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Flow-injection spectrophotometric determination of phenolic drugs and carbamate pesticides by coupling with diazotized 2,4,6-trimethylaniline.

A flow-injection (FI) spectrophotometric system is proposed for the determination of phenols and carbamates. In the FI manifolds, the solutions of phenols or carbamates (the latter after hydrolysis with NaOH) were injected into a diazonium ion carrier stream at pH 9.5 (buffered with tetrahydroborate), which was formed by mixing 2,4,6-trimethylaniline (TMA) with nitrate in a sodium dodecyl sulfate aqueous micellar medium. Absorbance was measured at 550 nm. The system combines the advantages derived from the use of TMA for the coupling of phenols in basic micellar media, because of the inhibition of the self-coupling reaction of the reagent, with the precision and speed of the FI procedures. Other diazotized reagents produced excessive blank signals. The procedures were successfully applied to the determination of phenolic drugs (epinephrine, acetaminophen, and gualacol) in pharmaceuticals and carbamates (bendiocarb, benfuracarb, carbaryl, carbofuran, methiocarb, promecarb, and propoxur) in pesticide products and water samples.

Acetaminophen↗

Glycosuria in organophosphate and carbamate poisoning.

OBJECTIVE: Puzzled by the observation of occurrence of transient glycosuria in several patients admitted with organophosphate and carbamate compound poisoning, we undertook a critical analysis of this observation. METHODS: Of the fifty-one consecutive patients admitted to the intensive care unit with organophosphate and carbamate compound poisoning, in 23 subjects the nature of the compound consumed was known; these were studied. The occurrence and duration of glycosuria, its magnitude, associated hyperglycemia if any, and correlation thereof were recorded. RESULTS: Sixteen out of the 23 subjects (69%) demonstrated transient glycosuria. There were 13 men and 10 women. 10 subjects had euglycemia associated with glycosuria; 6 subjects had transient glycosuria with hyperglycemia (defined as random glucose over 160 mg%). None of the subjects had diabetes mellitus and the pre-hospital-discharge blood sugars were in the normal range. CONCLUSION: Glycosuria (renal), albeit transient, was noted in a proportion of subjects admitted with organophosphate and carbamate poisoning. The exact etiology of this is unclear but in the light of recent literature, it is likely that oxidative stress at the renal tubular level leading to renal tubular damage may be the most likely explanation. Further, larger studies are needed to elucidate this is detail.

Adult↗

Piperidine-containing histamine H3-receptor antagonists of the carbamate series: variation of the spacer length.

Ten carbamate derivatives have been prepared from appropriate isocyanates and omega-piperidino-1-alkanols. All compounds belong to the new generation of non-imidazole histamine H3-receptor ligands which may have beneficial pharmacokinetic properties compared with the classical imidazole-containing H3-receptor antagonists. The carbamates were evaluated in vitro for antagonist activity at guinea-pig (gp) H3, H2, H1, and M3 receptors, respectively. They displayed moderate affinity for H3 receptors (pA2 5.8-7.0 in the gp ileum assay) as well as low to moderate selectivities vis-à-vis H2 (gp atrium), H1 (gp ileum), and M3 (gp ileum) receptors. A typical member of this series is 7-piperidino-1-heptyl N-(4-phenyl-1-butyl)carbamate (17) with pA2 values of 7.02 (H3), 5.92 (H1), and 6.38 (M3), respectively, and a pD'2 value of 5.46 (H2).

Animals↗

Further studies using carbamate esters as model compounds to investigate the role of lipophilicity in the gastrointestinal absorption of foreign compounds.

In order to examine the validity of models proposed previously for the gastrointestinal absorption of foreign compounds, the absorption behavior of a series of N-methylated carbamates has been studied in the rat. An optimal partition coefficient for the intestinal absorption of these compounds was demonstrated but this value was approximately one order higher than that reported earlier for a related series of unsubstituted carbamates. It is suggested that this difference is due to the modification in hydrogen bonding arising from N-methyl substitution. In contrast, an optimal partition coefficient for gastric absorption could not be demonstrated within the range of the apparent partition coefficient studied. The absorption behavior of the N-methylated carbamates tends to confirm the different trends previously observed between drug absorption from the intestine and that from the stomach.

