Biotransformation of trace organic compounds by activated sludge from a biological nutrient removal treatment system.

PubMed

Inyang, Mandu; Flowers, Riley; McAvoy, Drew; Dickenson, Eric

2016-09-01

The removal of trace organic compounds (TOrCs) and their biotransformation rates, kb (LgSS(-)(1)h(-)(1)) was investigated across different redox zones in a biological nutrient removal (BNR) system using an OECD batch test. Biodegradation kinetics of fourteen TOrCs with initial concentration of 1-36μgL(-)(1) in activated sludge were monitored over the course of 24h. Degradation kinetic behavior for the TOrCs fell into four groupings: Group 1 (atenolol) was biotransformed (0.018-0.22LgSS(-)(1)h(-)(1)) under anaerobic, anoxic, and aerobic conditions. Group 2 (meprobamate and trimethoprim) biotransformed (0.01-0.21LgSS(-)(1)h(-)(1)) under anoxic and aerobic conditions, Group 3 (DEET, gemfibrozil and triclosan) only biotransformed (0.034-0.26LgSS(-)(1)h(-)(1)) under aerobic conditions, and Group 4 (carbamazepine, primidone, sucralose and TCEP) exhibited little to no biotransformation (<0.001LgSS(-)(1)h(-)(1)) under any redox conditions. BNR treatment did not provide a barrier against Group 4 compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Possible malignant hyperthermia as reaction to an overdose of myotonolytic, antidepressive and sedative drugs (author's transl)].

PubMed

Hackl, J M; Engl, J; Hofstädter, F; Bonelli, S; Rumpl, E; Dworzak, E; Puschendorf, B

1981-08-07

A 51-year-old male patient with no history of musculo-skeletal or myopathic abnormalities, but suffering from manic-depressive psychosis, attempted suicide with an overdose of dolpersin hydrochloride (Mydocalm), dipenzepine hydrochloride (Noveril), meprobamate (Mepronox) and nitrazepam (Mogadon). He developed high fever, muscle rigidity, tachycardia, arrhythmias, hypotension and mottled cyanosis, symptoms well-known in persons with malignant hyperthermia, an autosomally inherited disease of skeletal muscle. There is also discussed the manifestation and the symptoms of an acute rhabdomyolysis. The diagnosis was confirmed by chemical pathological laboratory findings, including respiratory and metabolic acidosis, myoglobinaemia accompanied by myoglobin diuresis, and elevated creatine phosphokinase (CPK values up to 2790 U/l). Electron microscopic examination of muscle tissue revealed signs of myolysis and mitochondrial reactions with pleoconic hyperplasia. No inhalation anaesthetics or skeletal muscle relaxants, such as succinyl choline, were used in this case. Therefore, malignant hyperthermia might have been induced by a combination of drugs which were not known to induce this abnormal muscular reaction. However, the muscle relaxant effect of dolpersin hydrochloride may have acted as a possible inducer of the attack.

Convulsions induced by centrally administered NMDA in mice: effects of NMDA antagonists, benzodiazepines, minor tranquilizers and anticonvulsants.

PubMed Central

Moreau, J. L.; Pieri, L.; Prud'hon, B.

1989-01-01

1. Convulsions were induced reproducibly by intracerebroventricular injection of N-methyl-D-aspartic acid (NMDA) to conscious mice. 2. Competitive (carboxypiperazine-propylphosphonic acid, CPP; 2-amino-7-phosphonoheptanoic acid, AP7) and non-competitive (MK801; phencyclidine, PCP; thienylcyclohexylpiperidine, TCP; dextrorphan; dextromethorphan) NMDA antagonists prevented NMDA-induced convulsions. 3. Benzodiazepine receptor agonists and partial agonists (triazolam, diazepam, clonazepam, Ro 16-6028), classical anticonvulsants (diphenylhydantoin, phenobarbitone, sodium valproate) and meprobamate were also found to prevent NMDA-induced convulsions. 4. Flumazenil (a benzodiazepine receptor antagonist) and the GABA agonists THIP and muscimol (up to subtoxic doses) were without effect. 5. Flumazenil reversed the anticonvulsant action of diazepam, but not that of MK801. 6. Results obtained in this model differ somewhat from those described in a seizure model with systemic administration of NMDA. An explanation for this discrepancy is offered. 7. This model is a simple test for assessing the in vivo activity of NMDA antagonists and also expands the battery of chemically-induced seizure models for characterizing anticonvulsants not acting at NMDA receptors. PMID:2574061

Penetration of chemicals into the oocyte, uterine fluid, and preimplantation blastocyst

PubMed Central

Fabro, Sergio

1978-01-01

Chemicals, including commonly used drugs (e.g., penicillin, meprobamate, pyridium, and mercaptomerin) penetrate and persist for some time in the ovarian follicular fluid at concentrations approximately similar to that of the serum. Information as to the penetration of chemicals into the granulosa cells and into the oocyte is scanty, although there are some indications that these structures are also permeable to foreign chemicals. Similarly, caffeine, nicotine, thiopental, salicylic acid, antipyrine, barbital, and isoniazid enter the uterine secretion and penetrate the preimplantation blastocyst of mice, rats and rabbits. The pattern of distribution of compounds among ovarian follicular fluid, uterine luminal fluid, blastocyst and plasma varies from compound to compound and appears to be related to the molecular weight and degree of ionization of the compound and differs in pregnant and nonpregnant animals. Thus, nicotine and DDT accumulate in the uterine luminal fluid of pregnant but not in that of nonpregnant rabbits. The penetration of foreign chemicals into the oocyte, uterine luminal fluid, and preimplantation blastocyst may exert adverse effects on fertilization, implantation, and/or further development of the conceptus. The possible toxicological importance of this process to eutherian reproduction is discussed. PMID:17539150

Determination of halothane-induced sleeping time in the rat: effect of prior administration of centrally active drugs.

