R; Laitinen, Jarmo T; Parkkari, Teija

    2015-02-01

    At present, inhibitors of α/β-hydrolase domain 6 (ABHD6) are viewed as a promising approach to treat inflammation and metabolic disorders. This article describes the development of 1,2,5-thiadiazole carbamates as ABHD6 inhibitors. Altogether, 34 compounds were synthesized, and their inhibitory activity was tested using lysates of HEK293 cells transiently expressing human ABHD6 (hABHD6). Among the compound series, 4-morpholino-1,2,5-thiadiazol-3-yl cyclooctyl(methyl)carbamate (JZP-430) potently and irreversibly inhibited hABHD6 (IC50 =44 nM) and showed ∼230-fold selectivity over fatty acid amide hydrolase (FAAH) and lysosomal acid lipase (LAL), the main off-targets of related compounds. Additionally, activity-based protein profiling indicated that JZP-430 displays good selectivity among the serine hydrolases of the mouse brain membrane proteome. JZP-430 has been identified as a highly selective, irreversible inhibitor of hABHD6, which may provide a novel approach in the treatment of obesity and type II diabetes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Expanded insecticide catabolic activity gained by a single nucleotide substitution in a bacterial carbamate hydrolase gene.

    Science.gov (United States)

    Öztürk, Başak; Ghequire, Maarten; Nguyen, Thi Phi Oanh; De Mot, René; Wattiez, Ruddy; Springael, Dirk

    2016-12-01

    Carbofuran-mineralizing strain Novosphingobium sp. KN65.2 produces the CfdJ enzyme that converts the N-methylcarbamate insecticide to carbofuran phenol. Purified CfdJ shows a remarkably low K M towards carbofuran. Together with the carbaryl hydrolase CehA of Rhizobium sp. strain AC100, CfdJ represents a new protein family with several uncharacterized bacterial members outside the proteobacteria. Although both enzymes differ by only four amino acids, CehA does not recognize carbofuran as a substrate whereas CfdJ also hydrolyzes carbaryl. None of the CfdJ amino acids that differ from CehA were shown to be silent regarding carbofuran hydrolytic activity but one particular amino acid substitution, i.e., L152 to F152, proved crucial. CfdJ is more efficient in degrading methylcarbamate pesticides with an aromatic side chain whereas CehA is more efficient in degrading the oxime carbamate nematicide oxamyl. The presence of common flanking sequences suggest that the cfdJ gene is located on a remnant of the mobile genetic element Tnceh carrying cehA. Our results suggest that these enzymes can be acquired through horizontal gene transfer and can evolve to degrade new carbamate substrates by limited amino acid substitutions. We demonstrate that a carbaryl hydrolase can gain the additional capacity to degrade carbofuran by a single nucleotide transversion. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  20. Confirmed organophosphorus and carbamate pesticide poisonings in South African wildlife (2009–2014

    Directory of Open Access Journals (Sweden)

    Christo J. Botha

    2015-12-01

    Full Text Available During a six-year period (from January 2009 to December 2014, specimens collected from 344 cases of suspected organophosphorus and carbamate pesticide poisonings in wildlife, including birds, were submitted to the Toxicology Laboratory (ARC-OVI for analysis. A positive diagnosis was made in 135 (39% of these cases. The majority of cases were from birds, which included Cape vultures (Gyps coprotheres and African white-backed vultures (Gyps africanus and bateleur eagles (Terathopius ecaudatus. In one incident 49 vultures were killed when a farmer intentionally laced carcasses with carbofuran in an attempt to control jackal predation. There were 22 incidents of poisoning in helmeted guineafowl (Numida meleagris. On nine different occasions blue cranes (Anthropoides paradiseus were poisoned, in one incident 14 birds were reported to have been killed. Over the period of investigation, there were 20 cases of poisoning involving mammalian species, the majority being vervet monkeys (Chlorocebus pygerythrus. The carbamate pesticides were responsible for 57 incidents of poisoning. Aldicarb, carbofuran and methomyl were detected in 26, 18 and 12 cases respectively. The majority of organophosphorus pesticide poisonings were caused by diazinon (n = 19, monocrotophos (n = 13 and methamidophos (n = 10.

  1. Bioactive Paper Sensor Based on the Acetylcholinesterase for the Rapid Detection of Organophosphate and Carbamate Pesticides

    Directory of Open Access Journals (Sweden)

    Mohamed E. I. Badawy

    2014-01-01

    Full Text Available In many countries, people are becoming more concerned about pesticide residues which are present in or on food and feed products. For this reason, several methods have been developed to monitor the pesticide residue levels in food samples. In this study, a bioactive paper-based sensor was developed for detection of acetylcholinesterase (AChE inhibitors including organophosphate and carbamate pesticides. Based on the Ellman colorimetric assay, the assay strip is composed of a paper support (1×10 cm, onto which a biopolymer chitosan gel immobilized in crosslinking by glutaraldehyde with AChE and 5,5′-dithiobis(2-nitrobenzoic acid (DTNB and uses acetylthiocholine iodide (ATChI as an outside reagent. The assay protocol involves introducing the sample to sensing zone via dipping of a pesticide-containing solution. Following an incubation period, the paper is placed into ATChI solution to initiate enzyme catalyzed hydrolysis of the substrate, causing a yellow color change. The absence or decrease of the yellow color indicates the levels of the AChE inhibitors. The biosensor is able to detect organophosphate and carbamate pesticides with good detection limits (methomyl=6.16×10-4 mM and profenofos=0.27 mM and rapid response times (~5 min. The results show that the paper-based biosensor is rapid, sensitive, inexpensive, portable, disposable, and easy-to-use.

  2. Enrichment of 13C by chemical exchange between CO2 and amine carbamate in nonaqueous solvent

    International Nuclear Information System (INIS)

    Raica, Paula; Axente, D.

    2009-01-01

    Full text: Enrichment of 13 C by chemical exchange between CO 2 and amine carbamate in nonaqueous solvent has been mathematically modelled in two ways. The height equivalent to a theoretical plate and steady-state separation, based on the two models, have been obtained. If only the isotopic exchange between CO 2 gas and amine carbamate is considered, the model can estimate the process performance for pressures close to the atmospheric one and room temperature. For process analysis at pressures higher than atmospheric one and lower temperatures, a two-step model has been developed. Using the two models the effects of pressure increasing have been studied. At atmospheric pressure and 2M DNBA - methanol solution the isotope transfer rate is lower at 5 deg. C than at 25 deg. C. The isotope transfer is supported by pressure increasing according the increase of the CO 2 concentration in the amine solution. A lower temperature determines also an increase in the concentration of dissolved CO 2 and, for this reason, at 5 deg.C and higher pressures the isotope exchange reaction rate is higher than at 25 deg. C, HETP being lower with more than 100% at 5 deg. C than at 25 deg. C. (authors)

  3. Comparison of active sites of butyrylcholinesterase and acetylcholinesterase based on inhibition by geometric isomers of benzene-di-N-substituted carbamates.

    Science.gov (United States)

    Chiou, Shyh-Ying; Huang, Chuan-Fu; Hwang, Mei-Ting; Lin, Gialih

    2009-01-01

    We have reported that benzene-1,2-, 1,3-, and 1,4-di-N-substituted carbamates (1-15) are characterized as the conformationally constrained inhibitors of acetylcholinesterase and mimic gauche, eclipsed, and anti-conformations of acetylcholine, respectively (J Biochem Mol Toxicol 2007;21:348-353). We further report the inhibition of butyrylcholinesterase by these inhibitors. Carbamates 1-15 are also characterized as the pseudosubstrate inhibitors of butyrylcholinesterase as in the acetylcholinesterase catalysis. Benzene-1,4-di-N-n-hexylcarbamate (12) and benzene-1,4-di-N-n-octylcarbamate (13) are the two most potent inhibitors of butyrylcholinesterase among inhibitors 1-15. These two para compounds, with the angle of 180 degrees between two C(benzene)--O bonds, mimic the preferable anti C--O/C--N conformers for the choline ethylene backbone of butyrylcholine during the butyrylcholinesterase catalysis. The second n-hexylcarbamyl or n-octylcarbamyl moiety of inhibitors 12 and 13 is proposed to bind tightly to the peripheral anionic site of butyrylcholinesterase from molecular modeling. Butyrylcholinesterase prefers para-carbamates to ortho- and meta-carbamates, whereas acetylcholinesterase prefers para- and meta-carbamates to ortho-carbamates. This result implies that the anionic site of butyrylcholinesterase is relatively smaller than that of acetylcholinesterase because meta-carbamates, which may bind to the anionic sites of both enzymes, are not potent inhibitors of butyrylcholinesterase.

  4. Contribution to the standardization of the chromatographic conditions for the lipophilicity assessment of neutral and basic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Giaginis, Costas [Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Athens 15771 (Greece); Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75 Mikras Asias Street, Athens 11527 (Greece); Theocharis, Stamatios [Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75 Mikras Asias Street, Athens 11527 (Greece); Tsantili-Kakoulidou, Anna [Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Athens 15771 (Greece)]. E-mail: tsantili@pharm.uoa.gr

    2006-07-28

    The chromatographic conditions aiming to a better simulation of n-octanol-water partitioning using a base deactivated silica (BDS) column as stationary phase were investigated for structurally diverse basic and neutral drugs. Extrapolated retention factors log k{sub w}, determined using different methanol fractions as organic modifier, were considered as lipophilicity indices. The effect of n-decylamine and n-octanol as mobile phase additives was examined and the appropriateness of the final retention outcome to reproduce lipophilicity data was evaluated. Moreover, the influence of n-octanol on the linearity of the log k/methanol fraction relationship and on the uniformity of the retention mechanism was investigated. 1:1 correlation between log k{sub w} values and the logarithm of the distribution coefficient (log D) was established for basic drugs in presence of both n-decylamine and n-octanol as mobile phase additives. However, for neutral drugs n-decylamine proved to be a sufficient and more important factor than n-octanol.

  5. Ex vivo susceptibility of Plasmodium falciparum isolates from Dakar, Senegal, to seven standard anti-malarial drugs

    Directory of Open Access Journals (Sweden)

    Pradines Bruno

    2011-10-01

    Full Text Available Abstract Background As a result of widespread chloroquine and sulphadoxine-pyrimethamine resistance, artemisinin-based combination therapy (ACT (which includes artemether-lumefantrine and artesunate-amodiaquine has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Since then, there have been very few reports on the ex vivo susceptibility of Plasmodium falciparum to anti-malarial drugs. To examine whether parasite susceptibility has been affected by the widespread use of ACT, the ex vivo susceptibility of local isolates was assessed at the military hospital of Dakar. Methods The ex vivo susceptibility of 93 P. falciparum isolates from Dakar was successfully determined using the Plasmodium lactate dehydrogenase (pLDH ELISA for the following drugs: chloroquine (CQ, quinine (QN, mefloquine (MQ, monodesethylamodiaquine (MDAQ, lumefantrine (LMF, dihydroartemisinin (DHA and doxycycline (DOX. Results After transformation of the isolate IC50 in ratio of IC50 according to the susceptibility of the 3D7 reference strain (isolate IC50/3D7 IC50, the prevalence of the in vitro resistant isolates with reduced susceptibility was 50% for MQ, 22% for CQ, 12% for DOX, 6% for both QN and MDAQ and 1% for the drugs LMF and DHA. The highest significant positive correlations were shown between responses to CQ and MDAQ (r = 0.569; P r = 0.511; P r = 0.428; P = 0.0001, LMF and MQ (r = 0.413; P = 0.0002, QN and DHA (r = 0.402; P = 0.0003 and QN and MQ (r = 0.421; P = 0.0001. Conclusions The introduction of ACT in 2002 has not induced a decrease in P. falciparum susceptibility to the drugs DHA, MDAQ and LMF, which are common ACT components. However, the prevalence of P. falciparum isolates with reduced susceptibility has increased for both MQ and DOX. Taken together, these data suggest that intensive surveillance of the P. falciparum in vitro susceptibility to anti-malarial drugs in Senegal is required.

  6. Synthesis and biological evaluation of 2-aminoimidazole/carbamate hybrid anti-biofilm and anti-microbial agents.

    Science.gov (United States)

    Rogers, Steven A; Lindsey, Erick A; Whitehead, Daniel C; Mullikin, Trey; Melander, Christian

    2011-02-15

    The successful marriage of structural features from our 2-aminoimidazole and menthyl carbamate classes of anti-biofilm agents has resulted in the development of a novel hybrid scaffold of biofilm modulators. The compounds were evaluated against a panel of four bacterial strains for anti-biofilm and anti-microbial activity. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Copper-Mediated N-Alkynylation of Carbamates, Ureas, and Sulfonamides. A General Method for the Synthesis of Ynamides

    Science.gov (United States)

    Dunetz, Joshua R.; Danheiser, Rick L.

    2010-01-01

    A general amination strategy for the N-alkynylation of carbamates, sulfonamides, and chiral oxazolidinones and imidazolidinones is described. A variety of substituted ynamides are available by deprotonation of amides with KHMDS followed by reaction with CuI and an alkynyl bromide. PMID:14535766

  8. Synthesis and biological activity of beta-glucuronyl carbamate-based prodrugs of paclitaxel as potential candidates for ADEPT

    NARCIS (Netherlands)

    deBont, DBA; Leenders, RGG; Haisma, HJ; vanderMeulenMuileman, [No Value; Scheeren, HW

    The syntheses of prodrugs of paclitaxel, which can be used in ADEPT in order to target paclitaxel towards tumor cells, are described. The prodrugs 1 and 2a,b consist of a spacer molecule connected via a carbamate linkage to a beta-glucuronic acid. The spacer molecule is also connected via an ester

  9. The comparison of COCO and CO2/carbamate chemical exchange systems of the enrichment of 13C

    International Nuclear Information System (INIS)

    Yang Guohua

    1986-01-01

    The chemical exchange systems of CO/aqueous solution of Cu 2 Cl 2 .8NH 4 Cl, abbreviated as COCO, and CO 2 /carbamate in enrichment of 13 C were compared using identical experimental devices. The results indicate that the latter system is better than the former, and can be used to produce highly concentrated 13 C

  10. Leveling the playing field: bringing development of biomarkers and molecular diagnostics up to the standards for drug development.

    Science.gov (United States)

    Poste, George; Carbone, David P; Parkinson, David R; Verweij, Jaap; Hewitt, Stephen M; Jessup, J Milburn

    2012-03-15

    Molecular diagnostics are becoming increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, and to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify the pharmacogenetic risk of adverse drug reactions. The articles in this CCR Focus section on molecular diagnosis describe the development and use of markers to guide medical decisions regarding cancer patients. They define sources of preanalytic variability that need to be minimized, as well as the regulatory and financial challenges involved in developing diagnostics and integrating them into clinical practice. They also outline a National Cancer Institute program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation, with sensitivity, specificity, and validity comparable to those required for the development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome-sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval can be achieved. One way to accomplish this is to emphasize phase IV postmarketing, hypothesis-driven clinical trials with biological characterization that would permit an accurate definition of the association of low-prevalence gene alterations with toxicity or response in large cohorts.

  11. Dosing anticancer drugs in infants: Current approach and recommendations from the Children's Oncology Group's Chemotherapy Standardization Task Force.

    Science.gov (United States)

    Balis, Frank M; Womer, Richard B; Berg, Stacey; Winick, Naomi; Adamson, Peter C; Fox, Elizabeth

    2017-11-01

    An analysis of dose modifications for infants in 29 Children's Oncology Group protocols across 10 cancer types revealed 11 sets of criteria defining the infant population using age, weight, body surface area (BSA), or a combination of these parameters and eight dose modification methods. A new method of dosing anticancer drugs in infants was developed based on the rationale that prior modifications were implemented to reduce toxicity, which is not cancer-specific. The new method uses BSA dose banding in dosing tables for infants and children with a BSA <0.6 m 2 and gradually transitions from body weight based to BSA-based dosing. © 2017 Wiley Periodicals, Inc.

  12. A cross-sectional study of tuberculosis drug resistance among previously treated patients in a tertiary hospital in Accra, Ghana: public health implications of standardized regimens.

    Science.gov (United States)

    Forson, Audrey; Kwara, Awewura; Kudzawu, Samuel; Omari, Michael; Otu, Jacob; Gehre, Florian; de Jong, Bouke; Antonio, Martin

    2018-04-02

    Mycobacterium tuberculosis drug resistance is a major challenge to the use of standardized regimens for tuberculosis (TB) therapy, especially among previously treated patients. We aimed to investigate the frequency and pattern of drug resistance among previously treated patients with smear-positive pulmonary tuberculosis at the Korle-Bu Teaching Hospital Chest Clinic, Accra. This was a cross-sectional survey of mycobacterial isolates from previously treated patients referred to the Chest Clinic Laboratory between October 2010 and October 2013. The Bactec MGIT 960 system for mycobactrerial culture and drug sensitivity testing (DST) was used for sputum culture of AFB smear-positive patients with relapse, treatment failure, failure of smear conversion, or default. Descriptive statistics were used to summarize patient characteristics, and frequency and patterns of drug resistance. A total of 112 isolates were studied out of 155 from previously treated patients. Twenty contaminated (12.9%) and 23 non-viable isolates (14.8%) were excluded. Of the 112 studied isolates, 53 (47.3%) were pan-sensitive to all first-line drugs tested Any resistance (mono and poly resistance) to isoniazid was found in 44 isolates (39.3%) and any resistance to streptomycin in 43 (38.4%). Thirty-one (27.7%) were MDR-TB. Eleven (35.5%) out of 31 MDR-TB isolates were pre-XDR. MDR-TB isolates were more likely than non-MDR isolates to have streptomycin and ethambutol resistance. The main findings of this study were the high prevalence of MDR-TB and streptomycin resistance among previously treated TB patients, as well as a high prevalence of pre-XDR-TB among the MDR-TB patients, which suggest that first-line and second-line DST is essential to aid the design of effective regimens for these groups of patients in Ghana.

  13. Cost-Effectiveness of Endovascular Femoropopliteal Intervention Using Drug-Coated Balloons Versus Standard Percutaneous Transluminal Angioplasty: Results From the IN.PACT SFA II Trial.

    Science.gov (United States)

    Salisbury, Adam C; Li, Haiyan; Vilain, Katherine R; Jaff, Michael R; Schneider, Peter A; Laird, John R; Cohen, David J

    2016-11-28

    The aim of this study was to evaluate the cost-effectiveness of drug-coated balloon (DCB) angioplasty versus standard percutaneous transluminal angioplasty (PTA). Recent trials have reported lower rates of target lesion revascularization with DCB angioplasty versus standard PTA. However, the cost-effectiveness of DCB angioplasty is unknown. A prospective economic study was performed alongside the IN.PACT SFA II (IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA]) trial, which randomized 181 patients with femoropopliteal disease to the IN.PACT DCB versus standard PTA. Resource use data were collected over 2-year follow-up, and costs were assigned using resource-based accounting and billing data. Health utilities were assessed using the EuroQol 5-dimensions questionnaire. Cost-effectiveness was assessed as cost per quality-adjusted life-year (QALY) gained using a decision-analytic model on the basis of empirical data from the trial assuming identical long-term mortality. Initial costs were $1,129 per patient higher with DCB angioplasty than standard PTA, driven by higher costs for the DCB itself. Between discharge and 24 months, target limb-related costs were $1,212 per patient lower with DCB angioplasty such that discounted 2-year costs were similar for the 2 groups ($11,277 vs. $11,359, p = 0.97), whereas QALYs tended to be greater among patients treated with DCBs (1.53 ± 0.44 vs. 1.47 ± 0.42, p = 0.40). The probability that DCB angioplasty is cost-effective compared with standard PTA was 70% using a threshold of $50,000 per QALY gained and 79% at a threshold of $150,000 per QALY gained. For patients with femoropopliteal disease, DCB angioplasty is associated with better 2-year outcomes and similar target limb-related costs compared with standard PTA. Formal cost-effectiveness analysis on the basis of these results suggests that use of the DCB angioplasty

  14. Synthesis, structural, conformational and pharmacological study of some carbamates derived from 8-methyl-8-azabicyclo[3.2.1]octan-3α-ol

    Science.gov (United States)

    Iriepa, I.; Bellanato, J.

    2011-12-01

    A series of benzimidazole, thiazole, and benzothiazole carbamates derived from 8-methyl-8-azabicyclo[3.2.1]octan-3α-ol hydrochloride was synthesized and studied by 1H, 13C NMR and IR spectroscopy. To assist in the interpretation of the spectroscopic data, the free bases were obtained and studied by IR spectroscopy in different media. As in related compounds, spectroscopic results showed that two different carbamates (1-carbamate or 2-carbamate) could be obtained in the case of the hydrochlorides of benzimidazole derivatives. The hydrochlorides studied displayed in DMSO- d6 solution a preferred flattened chair-envelope conformation with the Nsbnd CH 3 substituent in an equatorial disposition. Pharmacological assays in vitro and in vivo were drawn to evaluate 5-HT 3 activity.

  15. Synthesis and evaluation of benzimidazole carbamates bearing indole moieties for antiproliferative and antitubulin activities.

    Science.gov (United States)

    Guan, Qi; Han, Chunming; Zuo, Daiying; Zhai, Min'an; Li, Zengqiang; Zhang, Qian; Zhai, Yanpeng; Jiang, Xuewei; Bao, Kai; Wu, Yingliang; Zhang, Weige

    2014-11-24

    A series of novel benzimidazole carbamates bearing indole moieties with sulphur or selenium atoms connecting the aromatic rings were synthesised and evaluated for their antiproliferative activities against three human cancer cell lines (SGC-7901, A-549 and HT-1080) using an MTT assay. Compounds 10a, 10b, 7a, 7b and 7f showed significant activities against these cell lines. The most potent compound in this series, 10a, was selected to investigate its antitumour mechanism. In addition, molecular docking studies suggested that compound 10a interacts very closely with the nocodazole docking pose through hydrogen bonds at the colchicine binding site of tubulin. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Computational evidence for the reactivation process of human acetylcholinesterase inhibited by carbamates.

    Science.gov (United States)

    Matos, Karina Silvia; da Cunha, Elaine F F; Abagyan, Ruben; Ramalho, Teodorico C

    2014-01-01

    Acetylcholinesterase (AChE) is responsible for hydrolysis of acetylcholine (ACh), a function, which if disrupted, leads to cholinergic syndrome. Carbamates (CB) and organophosphorus compounds (OP) are AChE inhibitors, toxic and capable of causing severe poisoning or death to exposed individuals. The AChE reactivation is considered the main function of the oximes. In case of poisoning by CB, there is no consistent data in the literature for an oxime reactivation mechanism. In this work, we evaluated the affinity and reactivity of oximes with activity already reported against AChE inhibited by the OP chemical warfare agent ciclosarin, with MmAChE and HsAChE active sites inhibited by the CB pesticide carbofuran. Thus, our theoretical data indicate that HLO-7, BI-6 and K005 compounds may be promising reactivators of AChE inhibited by carbofuran.

  17. Bismuth- and hafnium-catalyzed hydroamination of vinyl arenes with sulfonamides, carbamates, and carboxamides.

    Science.gov (United States)

    Qin, Hongbo; Yamagiwa, Noriyuki; Matsunaga, Shigeki; Shibasaki, Masakatsu

    2007-01-08

    Catalytic intermolecular hydroamination of vinyl arenes is described. Our initial investigation revealed that a Bi(OTf)3/[Cu(CH3CN)4]PF6 system previously developed for catalytic intermolecular hydroamination of 1,3-dienes was suitable for hydroamination of a styrene with sulfonamides, but the substrate generality of this system was unsatisfactory. Several metals were screened to expand the substrate scope, and a new Hf(OTf)4/[Cu(CH3CN)4]PF6 system was determined to be highly suitable. The combination of Hf(OTf)4 and [Cu(CH3CN)4]PF6 efficiently promoted the hydroamination of various vinyl arenes, including less-reactive vinyl arenes with electron-withdrawing groups. This strategy was applied to sulfonamides, carbamates, and carboxamides, and products were obtained in up to 99% yield with 0.3-10 mol % catalyst loading.

  18. Determination of carbamates and organophosphorus pesticides by SDME-GC in natural water.

    Science.gov (United States)

    López-Blanco, Carmen; Gómez-Alvarez, Sonia; Rey-Garrote, María; Cancho-Grande, Beatriz; Simal-Gándara, Jesús

    2005-10-01

    Water contamination due to the wide variety of pesticides used in agriculture practices is a global environmental pollution problem. Analytical methods with low quantification limits are necessary. The application of a new extraction technique, solvent drop microextraction (SDME), followed by gas chromatography with a nitrogen-phosphorus detector, was assessed for determining carbamates and organophosphorus pesticides in natural water. Experimental parameters which control the performance of SDME such as selection of microextraction solvent, optimization of organic drop volume, effects of sample stirring, salt addition, and, finally, sorption time profiles were studied. Once SDME was optimized, analytical parameters such as linearity (r 2>0.99), precision (pesticides from water in 14 min; the use of organic solvents and water samples for SDME is negligible compared to other extraction techniques.

  19. Children poisoning by carbamate: a descriptive study - doi:10.5020/18061230.2004.p193

    Directory of Open Access Journals (Sweden)

    Luiza Jane Eyre de Souza Vieira

    2012-01-01

    Full Text Available The study had as its aim to characterize the children under 5 years old, attended with exogenous poisoning by carbamate (popularly called “chumbinho” – “small shot” at an emergency hospital in Fortaleza and to relate the signs and symptoms detected in this type of poisoning. It concerned a descriptive study, with a sample of 65 children attended during the period of 1998 to 2000, in Fortaleza, Ceará. It was noticed that the most affected age group was of those with 1 to 3 years old, not being verified any significant difference between sexes. The most evident signs and symptoms were myosis, vomits, profuse perspiration and sialorrhea and the predominant treatment was the use of active coal. It is concluded, therefore, that there is a need of putting into effect the health education, calling the society’s attention to the risks of the inadequate “chumbinho” use in the domiciliar environment.

  20. Carbamate derivatives and sesquiterpenoids from the South China Sea gorgonian Melitodes squamata.

    Science.gov (United States)

    Huang, Li-Si; He, Fei; Huang, Hui; Zhang, Xiao-Yong; Qi, Shu-Hua

    2012-01-01

    Five carbamate derivatives, obtucarbamates C and D (1, 2), dimethyl ((carbonylbis(azanediyl))bis(2-methyl-5,1-phenylene))dicarbamate (3), obtucarbamates A and B (4, 5), and four aromadendrane-type sesquiterpenoids, (+)-4β-N-methenetauryl-10β-methoxy-1β,5α,6β,7β-aromadendrane (6), (-)-4β-N-methenetauryl-10β-methoxy-1β,5β,6α,7α-aromadendrane (7), (-)-4α,10β-aromadendranediol (8), (+)-4β,10β-aromadendranediol (9) were obtained from the South China Sea gorgonian coral Melitodes squamata Nutting. Compounds 1, 2, 6, and 7 were new, and their structures were established by spectroscopic analyses. Compounds 6 and 7 contained a taurine group that was rarely found in marine natural compounds, and 7 showed moderate antibacterial activity. The possible biosynthesis routes of 1-5 were conjectured.

  1. From immunotoxicity to carcinogenicity: the effects of carbamate pesticides on the immune system.

    Science.gov (United States)

    Dhouib, Ines; Jallouli, Manel; Annabi, Alya; Marzouki, Soumaya; Gharbi, Najoua; Elfazaa, Saloua; Lasram, Mohamed Montassar

    2016-05-01

    The immune system can be the target of many chemicals, with potentially severe adverse effects on the host's health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion.

  2. PdCl2 catalyzed efficient assembly of organic azides, CO, and alcohols under mild conditions: a direct approach to synthesize carbamates.

    Science.gov (United States)

    Ren, Long; Jiao, Ning

    2014-04-11

    A simple and readily available PdCl2 catalyzed carbamate synthesis method via isocyanate generation and application in situ has been developed. This chemistry provides an efficient and practical approach to synthesize carbamates from simple organic azides, CO atmosphere and alcohols. The broad scope, mild and neutral conditions, and only N2 as the byproduct make this transformation very useful. Moreover, simple examples of modification of bioactive molecules and construction of macrocycles were achieved through this protocol.

  3. Dynamic kinetic resolution of 1,3-dihydro-2H-isoindole-1-carboxylic acid methyl ester: asymmetric transformations toward isoindoline carbamates.

    Science.gov (United States)

    Morán-Ramallal, Roberto; Gotor-Fernández, Vicente; Laborda, Pedro; Sayago, Francisco J; Cativiela, Carlos; Gotor, Vicente

    2012-04-06

    Asymmetric syntheses of isoindoline carbamates have been successfully achieved through enzyme-mediated dynamic kinetic resolution processes and without requirement of metal or acid-base catalyst for the substrate racemization. Optically active carbamates were obtained in good yields and an excellent degree of stereoselectivity when Pseudomonas cepacia lipase (PSL) was used as biocatalyst, with diallyl or dibenzyl carbonates being both adequate reagents in alkoxycarbonylation reactions.

  4. Synthesis of 9-oxime-11,12-carbamate ketolides through a novel N-deamination reaction of 11,12-hydrazonocarbamate ketolide.

    Science.gov (United States)

    Denis, Alexis; Pejac, Jean-Marie; Bretin, François; Bonnefoy, Alain

    2003-05-29

    A series of 9-oxime-11,12-carbamate ketolides was synthesized for the first time through a key 11,12-hydrazonocarbamate intermediate that was first oximated and further deaminated to give the corresponding carbamate. The N-N bond cleavage was achieved through an original new reaction using glycoaldehyde dimer as deaminating reagent. The new compounds synthesized were shown to display improved antibacterial activities against Streptococcus pneumoniae and S. pyogenes resistant to erythromycin.