Absorption↗

[Xenopsylla cheopis (Siphonaptera: Xenopsyllinae), fleas in rural plague areas of high altitude Madagascar: level of sensitivity to DDT, pyrethroids and carbamates after 50 years of chemical vector control].

The resistance of Xenopsylla cheopis from urban area to pyrethroids, to DDT, and their susceptibility to carbamate are known. We have evaluated the susceptibility of X. cheopis collected from three rural localities: Ambodisiarivo (district of Antananarivo Avaradrano), Mandoto (district of Betafo), Analaroa (district of Anjozorobe) in the province of Antananarivo and in Besoa (district of Ambalavao) in the province of Fianarantsoa. The standard WHO protocol was used and four insecticides were tested: deltamethrin 0.025%, cyfluthrin 0.15% (pyrethroids), DDT 4% (organochlorine), propoxur 1% and bendiocarb 0.1% (carbamate). X. cheopis has been shown resistance to DDT 4%, to deltamethrin 0.025% but was susceptible in the rural area around Antananarivo City. They were tolerant to deltamethrin 0.025% and cyfluthrin 0.15% but susceptible to propoxur 0.1% and bendiocarbe 1% in the districts of Betafo and Anjozorobe. In Besoa, X. cheopis was resistant to DDT 4%, tolerant to deltamethrin 0.025% and cyfluthrin 0.15% but susceptible to propoxur 0.1% and bendiocarbe 1%. These results indicate that DDT and pyrethroids can not be recommended any more for the vector control in the rural area around the capital. The use of pyrethroids in the other districts of the central highland must be joined with a X. cheopis susceptibility control. In case of resistance to pyrethroids, carbamates would be proposed to control plague vector in the rural area. The high level of resistance to DDT and pyrethroid in the rural area around the capital confirms the importance of studying the flea population in different area of Madagascar and the possibility of the gene resistance propagation.

Altitude↗

THE STABILITY OF RESISTANCE TO CARBAMATE INSECTICIDES IN THE HOUSEFLY AFTER CESSATION OF SELECTION PRESSURE.

Two housefly strains selected for maximal resistance for 30 generations with Isolan (1-isopropyl-3-methyl-5-pyrazolyl dimethylcarbamate) and m-isopropylphenyl methylcarbamate, respectively, were released from insecticidal pressure and their responses to these two carbamates were studied through 62 further generations.In the Isolan-selected strain, resistance to both carbamates remained virtually unchanged up to the 41st generation; it regressed gradually thereafter, and by the 62nd generation the strain contained approximately 28% susceptible individuals. Resistance in the strain selected with m-isopropylphenyl methylcarbamate regressed rapidly, especially between the 11th and 19th generations; by the 54th generation the strain was almost as susceptible to both carbamates as before selection.The author concludes that insecticidal pressure with Isolan resulted in the development of a relatively stable resistant phenotype, while similar selection pressure with m-isopropylphenyl methylcarbamate on the same parental stock and for the same length of time produced an equally resistant but unstable phenotype. This differential stability of resistance is attributed to the incorporation of dissimilar modifying genes in the two strains during the process of selection for the character of resistance.

Animals↗

Multiresidue method for N-methyl carbamates and metabolite pesticide residues at the parts-per-billion level in selected representative commodities of fruit and vegetable crop groups.

