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Sample records for acetaminophen caffeine carbamazepine

  1. The role of sorption and biodegradation in the removal of acetaminophen, carbamazepine, caffeine, naproxen and sulfamethoxazole during soil contact: A kinetics study.

    PubMed

    Martínez-Hernández, Virtudes; Meffe, Raffaella; Herrera López, Sonia; de Bustamante, Irene

    2016-07-15

    In countries like Spain, where water is a limited resource, reusing effluents from wastewater treatment plants may imply the introduction of incompletely eliminated pollutants into the environment. Therefore, this work identified the role of sorption and biodegradation in attenuating pharmaceutical compounds (acetaminophen, carbamazepine, caffeine, naproxen and sulfamethoxazole) in natural soil. It also determined which sorption and removal ("sorption+biodegradation") kinetics models describe the behaviour of these substances in the water-soil system. Presence of potential transformation products (TPs) as a result of pharmaceuticals biodegradation was also studied. To this end, serial batch-type experiments were performed with a soil:water ratio of 1:4 and an initial pharmaceutical concentration of 100μgL(-1). Despite results are dependent on soil characteristics, they revealed that, for those substances with a higher affinity to the soil used (loamy sand), sorption seems to play a key role during the first 48h of contact with soil, and gives way to biodegradation afterwards. The sorption of the pharmaceuticals studied follows a pseudo second-order kinetics. Caffeine and sulfamethoxazole displayed the fastest initial sorption velocities (h=2055 and h=228μgkg(-1)h(-1), respectively). The removal kinetics experiments, satisfactorily simulated by the first-order kinetics model, indicated the presence of potential microbial adaptation to degradation. Indeed, half-lives decreased from 1.6- to 11.7-fold with respect to initial values. The microbial capacity to degrade sulfamethoxazole could be a matter of concern if bacteria have developed resistance to this antibiotic. Caffeine, acetaminophen and sulfamethoxazole were mitigated to a greater extent, whereas the removal of naproxen and carbamazepine was more limited. The appearance of epoxy-carbamazepine and N4-acetyl-sulfamethoxazole as possible TPs of carbamazepine and sulfamethoxazole, respectively, indicated that

  2. The role of sorption and biodegradation in the removal of acetaminophen, carbamazepine, caffeine, naproxen and sulfamethoxazole during soil contact: A kinetics study.

    PubMed

    Martínez-Hernández, Virtudes; Meffe, Raffaella; Herrera López, Sonia; de Bustamante, Irene

    2016-07-15

    In countries like Spain, where water is a limited resource, reusing effluents from wastewater treatment plants may imply the introduction of incompletely eliminated pollutants into the environment. Therefore, this work identified the role of sorption and biodegradation in attenuating pharmaceutical compounds (acetaminophen, carbamazepine, caffeine, naproxen and sulfamethoxazole) in natural soil. It also determined which sorption and removal ("sorption+biodegradation") kinetics models describe the behaviour of these substances in the water-soil system. Presence of potential transformation products (TPs) as a result of pharmaceuticals biodegradation was also studied. To this end, serial batch-type experiments were performed with a soil:water ratio of 1:4 and an initial pharmaceutical concentration of 100μgL(-1). Despite results are dependent on soil characteristics, they revealed that, for those substances with a higher affinity to the soil used (loamy sand), sorption seems to play a key role during the first 48h of contact with soil, and gives way to biodegradation afterwards. The sorption of the pharmaceuticals studied follows a pseudo second-order kinetics. Caffeine and sulfamethoxazole displayed the fastest initial sorption velocities (h=2055 and h=228μgkg(-1)h(-1), respectively). The removal kinetics experiments, satisfactorily simulated by the first-order kinetics model, indicated the presence of potential microbial adaptation to degradation. Indeed, half-lives decreased from 1.6- to 11.7-fold with respect to initial values. The microbial capacity to degrade sulfamethoxazole could be a matter of concern if bacteria have developed resistance to this antibiotic. Caffeine, acetaminophen and sulfamethoxazole were mitigated to a greater extent, whereas the removal of naproxen and carbamazepine was more limited. The appearance of epoxy-carbamazepine and N4-acetyl-sulfamethoxazole as possible TPs of carbamazepine and sulfamethoxazole, respectively, indicated that

  3. Acetaminophen toxicity with concomitant use of carbamazepine.

    PubMed

    Jickling, Glen; Heino, Angela; Ahmed, S Nizam

    2009-12-01

    Acetaminophen is a widely used analgesic that can cause acute liver failure when consumed above a maximum daily dose. Certain patients may be at increased risk of hepatocellular damage even at conventional therapeutic doses. We report a case of a 34-year-old man on carbamazepine for complex partial seizures who developed acute liver and renal failure on less than 2.5 grams a day of acetaminophen. This raises caution that patients on carbamazepine should avoid chronic use of acetaminophen, and if required use at lower doses with vigilant monitoring for signs of liver damage.

  4. Isocratic liquid chromatographic determination of theophylline, acetaminophen, chloramphenicol, caffeine, anticonvulsants, and barbiturates in serum.

    PubMed

    Meatherall, R; Ford, D

    1988-01-01

    An isocratic reverse-phase high-performance liquid chromatographic system is described for resolving theophylline, acetaminophen, caffeine, chloramphenicol, ethosuximide, primidone, phenobarbital, phenytoin, and carbamazepine within 7 min. A procedure for routinely measuring these drugs in serum is validated and has been extended to include the quantification of N-desmethylmethsuximide, barbital, amobarbital, secobarbital, pentobarbital, mephobarbital, and thiopental. A 250 x 4.6 mm column packed with trimethylsilyl (C-1)-coated 5-microns particles is used. The mobile phase is phosphate buffer (10 mmol/L, pH 6.3):methanol:acetonitrile, 65:17.5:17.5. A common solvent extraction procedure is used for all of these drugs. The extractant is chloroform:isopropanol (95:5), containing three internal standards: 3-isobutyl-l-methylxanthine (IMX), tolybarb, and methsuximide. Theophylline, acetaminophen, caffeine, and chloramphenicol are quantified at 273 nm with IMX as the internal standard. With two exceptions, the rest of the drugs are quantified at 204 nm using tolybarb as the internal standard; ethosuximide is quantified at 204 nm using methsuximide as the internal standard, and thiopental is quantified at 285 nm using IMX as the internal standard.

  5. Carbamazepine

    MedlinePlus

    ... control certain types of seizures in patients with epilepsy. It is also used to treat trigeminal neuralgia ( ... you are taking carbamazepine for the treatment of epilepsy, mental illness, or other conditions. A small number ...

  6. Carbamazepine.

    PubMed

    Alrashood, S T

    2016-01-01

    This chapter includes the aspects of carbamazepine. The drug is synthesized by the use of 5H-dibenz[b,f]azepine and phosgene followed by subsequent reaction with ammonia. Carbamazepine is generally used for the treatment of seizure disorders and neuropathic pain, it is also important as off-label for a second-line treatment for bipolar disorder and in combination with an antipsychotic in some cases of schizophrenia when treatment with a conventional antipsychotic alone has failed. Other uses may include attention deficit hyperactivity disorder, schizophrenia, phantom limb syndrome, complex regional pain syndrome, borderline personality disorder, and posttraumatic stress disorder. The chapter discusses the drug metabolism and pharmacokinetics and presents various methods of analysis of this drug such electrochemical analysis, spectroscopic analysis, and chromatographic techniques of separation. It also discusses its physical properties such as solubility characteristics, X-ray powder diffraction pattern, and thermal methods of analysis. The chapter is concluded with a discussion on its biological properties such as activity, toxicity, and safety. PMID:26940169

  7. Long-term exposure to caffeine and carbamazepine: Impacts on the regenerative capacity of the polychaete Diopatra neapolitana.

    PubMed

    Pires, Adília; Almeida, Ângela; Correia, Joana; Calisto, Vânia; Schneider, Rudolf J; Esteves, Valdemar I; Soares, Amadeu M V M; Figueira, Etelvina; Freitas, Rosa

    2016-03-01

    The toxicity induced in non-target organisms by pharmaceutical drugs has been the focus of several studies. In the aquatic environment, most of the studies have been devoted to fish and bivalves, while little is known on the impacts induced in polychaetes. The present study evaluated the impacts of carbamazepine and caffeine on the regenerative capacity of Diopatra neapolitana, a polychaete species with high ecological and economic relevance. Under laboratory controlled conditions polychaetes were exposed, during 28 days, to carbamazepine (Ctl-0.0; 0.3; 3.0; 6.0; 9.0 μg/L) and caffeine (Ctl-0.0; 0.5; 3.0; 18.0 μg/L). During the experiment, at days 11, 18, 25, 32, 39 and 46 after amputation, for each specimen, the percentage of the body width regenerated was determined and the number of new segments was counted. The regenerative capacity was assessed considering the number of days needed to achieve full regeneration and the total number of new segments. The obtained results revealed that with the increase of drugs concentrations organisms regenerated less new segments and took longer to completely regenerate.

  8. Identification and Quantitative Analysis of Acetaminophen, Acetylsalicylic Acid, and Caffeine in Commercial Analgesic Tablets by LC-MS

    ERIC Educational Resources Information Center

    Fenk, Christopher J.; Hickman, Nicole M.; Fincke, Melissa A.; Motry, Douglas H.; Lavine, Barry

    2010-01-01

    An undergraduate LC-MS experiment is described for the identification and quantitative determination of acetaminophen, acetylsalicylic acid, and caffeine in commercial analgesic tablets. This inquiry-based experimental procedure requires minimal sample preparation and provides good analytical results. Students are provided sufficient background…

  9. Yes, caffeine, ibuprofen, carbamazepine, novobiocin and tamoxifen have an effect on Corbicula fluminea (Müller, 1774).

    PubMed

    Aguirre-Martínez, Gabriela V; DelValls, Angel T; Laura Martín-Díaz, M

    2015-10-01

    Reports indicating the presence of pharmaceutical in fresh water environment in the ngL(-1) to µgL(-1) range are occurring with increasing frequency. It is also a fact that pharmaceuticals may produce adverse effects on aquatic organisms. Nevertheless, there is still a lack of knowledge regarding how these emergent contaminants may affect aquatic biota. The goal of this research was to evaluate the sublethal responses in Corbicula fluminea such as, general stress (lysosomal membrane stability [LMS]), biomarkers of phase I and II (etoxyresorufin O-deethylase [EROD], dibenzylfluorescein dealkylase [DBF], gluthathione-S-transferase [GST]), oxidative stress (gluthathione reductase [GR], gluthathione peroxidase [GPX], lipid peroxidation [LPO]), and biomarkers of effect (DNA damage) after 21 days of exposure to caffeine, ibuprofen, carbamazepine, novobiocin and tamoxifen at 0.1, 1, 5, 10, 15, 50µgL(-1). Environmental concentrations tested in this study caused general stress and produced changes on biomarkers tested. LMS, responses from phase I and II enzymatic activity, oxidative stress, and biomarker of effect represent important ecotoxicological information, and will provide a useful reference for the assessment of selected drugs and the effects which these compounds may have on aquatic invertebrates, using C. fluminea as a bioindicator species.

  10. Acetaminophen

    MedlinePlus

    ... headaches, muscle aches, menstrual periods, colds and sore throats, toothaches, backaches, and reactions to vaccinations (shots), and ... acetaminophen to a child who has a sore throat that is severe or does not go away, ...

  11. Chars from gasification of coal and pine activated with K2CO3: acetaminophen and caffeine adsorption from aqueous solutions.

    PubMed

    Galhetas, Margarida; Mestre, Ana S; Pinto, Moisés L; Gulyurtlu, Ibrahim; Lopes, Helena; Carvalho, Ana P

    2014-11-01

    The high carbon contents and low toxicity levels of chars from coal and pine gasification provide an incentive to consider their use as precursors of porous carbons obtained by chemical activation with K2CO3. Given the chars characteristics, previous demineralization and thermal treatments were made, but no improvement on the solids properties was observed. The highest porosity development was obtained with the biomass derived char (Pi). This char sample produced porous materials with preparation yields near 50% along with high porosity development (ABET≈1500m(2)g(-1)). For calcinations at 800°C, the control of the experimental conditions allowed the preparation of samples with a micropore system formed almost exclusively by larger micropores. A mesopore network was developed only for samples calcined at 900°C. Kinetic and equilibrium acetaminophen and caffeine adsorption data, showed that the processes obey to a pseudo-second order kinetic equation and to the Langmuir model, respectively. The results of sample Pi/1:3/800/2 outperformed those of the commercial carbons. Acetaminophen adsorption process was ruled by the micropore size distribution of the carbons. The caffeine monolayer capacities suggest a very efficient packing of this molecule in samples presenting monomodal micropore size distribution. The surface chemistry seems to be the determinant factor that controls the affinity of caffeine towards the carbons.

  12. Pharmacokinetic Herb-Drug Interaction between Essential Oil of Aniseed (Pimpinella anisum L., Apiaceae) and Acetaminophen and Caffeine: A Potential Risk for Clinical Practice.

    PubMed

    Samojlik, Isidora; Petković, Stojan; Stilinović, Nebojša; Vukmirović, Saša; Mijatović, Vesna; Božin, Biljana

    2016-02-01

    Aniseed (Pimpinella anisum L., Apiaceae) and its essential oil (EO) have been widely used. Because there are some data about the impact of aniseed EO on drug effects, this survey aimed to assess the potential of pharmacokinetic herb-drug interaction between aniseed EO and acetaminophen and caffeine in mice. The chemical analysis (gas chromatography-mass spectrometry) of aniseed EO has confirmed trans-anethole (87.96%) as the main component. The pharmacokinetic studies of intraperitoneally (i.p.) and orally applied acetaminophen (200 mg/kg) and caffeine (20 mg/kg) were performed in mice after 5 days of oral treatment with human equivalent dose of aniseed EO (0.3 mg/kg/day). The analysis of pharmacokinetic data showed that in the group treated by aniseed EO, the significant decrease in the peak plasma concentration of acetaminophen after oral application (p = 0.024) was revealed when compared with control group and the reduction of systemic exposure to the drug after oral application (74 ± 32% vs. 85 ± 35% in the control) was noted. The bioavailability of orally applied caffeine was also significantly decreased (p = 0.022) after the EO treatment in comparison with the control (57 ± 24% vs. 101 ± 29%). Therefore, the compromised therapeutic efficacy of acetaminophen and caffeine during the usage of aniseed EO preparations should be considered.

  13. Pharmacokinetic Herb-Drug Interaction between Essential Oil of Aniseed (Pimpinella anisum L., Apiaceae) and Acetaminophen and Caffeine: A Potential Risk for Clinical Practice.

    PubMed

    Samojlik, Isidora; Petković, Stojan; Stilinović, Nebojša; Vukmirović, Saša; Mijatović, Vesna; Božin, Biljana

    2016-02-01

    Aniseed (Pimpinella anisum L., Apiaceae) and its essential oil (EO) have been widely used. Because there are some data about the impact of aniseed EO on drug effects, this survey aimed to assess the potential of pharmacokinetic herb-drug interaction between aniseed EO and acetaminophen and caffeine in mice. The chemical analysis (gas chromatography-mass spectrometry) of aniseed EO has confirmed trans-anethole (87.96%) as the main component. The pharmacokinetic studies of intraperitoneally (i.p.) and orally applied acetaminophen (200 mg/kg) and caffeine (20 mg/kg) were performed in mice after 5 days of oral treatment with human equivalent dose of aniseed EO (0.3 mg/kg/day). The analysis of pharmacokinetic data showed that in the group treated by aniseed EO, the significant decrease in the peak plasma concentration of acetaminophen after oral application (p = 0.024) was revealed when compared with control group and the reduction of systemic exposure to the drug after oral application (74 ± 32% vs. 85 ± 35% in the control) was noted. The bioavailability of orally applied caffeine was also significantly decreased (p = 0.022) after the EO treatment in comparison with the control (57 ± 24% vs. 101 ± 29%). Therefore, the compromised therapeutic efficacy of acetaminophen and caffeine during the usage of aniseed EO preparations should be considered. PMID:26619825

  14. Caffeine

    MedlinePlus

    ... mood. Caffeine is in tea, coffee, chocolate, many soft drinks, and pain relievers and other over-the-counter ... Teens usually get most of their caffeine from soft drinks and energy drinks. (In addition to caffeine, these ...