PubMed Central

Turnbull, M J; Watkins, J W

1976-01-01

A method is described for the determination of halothane-induced sleeping time in the rat. 2 The sleeping time exhibited a diurnal variation which was due, at least in part, to a change in the sensitivity of the central nervous system (CNS) to the anaesthetic. 3 Tolerance to halothane did not develop in rats repeatedly exposed to the anaesthetic over a period of over 48 hours. 4 Repeated sleeping time determinations have been used to follow changes in the sensitivity of the CNS to the anaesthetic occurring with time. 5 A tolerance to halothane was induced by pretreatment of rats with doses of amylobarbitone, pentobarbitone or meprobamate sufficient to keep animals anaesthetized for approximately 12 hours. This tolerance was followed by a period of halothane-hypersensitivity. 6 Halothane-tolerant animals awakened with higher brain halothane concentrations and were also tolerant to intracerebroventricularly administered pentobarbitone. 7 Halothane-hypertensive rats awakened with lower brain halothane concentrations and were also hypersensitivity to intracerebroventricularly administered pentobarbitone. 8 The possibility that the induction of cross-tolerance to halothane may be indicative of a drug's potential to produce dependence is discussed. PMID:987820

Suspended solids moderate the degradation and sorption of waste water-derived pharmaceuticals in estuarine waters.

PubMed

Aminot, Yann; Fuster, Laura; Pardon, Patrick; Le Menach, Karyn; Budzinski, Hélène

2018-01-15

This study focuses on the fate of pharmaceuticals discharged into an estuarine environment, particularly into the Turbidity Maximum Zone (TMZ). Batch experiments were set up to investigate the factors regulating the degradation of 53 selected pharmaceuticals. Treated effluents from Bordeaux city (France) were mixed with water from the estuarine Garonne River during 4weeks under 6 characterized conditions in order to assess the influence of suspended particulates, sterilization, untreated wastewater input and dilution on the degradation kinetics. Of the 53 pharmaceuticals monitored, 43 were quantified at the initial time. Only 7 exhibited a persistent behavior (e.g. carbamazepine, meprobamate) while biotic degradation was shown to be the main attenuation process for 38 molecules (e.g. abacavir, ibuprofen highly degradable). Degradation was significantly enhanced by increasing concentrations of suspended solids. A persistence index based on the half-lives of the compounds has been calculated for each of the 43 pharmaceuticals to provide a practical estimate of their relative stability. The stability of pharmaceuticals in estuarine environments is likely to be highly variable and attenuated primarily by changes in suspended solid concentration. Copyright © 2017 Elsevier B.V. All rights reserved.

Fate and Transport of Pharmaceutical Compounds Applied to Turf-Covered Soil

NASA Astrophysics Data System (ADS)

Young, M.; Green, R. L.; Devitt, D.; McCullough, M.; Wright, L.; Vanderford, B. J.; Snyder, S. A.

2012-12-01

In arid and semi-arid regions, the use of treated wastewater for landscape irrigation is becoming common practice and a significant asset to conserve potable water supplies. Public interest and lack of field-scale data are leading to a concern that compounds found in reuse water could persist in the environment and contaminate groundwater. As part of a larger study, 2-yr experiments were conducted in CA and NV, where reuse water was the primary source of non-ambient water input. A total of 13 compounds were studied, all originating in irrigation water applied to soil covered in turf or left bare. The target compounds included atenolol, atorvastatin, carbamazepine, diazepam, diclofenac, fluoxetine, gemfibrozil, ibuprofen, meprobamate, naproxen, primidone, sulfamethoxazole, triclosan, and trimethoprim. Analytical protocols for all compounds (detection at ng/L range) were established before the study commenced. The goals of the research were to increase available data on the fate and transport of these target compounds in turfgrass/soil systems, and to use these data to assess long-term risk from using water containing these compounds. Experiments conducted at two scales are discussed here: lysimeter-scale and field-scale. At the lysimeter-scale, 24 drainage lysimeters (120 cm thick) were exposed to treated wastewater as an irrigation source. Lysimeters varied by soil type (two types), soil cover (bare- versus turf-covered) and leaching fraction (5% and 25%). Upper and lower boundary conditions were monitored throughout the study. Water samples were collected periodically after water breakthrough. After the study, soil samples were analyzed for compound mass, allowing compound mass balance and removal to be assessed. At the field-scale, passive drain gages (Decagon Devices) were installed in triplicate in fairways at four operational golf courses, one in NV and three in CA, all with histories of using treated wastewater. The gages measure water fluxes through the 60-cm thick column and store water for subsequent sampling and analysis. Irrigation water was sampled and analyzed for input mass. Using output mass, removal efficiencies could also be assessed. Results of the lysimeter study showed that mass fluxes were reduced to less than 1 g/ha/yr for all compounds (sulfamethoxazole was highest at 0.25 g/ha/yr). Solute breakthrough was concentrated during fall and winter periods when turf was overseeded and sites received winter precipitation. Results of the golf course study were similar, showing scalability. We report more than 100 instances of target compounds detected in water that percolated through the turf and upper 60 cm of soil, but with total mass fluxes of <0.1 g/ha throughout the study. Sulfamethoxazole, meprobamate, and carbamazepine were most commonly found in drainage water, but gemfibrozil, diclofenac, naproxen, and triclosan were also found in more than one sample. The results allowed for a preliminary risk assessment to be conducted. Based on our results, restricting the use of recycled water, based solely on the presence of PPCPs should only be considered at sites where soils are extremely sandy and irrigation regimes are not based on an evapotranspiration feedback approach.