  5. Kinetic characterization of arginine deiminase and carbamate kinase from Streptococcus pyogenes M49.

    Science.gov (United States)

    Hering, Silvio; Sieg, Antje; Kreikemeyer, Bernd; Fiedler, Tomas

    2013-09-01

    Streptococcus pyogenes (group A Streptococcus, GAS) is an important human pathogen causing mild superficial infections of skin and mucous membranes, but also life-threatening systemic diseases. S. pyogenes and other prokaryotic organisms use the arginine deiminase system (ADS) for survival in acidic environments. In this study, the arginine deiminase (AD), and carbamate kinase (CK) from S. pyogenes M49 strain 591 were heterologously expressed in Escherichia coli DH5α, purified, and kinetically characterized. AD and CK from S. pyogenes M49 share high amino acid sequence similarity with the respective enzymes from Lactococcus lactis subsp. lactis IL1403 (45.6% and 53.5% identical amino acids) and Enterococcus faecalis V583 (66.8% and 66.8% identical amino acids). We found that the arginine deiminase of S. pyogenes is not allosterically regulated by the intermediates and products of the arginine degradation (e.g., ATP, citrulline, carbamoyl phosphate). The Km and Vmax values for arginine were 1.13±0.12mM (mean±SD) and 1.51±0.07μmol/min/mg protein. The carbamate kinase is inhibited by ATP but unaffected by arginine and citrulline. The Km and Vmax values for ADP were 0.72±0.08mM and 1.10±0.10μmol/min/mg protein and the Km for carbamoyl phosphate was 0.65±0.07mM. The optimum pH and temperature for both enzymes were 6.5 and 37°C, respectively. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Canada’s highest court unchains injection drug users; implications for harm reduction as standard of healthcare

    Directory of Open Access Journals (Sweden)

    Small Dan

    2012-07-01

    Full Text Available Abstract North America’s only supervised injection facility, Insite, opened its doors in September of 2003 with a federal exemption as a three-year scientific study. The results of the study, evaluated by an independent research team, showed it to be successful in engaging the target group in healthcare, preventing overdose death and HIV infections while increasing uptake and retention in detox and treatment. The research, published in peer-reviewed medical and scientific journals, also showed that the program did not increase public disorder, crime or drug use. Despite the substantial evidence showing the effectiveness of the program, the future of Insite came under threat with the election of a conservative federal government in 2006. As a result, the PHS Community Services Society (PHS, the non-profit organization that operates Insite, launched a legal case to protect the program. On 30 September 2011, Supreme Court of Canada ruled in favour of Insite and underscored the rights of people with addictions to the security of their person under section 7 of the Charter of Rights and Freedoms (Charter of Rights. The decision clears the ground for other jurisdictions in Canada, and perhaps North America, to implement supervised injection and harm reduction where it is epidemiologically indicated. The legal case validates the personhood of people with addictions while metaphorically unchaining them from the criminal justice system.

  7. Prediction of Multi-Target Networks of Neuroprotective Compounds with Entropy Indices and Synthesis, Assay, and Theoretical Study of New Asymmetric 1,2-Rasagiline Carbamates

    Science.gov (United States)

    Romero Durán, Francisco J.; Alonso, Nerea; Caamaño, Olga; García-Mera, Xerardo; Yañez, Matilde; Prado-Prado, Francisco J.; González-Díaz, Humberto

    2014-01-01

    In a multi-target complex network, the links (Lij) represent the interactions between the drug (di) and the target (tj), characterized by different experimental measures (Ki, Km, IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (cj). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%–90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally. PMID:25255029

  8. Prediction of Multi-Target Networks of Neuroprotective Compounds with Entropy Indices and Synthesis, Assay, and Theoretical Study of New Asymmetric 1,2-Rasagiline Carbamates

    Directory of Open Access Journals (Sweden)

    Francisco J. Romero Durán

    2014-09-01

    Full Text Available In a multi-target complex network, the links (Lij represent the interactions between the drug (di and the target (tj, characterized by different experimental measures (Ki, Km, IC50, etc. obtained in pharmacological assays under diverse boundary conditions (cj. In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%–90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human. Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1 assay in absence of neurotoxic agents; (2 in the presence of glutamate; and (3 in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally.

  9. Prediction of multi-target networks of neuroprotective compounds with entropy indices and synthesis, assay, and theoretical study of new asymmetric 1,2-rasagiline carbamates.

    Science.gov (United States)

    Romero Durán, Francisco J; Alonso, Nerea; Caamaño, Olga; García-Mera, Xerardo; Yañez, Matilde; Prado-Prado, Francisco J; González-Díaz, Humberto

    2014-09-24

    In a multi-target complex network, the links (L(ij)) represent the interactions between the drug (d(i)) and the target (t(j)), characterized by different experimental measures (K(i), K(m), IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (c(j)). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%-90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally.

  10. Drug-Coated Balloon Versus Standard Percutaneous Transluminal Angioplasty for the Treatment of Superficial Femoral and Popliteal Peripheral Artery Disease

    Science.gov (United States)

    Tepe, Gunnar; Schneider, Peter; Brodmann, Marianne; Krishnan, Prakash; Micari, Antonio; Metzger, Christopher; Scheinert, Dierk; Zeller, Thomas; Cohen, David J.; Snead, David B.; Alexander, Beaux; Landini, Mario; Jaff, Michael R.

    2015-01-01

    Background— Drug-coated balloons (DCBs) have shown promise in improving the outcomes for patients with peripheral artery disease. We compared a paclitaxel-coated balloon with percutaneous transluminal angioplasty (PTA) for the treatment of symptomatic superficial femoral and popliteal artery disease. Methods and Results— The IN.PACT SFA Trial is a prospective, multicenter, single-blinded, randomized trial in which 331 patients with intermittent claudication or ischemic rest pain attributable to superficial femoral and popliteal peripheral artery disease were randomly assigned in a 2:1 ratio to treatment with DCB or PTA. The primary efficacy end point was primary patency, defined as freedom from restenosis or clinically driven target lesion revascularization at 12 months. Baseline characteristics were similar between the 2 groups. Mean lesion length and the percentage of total occlusions for the DCB and PTA arms were 8.94±4.89 and 8.81±5.12 cm (P=0.82) and 25.8% and 19.5% (P=0.22), respectively. DCB resulted in higher primary patency versus PTA (82.2% versus 52.4%; P<0.001). The rate of clinically driven target lesion revascularization was 2.4% in the DCB arm in comparison with 20.6% in the PTA arm (P<0.001). There was a low rate of vessel thrombosis in both arms (1.4% after DCB and 3.7% after PTA [P=0.10]). There were no device- or procedure-related deaths and no major amputations. Conclusions— In this prospective, multicenter, randomized trial, DCB was superior to PTA and had a favorable safety profile for the treatment of patients with symptomatic femoropopliteal peripheral artery disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT01175850 and NCT01566461. PMID:25472980

  11. Developing Calibration Weights and Standard-Error Estimates for a Survey of Drug-Related Emergency-Department Visits

    Directory of Open Access Journals (Sweden)

    Kott Phillip S.

    2014-09-01

    Full Text Available This article describes a two-step calibration-weighting scheme for a stratified simple random sample of hospital emergency departments. The first step adjusts for unit nonresponse. The second increases the statistical efficiency of most estimators of interest. Both use a measure of emergency-department size and other useful auxiliary variables contained in the sampling frame. Although many survey variables are roughly a linear function of the measure of size, response is better modeled as a function of the log of that measure. Consequently the log of size is a calibration variable in the nonresponse-adjustment step, while the measure of size itself is a calibration variable in the second calibration step. Nonlinear calibration procedures are employed in both steps. We show with 2010 DAWN data that estimating variances as if a one-step calibration weighting routine had been used when there were in fact two steps can, after appropriately adjusting the finite-population correct in some sense, produce standard-error estimates that tend to be slightly conservative.

  12. SMS for Life: a pilot project to improve anti-malarial drug supply management in rural Tanzania using standard technology

    Science.gov (United States)

    2010-01-01

    restricted availability of anti-malarial drugs or other medicines in rural or under-resourced areas. PMID:20979633

  13. Enteric-coated and highly standardized cranberry extract reduces antibiotic and nonsteroidal anti-inflammatory drug use for urinary tract infections during radiotherapy for prostate carcinoma

    Directory of Open Access Journals (Sweden)

    Bonetta A

    2017-04-01

    Full Text Available Alberto Bonetta,1 Giandomenico Roviello,2,3 Daniele Generali,3,4 Laura Zanotti,3 Maria Rosa Cappelletti,3 Chiara Pacifico,5 Francesco Di Pierro6 1Oncological Radiotherapy Operative Unit, ASST, Cremona, 2Department of Molecular and Translational Medicine, University of Brescia, Brescia, 3Molecular Therapy and Pharmacogenomics Unit, ASST, Cremona, 4Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, 5Department of Medical, Surgical and Neurological Sciences, University Hospital of Siena, Siena, 6Velleja Research Scientific Department, Milan, Italy Introduction: Worldwide, bacterial resistance to antibiotic therapy is a major concern for the medical community. Antibiotic resistance mainly affects Gram-negative bacteria that are an important cause of lower urinary tract infections (LUTIs. Pelvic irradiation for prostate cancer is a risk factor for LUTIs. Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic role of an enteric-coated, highly standardized cranberry extract (VO370® in reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory drug (NSAID and antibiotic use during radiotherapy for prostate carcinoma was evaluated. Methods: A total of 924 patients with prostate carcinoma treated by radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489 or not (n=435 the enteric-coated, highly standardized cranberry extract for 6–7 weeks concurrently with irradiation. Outcomes were analyzed by using Mann–Whitney U test and Pearson’s X2 test. Primary endpoint was the number of patients with LUTI; secondary endpoints were incidence of recurrence, days of treatment with antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria. Results: The treatment was very well tolerated, and there were no serious side effects. All enrolled patients completed the study. Urinary infections were detected in 53 of the 489 patients (10

  14. Efficient hydrogenation of organic carbonates, carbamates and formates indicates alternative routes to methanol based on CO2 and CO.

    Science.gov (United States)

    Balaraman, Ekambaram; Gunanathan, Chidambaram; Zhang, Jing; Shimon, Linda J W; Milstein, David

    2011-07-22

    Catalytic hydrogenation of organic carbonates, carbamates and formates is of significant interest both conceptually and practically, because these compounds can be produced from CO2 and CO, and their mild hydrogenation can provide alternative, mild approaches to the indirect hydrogenation of CO2 and CO to methanol, an important fuel and synthetic building block. Here, we report for the first time catalytic hydrogenation of organic carbonates to alcohols, and carbamates to alcohols and amines. Unprecedented homogeneously catalysed hydrogenation of organic formates to methanol has also been accomplished. The reactions are efficiently catalysed by dearomatized PNN Ru(II) pincer complexes derived from pyridine- and bipyridine-based tridentate ligands. These atom-economical reactions proceed under neutral, homogeneous conditions, at mild temperatures and under mild hydrogen pressures, and can operate in the absence of solvent with no generation of waste, representing the ultimate 'green' reactions. A possible mechanism involves metal-ligand cooperation by aromatization-dearomatization of the heteroaromatic pincer core.

  15. Design, synthesis, and fungicidal activity of novel carboxylic acid amides represented by N-benzhydryl valinamode carbamates.

    Science.gov (United States)

    Du, Xiu-Jiang; Bian, Qiang; Wang, Hong-Xue; Yu, Shu-Jing; Kou, Jun-Jie; Wang, Zhi-Peng; Li, Zheng-Ming; Zhao, Wei-Guang

    2014-08-07

    Carboxylic acid amide (CAA) fungicides are an important class of agricultural fungicide with oomycete activity and low toxicity toward mammalian cells. To find CAA analogues with high activity against resistant pathogens, a series of substituted N-benzhydryl valinamide carbamate derivatives were designed and synthesized by introducing substituted aromatic rings into valinamide carbamate leads. Bioassays showed that some title compounds exhibited very good in vitro fungicidal activity against Phytophthora capsici and in vivo fungicidal activities against Pseudoperonospora cubensis. Topomer CoMFA was performed to explore the structure-activity relationship on the basis of the in vitro data. The dimethoxy substituted aromatic analogue 9e was found to display higher in vitro fungicidal activity against Phytophthora capsici than iprovalicarb but lower activity than mandipropamid, and higher in vivo fungicidal activity against Pseudoperonospora cubensis than dimethomorph at a dosage of 6.25 μg mL(-1).

  16. QuEChERS-based method for the determination of carbamate residues in aromatic herbs by UHPLC-MS/MS.

    Science.gov (United States)

    Nantia, Edouard Akono; Moreno-González, David; Manfo, Faustin P T; Gámiz-Gracia, Laura; García-Campaña, Ana M

    2017-02-01

    A new reliable, fast and highly sensitive method based on ultra-high performance liquid chromatography tandem mass spectrometry has been developed and validated for the determination of 28 carbamates in aromatic herbs. A modified QuEChERS-based method was optimized for the extraction of carbamate residues from a wide variety of fresh herbal products. The proposed method allowed recoveries higher than 72%, achieving quantification limits of 2μgkg(-1), therefore below maximum residue limits established for this type of samples. The combination of QuEChERS with UHPLC-MS/MS introduces a high-throughput methodology for the monitoring of these residues in this type of matrices scarcely explored. The analysis of the real samples revealed that several samples sold in the European Union and in the North West region of Cameroon contain pesticides in concentrations below the maximum residue limits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Experimental and ab initio study on structures and internal barriers to rotation in α-stannyl, germanium, and silicon carbamates

    Science.gov (United States)

    Jadidi, Khosrow; Khaligh, Nader Ghaffari; Islami, Parisa; Aryan, Reza; Arvin-Nezhad, Hamid

    2009-02-01

    A detailed study of structural parameters and internal rotational barriers in α-stannyl, germanium and silicon carbamates 1 [H 3 CX-CH 2-N(Me)CO 2Me X dbnd C, Si, Ge, Sn] were calculated at HF/6-311G, HF/3-21G and B3LYP/3-21G//HF/3-21G levels and compared with DNMR data of synthesized molecules and a literature X-ray data. Two minimum-energy conformers, namely A and B, with almost similar energies were found for these molecules. Effect of heteroatom on structure and relative energies ( Erel) between the participants in the conformational equilibrium (A ↔ B) of these carbamates has been investigated.

  18. Japanese external quality assessment program to standardize HIV-1 drug-resistance testing (JEQS2010 program) using in vitro transcribed RNA as reference material.

    Science.gov (United States)

    Yoshida, Shigeru; Hattori, Junko; Matsuda, Masakazu; Okada, Kiyomi; Kazuyama, Yukumasa; Hashimoto, Osamu; Ibe, Shiro; Fujisawa, Shin-ichi; Chiba, Hitoshi; Tatsumi, Masashi; Kato, Shingo; Sugiura, Wataru

    2015-03-01

    To design appropriate antiretroviral therapy regimens and avoid the emergence of human immunodeficiency virus (HIV)-1 variants with reduced susceptibility to antiretroviral drugs, genotypic drug-resistance testing (HIV genotyping) is strongly recommended. To monitor the quality of HIV genotyping in Japan, we performed an external quality assessment (EQA), named the Japanese external quality assessment program, to standardize HIV genotyping (JEQS). To accurately evaluate the quality of HIV genotyping, we employed as reference material (RM) a well-characterized sample, in vitro transcribed RNA (trRNA) that includes the HIV gag-pol sequence, and created a JEQS2010 panel consisting of three single variant and three mixed trRNA samples. All 11 participating laboratories showed high concordance rates (>96%) for the single variant samples. Eight laboratories also showed good rates of detecting minor variants, but three laboratories failed to detect the variants comprising one-half of the sample. These three laboratories used a common primer that had four internal mismatches to the minor trRNA clone. This program showed the usefulness of trRNA as RM, the high quality of HIV genotyping, and extensive interlaboratory variation in the ability to detect minor variants. These results suggest that improving the quality of HIV genotyping in Japan requires regularly implementing the EQA program and improving the HIV genotyping protocol in each laboratory.

  19. Optimization of microwave-assisted extraction and supercritical fluid extraction of carbamate pesticides in soil by experimental design methodology.

    Science.gov (United States)

    Sun, Lei; Lee, Hian Kee

    2003-10-03

    Orthogonal array design (OAD) was applied for the first time to optimize microwave-assisted extraction (MAE) and supercritical fluid extraction (SFE) conditions for the analysis of four carbamates (propoxur, propham, methiocarb, chlorpropham) from soil. The theory and methodology of a new OA16 (4(4)) matrix derived from a OA16 (2(15)) matrix were developed during the MAE optimization. An analysis of variance technique was employed as the data analysis strategy in this study. Determinations of analytes were completed using high-performance liquid chromatography (HPLC) with UV detection. Four carbamates were successfully extracted from soil with recoveries ranging from 85 to 105% with good reproducibility (approximately 4.9% RSD) under the optimum MAE conditions: 30 ml methanol, 80 degrees C extraction temperature, and 6-min microwave heating. An OA8 (2(7)) matrix was employed for the SFE optimization. The average recoveries and RSD of the analytes from spiked soil by SFE were 92 and 5.5%, respectively except for propham (66.3+/-7.9%), under the following conditions: heating for 30 min at 60 degrees C under supercritical CO2 at 300 kg/cm2 modified with 10% (v/v) methanol. The composition of the supercritical fluid was demonstrated to be a crucial factor in the extraction. The addition of a small volume (10%) of methanol to CO2 greatly enhanced the recoveries of carbamates. A comparison of MAE with SFE was also conducted. The results indicated that >85% average recoveries were obtained by both optimized extraction techniques, and slightly higher recoveries of three carbamates (propoxur, propham and methiocarb) were achieved using MAE. SFE showed slightly higher recovery for chlorpropham (93 vs. 87% for MAE). The effects of time-aged soil on the extraction of analytes were examined and the results obtained by both methods were also compared.

  20. DETERMINATION OF CARBAMATE PESTICIDES USING A BIOSENSOR BASED ON ENZYME ACETYLCHOLINESTERASE AND CHOLIN OXIDASE ON PLATINUM ELECTRODE

    Directory of Open Access Journals (Sweden)

    Mashuni Mashuni

    2010-12-01

    Full Text Available In recent years, instead of their potential hazard to human health, carbamic pesticides are widely used in agriculture. Therefore, there is a growing interest in rapid and accurate determination for food safety and environmental monitoring. The aim of this research is to designs a biosensor for analyzing carbamate pesticides residue in sample with composite variables of glutaraldehyde (GA concentration in electrode membrane. Enzyme acetylcholinesterase (AChE was co-immobilised with choline oxidase (ChO onto a platinum (Pt surface using a solution of 5%, 10%, 15% cellulose acetate and 25% glutaraldehyde. The result of this research show that detection limit of the sensor using cellulose acetate 5%, 10 % and 15 % are 10-7.7 M, 10-8.7 M and 10-7.6 M respectively. The results are approximately equal to 2.2 ppb-0.2 ppb, which means that this biosensor is very sensitive for determining carbamates pesticides residue. Detection limit of biosensors are comparable to that of the conventional instrument such as Gas Chromatography (GC and High Pressure Liquid Chromatography (HPLC, i.e. 1.5 ppb and 2.0 ppb respectively. The proposed electrochemical pesticide sensitivity test exhibited high sensitivity, desirable accuracy, low cost and simplified procedure.

  1. Biodegradation of carbamate pesticides by natural river biofilms in different seasons and their effects on biofilm community structure

    International Nuclear Information System (INIS)

    Tien, Chien-Jung; Lin, Mon-Chu; Chiu, Wan-Hsin; Chen, Colin S.

    2013-01-01

    This study investigated the ability of natural river biofilms from different seasons to degrade the carbamate pesticides methomyl, carbaryl and carbofuran in single and multiple pesticide systems, and the effects of these pesticides on algal and bacterial communities within biofilms. Spring biofilms had the lowest biomass of algae and bacteria but showed the highest methomyl degradation (>99%) and dissipation rates, suggesting that they might contain microorganisms with high methomyl degradation abilities. Degradation of carbofuran (54.1–59.5%) by biofilms in four seasons was similar, but low degradation of carbaryl (0–27.5%) was observed. The coexistence of other pesticides was found to cause certain effects on pesticide degradation and primarily resulted in lower diversity of diatoms and bacteria than when using a single pesticide. The tolerant diatoms and bacteria potentially having the ability to degrade test pesticides were identified. River biofilms could be suitable biomaterials or used to isolate degraders for bioremediating pesticide-contaminated water. -- Highlights: •Natural river biofilms showed high ability to degrade methomyl and carbofuran. •The presence of other pesticides caused certain effects on pesticide degradation. •Carbamate pesticides caused adverse effects on communities of diatoms and bacteria. •The tolerant diatoms and bacteria were found as potential pesticide-degraders. -- Biodegradation of carbamate pesticides by river biofilms

  2. Possible mechanisms for sensitivity to organophosphorus and carbamate insecticides in eastern screech-owls and American kestrels

    Science.gov (United States)

    Vyas, N.B.; Thiele, L.A.; Garland, S.C.

    1998-01-01

    Effects of a single dietary exposure to fenthion and carbofuran on the survival, feeding behavior and brain ChE activity of eastern screech-owls, Otus asio and American kestrels, Falco sparverius, were evaluated. Birds were exposed to fenthion (23.6–189.0 ppm) or carbofuran (31.7–253.6 ppm) via meatballs. Carbofuran-exposed owls ate either ≤10% or ≥80% of the meatball whereas all kestrels ate ≤10% of the meatball before exhibiting acute signs of toxicity. Fenthion-exposed owls and kestrels displayed a wide spectrum of meatball consumption (kestrels exposed to fenthion and carbofuran and dead owls exposed to fenthion (P<0.0001). Brain ChE activity of owls exposed to carbofuran that survived was not different from that of controls (P=0.25). Data suggest: (1) slow feeding on a carbamate-contaminated item may provide limited protection from the toxicity of the chemical at certain rates of exposure; (2) the degree of ChE inhibition at neuromuscular junctions may be critical in determining the sensitivity of a species to a carbamate insecticide; (3) sensitivity may be a function of the ChE affinity for the carbamate inhibitor; and (4) the importance of neuromuscular junction ChE depression in determining the sensitivity of an animal may be species-specific.

  3. Betulinic acid derived hydroxamates and betulin derived carbamates are interesting scaffolds for the synthesis of novel cytotoxic compounds.

    Science.gov (United States)

    Wiemann, Jana; Heller, Lucie; Perl, Vincent; Kluge, Ralph; Ströhl, Dieter; Csuk, René

    2015-12-01

    The betulinic acid-derived hydroxamates 5-18, the amides 19-24, and betulin-derived bis-carbamates 25-28 as well as the carbamates 31-40 and 44-48 were prepared and evaluated for their antiproliferative activity in a photometric sulforhodamine B (SRB) assay against several human cancer cell lines and nonmalignant mouse fibroblasts (NIH 3T3). While for 3-O-acetyl hydroxamic acid 5 EC50 values as low as EC50 = 1.3 μM were found, N,O-bis-alkyl substituted hydroxamates showed lowered cytotoxicity (EC50 = 16-20 μM). In general, hydroxamic acid derivatives showed only reduced selectivity for tumor cells, except for allyl substituted compound 13 (EC50 = 5.9 μM for A2780 human ovarian carcinoma cells and EC50 > 30 μM for nonmalignant mouse fibroblasts). The cytotoxicity of betulinic acid derived amides 19-24 and of betulin derived bis-carbamates 25-28 was low, except for N-ethyl substituted 25. Hexyl substituted 39 showed EC50 = 5.6 μM (518A2 cells) while for mouse fibroblasts EC50 > 30 was determined. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Evaluation of a new modified QuEChERS method for the monitoring of carbamate residues in high-fat cheeses by using UHPLC-MS/MS.

    Science.gov (United States)

    Hamed, Ahmed M; Moreno-González, David; Gámiz-Gracia, Laura; García-Campaña, Ana M

    2017-01-01

    A simple and efficient method for the determination of 28 carbamates in high-fat cheeses is proposed. The methodology is based on a modified quick, easy, cheap, effective, rugged, and safe procedure as sample treatment using a new sorbent (Z-Sep + ) followed by ultra-high performance liquid chromatography with tandem mass spectrometry determination. The method has been validated in different kinds of cheese (Gorgonzola, Roquefort, and Camembert), achieving recoveries of 70-115%, relative standard deviations lower than 13% and limits of quantification lower than 5.4 μg/kg, below the maximum residue levels tolerated for these compounds by the European legislation. The matrix effect was lower than ±30% for all the studied pesticides. The combination of ultra-high performance liquid chromatography and tandem mass spectrometry with this modified quick, easy, cheap, effective, rugged, and safe procedure using Z-Sep + allowed a high sample throughput and an efficient cleaning of extracts for the control of these residues in cheeses with a high fat content. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Microwave accelerated selective Soxhlet extraction for the determination of organophosphorus and carbamate pesticides in ginseng with gas chromatography/mass spectrometry.

    Science.gov (United States)

    Zhou, Ting; Xiao, Xiaohua; Li, Gongke

    2012-07-03

    Microwave accelerated selective Soxhlet extraction (MA-SSE), a novel selective extraction technique, was investigated in this study. A Soxhlet extraction system containing a glass filter was designed as an extractor. During the procedure of MA-SSE, both the target analytes and the interfering components were extracted from the sample into the extraction solvent enhanced by microwave irradiation. After the solvent flowed though the sorbent, the interfering components were adsorbed by the sorbent, and the target analytes remaining in the solvent were collected in the extraction bottle. No cleanup or filtration was required after extraction. The efficiency of the MA-SSE approach was demonstrated in the determination of organophosphorus and carbamate pesticide residues in ginseng by gas chromatography/mass spectrometry (GC/MS). Under the optimized conditions, low limits of detection (0.050-0.50 μg/kg) were obtained. The recoveries were in the range of 72.0-110.1% with relative standard deviations less than 7.1%. Because of the effect of microwave irradiation, MA-SSE showed significant advantage compared with other extraction techniques. The sorbent used in this study showed good cleanup ability. The mechanism of MA-SSE was demonstrated to be based on the rupture of the cell walls according to the structural changes of ginseng samples. On the basis of the results, MA-SSE as a simple and effective sample preparation technique for the analysis of pesticide residues in complex matrixes shows great promise.

  6. Effects of central nervous system drugs on driving: speed variability versus standard deviation of lateral position as outcome measure of the on-the-road driving test.

    Science.gov (United States)

    Verster, Joris C; Roth, Thomas

    2014-01-01

    The on-the-road driving test in normal traffic is used to examine the impact of drugs on driving performance. This paper compares the sensitivity of standard deviation of lateral position (SDLP) and SD speed in detecting driving impairment. A literature search was conducted to identify studies applying the on-the-road driving test, examining the effects of anxiolytics, antidepressants, antihistamines, and hypnotics. The proportion of comparisons (treatment versus placebo) where a significant impairment was detected with SDLP and SD speed was compared. About 40% of 53 relevant papers did not report data on SD speed and/or SDLP. After placebo administration, the correlation between SDLP and SD speed was significant but did not explain much variance (r = 0.253, p = 0.0001). A significant correlation was found between ΔSDLP and ΔSD speed (treatment-placebo), explaining 48% of variance. When using SDLP as outcome measure, 67 significant treatment-placebo comparisons were found. Only 17 (25.4%) were significant when SD speed was used as outcome measure. Alternatively, for five treatment-placebo comparisons, a significant difference was found for SD speed but not for SDLP. Standard deviation of lateral position is a more sensitive outcome measure to detect driving impairment than speed variability.

  7. A mechanism-based 3D-QSAR approach for classification and prediction of acetylcholinesterase inhibitory potency of organophosphate and carbamate analogs

    Science.gov (United States)

    Lee, Sehan; Barron, Mace G.

    2016-04-01

    Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understanding, there has been no mechanism-based in silico approach for classification and prediction of the inhibitory potency of ether OPs or carbamates. This prompted us to develop a three dimensional prediction framework for OPs, carbamates, and their analogs. Inhibitory structures of a compound that can form the covalent bond were identified through analysis of docked conformations of the compound and its metabolites. Inhibitory potencies of the selected structures were then predicted using a previously developed three dimensional quantitative structure-active relationship. This approach was validated with a large number of structurally diverse OP and carbamate compounds encompassing widely used insecticides and structural analogs including OP flame retardants and thio- and dithiocarbamate pesticides. The modeling revealed that: (1) in addition to classical OP metabolic activation, the toxicity of carbamate compounds can be dependent on biotransformation, (2) OP and carbamate analogs such as OP flame retardants and thiocarbamate herbicides can act as AChEI, (3) hydrogen bonds at the oxyanion hole is critical for AChE inhibition through the covalent bond, and (4) π-π interaction with Trp86 is necessary for strong inhibition of AChE. Our combined computation approach provided detailed understanding of the mechanism of action of OP and carbamate compounds and may be useful for screening a diversity of chemical structures for AChE inhibitory potency.

  8. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial.

    Science.gov (United States)

    Zeller, Thomas; Baumgartner, Iris; Scheinert, Dierk; Brodmann, Marianne; Bosiers, Marc; Micari, Antonio; Peeters, Patrick; Vermassen, Frank; Landini, Mario; Snead, David B; Kent, K Craig; Rocha-Singh, Krishna J

    2014-10-14

    Drug-eluting balloons (DEB) may reduce infrapopliteal restenosis and reintervention rates versus percutaneous transluminal angioplasty (PTA) and improve wound healing/limb preservation. The goal of this clinical trial was to assess the efficacy and safety of IN.PACT Amphirion drug-eluting balloons (IA-DEB) compared to PTA for infrapopliteal arterial revascularization in patients with critical limb ischemia (CLI). Within a prospective, multicenter, randomized, controlled trial with independent clinical event adjudication and angiographic and wound core laboratories 358 CLI patients were randomized 2:1 to IA-DEB or PTA. The 2 coprimary efficacy endpoints through 12 months were clinically driven target lesion revascularization (CD-TLR) and late lumen loss (LLL). The primary safety endpoint through 6 months was a composite of all-cause mortality, major amputation, and CD-TLR. Clinical characteristics were similar between the 2 groups. Significant baseline differences between the IA-DEB and PTA arms included mean lesion length (10.2 cm vs. 12.9 cm; p = 0.002), impaired inflow (40.7% vs. 28.8%; p = 0.035), and previous target limb revascularization (32.2% vs. 21.8%; p = 0.047). Primary efficacy results of IA-DEB versus PTA were CD-TLR of 9.2% versus 13.1% (p = 0.291) and LLL of 0.61 ± 0.78 mm versus 0.62 ± 0.78 mm (p = 0.950). Primary safety endpoints were 17.7% versus 15.8% (p = 0.021) and met the noninferiority hypothesis. A safety signal driven by major amputations through 12 months was observed in the IA-DEB arm versus the PTA arm (8.8% vs. 3.6%; p = 0.080). In patients with CLI, IA-DEB had comparable efficacy to PTA. While primary safety was met, there was a trend towards an increased major amputation rate through 12 months compared to PTA. (Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia [INPACT-DEEP]; NCT00941733). Copyright © 2014 American College of Cardiology Foundation. Published

  9. Highly enantioselective (-)-sparteine-mediated lateral metalation-functionalization of remote silyl protected ortho-ethyl N,N-dialkyl aryl O-carbamates.