  15. Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation

    NASA Astrophysics Data System (ADS)

    Paluch, Andrew S.; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L.

    2015-01-01

    We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes.

  16. Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation.

    PubMed

    Paluch, Andrew S; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L

    2015-01-28

    We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes. PMID:25637996

  17. Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation

    PubMed Central

    Paluch, Andrew S.; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L.

    2015-01-01

    We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes. PMID:25637996

  18. Caffeine

    MedlinePlus

    Caffeine is a bitter substance found in coffee, tea, soft drinks, chocolate, kola nuts, and certain medicines. ... of energy. For most people, the amount of caffeine in two to four cups of coffee a ...

  19. Molecular and microscopic assessment of the effects of caffeine, acetaminophen, diclofenac, and their mixtures on river biofilm communities.

    PubMed

    Lawrence, John R; Zhu, Bin; Swerhone, George D W; Roy, Julie; Tumber, Vijay; Waiser, Marley J; Topp, Ed; Korber, Darren R

    2012-03-01

    The authors examined effects of three common contaminants, caffeine (CF), acetaminophen (AC), and diclofenac (DF), as well as their mixtures on the development, functioning, and biodiversity of river biofilm communities. Biofilms were cultivated in rotating annular reactors. Treatments included AC, CF, DF, AC + CF, AC + DF, CF + DF, AC + CF + DF at 5 µg/L, and their molar equivalent as carbon and nutrients. Incubations using ¹⁴C-labeled AC, DF, and CF indicated that 90% of the CF, 80% of the AC, and less than 2% of the DF were converted to CO₂. Digital imaging revealed a variety of effects on algal, cyanobacterial, and bacterial biomass. Algal biomass was unaffected by AC or CF in combination with DF but significantly reduced by all other treatments. Cyanobacterial biomass was influenced only by the AC + DF application. All treatments other than AC resulted in a significant decrease in bacterial biomass. Diclofenac or DF + CF and DF + AC resulted in increases in micrometazoan grazing. The denaturing gradient gel electrophoresis of Eubacterial community DNA, evaluated by principal component analysis and analysis of similarity, indicated that relative to the control, all treatments had effects on microbial community structure (r = 0.47, p < 0.001). However, the AC + CF + DF treatment was not significantly different from its molar equivalent carbon and nutrient additions. The Archaeal community differed significantly in its response to these exposures based on community analyses, confirming a need to integrate these organisms into ecotoxicological studies.

  20. Acetaminophen, Butalbital, and Caffeine

    MedlinePlus

    ... Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for ...

  1. Chemometric resolution of fully overlapped CE peaks: quantitation of carbamazepine in human serum in the presence of several interferences.

    PubMed

    Vera-Candioti, Luciana; Culzoni, María J; Olivieri, Alejandro C; Goicoechea, Héctor C

    2008-11-01

    Drug monitoring in serum samples was performed using second-order data generated by CE-DAD, processed with a suitable chemometric strategy. Carbamazepine could be accurately quantitated in the presence of its main metabolite (carbamazepine epoxide), other therapeutic drugs (lamotrigine, phenobarbital, phenytoin, phenylephrine, ibuprofen, acetaminophen, theophylline, caffeine, acetyl salicylic acid), and additional serum endogenous components. The analytical strategy consisted of the following steps: (i) serum sample clean-up to remove matrix interferences, (ii) data pre-processing, in order to reduce the background and to correct for electrophoretic time shifts, and (iii) resolution of fully overlapped CE peaks (corresponding to carbamazepine, its metabolite, lamotrigine and unexpected serum components) by the well-known multivariate curve resolution-alternating least squares algorithm, which extracts quantitative information that can be uniquely ascribed to the analyte of interest. The analyte concentration in serum samples ranged from 2.00 to 8.00 mg/L. Mean recoveries were 102.6% (s=7.7) for binary samples, and 94.8% (s=13.5) for spiked serum samples, while CV (%)=4.0 was computed for five replicate, indicative of the acceptable accuracy and precision of the proposed method. PMID:19035405

  2. Acetaminophen Injection

    MedlinePlus

    ... injection is also used in combination with opioid (narcotic) medications to relieve moderate to severe pain. Acetaminophen is in a class of medications called analgesics (pain relievers) and antipyretics (fever reducers). It works by changing ...

  3. Quantitative HPLC Analysis of an Analgesic/Caffeine Formulation: Determination of Caffeine

    NASA Astrophysics Data System (ADS)

    Ferguson, Glenda K.

    1998-04-01

    A modern high performance liquid chromatography (HPLC) laboratory experiment which entails the separation of acetaminophen, aspirin, and caffeine and the quantitative assay of caffeine in commercial mixtures of these compounds has been developed. Our HPLC protocol resolves these compounds in only three minutes with a straightforward chromatographic apparatus which consists of a C-18 column, an isocratic mobile phase, UV detection at 254 nm, and an integrator; an expensive, sophisticated system is not required. The separation is both repeatable and rapid. Moreover, the experiment can be completed in a single three-hour period. The experiment is appropriate for any chemistry student who has completed a minimum of one year of general chemistry and is ideal for an analytical or instrumental analysis course. The experiment detailed herein involves the determination of caffeine in Goody's Extra Strength Headache Powders, a commercially available medication which contains acetaminophen, aspirin, and caffeine as active ingredients. However, the separation scheme is not limited to this brand of medication nor is it limited to caffeine as the analyte. With only minor procedural modifications, students can simultaneously quantitate all of these compounds in a commercial mixture. In our procedure, students prepare a series of four caffeine standard solutions as well as a solution from a pharmaceutical analgesic/caffeine mixture, chromatographically analyze each solution in quadruplicate, and plot relative average caffeine standard peak area versus concentration. From the mathematical relationship that results, the concentration of caffeine in the commercial formulation is obtained. Finally, the absolute standard deviation of the mean concentration is calculated.

  4. Markedly Elevated Carbamazepine-10,11-epoxide/Carbamazepine Ratio in a Fatal Carbamazepine Ingestion

    PubMed Central

    Russell, Jason L.; Spiller, Henry A.; Baker, Daniel D.

    2015-01-01

    Carbamazepine is a widely used anticonvulsant. Its metabolite, carbamazepine-10,11-epoxide, has been found to display similar anticonvulsant and neurotoxic properties. While the ratio of parent to metabolite concentration varies significantly, at therapeutic doses the epoxide concentration is generally about 20% of the parent. We report a case of fatal carbamazepine overdose in which the epoxide metabolite concentration was found to be 450% higher than the parent compound, suggesting a potential role for metabolite quantification in severe toxicity. PMID:26550016

  5. Caffeine and Your Child

    MedlinePlus

    ... National Soft Drink Association previous continue What's Caffeine Sensitivity? Caffeine sensitivity refers to the amount of caffeine that will ... caffeine necessary to produce side effects. However, caffeine sensitivity is most affected by daily caffeine intake. People ...

  6. Caffeine overdose

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002579.htm Caffeine overdose To use the sharing features on this page, please enable JavaScript. Caffeine is a substance that exists naturally in certain ...

  7. Mechanochemical removal of carbamazepine.

    PubMed

    Samara, Mohamed; Nasser, Ahmed; Mingelgrin, Uri

    2016-10-01

    Carbamazepine (CBZ) is a drug used for treating epilepsy, neuropathic pain, schizophrenia and bipolar disorder. Its widespread use is indicated by its listing in the WHO's Model List of Essential Medicines. The accumulation of CBZ in various environmental compartments, specifically in crops irrigated with treated effluent or grown on soils containing biosolids, is often reported. Being a persistent PPCP (a pharmaceutical and personal care product), developing procedures to remove CBZ is of great importance. In the present study, the breakdown of CBZ by surface reactions in contact with various minerals was attempted. While Al-montmorillonite enhanced CBZ disappearance without the need to apply mechanical force, the efficiency of magnetite in enhancing the disappearance increased considerably upon applying such force. Ball milling with magnetite generated a virtually complete disappearance of CBZ (∼94% of the applied CBZ disappeared after milling for 30 min). HPLC, LC/MS and FTIR were employed in an attempt to elucidate the rate of disappearance and degradation mechanisms of CBZ. A small amount of the hydrolysis product iminostilbene was identified by LC/MS and the breaking off of carbamic acid from the fused rings skeleton of CBZ was indicated by FTIR spectroscopy, confirming the formation of iminostilbene. PMID:27389944

  8. Caffeine consumption.

    PubMed

    Barone, J J; Roberts, H R

    1996-01-01

    Scientific literature cites a wide range of values for caffeine content in food products. The authors suggest the following standard values for the United States: coffee (5 oz) 85 mg for ground roasted coffee, 60 mg for instant and 3 mg for decaffeinated; tea (5 oz): 30 mg for leaf/bag and 20 mg for instant; colas: 18 mg/6 oz serving; cocoa/hot chocolate: 4 mg/5 oz; chocolate milk: 4 mg/6 oz; chocolate candy: 1.5-6.0 mg/oz. Some products from the United Kingdom and Denmark have higher caffeine content. Caffeine consumption survey data are limited. Based on product usage and available consumption data, the authors suggest a mean daily caffeine intake for US consumers of 4 mg/kg. Among children younger than 18 years of age who are consumers of caffeine-containing foods, the mean daily caffeine intake is about 1 mg/kg. Both adults and children in Denmark and UK have higher levels of caffeine intake. PMID:8603790

  9. Caffeine in the diet

    MedlinePlus

    Diet - caffeine ... Caffeine is absorbed and passes quickly into the brain. It does not collect in the bloodstream or ... been consumed. There is no nutritional need for caffeine. It can be avoided in the diet. Caffeine ...

  10. Caffeine in Pregnancy

    MedlinePlus

    ... much caffeine they contain. Is caffeine safe during breastfeeding? The American Academy of Pediatrics (AAP) says it’s ... much caffeine they contain. Is caffeine safe during breastfeeding? The American Academy of Pediatrics (AAP) says it’s ...

  11. Phytoremediation of carbamazepine and its metabolite 10,11-epoxycarbamazepine by C3 and C4 plants.

    PubMed

    Ryšlavá, Helena; Pomeislová, Alice; Pšondrová, Šárka; Hýsková, Veronika; Smrček, Stanislav

    2015-12-01

    The anticonvulsant drug carbamazepine is considered as an indicator of sewage water pollution: however, its uptake by plants and effect on metabolism have not been sufficiently documented, let alone its metabolite (10,11-epoxycarbamazepine). In a model system of sterile, hydroponically cultivated Zea mays (as C4 plant) and Helianthus annuus (as C3 plant), the uptake and effect of carbamazepine and 10,11-epoxycarbamazepine were studied in comparison with those of acetaminophen and ibuprofen. Ibuprofen and acetaminophen were effectively extracted from drug-supplemented media by both plants, while the uptake of more hydrophobic carbamazepine was much lower. On the other hand, the carbamazepine metabolite, 10,11-epoxycarbamazepine, was, unlike sunflower, willingly taken up by maize plants (after 96 h 88 % of the initial concentration) and effectively stored in maize tissues. In addition, the effect of the studied pharmaceuticals on the plant metabolism (enzymes of Hatch-Slack cycle, peroxidases) was followed. The activity of bound peroxidases, which could cause xylem vessel lignification and reduction of xenobiotic uptake, was at the level of control plants in maize leaves contrary to sunflower. Therefore, our results indicate that maize has the potential to remove 10,11-epoxycarbamazepine from contaminated soils. PMID:26310701

  12. Phytoremediation of carbamazepine and its metabolite 10,11-epoxycarbamazepine by C3 and C4 plants.

    PubMed

    Ryšlavá, Helena; Pomeislová, Alice; Pšondrová, Šárka; Hýsková, Veronika; Smrček, Stanislav

    2015-12-01

    The anticonvulsant drug carbamazepine is considered as an indicator of sewage water pollution: however, its uptake by plants and effect on metabolism have not been sufficiently documented, let alone its metabolite (10,11-epoxycarbamazepine). In a model system of sterile, hydroponically cultivated Zea mays (as C4 plant) and Helianthus annuus (as C3 plant), the uptake and effect of carbamazepine and 10,11-epoxycarbamazepine were studied in comparison with those of acetaminophen and ibuprofen. Ibuprofen and acetaminophen were effectively extracted from drug-supplemented media by both plants, while the uptake of more hydrophobic carbamazepine was much lower. On the other hand, the carbamazepine metabolite, 10,11-epoxycarbamazepine, was, unlike sunflower, willingly taken up by maize plants (after 96 h 88 % of the initial concentration) and effectively stored in maize tissues. In addition, the effect of the studied pharmaceuticals on the plant metabolism (enzymes of Hatch-Slack cycle, peroxidases) was followed. The activity of bound peroxidases, which could cause xylem vessel lignification and reduction of xenobiotic uptake, was at the level of control plants in maize leaves contrary to sunflower. Therefore, our results indicate that maize has the potential to remove 10,11-epoxycarbamazepine from contaminated soils.

  13. Acetaminophen and Codeine

    MedlinePlus

    The combination of acetaminophen and codeine comes as a tablet, capsule, and liquid to take by mouth. It usually is taken every 6 ... explain any part you do not understand. Take acetaminophen and codeine exactly as directed.Codeine can be ...

  14. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service.

    PubMed

    Jerling, M; Lindström, L; Bondesson, U; Bertilsson, L

    1994-08-01

    Therapeutic drug monitoring data for clozapine were used to study interactions with other drugs. The distribution of the ratio concentration/dose (C/D) of clozapine was compared in four matched groups--patients simultaneously treated with benzodiazepines, patients on drugs that inhibit the cytochrome P450 enzyme CYP2D6, patients taking carbamazepine, and those not taking any of these drugs. No difference was seen among the monotherapy, CYP2D6, and benzodiazepine groups. Patients on carbamazepine had a mean 50% lower C/D than the monotherapy group (p < 0.001), indicating that carbamazepine is an inducer of the metabolism of clozapine. The C/D was inversely correlated to the daily dose of carbamazepine. Intraindividual comparisons in eight patients, with analyses both on and off carbamazepine, confirmed a substantial decrease of the clozapine concentration when carbamazepine was introduced. Four patients treated with clozapine were concomitantly given the antidepressant fluvoxamine. Three of them exhibited a much higher C/D ratio when on fluvoxamine compared with the monotherapy group. Two had their clozapine levels analyzed when on and off fluvoxamine. The dose-normalized clozapine concentration increased by a factor of 5-10 when fluvoxamine was added. We conclude that carbamazepine causes decreased clozapine plasma levels, while fluvoxamine increases the levels. The pathways are not known with certainty, but CYP1A2 may be of major importance for the metabolism of clozapine, since fluvoxamine is a potent inhibitor of this enzyme. A recent panel study suggests that determination of CYP1A2 activity with the caffeine test may be very useful for the dosing of clozapine. The induction of clozapine metabolism by carbamazepine might be partly mediated by CYP3A4.