Evaluation of enhanced coagulation pretreatment to improve ozone oxidation efficiency in wastewater.

PubMed

Wert, Eric C; Gonzales, Sarah; Dong, Mei Mei; Rosario-Ortiz, Fernando L

2011-10-15

Enhanced coagulation (EC) using ferric chloride was evaluated as a pretreatment process to improve the efficiency of ozone (O3) for the oxidation of trace organic contaminants in wastewater. At the applied dosages (10-30 mg/L as Fe), EC pretreatment removed between 10 and 47% of the dissolved organic carbon (DOC) from the three wastewaters studied. Size exclusion chromatography (SEC) showed that EC preferentially removed higher apparent molecular weight (AMW) compounds. Subsequent O3 testing was performed using an O3:DOC ratio of 1. Results showed that O3 exposures were similar even though the required doses were reduced by 10-47% by the EC pretreatment process. Hydroxyl radical (HO·) exposure, measured by parachlorobenzoic acid (pCBA), showed 10% reduction when using a FeCl3 dose of 30 mg/L, likely due to the lower O3 dose and decreased production of HO· during the initial phase of O3 decomposition (t<30 s). The oxidation of 13 trace organic contaminants (including atenolol, carbamazepine, DEET, diclofenac, dilantin, gemfibrozil, ibuprofen, meprobamate, naproxen, primidone, sulfamethoxazole, triclosan, and trimethoprim) was evaluated after EC and O3 treatment. EC was ineffective at removing any of the contaminants, while O3 oxidation reduced the concentration of compounds according to their reaction rate constants with O3 and HO·. Copyright © 2011. Published by Elsevier Ltd.

[Toxicologic blood emergency screening].

PubMed

Cohen, Sabine; Manat, Aurélie; Dumont, Benoit; Bévalot, Fabien; Manchon, Monique; Berny, Claudette

2010-01-01

In order to overcome the stop marketing by Biorad company of automated high performance liquid chromatograph with UV detection (Remedi), we developed a gas chromatography-mass spectrometry (GC-MS) to detect and to give an approximation of the overdose of molecules frequently encountered in drug intoxications. Therefore two hundred eighty seventeen blood samples were collected over a period of one year and allowed us to evaluate and compare the performance of these two techniques. As identification, GC-MS does not identify all molecules detected by Remedi in 24.2% of cases; there is a lack of sensitivity for opiates and the systematic absence of certain molecules such as betablockers. However, in 75.8% of cases the GC-MS detects all molecules found by Remedi and other molecules such as meprobamate, paracetamol, benzodiazepines and phenobarbital. The concentrations obtained are interpreted in terms of overdose showed 15.7% of discrepancy and 84.3% of concordance between the two techniques. The GC-MS technique described here is robust, fast and relatively simple to implement; the identification is facilitated by macro commands and the semi quantification remains manual. Despite a sequence of cleaning the column after each sample, carryover of a sample to the next remains possible. This technique can be used for toxicologic screening in acute intoxications. Nevertheless it must be supplemented by a HPLC with UV detection if molecules such as betablockers are suspected.

ECT-Related Anxiety: A Systematic Review.

PubMed

Obbels, Jasmien; Verwijk, Esmée; Bouckaert, Filip; Sienaert, Pascal

2017-12-01

A significant proportion of electroconvulsive therapy (ECT)-treated patients experience anxiety anticipating the treatment, often to such an extent that they refuse or discontinue a much-needed treatment. Despite its great impact on treatment adherence, anxiety in patients receiving ECT is underexposed in the scientific literature. We aimed to review the prevalence and specific subjects of ECT-related anxiety and therapeutic interventions to reduce it. We performed a computerized search (EMBASE, MEDLINE, and PsycINFO) for articles meeting the following inclusion criteria: (1) qualitative (interview) studies, quantitative (questionnaire) studies, or experimental (interventional) studies that (2) report on anxiety that is related to a planned, ongoing, or past ECT treatment. Of 1160 search results, 31 articles were included. Electroconvulsive therapy-related anxiety is estimated to be present in 14% to 75% of patients and is most often linked to worries about memory impairment or brain damage. Only a few interventions (chlorpromazine, meprobamate, propofol, a talking-through technique, an information leaflet, and animal-assisted therapy) have been proposed to reduce patients' ECT-related anxiety. Electroconvulsive therapy-related anxiety is a highly prevalent phenomenon, and the literature provides little guidance for its clinical management. Most studies are of a low methodological quality and suffer from significant limitations, thereby hampering generalized conclusions. Given the clinical importance of ECT-related anxiety, further study on its nature and evolution through the course of treatment and on anxiety-reducing interventions is warranted.