    Science.gov (United States)

    Fässler, Jürg; McCubbin, J Adam; Roglans, Anna; Kimachi, Tetsutaro; Hollett, Joshua W; Kunz, Roland W; Tinkl, Michael; Zhang, Yousheng; Wang, Ruiyao; Campbell, Michael; Snieckus, Victor

    2015-04-03

    We report the enantioselective, lateral deprotonation of ortho-protected or functionalized tertiary N,N-dialkyl aryl O-carbamates 5-7 (Scheme 2 ) and meta-protected carbamates 14, 15, and 20 (Schemes 5 and 7 ) by s-BuLi/(-)-sparteine and subsequent quench with a variety of electrophiles to give products 11-13 and 16, 17, and 21 in yields up to 96% and enantiomeric ratios up to 99:1. The influence of organolithium reagents, ratio of organolithium/(-)-sparteine pair versus N,N-dialkyl aryl O-carbamate starting materials, temperature, solvents, electrophiles, substituents located ortho or meta to the O-carbamate moiety, and O-carbamate N-substituents was investigated. The identical absolute configuration of the stereogenic center of the major enantiomers of the products, as established by single-crystal X-ray analysis for substrates (S)-11c, (S)-19, and (S)-21a, provides evidence for a consistent stereochemical course in the enantioselective deprotonation. Mechanistic investigations, including an estimate of the configurational stability of the benzyllithium species 9 (starting from 12e; Scheme 8 ) and 23 (starting from 17e; Scheme 9 ), both derived by tin-lithium exchange, and 24 (starting from 20; Scheme 9 ) are reported. The experimental results, together with semiempirical molecular orbital calculations (PM3/SMD), are consistent with a process in which enantioinduction occurs in the deprotonation step (Scheme 11 ).

  10. SERS-active Ag Nanostars Substrates for Sensitive Detection of Ethyl Carbamate in Wine.

    Science.gov (United States)

    Li, Manli; Zhao, Yuan; Cui, Malin; Wang, Chan; Song, Qijun

    2016-01-01

    A simple and sensitive surface-enhanced Raman scattering (SERS) method for the detection of ethyl carbamate (EC) is reported in this work. Star-shaped silver nanostars (Ag NSs) were used as a novel SERS substrate. In comparison to other plasmonic nanoparticles (NPs), including Au NPs, Au NSs and Ag NPs, Ag NSs exhibit best SERS activity. Raman signal of EC at a trace level can be enhanced by several orders of magnitude with the help of Ag NSs. The Raman intensity of EC increased linearly with an increase of the EC concentration in the range from 5 × 10(-9) mol L(-1) to 1.0 × 10(-4) mol L(-1) with detection limit (LOD) of 1.37 × 10(-9) mol L(-1) (S/N = 3). The developed SERS approach also has the advantages of being simple, fast and requiring less amount of the sample. It could serve as a useful technology for the rapid determination of EC in both alcoholic beverages and fermented food.

  11. Cyanate as an Active Precursor of Ethyl Carbamate Formation in Sugar Cane Spirit.

    Science.gov (United States)

    Galinaro, Carlos A; Ohe, Thiago H K; da Silva, Augusto C H; da Silva, Sebastião C; Franco, Douglas W

    2015-08-26

    The thermodynamic and kinetic aspects of ethyl carbamate (EC) formation through the reaction between cyanate and ethanol were investigated. The rate constant values for cyanate ion decay and EC formation are (8.0 ± 0.4) × 10(-5) and (8.9 ± 0.4) × 10(-5) s(-1), respectively, at 25 °C in 48% aqueous ethanolic solution at pH 4.5. Under the investigated experimental conditions, the rate constants are independent of the ethanol and cyanate concentrations but increase as the temperature increases (ΔH1(⧧) = 19.4 ± 1 kcal/mol, ΔS1(⧧) = −12.1 ± 1 cal/K, and ΔG1(⧧) = 23.0 ± 1 kcal/mol) and decrease as the solution pH increases. According to molecular modeling (DFT) that was performed to analyze the reaction mechanism, the isocyanic acid (HNCO) is the active EC precursor. The calculated ΔG1(⧧), ΔH1(⧧), and ΔS1(⧧) values are in very good agreement with the experimental ones.

  12. Highly porous regenerated cellulose hydrogel and aerogel prepared from hydrothermal synthesized cellulose carbamate

    Science.gov (United States)

    Gan, Sinyee; Chia, Chin Hua; Chen, Ruey Shan; Ellis, Amanda V.; Kaco, Hatika

    2017-01-01

    Here, a stable derivative of cellulose, called cellulose carbamate (CC), was produced from Kenaf (Hibiscus cannabinus) core pulp (KCP) and urea with the aid of a hydrothermal method. Further investigation was carried out for the amount of nitrogen yielded in CC as different urea concentrations were applied to react with cellulose. The effect of nitrogen concentration of CC on its solubility in a urea-alkaline system was also studied. Regenerated cellulose products (hydrogels and aerogels) were fabricated through the rapid dissolution of CC in a urea-alkaline system. The morphology of the regenerated cellulose products was viewed under Field emission scanning electron microscope (FESEM). The transformation of allomorphs in regenerated cellulose products was examined by X-ray diffraction (XRD). The transparency of regenerated cellulose products was determined by Ultraviolet–visible (UV–Vis) spectrophotometer. The degree of swelling (DS) of regenerated cellulose products was also evaluated. This investigation provides a simple and efficient procedure of CC determination which is useful in producing regenerated CC products. PMID:28296977

  13. Ethyl carbamate induces cell death through its effects on multiple metabolic pathways.

    Science.gov (United States)

    Liu, Huichang; Cui, Bo; Xu, Yi; Hu, Chaoyang; Liu, Ying; Qu, Guorun; Li, Dawei; Wu, Yongning; Zhang, Dabing; Quan, Sheng; Shi, Jianxin

    2017-11-01

    Ethyl carbamate (EC), a multisite carcinogenic chemical causing tumors in various animal species, is probably carcinogenic to humans. However, information about the possible carcinogenic and toxicological effects of EC in humans is quite limited. Because EC is found in many dietary foods (such as fermented foods) and tobacco and its products, and exposure of humans to EC often occurs inevitably, its toxicological effects in humans need to be studied. This study was conducted to understand the metabolomic and transcriptomic changes in human hepatocellular carcinoma cells (HepG2) exposed to 100 mM EC for short term (4 h) and long term (12 h) period, respectively. The results revealed multiple influences of EC on the metabolome and transcriptome of HepG2 cells, which was exposure time-dependent and well correlated with the kinetic changes of cell viability and mortality. EC treatment affected multiple metabolic pathways, inducing oxidative stress, reducing detoxification capacity, depleting energy, decreasing reducing power, disrupting membrane integrity, and damaging DNA and protein. These metabolomic and transcriptomic biomarkers of EC on human cell metabolism identified in this study would facilitate further studies on the risk assessment and the mitigation of dietary EC. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Organophosphorus and carbamates residues in milk and feedstuff supplied to dairy cattle

    Directory of Open Access Journals (Sweden)

    Rafael Fagnani

    2011-07-01

    Full Text Available Considering acute and chronic toxicity effects on human and animal health caused by pesticide residues in food, this study aimed to analyze organophosphorate (OP and carbamate (CB in feedstuff and water destined for dairy cattle, as well as in the milk produced by these animals, through gas chromatography (GC. In the Agreste region of Pernambuco, Brazil, 30 raw milk samples and all components of the animals' diet were collected from several farms. Out of the 30 milk of milk analyzed, six (20% were contaminated with OP, five (16.7% with CB, and one sample with both pesticides. From 48 analyzed feed samples, 15 (31.25% were contaminated with residues of OP, six (12.50% with CB, and one sample was contaminated with both pesticides. Out of 16 water samples analyzed, six (37.50% were contaminated with OP residues, but non with CB. In four dairy farms the pesticides detected in milk were compatible with the active principles found in water and/or foodstuff, suggesting them to be the source of contamination.

  15. Dual Palladium(II)/Tertiary Amine Catalysis for Asymmetric Regioselective Rearrangements of Allylic Carbamates.

    Science.gov (United States)

    Bauer, Johannes Moritz; Frey, Wolfgang; Peters, René

    2016-04-11

    The streamlined catalytic access to enantiopure allylic amines as valuable precursors towards chiral β- and γ-aminoalcohols as well as α- and β-aminoacids is desirable for industrial purposes. In this article an enantioselective method is described that transforms achiral allylic alcohols and N-tosylisocyanate in a single step into highly enantioenriched N-tosyl protected allylic amines via an allylic carbamate intermediate. The latter is likely to undergo a cyclisation-induced [3,3]-rearrangement catalysed by a planar chiral pentaphenylferrocene palladacycle in cooperation with a tertiary amine base. The otherwise often indispensable activation of palladacycle catalysts by a silver salt is not required in the present case and there is also no need for an inert gas atmosphere. To further improve the synthetic value, the rearrangement was used to form dimethylaminosulfonyl-protected allylic amines, which can be deprotected under non-reductive conditions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Neuropathological effect of carbamate molluscicides on the land snail, Eobania vermiculata.

    Science.gov (United States)

    Essawy, Amina E; Abdelmeguied, Nabila E; Radwan, Mohamed A; Hamed, Sherifa S; Hegazy, Amira E

    2009-06-01

    The present study was designed to investigate the neuropathological effect of the two carbamate pesticides: methomyl and methiocarb on the neurons of the buccal ganglia in the land snail Eobania vermiculata using topical application and baiting technique. Their in vivo effects on acetylcholinesterase (AChE, EC 3.1.1.7) activity were also investigated. Sublethal dose and concentration (1/4 LD(50) and 1/4 LC(50)) of both pesticides were used, and the experiment lasted for 14 days. Histopathological and ultrastuctural alterations in the buccal ganglia were more obvious after the baiting technique treatment than after the topical application method, and methomyl was found to be more toxic than methiocarb. These alterations included shrinkage of the perikarya of neurons, increased cytoplasmic basophilia, and extreme indentation of the plasma membrane. In addition, the nuclei appeared karyolitic, eccentric, and highly shrunken with an irregular nuclear envelope. The most outstanding symptom observed after topical application of methiocarb was a highly vacuolated cytoplasm with a peripheral increase in electron density associated with dense accumulations of free ribosomes. On the other hand, an increased number of lysosomes and autophagosomes were observed after topical application of methomyl. Mitochondrial damage, increased number of lipid droplets, and myelin figures were frequently observed in ganglia treated with either methomyl or methiocarb. Moreover, it was noticed that both compounds induced reductions in AChE activity. However, methomyl exhibited more potency in reducing AChE activity than methiocarb.

  17. Surface display of recombinant Drosophila melanogaster acetylcholinesterase for detection of organic phosphorus and carbamate pesticides.

    Science.gov (United States)

    Li, Jingquan; Qian Ba; Yin, Jun; Wu, Songjie; Zhuan, Fangfang; Xu, Songci; Li, Junyang; Salazar, Joelle K; Zhang, Wei; Wang, Hui

    2013-01-01

    Acetylcholinesterase (AChE) is commonly used for the detection of organophosphate (OP) and carbamate (CB) insecticides. However, the cost of this commercially available enzyme is high, making high-throughput insecticide detection improbable. In this study we constructed a new AChE yeast expression system in Saccharomyces cerevisiae for the expression of a highly reactive recombinant AChE originating from Drosophila melanogaster (DmAChE). Specifically, the coding sequence of DmAChE was fused with the 3'-terminal half of an α-agglutinin anchor region, along with an antigen tag for the detection of the recombinant protein. The target sequence was cloned into the yeast expression vector pYes-DEST52, and the signal peptide sequence was replaced with a glucoamylase secretion region for induced expression. The resultant engineered vector was transformed into S. cerevisiae. DmAChE was expressed and displayed on the cell surface after galactose induction. Our results showed that the recombinant protein displayed activity comparable to the commercial enzyme. We also detected different types of OP and CB insecticides through enzyme inhibition assays, with the expressed DmAChE showing high sensitivity. These results show the construction of a new yeast expression system for DmAChE, which can subsequently be used for detecting OP and CB insecticides with reduced economic costs.

  18. Absorption, distribution, metabolism and excretion of 14C-chlorphenesin carbamate in rats

    International Nuclear Information System (INIS)

    Nozu, Takashi; Aoyagi, Tadao; Setoyama, Kageyoshi; Suwa, Toshio; Tanaka, Ichiro

    1977-01-01

    Absorption, distribution, metabolism and excretion of chlorphenesin carbamate (CPC), a central acting muscle relaxant, were investigated in rats by use of 14 C-labeled CPC. After oral administration, 14 C-CPC was well absorbed from gastrointestinal tract and about 90% of the given radioactivity was excreted in urine and 5% in feces during 5 days. Approximately 36% was recovered in bile during 8 hr after oral administration. The highest blood level of 14 C was observed at 3-8 hr after oral administration and decreased slowly. The radioactivity was distributed widely in almost all tissues. The highest concentration of 14 C was observed in the liver and the higher was detected in the brain and spinal cord, suggesting a pharmacological effect of CPC. In pregnant rats given 14 C-CPC orally, the radioactivity in the fetuses was below 0.8% of the dose at 1-24 hr. The major metabolites in 48 hr urine was identified as CPC-glucuronide and the acidic metabolites, p-chlorophenoxylactic acid, p-chlorophenoxyacetic acid and p-chlorophenol, were also detected. After intravenous injection of the 14 C-labeled acidic metabolites, the radioactivity was not detected in the central nervous system and excreted rapidly. In the case of repeated administration of CPC and 14 C-CPC for 21 days, the radioactivity did not accumulated in any tissue of rats. (auth.)

  19. Immobilization of acetylcholinesterase via biocompatible interface of silk fibroin for detection of organophosphate and carbamate pesticides

    Science.gov (United States)

    Xue, Rui; Kang, Tian-Fang; Lu, Li-Ping; Cheng, Shui-Yuan

    2012-06-01

    An amperometric biosensor for the detection of organophosphate and carbamate pesticides was developed based on the immobilization of acetylcholinesterase (AChE) on regenerated silk fibroin (SF) matrix by non-covalent adsorption. SF and AChE were coated sequentially on the surface of the glassy carbon electrode (GCE) which was modified with multiwall carbon nanotube (MWNTs). The obtained biosensor was denoted as AChE-SF/MWNTs/GCE. The atomic force microscopy images showed that the SF matrix provided a more homogeneous interface for the AChE immobilization. The aggregation of immobilizing AChE was therefore avoided. The cyclic voltammogram of thiocholine at this biosensor exhibited a well defined oxidation peak at 0.667 V (vs. SCE). The inhibition rate of methyl parathion to the immobilized AChE was proportional to the logarithm of the concentration of methyl parathion over the range of the concentration of methyl parathion from 3.5 × 10-6 to 2.0 × 10-3 M with a detection limit of 5.0 × 10-7 M. Similarly, the linearly response range of carbaryl was from 1.0 × 10-7 to 3.0 × 10-5 M with a detection limit of 6.0 × 10-8 M. The experimental results indicate that AChE not only can be immobilized steadily on the SF matrix, but also the bioactivity of immobilizing AChE can be preserved effectively.

  20. The influence of organophosphate and carbamate on sperm chromatin and reproductive hormones among pesticide sprayers.

    Science.gov (United States)

    Jamal, Farrukh; Haque, Quazi S; Singh, Sangram; Rastogi, S K

    2016-08-01

    This study is aimed at evaluating the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality as well as levels of reproductive and thyroid hormones of pesticide sprayers in Malihabad, Lucknow, Uttar Pradesh, India. Thirty-five healthy men (unexposed group) and 64 male pesticide sprayers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. Evidence of pesticide exposure was found in 88.5% of sprayers and significant increments were observed in sperm DFI with significant decrease in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology, and vitality in these pesticide sprayers. The levels of Tt, PRL, FT4, and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. The results confirm the potential impact of chronic occupational exposure to OP and CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality, and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes. © The Author(s) 2015.

  1. Surface display of recombinant Drosophila melanogaster acetylcholinesterase for detection of organic phosphorus and carbamate pesticides.

    Directory of Open Access Journals (Sweden)

    Jingquan Li

    Full Text Available Acetylcholinesterase (AChE is commonly used for the detection of organophosphate (OP and carbamate (CB insecticides. However, the cost of this commercially available enzyme is high, making high-throughput insecticide detection improbable. In this study we constructed a new AChE yeast expression system in Saccharomyces cerevisiae for the expression of a highly reactive recombinant AChE originating from Drosophila melanogaster (DmAChE. Specifically, the coding sequence of DmAChE was fused with the 3'-terminal half of an α-agglutinin anchor region, along with an antigen tag for the detection of the recombinant protein. The target sequence was cloned into the yeast expression vector pYes-DEST52, and the signal peptide sequence was replaced with a glucoamylase secretion region for induced expression. The resultant engineered vector was transformed into S. cerevisiae. DmAChE was expressed and displayed on the cell surface after galactose induction. Our results showed that the recombinant protein displayed activity comparable to the commercial enzyme. We also detected different types of OP and CB insecticides through enzyme inhibition assays, with the expressed DmAChE showing high sensitivity. These results show the construction of a new yeast expression system for DmAChE, which can subsequently be used for detecting OP and CB insecticides with reduced economic costs.

  2. Molybdenum Carbamate Nanosheets as a New Class of Potential Phase Change Materials.

    Science.gov (United States)

    Zhukovskyi, Maksym; Plashnitsa, Vladimir; Petchsang, Nattasamon; Ruth, Anthony; Bajpai, Anshumaan; Vietmeyer, Felix; Wang, Yuanxing; Brennan, Michael; Pang, Yunsong; Werellapatha, Kalpani; Bunker, Bruce; Chattopadhyay, Soma; Luo, Tengfei; Janko, Boldizsar; Fay, Patrick; Kuno, Masaru

    2017-06-14

    We report for the first time the synthesis of large, free-standing, Mo 2 O 2 (μ-S) 2 (Et 2 dtc) 2 (MoDTC) nanosheets (NSs), which exhibit an electron-beam induced crystalline-to-amorphous phase transition. Both electron beam ionization and femtosecond (fs) optical excitation induce the phase transition, which is size-, morphology-, and composition-preserving. Resulting NSs are the largest, free-standing regularly shaped two-dimensional amorphous nanostructures made to date. More importantly, amorphization is accompanied by dramatic changes to the NS electrical and optical response wherein resulting amorphous species exhibit room-temperature conductivities 5 orders of magnitude larger than those of their crystalline counterparts. This enhancement likely stems from the amorphization-induced formation of sulfur vacancy-related defects and is supported by temperature-dependent transport measurements, which reveal efficient variable range hopping. MoDTC NSs represent one instance of a broader class of transition metal carbamates likely having applications because of their intriguing electrical properties as well as demonstrated ability to toggle metal oxidation states.

  3. Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion.

    Science.gov (United States)

    Williams, Hywel D; Anby, Mette U; Sassene, Philip; Kleberg, Karen; Bakala-N'Goma, Jean-Claude; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Carrière, Frédéric; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H

    2012-11-05

    The LFCS Consortium was established to develop standardized in vitro tests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitro digestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout. In general, increasing NaTDC concentrations increased the digestion of the most lipophilic LBFs and promoted lipid (and drug) trafficking from poorly dispersed oil phases to the aqueous colloidal phase (AP(DIGEST)). High NaTDC concentrations showed some capacity to reduce drug precipitation, although, at NaTDC concentrations ≥3 mM, NaTDC effects on either digestion or drug solubilization were modest. In contrast, increasing drug load had a marked impact on drug solubilization. For LBFs containing long-chain lipids, drug precipitation was limited even at drug loads approaching saturation in the formulation and concentrations of solubilized drug in AP(DIGEST) increased with increased drug load. For LBFs containing medium-chain lipids, however, significant precipitation was evident, especially at higher drug loads. Across all formulations a remarkably consistent trend emerged such that the likelihood of precipitation was almost entirely dependent on the maximum supersaturation ratio (SR(M)) attained on initiation of digestion. SR(M) defines the supersaturation "pressure" in the system and is calculated from the maximum attainable concentration in the AP(DIGEST) (assuming zero precipitation), divided by the solubility of the drug in the colloidal phases formed post digestion. For LBFs where phase separation of oil phases did not occur, a

  4. Indoline-3-propionate and 3-aminopropyl carbamates reduce lung injury and pro-inflammatory cytokines induced in mice by LPS.

    Science.gov (United States)

    Finkin-Groner, E; Moradov, D; Shifrin, H; Bejar, C; Nudelman, A; Weinstock, M

    2015-02-01

    In the search for safer and effective anti-inflammatory agents, we investigated the effect of methyl indoline-3-propionate and indoline-3-(3-aminopropyl) carbamates on LPS-induced lung injury and pro-inflammatory cytokines in mice. Their mechanism of action was determined in murine peritoneal macrophages. Lung injury was induced by intratracheal infusion of LPS and assessed by the change in lung weight and structure by light microscopy after staining by haematoxylin and eosin. In LPS-activated macrophages, MAPK proteins and IκBα were measured by Western blotting and the transcription factors, AP-1 and NF-κB by electromobility shift assay. Cytokines in the plasma and spleen of mice injected with LPS were measured by elisa-based assay. AN917 and AN680 (1-10 pM) decreased TNF-α protein in macrophages by inhibiting phosphorylation of p38 MAPK, IκBα degradation and activation of AP-1 and NF-κB without affecting cell viability. In vivo, these compounds (10 μmol · kg(-1)) markedly decreased lung injury induced by LPS and the elevation of TNF-α and IL-6 in lung, plasma and spleen. Activation of α-7nACh receptors contributed to the reduction of TNF-α by AN917, which inhibited AChE in the spleen by 35%. Indoline carbamates are potent inhibitors of pro-inflammatory mediators in murine macrophages and in mice injected with LPS, acting via the p38 MAPK, AP-1 and NF-κB cascades. Indirect α-7nACh receptor activation by AN917, through inhibition of AChE, contributes to its anti-inflammatory effect. Indoline carbamates may have therapeutic potential for lung injury and other diseases associated with chronic inflammation without causing immunosuppression. © 2014 The British Pharmacological Society.

  5. Practical metal-free C(sp(3))-H functionalization: construction of structurally diverse α-substituted N-benzyl and N-allyl carbamates.

    Science.gov (United States)

    Xie, Zhiyu; Liu, Lei; Chen, Wenfang; Zheng, Hongbo; Xu, Qingqing; Yuan, Huiqing; Lou, Hongxiang

    2014-04-07

    Described is a practical and universal CH functionalization of readily removable N-benzyl and N-allyl carbamates, with a wide range of nucleophiles at ambient temperature promoted by Ph3 CClO4 . The metal-free reaction has an excellent functional-group tolerance, and displays a broad scope with respect to both N-carbamates and nucleophile partners (a variety of organoboranes and CH compounds). The synthetic utility in target- as well as diversity-oriented syntheses is demonstrated. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Base-promoted coupling of carbon dioxide, amines, and N-tosylhydrazones: a novel and versatile approach to carbamates.

    Science.gov (United States)

    Xiong, Wenfang; Qi, Chaorong; He, Haitao; Ouyang, Lu; Zhang, Min; Jiang, Huanfeng

    2015-03-02

    A base-promoted three-component coupling of carbon dioxide, amines, and N-tosylhydrazones has been developed. The reaction is suggested to proceed via a carbocation intermediate and constitutes an efficient and versatile approach for the synthesis of a wide range of organic carbamates. The advantages of this method include the use of readily available substrates, excellent functional group tolerance, wide substrate scope, and a facile work-up procedure. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Amino(oxo)acetate moiety: A new functional group to improve the cytotoxicity of betulin derived carbamates.

    Science.gov (United States)

    Heller, Lucie; Perl, Vincent; Wiemann, Jana; Al-Harrasi, Ahmed; Csuk, René

    2016-06-15

    While 3-O-acetylated betulin derivatives carrying a carbamate moiety at position C-28 are of rather low cytotoxicity for human tumor cell lines, the corresponding C-3 amino(oxo) acetates show good cytotoxicity. For example, an EC50 as low as 2.0μM was found for (3β) 28-{[(hexylamino)carbonyl]oxy}lup-20(29)-en-3-yl amino(oxo)acetate (16) employing the ovarian cancer cell line A2780. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Piperazine and piperidine carboxamides and carbamates as inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).

    Science.gov (United States)

    Korhonen, Jani; Kuusisto, Anne; van Bruchem, John; Patel, Jayendra Z; Laitinen, Tuomo; Navia-Paldanius, Dina; Laitinen, Jarmo T; Savinainen, Juha R; Parkkari, Teija; Nevalainen, Tapio J

    2014-12-01

    The key hydrolytic enzymes of the endocannabinoid system, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), are potential targets for various therapeutic applications. In this paper, we present more extensively the results of our previous work on piperazine and piperidine carboxamides and carbamates as FAAH and MAGL inhibitors. The best compounds of these series function as potent and selective MAGL/FAAH inhibitors or as dual FAAH/MAGL inhibitors at nanomolar concentrations. This study revealed that MAGL inhibitors should comprise leaving-groups with a conjugate acid pKa of 8-10, while diverse leaving groups are tolerated for FAAH inhibitors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Chlorpropham and phenisopham: phototransformation and ecotoxicity of carbamates in the aquatic environment.

    Science.gov (United States)

    Passananti, Monica; Lavorgna, Margherita; Iesce, Maria Rosaria; DellaGreca, Marina; Criscuolo, Emma; Parrella, Alfredo; Isidori, Marina; Temussi, Fabio

    2014-04-01

    In this study, a comparison of two carbamic pesticides, chlorpropham and phenisopham, was carried out in terms of both photodegradability and ecotoxicity. The photochemical behaviour of the two pesticides was investigated under environmental-like conditions (aqueous media, UVB or solar irradiation). The photochemical kinetic parameters were calculated by irradiating 5 × 10(-5) M solutions (H₂O-CH₃CN, 9 : 1 v/v) using UVB lamps. For chlorpropham and phenisopham similar half-life times (39.0 and 55.0 min) were determined. Irradiation by sunlight leads to longer degradation half-life times (about 3 months), while it is possible to observe the formation of the same photoproducts. The well-known dechlorination reaction to a hydroxyphenylcarbamate was observed for chlorpropham. Phenisopham undergoes photo-Fries reaction to give rearranged products (hydroxybenzamides) and fragmentation products (hydroxyphenylcarbamate and N-ethylaniline). Acute and chronic toxicity tests of pesticides and their photoproducts were performed on organisms from two levels of the freshwater aquatic chain, the anostraca crustacean Thamnocephalus platyurus, the rotifer Brachionus calyciflorus and the alga Pseudokirchneriella subcapitata. The acute results showed that chlorpropham had median lethal concentrations for the crustacean T. platyurus and the rotifer B. calyciflorus of 10.16 and 35.19 mg L(-1), respectively, and phenisopham did not show any acute toxicity as the derivatives up to 10 mg L(-1). The only exception was N-ethylaniline which exhibited an acute LC₅₀ value of 0.46 mg L(-1). Phenisopham was the most toxic in the long term exposure while its five derivatives showed lower chronic potential for rotifers and algae. The same trend was observed for chlorpropham except for rotifers.

  10. Dynamic viscoelastic properties of cellulose carbamate dissolved in NaOH aqueous solution.

    Science.gov (United States)

    Guo, Yi; Zhou, Jinping; Zhang, Lina

    2011-05-09

    Dynamic viscoelastic properties of cellulose carbamate (CC) dissolved in NaOH aqueous solution were systematically studied for the first time. CC was microwave-assisted synthesized from the mixture of cellulose and urea and then dissolved in 7 wt % NaOH aqueous solution precooled to -7 °C. The obtained CC solution is transparent and has good liquidity. To clarify the rheological behavior of the solution, the CC solutions were investigated by dynamic viscoelastic measurements. The shear storage modulus (G') and loss modulus (G'') as a function of the angular frequency (ω), concentration (c), nitrogen content (N %), viscosity-average molecular weight (M(η)), temperature (T), and time (t) were analyzed and discussed in detail. The sol-gel transition temperature of CC (M(η) = 7.78 × 10(4)) solution decreased from 36.5 to 31.3 °C with an increase of the concentration from 3.0 to 4.3 wt % and decreased from 35.7 to 27.5 °C with an increase of the nitrogen content from 1.718 to 5.878%. The gelation temperature of a 3.8 wt % CC solution dropped from 38.2 to 34.4 °C with the M(η) of CC increased from 6.35 × 10(4) to 9.56 × 10(4). The gelation time of the CC solution was relatively short at 30 °C, but the solution was stable for a long time at about 15 °C. Moreover, the gels already formed at elevated temperature were irreversible; that is, after cooling to a lower temperature including the dissolution temperature (-7 °C), they could not be dissolved to become liquid.

  11. Urinary concentrations of organophosphate and carbamate pesticides in residents of a vegetarian community.

    Science.gov (United States)

    Berman, T; Göen, T; Novack, L; Beacher, L; Grinshpan, L; Segev, D; Tordjman, K

    2016-11-01

    Few population studies have measured urinary levels of pesticides in individuals with vegan, vegetarian, or organic diets. The objectives of this study were to evaluate whether a vegan/vegetarian diet was associated with increased exposure to organophosphate and carbamate pesticides, and to evaluate the impact of organic consumption on pesticide exposure in vegans and vegetarians. In the current pilot study conducted in 2013-2014, we collected spot urine samples and detailed 24h recall dietary data in 42 adult residents of Amirim, a vegetarian community in Northern Israel. We measured urinary levels of non-specific organophosphate pesticide metabolites (dialkylphosphates, (DAPs)) and specific metabolites of the current-use pesticides chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPy)), propoxur (-isopropoxyphenol (IPPX)), and carbaryl (1-naphthol). Six DAP metabolites were detected in between 67 and 100% of urine samples, with highest geometric mean concentrations for dimethylphosphate (19.2μg/g). Creatinine-adjusted median concentrations of total DAPs and of TCPy were significantly higher in Amirim residents compared to the general Jewish population in Israel (0.29μmol/g compared to 0.16, p25% of the produce they consume is organic (0.065μmol/L compared to 0.22, porganophosphate pesticide metabolite concentrations in residents of a vegetarian community, a positive association between vegetable intake and urinary levels of a chlorpyrifos specific metabolite, and lower levels of total dimethyl phosphate in individuals reporting higher intake of organic produce. Results suggest that consumption of organic produce may offer some protection from increased exposure to organophosphate pesticide residues in vegetarians. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Immobilization of acetylcholinesterase via biocompatible interface of silk fibroin for detection of organophosphate and carbamate pesticides

    Energy Technology Data Exchange (ETDEWEB)

    Xue Rui [College of Environmental and Energy Engineering, Beijing University of Technology, Beijing 100124 (China); Kang Tianfang, E-mail: kangtf@yahoo.cn [College of Environmental and Energy Engineering, Beijing University of Technology, Beijing 100124 (China); Lu Liping; Cheng Shuiyuan [College of Environmental and Energy Engineering, Beijing University of Technology, Beijing 100124 (China)

    2012-06-01

    An amperometric biosensor for the detection of organophosphate and carbamate pesticides was developed based on the immobilization of acetylcholinesterase (AChE) on regenerated silk fibroin (SF) matrix by non-covalent adsorption. SF and AChE were coated sequentially on the surface of the glassy carbon electrode (GCE) which was modified with multiwall carbon nanotube (MWNTs). The obtained biosensor was denoted as AChE-SF/MWNTs/GCE. The atomic force microscopy images showed that the SF matrix provided a more homogeneous interface for the AChE immobilization. The aggregation of immobilizing AChE was therefore avoided. The cyclic voltammogram of thiocholine at this biosensor exhibited a well defined oxidation peak at 0.667 V (vs. SCE). The inhibition rate of methyl parathion to the immobilized AChE was proportional to the logarithm of the concentration of methyl parathion over the range of the concentration of methyl parathion from 3.5 Multiplication-Sign 10{sup -6} to 2.0 Multiplication-Sign 10{sup -3} M with a detection limit of 5.0 Multiplication-Sign 10{sup -7} M. Similarly, the linearly response range of carbaryl was from 1.0 Multiplication-Sign 10{sup -7} to 3.0 Multiplication-Sign 10{sup -5} M with a detection limit of 6.0 Multiplication-Sign 10{sup -8} M. The experimental results indicate that AChE not only can be immobilized steadily on the SF matrix, but also the bioactivity of immobilizing AChE can be preserved effectively.