  15. Investigation of pharmaceutical drugs and caffeine-containing foods using Fourier and terahertz time-domain spectroscopy

    NASA Astrophysics Data System (ADS)

    KaraliÅ«nas, Mindaugas; Venckevičius, Rimvydas; Kašalynas, Irmantas; Puc, Uroš; Abina, Andreja; Jeglič, Anton; Zidanšek, Aleksander; Valušis, Gintaras

    2015-08-01

    Several pharmaceutical drugs, such as alprazolam, ibuprofen, acetaminophen, activated carbon and others, and caffeine-containing foods were tested using terahertz (THz) time domain spectroscopy in the range from 0.3 to 2 THz. The dry powder of pharmaceutical drugs was mixed with HDPE and pressed into the pellets using hydraulic press. The coffee grounds were also pressed into the pellets after ball-milling and mixing with HDPE. The caffeine containing liquid foods were dried out on the paper strips of various stacking. Experiments allow one to determine characteristic spectral signatures of the investigated substances within THz range caused by active pharmaceutical ingredients, like in the case of caffeine, as well as supporting pharmaceutical ingredients. Spectroscopic THz imaging approach is considered as a possible option to identify packaged pharmaceutical drugs. The caffeine spectral features in the tested caffeine containing foods are difficult to observed due to the low caffeine concentration and complex caffeine chemical surrounding.

  16. Aspirin, Butalbital, and Caffeine

    MedlinePlus

    The combination of aspirin, butalbital, and caffeine comes as a capsule and tablet to take by mouth. It usually is taken every 4 ... explain any part you do not understand. Take aspirin, butalbital, and caffeine exactly as directed. Do not ...

  17. Evaluating pharmaceuticals and caffeine as indicators of fecal contamination in drinking water sources of the Greater Montreal region.

    PubMed

    Daneshvar, Atlasi; Aboulfadl, Khadija; Viglino, Liza; Broséus, Romain; Sauvé, Sébastien; Madoux-Humery, Anne-Sophie; Weyhenmeyer, Gesa A; Prévost, Michèle

    2012-06-01

    We surveyed four different river systems in the Greater Montreal region, upstream and downstream of entry points of contamination, from April 2007 to January 2009. The studied compounds belong to three different groups: PPCPs (caffeine, carbamazepine, naproxen, gemfibrozil, and trimethoprim), hormones (progesterone, estrone, and estradiol), and triazine herbicides and their metabolites (atrazine, deethylatrazine, deisopropylatrazine, simazine, and cyanazine). In the system A, B, and C having low flow rate and high TOC, we observed the highest detection frequencies and mass flows of PPCPs compared to the other compounds, reflecting discharge of urban contaminations through WWTPs and CSOs. However, in River D, having high flow rate and low TOC, comparable frequency of detection of triazine and their by-products and PPCPs, reflecting cumulative loads of these compounds from the Great Lakes as well as persistency against natural attenuation processes. Considering large differences in the removal efficiencies of caffeine and carbamazepine, a high ratio of caffeine/carbamazepine might be an indicative of a greater proportion of raw sewage versus treated wastewater in surface waters. In addition, caffeine appeared to be a promising indicator of recent urban fecal contaminations, as shown by the significant correlation with FC (R(2)=0.45), while carbamazepine is a good indicator of cumulative persistence compounds.

  18. Cardiovascular Effects of Caffeine

    PubMed Central

    Myers, Martin G.

    1992-01-01

    A review of the literature on the cardiovascular effects of caffeine indicates that moderate caffeine consumption does not cause cardiac arrhythmias, hypertension, or an increased incidence of coronary heart disease. Caffeine use is often associated with atherogenic behavior, such as cigarette smoking. Failure to take into account covariables for cardiovascular disease could be responsible for commonly held misconceptions about caffeine and heart disease. PMID:21221403

  19. The effects of carbamazepine on stuttering.

    PubMed

    Harvey, J E; Culatta, R; Halikas, J A; Sorenson, J; Luxenberg, M; Pearson, V

    1992-07-01

    No pharmacological treatment protocol has proven generally useful for all patients who stutter. Various medications, behavior therapy, relaxation, suggestion, and social-based therapies have been used. For this drug treatment study, two groups of adult stutterers were followed in an 8-week open label protocol. All subjects had in the past received speech therapy; none had been treated previously with medication for stuttering. The first group (N = 12) received a maximum dose of 800 mg of carbamazepine; the second group (N = 8) received a maximum dose of 400 mg of carbamazepine. Each patient served as his or her own control. A series of systematic speech tests was given weekly to determine the variability of fluency for each subject. A statistically significant change occurred for a number of "expectancy to stutter" characteristics. Subjects felt that they stuttered less often while taking carbamazepine. Subjective effects began before medication and continued after patients discontinued the medication. Struggle characteristics also subjectively decreased. However, no objective improvement was found. No change was found in percentage of words stuttered, reading improvement, or improvement in spontaneous speech rate. Interrater reliability showed a correlation of .996. Three carbamazepine serum level therapeutic windows were inspected with negative results. Interestingly, naive listener ratings did show a statistically significant improvement on carbamazepine versus placebo. Future anecdotal reports of pharmacological improvement of stuttering should be subjected to rigorous objective testing before general acceptance.

  20. Caffeine Use and Extroversion.

    ERIC Educational Resources Information Center

    Landrum, R. Eric; Meliska, Charles J.

    Some research on the stimulant effect of caffeine suggests that the amount of behavioral enhancement produced by caffeine may depend on subjects' prior experience with the task and the drug. A study was undertaken to test whether prior experience with a task while under the influence of caffeine would facilitate performance of that task. Male…

  1. Platelets mediate acetaminophen hepatotoxicity.

    PubMed

    Lam, Fong W; Rumbaut, Rolando E

    2015-10-01

    In this issue of Blood, Miyakawa et al show that platelets and protease-activated receptor (PAR)-4 contribute to acetaminophen (APAP)-induced liver damage. Using various strategies in a mouse model of APAP overdose, the authors demonstrate that platelets participate in the progression of liver damage, and that the direct thrombin inhibitor lepirudin and PAR-4 deficiency attenuate hepatotoxicity. These findings have the potential to help identify future therapeutic targets for APAP-induced hepatotoxicity. PMID:26450954

  2. Carbamazepine degradation by photolysis and titanium dioxide photocatalysis.

    PubMed

    Im, Jong-Kwon; Son, Hyun-Seok; Kang, Young-Min; Zoh, Kyung-Duk

    2012-07-01

    We investigated the degradation of carbamazepine by photolysis/ultraviolet (UV)-C only and titanium dioxide photocatalysis. The degradation of carbamazepine by UV-only and titanium-dioxide-only (adsorption) reactions were inefficient, however, complete degradation of carbamazepine was observed by titanium dioxide photocatalysis within 30 min. The rate of degradation increased as initial carbamazepine concentration decreased, and the removal kinetics fit well with the Langmuir-Hinshelwood model. The addition of methanol, a radical scavenger, decreased carbamazepine removal, suggesting that the hydroxide radical played an important role during carbamazepine degradation. The addition of oxygen during titanium dioxide photocatalysis accelerated hydroxide radical production, thus improving mineralization activity. The photocatalytic degradation was more efficient at a higher pH, whereas the removal of carbamazepine and acridine (a major intermediate) were more efficient under aerobic conditions. The mineralization of carbamazepine during photocatalysis produced various ionic by-products such as ammonium and nitrate by way of nitrogen dioxide.

  3. Caffeine: Friend or Foe?

    PubMed

    Doepker, Candace; Lieberman, Harris R; Smith, Andrew Paul; Peck, Jennifer D; El-Sohemy, Ahmed; Welsh, Brian T

    2016-01-01

    The debate on the safety of and regulatory approaches for caffeine continues among various stakeholders and regulatory authorities. This decision-making process comes with significant challenges, particularly when considering the complexities of the available scientific data, making the formulation of clear science-based regulatory guidance more difficult. To allow for discussions of a number of key issues, the North American Branch of the International Life Sciences Institute (ILSI) convened a panel of subject matter experts for a caffeine-focused session entitled "Caffeine: Friend or Foe?," which was held during the 2015 ILSI Annual Meeting. The panelists' expertise covered topics ranging from the natural occurrence of caffeine in plants and interindividual metabolism of caffeine in humans to specific behavioral, reproductive, and cardiovascular effects related to caffeine consumption. Each presentation highlighted the potential risks, benefits, and challenges that inform whether caffeine exposure warrants concern. This paper aims to summarize the key topics discussed during the session.

  4. Caffeine: Friend or Foe?

    PubMed

    Doepker, Candace; Lieberman, Harris R; Smith, Andrew Paul; Peck, Jennifer D; El-Sohemy, Ahmed; Welsh, Brian T

    2016-01-01

    The debate on the safety of and regulatory approaches for caffeine continues among various stakeholders and regulatory authorities. This decision-making process comes with significant challenges, particularly when considering the complexities of the available scientific data, making the formulation of clear science-based regulatory guidance more difficult. To allow for discussions of a number of key issues, the North American Branch of the International Life Sciences Institute (ILSI) convened a panel of subject matter experts for a caffeine-focused session entitled "Caffeine: Friend or Foe?," which was held during the 2015 ILSI Annual Meeting. The panelists' expertise covered topics ranging from the natural occurrence of caffeine in plants and interindividual metabolism of caffeine in humans to specific behavioral, reproductive, and cardiovascular effects related to caffeine consumption. Each presentation highlighted the potential risks, benefits, and challenges that inform whether caffeine exposure warrants concern. This paper aims to summarize the key topics discussed during the session. PMID:26735800

  5. Caffeine and exercise.

    PubMed

    Paluska, Scott A

    2003-08-01

    Caffeine is the most commonly consumed drug in the world, and athletes frequently use it as an ergogenic aid. It improves performance and endurance during prolonged, exhaustive exercise. To a lesser degree it also enhances short-term, high-intensity athletic performance. Caffeine improves concentration, reduces fatigue, and enhances alertness. Habitual intake does not diminish caffeine's ergogenic properties. Several mechanisms have been proposed to explain the physiologic effects of caffeine, but adenosine receptor antagonism most likely accounts for the primary mode of action. It is relatively safe and has no known negative performance effects, nor does it cause significant dehydration or electrolyte imbalance during exercise. Routine caffeine consumption may cause tolerance or dependence, and abrupt discontinuation produces irritability, mood shifts, headache, drowsiness, or fatigue. Major sport governing bodies ban excessive use of caffeine, but current monitoring techniques are inadequate, and ethical dilemmas persist regarding caffeine intake by athletes. PMID:12834577

  6. Intravenous acetaminophen use in pediatrics.

    PubMed

    Shastri, Nirav

    2015-06-01

    Acetaminophen is a commonly used pediatric medication that has recently been approved for intravenous use in the United States. The purpose of this article was to review the pharmacodynamics, indications, contraindications, and precautions for the use of intravenous acetaminophen in pediatrics.

  7. Caffeine Consumption by College Undergraduates.

    ERIC Educational Resources Information Center

    Loke, Wing Hong

    1988-01-01

    Surveyed 542 undergraduates concerning their caffeine consumption. Found that subjects consumed less caffeine than average caffeine-drinking population. Coffee was main beverage used. Subjects reported drinking more caffeine when preparing for examinations. Suggests that caffeine may have some beneficial effects on learning. (Author/NB)

  8. Caffeine Consumption, Expectancies of Caffeine-Enhanced Performance, and Caffeinism Symptoms among University Students.

    ERIC Educational Resources Information Center

    Bradley, John R.; Petree, Allen

    1990-01-01

    Gathered self-report data on college students' (n=797) expectations of caffeine-enhanced performance, level of beverage caffeine consumed daily, and caffeinism signs experienced after consumption of caffeinated beverages. Results supported extending the expectancies model of substance use motivation from alcohol to caffeine. (Author/ABL)

  9. Pharmacokinetics of acetaminophen in children.

    PubMed

    Peterson, R G; Rumack, B H

    1978-11-01

    Acetaminophen absorption may occur at a somewhat greater rate in children if the syrup form is utilized. The overall plasma elimination of acetaminophen is somewhat slow in the neonate, but is comparable to that of adults in both children and adolescents, as judged by half-life determinations. This would suggest that the frequency of acetaminophen administration in children should be similar to the schedule recommended for adults and that a dosing interval of four hours should not result in drug accumulation. The question of a toxic quantity of acetaminophen for young children must remain open until adequate metabolic or retrospective toxicologic data become known. Since the volumes of distribution appear to be the same in both adults and children, the same dose should apply in both groups; currently, 10 mg/kg is considered to be both safe and effective for antipyresis. PMID:364399

  10. Advanced photochemical oxidation of emergent micropollutants: carbamazepine.

    PubMed

    Domínguez, Joaquín R; González, Teresa; Palo, Patricia; Cuerda-Correa, Eduardo M

    2014-01-01

    The combination of UV radiation with hydrogen peroxide has been widely used for the photodegradation of pollutants in aqueous solutions. Statistical design of experiments is a powerful tool to optimize this kind of process. Initial hydrogen peroxide concentration, pH and temperature were considered as the variables for the process optimization. The interactions existing between these three variables were analyzed. Initial concentration of hydrogen peroxide proved to be the most important variable conditioning the removal efficiency, followed by temperature, and pH shows a non-significant positive influence along the whole operation interval. The ANOVA test reported significance for five of the nine involved variables. The Response Surface Methodology technique was used to optimize carbamazepine degradation. Under optimal conditions (hydrogen peroxide concentration = 0.38·10(-3) mol L(-1), pH = 1 and temperature = 35.6°C) total carbamazepine degradation was achieved. PMID:24798897

  11. Carbamazepine-induced dystonia in an adolescent

    PubMed Central

    Bansal, Shwetank; Gill, Manpreet; Bhasin, Chhavi

    2016-01-01

    Dystonia is sustained muscle contraction, which may be primary or secondary to other causes. Drugs comprise one of the most important causes for the secondary dystonia, the usual mechanism being a dopaminergic blockade. There are very few reports describing dystonia resulting from carbamazepine (CBZ) administration. In this case report, a 16-year-old male with mental retardation and seizure disorder developed dystonia at therapeutic blood levels of CBZ. PMID:27298509

  12. Acetaminophen hepatotoxicity: an updated review.

    PubMed

    Lancaster, Elizabeth M; Hiatt, Jonathan R; Zarrinpar, Ali

    2015-02-01

    As the most common cause of acute liver failure (ALF) in the USA and UK, acetaminophen-induced hepatotoxicity remains a significant public health concern and common indication for emergent liver transplantation. This problem is largely attributable to acetaminophen combination products frequently prescribed by physicians and other healthcare professionals, with unintentional and chronic overdose accounting for over 50 % of cases of acetaminophen-related ALF. Treatment with N-acetylcysteine can effectively reduce progression to ALF if given early after an acute overdose; however, liver transplantation is the only routinely used life-saving therapy once ALF has developed. With the rapid course of acetaminophen-related ALF and limited supply of donor livers, early and accurate diagnosis of patients that will require transplantation for survival is crucial. Efforts in developing novel treatments for acetaminophen-induced ALF are directed toward bridging patients to recovery. These include auxiliary, artificial, and bioartificial support systems. This review outlines the most recent developments in diagnosis and management of acetaminophen-induced ALF.