Drugs in breast milk.

PubMed

Hervada, A R; Feit, E; Sagraves, R

1978-09-01

The amount of drug excreted into breast milk is dependent upon the lipid solubility of the medication, the mechanism of transport, the degree of ionization, and change in plasma pH. The higher the lipid solubility, the greater the concentration in human milk. The majority of drugs are transported into mammary blood capillaries by passive diffusion. The rest are transported by reverse pinocytosis. Once the drug has entered the epithelial cells of breast tissue, the drug molecules are excreted into the human milk by active transport, passive diffusion, or apocrine secretion. The amount of free (active) drug available for transport depends on the degree of protein binding the plasma pH. Another factor affecting excretion of drugs is the time when breast feeding occurs. In the 1st few days of life, when colostrum is present, water-soluble drugs pass through the breast more easily than afterwards when milk is produced. Then lipid-soluble drugs cross in higher concentrations. The effect on nursing infants is dependent on the amount excreted into the milk, the total amount absorbed by the infant, and the toxicity of the drug. The use of the following drugs in breast feeding mothers is reviewed: anticoagulants, antihypertensives and diuretics, antimicrobials, drugs affecting the central nervous system (alcohol, chloral hydrate, meprobamate, lithium, and aspirin), marijuana, other drugs (antihistamines, atropine, ergot alkaloids, laxatives, nicotine, iodides, propylthiouracil, theophylline), hormones (insulin, thyroxine, and oral contraceptives), and radiopharmaceuticals.

Predicting trace organic compound attenuation by ozone oxidation: Development of indicator and surrogate models.

PubMed

Park, Minkyu; Anumol, Tarun; Daniels, Kevin D; Wu, Shimin; Ziska, Austin D; Snyder, Shane A

2017-08-01

Ozone oxidation has been demonstrated to be an effective treatment process for the attenuation of trace organic compounds (TOrCs); however, predicting TOrC attenuation by ozone processes is challenging in wastewaters. Since ozone is rapidly consumed, determining the exposure times of ozone and hydroxyl radical proves to be difficult. As direct potable reuse schemes continue to gain traction, there is an increasing need for the development of real-time monitoring strategies for TOrC abatement in ozone oxidation processes. Hence, this study is primarily aimed at developing indicator and surrogate models for the prediction of TOrC attenuation by ozone oxidation. To this end, the second-order kinetic equations with a second-phase R ct value (ratio of hydroxyl radical exposure to molecular ozone exposure) were used to calculate comparative kinetics of TOrC attenuation and the reduction of indicator and spectroscopic surrogate parameters, including UV absorbance at 254 nm (UVA 254 ) and total fluorescence (TF). The developed indicator model using meprobamate as an indicator compound and the surrogate models with UVA 254 and TF exhibited good predictive power for the attenuation of 13 kinetically distinct TOrCs in five filtered and unfiltered wastewater effluents (R 2 values > 0.8). This study is intended to help provide a guideline for the implementation of indicator/surrogate models for real-time monitoring of TOrC abatement with ozone processes and integrate them into a regulatory framework in water reuse. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using ultraviolet absorbance and color to assess pharmaceutical oxidation during ozonation of wastewater.

PubMed

Wert, Eric C; Rosario-Ortiz, Fernando L; Snyder, Shane A

2009-07-01

The reduction of ultraviolet (UV) absorbance at 254 nm (UV254) and true color were identified as appropriate surrogates to assess the oxidation of six pharmaceuticals (i.e., carbamazepine, meprobamate, dilantin, primidone, atenolol, and iopromide) during ozonation of wastewater. Three tertiary-treated wastewaters were evaluated during oxidation with ozone (O3) and O3 coupled with hydrogen peroxide (O3/H2O2). The correlation between pharmaceutical oxidation and removal of UV254 was dependent upon the reactivity of each specific compound toward ozone, as measured by the second-order rate constant (k'(O3)). Oxidation of compounds with k'(O3) > 10(3) M(-1) s(-1) correlated well (R2 > 0.73) with UV254 reduction between 0-50%. Oxidation of compounds with apparent k'(O3) < 10 M(-1) s(-1) resulted primarily from hydroxyl radicals and correlated well (R2 > 0.80) with the UV254 reduction of 15-85%. The removal of true color also correlated well (R2 > 0.85) with the oxidation of pharmaceuticals during the ozonation of two wastewaters. These correlations demonstrate that UV254 reduction and true color removal may be used as surrogates to evaluate pharmaceutical oxidation in the presence or absence of dissolved ozone residual during advanced wastewater treatment with O3 or O3/H2O2. The use of online UV254 measurements would allow wastewater utilities to optimize the ozone dose required to meet their specific treatment objectives.