A reversed-phase liquid chromatographic method with both fluorescence and mass spectrometric detection is presented for the determination of 13 parent N-methyl carbamate pesticides and their metabolites, as well as piperonyl butoxide, for a total of 24 compounds in selected fruits and vegetables. The commodities chosen were of special concern to the U.S. Environmental Protection Agency (EPA) because they had the least amount of monitoring data for dietary exposure estimates used in risk assessment. The method is based on a judicious selection of procedures from U.S. Food and Drug Administration sources such as the Pesticide Analytical Manual (Volume I), and Laboratory Information Bulletins, plus additional material from the chemical literature combined in a manner to recover the N-methyl carbamates and their metabolites at the 1 microg/kg or 1 part-per-billion level. The method uses an acetone extraction, followed by an aminopropyl solid-phase extraction cleanup. Determination of residues is by RP-LC, in which the liquid chromatograph is interfaced with either a fluorescence or a mass spectrometric detector. The method is designed so that a set of 6 samples can be prepared in 1 working day for overnight instrumental analysis. Recovery data are presented from analyses of selected commodities in some of EPA's fruit and vegetable crop groupings. A table listing relative retention times is presented for the N-methyl carbamates and their metabolites.

Carbamates↗

[Separation and detection of seven carbamate pesticides in biological samples by solid phase extraction and high performance liquid chromatography].

Methomyl, metolcarb, propoxur, carbaryl, isoprocarb, diuron and bassa are all carbamate pesticides. In this paper, a reversed-phase HPLC method is described for analysis of these carbamate pesticides in biological samples with Spherisorb C18 column (150 mm x 2.0 mm i.d., 5 microm), 60:40 (V/V) MeOH-H20 eluent and photodiode array detector. These pesticides were identified by their spectrum characteristics and retention times. Their quantity was determined by their peak area. The biological samples were extracted with C18 cartridge and eluted with ethyl acetate, and then analysed by HPLC. The sensitivity of detection for the seven carbamates was in the range of 1-2 mg/L of blood sample and 5-10 mg/L of urine sample. The recoveries of blood and urine samples were 70%-80% and 65%-82%, respectively. The method is simple, rapid and highly sensitive.

Carbamates↗

Molecular electrostatic potential-anthelmintic activity relationships of 5H-mebendazole and some related heterocyclic carbamates.

5H-Mebendazole and some related heterocyclic methyl carbamates were synthesized and their anthelmintic activity against Caenorhabditis elegans was determined. In order to study the influence of the heteroaromatic region with regard to the carbamate moiety on biological activity, the molecular electrostatic potentials (MEP) of all structures were calculated and a structure-activity relationship (SAR) was established. The electrostatic pattern of activity includes two minima of the carbamate moiety, a third heterocyclic minimum, and a pi-electronic region.

Animals↗

Immune functions in methyl and ethyl carbamate treated mice.

Female B6C3F1 hybrid mice (5-7 weeks of age) were given methyl or ethyl carbamate over a 2 week period and subsequently examined for alterations in various immunological parameters. Exposure to methyl carbamate, a non-carcinogen, did not cause any alterations in the parameters examined. In contrast, exposure to the multipotential carcinogen, ethyl carbamate (urethan) at tumourigenic dosages caused severe myelotoxicity at all dosage levels. Related to the myelotoxicity was a marked depression of natural killer cell activity. Other parameters including susceptibility to tumour cell challenge, humoral immunity, cellular immunity and macrophage function were less affected. These studies indicate that non-toxic, but carcinogenic dosages of urethan, have profound but selective effects on the immune system which can be related to alterations in bone marrow functions.

Animals↗

[Thiocarbamic and carbamic esters of benzenedithiols with antimycotic activity].

o-, m- and p-phenylen esters of some dithio and thiol carbamic acids N-monosubstituted were prepared and tested for in vitro antifungal activity. The substances studied [Tables I leads to III; substances (I leads to XXI) were all new and were prepared by the reaction of benzenethiols with suitable isothiocyanates or isocyanates. The fungistatic activity of the products was tested in vitro against the four following strains: Candida albicans, Candida tropicalis, Saccharomyces cerevisiae and Trichophyton mentagrophytes. The results show that the diesters of N-monosubstituted carbamic acids of benzen-1,2-dithhiol (Table I) have marked antimycotic activity, of the same order or greater than that of clotrimazol. Among the thiocarbamic and carbamic diesters of benzen-1,3- and 1,4-dithiol, the most active are the N-benzyl- and N-beta-phenyethyldithiocarbamic derivatives.