  13. Nitric oxide releasing acetaminophen (nitroacetaminophen).

    PubMed

    Moore, P K; Marshall, M

    2003-05-01

    The nitric oxide releasing derivative of acetaminophen (nitroacetaminophen) exhibits potent anti-inflammatory and anti-nociceptive activity in a variety of animal models. On a mol for mol basis nitroacetaminophen is some 3-20 times more potent than acetaminophen. Nitroacetaminophen exhibits little or no hepatotoxicity following administration in rat or mouse and indeed protects against the hepatotoxic activity of acetaminophen. Nitroacetaminophen does not affect blood pressure or heart rate of anaesthetised rats but has similar potency to acetaminophen as an anti-pyretic agent. The enhanced anti-inflammatory and anti-nociceptive activity of nitroacetaminophen and the reduced hepatotoxicity in these animal models is likely to be secondary to the slow release of nitric oxide from the molecule. As yet the precise molecular mechanism(s) underlying these actions of nitroacetaminophen are not clear. Evidence for inhibition of cytokine-directed formation of pro-inflammatory molecule production (e.g. COX-2, iNOS) by an effect on the NF-kappaB transduction system and/or nitrosylation (and thence inhibition) of caspase enzyme activity has been reported. Data described in this review indicate that the profile of pharmacological activity of nitroacetaminophen and acetaminophen are markedly different. The possibility that nitroacetaminophen could be an attractive alternative to acetaminophen in the clinic is discussed. PMID:12846444

  14. Spectrophotometric Analysis of Caffeine

    PubMed Central

    Ahmad Bhawani, Showkat; Fong, Sim Siong; Mohamad Ibrahim, Mohamad Nasir

    2015-01-01

    The nature of caffeine reveals that it is a bitter white crystalline alkaloid. It is a common ingredient in a variety of drinks (soft and energy drinks) and is also used in combination with various medicines. In order to maintain the optimum level of caffeine, various spectrophotometric methods have been developed. The monitoring of caffeine is very important aspect because of its consumption in higher doses that can lead to various physiological disorders. This paper incorporates various spectrophotometric methods used in the analysis of caffeine in various environmental samples such as pharmaceuticals, soft and energy drinks, tea, and coffee. A range of spectrophotometric methodologies including chemometric techniques and derivatization of spectra have been used to analyse the caffeine. PMID:26604926

  15. Spectrophotometric Analysis of Caffeine.

    PubMed

    Ahmad Bhawani, Showkat; Fong, Sim Siong; Mohamad Ibrahim, Mohamad Nasir

    2015-01-01

    The nature of caffeine reveals that it is a bitter white crystalline alkaloid. It is a common ingredient in a variety of drinks (soft and energy drinks) and is also used in combination with various medicines. In order to maintain the optimum level of caffeine, various spectrophotometric methods have been developed. The monitoring of caffeine is very important aspect because of its consumption in higher doses that can lead to various physiological disorders. This paper incorporates various spectrophotometric methods used in the analysis of caffeine in various environmental samples such as pharmaceuticals, soft and energy drinks, tea, and coffee. A range of spectrophotometric methodologies including chemometric techniques and derivatization of spectra have been used to analyse the caffeine. PMID:26604926

  16. Know Concentration Before Giving Acetaminophen to Infants

    MedlinePlus

    ... urging consumers to carefully read the labels of liquid acetaminophen marketed for infants to avoid giving the ... less concentrated version for all children. Until now, liquid acetaminophen marketed for infants has only been available ...

  17. The treatment of acetaminophen poisoning

    SciTech Connect

    Prescott, L.F.; Critchley, J.A.

    1983-01-01

    Acetaminophen has become a very popular over-the-counter analgesic in some countries and as a result it is used increasingly as an agent for self-poisoning. Without treatment only a minority of patients develop severe liver damage and 1 to 2% die in hepatic failure. Until Mitchell and his colleagues discovered the biochemical mechanisms of toxicity in 1973 there was no effective treatment. They showed that the metabolic activation of acetaminophen resulted in the formation of a reactive arylating intermediate, and that hepatic reduced glutathione played an essential protective role by preferential conjugation and inactivation of the metabolite. Early treatment with sulphydryl compounds and glutathione precursors has been dramatically effective in preventing liver damage, renal failure, and death following acetaminophen overdosage. It seems likely that these agents act primarily by stimulating glutathione synthesis. Inhibition of the metabolic activation of acetaminophen is another potential therapeutic approach that has not yet been put to the test clinically. The clinical management of acetaminophen poisoning has been transformed and it is particularly gratifying to have effective treatment based on a well established biochemical mechanism of toxicity. It is likely that effective treatment will be developed for toxicity caused through similar mechanisms by other agents.

  18. Caffeine content of specialty coffees.

    PubMed

    McCusker, Rachel R; Goldberger, Bruce A; Cone, Edward J

    2003-10-01

    Caffeine is the world's most widely consumed drug with its main source found in coffee. We evaluated the caffeine content of caffeinated and decaffeinated specialty coffee samples obtained from coffee shops. Caffeine was isolated from the coffee by liquid-liquid extraction and analyzed by gas chromatography with nitrogen-phosphorus detection. In this study, the coffees sold as decaffeinated were found to have caffeine concentrations less than 17.7 mg/dose. There was a wide range in caffeine content present in caffeinated coffees ranging from 58 to 259 mg/dose. The mean (SD) caffeine content of the brewed specialty coffees was 188 (36) mg for a 16-oz cup. Another notable find is the wide range of caffeine concentrations (259-564 mg/dose) in the same coffee beverage obtained from the same outlet on six consecutive days. PMID:14607010

  19. Intravenous paracetamol (acetaminophen).

    PubMed

    Duggan, Sean T; Scott, Lesley J

    2009-01-01

    Intravenous paracetamol (rINN)/intravenous acetaminophen (USAN) is an analgesic and antipyretic agent, recommended worldwide as a first-line agent for the treatment of pain and fever in adults and children. In double-blind clinical trials, single or multiple doses of intravenous paracetamol 1 g generally provided significantly better analgesic efficacy than placebo treatment (as determined by primary efficacy endpoints) in adult patients who had undergone dental, orthopaedic or gynaecological surgery. Furthermore, where evaluated, intravenous paracetamol 1 g generally showed similar analgesic efficacy to a bioequivalent dose of propacetamol, and a reduced need for opioid rescue medication. In paediatric surgical patients, recommended doses of intravenous paracetamol 15 mg/kg were not significantly different from propacetamol 30 mg/kg for the treatment of pain, and showed equivocal analgesic efficacy compared with intramuscular pethidine 1 mg/kg in several randomized, active comparator-controlled studies. In a randomized, noninferiority study in paediatric patients with an infection-induced fever, intravenous paracetamol 15 mg/kg treatment was shown to be no less effective than propacetamol 30 mg/kg in terms of antipyretic efficacy. Intravenous paracetamol was well tolerated in clinical trials, having a tolerability profile similar to placebo. Additionally, adverse reactions emerging from the use of the intravenous formulation of paracetamol are extremely rare (<1/10 000). [table: see text]. PMID:19192939

  20. Carbamazepine Withdrawal-induced Hyperalgesia in Chronic Neuropathic Pain.

    PubMed

    Ren, Zhenyu; Yang, Bing; Yang, Bin; Shi, Le; Sun, Qing-Li; Sun, A-Ping; Lu, Lin; Liu, Xiaoguang; Zhao, Rongsheng; Zhai, Suodi

    2015-11-01

    Combined pharmacological treatments are the most used approach for neuropathic pain. Carbamazepine, an antiepileptic agent, is generally used as a third-line treatment for neuropathic pain and can be considered an option only when patients have not responded to the first- and second-line medications. In the case presented herein, a patient with neuropathic pain was treated using a combined pharmacological regimen. The patient's pain deteriorated, despite increasing the doses of opioids, when carbamazepine was discontinued, potentially because carbamazepine withdrawal disrupted the balance that was achieved by the multifaceted pharmacological regimen, thus inducing hyperalgesia. Interestingly, when carbamazepine was prescribed again, the patient's pain was successfully managed. Animal research has reported that carbamazepine can potentiate the analgesic effectiveness of morphine in rodent models of neuropathic pain and postoperative pain. This clinical case demonstrates that carbamazepine may have a synergistic effect on the analgesic effectiveness of morphine and may inhibit or postpone opioid-induced hyperalgesia. We postulate that a probable mechanism of action of carbamazepine may involve -aminobutyric acid-ergic potentiation and the interruption of glutamatergic function via N-methyl-D-aspartate receptors. Further research is warranted to clarify the analgesic action of carbamazepine and its potential use for the prevention of opioid-induced hyperalgesia in chronic neuropathic pain patients.

  1. Acetaminophen injection: a review of clinical information.

    PubMed

    Jones, Virginia M

    2011-01-01

    Acetaminophen injection is an antipyretic and analgesic agent recently marketed in the United States as Ofirmev. Five published trials directly compare acetaminophen injection to drugs available in the United States. For management of pain in adults, acetaminophen injection was at least as effective as morphine injection in renal colic, oral ibuprofen after cesarean delivery, and oral acetaminophen after coronary artery bypass surgery. In children (3 to 16 years old), single-dose acetaminophen injection was similar to meperidine intramuscular (i.m.) for pain after tonsillectomy; readiness for discharge from the recovery room was shorter with acetaminophen injection (median 15 minutes) compared with meperidine i.m. (median 25 minutes), P = .005. In children (2 to 5 years old) postoperative adenotonsillectomy or adenoidectomy, the time to rescue analgesia was superior with high-dose acetaminophen rectal suppository (median 10 hours) compared with acetaminophen injection (median 7 hours), P = .01. One published trial demonstrated acetaminophen injection is noninferior to propacetamol injection for fever related to infection in pediatric patients. Dosing adjustments are not required when switching between oral and injectable acetaminophen formulations in adult and adolescent patients. Acetaminophen injection represents another agent for multimodal pain management. PMID:21936636

  2. Transcriptomic studies on liver toxicity of acetaminophen.

    PubMed

    Toska, Endrit; Zagorsky, Robert; Figler, Bryan; Cheng, Feng

    2014-09-01

    Acetaminophen is widely used as a pain reliever and to reduce fever. At high doses, it can cause severe hepatotoxicity. Acetaminophen overdose has become the leading cause of acute liver failure in the US. The mechanisms for acetaminophen-induced liver injury are unclear. Transcriptomic studies can identify the changes in expression of thousands of genes when exposed to supratherapeutic doses of acetaminophen. These studies elucidated the mechanism of acetaminophen-induced hepatotoxicity and also provide insight into future development of diagnosis and treatment options for acetaminophen-induced acute liver failure. The following is a brief overview of some recent transcriptomic studies and gene-expression-based prediction models on liver toxicity induced by acetaminophen.

  3. Carbamazepine for acute and chronic pain in adults

    PubMed Central

    Wiffen, Philip J; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Carbamazepine is used to treat chronic neuropathic pain. Objectives Evaluation of analgesic efficacy and adverse effects of carbamazepine for acute and chronic pain management (except headaches). Search methods Randomised controlled trials (RCTs) of carbamazepine in acute, chronic or cancer pain were identified, searching MEDLINE, EMBASE, SIGLE and Cochrane CENTRAL to June 2010, reference lists of retrieved papers, and reviews. Selection criteria RCTs reporting the analgesic effects of carbamazepine. Data collection and analysis Two authors independently extracted results and scored for quality. Numbers needed to treat to benefit (NNT) or harm (NNH) with 95% confidence intervals (CI) were calculated from dichotomous data for effectiveness, adverse effects and adverse event withdrawal. Issues of study quality, size, duration, and outcomes were examined. Main results Fifteen included studies (12 cross-over design; three parallel-group) with 629 participants. Carbamazepine was less effective than prednisolone in preventing postherpetic neuralgia following acute herpes zoster (1 study, 40 participants). No studies examined acute postoperative pain. Fourteen studies investigated chronic neuropathic pain: two lasted eight weeks, others were four weeks or less (mean 3 weeks, median 2 weeks). Five had low reporting quality. Ten involved fewer than 50 participants; mean and median maximum treatment group sizes were 34 and 29. Outcome reporting was inconsistent. Most placebo controlled studies indicated that carbamazepine was better than placebo. Five studies with 298 participants provided dichotomous results; 70% improved with carbamazepine and 12% with placebo. Carbamazepine at any dose, using any definition of improvement was significantly better than placebo (70% versus 12% improved; 5 studies, 298 participants); relative benefit 6.1 (3.9 to 9.7), NNT 1.7 (1.5 to 2.0). Four studies (188 participants) reporting outcomes equivalent to 50% pain reduction or more

  4. Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen

    PubMed Central

    Zhao, Yanli; Harmatz, Jerold S; Epstein, Carol R; Nakagawa, Yukako; Kurosaki, Chie; Nakamura, Tetsuro; Kadota, Takumi; Giesing, Dennis; Court, Michael H; Greenblatt, David J

    2015-01-01

    Aims The antiviral agent favipiravir is likely to be co-prescribed with acetaminophen (paracetamol). The present study evaluated the possiblility of a pharmacokinetic interaction between favipiravir and acetaminophen, in vitro and in vivo. Methods The effect of favipivir on the transformation of acetaminophen to its glucuronide and sulfate metabolites was studied using a pooled human hepatic S9 fraction in vitro. The effect of acute and extended adminstration of favipiravir on the pharmacokinetics of acetaminophen and metabolites was evaluated in human volunteers. Results Favipiravir inhibited the in vitro formation of acetaminophen sulfate, but not acetaminophen glucuronide. In human volunteers, both acute (1 day) and extended (6 days) administration of favipiravir slightly but significantly increased (by about 20 %) systemic exposure to acetaminophen (total AUC), whereas Cmax was not significantly changed. AUC for acetaminophen glucuronide was increased by 23 to 35 % above control by favipiravir, while AUC for acetaminophen sulfate was reduced by about 20 % compared to control. Urinary excretion of acetaminophen sulfate was likewise reduced to 44 to 65 % of control values during favipiravir co-administration, while excretion of acetaminophen glucuronide increased to 17 to 32 % above control. Conclusion Favipiravir inhibits acetaminophen sulfate formation in vitro and in vivo. However the increase in systemic exposure to acetaminophen due to favipiravir co-administration, though statistically significant, is small in magnitude and unlikely to be of clinical importance. PMID:25808818

  5. Caffeine content of decaffeinated coffee.

    PubMed

    McCusker, Rachel R; Fuehrlein, Brian; Goldberger, Bruce A; Gold, Mark S; Cone, Edward J

    2006-10-01

    Caffeine is the most widely consumed drug in the world with coffee representing a major source of intake. Despite widespread availability, various medical conditions necessitate caffeine-restricted diets. Patients on certain prescription medications are advised to discontinue caffeine intake. Such admonition has implications for certain psychiatric patients because of pharmacokinetic interactions between caffeine and certain anti-anxiety drugs. In an effort to abstain from caffeine, patients may substitute decaffeinated for caffeinated coffee. However, decaffeinated beverages are known to contain caffeine in varying amounts. The present study determined the caffeine content in a variety of decaffeinated coffee drinks. In phase 1 of the study, 10 decaffeinated samples were collected from different coffee establishments. In phase 2 of the study, Starbucks espresso decaffeinated (N=6) and Starbucks brewed decaffeinated coffee (N=6) samples were collected from the same outlet to evaluate variability of caffeine content of the same drink. The 10 decaffeinated coffee samples from different outlets contained caffeine in the range of 0-13.9 mg/16-oz serving. The caffeine content for the Starbucks espresso and the Starbucks brewed samples collected from the same outlet were 3.0-15.8 mg/shot and 12.0-13.4 mg/16-oz serving, respectively. Patients vulnerable to caffeine effects should be advised that caffeine may be present in coffees purported to be decaffeinated. Further research is warranted on the potential deleterious effects of consumption of "decaffeinated" coffee that contains caffeine on caffeine-restricted patients. Additionally, further exploration is merited for the possible physical dependence potential of low doses of caffeine such as those concentrations found in decaffeinated coffee. PMID:17132260

  6. Caffeine content of decaffeinated coffee.

    PubMed

    McCusker, Rachel R; Fuehrlein, Brian; Goldberger, Bruce A; Gold, Mark S; Cone, Edward J

    2006-10-01

    Caffeine is the most widely consumed drug in the world with coffee representing a major source of intake. Despite widespread availability, various medical conditions necessitate caffeine-restricted diets. Patients on certain prescription medications are advised to discontinue caffeine intake. Such admonition has implications for certain psychiatric patients because of pharmacokinetic interactions between caffeine and certain anti-anxiety drugs. In an effort to abstain from caffeine, patients may substitute decaffeinated for caffeinated coffee. However, decaffeinated beverages are known to contain caffeine in varying amounts. The present study determined the caffeine content in a variety of decaffeinated coffee drinks. In phase 1 of the study, 10 decaffeinated samples were collected from different coffee establishments. In phase 2 of the study, Starbucks espresso decaffeinated (N=6) and Starbucks brewed decaffeinated coffee (N=6) samples were collected from the same outlet to evaluate variability of caffeine content of the same drink. The 10 decaffeinated coffee samples from different outlets contained caffeine in the range of 0-13.9 mg/16-oz serving. The caffeine content for the Starbucks espresso and the Starbucks brewed samples collected from the same outlet were 3.0-15.8 mg/shot and 12.0-13.4 mg/16-oz serving, respectively. Patients vulnerable to caffeine effects should be advised that caffeine may be present in coffees purported to be decaffeinated. Further research is warranted on the potential deleterious effects of consumption of "decaffeinated" coffee that contains caffeine on caffeine-restricted patients. Additionally, further exploration is merited for the possible physical dependence potential of low doses of caffeine such as those concentrations found in decaffeinated coffee.