[Gender differences in suicidal behavior].

PubMed

Vörös, Viktor; Osváth, Péter; Fekete, Sándor

2004-06-01

Gender-specific differences in suicidal behaviour have been analysed in a number of recent studies. According to these, several socioeconomic, demographic, psychiatric, familial, help-seeking differences can be identified in protective and risk factors between males and females. Gender is one of the most replicated predictors for suicide. In the framework of the WHO/EURO Multicentre Study on Suicidal Behaviour, more than fifty thousand suicide attempts have been registered so far. Until now data on more than 1200 monitored suicidal events have been collected in Pecs centre. In most countries male suicid rates are higher. In contrast to suicides, rates of suicide attempts are usually higher in females. Concerning the differences in methods, it is a recognised fact that males use violent methods of both suicide and attempted suicide more often than females. The summarised clinical impression suggests that compliance of male patients is poorer than that of females. According to our data, a typical male attempter is characterised as follows: unemployed, never married, lives alone. He tends to use violent methods; if he takes drugs, it is mostly meprobamate or carbamazepine. A lot of male attempters have alcohol problems or dependence. As for the females, we found high odds ratios in the following cases: divorced or widowed, economically inactive, depressive state in the anamnesis. Female attempters are mainly repeaters using the method of self-poisoning, mostly with benzodiazepines. As suicide is a multicausal phenomenon, its therapy and prevention should also be complex and gender differences should be taken into account in building up our helping strategies.

Validated semiquantitative/quantitative screening of 51 drugs in whole blood as silylated derivatives by gas chromatography-selected ion monitoring mass spectrometry and gas chromatography electron capture detection.

PubMed

Gunnar, Teemu; Mykkänen, Sirpa; Ariniemi, Kari; Lillsunde, Pirjo

2004-07-05

A comprehensively validated procedure is presented for simultaneous semiquantitative/quantitative screening of 51 drugs of abuse or drugs potentially hazardous for traffic safety in serum, plasma or whole blood. Benzodiazepines (12), cannabinoids (3), opioids (8), cocaine, antidepressants (13), antipsychotics (5) and antiepileptics (2) as well as zolpidem, zaleplon, zopiclone, meprobamate, carisoprodol, tizanidine and orphenadrine and internal standard flurazepam, were isolated by high-yield liquid-liquid extraction (LLE). The dried extracts were derivatized by two-step silylation and analyzed by the combination of two different gas chromatographic (GC) separations with both electron capture detection (ECD) and mass spectrometry (MS) operating in a selected ion-monitoring (SIM) mode. Quantitative or semiquantitative results were obtained for each substance based on four-point calibration. In the validation tests, accuracy, reproducibility, linearity, limit of detection (LOD) and limit of quantitation (LOQ), selectivity, as well as extraction efficiency and stability of standard stock solutions were tested, and derivatization was optimized in detail. Intra- and inter-day precisions were within 2.5-21.8 and 6.0-22.5%, and square of correlation coefficients of linearity ranged from 0.9896 to 0.9999. The limit of quantitation (LOQ) varied from 2 to 2000 ng/ml due to a variety of the relevant concentrations of the analyzed substances in blood. The method is feasible for highly sensitive, reliable and possibly routinely performed clinical and forensic toxicological analyses.

Metabolism of pharmaceutical and personal care products by carrot cell cultures.

PubMed

Wu, Xiaoqin; Fu, Qiuguo; Gan, Jay

2016-04-01

With the increasing use of treated wastewater and biosolids in agriculture, residues of pharmaceutical and personal care products (PPCPs) in these reused resources may contaminate food produce via plant uptake, constituting a route for human exposure. Although various PPCPs have been reported to be taken up by plants in laboratories or under field conditions, at present little information is available on their metabolism in plants. In this study, we applied carrot cell cultures to investigate the plant metabolism of PPCPs. Five phase I metabolites of carbamazepine were identified and the potential metabolism pathways of carbamazepine were proposed. We also used the carrot cell cultures as a rapid screening tool to initially assess the metabolism potentials of 18 PPCPs. Eleven PPCPs, including acetaminophen, caffeine, meprobamate, primidone, atenolol, trimethoprim, DEET, carbamazepine, dilantin, diazepam, and triclocarban, were found to be recalcitrant to metabolism. The other 7 PPCPs, including triclosan, naproxen, diclofenac, ibuprofen, gemfibrozil, sulfamethoxazole, and atorvastatin, displayed rapid metabolism, with 0.4-47.3% remaining in the culture at the end of the experiment. Further investigation using glycosidase hydrolysis showed that 1.3-20.6% of initially spiked naproxen, diclofenac, ibuprofen, and gemfibrozil were transformed into glycoside conjugates. Results from this study showed that plant cell cultures may be a useful tool for initially exploring the potential metabolites of PPCPs in plants as well as for rapidly screening the metabolism potentials of a variety of PPCPs or other emerging contaminants, and therefore may be used for prioritizing compounds for further comprehensive evaluations. Copyright © 2015 Elsevier Ltd. All rights reserved.