  13. High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka – implications for global suicide prevention

    Science.gov (United States)

    Lamb, Thomas; Selvarajah, Liza R.; Mohamed, Fahim; Jayamanne, Shaluka; Gawarammana, Indika; Mostafa, Ahmed; Buckley, Nicholas A.; Roberts, Michael S.; Eddleston, Michael

    2016-01-01

    Abstract Background: Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides. Methods: We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested. Findings: Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0–9.8); fenobucarb 6.3%, OR 3.0 (1.2–7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9–8.3); fenobucarb 18.9%, OR 3.6 (2.1–6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3 h (IQR 5.5–67.3), carbosulfan 21.3 h (11.5–71.3), and fenobucarb 25.3 h (17.3–72.1) (p = 0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8 h (IQR 27.5–118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS. Conclusions: We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate

  14. The legal standards for the radioactive or non radioactive drugs research and approval in the European Community and in Germany after the thalidomide catastrophe.

    Science.gov (United States)

    Barsch, Michael; Otte, Andreas

    2010-01-01

    The drug thalidomide was contained in the blockbuster Contergan, which has been used as a non- prescription sedative drug and a potent treatment for occurring morning sickness in pregnant women during the 1950s and the early 1960s. This therapeutic use has led to one of the most prominent disasters in the history of drug development due to peripheral neuritis and malformations, e.g. phocomelia, in babies whose mothers had taken thalidomide within their pregnancies. Moreover, this catastrophe initiated a change of paradigm in Germany as well as in Europe with regard to drug safety and the regulatory setting. This article describes the history of the use of thalidomide and the regulatory framework of drug approval at that time as well as changes after the Contergan disaster including considerations to radiopharmaceuticals. Additionally, aspects of drug safety in the different development phases of pharmaceuticals as well as radiopharmaceuticals, i.e. pre-clinical and clinical phases, are characterised. However, many drugs have been withdrawn from the market after approval due to changes with regard of their risk-benefit balance after the occurrence of adverse drug reactions. Thus, pharmacovigilance activities are also mentioned in this review article. Last, obstacles and future perspectives in the arena of drug research and development also considering the use of radiopharmaceuticals are delineated.

  15. Analysis of carbamate and phenylurea pesticide residues in fruit juices by solid-phase microextraction and liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Sagratini, Gianni; Mañes, Jordi; Giardiná, Dario; Damiani, Pietro; Picó, Yolanda

    2007-04-20

    A new analysis method to detect carbamates and phenylurea pesticide residues in fruit juices was developed using solid-phase microextraction (SPME) coupled with liquid chromatography-single quadrupole mass spectrometry (LC/MS) and liquid chromatography-quadrupole ion trap mass spectrometry (LC/QIT-MS). The pesticide residues present in watery matrices as fruit juices were extracted using three types of fibers: 50-microm Carbowax/templated resin (CW/TPR), 60-mum poly(dimethylsiloxane)/divinylbenzene (PDMS/DVB) and 85-microm polyacrylate. The different extraction conditions were evaluated choosing as the best parameters 90 min (time), 20 degrees C (temperature) and 1 ml (volume). After extraction, the desorption (in a static mode) was performed in the specific interface chamber SPME/HPLC, previously filled with 70% methanol and 30% water. The best recoveries, evaluated at two fortification levels (0.2 and 0.5 mg kg(-1)) in fruit juices, were obtained using PDMS/DVB and CW/TPR fibers, and ranged from 25 to 82% (monolinuron, diuron and diethofencarb), with relative standard deviations (RSDs) from 1 to 17%. All the limits of quantification (LOQs) were in the range of 0.005-0.05 microg ml(-1) and, in any case, equal to, or lower than, maximum residue limits (MRLs) established by Italian and Spanish legislations. The mass spectrometry analyses were carried out using an electrospray ionization (ESI) source operating in the positive mode both for single quadrupole and for QIT mass analysers, operating in selected ion monitoring (SIM) and in multiple reaction monitoring (MRM) modes, respectively. The proposed new method can be applied to the determination of selected pesticides in real samples of fruit juices.

  16. Optimization and validation of liquid-liquid extraction with low temperature partitioning for determination of carbamates in water.

    Science.gov (United States)

    Goulart, Simone Machado; Alves, Renata Domingos; Neves, Antônio Augusto; de Queiroz, José Humberto; de Assis, Tamires Condé; de Queiroz, Maria Eliana L R

    2010-06-25

    Using a 2(3) experimental design, liquid-liquid extraction with low temperature partitioning (LLE-LTP) was optimized and validated for analysis of three carbamates (aldicarb, carbofuran and carbaryl) in water samples. In this method, 2.0 mL of sample is placed in contact with 4.0 mL of acetonitrile. After agitation, the sample is placed in a freezer for 3 h for phase separation. The organic extract is analyzed by high performance liquid chromatography with ultraviolet detection (HPLC-UV). For validation of the technique, the following figures of merit were evaluated: accuracy, precision, detection and quantification limits, linearity, sensibility and selectivity. Extraction recovery percentages of the carbamates aldicarb, carbofuran and carbaryl were 90%, 95% and 96%, respectively. Even though extremely low volumes of sample and solvent were used, the extraction method was selective and the detection and quantification limits were between 5.0 and 10.0 microg L(-1), and 17.0 and 33.0 microg L(-1), respectively. Copyright 2010 Elsevier B.V. All rights reserved.

  17. Carbamates: A study on genotoxic, cytotoxic, and apoptotic effects induced in Chinese hamster ovary (CHO-K1) cells.

    Science.gov (United States)

    Soloneski, Sonia; Kujawski, Maciej; Scuto, Anna; Larramendy, Marcelo L

    2015-08-01

    In vitro effects of the carbamates pirimicarb and zineb and their formulations Aficida® (50% pirimicarb) and Azzurro® (70% zineb), respectively, were evaluated in Chinese hamster ovary (CHO-K1) cells. Whereas the cytokinesis-blocked micronucleus cytome assay was employed to test for genotoxicity, MTT, neutral red (NR), and apoptosis evaluation were used as tests for estimating cell viability and succinic dehydrogenase activity, respectively. Concentrations tested were 10-300 μg/ml for pirimicarb and Aficida®, and 1-50 μg/ml for zineb and Azzurro®. All compounds were able to increase the frequency of micronuclei. A marked reduction in the nuclear division index was observed after treatment with 5 μg/ml of zineb and Azzurro® and 10 μg/ml of Azzurro®. Alterations in the cellular morphology not allowing the recognition of binucleated cells exposed to 300 μg/ml pirimicarb and Aficida® as well as 10-50 μg/ml zineb and Azzurro®. All four compounds induced inhibition of both cell viability and succinic dehydrogenase activity and trigger apoptosis in CHO-K1 cells, at least when exposed for 24 h. The data herein demonstrate the genotoxic and cytotoxic effects exerted by these carbamates and reveal the potential risk factor of these pesticides, still extensively used worldwide, for both human health and the environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. One-pot synthesis and biological evaluation of N-(aminosulfonyl)-4-podophyllotoxin carbamates as potential anticancer agents.

    Science.gov (United States)

    Xu, Xiao-Hui; Guan, Xiao-Wen; Feng, Shi-Liang; Ma, You-Zhen; Chen, Shi-Wu; Hui, Ling

    2017-07-01

    A series of N-(aminosulfonyl)-4-podophyllotoxin carbamates were synthesized via the Burgess-type intermediate, and their antiproliferative activities were evaluated. Most of them possessed more potent cytotoxic effects against four human tumor cell lines (HeLa, A-549, HCT-8 and HepG2) and less toxic to normal human fetal lung fibroblast WI-38 cells than etoposide. In particular, N-(morpholinosulfonyl)-4-podophyllotoxin carbamate (9) exhibited the most potent activity towards these four tumor cells with IC 50 values in the range of 0.5-16.5μM. Furthermore, immunofluorescence analysis revealed that 9 induced cell apoptosis by up-regulating the expression of p53 and ROS. Meanwhile, 9 effectively inhibited tubulin polymerization and microtubule assembly at cellular levels in HeLa cells. In addition, 9 could induce cell cycle arrest in the G2/M phase in HeLa cells by up-regulating levels of cyclinB1 and cdc2 and decreasing the expression of p-cdc2. These results indicated that 9 had potential for further development as anticancer agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Monitoring of N-methyl carbamate pesticide residues in water using hollow fibre supported liquid membrane and solid phase extraction

    Science.gov (United States)

    Msagati, Titus A. M.; Mamba, Bhekie B.

    The aim of this work was to develop a method for the determination of N-methyl carbamates in water involving hollow fibre supported liquid membrane (HFSLM) and solid phase extraction (SPE) as sample preparation methods. Four N-methyl carbamate pesticides, aldicarb, carbaryl, carbofuran and methiocarb sulfoxide, were simultaneously extracted and analysed by a liquid chromatograph with a diode array detector (LC-UV/DAD) and a liquid chromatograph coupled to a ion trap quadrupole mass spectrometer (LC-ESI-MS). The high performance liquid chromatography (HPLC) separation of carabamate extracts was performed on a C18 column with water-acetonitrile as the mobile phase. The mass spectrometry analyses were carried out in the positive mode, operating under both the selected ion monitoring (SIM) and full scan modes. The solid phase recoveries of the extracts ranged between 8% and 98%, with aldicarb having the highest recoveries, followed by carbaryl, carbofuran and methiocarb had the lowest recovery. The HFSLM recovery ranged between 8% and 58% and the order of recovery was similar to the SPE trend. Factors controlling the efficiency of the HFSLM extraction such as sample pH, stripping phase pH, enrichment time, stirring speed as well as organic solvent used for entrapment of analytes, were optimised to achieve the highest enrichment factors.

  20. Efficient hydrogenation of organic carbonates, carbamates and formates indicates alternative routes to methanol based on CO2 and CO

    Science.gov (United States)

    Balaraman, Ekambaram; Gunanathan, Chidambaram; Zhang, Jing; Shimon, Linda J. W.; Milstein, David

    2011-08-01

    Catalytic hydrogenation of organic carbonates, carbamates and formates is of significant interest both conceptually and practically, because these compounds can be produced from CO2 and CO, and their mild hydrogenation can provide alternative, mild approaches to the indirect hydrogenation of CO2 and CO to methanol, an important fuel and synthetic building block. Here, we report for the first time catalytic hydrogenation of organic carbonates to alcohols, and carbamates to alcohols and amines. Unprecedented homogeneously catalysed hydrogenation of organic formates to methanol has also been accomplished. The reactions are efficiently catalysed by dearomatized PNN Ru(II) pincer complexes derived from pyridine- and bipyridine-based tridentate ligands. These atom-economical reactions proceed under neutral, homogeneous conditions, at mild temperatures and under mild hydrogen pressures, and can operate in the absence of solvent with no generation of waste, representing the ultimate ‘green’ reactions. A possible mechanism involves metal-ligand cooperation by aromatization-dearomatization of the heteroaromatic pincer core.

  1. Determination of Carbamate and Organophosphorus Pesticides in Vegetable Samples and the Efficiency of Gamma-Radiation in Their Removal

    Directory of Open Access Journals (Sweden)

    Muhammed Alamgir Zaman Chowdhury

    2014-01-01

    Full Text Available In the present study, the residual pesticide levels were determined in eggplants (Solanum melongena (n=16, purchased from four different markets in Dhaka, Bangladesh. The carbamate and organophosphorus pesticide residual levels were determined by high performance liquid chromatography (HPLC, and the efficiency of gamma radiation on pesticide removal in three different types of vegetables was also studied. Many (50% of the samples contained pesticides, and three samples had residual levels above the maximum residue levels determined by the World Health Organisation. Three carbamates (carbaryl, carbofuran, and pirimicarb and six organophosphates (phenthoate, diazinon, parathion, dimethoate, phosphamidon, and pirimiphos-methyl were detected in eggplant samples; the highest carbofuran level detected was 1.86 mg/kg, while phenthoate was detected at 0.311 mg/kg. Gamma radiation decreased pesticide levels proportionately with increasing radiation doses. Diazinon, chlorpyrifos, and phosphamidon were reduced by 40–48%, 35–43%, and 30–45%, respectively, when a radiation strength of 0.5 kGy was utilized. However, when the radiation dose was increased to 1.0 kGy, the levels of the pesticides were reduced to 85–90%, 80–91%, and 90–95%, respectively. In summary, our study revealed that pesticide residues are present at high amounts in vegetable samples and that gamma radiation at 1.0 kGy can remove 80–95% of some pesticides.

  2. Equilibrium Dynamics of β-N-Methylamino-L-Alanine (BMAA) and Its Carbamate Adducts at Physiological Conditions

    Science.gov (United States)

    Zimmerman, David; Goto, Joy J.; Krishnan, Viswanathan V

    2016-01-01

    Elevated incidences of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia complex (ALS/PDC) is associated with β-methylamino-L-alanine (BMAA), a non-protein amino acid. In particular, the native Chamorro people living in the island of Guam were exposed to BMAA by consuming a diet based on the cycad seeds. Carbamylated forms of BMAA are glutamate analogues. The mechanism of neurotoxicity of the BMAA is not completely understood, and BMAA acting as a glutamate receptor agonist may lead to excitotoxicity that interferes with glutamate transport systems. Though the interaction of BMAA with bicarbonate is known to produce carbamate adducts, here we demonstrate that BMAA and its primary and secondary adducts coexist in solution and undergoes a chemical exchange among them. Furthermore, we determined the rates of formation/cleavage of the carbamate adducts under equilibrium conditions using two-dimensional proton exchange NMR spectroscopy (EXSY). The coexistence of the multiple forms of BMAA at physiological conditions adds to the complexity of the mechanisms by which BMAA functions as a neurotoxin. PMID:27513925

  3. Pattern of acute food, drug, and chemical poisoning in Sari City, Northern Iran.

    Science.gov (United States)

    Ahmadi, Amirhossein; Pakravan, Nasrin; Ghazizadeh, Zeynab

    2010-09-01

    This descriptive and retrospective study was conducted at the poisoning ward of Imam teaching hospital, Sari, Iran, with the aim of evaluating the pattern of poisoning. Hence, the medical profiles of 2057 patients, who were admitted, were carefully reviewed during the period from April 2006 to March 2008 for 2 years. During this period, 2057 cases, 53.9% female and 46.1% male, were admitted with the indication of acute poisoning. The greatest proportion of poisoning occurred between the ages of 18 and 29 years, with suicidal intentions. Most cases of poisoning were intentional (85%). The most common agents involved in acute poisoning were drugs (77.7%), especially sedatives/hypnotics such as benzodiazepines, followed by opioid analgesics. Organophosphate and carbamate insecticides were the third major agent that induced poisoning. Twenty-seven patients (1.3%) who were mostly females and young adults died. Death mostly occurred due to organophosphate and carbamate insecticides (19 cases) poisoning, followed by sedatives/hypnotics like benzodiazepines (3 cases). High prevalence of intentional overdose and mortality among young adults requires considerable attention and further studies to find out the underlying causes. In addition, strict rules must be followed regarding the sale of central nervous system drugs and pesticides, particularly organophosphate and carbamate insecticides. Establishing poison information centers in different parts of the country, preparing national treatment guidelines, training healthcare providers, and ensuring easy availability of the antidotes are also recommended.

  4. Novel carbamates as orally active acetylcholinesterase inhibitors found to improve scopolamine-induced cognition impairment: pharmacophore-based virtual screening, synthesis, and pharmacology.

    Science.gov (United States)

    Chaudhaery, Shailendra S; Roy, Kuldeep K; Shakya, Neeraj; Saxena, Gunjan; Sammi, Shreesh Raj; Nazir, Aamir; Nath, Chandishwar; Saxena, Anil K

    2010-09-09

    A systematic virtual screening (VS) experiment, consisting of the development of 3D-pharmacophore, screening of virtual library, synthesis, and pharmacology, is reported. The predictive pharmacophore model (correlation = 0.955) with one H-bond donor and three hydrophobic features was developed using HypoGen on a training set of 24 carbamates as AChE inhibitors. The model was validated on a test set of 40 carbamates (correlation = 0.844). The pharmacophore-based VS of virtual library led to the identification of novel carbamates as potent AChE inhibitors. The synthesis and pharmacological evaluation of nine carbamates against three diverse assay systems, namely (i) in vitro Ellman method, (ii) in vivo passive avoidance test, and (iii) aldicarb-sensitivity assay, led to the discovery of orally active novel AChE inhibitors which improved scopolamine-induce cognition impairment in Swiss male mice. Finally, two novel lead compounds 85 and 86 are selected as candidate molecules for further optimization.

  5. A Mechanism-based 3D-QSAR Approach for Classification and Prediction of Acetylcholinesterase Inhibitory Potency of Organophosphate and Carbamate Analogs

    Science.gov (United States)

    Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understandi...

  6. Latrunculin A and Its C-17-O-Carbamates Inhibit Prostate Tumor Cell Invasion and HIF-1 Activation in Breast Tumor Cells⊥

    Science.gov (United States)

    El Sayed, Khalid A.; Shallal, Hassan M.; Khanfar, Mohammad A.; Muralidharan, A.; Awate, Bhushan; Youssef, Diaa T.A.; Liu, Yang; Zhou, Yu-Dong; Nagle, Dale G.; Shah, Girish

    2010-01-01

    The marine-derived macrolides latrunculins A (1) and B, from the Red Sea sponge Negombata magnifica, have been found to reversibly bind actin monomers, forming a 1:1 complex with G-actin and disrupting its polymerization. The microfilament protein actin is responsible for several essential functions within the cell such as cytokinesis and cell migration. One of the main binding pharmacophores of 1 to G-actin was identified as the C-17 lactol hydroxyl moiety that binds arginine 210 NH. Latrunculin A-17-O-carbamates 2–6 were prepared by reaction with the corresponding isocyanates. Latrunculin A (1) and carbamates 4–6 displayed potent anti-invasive activity against the human highly metastatic human prostate cancer PC-3M cells in a Matrigel™ assay at a concentration range of 50 nM-1 µM. Latrunculin A (1, 500 nM) decreased the disaggregation and cell migration of PC-3M-CT+ spheroids by three-fold. Carbamates 4 and 5 were two and half and five-fold more active than 1, respectively, in this assay with less actin binding affinity. Latrunculin A (1, IC50 6.7 µM) and its 17-O-[N-(benzyl)carbamate (6, IC50 29 µM) suppress hypoxia-induced HIF-1 activation in T47D breast tumor cells. PMID:18298079

  7. INTERLABORATORY STUDY OF A THERMOSPRAY-LIQUID CHROMATOGRAPHIC/MASS SPECTROMETRIC METHOD FOR SELECTED N-METHYL CARBAMATES, N-METHYL CARBAMOYLOXIMES, AND SUBSTITUTED UREA PESTICIDES

    Science.gov (United States)

    A thermospray-liquid chromatographic/mass spectrometric (TS-LC/MS) method was evaluated in an interlaboratory study for determining 3 N-methyl carbamates (bendiocarb, carbaryl, and carbofuran), 3-N-methyl carbamoyloximes (aldicarb, methomyl, and oxamyl), 2 substituted urea pestic...

  8. A PHYSIOLOGICALLY BASED PHARMACOKINETIC/PHARMACODYNAMIC (PBPK/PD) MODEL FOR ESTIMATION OF CUMULATIVE RISK FROM EXPOSURE TO THREE N-METHYL CARBAMATES: CARBARYL, ALDICARB, AND CARBOFURAN

    Science.gov (United States)

    A physiologically-based pharmacokinetic (PBPK) model for a mixture of N-methyl carbamate pesticides was developed based on single chemical models. The model was used to compare urinary metabolite concentrations to levels from National Health and Nutrition Examination Survey (NHA...

  9. [(18)F]Fluorobenzoyllysinepentanedioic Acid Carbamates: New Scaffolds for Positron Emission Tomography (PET) Imaging of Prostate-Specific Membrane Antigen (PSMA).

    Science.gov (United States)

    Yang, Xing; Mease, Ronnie C; Pullambhatla, Mrudula; Lisok, Ala; Chen, Ying; Foss, Catherine A; Wang, Yuchuan; Shallal, Hassan; Edelman, Hannah; Hoye, Adam T; Attardo, Giorgio; Nimmagadda, Sridhar; Pomper, Martin G

    2016-01-14

    Radiolabeled urea-based low-molecular weight inhibitors of the prostate-specific membrane antigen (PSMA) are under intense investigation as imaging and therapeutic agents for prostate and other cancers. In an effort to provide agents with less nontarget organ uptake than the ureas, we synthesized four (18)F-labeled inhibitors of PSMA based on carbamate scaffolds. 4-Bromo-2-[(18)F]fluorobenzoyllysineoxypentanedioic acid (OPA) carbamate [(18)F]23 and 4-iodo-2-[(18)F]fluorobenzoyllysine OPA carbamate [(18)F]24 in particular exhibited high target-selective uptake in PSMA+ PC3 PIP tumor xenografts, with tumor-to-kidney ratios of >1 by 4 h postinjection, an important benchmark. Because of its high tumor uptake (90% injected dose per gram of tissue at 2 h postinjection) and high tumor-to-organ ratios, [(18)F]23 is promising for clinical translation. Prolonged tumor-specific uptake demonstrated by [(18)F]24, which did not reach equilibrium during the 4 h study period, suggests carbamates as alternative scaffolds for mitigating dose to nontarget tissues.

  10. A small-volume bioassay for quantification of the esterase inhibiting potency of mixtures of organophosphate and carbamate insecticides in rainwater : development and optimization

    NARCIS (Netherlands)

    Hamers, T.; Molin, K.R.J.; Koeman, J.H.; Murk, A.J.

    2000-01-01

    The goal of this study was to develop a sensitive in vitro bioassay for quantification of the total esterase inhibiting potency of low concentrations of organophosphate and carbamate insecticides in relatively small rainwater samples. Purified acetylcholinesterase (AChE) from electric eel

  11. Catalytic aziridination of electron-deficient olefins with an N-chloro-N-sodio carbamate and application of this novel method to asymmetric synthesis.

    Science.gov (United States)

    Minakata, Satoshi; Murakami, Yuta; Tsuruoka, Ryoji; Kitanaka, Shinsuke; Komatsu, Mitsuo

    2008-12-21

    A new method for the aziridination of electron-deficient olefins using an N-chloro-N-sodio carbamate is described; the reaction was promoted by phase-transfer catalysis (solid-liquid) and afforded aziridines from alpha,beta-unsaturated ketones, esters, sulfones and amides.

  12. Transition state-based ST6Gal I inhibitors: Mimicking the phosphodiester linkage with a triazole or carbamate through an enthalpy-entropy compensation.

    Science.gov (United States)

    Montgomery, Andrew P; Skropeta, Danielle; Yu, Haibo

    2017-10-31

    Human β-galactoside α-2,6-sialyltransferase I (ST6Gal I) catalyses the synthesis of sialylated glycoconjugates. Overexpression of ST6Gal I is observed in many cancers, where it promotes metastasis through altered cell surface sialylation. A wide range of sialyltransferase inhibitors have been developed, with analogues structurally similar to the transition state exhibiting the highest inhibitory activity. To improve synthetic accessibility and pharmacokinetics of previously reported inhibitors, the replacement of the charged phosphodiester linker with a potential neutral isostere such as a carbamate or a 1,2,3-triazole has been investigated. Extensive molecular dynamics simulations have demonstrated that compounds with the alternate linkers could maintain key interactions with the human ST6Gal I active site, demonstrating the potential of a carbamate or a 1,2,3-triazole as a phosphodiester isostere. Free energy perturbation calculations provided energetic evidence suggesting that the carbamate and 1,2,3-triazole were slightly more favourable than the phosphodiester. Further exploration with free energy component, quasi-harmonic and cluster analysis suggested that there is an enthalpy-entropy compensation accounting for the replacement of the flexible charged phosphodiester with a neutral and rigid isostere. Overall, these simulations provide a strong rationale for the use of a carbamate or 1,2,3-triazole as a phosphodiester isostere in the development of novel inhibitors of human ST6Gal I.

  13. Is the carbamate juvenoid W-328 an insect growth regulator for the cockroach .I.Blaberus craniifer./I. Br. (Insecta, Dictyoptera)?

    Czech Academy of Sciences Publication Activity Database

    Goudey-Perriere, F.; Lemonnier, F.; Perriere, C.; Dahmani, F. Z.; Wimmer, Zdeněk

    2003-01-01

    Roč. 75, - (2003), s. 47-59 ISSN 0048-3575 Institutional research plan: CEZ:AV0Z4055905 Keywords : Blaberus craniifer * Blattella germanica * carbamate juvenoids Subject RIV: CC - Organic Chemistry Impact factor: 0.768, year: 2003

  14. Distribution and persistence of the anti sea-lice drug teflubenzuron in wild fauna and sediments around a salmon farm, following a standard treatment

    Energy Technology Data Exchange (ETDEWEB)

    Samuelsen, Ole B. [Institute of Marine Research, P.O. Box 1870 Nordnes, N-5817 Bergen (Norway); Lunestad, Bjørn T.; Hannisdal, Rita [National Institute of Nutrition and Seafood Research, P.O. Box 2029 Nordnes, N-5817 Bergen (Norway); Bannister, Raymond; Olsen, Siri [Institute of Marine Research, P.O. Box 1870 Nordnes, N-5817 Bergen (Norway); Tjensvoll, Tore [National Institute of Nutrition and Seafood Research, P.O. Box 2029 Nordnes, N-5817 Bergen (Norway); Farestveit, Eva; Ervik, Arne [Institute of Marine Research, P.O. Box 1870 Nordnes, N-5817 Bergen (Norway)

    2015-03-01

    The salmon louse (Lepeoptheirus salmonis) is a challenge in the farming of Atlantic salmon (Salmo salar). To treat an infestation, different insecticides are used like the orally administered chitin synthetase inhibitor teflubenzuron. The concentrations and distribution of teflubenzuron were measured in water, organic particles, marine sediment and biota caught in the vicinity of a fish farm following a standard medication. Low concentrations were found in water samples whereas the organic waste from the farm, collected by sediment traps had concentrations higher than the medicated feed. Most of the organic waste was distributed to the bottom close to the farm but organic particles containing teflubenzuron were collected 1100 m from the farm. The sediment under the farm consisted of 5 to 10% organic material and therefore the concentration of teflubenzuron was much lower than in the organic waste. Teflubenzuron was persistent in the sediment with a stipulated halflife of 170 days. Sediment consuming polychaetes had high but decreasing concentrations of teflubenzuron throughout the experimental period, reflecting the decrease of teflubenzuron in the sediment. During medication most wild fauna contained teflubenzuron residues and where polychaetes and saith had highest concentrations. Eight months later only polychaetes and some crustaceans contained drug residues. What dosages that induce mortality in various crustaceans following short or long-term exposure is not known but the results indicate that the concentrations in defined individuals of king crab, shrimp, squat lobster and Norway lobster were high enough shortly after medication to induce mortality if moulting was imminent. Considering food safety, saith and the brown meat of crustaceans contained at first sampling concentrations of teflubenzuron higher than the MRL-value set for Atlantic salmon. The concentrations were, however, moderate and the amount of saith fillet or brown meat of crustaceans to be

  15. Evidence of carbamate resistance in urban populations of Anopheles gambiae s.s. mosquitoes resistant to DDT and deltamethrin insecticides in Lagos, South-Western Nigeria

    Directory of Open Access Journals (Sweden)

    Oduola Adedayo O

    2012-06-01

    Full Text Available Abstract Background Resistance monitoring is essential in ensuring the success of insecticide based vector control programmes. This study was carried out to assess the susceptibility status of urban populations of Anopheles gambiae to carbamate insecticide being considered for vector control in mosquito populations previously reported to be resistant to DDT and permethrin. Methods Two – three day old adult female Anopheles mosquitoes reared from larval collections in 11 study sites from Local Government Areas of Lagos were exposed to test papers impregnated with DDT 4%, deltamethrin 0.05% and propoxur 0.1% insecticides. Additional tests were carried out to determine the susceptibility status of the Anopheles gambiae population to bendiocarb insecticide. Members of the A. gambiae complex, the molecular forms, were identified by PCR assays. The involvement of metabolic enzymes in carbamate resistance was assessed using Piperonyl butoxide (PBO synergist assays. The presence of kdr-w/e and ace-1R point mutations responsible for DDT-pyrethroid and carbamate resistance mechanisms was also investigated by PCR. Results Propoxur resistance was found in 10 out of the 11 study sites. Resistance to three classes of insecticides was observed in five urban localities. Mortality rates in mosquitoes exposed to deltamethrin and propoxur did not show any significant difference (P > 0.05 but was significantly higher (P A. gambiae s.s (M form. The kdr -w point mutation at allelic frequencies between 45%-77% was identified as one of the resistant mechanisms responsible for DDT and pyrethroid resistance. Ace-1R point mutation was absent in the carbamate resistant population. However, the possible involvement of metabolic resistance was confirmed by synergistic assays conducted. Conclusion Evidence of carbamate resistance in A. gambiae populations already harbouring resistance to DDT and permethrin is a clear indication that calls for the implementation of

  16. Synthesis, screening for antiacetylcholinesterase activity and binding mode prediction of a new series of [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters

    International Nuclear Information System (INIS)

    Zanatta, Nilo; Marchi, Tiago M.; Bonacorso, Helio G.; Martins, Marcos A.P.; Flores, Alex F.C.; Borchhardt, Deise M.; Andricopulo, Adriano D.; Salum, Livia B.; Carpes, Adriana D.; Schetinger, Maria R.C.