Antifungal Agents↗

Synthesis of esters of aliphatic and aromatic carbamic acids. A comparative study of properties and local anesthetic activity of these compounds.

Four basic esters of cyclohexancarbamic acid and their salts with hydrochloride were synthesized and evaluated for local anesthetic activity. It was found that also aliphatic carbamates studied exhibit local anesthetic activity comparable with the activity of analogous esters of aromatic (2-methoxyphenyl) carbamic acid. Our comparative investigation shows that the presence of aromatic group in the ester of carbamic acid influences local anesthetic activity, however the occurrence of aromatic moiety is not necessary condition for their activity.

Anesthetics, Local↗

[Anti-ulcer effectiveness of mono- and dibasic carbamates with local anesthetic effects].

An evaluation of anti-ulcer effects of mono- and dibasic carbamate local anaesthetics was performed using two experimental models of gastric ulcers, i.e. those induced by stress, or by ligation of the pylorus. These models have been found not to be identical. In the case of stress-induced ulcers, no experimental animal died as compared to the second experimental group with a 30% mortality rate due to the more frequent occurrence of ulcer perforations. Result similarities of both models could only be found with respect to the range of damage of the mucous membrane of the stomach. A premedication with a majority of basic carbamates decreased the incidence and range of ulcer lesion. The anti-ulcer activity of monobasic carbamates was more significant when compared with dibasic compounds.

Anesthetics, Local↗

Influence of pretreatment of carbamates on dynamic pulmonary mechanics in rats exposed to sarin aerosols.

The effect of pretreatment of two carbamates, pyridostigmine and physostigmine on dynamic pulmonary mechanics has been studied in rats exposed to sarin aerosols. Sign-free dose of pyridostigmine (0.075 mg/kg, i.m.) or physostigmine (0.1 mg/kg, i.m.) did not significantly alter the parameters of the dynamic pulmonary mechanics 20 min after treatment. However, sarin (51.2 mg/m3, for 15 min) depressed the respiratory rate, air flow and minute volume and enhanced the transthoracic pressure and tidal volume. Pretreatment with carbamates 20 min prior to sarin exposure significantly modified or counteracted the above induced changes. It is concluded that the protective effect of carbamates is mainly due to the correction of respiratory changes caused by sarin aerosols in rats.

Aerosols↗

Characterization of resistance to organophosphate, carbamate, and pyrethroid insecticides in field populations of Aedes aegypti from Venezuela.

Resistance to the organophosphates (OP) temephos, malathion, and pirimiphos methyl, and the carbamate propoxur was found to be low (< 5-fold) in 3 Aedes aegypti populations collected from Falcon and Aragua states of Venezuela. Resistance to chlorpyrifos (OP), permethrin, and lambda-cyhalothrin (pyrethroids) was moderate (7-fold) in both populations. Mechanisms of resistance were investigated with the synergists piperonyl butoxide (mixed function oxidase inhibitor) and S, S, S-tributyl phosphorothioate (DEF, an esterase inhibitor). Nonspecific esterase and oxidase enzymes played a significant role in OP and carbamate resistance, respectively. Resistance to pyrethroid insecticides was not affected by DEF or piperonyl butoxide. This suggested the presence of another mechanism such as altered target site sensitivity (kdr). Biochemical tests showed significantly greater amounts of esterase activity in field strains, whereas insensitive acetylcholinesterase was not involved in either OP or carbamate resistance. These results must be considered in future control programs for Ae. aegypti, because OPs and pyrethroids are currently used in vector control in most countries of Central and South America.

Aedes↗

Multiorgan damage in acute oral carbamates poisonings.