New Approaches to Clarify Antinociceptive and Anti-Inflammatory Effects of the Ethanol Extract from Vernonia condensata Leaves

PubMed Central

da Silva, Jucélia Barbosa; Temponi, Vanessa dos Santos; Fernandes, Felipe Valente; de Assis Dias Alves, Geórgia; de Matos, Dalyara Mendonça; Gasparetto, Carolina Miranda; Ribeiro, Antônia; de Pinho, José de Jesus R. G.; Alves, Maria Silvana; de Sousa, Orlando Vieira

2011-01-01

The present study was aimed at evaluating the antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves in animal models, in order to afford a better understanding of these properties. The extract reduced the number of abdominal contortions at doses of 100 (51.00 ± 3.00), 200 (42.00 ± 2.98) and 400 mg/kg (39.00 ± 4.00). In formalin tests, a significant reduction in the licking time (p < 0.01) was observed in the first phase by 25.14 (200 mg/kg = 51.50 ± 4.44) and 31.15% (400 mg/kg = 48.00 ± 4.37). The doses of 100 (43.37 ± 5.15), 200 (34.62 ± 4.16) and 400 mg/kg (28.37 ± 3.98) inhibited (p < 0.001) the second phase. After 60 and 90 min of treatment, a dose of 400 mg/kg (10.13 ± 0.39 and 11.14 ± 1.33, respectively) increased the latency time. Doses of 200 and 400 mg/kg potentiated the sleeping time induced by diazepam, pentobarbital and meprobamate. The extracts (100, 200 and 400 mg/kg) showed anti-inflammatory effects by a decrease in paw edema. The extracts also reduced the exudate volume at the doses of 200 and 400 mg/kg. The leukocyte migration had significant effect (p < 0.001) at doses of 100, 200 and 400 mg/kg. The completion of additional experiments in the investigation of the antinociceptive and anti-inflammatory activities of V. condensata allowed a better understanding of the central and peripheral mechanisms involved. PMID:22272116

New trends in the treatment of nicotine addiction.

PubMed

Sliwińska-Mossoń, Mariola; Zieleń, Iwona; Milnerowicz, Halina

2014-01-01

The aim of this study was to discuss the therapeutic substances used to treat nicotine addiction, not registered in Poland. This paper presents the results of the latest clinical trials and the possibility of their use in the treatment of nicotine addiction. The first two discussed drugs clonidine and nortriptyline are recommended by clinical practice guidelines AHRQ (Agency for Healthcare Research and Quality) as the substance of the second line in the fight against addiction. Nortriptyline belongs to tricyclic antidepressants. Its mechanism of action is the inhibition of the reuptake of norepinephrine. It is suggested as the antagonist of activity of nicotinic receptors. The results confirm its efficacy in the treatment of nicotine addiction, but many side effects limit its use. Clonidine acts presumably by inhibition of sympathetic hyperactivity characteristic of symptoms associated with nicotine rehab. The remaining compounds under discussion, such as: venlafaxine, fluoxetine, moclobemide and rimonabant, are not registered in any country with an indication to use in the treatment of nicotine addiction, however, due to the mechanism in which they act, the possibility of their use in the treatment of this disease is considered. The possibility of using anxiolytics such as: buspirone, diazepam, meprobamate and beta-blockers: metoprolol and oxprenolol is also considered in order to treat the anxiety appearing as one of the symptoms of abstinence. An interesting proposal to combat nicotine addiction are vaccines--NicVAX, CYT002-NicQb and TA-NIC. Currently, they are in clinical phase I and II of their development. Their operation would be based on the induction of specific antibodies that bind nicotine in the plasma, thus prevent it reaching the nicotinic receptors. Preliminary results confirm the possible positive effects in the prevention and treatment of nicotine addiction.

Assessment of full-scale biological nutrient removal systems upgraded with physico-chemical processes for the removal of emerging pollutants present in wastewaters from Mexico.

PubMed

Estrada-Arriaga, Edson Baltazar; Cortés-Muñoz, Juana Enriqueta; González-Herrera, Arturo; Calderón-Mólgora, César Guillermo; de Lourdes Rivera-Huerta, Ma; Ramírez-Camperos, Esperanza; Montellano-Palacios, Leticia; Gelover-Santiago, Silvia Lucila; Pérez-Castrejón, Sara; Cardoso-Vigueros, Lina; Martín-Domínguez, Alejandra; García-Sánchez, Liliana

2016-11-15

Two full-scale biological nutrient removal systems upgraded with three physico-chemical processes (coagulation, chemical precipitation, and neutral Fenton) were evaluated in order to determine the removal of emerging pollutants (EPs) present in municipal wastewater from Mexico. Between 41 and 55 EPs were detected in the influents of two wastewater treatment plants (WWTPs), including personal care products (PPCPs), antibiotics, analgesics, antiepileptics, antilipidemics, antihypertensives, antiseptics, stimulants, and hormones. Emerging pollutants were detected at concentrations ranging from 0.69ng/L to 94,600ng/L. High concentrations of emerging pollutants were found during dry season. WWTP 1, integrated by oxidation ditches and UV light lamps, showed removal efficiencies of EPs between 20% and 22%. On the other hand, WWTP 2 consisted of anaerobic/anoxic/aerobic tanks coupled with two disinfection processes; chlorine dioxide and UV light lamps, for which the removal of EPs was significant (up to 80%). The concentrations of emerging pollutants in WWTP 1 effluent was found within a range

Predicting trace organic compound breakthrough in granular activated carbon using fluorescence and UV absorbance as surrogates.