    2008-01-01

    A series of nine new [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters (phosphate-carbamate compounds) was obtained through the reaction of (4,4,4-trifluoro-3-hydroxybut-1-yl)-carbamic acid ethyl esters with phosphorus oxychloride followed by the addition of alcohols. The products were characterized by 1 H, 13 C, 31 P, and 19 F NMR spectroscopy, GC-MS, and elemental analysis. All the synthesized compounds were screened for acetylcholinesterase (AChE) inhibitory activity using the Ellman method. All compounds containing phosphate and carbamate pharmacophores in their structures showed enzyme inhibition, being the compound bearing the diethoxy phosphate group (2b) the most active compound. Molecular modeling studies were performed to investigate the detailed interactions between AChE active site and small-molecule inhibitor candidates, providing valuable structural insights into AChE inhibition. (author)

  17. Different hydrogen-bonded chains in the crystal structures of three alkyl N-[(E-1-(2-benzylidene-1-methylhydrazinyl-3-hydroxy-1-oxopropan-2-yl]carbamates

    Directory of Open Access Journals (Sweden)

    Thais C. M. Noguiera

    2015-07-01

    Full Text Available The crystal structures of three methylated hydrazine carbamate derivatives prepared by multi-step syntheses from l-serine are presented, namely benzyl N-{(E-1-[2-(4-cyanobenzylidene-1-methylhydrazinyl]-3-hydroxy-1-oxopropan-2-yl}carbamate, C20H20N4O4, tert-butyl N-{(E-1-[2-(4-cyanobenzylidene-1-methylhydrazinyl]-3-hydroxy-1-oxopropan-2-yl}carbamate, C17H22N4O4, and tert-butyl N-[(E-1-(2-benzylidene-1-methylhydrazinyl-3-hydroxy-1-oxopropan-2-yl]carbamate, C16H23N3O4. One of them shows that an unexpected racemization has occurred during the mild-condition methylation reaction. In each crystal structure, the molecules are linked into chains by O—H...O hydrogen bonds, but with significant differences between them.

  18. Different hydrogen-bonded chains in the crystal structures of three alkyl N-[(E)-1-(2-benzyl?idene-1-methyl?hydrazin?yl)-3-hy?droxy-1-oxopropan-2-yl]carbamates

    OpenAIRE

    Noguiera, Thais C. M.; Pinheiro, Alessandra C.; Wardell, James L.; de Souza, Marcus V. N.; Abberley, Jordan P.; Harrison, William T. A.

    2015-01-01

    The crystal structures of three methyl?ated hydrazine carbamate derivatives prepared by multi-step syntheses from l-serine are presented, namely benzyl N-{(E)-1-[2-(4-cyanobenzylidene)-1-methylhydrazinyl]-3-hydroxy-1-oxopro?pan-2-yl}carbamate, C20H20N4O4, tert-butyl N-{(E)-1-[2-(4-cyanobenzylidene)-1-methylhydrazinyl]-3-hydroxy-1-oxopropan-2-yl}carbamate, C17H22N4O4, and tert-butyl N-[(E)-1-(2-benzylidene-1-methylhydrazinyl)-3-hydroxy-1-oxopro?pan-2-yl]carbamate, C16H23N3O4. One of them shows...

  19. Nonracemic, chiral homoenolate reagents derived from (cycloalk-1-enyl)methyl carbamates and evaluation of their configurational stabilities

    DEFF Research Database (Denmark)

    Özlügedik, M.; Kristensen, Jesper Langgaard; Wibbeling, B.

    2002-01-01

    11d, 11e and 11j. These turned out to be valuable reagents for enantioselective homoaldol reaction; er values of up to 96:4 could be achieved. X-ray crystal structure analyses with anomalous diffraction, obtained from the heavy atom containing products 22, 23b, 27d, and 27e derived from (2......Several (cycloalk-1-enyl)methyl N,N-diisopropylcarbamates 11 were synthesised by three different methods and their asymmetric deprotonation by butyllithium/(-)-sparteine was investigated. The ratios of epimeric ion pairs 18·4/epi-18·4 were determined by (stereospecific) trimethylsilylation, forming......-methylcyclopentenyl)methyl and (2-methyl-cyclohexenyl)methyl reagents, established the (1S) configuration of the major lithium compound. Thus, the kinetically controlled deprotonation of the corresponding allyl carbamates removes the (pro-S) proton. Overall, a simple method for the enantioselective synthesis...

  20. Determination of bromoxynil and ioxynil in the presence of carbamates by supported liquid membrane-liquid chromatography in river waters

    Directory of Open Access Journals (Sweden)

    Titus Motswadi Maswabi

    2003-12-01

    Full Text Available Sample pre-treatment and enrichment using the supported liquid membrane (SLM technique for the determination of phenolic nitrile herbicides in presence of carbamates in river water samples was investigated. The uncharged herbicide molecules from the flowing aqueous solution diffuse through an immobilized water-immiscible organic solvent, supported by a porous polytetrafluoroethylene (PTFE membrane, and trapped in a stagnant acidic acceptor phase in an ionic form. Using n-undecane as a membrane solvent, the SLM extraction methodology was successfully used for the enrichment and separation of phenolic nitrile herbicides in environmental waters with extraction efficiencies of 60% or better. A RDS (% of 2.1 and 1.8 was obtained for the extraction of ioxynil and bromoxynil from river water, respectively.

  1. Ethyl carbamate in alcoholic beverages from Mexico (tequila, mezcal, bacanora, sotol) and Guatemala (cuxa): market survey and risk assessment.

    Science.gov (United States)

    Lachenmeier, Dirk W; Kanteres, Fotis; Kuballa, Thomas; López, Mercedes G; Rehm, Jürgen

    2009-01-01

    Ethyl carbamate (EC) is a recognized genotoxic carcinogen, with widespread occurrence in fermented foods and beverages. No data on its occurrence in alcoholic beverages from Mexico or Central America is available. Samples of agave spirits including tequila, mezcal, bacanora and sotol (n=110), and of the sugarcane spirit cuxa (n=16) were purchased in Mexico and Guatemala, respectively, and analyzed for EC. The incidence of EC contamination was higher in Mexico than in Guatemala, however, concentrations were below international guideline levels (<0.15 mg/L). Risk assessment found the Margin of Exposure (MOE) in line with that of European spirits. It is therefore unlikely that EC plays a role in high rates of liver cirrhosis reported in Mexico.

  2. Ethyl Carbamate in Alcoholic Beverages from Mexico (Tequila, Mezcal, Bacanora, Sotol and Guatemala (Cuxa: Market Survey and Risk Assessment

    Directory of Open Access Journals (Sweden)

    Jürgen Rehm

    2009-01-01

    Full Text Available Ethyl carbamate (EC is a recognized genotoxic carcinogen, with widespread occurrence in fermented foods and beverages. No data on its occurrence in alcoholic beverages from Mexico or Central America is available. Samples of agave spirits including tequila, mezcal, bacanora and sotol (n=110, and of the sugarcane spirit cuxa (n=16 were purchased in Mexico and Guatemala, respectively, and analyzed for EC. The incidence of EC contamination was higher in Mexico than in Guatemala, however, concentrations were below international guideline levels (<0.15 mg/L. Risk assessment found the Margin of Exposure (MOE in line with that of European spirits. It is therefore unlikely that EC plays a role in high rates of liver cirrhosis reported in Mexico.

  3. (NHC)Cu-Catalyzed Mild C-H Amidation of (Hetero)arenes with Deprotectable Carbamates: Scope and Mechanistic Studies.

    Science.gov (United States)

    Xie, Weilong; Yoon, Jung Hee; Chang, Sukbok

    2016-09-28

    Primary arylamines are an important unit broadly found in synthetic, biological, and materials science. Herein we describe the development of a (NHC)Cu system that mediates a direct C-H amidation of (hetero)arenes by using N-chlorocarbamates or their sodio derivatives as the practical amino sources. A facile stoichiometric reaction of reactive copper-aryl intermediates with the amidating reagent led us to isolate key copper arylcarbamate species with the formation of a C-N bond. The use of (t)BuONa base made this transformation catalytic under mild conditions. The present (NHC)Cu-catalyzed C-H amidation works efficiently and selectively on a large scale over a range of arenes including polyfluorobenzenes, azoles, and quinoline N-oxides. Deprotection of the newly installed carbamate groups such as Boc and Cbz was readily performed to afford the corresponding primary arylamines.

  4. Chiral separation on sulfonated cellulose tris(3,5-dimethylphenyl carbamate)-coated zirconia monolith by capillary electro chromatography

    International Nuclear Information System (INIS)

    Lee, Jeongmi; Park, Jung Hag; Jang, Myung Duk

    2012-01-01

    Sulfonated cellulose tris(3,5-dimethylphenyl carbamate) (SCDMPC)-coated zirconia monolith (ZM) was used as the chiral stationary phase in capillary electro chromatography for separation of enantiomers of ten chiral compounds in acetonitrile (ACN)-phosphate buffer mixtures as the eluent. Influences of the ACN content, buffer concentration and pH on chiral separation have been investigated. Separation data on SCDMPC-ZM have been compared with those on CDMPC-ZM. Resolution factors were better on SCDMPC-ZM than CDMPC-ZM while retention factors were in general shorter on the former than the latter. Best chiral resolutions on SCDMPC-ZM were obtained with the eluent of 50% ACN containing 50 mM phosphate at pH around 4

  5. Drug Facts

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    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  6. The Mancozeb-containing carbamate fungicide tattoo induces mild oxidative stress in goldfish brain, liver, and kidney.

    Science.gov (United States)

    Atamaniuk, Tetiana M; Kubrak, Olga I; Husak, Viktor V; Storey, Kenneth B; Lushchak, Volodymyr I

    2014-11-01

    Tattoo belongs to the group of carbamate fungicides and contains Mancozeb (ethylene(bis)dithiocarbamate) as its main constituent. The toxicity of Mancozeb to living organisms, particularly fish, is not resolved. This work investigated the effects of 96 h of exposure to 3, 5, or 10 mg L(-1) of Tattoo (corresponding to 0.9, 1.5, or 3 mg L(-1) of Mancozeb) on the levels of oxidative stress markers and the antioxidant enzyme system of brain, liver, and kidney of goldfish, Carassius auratus). In liver, Tattoo exposure resulted in increased activities of superoxide dismutase (SOD) by 70%-79%, catalase by 23%-52% and glutathione peroxidase (GPx) by 49%. The content of protein carbonyls (CP) in liver was also enhanced by 92%-125% indicating extensive damage to proteins. Similar increases in CP levels (by 98%-111%) accompanied by reduced glucose-6-phosphate dehydrogenase activity (by 13%-15%) was observed in kidney of fish exposed to Tattoo; however, SOD activity increased by 37% in this tissue after treatment with 10 mg L(-1) Tattoo. In brain, a rise in lipid peroxide level (by 29%) took place after exposure to 10 mg L(-1) Tattoo and was accompanied by elevation of high-molecular mass thiols (by 14%). Tattoo exposure also resulted in a concentration-dependent decrease in glutathione reductase activity (by 26%-37%) in brain. The data collectively show that exposure of goldfish to 3-10 mg L(-1) of the carbamate fungicide Tattoo resulted in the development of mild oxidative stress and activation of antioxidant defense systems in goldfish tissues. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

  7. Probabilistic acute risk assessment of cumulative exposure to organophosphorus and carbamate pesticides from dietary vegetables and fruits in Shanghai populations.

    Science.gov (United States)

    Li, Fan; Yuan, Yaqun; Meng, Pai; Wu, Min; Li, Shuguang; Chen, Bo

    2017-05-01

    Organophosphorus pesticides (OPs) and carbamate pesticides (CPs) are among the most widely used pesticides in China, playing a major role in protecting agricultural commodities. In this study, we determined the cumulative acute exposure to OPs and CPs of Shanghai residents from vegetables and fruits (VFs). The food consumption data were obtained from the Shanghai Food Consumption Survey (SHFCS) of 2012-14 including a total of 1973 participants aged 2-90 years. The pesticide residue data were obtained from the Shanghai monitoring programme during 2008-11 with 34 organophosphates and 11 carbamates analysed in a total of 5335 samples of VFs. A probabilistic approach was performed as recommended by the EFSA, using the optimistic model with non-detects set as zero and with processing factors (PFs) being used and the pessimistic model with non-detects replaced by limit of detection (LOD) and without PFs. We used the relative potency factor (RPF) method to normalise the various pesticides to the index compound (IC) of methamidophos and chlorpyrifos separately. Only in the pessimistic model using methamidophos as the IC was there was small risk of exposure exceeding the ARfD (3 µg kg - 1 bw day - 1 ) in the populations of preschool children (0.029%), school-age children (0.022%) and adults (0.002%). There were no risk of exposure exceeding the ARfD of methamidophos in the optimistic model and of chlorpyrifos (100 µg kg - 1 bw day - 1 ) in both optimistic and pessimistic models in all three populations. Considering the Chinese habits of overwhelmingly eating processed food (vegetables being cooked, and fruits being washed or peeled), we conclude that little acute risk was found for the exposure to VF-sourced OPs and CPs in Shanghai.

  8. Indoor Use of Plastic Sheeting Impregnated with Carbamate Combined with Long-Lasting Insecticidal Mosquito Nets for the Control of Pyrethroid-Resistant Malaria Vectors

    Science.gov (United States)

    Djènontin, Armel; Chandre, Fabrice; Dabiré, K. Roch; Chabi, Joseph; N'Guessan, Raphael; Baldet, Thierry; Akogbéto, Martin; Corbel, Vincent

    2010-01-01

    The combined efficacy of a long-lasting insecticidal net (LLIN) and a carbamate-treated plastic sheeting (CTPS) or indoor residual spraying (IRS) for control of insecticide-resistant mosquitoes was evaluated in experimental huts in Burkina Faso. Anopheles gambiae from the area is resistant to pyrethroids and to a lesser extent, carbamates. Relatively low mortality rates were observed with the LLIN (44%), IRS (42%), and CTPS (52%), whereas both combinations killed significantly more mosquitoes (~70% for LLIN + CTPS and LLIN + IRS). Blood feeding by An. gambiae was uninhibited by IRS and CTPS compared with LLIN (43%), LLIN + CTPS (58%), and LLIN + IRS (56%). No evidence for selection of the kdr and ace-1R alleles was observed with the combinations, whereas a survival advantage of mosquitoes bearing the ace-1R mutation was observed with IRS and CTPS. The results suggest that the combination of the two interventions constitutes a potential tool for vector-resistance management. PMID:20682865

  9. Drug Facts

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  11. Drug Facts

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    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  12. Design and Synthesis of 4-Alkylidene-β-lactams: Benzyl- and Phenethyl-carbamates as Key Fragments to Switch on Antibacterial Activity.

    Science.gov (United States)

    Giacomini, Daria; Martelli, Giulia; Piccichè, Miriam; Calaresu, Enrico; Cocuzza, Clementina Elvezia; Musumeci, Rosario

    2017-09-21

    The emergence of multidrug-resistant bacterial strains is particularly important in chronic pathologies such as cystic fibrosis (CF), in which persistent colonization and selection of resistant strains is favored by the frequent and repeated use of antibacterial agents. Staphylococcus aureus is a common pathogen in CF patients that has an associated increased multidrug resistance. In previous studies we demonstrated that the presence of a 4-alkylidene side chain directly linked to a β-lactam appeared to strengthen the potency against S. aureus, especially against methicillin-resistant S. aureus (MRSA) strains. In the present study, 21 new 4-alkylidene-β-lactams were synthesized and evaluated for antibacterial activity. We designed the new compounds to have aryl, benzyl, or phenethyl-carbamate groups on the C3 hydroxyethyl side chain. We found a correlation between biological activity and the nitrogen substituent of the carbamate group, and two phenethyl-carbamate β-lactams were shown to be valuable antibacterial agents against selected linezolid-resistant strains, with a minimum inhibitory concentrations of 2-4 mg L -1 . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Evidence of carbamate resistance in urban populations of Anopheles gambiae s.s. mosquitoes resistant to DDT and deltamethrin insecticides in Lagos, South-Western Nigeria

    Science.gov (United States)

    2012-01-01

    Background Resistance monitoring is essential in ensuring the success of insecticide based vector control programmes. This study was carried out to assess the susceptibility status of urban populations of Anopheles gambiae to carbamate insecticide being considered for vector control in mosquito populations previously reported to be resistant to DDT and permethrin. Methods Two – three day old adult female Anopheles mosquitoes reared from larval collections in 11 study sites from Local Government Areas of Lagos were exposed to test papers impregnated with DDT 4%, deltamethrin 0.05% and propoxur 0.1% insecticides. Additional tests were carried out to determine the susceptibility status of the Anopheles gambiae population to bendiocarb insecticide. Members of the A. gambiae complex, the molecular forms, were identified by PCR assays. The involvement of metabolic enzymes in carbamate resistance was assessed using Piperonyl butoxide (PBO) synergist assays. The presence of kdr-w/e and ace-1R point mutations responsible for DDT-pyrethroid and carbamate resistance mechanisms was also investigated by PCR. Results Propoxur resistance was found in 10 out of the 11 study sites. Resistance to three classes of insecticides was observed in five urban localities. Mortality rates in mosquitoes exposed to deltamethrin and propoxur did not show any significant difference (P > 0.05) but was significantly higher (P insecticide resistance management strategies to combat the multiple resistance identified. PMID:22686575

  14. Wild Raspberry Subjected to Simulated Gastrointestinal Digestion Improves the Protective Capacity against Ethyl Carbamate-Induced Oxidative Damage in Caco-2 Cells.

    Science.gov (United States)

    Chen, Wei; Xu, Yang; Zhang, Lingxia; Li, Ya; Zheng, Xiaodong

    2016-01-01

    Ethyl carbamate (EC), a probable human carcinogen, occurs widely in many fermented foods. Previous studies indicated that EC-induced cytotoxicity was associated with oxidative stress. Wild raspberries are rich in polyphenolic compounds, which possess potent antioxidant activity. This study was conducted to investigate the protective effect of wild raspberry extracts produced before (RE) and after in vitro simulated gastrointestinal digestion (RD) on EC-induced oxidative damage in Caco-2 cells. Our primary data showed that ethyl carbamate could result in cytotoxicity and genotoxicity in Caco-2 cells and raspberry extract after digestion (RD) may be more effective than that before digestion (RE) in attenuating toxicity caused by ethyl carbamate. Further investigation by fluorescence microscope revealed that RD may significantly ameliorate EC-induced oxidative damage by scavenging the overproduction of intracellular reactive oxygen species (ROS), maintaining mitochondrial function and preventing glutathione (GSH) depletion. In addition, HPLC-ESI-MS results showed that the contents of identified polyphenolic compounds (esculin, kaempferol O-hexoside, and pelargonidin O-hexoside) were remarkably increased after digestion, which might be related to the better protective effect of RD. Overall, our results demonstrated that raspberry extract undergoing simulated gastrointestinal digestion may improve the protective effect against EC-induced oxidative damage in Caco-2 cells.

  15. Determination of carbamates in edible vegetable oils by ultra-high performance liquid chromatography-tandem mass spectrometry using a new clean-up based on zirconia for QuEChERS methodology.

    Science.gov (United States)

    Moreno-González, David; Huertas-Pérez, José F; García-Campaña, Ana M; Gámiz-Gracia, Laura

    2014-10-01

    In this study a fast, selective and sensitive multiresidue method based on QuEChERS methodology has been evaluated and validated for the determination of carbamate pesticides, in edible vegetable oils by UHPLC-MS/MS. A new clean-up sorbent, Supel(TM) QuE Z-Sep(+), has been successfully applied in vegetable oil extracts. Z-Sep(+) was compared with other sorbents (i.e. mixture of C18 and PSA) previously used for dispersive solid phase extraction of these matrices, reducing more effectively matrix effects without a significant decrease of analyte recoveries. Matrix effect was studied in different matrices (extra-virgin olive, sunflower, maize, linseed and sesame oil) being ≤│30│% for most of the studied pesticides. Under optimum conditions, recoveries ranged from 74% to 101%, with relative standard deviations lower than 10%. Limits of quantification ranged from 0.09 to 2.0 µg kg(-1), allowing their determination at the low concentration levels demanding by current legislation. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. The impact of a brief motivational intervention on unprotected sex and sex while high among drug-positive emergency department patients who receive STI/HIV VC/T and drug treatment referral as standard of care.

    Science.gov (United States)

    Bernstein, Edward; Ashong, Desiree; Heeren, Timothy; Winter, Michael; Bliss, Caleb; Madico, Guillermo; Bernstein, Judith

    2012-07-01

    This randomized, controlled trial, conducted among out-of-treatment heroin/cocaine users at an emergency department visit, tests the impact on sexual risk of adding brief motivational intervention (B-MI) to point-of-service testing, counseling and drug treatment referral. 1,030 enrollees aged 18-54 received either voluntary counseling/testing (VC/T) with drug treatment referral, or VC/T, referral, and B-MI, delivered by an outreach worker. We measured number and proportion of non-protected sex acts (last 30 days) at 6 and 12 months (n = 802). At baseline, 70% of past-30-days sex acts were non-protected; 35% of sex acts occurred while high; 64% of sexual acts involved main, 24% casual and 12% transactional sex partners; 1.7% tested positive for an STI, and 8.8% for HIV. At six or 12 month follow-up, 20 enrollees tested positive for Chlamydia and/or Gonorrhea, and 6 enrollees HIV sero-converted. Self-reported high-risk behaviors declined in both groups with no significant between-group differences in behaviors or STI/HIV incidence.

  17. Drug Addiction

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    ... attempt to stop taking the drug Recognizing unhealthy drug use in family members Sometimes it's difficult to ... sold to support drug use Recognizing signs of drug use or intoxication Signs and symptoms of drug ...

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    ... Seizure Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days ... reaction the first time you take the drug. Drugs commonly linked to allergies Although any drug can ...

  19. Different responses of biochemical markers in frogs (Rana ridibunda) from urban and rural wetlands to the effect of carbamate fungicide.

    Science.gov (United States)

    Falfushinska, Halina I; Romanchuk, Liliya D; Stolyar, Oksana B

    2008-09-01

    Laboratory studies were conducted to determine the effects of carbamate fungicide TATTU (mixture of propamocarb and mancozeb, 0.091 mg L(-1)) on biochemical markers of exposure in Rana ridibunda from clean (reference) and polluted sites. The untreated animals from the polluted site had lower Cu,Zn- and Mn-superoxide dismutase (SOD) and acetylcholinesterase activity, the levels of lipid peroxidation products (TBARS) and protein carbonyls in the liver and vitellogenin-like proteins (Vtg-LP) in the serum, but higher levels of glutathione in the liver in comparison with untreated frogs from the reference site. Catalase activity, superoxide anion and metallothionein levels were the same in both groups. The animals from two sites demonstrate different response on the effect of TATTU during 14 days. In the frogs from polluted site the oxidative damage (the decrease of Mn-SOD activity, lipids and protein oxidative destruction), neurotoxicity (depletion of acetylcholinesterase activity), and endocrine disruption (increase of Vtg-LP level) were revealed. On the other hand, the part of the indices in the animals from the reference site was unchanged after the treatment and the level of metallothionein was elevated demonstrating the satisfactory ability for the adaptation to unfavourable conditions.

  20. The Stepwise Behavioral Responses: Behavioral Adjustment of the Chinese Rare Minnow (Gobiocypris rarus in the Exposure of Carbamate Pesticides

    Directory of Open Access Journals (Sweden)

    Zongming Ren

    2013-01-01

    Full Text Available In order to illustrate the behavioral regulation in environmental stress, the behavioral responses of the Chinese rare minnow (Gobiocypris rarus to arprocarb, carbofuran, and oxamyl were analyzed with an online monitoring system. The Self-Organizing Map (SOM was used to define the patterns of the behavioral data obtained from treatments at concentrations of 0.1 toxic unit (TU, 1 TU, 2 TU, 5 TU, 10 TU, and 20 TU and a control. In certain cases, differences among the carbamate pesticides (CPs tested were observed. The profiles of behavioral strength (BS in SOM varied according to the concentration used. The time of the first significant decrease of the BS varied inversely with the CP concentrations. The results suggested that the behavioral regulation in the stepwise behavioral responses (SBR was evident. The primary movement behaviors shown by the SBR model included no effect, stimulation, acclimation, adjustment (readjustment, and toxic effect, especially at the lower concentrations. However, higher stress (10 TU and 20 TU might limit the function of the behavioral adjustment produced by the intrinsic response mechanisms. It was concluded that SBR, which were affected by both the concentration and the exposure time, could be used as a suitable indicator in the ecotoxicological risk assessment of CPs.

  1. Use of an ionic liquid-based surfactant as pseudostationary phase in the analysis of carbamates by micellar electrokinetic chromatography.

    Science.gov (United States)

    Tejada-Casado, Carmen; Moreno-González, David; García-Campaña, Ana M; del Olmo-Iruela, Monsalud

    2015-03-01

    The applicability of an ionic liquid-based cationic surfactant 1-dodecyl-3-methyl-imidazolium tetrafluoroborate (C12 MImBF4 ) as pseudostationary phase in MEKC has been evaluated for the analysis of 11 carbamate pesticides (promecarb, carbofuran, metolcarb, fenobucarb, aldicarb, propoxur, asulam, benomyl, carbendazim, ethiofencarb, isoprocarb) in juice samples. Under optimum conditions (separation buffer, 35 mM NaHCO3 and 20 mM C12 MImBF4 , pH 9.0; capillary temperature 25°C; voltage -22 kV) the analysis was carried out in less than 12 min, using hydrodynamic injection (50 mbar for 7.5 s) and detection at 200 nm. For the extraction of these CRBs from juice samples, a dispersive liquid-liquid microextraction (DLLME) procedure has been proposed, by optimization of variables affecting the efficiency of the extraction. Following this treatment, sample throughput was approximately 12 samples per hour, obtaining a preconcentration factor of 20. Matrix-matched calibration curves were established using tomato juice as representative matrix (from 5 to 250 μg/L for CBZ, BY, PX, CF, FEN, ETH, ISP, and 25-250 μg/L for ASL, ALD, PRC, MTL), obtaining quantification limits ranging from 1 to 18 μg/L and recoveries from 70 to 96%, with RSDs lower than 9%. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Radiosynthesis and Evaluation of [11C-Carbonyl]-Labeled Carbamates as Fatty Acid Amide Hydrolase Radiotracers for Positron Emission Tomography

    Science.gov (United States)

    2012-01-01

    Fatty acid amide hydrolase (FAAH) plays a key role in regulating the tone of the endocannabinoid system. Radiotracers are required to image and quantify FAAH activity in vivo. We have synthesized a series of potent FAAH inhibitors encompassing two classes of N-alkyl-O-arylcarbamates and radiolabeled eight of them with carbon-11. The [11C-carbonyl]-radiotracers were evaluated in vitro and ex vivo in rats as potential FAAH imaging agents for positron emission tomography (PET). Both sets of [11C]O-arylcarbamates showed good to excellent brain penetration and an appropriate regional distribution. Pretreatments with a FAAH inhibitor demonstrated that 80–95% of brain uptake of radioactivity constituted binding of the radiotracers to FAAH. Brain extraction measurements showed that binding to FAAH was irreversible and kinetically different for the two classes of carbamates. These promising results are discussed in terms of the requirements of a suitable radiotracer for the in vivo imaging of FAAH using PET. PMID:23214511

  3. The effect of mixtures of organophosphate and carbamate pesticides on acetylcholinesterase and application of chemometrics to identify pesticides in mixtures.

    Science.gov (United States)

    Mwila, K; Burton, M H; Van Dyk, J S; Pletschke, B I

    2013-03-01

    Organophosphate (OP) and carbamate (CP) pesticides act by the inhibition of acetylcholinesterase (AChE). This enables the use of this enzyme for the detection of these pesticides in the environment. While many studies have looked at the effect of single pesticides on AChE, the effect of mixtures of pesticides still requires extensive investigation. This is important to evaluate the cumulative risk in the case of simultaneous exposure to multiple pesticides. Therefore we examined the effect of five different pesticides (carbaryl, carbofuran, parathion, demeton-S-methyl, and aldicarb) on AChE activity to determine whether combinations had an additive, synergistic, or antagonistic inhibitory effect. Results indicated that the mixtures had an additive inhibitory effect on AChE activity. The data from the assays of the mixtures were used to develop and train an artificial neural network (ANN) which was then utilised successfully for the identification of pesticides and their concentrations in mixtures. This study is significant because it evaluated mixtures of OPs and CPs where previous studies focused on either OPs or CPs. Previous studies have only examined up to three pesticides while this study evaluated mixtures of five pesticides simultaneously. This is also the first study where an ANN was able to utilise data from the inhibition of a single enzyme to differentiate five different pesticides and their concentrations from mixtures.

  4. Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review.

    Science.gov (United States)

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2011-09-01

    Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963-2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.

  5. Ethyl carbamate in cachaça (Brazilian sugarcane spirit): Extended survey confirms simple mitigation approaches in pot still distillation.

    Science.gov (United States)

    Nóbrega, Ian C C; Pereira, José A P; Paiva, José E; Lachenmeier, Dirk W

    2011-08-01

    In 2009, we reported an association between low levels of ethyl carbamate (EC) in pot still cachaças from Paraíba State, Brazil, and distillation in copper pot stills equipped with cooled columns. To strengthen these observations, we extended our study to Pernambuco State and assessed 13 pot still and 20 column still cachaça brands. An EC range from <40 to 532μg/l was found; 18 brands exceeded the Brazilian limit (150μg/l), 89% of which were column still types. Mean EC concentration of pot still cachaças was very low (64μg/l), and was well below the Paraíba study (220μg/l). An on-site investigation of pot still distilleries associated with <40μg/l brands showed a connection to differences in the distillation apparatus. Maximising distillation reflux ratios in the ascending parts and minimising exposure to copper in the descending parts (through the use of stainless steel) can reduce EC, and also avoid copper contamination. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Drug: D09520 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09520 Crude ... Drug Soft shell turtle carapace (non-JP); Amyda carapace; Amydae ... ... Trionychidae Amyda japonica, Amyda sinensis carapace; Standards for non-pharmacopoeial crude drugs ... PubChem: 96026200 ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely ... So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug ...