  7. Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity.

    PubMed

    James, Laura; Yan, Ke; Pence, Lisa; Simpson, Pippa; Bhattacharyya, Sudeepa; Gill, Pritmohinder; Letzig, Lynda; Kearns, Gregory; Beger, Richard

    2015-01-01

    Metabolomics approaches have enabled the study of new mechanisms of liver injury in experimental models of drug toxicity. Disruption of bile acid homeostasis is a known mechanism of drug induced liver injury. The relationship of individual bile acids to indicators of oxidative drug metabolism (acetaminophen protein adducts) and liver injury was examined in children with acetaminophen overdose, hospitalized children with low dose exposure to acetaminophen, and children with no recent exposure to acetaminophen. Nine bile acids were quantified through targeted metabolomic analysis in the serum samples of the three groups. Bile acids were compared to serum levels of acetaminophen protein adducts and alanine aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and glycochenodeoxycholic acid were significantly increased in children with acetaminophen overdose compared to healthy controls. Among patients with acetaminophen overdose, bile acids were higher in subjects with acetaminophen protein adduct values > 1.0 nmol/mL and modest correlations were noted for three bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid (R=0.604; p<0.001), glycodeoxycholic acid (R=0.581; p<0.001), and glycochenodeoxycholic acid (R=0.571; p<0.001). Variability in bile acids was greater among hospitalized children receiving low doses of acetaminophen than in healthy children with no recent acetaminophen exposure. Compared to bile acids, acetaminophen protein adducts more accurately discriminated among children with acetaminophen overdose, children with low dose exposure to acetaminophen, and healthy control subjects. In children with acetaminophen overdose, elevations of conjugated bile acids were associated with specific indicators of acetaminophen metabolism and non-specific indicators of liver injury. PMID:26208104

  8. Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity.

    PubMed

    James, Laura; Yan, Ke; Pence, Lisa; Simpson, Pippa; Bhattacharyya, Sudeepa; Gill, Pritmohinder; Letzig, Lynda; Kearns, Gregory; Beger, Richard

    2015-01-01

    Metabolomics approaches have enabled the study of new mechanisms of liver injury in experimental models of drug toxicity. Disruption of bile acid homeostasis is a known mechanism of drug induced liver injury. The relationship of individual bile acids to indicators of oxidative drug metabolism (acetaminophen protein adducts) and liver injury was examined in children with acetaminophen overdose, hospitalized children with low dose exposure to acetaminophen, and children with no recent exposure to acetaminophen. Nine bile acids were quantified through targeted metabolomic analysis in the serum samples of the three groups. Bile acids were compared to serum levels of acetaminophen protein adducts and alanine aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and glycochenodeoxycholic acid were significantly increased in children with acetaminophen overdose compared to healthy controls. Among patients with acetaminophen overdose, bile acids were higher in subjects with acetaminophen protein adduct values > 1.0 nmol/mL and modest correlations were noted for three bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid (R=0.604; p<0.001), glycodeoxycholic acid (R=0.581; p<0.001), and glycochenodeoxycholic acid (R=0.571; p<0.001). Variability in bile acids was greater among hospitalized children receiving low doses of acetaminophen than in healthy children with no recent acetaminophen exposure. Compared to bile acids, acetaminophen protein adducts more accurately discriminated among children with acetaminophen overdose, children with low dose exposure to acetaminophen, and healthy control subjects. In children with acetaminophen overdose, elevations of conjugated bile acids were associated with specific indicators of acetaminophen metabolism and non-specific indicators of liver injury.

  9. Soil persistence and fate of carbamazepine, lincomycin, caffeine, and iburpofen from wastewater

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The reuse of treated wastewater for groundwater recharge is an effective way to provide advanced treatment and water storage in the desert southwest. Contaminants such as human drugs, found in treated effluent, have been identified as a potential problem for use of this water. The town of Gilbert, A...

  10. Caffeine and pharmaceuticals as indicators of waste water contamination in wells

    USGS Publications Warehouse

    Seiler, R.L.; Zaugg, S.D.; Thomas, J.M.; Howcroft, D.L.

    1999-01-01

    The presence of caffeine or human pharmaceuticals in ground water with elevated nitrate concentrations can provide a clear, unambiguous indication that domestic waste water is a source of some of the nitrate. Water from domestic, public supply, and monitoring wells in three communities near Reno, Nevada, was sampled to test if caffeine or pharmaceuticals are common, persistent, and mobile enough in the environment that they can be detected in nitrate-contaminated ground water and, thus, can be useful indicators of recharge from domestic waste water. Results of this study indicate that these compounds can be used as indicators of recharge from domestic waste water, although their usefulness is limited because caffeine is apparently nonconservative and the presence of prescription pharmaceuticals is unpredictable. The absence of caffeine or pharmaceuticals in ground water with elevated nitrate concentrations does not demonstrate that the aquifer is free of waste water contamination. Caffeine was detected in ground water samples at concentrations up to 0.23 ??g/L. The human pharmaceuticals chlorpropamide, phensuximide, and carbamazepine also were detected in some samples.

  11. Caffeine and Migraine

    MedlinePlus

    ... Google+ Follow us on Twitter Follow us on Facebook Follow us on YouTube Follow us on Pinterest Follow us on Instagram DONATE TODAY Caffeine and Migraine Abuse, Maltreatment, and PTSD and Their Relationship to Migraine Altitude, Acute Mountain Sickness and Headache ...

  12. Teratogenic effect of Carbamazepine use during pregnancy in the mice.

    PubMed

    Elshama, Said Said; Osman, Hosam Eldin Hussein; El-Kenawy, Ayman El-Meghawry

    2015-01-01

    Carbamazepine use is the first choice of antiepileptic drugs among epileptic pregnant females. There are many inconclusive studies regard the safety of carbamazepine use during pregnancy. This study aims to investigate the morphological and histopathological teratogenic effects of carbamazepine use during pregnancy. The healthy pregnant females mice divided into equal five groups (each n=20). The first (control) group received distilled water/day. Second, third, fourth and fifth group received 8.75, 22.75, 52.5, 65 mg of carbamazepine/day respectively. Carbamazepine and water were given by gastric gavage throughout gestational period. Fetuses were delivered on the 18th day of gestation by hysterectomy. Fetal measurements and appearance were assessed with investigation the histopathological changes of brain and spinal cord. There was a significant decrease of weight, different organs weight, length, upper and lower limb length of mice in the first day of delivery in fifth group. There was a significant increase of weight, different organs weight, length, upper and lower limb length in the third group. Many congenital anomalies such as spina bifida, meromelia, microphalmia, oligodactyly, anencephaly, neurodegeneration of brain and spinal cord were noticedin fifth group. Teratogenic effect of carbamazepine represented as growth retardation and neurodevelopmental toxicity depending on its overdose degree. PMID:25553681

  13. Caffeine Reinforces Flavor Preference and Behavior in Moderate Users but Not in Low Caffeine Users

    ERIC Educational Resources Information Center

    Dack, Charlotte; Reed, Phil

    2009-01-01

    The study examined the role of caffeine consumption in caffeine reinforcement. Previous findings have shown that caffeine reinforced flavor preference in moderate caffeine consumers who are caffeine deprived. However, most of these studies have employed rating procedures only, and have not shown the effectiveness of caffeine to reinforce behaviors…

  14. [Tramadol/acetaminophen combination tablets].

    PubMed

    Yokotsuka, Shoko; Kato, Jitsu

    2013-07-01

    Tramadol/acetaminophen fixed-dose combination tablets (Tramse) combine tramadol, a centrally acting week opioid analgesic, with low-dose acetaminophen. The action of tramadol may be described as a weak agonist at the mu-opioid receptor, inhibition of serotonin reuptake, and inhibition of noradrenaline reuptake. The second component in these tablets, acetaminophen mainly appears to act through central mechanism. Chronic pain may be broadly classified into nociceptive, neuropathic and mixed. Tramset may exert additive or synergic benefits in treating the multiple mechanism of pain. Clinical studies have revealed its efficacy and safety for a variety of pain condition such as chronic low back pain, rheumatoid arthritis, fibromyalgia and painful diabetic peripheral neuropathy. It is expected that Tramset is going to induce pain relief and to improve disturbance of daily life in patients with intractable chronic pain. However overuse of Tramset may induce severe adverse effects such as addiction, abuse and hepatotoxicity. Therefore clinician should continuously assess pain intensity, activity of daily life, mode of its consumption, and adverse effects after prescription. PMID:23905401

  15. Caffeine content of brewed teas.

    PubMed

    Chin, Jenna M; Merves, Michele L; Goldberger, Bruce A; Sampson-Cone, Angela; Cone, Edward J

    2008-10-01

    Caffeine is the world's most popular drug and can be found in many beverages including tea. It is a psychostimulant that is widely used to enhance alertness and improve performance. This study was conducted to determine the concentration of caffeine in 20 assorted commercial tea products. The teas were brewed under a variety of conditions including different serving sizes and steep-times. Caffeine was isolated from the teas with liquid-liquid extraction and quantitated by gas chromatography with nitrogen-phosphorus detection. Caffeine concentrations in white, green, and black teas ranged from 14 to 61 mg per serving (6 or 8 oz) with no observable trend in caffeine concentration due to the variety of tea. The decaffeinated teas contained less than 12 mg of caffeine per serving, and caffeine was not detected in the herbal tea varieties. In most instances, the 6- and 8-oz serving sizes contained similar caffeine concentrations per ounce, but the steep-time affected the caffeine concentration of the tea. These findings indicate that most brewed teas contain less caffeine per serving than brewed coffee. PMID:19007524

  16. The perspective of caffeine and caffeine derived compounds in therapy.

    PubMed

    Pohanka, M

    2015-01-01

    Caffeine (1,3,7-trimethylxanthine) is a plant secondary metabolite with a significant impact on multiple processes and regulatory pathways in the body. Though major part of the population meets caffeine via coffee, tea or chocolate, it has also an important role in pharmacology and it is used as a supplementary substance in medicaments. Currently, the ability of caffeine to ameliorate some neurodegenerative disorders is proved in some studies. This review describes basic data about caffeine including toxicity, pharmacokinetics, biological mechanism of the action, and metabolism. Beside this, promising applications of caffeine, new medicaments and derivatives are discussed. Relevant papers and inventions are depicted in the manuscript. Caffeine is a pharmacologically promising substance that deserves big consideration in the current research and development. The compound has several reasons to be an object of scientific interest and to be used for pharmacology purposes. Despite an extensive research for a long time, no significantly negative effects on human health were proved hence caffeine can be considered as a completely safe compound. The recent data about amelioration of neurodegenerative and other disorders are promising and deserving more work on the issue. ARTICLE HIGHLIGHTS: Caffeine is a purine alkaloid from plants and it has a broad use in current pharmacology. Caffeine is a competitive antagonist of neurotransmitter adenosine on adenosine receptors. The substance is added as a supplementary to drugs and food.Besides interfering on adenosine receptors, caffeine interacts with acetylcholinesterase, monoamine oxidase, phosphodiesterase, ryanodine receptors and others.Current research is devoted to the role of caffeine in neurodegenerative diseases and immunity alteration. New chemical compounds based on caffeine moiety are prepared (Tab. 4, Fig. 6, Ref. 149). PMID:26435014

  17. The perspective of caffeine and caffeine derived compounds in therapy.

    PubMed

    Pohanka, M

    2015-01-01

    Caffeine (1,3,7-trimethylxanthine) is a plant secondary metabolite with a significant impact on multiple processes and regulatory pathways in the body. Though major part of the population meets caffeine via coffee, tea or chocolate, it has also an important role in pharmacology and it is used as a supplementary substance in medicaments. Currently, the ability of caffeine to ameliorate some neurodegenerative disorders is proved in some studies. This review describes basic data about caffeine including toxicity, pharmacokinetics, biological mechanism of the action, and metabolism. Beside this, promising applications of caffeine, new medicaments and derivatives are discussed. Relevant papers and inventions are depicted in the manuscript. Caffeine is a pharmacologically promising substance that deserves big consideration in the current research and development. The compound has several reasons to be an object of scientific interest and to be used for pharmacology purposes. Despite an extensive research for a long time, no significantly negative effects on human health were proved hence caffeine can be considered as a completely safe compound. The recent data about amelioration of neurodegenerative and other disorders are promising and deserving more work on the issue. ARTICLE HIGHLIGHTS: Caffeine is a purine alkaloid from plants and it has a broad use in current pharmacology. Caffeine is a competitive antagonist of neurotransmitter adenosine on adenosine receptors. The substance is added as a supplementary to drugs and food.Besides interfering on adenosine receptors, caffeine interacts with acetylcholinesterase, monoamine oxidase, phosphodiesterase, ryanodine receptors and others.Current research is devoted to the role of caffeine in neurodegenerative diseases and immunity alteration. New chemical compounds based on caffeine moiety are prepared (Tab. 4, Fig. 6, Ref. 149).

  18. 21 CFR 862.3030 - Acetaminophen test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Acetaminophen test system. 862.3030 Section 862....3030 Acetaminophen test system. (a) Identification. An acetaminophen test system is a device intended to measure acetaminophen, an analgestic and fever reducing drug, in serum. Measurements obtained...

  19. 21 CFR 862.3030 - Acetaminophen test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Acetaminophen test system. 862.3030 Section 862....3030 Acetaminophen test system. (a) Identification. An acetaminophen test system is a device intended to measure acetaminophen, an analgestic and fever reducing drug, in serum. Measurements obtained...

  20. 21 CFR 862.3030 - Acetaminophen test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Acetaminophen test system. 862.3030 Section 862....3030 Acetaminophen test system. (a) Identification. An acetaminophen test system is a device intended to measure acetaminophen, an analgestic and fever reducing drug, in serum. Measurements obtained...

  1. 21 CFR 862.3030 - Acetaminophen test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Acetaminophen test system. 862.3030 Section 862....3030 Acetaminophen test system. (a) Identification. An acetaminophen test system is a device intended to measure acetaminophen, an analgestic and fever reducing drug, in serum. Measurements obtained...

  2. 21 CFR 862.3030 - Acetaminophen test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Acetaminophen test system. 862.3030 Section 862....3030 Acetaminophen test system. (a) Identification. An acetaminophen test system is a device intended to measure acetaminophen, an analgestic and fever reducing drug, in serum. Measurements obtained...