PubMed

Anumol, Tarun; Sgroi, Massimiliano; Park, Minkyu; Roccaro, Paolo; Snyder, Shane A

2015-06-01

This study investigated the applicability of bulk organic parameters like dissolved organic carbon (DOC), UV absorbance at 254 nm (UV254), and total fluorescence (TF) to act as surrogates in predicting trace organic compound (TOrC) removal by granular activated carbon in water reuse applications. Using rapid small-scale column testing, empirical linear correlations for thirteen TOrCs were determined with DOC, UV254, and TF in four wastewater effluents. Linear correlations (R(2) > 0.7) were obtained for eight TOrCs in each water quality in the UV254 model, while ten TOrCs had R(2) > 0.7 in the TF model. Conversely, DOC was shown to be a poor surrogate for TOrC breakthrough prediction. When the data from all four water qualities was combined, good linear correlations were still obtained with TF having higher R(2) than UV254 especially for TOrCs with log Dow>1. Excellent linear relationship (R(2) > 0.9) between log Dow and the removal of TOrC at 0% surrogate removal (y-intercept) were obtained for the five neutral TOrCs tested in this study. Positively charged TOrCs had enhanced removals due to electrostatic interactions with negatively charged GAC that caused them to deviate from removals that would be expected with their log Dow. Application of the empirical linear correlation models to full-scale samples provided good results for six of seven TOrCs (except meprobamate) tested when comparing predicted TOrC removal by UV254 and TF with actual removals for GAC in all the five samples tested. Surrogate predictions using UV254 and TF provide valuable tools for rapid or on-line monitoring of GAC performance and can result in cost savings by extended GAC run times as compared to using DOC breakthrough to trigger regeneration or replacement. Copyright © 2015 Elsevier Ltd. All rights reserved.

Groundwater dating with the helium-tritium method to assess the long-term persistence of pharmaceuticals and their residues in groundwater

NASA Astrophysics Data System (ADS)

Massmann, G.; Burke, V.; Hass, U.; Dünnbier, U.

2012-04-01

The helium-tritium dating method is based on the analysis of tritium combined with its decay product, the lighter and rare 3He isotope. It was first suggested by Tolstikhin and Kamenskiy (1969) and has since been used in many groundwater studies. We applied the method to date groundwater recharged by bank filtration and former sewage irrigation onto sewage farms in Berlin, Germany, in order to assess the long-term persistence of several organic trace pollutants. In recent years, the occurrence of organic trace pollutants, such as pharmaceuticals and personal care products (PPCPs) as well as their metabolites, in the aquatic environment has been of increasing public and scientific interest (e.g. Schwarzenbach et al., 2006). In (urban) partly closed water cycles like Berlin, poorly biodegradable polar compounds may travel along the water path from wastewater via surface water to the raw water used for drinking water production (Reemtsma et al., 2006). In addition, raw or treated sewage irrigation onto sewage farms and/or agricultural land was common practice in Berlin until the 80s. Combined age dating and trace compound analysis revealed that several phenazone-type compounds (AMDOPH, AMPH, FAA and AAA) as well as a number of psychoactive compounds (meprobamate, pyrithyldione, primidone, and its metabolites phenobarbital and phenylethylmalonamide) are present in three decade old groundwater down gradient of a decommissioned sewage farm in Berlin, while a number of phenazone-type compounds (phenazone, propyphenazone, AMDOPH, AMPH) were present in decade-old bank filtrate. The results prove the long-term-persistence of the respective compounds under anoxic redox conditions, which are prevalent at the investigated sites. At the bank filtration sites, some of the compounds may regionally even be used as time markers for a certain infiltration period and reflect the surface water quality changes of the past few decades.

Trends in laboratory test volumes for Medicare Part B reimbursements, 2000-2010.

PubMed

Shahangian, Shahram; Alspach, Todd D; Astles, J Rex; Yesupriya, Ajay; Dettwyler, William K