  8. Prevention of Malaria Resurgence in Greece through the Association of Mass Drug Administration (MDA) to Immigrants from Malaria-Endemic Regions and Standard Control Measures

    Science.gov (United States)

    Tseroni, Maria; Baka, Agoritsa; Kapizioni, Christina; Snounou, Georges; Tsiodras, Sotirios; Charvalakou, Maria; Georgitsou, Maria; Panoutsakou, Maria; Psinaki, Ioanna; Tsoromokou, Maria; Karakitsos, George; Pervanidou, Danai; Vakali, Annita; Mouchtouri, Varvara; Georgakopoulou, Theano; Mamuris, Zissis; Papadopoulos, Nikos; Koliopoulos, George; Badieritakis, Evangelos; Diamantopoulos, Vasilis; Tsakris, Athanasios; Kremastinou, Jenny; Hadjichristodoulou, Christos

    2015-01-01

    Greece was declared malaria-free in 1974 after a long antimalarial fight. In 2011–2012, an outbreak of P. vivax malaria was reported in Evrotas, an agricultural area in Southern Greece, where a large number of immigrants from endemic countries live and work. A total of 46 locally acquired and 38 imported malaria cases were detected. Despite a significant decrease of the number of malaria cases in 2012, a mass drug administration (MDA) program was considered as an additional measure to prevent reestablishment of the disease in the area. During 2013 and 2014, a combination of 3-day chloroquine and 14-day primaquine treatment was administered under direct observation to immigrants living in the epicenter of the 2011 outbreak in Evrotas. Adverse events were managed and recorded on a daily basis. The control measures implemented since 2011 continued during the period of 2013–2014 as a part of a national integrated malaria control program that included active case detection (ACD), vector control measures and community education. The MDA program was started prior to the transmission periods (from May to December). One thousand ninety four (1094) immigrants successfully completed the treatment, corresponding to 87.3% coverage of the target population. A total of 688 adverse events were recorded in 397 (36.2%, 95% C.I.: 33.4–39.1) persons, the vast majority minor, predominantly dizziness and headache for chloroquine (284 events) and abdominal pain (85 events) for primaquine. A single case of primaquine-induced hemolysis was recorded in a person whose initial G6PD test proved incorrect. No malaria cases were recorded in Evrotas, Laconia, in 2013 and 2014, though three locally acquired malaria cases were recorded in other regions of Greece in 2013. Preventive antimalarial MDA to a high-risk population in a low transmission setting appears to have synergized with the usual antimalarial activities to achieve malaria elimination. This study suggests that judicious use of

  9. Prevention of Malaria Resurgence in Greece through the Association of Mass Drug Administration (MDA) to Immigrants from Malaria-Endemic Regions and Standard Control Measures.

    Science.gov (United States)

    Tseroni, Maria; Baka, Agoritsa; Kapizioni, Christina; Snounou, Georges; Tsiodras, Sotirios; Charvalakou, Maria; Georgitsou, Maria; Panoutsakou, Maria; Psinaki, Ioanna; Tsoromokou, Maria; Karakitsos, George; Pervanidou, Danai; Vakali, Annita; Mouchtouri, Varvara; Georgakopoulou, Theano; Mamuris, Zissis; Papadopoulos, Nikos; Koliopoulos, George; Badieritakis, Evangelos; Diamantopoulos, Vasilis; Tsakris, Athanasios; Kremastinou, Jenny; Hadjichristodoulou, Christos

    2015-11-01

    Greece was declared malaria-free in 1974 after a long antimalarial fight. In 2011-2012, an outbreak of P. vivax malaria was reported in Evrotas, an agricultural area in Southern Greece, where a large number of immigrants from endemic countries live and work. A total of 46 locally acquired and 38 imported malaria cases were detected. Despite a significant decrease of the number of malaria cases in 2012, a mass drug administration (MDA) program was considered as an additional measure to prevent reestablishment of the disease in the area. During 2013 and 2014, a combination of 3-day chloroquine and 14-day primaquine treatment was administered under direct observation to immigrants living in the epicenter of the 2011 outbreak in Evrotas. Adverse events were managed and recorded on a daily basis. The control measures implemented since 2011 continued during the period of 2013-2014 as a part of a national integrated malaria control program that included active case detection (ACD), vector control measures and community education. The MDA program was started prior to the transmission periods (from May to December). One thousand ninety four (1094) immigrants successfully completed the treatment, corresponding to 87.3% coverage of the target population. A total of 688 adverse events were recorded in 397 (36.2%, 95% C.I.: 33.4-39.1) persons, the vast majority minor, predominantly dizziness and headache for chloroquine (284 events) and abdominal pain (85 events) for primaquine. A single case of primaquine-induced hemolysis was recorded in a person whose initial G6PD test proved incorrect. No malaria cases were recorded in Evrotas, Laconia, in 2013 and 2014, though three locally acquired malaria cases were recorded in other regions of Greece in 2013. Preventive antimalarial MDA to a high-risk population in a low transmission setting appears to have synergized with the usual antimalarial activities to achieve malaria elimination. This study suggests that judicious use of MDA can

  10. Evaluation of the analgesic effect of 4-anilidopiperidine scaffold containing ureas and carbamates.

    Science.gov (United States)

    Monti, Ludovica; Stefanucci, Azzurra; Pieretti, Stefano; Marzoli, Francesca; Fidanza, Lorenzo; Mollica, Adriano; Mirzaie, Sako; Carradori, Simone; De Petrocellis, Luciano; Schiano Moriello, Aniello; Benyhe, Sándor; Zádor, Ferenc; Szűcs, Edina; Ötvös, Ferenc; Erdei, Anna I; Samavati, Reza; Dvorácskó, Szabolcs; Tömböly, Csaba; Novellino, Ettore

    2016-12-01

    Fentanyl is a powerful opiate analgesic typically used for the treatment of severe and chronic pain, but its prescription is strongly limited by the well-documented side-effects. Different approaches have been applied to develop strong analgesic drugs with reduced pharmacologic side-effects. One of the most promising is the design of multitarget drugs. In this paper we report the synthesis, characterization and biological evaluation of twelve new 4-anilidopiperidine (fentanyl analogues). In vivo hot-Plate test, shows a moderate antinociceptive activity for compounds OMDM585 and OMDM586, despite the weak binding affinity on both μ and δ-opioid receptors. A strong inverse agonist activity in the GTP-binding assay was revealed suggesting the involvement of alternative systems in the brain. Fatty acid amide hydrolase inhibition was evaluated, together with binding assays of cannabinoid receptors. We can conclude that compounds OMDM585 and 586 are capable to elicit antinociception due to their multitarget activity on different systems involved in pain modulation.

  11. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  12. Drug: D09140 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ... Same as: E00207 Therapeutic category: 5100 ... Caprifoliaceae (honeysuckle family) Lonicera japonica flower bud; Standards for non-pharmacopoeial crude drugs ... PubChem: 96025820 ...

  13. THE INFLUENCE OF BIOFEEDBACK SESSIONS IN CLOSED LOOP OF HEART RATE VARIABILITY AND PACED BREATHING ON SYSTOLIC BLOOD PRESSURE CONTROL DURING STANDARD DRUG THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    S. A. S. Belal

    2015-06-01

    Full Text Available Changes of systolic blood pressure (SBP in biofeedback (BFB sessions with closed loop of paced breathing (PB and heart rate variability (HRV during standard drug therapy of arterial hypertension (AH was studied. 275 patients with 1-3 degree of AH (143 men and 132 women, mean age 58,55 ± 7,99 years was divided into two comparable groups: 1 - BFB (139 patients in investigated PB loop, 2 - control group (136 patients with BFB without PB. In both groups was performed 10 sessions of BFB. Changes of SBP depending on the stage and degree of AH, gender and age was assessed. BP was measured by the method of Korotkov’s with monometer Microlife BP AG1-20 in same conditions. Data were processed by parametric and nonparametric statistics. It is proved that the use of biofeedback in the loop of PB and HRV significantly (p < 0.01 exceeds in efficiency an isolated drug therapy in control of SBP at any stage and degree of AH in patients of both sexes in all age groups. Extent of the effect increases with the stage and degree of the disease and not related to the sex and age of the patient. Findings allow to recommend this technique in clinical practice.

  14. Potassium channel antagonists 4-aminopyridine and the T-butyl carbamate derivative of 4-aminopyridine improve hind limb function in chronically non-ambulatory dogs; a blinded, placebo-controlled trial.

    Science.gov (United States)

    Lim, Ji-Hey; Muguet-Chanoit, Audrey C; Smith, Daniel T; Laber, Eric; Olby, Natasha J

    2014-01-01

    4-Aminopyridine (4-AP) blocks voltage gated potassium channels, restoring conduction to demyelinated axons and improving function in demyelinating conditions, but its use is associated with adverse effects and benefit in spinal cord injury is limited. Derivatives of 4-AP have been developed to improve clinical efficacy while reducing toxicity. We compared the therapeutic effects of orally administered 4-AP and its t-butyl carbamate derivative (t-butyl) with placebo in dogs that had suffered an acute spinal cord injury that left them chronically paralyzed. Nineteen dogs were entered into the trial, conducted in two-week treatment blocks starting with placebo, followed by random assignment to 4-AP or t-butyl, a washout and then the opposite medication followed by placebo. Investigators and owners were blinded to treatment group. Primary outcome measures included open field gait score (OFS), and treadmill based stepping score and regularity index, with additional secondary measures also considered. Thirteen of 19 dogs completed the protocol. Two were euthanized due to unrelated heath problems, two developed side effects and two were unable to complete for unrelated reasons. Dogs showed significant improvement in supported stepping score (from 17.39 to 37.24% with 4-AP; 16.85 to 29.18% with t-butyl pdogs that were able to walk without support with treatment. No significant difference was found between 4-AP and t-butyl. No adverse effects were reported with t-butyl but gastrointestinal upset and seizures were observed in two dogs with 4-AP. In conclusion, both 4-AP and t-butyl significantly improved supported stepping ability in dogs with chronic spinal cord injury with no adverse effects noted with t-butyl. Drug response varied widely between individuals, highlighting the need to understand the factors that influence canine and human patients' response to therapy.

  15. Efficacy of Recommended Pre-Hospital Human Equivalent Doses of Atropine and Pralidoxime against the Toxic Effects of Carbamate Poisoning in the Hartley Guinea Pig

    Science.gov (United States)

    Brittain, Matthew K.; McGarry, Kevin G.; Moyer, Robert A.; Babin, Michael C.; Jett, David A.; Platoff, Gennady E.; Yeung, David T.

    2016-01-01

    Purpose Aldicarb and methomyl are carbamate pesticides commonly implicated in human poisonings. The primary toxic mechanism of action for carbamate poisoning is cholinesterase (ChE) inhibition. As such, it is logical to assume that the currently accepted therapies for organophosphate poisoning [muscarinic antagonist atropine and the oxime acetylcholinesterase reactivator pralidoxime chloride (2-PAM Cl),], could afford therapeutic protection. However, oximes have been shown to be contraindicated for poisoning by some carbamates. Methods A protective ratio study was conducted in guinea pigs to evaluate the efficacy of atropine and 2-PAM Cl. ChE activity was determined in both the blood and cerebral cortex.. Results Co-administration of atropine free base (0.4 mg/kg) and 2-PAM Cl (25.7 mg/kg) demonstrated protective ratios of 2 and 3 against aldicarb and methomyl, respectively, relative to saline. The data reported here show that this protection was primarily mediated by the action of atropine. The reactivator 2-PAM Cl had neither positive nor negative effects on survival. Both blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were significantly reduced at 15 minutes post-challenge but gradually returned to normal within 24 h. Analysis of cerebral cortex showed that BChE, but not AChE, activity was reduced in animals that succumbed prior to 24 h after challenge. Conclusion The results suggest that co-administration of atropine and 2-PAM Cl at the currently recommended human equivalent doses for use in the pre-hospital setting to treat organophosphorus nerve agent and pesticide poisoning would likely also be effective against aldicarb or methomyl poisoning. PMID:27102179

  16. Treatment rationale for dogs poisoned with aldicarb (carbamate pesticide : clinical review

    Directory of Open Access Journals (Sweden)

    L. F. Arnot

    2011-05-01

    Full Text Available The treatment rationale for dogs poisoned by aldicarb is reviewed from a pharmacological perspective. The illegal use of aldicarb to maliciously poison dogs is a major problem in some parts of the world. In South Africa, it is probably the most common canine poisoning treated by companion animal veterinarians. Aldicarb poisoning is an emergency and veterinarians need to be able to diagnose it and start with effective treatment immediately to ensure a reasonable prognosis. Successful treatment depends on the timely use of an anti-muscarinic drug (e.g. atropine. Additional supportive treatment options, including fluid therapy, diphenhydramine, benzodiazepines and the prevention of further absorption (activated charcoal should also be considered. Possible complications after treatment are also briefly discussed.

  17. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  18. Drug Facts

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    Full Text Available ... Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  20. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ... Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use ...

  2. Teaching Old Compounds New Tricks: DDQ-Photocatalyzed C-H Amination of Arenes with Carbamates, Urea, and N-Heterocycles.

    Science.gov (United States)

    Das, Somnath; Natarajan, Palani; König, Burkhard

    2017-12-22

    The C-H amination of benzene derivatives was achieved using DDQ as photocatalyst and BocNH 2 as the amine source under aerobic conditions and visible light irradiation. Electron-deficient and electron-rich benzenes react as substrates with moderate to good product yields. The amine scope of the reaction comprises Boc-amine, carbamates, pyrazoles, sulfonimides and urea. Preliminary mechanistic investigations indicate arene oxidation by the triplet of DDQ to radical cations with different electrophilicity and a charge transfer complex between the amine and DDQ as intermediate of the reaction. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Distribution of ace-1R and resistance to carbamates and organophosphates in Anopheles gambiae s.s. populations from Côte d'Ivoire

    Science.gov (United States)

    2010-01-01

    Background The spread of pyrethroid resistance in Anopheles gambiae s.s. is a critical issue for malaria vector control based on the use of insecticide-treated nets. Carbamates and organophosphates insecticides are regarded as alternatives or supplements to pyrethroids used in nets treatment. It is, therefore, essential to investigate on the susceptibility of pyrethroid resistant populations of An. gambiae s.s. to these alternative products. Methods In September 2004, a cross sectional survey was conducted in six localities in Côte d'Ivoire: Toumbokro, Yamoussoukro, Toumodi in the Southern Guinea savannah, Tiassalé in semi-deciduous forest, then Nieky and Abidjan in evergreen forest area. An. gambiae populations from these localities were previously reported to be highly resistant to pyrethroids insecticides. Anopheline larvae were collected from the field and reared to adults. Resistance/susceptibility to carbamates (0.4% carbosulfan, 0.1% propoxur) and organophosphates (0.4% chlorpyrifos-methyl, 1% fenitrothion) was assessed using WHO bioassay test kits for adult mosquitoes. Then, PCR assays were run to determine the molecular forms (M) and (S), as well as phenotypes for insensitive acetylcholinesterase (AChE1) due to G119S mutation. Results Bioassays showed carbamates (carbosulfan and propoxur) resistance in all tested populations of An. gambiae s.s. In addition, two out of the six tested populations (Toumodi and Tiassalé) were also resistant to organophosphates (mortality rates ranged from 29.5% to 93.3%). The M-form was predominant in tested samples (91.8%). M and S molecular forms were sympatric at two localities but no M/S hybrids were detected. The highest proportion of S-form (7.9% of An. gambiae identified) was in sample from Toumbokro, in the southern Guinea savannah. The G119S mutation was found in both M and S molecular forms with frequency from 30.9 to 35.2%. Conclusion This study revealed a wide distribution of insensitive acetylcholinesterase due

  4. DNA-Directed alkylating agents. 7. Synthesis, DNA interaction, and antitumor activity of bis(hydroxymethyl)- and bis(carbamate)-substituted pyrrolizines and imidazoles.

    Science.gov (United States)

    Atwell, G J; Fan, J Y; Tan, K; Denny, W A

    1998-11-19

    A series of bis(hydroxymethyl)-substituted imidazoles, thioimidazoles, and pyrrolizines and related bis(carbamates), linked to either 9-anilinoacridine (intercalating) or 4-(4-quinolinylamino)benzamide (minor groove binding) carriers, were synthesized and evaluated for sequence-specific DNA alkylation and cytotoxicity. The imidazole and thioimidazole analogues were prepared by initial synthesis of [(4-aminophenyl)alkyl]imidazole-, thioimidazole-, or pyrrolizine dicarboxylates, coupling of these with the desired carrier, and reduction to give the required bis(hydroxymethyl) alkylating moiety. The pyrrolizines were the most reactive alkylators, followed by the thioimidazoles, while the imidazoles were unreactive. The pyrrolizines and some of the thioimidazoles cross-linked DNA, as measured by agarose gel electrophoresis. Strand cleavage assays showed that none of the compounds reacted at purine N7 or N3 sites in the gpt region of the plasmid gpt2Eco, but the polymerase stop assay showed patterns of G-alkylation in C-rich regions. The corresponding thioimidazole bis(carbamates) were more selective than the bis(hydroxymethyl) pyrrolizines, with high-intensity bands at 5'-NCCN, 5'-NGCN and 5'-NCGN sequences in the PCR stopping assay ( indicates block sites). The data suggest that these targeted compounds, like the known thioimidazole bis(carbamate) carmethizole, alkylate exclusively at guanine residues via the 2-amino group, with little or no alkylation at N3 and N7 guanine or adenine sites. The cytotoxicities of the compounds correlated broadly with their reactivities, with the bis(hydroxymethyl)imidazoles being the least cytotoxic (IC50s >1 microM; P388 leukemia) and with the intercalator-linked analogues being more cytotoxic than the corresponding minor-groove-targeted ones. This was true also for the more reactive thioimidazole bis(carbamates) (IC50s 0.8 and 11 microM, respectively), but both were more active than the analogous "untargeted" carmethizole (IC50 20

  5. A Two-Step Procedure for the Overall Transamidation of 8-Aminoquinoline Amides Proceeding via the Intermediate N-Acyl-Boc-Carbamates.

    Science.gov (United States)

    Verho, Oscar; Pourghasemi Lati, Monireh; Oschmann, Michael

    2018-04-03

    Herein a two-step strategy for achieving overall transamidation of 8-aminoquinoline amides has been explored. In this protocol, the 8-aminoquinoline amides were first treated with Boc 2 O and DMAP to form the corresponding N-acyl-Boc-carbamates, which were found to be sufficiently reactive to undergo subsequent aminolysis with different amines in the absence of any additional reagents or catalysts. To demonstrate the utility of this approach, it was applied on a number of 8-aminoquinoline amides from the recent C-H functionalization literature, enabling access to a range of elaborate amide derivatives in good to high yields.

  6. Radiosynthesis and ex vivo evaluation of [11C-carbonyl]carbamate- and urea-based monoacylglycerol lipase inhibitors

    International Nuclear Information System (INIS)

    Hicks, Justin W.; Parkes, Jun; Tong, Junchao; Houle, Sylvain; Vasdev, Neil; Wilson, Alan A.

    2014-01-01

    Introduction: Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are the two primary enzymes that regulate the tone of endocannabinoid signaling. Although new PET radiotracers have been discovered for imaging FAAH in vivo, no such radiotracer exists for imaging MAGL. Here we report the radiosynthesis of five candidate MAGL radiotracers and their ex vivo evaluations in mice and rats. Methods: Candidate carbamate and urea MAGL inhibitors were radiolabeled at the carbonyl position by [ 11 C]CO 2 fixation. Radiotracers were administered (tail-vein injection) to rodents and brain uptake of radioactivity measured at early and late time points ex vivo. Specificity of uptake was explored by pretreatment with unlabeled inhibitors (2 mg/kg, ip) 30 min prior to radiotracer administration. Results: All five candidate MAGL radiotracers were prepared in high specific activity (> 65 GBq/μmol) and radiochemical purity (> 98%). Moderate brain uptake (0.2–0.8 SUV) was observed for each candidate while pretreatment did not reduce uptake for four of the five tested. For two candidates ([ 11 C]12 and [ 11 C]14), high retention of radioactivity was observed in the blood (ca. 10 and 4 SUV at 40 min) which was blocked by pretreatment with unlabeled inhibitors. The most promising candidate, [ 11 C]18, demonstrated moderate brain uptake (ca. 0.8 SUV) which showed circa 50% blockade by pretreatment with unlabeled 18. Conclusion: One putative and four reported potent and selective MAGL inhibitors have been radiolabeled via [ 11 C]CO 2 fixation as radiotracers for this enzyme. Despite the promising in vitro pharmacological profile, none of the five candidate radiotracers exhibited in vivo behavior suitable for PET neuroimaging

  7. Comparative study on germ cell mutation induced by urethane (ethyl carbamate) gas and X-rays in drosophila melanogaster

    International Nuclear Information System (INIS)

    Nomura, Taisei; Kurokawa, Nobuo

    1997-01-01

    Although its mutagenicity has not been confirmed in mouse germ cells, urethane (ethyl carbamate) gas induces a significant increase of X-linked recessive lethal mutations in the germ cells of Drosophila melanogaster. The mutation frequency increased as the exposure time was changed from 3.5 to 5.5 h. Mutations were also induced by X-rays (20 to 40 Gy) and N-methyl-N-nitrosourea (MNU) (0.06 to 0.10%). However, no significant increase of chromosomal changes (partial loss of the Y chromosome, total loss of X or Y, and translocations) was produced by urethane, although these were readily induced by X-rays. There were large and significant increases in chromosomal changes caused by X-rays (20 Gy) compared to urethane (5.5 h) or MNU (0.06%). In contrast, there were no substantial differences among these three treatments as regards recessive lethal mutations. Urethane-induced DNA lesions detected as recessive lethals appear to be intragenic mutations. Complementation analysis with 15 reference single-site loci (cistrons) in the zeste-white region of the X chromosome revealed that 29 of 723 urethane-induced recessive lethals were located in the zeste-white region and all were restricted to a single locus. However, among 28 of 890 X-ray-induced lethals, 2 were non-complementary to 2 or 3 adjacent loci, indicating deletions encompassing 2 or 3 loci. In addition, 3 of these lethal chromosomes included mutations outside the zeste-white region. Another difference between urethane and X-rays was in the distribution of mutation sites. Urethane-induced mutations were strikingly non-random with two hot spots at zw-1 and zw-2, whereas the distribution of X-ray-induced mutations was more nearly random. (author)

  8. Allergic reaction induced by dermal and/or respiratory exposure to low-dose phenoxyacetic acid, organophosphorus, and carbamate pesticides

    International Nuclear Information System (INIS)

    Fukuyama, Tomoki; Tajima, Yukari; Ueda, Hideo; Hayashi, Koichi; Shutoh, Yasufumi; Harada, Takanori; Kosaka, Tadashi

    2009-01-01

    Several types of pesticides, such as organophosphates, phenoxyacetic acid, and carbamate have a high risk of affecting human health, causing allergic rhinitis and bronchial asthma-like diseases. We used our long-term sensitization method and a local lymph node assay to examine the allergic reactions caused by several types of pesticides. BALB/c mice were topically sensitized (9 times in 3 weeks), then challenged dermally or intratracheally with 2,4-D, BRP, or furathiocarb. One day post-challenge, the mice were processed to obtain biologic materials for use in assays of total IgE levels in serum and bronchoalveolar lavage fluid (BALF); differential cell counts and chemokine levels in BALF; lymphocyte counts and surface antigen expression on B-cells within regional lymph nodes (LNs); and, ex situ cytokine production by cells from these LNs. 2,4-D-induced immune responses characteristic of immediate-type respiratory reactions, as evidenced by increased total IgE levels in both serum and BALF; an influx of eosinophils, neutrophils, and chemokines (MCP-1, eotaxin, and MIP-1β) in BALF; increased surface antigen expression on B-cells IgE and MHC class II production) in both auricular and the lung-associated LNs; and increased Th2 cytokine production (IL-4, IL-5, IL-10, and IL-13) in both auricular and the lung-associated LN cells. In contrast, BRP and furathiocarb treatment yielded, at most, non-significant increases in all respiratory allergic parameters. BRP and furathiocarb induced marked proliferation of MHC Class II-positive B-cells and Th1 cytokines (IL-2, TNF-α, and IFN-γ) in only auricular LN cells. These results suggest that 2,4-D is a respiratory allergen and BRP and furathiocarb are contact allergens. As our protocol detected classified allergic responses to low-molecular-weight chemicals, it thus may be useful for detecting environmental chemical-related allergy.

  9. Occupational exposure to organophosphate and carbamate pesticides affects sperm chromatin integrity and reproductive hormone levels among Venezuelan farm workers.

    Science.gov (United States)

    Miranda-Contreras, Leticia; Gómez-Pérez, Roald; Rojas, Gerardo; Cruz, Ibis; Berrueta, Lisbeth; Salmen, Siham; Colmenares, Melisa; Barreto, Silvio; Balza, Alirio; Zavala, Leisalba; Morales, Yasmin; Molina, Yuri; Valeri, Lenin; Contreras, Carlos A; Osuna, Jesús A

    2013-01-01

    Several reports suggest that chronic pesticide exposure may affect semen quality and male fertility in humans. The objective of this study was to evaluate the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality, as well as levels of reproductive and thyroid hormones of Venezuelan farm workers. Thirty-five healthy men (unexposed group) and 64 male agricultural workers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH) and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. Evidence of pesticide exposure was found in 87.5% of farmers based on AChE and BuChE inhibition. Significant increments were observed in sperm DFI with significant decreases in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology and vitality in these workers. The levels of Tt, PRL, FT4 and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. Our results confirm the potential impact of chronic occupational exposure to OP/CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes.

  10. Chromogenic platform based on recombinant Drosophila melanogaster acetylcholinesterase for visible unidirectional assay of organophosphate and carbamate insecticide residues

    Energy Technology Data Exchange (ETDEWEB)

    Han Zheng [Institute for Agri-food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, 1018 Jinqi Road, Shanghai 201403 (China); Chi Chensen [School of Life Science and Biotechnology, Bor Luh Food Safety Center, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); Bai Bing; Liu Gang; Rao Qinxiong [Institute for Agri-food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, 1018 Jinqi Road, Shanghai 201403 (China); Peng Shaojie [Institute of Shanghai Food and Drug Supervision, 615 Liuzhou Road, Shanghai 200233 (China); Liu Hong [Shanghai Municipal Center for Disease Control and Prevention, 1380 Zhongshan West Road, Shanghai 200336 (China); Zhao Zhihui [Institute for Agri-food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, 1018 Jinqi Road, Shanghai 201403 (China); Zhang Dabing [School of Life Science and Biotechnology, Bor Luh Food Safety Center, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); Wu Aibo, E-mail: wuaibo@saas.sh.cn [Institute for Agri-food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, 1018 Jinqi Road, Shanghai 201403 (China)

    2012-03-30

    Highlight: Black-Right-Pointing-Pointer A visible chromogenic platform for rapid analysis of OP and CM insecticide residues was developed. Black-Right-Pointing-Pointer The assay has the capabilities of both qualitative measurement and quantitative analysis. Black-Right-Pointing-Pointer The sensitivity, capabilities of resisting interferences and storage stability were desirable. Black-Right-Pointing-Pointer Matrix effects were acceptable and detection performance was satisfactory in real application. - Abstract: In this study we propose a chromogenic platform for rapid analysis of organophosphate (OP) and carbamate (CM) insecticide residues, based on recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE) as enzyme and indoxyl acetate as substrate. The visible chromogenic strip had the advantages identical to those of commonly used lateral flow assays (LFAs) with utmost simplicity in sample loading and result observation. After optimization, depending on the color intensity (CI) values, the well-established assay has the capabilities of both qualitative measurement via naked eyes and quantitative analysis by colorimetric reader with the desirable IC{sub 50} values against the tested six insecticides (0.06 {mu}g mL{sup -1} of carbofuran, 0.28 {mu}g mL{sup -1} of methomyl, 0.03 {mu}g mL{sup -1} of dichlorvos, 31.6 {mu}g mL{sup -1} of methamidophos, 2.0 {mu}g mL{sup -1} of monocrotophos, 6.3 {mu}g mL{sup -1} of omethoate). Acceptable matrix effects and satisfactory detection performance were confirmed by in-parallel LC-MS/MS analysis in different vegetable varieties at various spiked levels of 10{sup -3} to 10{sup 1} {mu}g g{sup -1}. Overall, the testified suitability and applicability of this novel platform meet the requirements for practical use in food safety management and environmental monitoring, especially in the developing world.

  11. Novel (coumarin-3-yl)carbamates as selective MAO-B inhibitors: synthesis, in vitro and in vivo assays, theoretical evaluation of ADME properties and docking study.

    Science.gov (United States)

    Matos, Maria J; Vilar, Santiago; Gonzalez-Franco, Rosa Ma; Uriarte, Eugenio; Santana, Lourdes; Friedman, Carol; Tatonetti, Nicholas P; Viña, Dolores; Fontenla, Jose A

    2013-05-01

    A series of (coumarin-3-yl)carbamates was synthesized and evaluated in vitro as monoamine oxidase (MAO-A and MAO-B) inhibitors. Most of the new compounds selectively inhibited MAO-B isoenzyme with IC50 values in the micro or nanoMolar ranges. Since these compounds must achieve the brain cells, theoretical evaluation of ADME properties were also carried out. Compound 8 (benzyl(coumarin-3-yl)carbamate), which presented the most interesting in vitro MAO-B inhibitory profile (IC50 against MAO-B = 45 nM), was subjected to further studies. This in vitro MAO-B inhibitory activity is comparable with that of the selegiline, the reference compound (IC50 against MAO-B = 20 nM). Taking into account the in vitro results of compound 8, in vivo assays and docking calculations were also carried out for this derivative. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  12. Discovery of vinylogous carbamates as a novel class of β-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors.

    Science.gov (United States)

    Li, Huan-Qiu; Luo, Yin; Zhu, Hai-Liang

    2011-08-01

    β-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria. The important role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of new FabH inhibitors. We first used a structure-based approach to develop 24 new vinylogous carbamates (4a-15a, 4b-15b) that target FabH for the development of new antibiotics in this paper. Potent FabH inhibitory and selective anti- Gram-negative bacteria activities were observed in most of these vinylogous carbamates. Especially, compound 6a and 7a showed the most potent FabH inhibitory activity with IC₅₀ of 2.6 and 3.3 μM, respectively. Docking simulation was performed to position compound 6a into the Escherichia coli FabH active site and the possible binding conformation of compounds has been proposed. The biological data and molecular docking indicated that compounds 6a and 7a were potent inhibitors of E. coli FabH as antibiotics deserving further research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Vortex-Assisted Dispersive Micro-Solid Phase Extraction Using CTAB-Modified Zeolite NaY Sorbent Coupled with HPLC for the Determination of Carbamate Insecticides.