The aim of the study was to evaluate the frequency and the kind of multiorgan damage in acute oral carbamates poisonings. Under analysis there were 36 carbamates orally poisoned patients treated at the Department of Clinical Toxicology in the years 1987-1997. Patients with the liver or biliary tract diseases, chronic circulatory insufficiency symptoms, HBs antigen carriers, who suffered head traumas, CNS illness and heavy drinkers were excluded from the study. The organs damage was noted in 91.7% of the poisoned patients. The respiratory system followed by the CNS and the liver were mostly affected by carbamates toxicity. The frequency of pathological changes in the kidney and circulatory system was relatively lower. Only in a few persons peripheral nervous system injuries were noted. In 15% of the examined group the injuries of one organ only was stated. In 48.5% of the patients simultaneous injury of two and three organs or systems were noted. 36.3% of the patients suffered from multiorgan (four or more) damage. In all the severely poisoned patients (III degree) the organs damage was noted. In 53% of them the simultaneous damage of four or more organs/systems was noted. In the group of patients stated as moderately poisoned on admission to the clinic, the multiorgan damage (2-3 organs/systems) was found in 77% of the patients. The lowest number of organ damage was observed in the group of slightly poisoned patients.

Acetylcholinesterase↗

Anticholinesterase action of 3-diethylaminophenyl-N-methyl-carbamate methiodide in vitro and in vivo.

The inhibitory effect of 3-diethylaminophenyl-N-methylcarbamate methiodide on rat brain acetylcholinesterase and horse plasma butyrylcholinesterase was studied in vitro. This quaternary carbamate is a more potent inhibitor of acetylcholinesterase than butyrylcholinesterase. Complete inhibition of acetylcholinesterase may be achieved without any inhibition of butyrylcholinesterase, i.e. that 3-diethylaminophenyl-N-methylcarbamate methiodide is a selective inhibitor of acetylcholinesterase. The inhibitory effect of different doses of this compound on plasma and liver butyrylcholinesterase and erythrocyte, brain, heart and diaphragm acetylcholinesterase of the rat was studied in vivo. With increasing doses of carbamate the inhibition of the enzymes in the plasma, erythrocytes, liver, heart, and diaphragm increased while the brain acetylcholinesterase was unaffected. The toxic action of carbamate studied was preferably due to acetylcholin esterase inhibition in the peripheral nervous system and this compound cannot penetrate the blood-brain barrier.

Animals↗

Expression of human Krev-1 gene in lungs of transgenic mice and subsequent reduction in multiplicity of ethyl carbamate-induced lung adenomas.

Mice of the A/J strain are useful models of lung cancer because they develop tumors spontaneously or after treatment with ethyl carbamate. These tumors are thought to arise from either Clara cells (papillary tumors) or alveolar type 2 cells (alveolar tumors); like many human lung adenocarcinomas, the mouse tumors involve Kiras activation. Transformation with Ki-ras can be reversed by coexpression of the Krev-1 gene in tissue culture. To test the tumor suppressor activity of Krev-1 in vivo, we produced transgenic A/J mice expressing Krev-1 under the control of the rabbit uteroglobin promoter, which directs expression of heterologous genes to the lung Clara cells. Krev-1 was expressed specifically in the lungs of transgenic mice. Sixty-six mice (35 transgenic and 31 nontransgenic) from three lines were given ethyl carbamate, and the numbers of resulting lung tumors were compared between transgenic and nontransgenic animals. The mean number (+/-standard deviation) of ethyl carbamate-induced lung tumors was 21.7 +/- 1.3 in transgenic mice and 26.9 +/- 1.3 in their nontransgenic littermates (P < 0.01). Sequencing of polymerase chain reaction-amplified ras DNA from 15 transgenic mouse tumors and 16 nontransgenic mouse tumors (controls) detected mutations in codon 61 in 13 tumors from the transgenic group and 11 tumors in the control group, whereas mutations in codon 12 were detected in only one tumor in the transgenic group and in four tumors in the controls. Together, these data demonstrate for the first time the tumor suppressor activity of Krev-1 in vivo and suggest that Krev-1 tumor suppressor activity may be specific for cells harboring mutations in codon 12 of ras.

Adenoma↗