2014-02-01

Changes in reimbursements for clinical laboratory testing may help us assess the effect of various variables, such as testing recommendations, market forces, changes in testing technology, and changes in clinical or laboratory practices, and provide information that can influence health care and public health policy decisions. To date, however, there has been no report, to our knowledge, of longitudinal trends in national laboratory test use. To evaluate Medicare Part B-reimbursed volumes of selected laboratory tests per 10,000 enrollees from 2000 through 2010. Laboratory test reimbursement volumes per 10,000 enrollees in Medicare Part B were obtained from the Centers for Medicare & Medicaid Services (Baltimore, Maryland). The ratio of the most recent (2010) reimbursed test volume per 10,000 Medicare enrollees, divided by the oldest data (usually 2000) during this decade, called the volume ratio, was used to measure trends in test reimbursement. Laboratory tests with a reimbursement claim frequency of at least 10 per 10,000 Medicare enrollees in 2010 were selected, provided there was more than a 50% change in test reimbursement volume during the 2000-2010 decade. We combined the reimbursed test volumes for the few tests that were listed under more than one code in the Current Procedural Terminology (American Medical Association, Chicago, Illinois). A 2-sided Poisson regression, adjusted for potential overdispersion, was used to determine P values for the trend; trends were considered significant at P < .05. Tests with the greatest decrease in reimbursement volumes were electrolytes, digoxin, carbamazepine, phenytoin, and lithium, with volume ratios ranging from 0.27 to 0.64 (P < .001). Tests with the greatest increase in reimbursement volumes were meprobamate, opiates, methadone, phencyclidine, amphetamines, cocaine, and vitamin D, with volume ratios ranging from 83 to 1510 (P < .001). Although reimbursement volumes increased for most of the selected tests, other tests exhibited statistically significant downward trends in annual reimbursement volumes. The observed changes in reimbursement volumes may be explained by disease prevalence and severity, patterns of drug use, clinical or laboratory practices, and testing recommendations and guidelines, among others. These data may be useful to policy makers, health systems researchers, laboratory directors, and industry scientists to understand, address, and anticipate trends in laboratory testing in the Medicare population.

[The first film presentation of REM sleep behavior disorder precedes its scientific debut by 35 years].

PubMed

Janković, Slavko M; Sokić, Dragoslav V; Vojvodić, Nikola M; Ristić, Aleksandar J

2006-01-01

The perplexing and tantalizing disease of rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats. In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication, and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse. wever, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia. To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al [n 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep". Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene in a barn, clumsy and goofy dog Bruno is, as dogs usually do, lying on a mat deeply asleep and obviously dreaming of his enemy cat Lucifer. This is clearly implied by a preceding scene showing Lucifer being extremely frightened while observing the dreaming dog in action. The cat Lucifer is instantly aware that the dog is chasing him in a dream and is horrified (Pictures 1-3). In a film sequence lasting only 16 seconds, we see Cinderella being aware that Bruno is firmly asleep, apparently having a terrible dream. While lying on the ground with total absence of any muscle atonia, the dog Bruno chases the cat Lucifer in his dream. He is running and barking, and when in his dream he catches Lucifer, he tries to devour the cat. Cinderella tries to wake him up by calling his name twice, first gently and then more vigorously, as she becomes aware of the content of Lucifer's dream and his intention. The dog is deeply asleep and does not awake in spite of being exposed to sunlight through the opening door of the barn, and called by name by Cinderella (Pictures 4-14). For such a behavior he is reprimanded by Cinderella who definitely recognized the content of his dream (Pictures 15-36). Immediately upon awakening, Bruno shows his good natured temper and amiable character (Pictures 37-40). The film shows that the producer (Walt Disney) and film directors (Wilfred Jackson, Clyde Geronimi and Hamilton Luske) were obviously aware that a dog might enact the content of a dream. It also implies that their observation from day-to-day (better to say night-to-night) life of the dream enactment is not a rare phenomenon, and that it deserves to be shown in the film. These authors were also aware that dogs having RBD were good-natured during wakefulness and that only in dreams they showed unrestrained aggression; while awake, dog Bruno was only an opponent or enemy to the cat Lucifer, but in dreams the animosity grew to aggression. Disney noticed this peculiar kind of sleep behavior and most probably was aware of its frequency and importance, and certainly not knowing it is a disease, he used it to color his cartoon character making it more likable to the observer. Since the film was nominated for Best Score, Best Song and Best Sound, it not only reflected the artistic and observational abilities of the producer, but also his sense of the importance of the phenomenon, awareness of its frequency and presence in animals. The onlooker is tempted to speculate that Disney, while obviously having been aware of such a behavior in animals, might also have knowledge of its presence in humans. Even more, since Disney's films frequently present different sleep disturbances (e.g., obstructive sleep apnea (OSA) in dwarfs, hypersomnolence in the dwarf Sleepy, orjactatio capitis noctuma in the dwarf Dopey in film "The Snow White"), it seems plausible that he first observed RBD in man, and then artistically transferred it to his cartoon animal characters. Since the whole incident took place during the day, we assume that Bruno, apart from suffering from RBD, had another sleep disorder causing daytime REM intrusions (possibly narcolepsy and probably not OSA, as is frequent in Disney's films, since there is no excessive daytime sleepiness). The odd thing about RBD is that it may easily, as it probably did for centuries, go as peculiar behavior in sleep--rather than disease. While Lucifer was presented as sober and prudent cat, Bruno was clumsy and forgetful dog. We will refrain from speculating that dog's clumsy nature could be the consequence of the CNS involvement by neuro-degenerative disease (i.e., synucleinopathy). Although we are aware that, in interpreting this episode we assumed to be at least as imaginative as the cartoon films of Walt Disney are, the fact remains that the artistic film presentation of RBD precedes its scientific description by at least 35 years. AC KNOWLEDGEMENT TheauthorsthankDr. NikolaTrajanovid, ABSM, FAASM (Canada) for valuable suggestions, and Dr. Carlos Schenck from the Minnesota Regional Sleep Disorders Center (USA) for reading the manuscript.