    Science.gov (United States)

    Salisaeng, Pawina; Arnnok, Prapha; Patdhanagul, Nopbhasinthu; Burakham, Rodjana

    2016-03-16

    A vortex-assisted dispersive micro-solid phase extraction (VA-D-μ-SPE) based on cetyltrimethylammonium bromide (CTAB)-modified zeolite NaY was developed for preconcentration of carbamate pesticides in fruits, vegetables, and natural surface water prior to analysis by high performance liquid chromatography with photodiode array detection. The small amounts of solid sorbent were dispersed in a sample solution, and extraction occurred by adsorption in a short time, which was accelerated by vortex agitation. Finally, the sorbents were filtered from the solution, and the analytes were subsequently desorbed using an appropriate solvent. Parameters affecting the VA-D-μ-SPE performance including sorbent amount, sample volume, desorption solvent ,and vortex time were optimized. Under the optimum condition, linear dynamic ranges were achieved between 0.004-24.000 mg kg(-1) (R(2) > 0.9946). The limits of detection (LODs) ranged from 0.004-4.000 mg kg(-1). The applicability of the developed procedure was successfully evaluated by the determination of the carbamate residues in fruits (dragon fruit, rambutan, and watermelon), vegetables (cabbage, cauliflower, and cucumber), and natural surface water.

  14. Sequential injection kinetic spectrophotometric determination of quaternary mixtures of carbamate pesticides in water and fruit samples using artificial neural networks for multivariate calibration

    Science.gov (United States)

    Chu, Ning; Fan, Shihua

    2009-12-01

    A new analytical method was developed for the simultaneous kinetic spectrophotometric determination of a quaternary carbamate pesticide mixture consisting of carbofuran, propoxur, metolcarb and fenobucarb using sequential injection analysis (SIA). The procedure was based upon the different kinetic properties between the analytes reacted with reagent in flow system in the non-stopped-flow mode, in which their hydrolysis products coupled with diazotized p-nitroaniline in an alkaline medium to form the corresponding colored complexes. The absorbance data from SIA peak time profile were recorded at 510 nm and resolved by the use of back-propagation-artificial neural network (BP-ANN) algorithms for multivariate quantitative analysis. The experimental variables and main network parameters were optimized and each of the pesticides could be determined in the concentration range of 0.5-10.0 μg mL -1, at a sampling frequency of 18 h -1. The proposed method was compared to other spectrophotometric methods for simultaneous determination of mixtures of carbamate pesticides, and it was proved to be adequately reliable and was successfully applied to the simultaneous determination of the four pesticide residues in water and fruit samples, obtaining the satisfactory results based on recovery studies (84.7-116.0%).

  15. Consumption of fruits and vegetables and probabilistic assessment of the cumulative acute exposure to organophosphorus and carbamate pesticides of schoolchildren in Slovenia.

    Science.gov (United States)

    Blaznik, Urška; Yngve, Agneta; Eržen, Ivan; Hlastan Ribič, Cirila

    2016-02-01

    Adequate consumption of fruits and vegetables is a part of recommendations for a healthy diet. The aim of the present study was to assess acute cumulative dietary exposure to organophosphorus and carbamate pesticides via fruit and vegetable consumption by the population of schoolchildren aged 11-12 years and the level of risk for their health. Cumulative probabilistic risk assessment methodology with the index compound approach was applied. Slovenia, primary schools. Schoolchildren (n 1145) from thirty-one primary schools in Slovenia. Children were part of the PRO GREENS study 2009/10 which assessed 11-year-olds' consumption of fruit and vegetables in ten European countries. The cumulative acute exposure amounted to 8.3 (95% CI 7.7, 10.6) % of the acute reference dose (ARfD) for acephate as index compound (100 µg/kg body weight per d) at the 99.9th percentile for daily intake and to 4.5 (95% CI 3.5, 4.7) % of the ARfD at the 99.9th percentile for intakes during school time and at lunch. Apples, bananas, oranges and lettuce contributed most to the total acute pesticides intake. The estimations showed that acute dietary exposure to organophosphorus and carbamate pesticides is not a health concern for schoolchildren with the assessed dietary patterns of fruit and vegetable consumption.

  16. Characterization of acetylcholinesterase from the brain of the Amazonian tambaqui (Colossoma macropomum) and in vitro effect of organophosphorus and carbamate pesticides.

    Science.gov (United States)

    Assis, Caio Rodrigo Dias; Castro, Patrícia Fernandes; Amaral, Ian Porto Gurgel; Carvalho, Elba Verônica Matoso Maciel; Carvalho, Luiz Bezerra; Bezerra, Ranilson Souza

    2010-10-01

    In the present study, acetylcholinesterase (AChE) from the brain of the Amazonian fish tambaqui (Colossoma macropomum) was partially characterized and its activity was assayed in the presence of five organophosphates (dichlorvos, diazinon, chlorpyrifos, and tetraethyl pyrophosphate [TEPP]) and two carbamates (carbaryl and carbofuran) insecticides. Optimal pH and temperature were 7.0 to 8.0 and 45°C, respectively. The enzyme retained approximately 70% of activity after incubation at 50°C for 30 min. The insecticide concentration capable of inhibiting half of the enzyme activity (IC50) for dichlorvos, chlorpyrifos, and TEPP were calculated as 0.04 µmol/L, 7.6 µmol/L, and 3.7 µmol/L, respectively. Diazinon and temephos did not inhibit the enzyme. The IC50 values for carbaryl and carbofuran were estimated as 33.8 µmol/L and 0.92 µmol/L, respectively. These results suggest that AChE from the juvenile C. macropomum brain could be used as an alternative biocomponent of organophosphorus and carbamate biosensors in routine pesticide screening in the environment. Environ. Toxicol. Chem. 2010;29:2243-2248. © 2010 SETAC.

  17. Drug Facts

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    Full Text Available ... Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What ... Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , the principal biomedical and behavioral research agency ...

  18. Synthesis, structural characterization, docking, lipophilicity and cytotoxicity of 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-alkyl carbamates, novel acetylcholinesterase and butyrylcholinesterase pseudo-irreversible inhibitors

    Czech Academy of Sciences Publication Activity Database

    Pejchal, V.; Štěpánková, Š.; Pejchalová, M.; Královec, K.; Havelek, R.; Růžičková, Z.; Ajani, Haresh; Lo, Rabindranath; Lepšík, Martin

    2016-01-01

    Roč. 24, č. 7 (2016), s. 1560-1572 ISSN 0968-0896 R&D Projects: GA ČR GBP208/12/G016 Institutional support: RVO:61388963 Keywords : halogenated benzothiazole * carbamates * acetylcholinesterase * butyrylcholinesterase inhibition * pseudo-irreversible mechanism * covalent docking Subject RIV: CC - Organic Chemistry Impact factor: 2.930, year: 2016

  19. Examining pyrethroids, carbamates and neonicotenoids in fish, water and sediments from the Indus River for potential health risks.

    Science.gov (United States)

    Jabeen, Farhat; Chaudhry, Abdul Shakoor; Manzoor, Sadia; Shaheen, Tayybah

    2015-02-01

    This 3 × 3 factorial study assessed pyrethroids, carbamates and neonicotenoids groups of pesticides in replicated samples of three fish species from low (S1, reference), medium (S2) and heavy (S3) polluted sites receiving agricultural run-offs around the Indus River. Water and sediment samples from the same sites were also analysed for these pesticides by using high-performance liquid chromatography. Out of nine investigated pesticides, only three pesticides (deltamethrin, carbofuran and cypermethrin) were detected in fish and sediment samples. Deltamethrin in Cyprinus carpio ranged from 0.490 to 0.839 μg/g, mostly exceeding 0.5 μg/g as the maximum residual limit suggested by FAO-WHO, whereas it ranged from 0.214 to 0.318 μg/g in the sampled sediments. The carbofuran concentrations were 0.0425-0.066 and 0.613-0.946 μg/g in Labeo rohita and Channa marulius muscles respectively and 0.069-0.081 μg/g in the corresponding sediment samples. These values were either higher or lower than the maximum limit (0.1 μg/g) as suggested by FAO-WHO. Conversely, the cypermethrin concentration ranged from 0.141 to 0.174 in Ch. marulius and 0.183-0.197 μg/g in sediments which were both below the FAO-WHO maximum limit of 2 μg/g. No pesticide residues were detected in water from these sampling sites. Most selected physicochemical variables were within the acceptable range of World Health Organization for the water quality for aquatic life. The detected pesticide contents were mostly higher in fish muscles from heavily polluted sites. This is worrying because these pesticides may pose health risks for the fish and people of the study area. However, a preliminary risk assessment indicated that the calculated daily intake of detected pesticides by people consuming fish from the Indus River was low and did not present an immediate risk to the fish-consuming people. This study may be used as a benchmark to determine the safety of fish meat in order to develop intervention

  20. Determination of poorly fluorescent carbamate pesticides in water, bendiocarb and promecarb, using cyclodextrin nanocavities and related media

    Energy Technology Data Exchange (ETDEWEB)

    Pacioni, Natalia L. [Instituto de Investigaciones en Fisico Quimica de Cordoba (INFIQC), Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Ciudad Universitaria, 5000 Cordoba (Argentina); Veglia, Alicia V. [Instituto de Investigaciones en Fisico Quimica de Cordoba (INFIQC), Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Ciudad Universitaria, 5000 Cordoba (Argentina)]. E-mail: aveglia@mail.fcq.unc.edu.ar

    2007-01-30

    The effect of native cyclodextrins ({alpha}, {beta}, or {gamma}CD with six, seven and eight glucose units, respectively), hydroxypropyl-{beta}-cyclodextrin (HPCD), chitosan (CHT) and glucose in water solution or water with n-propylamine (PA) as co-solvent upon the UV-vis and fluorescence properties of poorly fluorescent N-methyl carbamates pesticides (C) as bendiocarb (2,2-dimethyl-1,3-benzodioxol-4-ol methylcarbamate, BC) and promecarb (3-methyl-5-(1-methylethyl)phenol methylcarbame, PC) was examined. Fluorescent enhancement was found for both substrates with all CDs in water or PA-water except from PC with {alpha}CD. The addition of CHT increases the fluorescence of BC but decreases the fluorescence of PC, and glucose addition gives in both cases no spectral changes. Host-guest interaction was clearly determined by fluorescence enhancement with {beta}CD and HPCD with a 1:1 stoichiometry for the complexes (C:CD). The values obtained for the association constants (K {sub A}, M{sup -1}) were (6 {+-} 2) x 10{sup 2} and (2.3 {+-} 0.3) x 10{sup 2} for BC:{beta}CD and BC:HPCD complexes, respectively. For PC:{beta}CD and PC:HPCD the values of K {sub A} were (19 {+-} 2) x 10{sup 2} and (21 {+-} 2) x 10{sup 2}, respectively. The ratio of the fluorescence quantum yields for the bound and free substrates ({phi} {sup CCD}/{phi} {sup C}) was in the range 1.74-3.8. The limits of detection (L {sub D}, {mu}g mL{sup -1}) for the best conditions were (0.57 {+-} 0.02) for BC with HPCD and (0.091 {+-} 0.002) for PC with {beta}CD in water. Application to the analysis in pesticide spiked samples of tap water and fruit yields satisfactory apparent recoveries (84-114%), and for the extraction procedure in fruits and a commercial formulation, recoveries were of 81-98% and 104%, respectively. The method is rapid, simple, direct, sensitive and useful for pesticide analysis.

  1. Probit Analysis of Carbamate-Pesticide-Toxicity at Soil-Water Interface to N2-Fixing Cyanobacterium Cylindrospermum sp

    Directory of Open Access Journals (Sweden)

    Rabindra N. Padhy

    2015-03-01

    Full Text Available Toxicity-data of two carbamate insecticides, carbaryl and carbofuran, and three fungicides, ziram, zineb and mancozeb with rice-field N2-fixing cyanobacterium Cylindrospermum sp., obtained by in vitro growth and at soil-water interface, were analyzed by the probit method. Growth enhancing concentration, no-observed effective concentration, minimum inhibitory concentration, the highest permissive concentration and lethal concentration100 (LC100 were determined experimentally. The LC50 values of carbaryl, carbofuran, ziram, zineb and mancozeb in N2-fixing liquid medium were 56.2, 588.8, 0.07, 4.2 and 3.4 μg/mL, respectively, whereas the corresponding LC100 values were 100.0, 1500.0, 0.17, 25.0 and 9.0 μg/mL, respectively. The LC50 values of these pesticides in succession in N2-fixing agar medium were 44.7, 239.9, 0.07, 1.8 and 2.3 μg/mL, respectively, whereas the corresponding LC100 values were 100.0, 600.0, 0.17, 10.0 and 7.0 μg/mL, respectively. Similar results with nitrate supplemented liquid and agar media indicated that nitrate supplementation had toxicity reducing effect. The LC50 and LC100 values of toxicity in the N2-fixing liquid medium at soil-water interface were 91.2 and 200.0 μg/mL for carbaryl, 2 317 and 6 000 μg/mL for carbofuran, 0.15 and 0.50 μg/mL for ziram, 16.4 and 50.0 μg/mL for zineb, and 7.2 and 25.0 μg/mL for mancozeb, respectively. Each LC100 value at soil-water interface with a pesticide was significantly higher than its corresponding LC100 value at liquid/agar media. It can be concluded that, under the N2-fixing conditions, the cyanobacterium tolerated higher levels of each pesticide at soil-water interface.

  2. 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

  3. Drug Facts

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    Full Text Available ... Where Can Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking ... You Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English ...

  4. Hazardous Drugs

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    ... and hazardous drugs in the workplace. Pharmacy . OSHA Hospital eTool. Reviews safety and health topics related to hazardous drugs including drug handling, administration, storage, and disposal. OSHA has identified worker exposure ...

  5. Drug Facts

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    Full Text Available ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662-HELP (4357) at any time to find drug treatment ...

  6. Drug Reactions

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    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  7. Drug Facts

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    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to ...

  8. Club Drugs

    Science.gov (United States)

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... regarding prevention and treatment of MDMA. ( September 2017 ) View all related publications Related NIDA Notes Articles Narrative ...

  9. Drug Facts

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    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  10. Drug Facts

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    Full Text Available ... Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ...

  11. Drug Facts

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    Full Text Available ... Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her ...

  12. ['Gold standard', not 'golden standard'

    NARCIS (Netherlands)

    Claassen, J.A.H.R.

    2005-01-01

    In medical literature, both 'gold standard' and 'golden standard' are employed to describe a reference test used for comparison with a novel method. The term 'gold standard' in its current sense in medical research was coined by Rudd in 1979, in reference to the monetary gold standard. In the same

  13. Drug abuse: newly-emerging drugs and trends.

    Science.gov (United States)

    Davis, Gregory G

    2012-09-01

    Drug abusers have access to new, more potent compounds that evade existing laws by virtue of their novel chemical structures. These drugs are available for purchase at stores and over the internet. The drugs are not illegal because they are so new that laws have not yet been passed to ban them. These drugs are leading to emergency department visits for cardiovascular, neurologic, and psychiatric complications. Standard drug screens are not designed to detect these new substances. The internet provides access to drugs for substance abusers but also provides physicians speed of access to the habits of substance abusers.

  14. Drug Information in Space Medicine

    Science.gov (United States)

    Bayuse, Tina M.

    2009-01-01

    Published drug information is widely available for terrestrial conditions. However, information on dosing, administration, drug interactions, stability, and side effects is scant as it relates to use in Space Medicine. Multinational crews on board the International Space Station present additional challenges for drug information because medication nomenclature, information available for the drug as well as the intended use for the drug is not standard across countries. This presentation will look at unique needs for drug information and how the information is managed in Space Medicine. A review was conducted of the drug information requests submitted to the Johnson Space Center Pharmacy by Space Medicine practitioners, astronaut crewmembers and researchers. The information requested was defined and cataloged. A list of references used was maintained. The wide range of information was identified. Due to the information needs for the medications in the on-board medical kits, the Drug Monograph Project was created. A standard method for answering specific drug information questions was generated and maintained by the Johnson Space Center Pharmacy. The Drug Monograph Project will be presented. Topic-centered requests, including multinational drug information, drug-induced adverse reactions, and medication events due to the environment will be highlighted. Information management of the drug information will be explained. Future considerations for drug information needs will be outlined.

  15. Accounting standards

    NARCIS (Netherlands)

    Stellinga, B.; Mügge, D.

    2014-01-01

    The European and global regulation of accounting standards have witnessed remarkable changes over the past twenty years. In the early 1990s, EU accounting practices were fragmented along national lines and US accounting standards were the de facto global standards. Since 2005, all EU listed

  16. Drug Facts

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    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath ... Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  17. Drug Facts

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    Full Text Available ... 4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from drugs. But she's afraid ...

  18. Drug Facts

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    Full Text Available ... Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Information about this page Click on the button that says "Listen" on any page and the computer will read the text to you. This website talks ...

  19. Identifying Drugs

    Science.gov (United States)

    ... and Affect Teens The Negative Health Effects of Marijuana Use State and Federal Drug Laws Treatment and Recovery Federal Student Aid and Consequences of a Drug Conviction School Failure VIDEO: Taking Prescription Drugs to Get High—A Bad Idea Drugged Driving—What You Should Know How ...

  20. Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA

    DEFF Research Database (Denmark)

    Douthwaite, S; Hansen, L H; Mauvais, P

    2000-01-01

    The macrolide antibiotic erythromycin and its 6-O-methyl derivative (clarithromycin) bind to bacterial ribosomes primarily through interactions with nucleotides in domains II and V of 23S rRNA. The domain II interaction occurs between nucleotide A752 and the macrolide 3-cladinose moiety. Removal...... cause of drug resistance in some clinical pathogens. The 2058G mutation disrupts the drug-domain V contact and leads to a further > 25 000-fold decrease in the binding of RU 56006. Drug binding to resistant ribosomes can be improved over 3000-fold by forming an alternative and more effective contact...... to A752 via alkyl-aryl groups linked to a carbamate at the drug 11/12 position (in the ketolide antibiotics HMR 3647 and HMR 3004). The data indicate that simultaneous drug interactions with domains II and V strengthen binding and that the domain II contact is of particular importance to achieve...

  1. Drug therapy of leprosy

    Directory of Open Access Journals (Sweden)

    A. A. Kubanov

    2016-01-01

    Full Text Available Leprosy (Hansen’s disease is a chronic granulomatous bacterial infection mainly affecting the skin and peripheral nervous system yet also involving other organs and systems as a result of a pathological process. The causative agent of leprosy - Mycobacterium leprae - is an obligate intracellular microorganism. Despite the removal of a threat of a leprosy epidemic, European countries still record outbreaks of the disease mainly among migrants coming from endemic areas. A golden standard of the treatment of leprosy is a WHO-recommended combined drug therapy comprising drugs such as dapsone, clofazimine and rifampicin. The article provides current data on the mechanisms of action, efficacy and safety of these drugs and their combined scheme of treatment obtained as a result of clinical trials. Moreover, it also reviews new regimens of the drug therapy of leprosy including those with the use of drugs from the group of fluoroquinols as well as immunotherapy of the disease.

  2. Ethyl Carbamate Formation Regulated by Lactic Acid Bacteria and Nonconventional Yeasts in Solid-State Fermentation of Chinese Moutai-Flavor Liquor.

    Science.gov (United States)

    Du, Hai; Song, Zhewei; Xu, Yan

    2018-01-10

    This study aimed to identify specific microorganisms related to the formation of precursors of EC (ethyl carbamate) in the solid-state fermentation of Chinese Moutai-flavor liquor. The EC content was significantly correlated with the urea content during the fermentation process (R 2 = 0.772, P < 0.01). Differences in urea production and degradation were found at both species and functional gene levels by metatranscriptomic sequencing and culture-dependent analysis. Lactobacillus spp. could competitively degrade arginine through the arginine deiminase pathway with yeasts, and most Lactobacillus species were capable of degrading urea. Some dominant nonconventional yeasts, such as Pichia, Schizosaccharomyces, and Zygosaccharomyces species, were shown to produce low amounts of urea relative to Saccharomyces cerevisiae. Moreover, unusual urea degradation pathways (urea carboxylase, allophanate hydrolase, and ATP-independent urease) were identified. Our results indicate that EC precursor levels in the solid-state fermentation can be controlled using lactic acid bacteria and nonconventional yeasts.

  3. Synthesis and evaluation of new α-methylene-γ-lactone carbamates with NO production inhibitory effects in lipopolysaccharide-induced RAW 264.7 macrophages.

    Science.gov (United States)

    Shao, Wen-Hao; Chen, Bing-Yang; Cheng, Xiang-Rong; Yuan, Hu; Chen, Hao; Chang, Wan-Lin; Ye, Ji; Lin, Shan; Sun, Qing-Yan; Zhang, Wei-Dong

    2015-03-26

    A series of new α-methylene-γ-lactone carbamates were synthesized by an asymmetric synthetic route. The activities on inhibiting nitric oxide (NO) release of these compounds were evaluated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. The results indicated that most of the compounds except one exhibited potent NO inhibitory effect with IC50 value more than 2 μΜ. The cytotoxicities of these compounds were estimated via MTT assays. The results suggested that six compounds were accompanied by low cytotoxicity. The structure-activity relationships were also discussed. The S configuration of C3 on lactones ring would be more helpful to NO inhibitory effect. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Laboratory and clinical evaluation of the radiation-potentiating activity of ethyl-N-bis (2,2-dimethylethylamidinophosphoro) carbamate (AB-132)

    International Nuclear Information System (INIS)

    Regelson, W.; Hananian, J.; Bozzini, M.; Ambrus, C.M.; Bardos, T.J.; Ambrus, J.L.

    1975-01-01

    Ethyl-N-bis (2,2(dimethylethylamidinophosphoro) carbamate (AB-132) has been shown to potentiate the effect of whole-body radiation on inhibition of splenomegaly induced by Friend leukemia virus in ICR/H Swiss mice. The combined effect of AB-132 and radiation does not appear to be related to Friend virus inhibition but seems to act on the proliferating tumor in the spleen. Nine children with advanced cancer were treated with combined adminstration of local radiation and systemic AB-132. Although regression of tumor was seen, no dramatic effect on survival was apparent. One case of metastatic Ewing's sarcoma showed systemic tumor response to AB-132 in addition to localized response to radiation. Bone marrow depression appeared to be the main side effect of combination therapy

  5. 21 CFR 130.9 - Sulfites in standardized food.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Sulfites in standardized food. 130.9 Section 130.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION FOOD STANDARDS: GENERAL General Provisions § 130.9 Sulfites in standardized food...

  6. Enantioseparation of 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate tagged amino acids and other zwitterionic compounds on cinchona-based chiral stationary phases.

    Science.gov (United States)

    Hellinger, Roland; Horak, Jeannie; Lindner, Wolfgang

    2013-10-01

    The fluorescent tag 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC; AccQ Fluor reagent kit from Waters) is a commercial N-terminal label for proteinogenic amino acids (AAs), designed for reversed-phase separation and quantification of the AA racemates. The applicability of AQC-tagged AAs and AA-type zwitterionic compounds was tested for enantiomer separation on the tert-butyl carbamate modified quinine and quinidine based chiral stationary phases, QN-AX and QD-AX employing polar-organic elution conditions. The investigated test analytes included the enantiomers of the positional isomers of isoleucine (Ile), threonine, homoserine, and 4-hydroxyproline. Furthermore, β-AAs, cyclic, and heterocyclic AAs including trans-2-amino-cyclohexane carboxylic acid and trans-2-aminocyclohexyl sulfonic acid, phenylalanine derivatives substituted with halides with increasing electronegativity and 3,4-dihydroxyphenylalanine, cysteine-related derivatives including homocysteic acid, methionine sulfone, cysteine-S-acetic acid, and cysteine-S-acetamide as well as a small range of aminophosphonic acids were enantioseparated. A mechanistic interaction study of AQC-AAs in comparison with fluoresceine isothiocyanate-labeled AAs was performed. The chiral and chemoselective recognition processes involved in enantiomer separation and retention was systematically discussed. Special emphasis was set on the influential factors exhibited by the chemistry, branching position, and spatial properties of the investigated zwitterionic analytes. The general interest to separate and distinguish between different types of branched-chained AAs and metabolic side products thereof lies in the toxicity of some of these compounds, which makes for instance allo-Ile an attractive candidate in disease-related biomarker research.

  7. Organophosphorus and Carbamate Pesticide Residues Detected in Water Samples Collected from Paddy and Vegetable Fields of the Savar and Dhamrai Upazilas in Bangladesh

    Directory of Open Access Journals (Sweden)

    Nurul Karim

    2012-09-01

    Full Text Available Several types of organophosphorous and carbamate pesticides have been used extensively by the farmers in Bangladesh during the last few decades. Twenty seven water samples collected from both paddy and vegetable fields in the Savar and Dhamrai Upazilas in Bangladesh were analyzed to determine the occurrence and distribution of organo-phosphorus (chlorpyrifos, malathion and diazinon and carbamate (carbaryl and carbofuran pesticide residues. A high performance liquid chromatograph instrument equipped with a photodiode array detector was used to determine the concentrations of these pesticide residues. Diazinon and carbofuran were detected in water samples collected from Savar Upazila at 0.9 μg/L and 198.7 μg/L, respectively. Malathion was also detected in a single water sample at 105.2 μg/L from Dhamrai Upazila. Carbaryl was the most common pesticide detected in Dhamrai Upazila at 14.1 and 18.1 μg/L, while another water sample from Dhamrai Upazila was contaminated with carbofuran at 105.2 μg/L. Chlorpyrifos was not detected in any sample. Overall, the pesticide residues detected were well above the maximum acceptable levels of total and individual pesticide contamination, at 0.5 and 0.1 μg/L, respectively, in water samples recommended by the European Economic Community (Directive 98/83/EC. The presence of these pesticide residues may be attributed by their intense use by the farmers living in these areas. Proper handling of these pesticides should be ensured to avoid direct or indirect exposure to these pesticides.

  8. A fluorescence-based method for cyanate analysis in ethanol/water media: correlation between cyanate presence and ethyl carbamate formation in sugar cane spirit.

    Science.gov (United States)

    Ohe, Thiago Hideyuki Kobe; da Silva, Alexandre Ataide; Rocha, Thaís da Silva; de Godoy, Flávio Schutzer; Franco, Douglas Wagner

    2014-10-01

    Based on the fluorescence properties of 2,4-(1H,3H)-quinazolinedione, a product of the reaction between cyanate and 2-aminobenzoic acid, a simple, sensitive, selective, and reproducible method for the cyanate analysis in aqueous ethanolic media is proposed. In this method, λ(exc) and λ(em) are 310 and 410 nm, respectively, and the limits of detection and quantification are 2.2 × 10(-7) and 6.7 × 10(-7) mol/L, respectively. Under optimal conditions (pH = 4.5, 40% ethanol), a concentration of 5.0 × 10(-6) mol/L cyanate can be determined in a single measurement, at a 95% level of confidence, with an uncertainty of ± 0.13 × 10(-6) mol/L. Cyanide, thiocyanate, chloride, nitrate, and sulfate ions, as well as urea and urethane in concentrations 1 × 10(3) higher than that of cyanate do not interfere with the measurement. The methodology was applied to cyanate analyses in the different fractions of the sugarcane distillate and the data strongly suggest a correlation between the presence of urea in wine, and the cyanate and ethyl carbamate concentrations in the spirit. Based on the fluorescence properties of the reaction product between cyanate and 2-aminobenzoic acid, a method for assaying cyanate was devised. This procedure applied to the sugarcane distillate showed for the first time a correlation between cyanate presence and ethyl carbamate (EC) formation in the different fractions of the product. Therefore, the proposed methodology can be used to predict in freshly distillate sugar cane spirits the potential total concentration of EC to be formed. Therefore, these data could be used to advise about the necessity of implementing a procedure to reduce spirit EC concentration before the product reaches the market. © 2014 Institute of Food Technologists®

  9. Pyrethroid and carbamate resistance in Australian Helicoverpa armigera (Lepidoptera: Noctuidae) from 2008 to 2015: what has changed since the introduction of Bt cotton?

    Science.gov (United States)

    Bird, L J

    2018-01-23

    Pyrethroid and carbamate resistance was evaluated in Helicoverpa armigera from 2008 to 2015. Insects were collected as eggs primarily from cultivated hosts in the major cropping areas of New South Wales and Queensland, Australia. Larvae reared from eggs were tested for resistance to fenvalerate, bifenthrin or methomyl in the F 0 generation using a topical application of a discriminating dose of insecticide. In 2008-2009, resistance to fenvalerate was 71% and no resistance to bifenthrin was recorded. In the following two seasons, resistance to pyrethroids was relatively stable with fenvalerate resistance ranging from 63% to 67% and bifenthrin resistance ranging from 5.6% and 6.4% in 2009-2010 and 2010-2011, respectively. However, in 2011-2012, pyrethroid resistance had increased to 91% and 36% for fenvalerate and bifenthrin, respectively. Resistance remained above 90% for fenvalerate and above 35% for bifenthrin in the following three seasons from 2012 to 2015. In 2008-2009, methomyl resistance was 33% and declined to 22% and 15% in 2009-2010 and 2010-2011, respectively. Methomyl resistance remained at moderate levels from 2011-12 to 2014-15, ranging from 21% to 40%. Factors that influenced selection pressure of pyrethroid and carbamate insecticides and impacted resistance frequency in H. armigera may have been associated with changes in the composition of the cropping landscape. The rapid expansion of the pulse industry and the commensurate increased use of insecticide may have played a role in reselection of high-level pyrethroid resistance, and highlights the need for an urgent and strategic response to insecticide resistance management in the Australian grains industry.

  10. Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children.

    Science.gov (United States)

    Rowe, Christopher; Gunier, Robert; Bradman, Asa; Harley, Kim G; Kogut, Katherine; Parra, Kimberly; Eskenazi, Brenda

    2016-10-01

    Low-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity. To examine associations between residential proximity to toxicity-weighted organophosphate (OP) and carbamate pesticide use during pregnancy, household- and neighborhood-level poverty during childhood, and IQ scores in 10-year-old children. We evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression. Children of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [β = -3.0; 95% Confidence Interval (CI) = (-5.6, -0.3)], Perceptual Reasoning [β = -4.0; (-7.6, -0.4)], and Working Memory [β = -2.8; (-5.6, -0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory. Residential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Reactions of CO2 with aqueous piperazine solutions: formation and decomposition of mono- and dicarbamic acids/carbamates of piperazine at 25.0 °C.