  3. Simultaneous quantification of caffeine and its three primary metabolites in rat plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Choi, Eu Jin; Bae, Soo Hyeon; Park, Jung Bae; Kwon, Min Jo; Jang, Su Min; Zheng, Yu Fen; Lee, Young Sun; Lee, Su-Jun; Bae, Soo Kyung

    2013-12-01

    A rapid, sensitive, simple and accurate LC-MS/MS method for the simultaneous quantitation of caffeine, and its three primary metabolites, theobromine, paraxanthine, and theophylline, in rat plasma was developed and validated. Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18 column using 1 μg/mL acetaminophen as an internal standard. Each sample was run at 0.5 mL/min for a total run time of 7 min/sample. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with positive electrospray ionization. The lower limit of quantification was 5 ng/mL for all analytes with linear ranges up to 5000 ng/mL for caffeine and 1000 ng/mL for its metabolites. The coefficient of variation for assay precision was less than 12.6%, with an accuracy of 93.5-114%. The assay was successfully applied to determine plasma concentrations of caffeine, theobromine, paraxanthine, and theophylline in rat administered various energy drinks containing the same caffeine content. Various energy drinks exhibited considerable variability in the pharmacokinetic profiles of caffeine and its three primary metabolites, even containing the same caffeine. Different additives of energy drinks might contribute to these results.

  4. Caffeine addiction? Caffeine for youth? Time to act!

    PubMed

    Budney, Alan J; Emond, Jennifer A

    2014-11-01

    While data accumulate and discussion evolves on the clinical importance of caffeine addiction and its classification, the growing practices of (i) adding increasing amounts of caffeine to drinks and other consumables, (ii) promoting these as performance enhancers and (iii) targeting youth as the consumer raise concerns that require immediate action.

  5. Interaction of Carbamazepine with Herbs, Dietary Supplements, and Food: A Systematic Review

    PubMed Central

    Zuo, Zhong

    2013-01-01

    Background. Carbamazepine (CBZ) is a first-line antiepileptic drug which may be prone to drug interactions. Systematic review of herb- and food-drug interactions on CBZ is warranted to provide guidance for medical professionals when prescribing CBZ. Method. A systematic review was conducted on six English databases and four Chinese databases. Results. 196 out of 3179 articles fulfilled inclusion criteria, of which 74 articles were reviewed and 33 herbal products/dietary supplement/food interacting with CBZ were identified. No fatal or severe interactions were documented. The majority of the interactions were pharmacokinetic-based (80%). Traditional Chinese medicine accounted for most of the interactions (n = 17), followed by food (n = 10), dietary supplements (n = 3), and other herbs/botanicals (n = 3). Coadministration of 11 and 12 of the studied herbal products/dietary supplement/food significantly decreased or increased the plasma concentrations of CBZ. Regarding pharmacodynamic interaction, Xiao-yao-san, melatonin, and alcohol increased the side effects of CBZ while caffeine lowered the antiepileptic efficacy of CBZ. Conclusion. This review provides a comprehensive summary of the documented interactions between CBZ and herbal products/food/dietary supplements which assists healthcare professionals to identify potential herb-drug and food-drug interactions, thereby preventing potential adverse events and improving patients' therapeutic outcomes when prescribing CBZ. PMID:24023584

  6. Evaluating Dependence Criteria for Caffeine.

    PubMed

    Striley, Catherine L W; Griffiths, Roland R; Cottler, Linda B

    2011-12-01

    Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who reported caffeine use in the last 7 days and also reported use of alcohol, nicotine, or illicit drugs within the past year (n=167). Results: Thirty-five percent met the criteria for dependence when all seven of the adopted DSM dependence criteria were used. Rates of endorsement of several of the most applicable diagnostic criteria were as follows: 26% withdrawal, 23% desire to cut down or control use, and 44% continued use despite harm. In addition, 34% endorsed craving, 26% said they needed caffeine to function, and 10% indicated that they talked to a physician or counselor about problems experienced with caffeine. There was a trend towards increased caffeine dependence among those dependent on nicotine or alcohol. Within a subgroup that had used caffeine, alcohol, and nicotine in the past year, 28% fulfilled criteria for caffeine dependence compared to 50% for alcohol and 80% for nicotine. Conclusion: The present study adds to a growing literature suggesting the reliability, validity, and clinical utility of the caffeine dependence diagnosis. Recognition of caffeine dependence in the DSM-V may be clinically useful. PMID:24761264

  7. [The comparison of tianeptine and carbamazepine in benzodiazepines withdrawal symptoms].

    PubMed

    Kornowski, Jarosław

    2002-01-01

    Dealing with benzodiazepine dependent creates as serious clinical problem that requires knowledge and experience. Abrupt discontinuation of benzodiazepines, particularly those with short half-life is not advised to avoid severe withdrawal syndrome. Reports from literature suggest use of carbamazepine and recently tianeptine as substances useful in treatment of benzodiazepine dependence. This paper presents a double-blind trial in which both, carbamazepine and tianeptine were used in treatment of benzodiazepiene withdrawal syndrome. Patient mental state was evaluated by using questionnaire SCL-90, Beck Depression Inventory and specifically designed questionnaire assessing severity of symptoms following benzodiazepine withdrawal. It appears from this study that both drugs (carbamazepine and tianeptine) are comparable, safe and efficient in treating benzodiazepine withdrawal symptoms.

  8. The Social Side Effects of Acetaminophen

    NASA Astrophysics Data System (ADS)

    Mischkowski, Dominik

    About 23% of all adults in the US take acetaminophen during an average week (Kaufman, Kelly, Rosenberg, Anderson, & Mitchell, 2002) because acetaminophen is an effective physical painkiller and easily accessible over the counter. The physiological side effects of acetaminophen are well documented and generally mild when acetaminophen is consumed in the appropriate dosage. In contrast, the psychological and social side effects of acetaminophen are largely unknown. Recent functional neuroimaging research suggests that the experience of physical pain is fundamentally related to the experience of empathy for the pain of other people, indicating that pharmacologically reducing responsiveness to physical pain also reduces cognitive, affective, and behavioral responsiveness to the pain of others. I tested this hypothesis across three double-blind between-subjects drug intervention studies. Two experiments showed that acetaminophen had moderate effects on empathic affect, specifically personal distress and empathic concern, and a small effect on empathic cognition, specifically perceived pain, when facing physical and social pain of others. The same two experiments and a third experiment also showed that acetaminophen can increase the willingness to inflict pain on other people, i.e., actual aggressive behavior. This effect was especially pronounced among people low in dispositional empathic concern. Together, these findings suggest that the physical pain system is more involved in the regulation of social cognition, affect, and behavior than previously assumed and that the experience of physical pain and responsiveness to the pain of others share a common neurochemical basis. Furthermore, these findings suggest that acetaminophen has unappreciated but serious social side effects, and that these side effects may depend on psychological characteristics of the drug consumer. This idea is consistent with recent theory and research on the context-dependency of neurochemical

  9. Demonstrating Advanced Oxidation Coupled with Biodegradation for Removal of Carbamazepine (WERF Report INFR6SG09)

    EPA Science Inventory

    Carbamazepine is an anthropogenic pharmaceutical found in wastewater effluents that is quite resistant to removal by conventional wastewater treatment processes. Hydroxyl radical-based advanced oxidation processes can transform carbamazepine into degradation products but cannot m...

  10. The Effects of Caffeine on Athletic Performance

    ERIC Educational Resources Information Center

    McDaniel, Larry W.; McIntire, Kyle; Streitz, Carmyn; Jackson, Allen; Gaudet, Laura

    2010-01-01

    Athletes who use caffeine before exercising or competition may be upgrading themselves more than they realize. Caffeine is classified as a stimulant and is the most commonly used drug in the world. Caffeine has the same affects that amphetamines and cocaine have, just to a lesser degree. Caffeine crosses the membranes of all the body's tissues. It…

  11. Perceived consequences of drinking caffeinated beverages.

    PubMed

    Page, R M

    1987-12-01

    A survey of 238 college students indicated that those who prefer to drink caffeine containing drinks maintain different perceptions about the negative and positive consequences of drinking caffeinated drinks from those who do not prefer to drink caffeinated drinks. 154 of the students reported that the last soft drink they consumed was caffeinated.

  12. Occurrence and removal of emerging pharmaceutical, personal care compounds and caffeine tracer in municipal sewage treatment plant in Western Greece.

    PubMed

    Stamatis, Nikolaos K; Konstantinou, Ioannis K

    2013-01-01

    A fourteen-month monitoring period (April 2007-May 2008) was realized to investigate the removal and occurrence of eight pharmaceutical and personal care compounds, two metabolites and caffeine across the municipal wastewater treatment plant (WWTP) of Agrinio city, located in Western Greece as well as in the discharging sampling point in Acheloos River, which receives the effluents of the plant. Solid-phase extraction (SPE) was used for the isolation and pre-concentration of the target pollutants and gas chromatography mass spectrometry (GC-MS) for their detection and quantification. All the selected compounds were detected in the wastewater samples. The concentrations determined in the influent of the municipal WWTP ranged between 65.3 and 6679 ng L(-1) recorded for triclosan and caffeine respectively, while in the effluent ranged between 24.9 and 552 ng L(-1) observed for triclosan and carbamazepine, respectively. The detected concentration levels in Acheloos River ranged from 37.6 ng L(-1) for caffeine to 305 ng L(-1) for paracetamol. Mean total removal efficiencies ranged between 46.3% for carbamazepine and 96.8% for naproxen. The results of this study demonstrate that most of the compounds are being reduced in low levels by municipal wastewater treatment processes but quite significant levels of pharmaceuticals enter river waterways.

  13. Did acetaminophen provoke the autism epidemic?

    PubMed

    Good, Peter

    2009-12-01

    Schultz et al (2008) raised the question whether regression into autism is triggered, not by the measles-mumps-rubella (MMR) vaccine, but by acetaminophen (Tylenol) given for its fever and pain. Considerable evidence supports this contention, most notably the exponential rise in the incidence of autism since 1980, when acetaminophen began to replace aspirin for infants and young children. The impetus for this shift - a Centers for Disease Control and Prevention warning that aspirin was associated with Reye's syndrome - has since been compellingly debunked. If aspirin is not to be feared as a cause of Reyes syndrome, and acetaminophen is to be feared as a cause of autism, can the autism epidemic be reversed by replacing acetaminophen with aspirin or other remedies?

  14. Acetaminophen (paracetamol) oral absorption and clinical influences.

    PubMed

    Raffa, Robert B; Pergolizzi, Joseph V; Taylor, Robert; Decker, John F; Patrick, Jeffrey T

    2014-09-01

    Acetaminophen (paracetamol) is a widely used nonopioid, non-NSAID analgesic that is effective against a variety of pain types, but the consequences of overdose can be severe. Because acetaminophen is so widely available as a single agent and is increasingly being formulated in fixed-ratio combination analgesic products for the potential additive or synergistic analgesic effect and/or reduced adverse effects, accidental cumulative overdose is an emergent concern. This has rekindled interest in the sites, processes, and pharmacokinetics of acetaminophen oral absorption and the clinical factors that can influence these. The absorption of oral acetaminophen occurs primarily along the small intestine by passive diffusion. Therefore, the rate-limiting step is the rate of gastric emptying into the intestines. Several clinical factors can affect absorption per se or the rate of gastric emptying, such as diet, concomitant medication, surgery, pregnancy, and others. Although acetaminophen does not have the abuse potential of opioids or the gastrointestinal bleeding or organ adverse effects of NSAIDs, excess amounts can produce serious hepatic injury. Thus, an understanding of the sites and features of acetaminophen absorption--and how they might be influenced by factors encountered in clinical practice--is important for pain management using this agent. It can also provide insight for design of formulations that would be less susceptible to clinical variables.

  15. Hydroxyapatite crystallization in the presence of acetaminophen

    NASA Astrophysics Data System (ADS)

    Mangood, A.; Malkaj, P.; Dalas, E.

    2006-05-01

    The effect of acetaminophen; a widely used analgesic and fever reducing medicine; in supersaturated solutions of calcium phosphate was investigated under plethostatic conditions, at 37 °C, 0.15 M NaCl, pH 7.40. The rates of crystal growth measured in the presence of acetaminophen 1.654×10 -4 mol dm -3 to 6.616×10 -4 mol dm -3 were reduced by 43% to 79%, respectively. The inhibition effect on the crystal growth rate may be explained through adsorption onto the active growth sites. Kinetic analysis suggested Langmuir-type adsorption of acetaminophen on the HAP surface with a affinity value of 2.4×10 -4 dm 3 mol -1, for the substrate in the concentration range investigated. The electrophoretic mobility measurements showed that in the presence of acetaminophen the charge of the acetaminophen covered HAP particles was shifted to more negative values as compared to bare HAP. In the presence of acetaminophen no changes observed in the HAP overgrown morphology or in the apparent order of crystallization.

  16. Acetaminophen (paracetamol) oral absorption and clinical influences.

    PubMed

    Raffa, Robert B; Pergolizzi, Joseph V; Taylor, Robert; Decker, John F; Patrick, Jeffrey T

    2014-09-01

    Acetaminophen (paracetamol) is a widely used nonopioid, non-NSAID analgesic that is effective against a variety of pain types, but the consequences of overdose can be severe. Because acetaminophen is so widely available as a single agent and is increasingly being formulated in fixed-ratio combination analgesic products for the potential additive or synergistic analgesic effect and/or reduced adverse effects, accidental cumulative overdose is an emergent concern. This has rekindled interest in the sites, processes, and pharmacokinetics of acetaminophen oral absorption and the clinical factors that can influence these. The absorption of oral acetaminophen occurs primarily along the small intestine by passive diffusion. Therefore, the rate-limiting step is the rate of gastric emptying into the intestines. Several clinical factors can affect absorption per se or the rate of gastric emptying, such as diet, concomitant medication, surgery, pregnancy, and others. Although acetaminophen does not have the abuse potential of opioids or the gastrointestinal bleeding or organ adverse effects of NSAIDs, excess amounts can produce serious hepatic injury. Thus, an understanding of the sites and features of acetaminophen absorption--and how they might be influenced by factors encountered in clinical practice--is important for pain management using this agent. It can also provide insight for design of formulations that would be less susceptible to clinical variables. PMID:26013309

  17. Detection of Acetaminophen-Protein Adducts in Decedents with Suspected Opioid-Acetaminophen Combination Product Overdose.

    PubMed

    Thomas, Karen C; Wilkins, Diana G; Curry, Steven C; Grey, Todd C; Andrenyak, David M; McGill, Lawrence D; Rollins, Douglas E

    2016-09-01

    Acetaminophen overdose is a leading cause of drug-induced liver failure in the United States. Acetaminophen-protein adducts have been suggested as a biomarker of hepatotoxicity. The purpose of this study was to determine whether protein-derived acetaminophen-protein adducts are quantifiable in postmortem samples. Heart blood, femoral blood, and liver tissue were collected at autopsy from 22 decedents suspected of opioid-acetaminophen overdose. Samples were assayed for protein-derived acetaminophen-protein adducts, acetaminophen, and selected opioids found in combination products containing acetaminophen. Protein-derived APAP-CYS was detected in 17 of 22 decedents and was measurable in blood that was not degraded or hemolyzed. Heart blood concentrations ranged from 11 ng/mL (0.1 μM) to 7817 ng/mL (28.9 μM). Protein-derived acetaminophen-protein adducts were detectable in liver tissue for 20 of 22 decedents. Liver histology was also performed for all decedents, and no evidence of centrilobular hepatic necrosis was observed. PMID:27479586

  18. Acetaminophen During Pregnancy May Up Risk of ADHD in Kids

    MedlinePlus

    ... html Acetaminophen During Pregnancy May Up Risk of ADHD in Kids But only association found, and researchers ... their child will develop behavioral problems such as attention-deficit/hyperactivity disorder (ADHD), a new study suggests. Acetaminophen is generally ...

  19. Inadequacy of carbamazepine-spiked model wastewaters for testing photocatalysis efficiency.

    PubMed

    Gulyas, Holger; Ogun, Moses Kolade; Meyer, Wibke; Reich, Margrit; Otterpohl, Ralf

    2016-01-15

    The study was performed in order to clarify whether carbamazepine-spiked solutions used as model wastewaters are suitable for the assessment of carbamazepine removal from real secondary municipal effluents by photocatalytic oxidation in the presence and absence of activated carbon. Therefore, carbamazepine (10 mg L(-1)) was dissolved in deionized water or in secondary municipal effluent. Photocatalytic oxidation of these model wastewaters was carried out with TiO2 "P25" (100 mg L(-1)) and UV-A lamps in the absence and in the presence of 20 mg L(-1) powdered activated carbon (PAC). Carbamazepine was analyzed photometrically. In deionized water at pH 5.5, carbamazepine was nearly completely removed with a UV dose of 6.48 kJ L(-1). A similar efficiency of photocatalytic oxidation of carbamazepine added to secondary effluent was observed when the suspension pH was 2.7, while at pH 8 and 10.6, carbamazepine removal from spiked secondary effluent with the same UV dose was only 40 and 60%, respectively. Although PAC addition resulted in an initial adsorptive carbamazepine reduction of 20 to 35% from the model wastewaters, it did not lead to markedly enhanced carbamazepine removal in the subsequent photocatalysis phase. During photocatalytic oxidation of unspiked secondary effluent (initial carbamazepine concentration: 133 ng L(-1)) at pH 7.3 with and without PAC, carbamazepine concentrations were analyzed by HPLC/MS/MS. While PAC addition resulted in the adsorption of about 90% of the initial carbamazepine, photocatalysis did not lead to any carbamazepine removal at all. This indicates that the experiments with spiked model wastewaters – even in a secondary effluent matrix – are absolutely inadequate for predicting photocatalytic carbamazepine removal under real conditions. PMID:26544890

  20. Caffeine's Vascular Mechanisms of Action

    PubMed Central

    Echeverri, Darío; Montes, Félix R.; Cabrera, Mariana; Galán, Angélica; Prieto, Angélica

    2010-01-01

    Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial. PMID:21188209

  1. Caffeine, exercise and the brain.

    PubMed

    Meeusen, Romain; Roelands, Bart; Spriet, Lawrence L

    2013-01-01

    Caffeine can improve exercise performance when it is ingested at moderate doses (3-6 mg/kg body mass). Caffeine also has an effect on the central nervous system (CNS), and it is now recognized that most of the performance-enhancing effect of caffeine is accomplished through the antagonism of the adenosine receptors, influencing the dopaminergic and other neurotransmitter systems. Adenosine and dopamine interact in the brain, and this might be one mechanism to explain how the important components of motivation (i.e. vigor, persistence and work output) and higher-order brain processes are involved in motor control. Caffeine maintains a higher dopamine concentration especially in those brain areas linked with 'attention'. Through this neurochemical interaction, caffeine improves sustained attention, vigilance, and reduces symptoms of fatigue. Other aspects that are localized in the CNS are a reduction in skeletal muscle pain and force sensation, leading to a reduction in perception of effort during exercise and therefore influencing the motivational factors to sustain effort during exercise. Because not all CNS aspects have been examined in detail, one should consider that a placebo effect may also be present. Overall, it appears that the performance-enhancing effects of caffeine reside in the brain, although more research is necessary to reveal the exact mechanisms through which the CNS effect is established.

  2. Caffeine, a naturally occurring acaricide.

    PubMed

    Russell, D W; Fernández-Caldas, E; Swanson, M C; Seleznick, M J; Trudeau, W L; Lockey, R F

    1991-01-01

    Since caffeine is a plant alkaloid that has been described as a naturally occurring insecticide, its acaricidal effect on Dermatophagoides pteronyssinus (Dp) was investigated. Twelve cultures were established by adding 30 Dp to 200 mg of Tetramin fish food and brewer's yeast (8:2 ratio); six cultures were treated with 20 mg of finely ground caffeine. All 12 cultures were incubated at 75% relative humidity, 25 degrees C, and observed during 8 weeks. Live mites were then counted under a stereoscope, cultures were extracted, and supernatants were analyzed for Der p I and Der f I allergen content with a two-site monoclonal RIA. Live mite counts in untreated cultures varied from 146 to 274 (215 +/- 47.1), and in caffeine-treated cultures from 0 to 3 (1 +/- 1.2; p less than or equal to 0.0001). Der p I concentrations in untreated cultures varied from 588 to 9000 ng/gm (3138.3 +/- 2990.8 ng/gm), and in caffeine-treated cultures from 52 to 117 ng/gm (78 +/- 23.8 ng/gm; p less than or equal to 0.01). Der p I was not detected in the food media or caffeine; Der f I was not detected in any of the cultures. Results demonstrate that caffeine inhibits mite growth and allergen production.

  3. Carbamazepine in Bipolar Disorder With Pain: Reviewing Treatment Guidelines

    PubMed Central

    Campbell, Austin; O’Connell, Christopher R.; Nallapula, Kishan

    2014-01-01

    Objective: To determine if any monotherapy drug treatment has robust efficacy to treat comorbid bipolar disorder and chronic pain. Data Sources: The American Psychiatric Association (APA) treatment guidelines for bipolar mood disorder and the 2012 Cochrane database for pain disorders. Study Selection: We relied on the treatment guides to determine if the drugs that are APA guideline–supported to treat bipolar disorder have supporting data from the Cochrane database for chronic pain. Data Synthesis: No single drug was mentioned by either guideline to treat this comorbidity. However, carbamazepine was the only drug that has guideline-supported robust efficacy in the management of each condition separately. Conclusions: Carbamazepine was found to have strong preclinical data for the treatment of comorbid bipolar mood disorder and chronic pain disorders. While requiring more studies in this population, we propose that this treatment modality may benefit patients. PMID:25667814

  4. [Skin reaction to carbamazepine or DRESS syndrome: a case presentation].

    PubMed

    Cabrera Fundora, Emigdio Jesús; Cabrera Osorio, Yuliet; Cabrera Osorio, Claudia

    2016-02-25

    Carbamazepine is a frequently used drug that can produce adverse reactions like vertigo, somnolence and severe skin reactions like Drug Rash with Eosinophilia and Systemic Symptoms Syndrome (DRESS Syndrome). This syndrome is characterized by a late-appearing, slow-progressing cutaneous eruption accompanied by atypical lymphocytes, eosinophilia, and systemic symptoms such as fever, lymphadenopathy, hepatic compromise, and renal dysfunction that can be severe enough to cause death. We present a case that aims to highlight the importance of an early diagnosis of DRESS syndrome to adjust therapy and improve survival. The patient is a female patient prescribed carbamazepine for trigeminal neuralgia who presented with skin lesions, which were initially attributed to a hypersensitivity reaction. The lesions worsened in spite of treatment and systemic symptoms ensued. A diagnosis of DRESS syndrome was proposed and steroid treatment was initiated with rapid improvement.

  5. Safety of rapid intravenous of infusion acetaminophen

    PubMed Central

    2013-01-01

    Intravenous acetaminophen, Ofirmev®, is approved for management of mild to moderate pain, management of moderate to severe pain with adjunctive opioids, and reduction of fever. The product is supplied as a 100 mL glass vial. As stated in the prescribing information, it is recommended to be infused over 15 minutes. This recommendation is related to the formulation propacetamol, the prodrug to acetaminophen, approved in Europe, which caused pain on infusion, and data from the clinical development of acetaminophen. The objective of this retrospective chart review study was to show the lack of side effects of rapidly infusing intravenous acetaminophen. Charts of American Society of Anesthesiology (ASA) Class I–III ambulatory surgical patients who received only acetaminophen in the preoperative setting were reviewed for any infusion-related side effects. Using standard binomial proportion analyses and employing SAS/JMP software, all vital signs were analyzed for statistically significant changes between pre- and postinfusion values. One hundred charts were reviewed. Only one patient had pain on infusion, which lasted 10 seconds. No reported side effects or erythema was seen at the injection site. No infusions had to be slowed or discontinued. The median infusion time was 3:41 minutes. Of the vital signs monitored, only the systolic (P < 0.0001) and diastolic (P < 0.0099) blood pressures had statistically significant changes from pre- to postinfusion; however, they were of no clinical relevance. Acetaminophen can be administered as a rapid infusion with no significant infusion-related side effects or complications. PMID:23814378

  6. Safety of rapid intravenous of infusion acetaminophen.

    PubMed

    Needleman, Steven M

    2013-07-01

    Intravenous acetaminophen, Ofirmev®, is approved for management of mild to moderate pain, management of moderate to severe pain with adjunctive opioids, and reduction of fever. The product is supplied as a 100 mL glass vial. As stated in the prescribing information, it is recommended to be infused over 15 minutes. This recommendation is related to the formulation propacetamol, the prodrug to acetaminophen, approved in Europe, which caused pain on infusion, and data from the clinical development of acetaminophen. The objective of this retrospective chart review study was to show the lack of side effects of rapidly infusing intravenous acetaminophen. Charts of American Society of Anesthesiology (ASA) Class I-III ambulatory surgical patients who received only acetaminophen in the preoperative setting were reviewed for any infusion-related side effects. Using standard binomial proportion analyses and employing SAS/JMP software, all vital signs were analyzed for statistically significant changes between pre- and postinfusion values. One hundred charts were reviewed. Only one patient had pain on infusion, which lasted 10 seconds. No reported side effects or erythema was seen at the injection site. No infusions had to be slowed or discontinued. The median infusion time was 3:41 minutes. Of the vital signs monitored, only the systolic (P < 0.0001) and diastolic (P < 0.0099) blood pressures had statistically significant changes from pre- to postinfusion; however, they were of no clinical relevance. Acetaminophen can be administered as a rapid infusion with no significant infusion-related side effects or complications. PMID:23814378

  7. Caffeine content of beverages as consumed.

    PubMed Central

    Gilbert, R. M.; Marshman, J. A.; Schwieder, M.; Berg, R.

    1976-01-01

    Quantitative analysis of beverages prepared at home by staff of the Addiction Research Foundation revealed a lower and much more variable caffeine content of both tea and coffee than had been reported in earlier studies, most of which were based on analysis of laboratory-prepared beverages. Median caffeine concentration of 37 home-prepared samples of tea was 27 mg per cup (range, 8 to 91 mg); for 46 coffee samples the median concentration was 74 mg per cup (range, 29 to 176 mg). If tea and coffee as drunk contain less caffeine than generally supposed, the potency of caffeine may be greater than commonly realized, as may the relative caffeine content of certain commercial preparations, including chocolate and colas. The substantial variation in caffeine content emphasizes the need to establish actual caffeine intake in clinical, epidemiologic and experimental investigations of caffeine effects. PMID:1032351

  8. Caffeine Intake Among Adolescents in Delhi

    PubMed Central

    Gera, Mridul; Kalra, Swati; Gupta, Piyush

    2016-01-01

    Background: Availability and advertising of caffeinated drinks is on the rise in Indian market. Excess caffeine intake may have deleterious effects on health. Objective: To estimate the daily consumption of caffeine among urban school-going adolescents from Delhi. Materials and Methods: A school-based survey was conducted to determine the amount and pattern of caffeine consumption among students of classes 9-12, using a self-administered questionnaire. Results: Of 300 participants (median age 15 year, 174 boys), 291 (97%) were consuming caffeine [mean (SD): 121.0 (98.2) mg/day]. Nineteen (6%) students were consuming more than 300 mg of caffeine per day. Tea/coffee contributed to more than 50% of the caffeine intake. The rest was derived from cola beverages, chocolates, and energy drinks. Conclusion: Average caffeine consumption among school-going adolescents from Delhi is high. The findings of this preliminary survey need to be confirmed in larger data sets. PMID:27051091

  9. Effects of acute caffeine administration on adolescents.

    PubMed

    Temple, Jennifer L; Dewey, Amber M; Briatico, Laura N

    2010-12-01

    Acute caffeine administration has physiological, behavioral, and subjective effects. Despite its widespread use, few studies have described the impact of caffeine consumption in children and adolescents. The purpose of this study was to investigate the effects of acute caffeine administration in adolescents. We measured cardiovascular responses and snack food intake after acute administration of 0 mg, 50 mg, 100 mg, and 200 mg of caffeine. We also compared usual food intake and subjective effects of caffeine between high- and low-caffeine consumers. Finally, we conducted a detailed analysis of caffeine sources and consumption levels. We found main effects of caffeine dose on heart rate (HR) and diastolic blood pressure (DBP), with HR decreasing and DBP increasing with increasing caffeine dose. There were significant interactions among gender, caffeine use, and time on DBP. High caffeine consumers (>50 mg/day) reported using caffeine to stay awake and drinking coffee, tea, soda, and energy drinks more than low consumers (<50 mg/day). Boys were more likely than girls to report using getting a rush, more energy, or improved athletic performance from caffeine. Finally, when we examined energy and macronutrient intake, we found that caffeine consumption was positively associated with laboratory energy intake, specifically from high-sugar, low-fat foods and also positively associated with protein and fat consumption outside of the laboratory. When taken together, these data suggest that acute caffeine administration has a broad range of effects in adolescents and that the magnitude of these effects is moderated by gender and chronic caffeine consumption. PMID:21186925

  10. 21 CFR 182.1180 - Caffeine.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Caffeine. 182.1180 Section 182.1180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1180 Caffeine. (a) Product. Caffeine. (b) Tolerance. 0.02 percent. (c) Limitations, restrictions,...

  11. 21 CFR 182.1180 - Caffeine.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Caffeine. 182.1180 Section 182.1180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1180 Caffeine. (a) Product. Caffeine....

  12. Caffeine Use and Young Adult Women.

    ERIC Educational Resources Information Center

    Vener, Arthur M.; Krupka, Lawrence R.

    1982-01-01

    Surveyed college women and men and found that caffeine was consumed by a large proportion of the respondents. Women consumed a larger amount of caffeine and used more substances containing this drug. An increase in caffeine usage with increased psychic stress was observed for women only. (Author)

  13. 21 CFR 182.1180 - Caffeine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Caffeine. 182.1180 Section 182.1180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1180 Caffeine. (a) Product. Caffeine. (b) Tolerance. 0.02 percent. (c) Limitations, restrictions,...

  14. 21 CFR 182.1180 - Caffeine.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Caffeine. 182.1180 Section 182.1180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1180 Caffeine. (a) Product. Caffeine. (b) Tolerance. 0.02 percent. (c) Limitations, restrictions,...

  15. 21 CFR 182.1180 - Caffeine.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Caffeine. 182.1180 Section 182.1180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1180 Caffeine. (a) Product. Caffeine. (b) Tolerance. 0.02 percent. (c) Limitations, restrictions,...

  16. Molecular recognition study of Carbamazepine, antiseizure drug, by p-t-butyl calix(8)arene.

    PubMed

    Meenakshi, C; Jayabal, P; Ramakrishnan, V

    2014-03-25

    The formation of inclusion complex of Carbamazepine, a antiseizure drug molecule, with the supra molecule, p-t-butyl calix(8)arene was studied. p-t-Butyl calix(8)arene was the host molecule and Carbamazepine was the guest molecule. Optical absorption spectral studies were carried out to study the molecular recognition properties of p-t-butyl calix(8)arene with Carbamazepine. The stochiometry of the host-guest complex and the binding constant were determined.

  17. [Use of acetaminophen in the community].