    Science.gov (United States)

    Conway, William; Fernandes, Debra; Beyad, Yaser; Burns, Robert; Lawrance, Geoffrey; Puxty, Graeme; Maeder, Marcel

    2013-02-07

    Piperazine (PZ) is widely recognized as a promising solvent for postcombustion capture (PCC) of carbon dioxide (CO(2)). In view of the highly conflicting data describing the kinetic reactions of CO(2)(aq) in piperazine solutions, the present study focuses on the identification of the chemical mechanism, specifically the kinetic pathways for CO(2)(aq) in piperazine solutions that form the mono- and dicarbamates, using the analysis of stopped-flow spectrophotometric kinetic measurements and (1)H NMR spectroscopic data at 25.0 °C. The complete set of rate and equilibrium constants for the kinetic pathways, including estimations for the protonation constants of the suite of piperazine carbamates/carbamic acids, is reported here using an extended kinetic model which incorporates all possible reactions for CO(2)(aq) in piperazine solutions. From the kinetic data determined in the present study, the reaction of CO(2)(aq) with free PZ was found to be the dominant reactive pathway. The superior reactivity of piperazine is confirmed in the kinetic rate constant determined for the formation of piperazine monocarbamic acid (k(7) = 2.43(3) × 10(4) M(-1) s(-1)), which is within the wide range of published values, making it one of the faster reacting amines. The corresponding equilibrium constant for the formation of the monocarbamic acid, K(7), markedly exceeds that of other monoamines. Kinetic and equilibrium constants for the remaining pathways indicate a minor contribution to the overall kinetics at high pH; however, these pathways may become more significant at higher CO(2) loadings and lower pH values where the concentrations of the reactive species are correspondingly higher.

  12. Communications standards

    CERN Document Server

    Stokes, A V

    1986-01-01

    Communications Standards deals with the standardization of computer communication networks. This book examines the types of local area networks (LANs) that have been developed and looks at some of the relevant protocols in more detail. The work of Project 802 is briefly discussed, along with a protocol which has developed from one of the LAN standards and is now a de facto standard in one particular area, namely the Manufacturing Automation Protocol (MAP). Factors that affect the usage of networks, such as network management and security, are also considered. This book is divided into three se

  13. Potassium channel antagonists 4-aminopyridine and the T-butyl carbamate derivative of 4-aminopyridine improve hind limb function in chronically non-ambulatory dogs; a blinded, placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Ji-Hey Lim

    Full Text Available 4-Aminopyridine (4-AP blocks voltage gated potassium channels, restoring conduction to demyelinated axons and improving function in demyelinating conditions, but its use is associated with adverse effects and benefit in spinal cord injury is limited. Derivatives of 4-AP have been developed to improve clinical efficacy while reducing toxicity. We compared the therapeutic effects of orally administered 4-AP and its t-butyl carbamate derivative (t-butyl with placebo in dogs that had suffered an acute spinal cord injury that left them chronically paralyzed. Nineteen dogs were entered into the trial, conducted in two-week treatment blocks starting with placebo, followed by random assignment to 4-AP or t-butyl, a washout and then the opposite medication followed by placebo. Investigators and owners were blinded to treatment group. Primary outcome measures included open field gait score (OFS, and treadmill based stepping score and regularity index, with additional secondary measures also considered. Thirteen of 19 dogs completed the protocol. Two were euthanized due to unrelated heath problems, two developed side effects and two were unable to complete for unrelated reasons. Dogs showed significant improvement in supported stepping score (from 17.39 to 37.24% with 4-AP; 16.85 to 29.18% with t-butyl p<0.0001 and OFS (from 3.63 to 4.73 with 4-AP; 3.78 to 4.45 with t-butyl, p = 0.005. Response was individually variable and most dramatic in three dogs that were able to walk without support with treatment. No significant difference was found between 4-AP and t-butyl. No adverse effects were reported with t-butyl but gastrointestinal upset and seizures were observed in two dogs with 4-AP. In conclusion, both 4-AP and t-butyl significantly improved supported stepping ability in dogs with chronic spinal cord injury with no adverse effects noted with t-butyl. Drug response varied widely between individuals, highlighting the need to understand the factors

  14. Substance use - prescription drugs

    Science.gov (United States)

    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

  15. Achieving Standardization

    DEFF Research Database (Denmark)

    Henningsson, Stefan

    2016-01-01

    competitive, national customs and regional economic organizations are seeking to establish a standardized solution for digital reporting of customs data. However, standardization has proven hard to achieve in the socio-technical e-Customs solution. In this chapter, the authors identify and describe what has......International e-Customs is going through a standardization process. Driven by the need to increase control in the trade process to address security challenges stemming from threats of terrorists, diseases, and counterfeit products, and to lower the administrative burdens on traders to stay...... to be harmonized in order for a global company to perceive e-Customs as standardized. In doing so, they contribute an explanation of the challenges associated with using a standardization mechanism for harmonizing socio-technical information systems....

  16. Achieving Standardization

    DEFF Research Database (Denmark)

    Henningsson, Stefan

    2014-01-01

    competitive, national customs and regional economic organizations are seeking to establish a standardized solution for digital reporting of customs data. However, standardization has proven hard to achieve in the socio-technical e-Customs solution. In this chapter, the authors identify and describe what has......International e-Customs is going through a standardization process. Driven by the need to increase control in the trade process to address security challenges stemming from threats of terrorists, diseases, and counterfeit products, and to lower the administrative burdens on traders to stay...... to be harmonized in order for a global company to perceive e-Customs as standardized. In doing so, they contribute an explanation of the challenges associated with using a standardization mechanism for harmonizing socio-technical information systems....

  17. Training Standardization

    International Nuclear Information System (INIS)

    Agnihotri, Newal

    2003-01-01

    The article describes the benefits of and required process and recommendations for implementing the standardization of training in the nuclear power industry in the United States and abroad. Current Information and Communication Technologies (ICT) enable training standardization in the nuclear power industry. The delivery of training through the Internet, Intranet and video over IP will facilitate this standardization and bring multiple benefits to the nuclear power industry worldwide. As the amount of available qualified and experienced professionals decreases because of retirements and fewer nuclear engineering institutions, standardized training will help increase the number of available professionals in the industry. Technology will make it possible to use the experience of retired professionals who may be interested in working part-time from a remote location. Well-planned standardized training will prevent a fragmented approach among utilities, and it will save the industry considerable resources in the long run. It will also ensure cost-effective and safe nuclear power plant operation

  18. [Drugs and light].

    Science.gov (United States)

    Tønnesen, H H

    1997-06-30

    The number of drugs that are found to be photochemically unstable or able to induce phototoxic side-effects is steadily increasing. It can be difficult, however, to obtain relevant information on the photoreactivity of drugs or drug products from the commonly used handbooks. This is because of lack of standard methods of evaluation or a requirement for official specifications for a given product. The author points to the main problems connected with interactions between drugs and light in vitro and in vivo. The most obvious result of exposure to light is reduced potency of the drug because of photodecomposition. Adverse effects due to the formation of photodegradation products during storage and use have also been reported. The drug substance can further cause light-induced side-effects after administration to the patient, e.g. phototoxicity and photoallergy. More data on photoreactivity are needed in order to minimize the side-effects of frequently used drugs. The article includes a list of potential photosensitizing drug substances on the Norwegian market.

  19. Drug Facts

    Medline Plus

    Full Text Available ... Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone with ... problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ...

  1. Drug Abuse

    Science.gov (United States)

    ... and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug ...

  2. Drug Facts

    Medline Plus

    Full Text Available ... Numbers and Websites Search Share Listen English Español Information about this page Click on the button that ... about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice ( ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes ... Options? What Is Recovery? What Is a Relapse? How Can Friends and Family Help? Where Can Someone ...

  5. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    Drug metabolism may be defined as the biochemical modifica- tion of one chemical form to another, occurring usually through ..... Endogenous. Enzyme. Drugs. Cofactor. Glucuronidation. UDP glucoronic. UDP-. Chloramphenicol, acid glucuronosyltransferase morphine, paracetamol, salicylic acid, fenoprofen, desipramine,.

  6. Drug Facts

    Medline Plus

    Full Text Available ... Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) ... Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted ...

  8. Study Drugs

    Science.gov (United States)

    ... What Are Study Drugs? Doctors prescribe medicines like Adderall and Ritalin to treat conditions like attention deficit ... stimulants are used as study drugs: amphetamines like Adderall, Dexedrine, or Vyvanse methylphenidates like Ritalin or Concerta ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  10. Drug Facts

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    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  12. Orphan drugs

    OpenAIRE

    Goločorbin-Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojša; Mikov, Momir

    2013-01-01

    Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs ... adicción. English Español About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  16. Drug Facts

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    Full Text Available ... to main content Easy-to-Read Drug Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts ... Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page ...

  17. Drug Facts

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    Full Text Available ... the computer will read the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  18. Drug Resistance

    Science.gov (United States)

    ... infected with a drug-resistant strain of HIV. Drug-resistance testing results are used to decide which HIV medicines to include in a person’s first HIV regimen. After treatment is started, drug-resistance testing is repeated if ...

  19. Drug allergy

    Directory of Open Access Journals (Sweden)

    Warrington Richard

    2011-11-01

    Full Text Available Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA and non-steroidal anti-inflammatory drugs.

  20. Drug: D10237 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ffusus [TAX:13579] ... Same as: E00299 ... Juncaceae (rush family) Juncus effusus stem or above ground part; Standards for non-pharmacopoeial crude drugs ... PubChem: 163312268 ...

  1. Drug: D10235 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 571] ... Same as: E00338 ... Rutaceae (rue family) Citrus unshiu, Citrus reticulata immature fruit and fruit peel; Standards for non-pharmacopoeial crude drugs ... PubChem: 163312266 ...

  2. Drug: D10238 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ucris; Adlay ... Coix lacryma-jobi [TAX:714458] ... Same as: E00845 ... Poaceae (grass family) Adlay fruit and bract; Standards for non-pharmacopoeial crude drugs ... PubChem: 163312269 ...

  3. Short Duration vs Standard Duration of Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents - A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Wassef, Anthony W A; Khafaji, Hadi; Syed, Ishba; Yan, Andrew T; Udell, Jacob A; Goodman, Shaun G; Cheema, Asim N; Bagai, Akshay

    2016-12-01

    Current guidelines recommend 12 months of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation. Whether the duration of DAPT can be safely shortened with use of second-generation DESs is unclear. We conducted a meta-analysis of randomized controlled trials comparing short duration (SD) (3-6 months) with standard longer duration (LD) (≥12 months) DAPT in patients treated with primarily second-generation DES implantation. Meta-regression was performed to explore the relationship between acute coronary syndrome (ACS) and the effect of DAPT duration. Six studies were included, with 12,752/13,928 (91.5%) patients receiving second-generation DESs. A total of 5367 patients (39%) had PCI in the setting of ACS. There was no difference in all-cause mortality (1.1% vs 1.2%; odds ratio [OR], 0.86; 95% confidence interval [CI], 0.63-1.18; P=.36) or cardiac mortality (0.9% vs 1.0%; OR, 0.92; 95% CI, 0.61-1.39; P=.69) with SD-DAPT vs LD-DAPT, respectively. Definite/probable stent thrombosis (0.5% vs 0.3%; OR, 1.33; 95% CI, 0.75-2.34; P=.51), myocardial infarction (1.5% vs 1.3%; OR, 1.17; 95% CI, 0.88-1.56; P=.29), and stroke (0.4% vs 0.4%; OR, 1.04; 95% CI, 0.60-1.81; P=.88) were similar between the groups. Compared with LD-DAPT, SD-DAPT was associated with lower clinically significant bleeding (0.9% vs 1.4%; OR, 0.64; 95% CI, 0.46-0.89; P=.01). Meta-regression analysis showed no significant association between the proportion of ACS patients in trials and duration of DAPT for the outcomes of mortality (P=.95), myocardial infarction (P=.98), or stent thrombosis (P=.89). In low-risk patients treated with contemporary second-generation DES implantation, SD-DAPT has similar rates of mortality, myocardial infarction, and stent thrombosis, with lower rates of bleeding compared with LD-DAPT.

  4. Métathèse croisée d'alcènes contenant des N-hétéroaryles. Trifluorométhylation d'ène-carbamates cycliques et dérivés

    OpenAIRE

    Lafaye , Kévin

    2015-01-01

    Has now been applied to the synthesis of a wide range of compounds such as polymers, petrochemicals, pharmaceuticals and naturals compounds. A large range of functional groups are well tolerated including alcohols, amides, carbamates and sulfonamides. However, some limitations still have to be overcome Olefin metathesis has emerged has one of the most efficient carbon-carbon bond forming reaction and such as rich N-heteroaryles which are probably causing desactivation of the ruthenium catalys...

  5. WAr on DrugS

    African Journals Online (AJOL)

    2009-04-12

    Apr 12, 2009 ... tion of drugs, especially hemp (Cannabis. Sativa), became entrenched. Oloruntoba. (2006) explained that the vigour and sus- tained efforts to legislate against drugs in contemporary Nigeria was because of the growing notoriety of the country as a transit point or centre for recruitment of drug couriers, and a ...

  6. Dose calculation of anticancer drugs

    NARCIS (Netherlands)

    Gao, Bo; Klumpen, Heinz-Josef; Gurney, Howard

    2008-01-01

    BACKGROUND: Anticancer drugs are characterized by a narrow therapeutic window and significant inter-patient variability in therapeutic and toxic effects. Current body surface area (BSA)-based dosing fails to standardize systemic anticancer drug exposure and other alternative dosing strategies also

  7. [Standards used in the regulation of medical device in USA].

    Science.gov (United States)

    Hu, Wei; Gu, Hanqing

    2007-11-01

    To study the USA government's administrative system about medical device standards as well as the standard making. The relevant documents, regulations, website that USA Food and Drug Administration announced were extensively reviewed, knowing the USA medical device standards synthetically. The USA standards system of medical device included regulatory requirements and voluntary consensus standards. This article simply introduced the laws, regulations, performance standards and consensus standards. The USA's administrative system about medical device standards as well as many standards can be referenced.

  8. Frequency standards

    CERN Document Server

    Riehle, Fritz

    2006-01-01

    Of all measurement units, frequency is the one that may be determined with the highest degree of accuracy. It equally allows precise measurements of other physical and technical quantities, whenever they can be measured in terms of frequency.This volume covers the central methods and techniques relevant for frequency standards developed in physics, electronics, quantum electronics, and statistics. After a review of the basic principles, the book looks at the realisation of commonly used components. It then continues with the description and characterisation of important frequency standards

  9. [NEPHROTOXIC DRUGS].

    Science.gov (United States)

    Popović, B; Šutić, I; Marković, N Bašić

    2016-12-01

    Renal tissue is sensitive to the effect of potentially nephrotoxic drugs and other substances that are available over-the-counter or can be purchased at healthy food stores or elsewhere, and harmful substances from the environment. The harmful effects of these substances lead to the development of recognizable clinical syndromes, including acute or chronic renal failure, tubulopathy, and proteinuria. Risk factors that influence the development of kidney disease induced by drugs are divided into those related to patient characteristics, drug characteristics, and renal function. Drugs that commonly exhibit nephrotoxic effects are analgesics, antimicrobials, chemotherapeutics, contrast agents, immunosuppressants, herbal preparations and substances containing heavy metals. Family physician must carefully observe their patients, nurturing individual approach to drug selection and determining the dose. Renal function can quickly return to normal if the damage is recognized on time. Recent research yields insights into the identification of new biomarkers that will contribute to early detection of drug induced kidney damage.

  10. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  11. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  12. Design, synthesis and in-vitro evaluation of novel tetrahydroquinoline carbamates as HIV-1 RT inhibitor and their antifungal activity.

    Science.gov (United States)

    Chander, Subhash; Ashok, Penta; Zheng, Yong-Tang; Wang, Ping; Raja, Krishnamohan S; Taneja, Akash; Murugesan, Sankaranarayanan

    2016-02-01

    Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are vital class of drugs in treating HIV-1 infection, but drug resistance and toxicity drive the need for effective new inhibitors with potent antiviral activity, less toxicity and improved physicochemical properties. In the present study, twelve novel 1-(4-chlorophenyl)-2-(3,4-dihydroquinolin-1(2H)-yl)ethyl phenylcarbamate derivatives were designed as inhibitor of HIV-1 RT using the ligand based drug design approach and in-silico evaluated for drug-likeness properties. Designed compounds were synthesized, characterized and in-vitro evaluated for RT inhibitory activity against wild HIV-1 RT. Among these, four compounds (6b, 6i, 6j and 6l) exhibited significant inhibition of HIV-1 RT (IC50 ⩽ 20 μM). Among four compounds, most active compounds 6b and 6j inhibited the RT activity with IC50 8.12 and 5.42 μM respectively. Docking studies of compounds 6b and 6j were performed against wild HIV-1 RT in order to predict their putative binding mode with selected target. Further, cytotoxicity and anti-HIV activity of compounds 6b and 6j were evaluated on T lymphocytes (C8166 cells). All the synthesized compounds were also evaluated for antifungal activity against Candida albicans and Aspergillus niger fungal strains. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Relevant Standards

    Indian Academy of Sciences (India)

    .86: Ethernet over LAPS. Standard in China and India. G.7041: Generic Framing Procedure (GFP). Supports Ethernet as well as other data formats (e.g., Fibre Channel); Protocol of ... IEEE 802.3x for flow control of incoming Ethernet data ...

  14. AIDSinfo Drug Database

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content Drugs Home Drugs Find information on FDA-approved HIV/ ... infection drugs and investigational HIV/AIDS drugs. Search Drugs Search drug Search Icon What's this? Close Popup ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? ... Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  16. Antineoplastic Drugs

    Science.gov (United States)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  17. Drug Facts

    Medline Plus

    Full Text Available ... Say if You Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button that says "Listen" on any page and the computer will read the ... Videos Information About ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often ... NIH is a component of the U.S. Department of Health and Human Services . PDF documents require the free Adobe Reader . ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What ... Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800- ...

  20. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    Chemistry of Drug Metabolism. Drug metabolism is a chemical process, where enzymes play a crucial role in the conversion of one chemical species to another. The major family of enzymes associated with these metabolic reactions is the cytochrome P450 family. The structural features and functional activity of these ...

  1. Drugged Driving

    Science.gov (United States)

    ... Survey Results Synthetic Cannabinoids (K2/Spice) Unpredictable Danger Drug and Alcohol Use in College-Age Adults in 2016 Monitoring the Future 2016 Survey Results Drug and Alcohol Use in College-Age Adults in 2015 View All NIDA Home ...

  2. Capping Drugs

    Indian Academy of Sciences (India)

    In the process of treatment, drugs are also used for medical diagnosis and for ... ing cells. Since cancer cells grow at a faster rate than the normal .... ity characteristics. After intake, the N-methyl group is cleaved in the liver to release the physiologically active drug. Similarly, membrane transportation characteristics of the neu-.

  3. The utilisation of short-lived radionuclides in the assessment of formulation and in vivo disposition of drugs

    International Nuclear Information System (INIS)

    Digenis, G.A.

    1982-01-01

    The utilisation of short-lived radionuclides in the assessment of drug formulations, and the in vivo distribution of drugs is discussed. Disintegration of tablets and capsules as a function of the formulation, and gastric emptying are important. The applicability of perturbed angular correlation to the study of the dissolution of water soluble substances from solid dosages in man is shown. Examples are given to illustrate how external scintigraphy can be applied to study the tissue distribution of 18 F-haloperidol, 82 Br-bromperidol, in rat and monkey. 11 C, L-andD-phenylalanine in rats, 11 C, D-leucine in mice with human colon tumours; 13 N-nitrosoureas and 13 N-nitroso-carbamates. (U.K.)

  4. Metabolic Engineering of the Regulators in Nitrogen Catabolite Repression To Reduce the Production of Ethyl Carbamate in a Model Rice Wine System

    Science.gov (United States)

    Zhao, Xinrui; Zou, Huijun; Fu, Jianwei; Chen, Jian

    2014-01-01

    Rice wine has been one of the most popular traditional alcoholic drinks in China. However, the presence of potentially carcinogenic ethyl carbamate (EC) in rice wine has raised a series of food safety issues. During rice wine production, the key reason for EC formation is urea accumulation, which occurs because of nitrogen catabolite repression (NCR) in Saccharomyces cerevisiae. NCR represses urea utilization by retaining Gln3p in the cytoplasm when preferred nitrogen sources are present. In order to increase the nuclear localization of Gln3p, some possible phosphorylation sites on the nuclear localization signal were mutated and the nuclear localization regulation signal was truncated, and the disruption of URE2 provided an additional method of reducing urea accumulation. By combining these strategies, the genes involved in urea utilization (DUR1,2 and DUR3) could be significantly activated in the presence of glutamine. During shake flask fermentations of the genetically modified strains, very little urea accumulated in the medium. Furthermore, the concentrations of urea and EC were reduced by 63% and 72%, respectively, in a model rice wine system. Examination of the normal nutrients in rice wine indicated that there were few differences in fermentation characteristics between the wild-type strain and the genetically modified strain. These results show that metabolic engineering of the NCR regulators has great potential as a method for eliminating EC during rice wine production. PMID:24185848

  5. Chronic cumulative risk assessment of the exposure to organophosphorus, carbamate and pyrethroid and pyrethrin pesticides through fruit and vegetables consumption in the region of Valencia (Spain).

    Science.gov (United States)

    Quijano, Leyre; Yusà, Vicent; Font, Guillermina; Pardo, Olga

    2016-03-01

    In the present study, the chronic cumulative exposure to organophosphorus (OPs), carbamates (CBs) and pyrethroid and pyrethrin (PPs) pesticides in the region of Valencia through fruit and vegetables consumption is presented. A total of 752 samples and 84 pesticides were studied of which, 52 were OPs, 23 CBs and 9 PPs. Residue data were derived from the Valencia Region monitoring program 2007-2011 and food consumption levels from a questionnaire-based dietary survey conducted in 2010 in the same area. The relative potency factor (RPFs) approach was used to estimate chronic cumulative dietary exposure to OPs, CBs and PPs using acephate, oxamyl and deltamethrin as index compounds, respectively. The exposure was estimated using a deterministic approach and two scenarios were assumed for left-censored results: the lower-bound (LB) scenario, in which unquantified results (below the limit of quantification (LOQ)) were set to zero and the upper-bound (UB) scenario, in which unquantified results were set to the LOQ. Results demonstrate that the chronic exposure of the young (fruits and vegetables is under control (even at high or frequent consumption of fruits and vegetables), for the three groups of pesticides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Radiosynthesis and evaluation of [¹¹C-carbonyl]-labeled carbamates as fatty acid amide hydrolase radiotracers for positron emission tomography.

    Science.gov (United States)

    Wilson, Alan A; Hicks, Justin W; Sadovski, Oleg; Parkes, Jun; Tong, Junchao; Houle, Sylvain; Fowler, Christopher J; Vasdev, Neil

    2013-01-10

    Fatty acid amide hydrolase (FAAH) plays a key role in regulating the tone of the endocannabinoid system. Radiotracers are required to image and quantify FAAH activity in vivo. We have synthesized a series of potent FAAH inhibitors encompassing two classes of N-alkyl-O-arylcarbamates and radiolabeled eight of them with carbon-11. The [¹¹C-carbonyl]-radiotracers were evaluated in vitro and ex vivo in rats as potential FAAH imaging agents for positron emission tomography (PET). Both sets of [¹¹C]O-arylcarbamates showed good to excellent brain penetration and an appropriate regional distribution. Pretreatments with a FAAH inhibitor demonstrated that 80-95% of brain uptake of radioactivity constituted binding of the radiotracers to FAAH. Brain extraction measurements showed that binding to FAAH was irreversible and kinetically different for the two classes of carbamates. These promising results are discussed in terms of the requirements of a suitable radiotracer for the in vivo imaging of FAAH using PET.

  7. Synthesis and evaluation of substituted 4-methyl-2-oxo-2H-chromen-7-yl phenyl carbamates as potent acetylcholinesterase inhibitors and anti- amnestic agents.

    Science.gov (United States)

    Anand, Preet; Singh, Baldev

    2013-08-01

    The study aimed to synthesize and evaluate substituted 4-methyl-2-oxo-2H-chromen-7-yl phenylcarbamates as potent acetylcholinesterase (AChE) inhibitors and anti-amnestic agents. The compounds were evaluated for AChE and butyrylcholinesterase (BuChE) inhibitory activity in rat brain homogenate and plasma, respectively. The most potent test compound 4d was evaluated for memory testing in scopolamine-induced amnesia. The phenylcarbamate substituted coumarins (4a-4h) demonstrated more potent AChE inhibitory as compared to parent 7-hydroxy-4-methylcoumarin. The introduction of phenylcarbamate moiety to coumarin template also significantly increased BuChE inhibitory activity, albeit less than AChE inhibitory activity with approximate BuChE/AChE selectivity ratio of 20. The compound 4d displayed the most potent AChE inhibitory activity with IC50 = 13.5 ± 1.7 nM, along with amelioration of amnesia in mice in terms of restoration of time spent in target quadrant and escap latency time. It is concluded that carbamate derivatives of coumarin may be employed as potential AChE inhibitors and anti-amnestic agents.

  8. Determination of N-glycans by high performance liquid chromatography using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate as the glycosylamine labeling reagent.

    Science.gov (United States)

    Wu, Yike; Sha, Qiuyue; Du, Juan; Wang, Chang; Zhang, Liang; Liu, Bi-Feng; Lin, Yawei; Liu, Xin

    2018-02-02

    Robust, efficient identification and accurate quantification of N-glycans are of great significance in N-glycomics analysis. Here, a simple and rapid derivatization method, based on the combination of microwave-assisted deglycosylation and 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) labeling, was developed for the analysis of N-glycan by high performance liquid chromatography with fluorescence detection (HPLC-FLD). After optimizing various parameters affecting deglycosylation and derivatization by RNase B, the time for N-glycan labeling was shortened to 50 min with ∼10-fold enhancement in detection sensitivity comparing to conventional 2-aminobenzoic acid (2-AA) labeling method. Additionally, the method showed good linearity (correlation coefficients > 0.991) and reproducibility (RSD N-glycome for preliminary diagnosis of human lung cancer was conducted, where significant changes of several N-glycans corresponding to core-fucosylated, mono- and disialylated glycans have been evidenced by a series of statistical analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Constitutive expression of the DUR1,2 gene in an industrial yeast strain to minimize ethyl carbamate production during Chinese rice wine fermentation.

    Science.gov (United States)

    Wu, Dianhui; Li, Xiaomin; Lu, Jian; Chen, Jian; Zhang, Liang; Xie, Guangfa

    2016-01-01

    Urea and ethanol are the main precursors of ethyl carbamate (EC) in Chinese rice wine. During fermentation, urea is generated from arginine by arginase in Saccharomyces cerevisiae, and subsequently cleaved by urea amidolyase or directly transported out of the cell into the fermentation liquor, where it reacts with ethanol to form EC. To reduce the amount of EC in Chinese rice wine, we metabolically engineered two yeast strains, N85(DUR1,2) and N85(DUR1,2)-c, from the wild-type Chinese rice wine yeast strain N85. Both new strains were capable of constitutively expressing DUR1,2 (encodes urea amidolyase) and thus enhancing urea degradation. The use of N85(DUR1,2) and N85(DUR1,2)-c reduced the concentration of EC in Chinese rice wine fermented on a small-scale by 49.1% and 55.3%, respectively, relative to fermentation with the parental strain. All of the engineered strains showed good genetic stability and minimized the production of urea during fermentation, with no exogenous genes introduced during genetic manipulation, and were therefore suitable for commercialization to increase the safety of Chinese rice wine. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. RP-HPLC method using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate incorporated with normalization technique in principal component analysis to differentiate the bovine, porcine and fish gelatins.

    Science.gov (United States)

    Azilawati, M I; Hashim, D M; Jamilah, B; Amin, I

    2015-04-01

    The amino acid compositions of bovine, porcine and fish gelatin were determined by amino acid analysis using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate as derivatization reagent. Sixteen amino acids were identified with similar spectral chromatograms. Data pre-treatment via centering and transformation of data by normalization were performed to provide data that are more suitable for analysis and easier to be interpreted. Principal component analysis (PCA) transformed the original data matrix into a number of principal components (PCs). Three principal components (PCs) described 96.5% of the total variance, and 2 PCs (91%) explained the highest variances. The PCA model demonstrated the relationships among amino acids in the correlation loadings plot to the group of gelatins in the scores plot. Fish gelatin was correlated to threonine, serine and methionine on the positive side of PC1; bovine gelatin was correlated to the non-polar side chains amino acids that were proline, hydroxyproline, leucine, isoleucine and valine on the negative side of PC1 and porcine gelatin was correlated to the polar side chains amino acids that were aspartate, glutamic acid, lysine and tyrosine on the negative side of PC2. Verification on the database using 12 samples from commercial products gelatin-based had confirmed the grouping patterns and the variables correlations. Therefore, this quantitative method is very useful as a screening method to determine gelatin from various sources. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Antagonism at combined effects of chemical fertilizers and carbamate insecticides on the rice-field N2-fixing cyanobacterium Cylindrospermum sp. in vitro

    Directory of Open Access Journals (Sweden)

    Padhy Rabindra N.

    2014-03-01

    Full Text Available Effects of chemical fertilizers (urea, super phosphate and potash on toxicities of two carbamate insecticides, carbaryl and carbofuran, individually to the N2-fixing cyanobacterium, Cylindrospermum sp. were studied in vitro at partially lethal levels (below highest permissive concentrations of each insecticide. The average number of vegetative cells between two polar heterocysts was 16.3 in control cultures, while the mean value of filament length increased in the presence of chemical fertilizers, individually. Urea at the 10 ppm level was growth stimulatory and at the 50 ppm level it was growth inhibitory in control cultures, while at 100 ppm it was antagonistic, i.e. toxicity-enhancing along with carbaryl, individually to the cyanobacterium, antagonism was recorded. Urea at 50 ppm had toxicity reducing effect with carbaryl or carbofuran. At 100 and 250 ppm carbofuran levels, 50 ppm urea only had a progressive growth enhancing effect, which was marked well at 250 ppm carbofuran level, a situation of synergism. Super phosphate at the 10 ppm level only was growth promoting in control cultures, but it was antagonistic at its higher levels (50 and 100 ppm along with both insecticides, individually. Potash (100, 200, 300 and 400 ppm reduced toxicity due to carbaryl 20 and carbofuran 250 ppm levels, but potash was antagonistic at the other insecticide levels. The data clearly showed that the chemical fertilizers used were antagonistic with both the insecticides during toxicity to Cylindrospermum sp.

  12. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  13. Drug Facts

    Science.gov (United States)

    ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  14. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  15. Drug Facts

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    Full Text Available ... Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA ( ... Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/ ...

  16. Drug Facts

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    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  17. Drug Facts

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    Full Text Available ... MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco ... Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth ( ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  19. Drug Facts

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  20. Drug Facts

    Medline Plus

    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... changes in her life. She finds support from family and friends who don't use marijuana. Haga ...