    PubMed

    Guberman, D

    1990-01-01

    Acetaminophen (Acamol) is one of the most widely used medications in children. The recommended dose is 10-15 mg/kg every 4 hours, and up to 5 doses a day. In a prospective study in an outpatient clinic, 101 parents of children 5 years old or younger were asked to describe their use of acetaminophen for their children, including dose, mode administration and maximal frequency of administration for fever. 2/3 used the syrup and 1/3 used suppositories. The average single dose was 13.8 +/- 5.5 mg/kg. Only 61% of the children received reasonable quantities of acetaminophen per dose. While 12% got an overdose of 20 mg/kg or more, 27% got an underdose of less than 10 mg/kg. Treatment was as often as every 2-3 hours in 13% of the children but only once every 8-24 hours in 22%. To overcome inadequate administration of acetaminophen, parents must be properly educated. PMID:2303194

  18. Caffeine during pregnancy? In moderation.

    PubMed Central

    Koren, G.

    2000-01-01

    QUESTION: Many of my female patients, those who plan pregnancy or have conceived, are afraid of any intake of caffeine. This often makes their lives miserable during pregnancy. Is this justified scientifically? ANSWER: Motherisk's recent meta-analysis suggests that the risks for miscarriage and fetal growth retardation increase only with daily doses of caffeine above 150 mg/d, equivalent to six typical cups of coffee a day. It is possible that some of this presumed risk is due to confounders, such as cigarette smoking. PMID:10790810

  19. Effects of Acetaminophen on Left Atrial Contractility

    PubMed Central

    Chang, Jun-Hei; Cheng, Pao-Yun; Hsu, Chih-Hsueng; Chen, Yao-Chang; Hong, Po-Da

    2016-01-01

    Background It has been observed that acetaminophen shows cardioprotective efficacy in mammals. In this study, we investigated the electromechanical effects of acetaminophen on the left atrium (LA). Methods Conventional microelectrodes were used to record the action potentials (AP) in rabbit LA preparations. The action potential duration (APD) at repolarization levels of 90%, 50% and 20% of the AP amplitude (APD90, APD50, and APD20, respectively), resting membrane potential, and contractile force were measured during 2 Hz electrical stimulation before and after sequential acetaminophen administration to the LA. Results Acetaminophen (0.1, 0.3, 1, and 3 mM) reduced APD20 from 9.4 ± 1.2 to 8.0 ± 1.1 (p < 0.05), 7.1 ± 0.8 (p < 0.05), 7.8 ± 1.1, and 6.8 ± 1.2 ms (p < 0.05), respectively, and APD50 from 20.2 ± 1.9 to 17.4 ± 2.0, 15.6 ± 1.8 (p < 0.05), 15.8 ± 2.2 (p < 0.05), and 14.1 ± 2.4 ms (p < 0.05), respectively, in a concentration-dependent manner. APD90 was reduced from 72.0 ± 3.6 to 64.7 ± 4.2, 61.9 ± 4.3, 60.5 ± 3.7, and 53.4 ± 4.4 ms (p < 0.05), respectively. Acetaminophen increased LA contractility from 45 ± 9 to 52 ± 10 (p < 0.05), 55 ± 9 (p < 0.01), 58 ± 9 (p < 0.01), and 60 ± 9 mg (p < 0.01), respectively, in a concentration-dependent manner. In the presence of the NOS inhibitor L-NAME or PKG-I inhibitor DT-2, additional acetaminophen treatment did not significantly increase LA contractility. Conclusions Acetaminophen modulated the electromechanical characteristics of LA by inhibiting the NOS and PKG I pathway, and then contributed to the positive inotropic effect. PMID:27471362

  20. Make Caffeine Visible: a Fluorescent Caffeine “Traffic Light” Detector

    NASA Astrophysics Data System (ADS)

    Xu, Wang; Kim, Tae-Hyeong; Zhai, Duanting; Er, Jun Cheng; Zhang, Liyun; Kale, Anup Atul; Agrawalla, Bikram Keshari; Cho, Yoon-Kyoung; Chang, Young-Tae

    2013-07-01

    Caffeine has attracted abundant attention due to its extensive existence in beverages and medicines. However, to detect it sensitively and conveniently remains a challenge, especially in resource-limited regions. Here we report a novel aqueous phase fluorescent caffeine sensor named Caffeine Orange which exhibits 250-fold fluorescence enhancement upon caffeine activation and high selectivity. Nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy indicate that π-stacking and hydrogen-bonding contribute to their interactions while dynamic light scattering and transmission electron microscopy experiments demonstrate the change of Caffeine Orange ambient environment induces its fluorescence emission. To utilize this probe in real life, we developed a non-toxic caffeine detection kit and tested it for caffeine quantification in various beverages. Naked-eye sensing of various caffeine concentrations was possible based on color changes upon irradiation with a laser pointer. Lastly, we performed the whole system on a microfluidic device to make caffeine detection quick, sensitive and automated.

  1. Make Caffeine Visible: a Fluorescent Caffeine “Traffic Light” Detector

    PubMed Central

    Xu, Wang; Kim, Tae-Hyeong; Zhai, Duanting; Er, Jun Cheng; Zhang, Liyun; Kale, Anup Atul; Agrawalla, Bikram Keshari; Cho, Yoon-Kyoung; Chang, Young-Tae

    2013-01-01

    Caffeine has attracted abundant attention due to its extensive existence in beverages and medicines. However, to detect it sensitively and conveniently remains a challenge, especially in resource-limited regions. Here we report a novel aqueous phase fluorescent caffeine sensor named Caffeine Orange which exhibits 250-fold fluorescence enhancement upon caffeine activation and high selectivity. Nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy indicate that π-stacking and hydrogen-bonding contribute to their interactions while dynamic light scattering and transmission electron microscopy experiments demonstrate the change of Caffeine Orange ambient environment induces its fluorescence emission. To utilize this probe in real life, we developed a non-toxic caffeine detection kit and tested it for caffeine quantification in various beverages. Naked-eye sensing of various caffeine concentrations was possible based on color changes upon irradiation with a laser pointer. Lastly, we performed the whole system on a microfluidic device to make caffeine detection quick, sensitive and automated. PMID:23877095

  2. Improvement of physicomechanical properties of carbamazepine by recrystallization at different pH values.

    PubMed

    Javadzadeh, Yousef; Mohammadi, Ameneh; Khoei, Nazaninossadat Seyed; Nokhodchi, Ali

    2009-06-01

    The morphology of crystals has an appreciable impact role on the physicochemical properties of drugs. Drug properties such as flowability, dissolution, hardness and bioavailability may be affected by crystallinity behaviours of drugs. The objective of this study was to achieve an improved physicomechanical property of carbamazepine powder through recrystallization from aqueous solutions at different pH values. For this purpose, carbamazapine was recrystallized from aqueous solutions at different pH values (1, 7, 11). The morphology of crystals was investigated using scanning electron microscopy; X-ray powder diffraction (XRPD) was used to identify polymorphism; thermodynamic properties were analyzed using differential scanning calorimetery (DSC). Dissolution rate was determined using USP dissolution apparatus. Mechanical behavior of recrystallized carbamazepine powders was investigated by making tablets under different compaction pressure and measuring their hardness. SEM studies showed that the carbamazepine crystallization in different media affected the morphology and size of carbamazepine crystals. The shape of carbamazepine crystals changed from flaky or thin plate-like to needle shape. XRPD and DSC results ruled out any crystallinity changes occurring due to the temperature during recrystallization procedure or pH of crystallization media. The crushing strength of tablets indicated that all of the recrystallized carbamazepine samples had better compactiblity than the original carbamazepine powder. In vitro dissolution studies of carbamazepine samples showed a higher dissolution rate for carbamazepine crystals obtained from media with pH 11 and 1. Carbamazepine particles recrystallized from aqueous solutions of different pH values (all media) appeared to have superior mechanical properties to those of the original carbamazepine sample.

  3. Three-Dimensional Printing of Carbamazepine Sustained-Release Scaffold.

    PubMed

    Lim, Seng Han; Chia, Samuel Ming Yuan; Kang, Lifeng; Yap, Kevin Yi-Lwern

    2016-07-01

    Carbamazepine is the first-line anti-epileptic drug for focal seizures and generalized tonic-clonic seizures. Although sustained-release formulations exist, an initial burst of drug release is still present and this results in side effects. Zero-order release formulations reduce fluctuations in serum drug concentrations, thereby reducing side effects. Three-dimensional printing can potentially fabricate zero-order release formulations with complex geometries. 3D printed scaffolds with varying hole positions (side and top/bottom), number of holes (4, 8, and 12), and hole diameters (1, 1.5, and 2 mm) were designed. Dissolution tests and high performance liquid chromatography analysis were conducted. Good correlations in the linear release profiles of all carbamazepine-containing scaffolds with side holes (R(2) of at least 0.91) were observed. Increasing the hole diameters (1, 1.5, and 2 mm) resulted in increased rate of drug release in the scaffolds with 4 holes (0.0048, 0.0065, and 0.0074 mg/min) and 12 holes (0.0021, 0.0050, and 0.0092 mg/min), and the initial amount of carbamazepine released in the scaffolds with 8 holes (0.4348, 0.7246, and 1.0246 mg) and 12 holes (0.1995, 0.8598, and 1.4366 mg). The ultimate goal of this research is to improve the compliance of patients through a dosage form that provides a zero-order drug release profile for anti-epileptic drugs, so as to achieve therapeutic doses and minimize side effects. PMID:27290630

  4. Caffeine Modulates Attention Network Function

    ERIC Educational Resources Information Center

    Brunye, Tad T.; Mahoney, Caroline R.; Lieberman, Harris R.; Taylor, Holly A.

    2010-01-01

    The present work investigated the effects of caffeine (0 mg, 100 mg, 200 mg, 400 mg) on a flanker task designed to test Posner's three visual attention network functions: alerting, orienting, and executive control [Posner, M. I. (2004). "Cognitive neuroscience of attention". New York, NY: Guilford Press]. In a placebo-controlled, double-blind…

  5. Caffeine Use Affects Pregnancy Outcome

    ERIC Educational Resources Information Center

    Diego, Miguel; Field, Tiffany; Hernandez-Reif, Maria; Vera, Yanexy; Gil, Karla; Gonzalez-Garcia, Adolfo

    2008-01-01

    A sample of 750 women were interviewed during pregnancy on their depression and anxiety symptoms, substance use and demographic variables. A subsample was seen again at the neonatal stage (n = 152), and their infants were observed for sleep-wake behavior. Symptoms of depression and anxiety were related to caffeine use. Mothers who consumed more…

  6. Caffeine ingestion and isokinetic strength.

    PubMed Central

    Bond, V; Gresham, K; McRae, J; Tearney, R J

    1986-01-01

    The purpose of this study was to investigate the effects of caffeine on maximum voluntary contractions of the dominant knee extension and flexion muscles in 12 male intercollegiate track sprinters. Caffeine (5 mg.kg-1) and placebo (225 mg methylcellulose) gelatin capsules were administered orally in randomly assigned order. Muscle function was measured isokinetically by a Cybex II dynamometer interfaced with a data reduction computer. Six repetitions maximum of the extensors and flexors were performed at three sequential ordered speeds (30 degrees, 150 degrees and 300 degrees s-1) with a one-minute rest between varying velocities. Peake torque and power were than assessed after treatment conditions, as well as a fatigue index calculated from a series of 60 repetitions maximum ato 150 degrees s-1. Results of the 2 X 3 ANOVA and paired t-test indicated no difference in measures of peak torque and power at the varying contracting velocities and fatigue index after caffeine ingestion. These findings indicate the ingestion of caffeine in a small dose exerts no ergogenic effect on muscle function under anaerobic conditions. PMID:3779343

  7. Comparison of equilibrium and non-equilibrium distribution coefficients for the human drug carbamazepine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The distribution coefficient (KD) for the human drug carbamazepine was measured using a non-equilibrium technique. Repacked soil columns were prepared using an Airport silt loam (Typic Natrustalf) with an average organic matter content of 2.45%. Carbamazepine solutions were then leached through th...

  8. Effects of prenatal exposure to carbamazepine on brainstem auditory evoked potentials in infants of epileptic mothers.

    PubMed

    Poblano, Adrián; Belmont, Aurora; Sosa, Jesús; Ibarra, Jorge; Rosas, Yolanda; López, Vivián; Garza, Saúl

    2002-05-01

    The purpose of this study was to determine if there are any correlations between carbamazepine serum levels of epileptic mothers during pregnancy and the brainstem auditory evoked potentials in their infants as an index of drug neurotoxicity in newborns exposed prenatally. We included 20 epileptic mothers with carbamazepine medication and their 20 otherwise healthy infants. The study was conducted from September 1, 1993, to December 15, 1999. Serum carbamazepine determinations were performed monthly by enzymatic immunoanalysis in the mothers, and the averages for each trimester during pregnancy were calculated. Brainstem auditory evoked potentials were performed at 10.2 +/- 4.6 weeks of postnatal life. Pearson's correlations were calculated between carbamazepine serum levels during pregnancy and waves and interwave intervals of brainstem auditory evoked potentials. Both examinations were performed without knowledge of the results of the other investigations. No alterations in the infants' brainstem auditory evoked potentials were evident, and carbamazepine determinations were within therapeutic levels. Significant Pearson's correlations between latencies of waves III and V and third trimester of carbamazepine serum concentration levels and I-V interwave intervals to third-trimester minimum serum levels of carbamazepine were found. The findings suggest that the higher carbamazepine levels in mothers are related to increased latencies in waves III and V and I-V interwave intervals in infants subclinically, which could be an early index of fetal neurotoxicity.

  9. Consumption of caffeinated beverages and the awareness of their caffeine content among Dutch students.

    PubMed

    Mackus, Marlou; van de Loo, Aurora J A E; Benson, Sarah; Scholey, Andrew; Verster, Joris C

    2016-08-01

    The purpose of the current study was to examine the knowledge of caffeine content of a variety of caffeinated beverages among Dutch university students. A pencil-and-paper survey was conducted among N = 800 Dutch students. Most participants (87.8%) reported consuming caffeinated beverages during the past 24 h. Their mean ± SD past 24-h caffeine intake from beverages was 144.2 ± 169.5 mg (2.2 ± 3.0 mg/kg bw). Most prevalent sources of caffeine were coffee beverages (50.8%) and tea (34.8%), followed by energy drink (9.2%), cola (4.7%), and chocolate milk (0.5%). Participants had poor knowledge on the relative caffeine content of caffeinated beverages. That is, they overestimated the caffeine content of energy drinks and cola, and underestimated the caffeine content of coffee beverages. If caffeine consumption is a concern, it is important to inform consumers about the caffeine content of all caffeine containing beverages, including coffee and tea. The current findings support previous research that the most effective way to reduce caffeine intake is to limit the consumption of coffee beverages and tea. PMID:27142708

  10. Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence

    SciTech Connect

    Chou, D.T.; Khan, S.; Forde, J.; Hirsh, K.R.

    1985-06-17

    The development of tolerance to the stimulatory action of caffeine upon mesencephalic reticular neurons and upon spontaneous locomotor activity was evaluated in rats after two weeks of chronic exposure to low doses of caffeine (5-10 mg/kg/day via their drinking water). These doses are achievable through dietary intake of caffeine-containing beverages in man. Concomitant measurement of (/sup 3/H)-CHA binding in the mesencephalic reticular formation was also carried out in order to explore the neurochemical basis of the development of tolerance. Caffeine, 2.5 mg/kg i.v., markedly increased the firing rate of reticular neurons in caffeine naive rats but failed to modify the neuronal activity in a group exposed chronically to low doses of caffeine. In addition, in spontaneous locomotor activity studies, the data show a distinct shift to the right of the caffeine dose-response curve in caffeine pretreated rats. These results clearly indicate that tolerance develops to the stimulatory action of caffeine upon the reticular formation at the single neuronal activity level as well as upon spontaneous locomotor activity. Furthermore, in chronically caffeine exposed rats, an increase in the number of binding sites for (/sup 3/H)-CHA was observed in reticular formation membranes without any change in receptor affinity. 28 references, 4 figures.

  11. Psychophysiological interactions between caffeine and nicotine.

    PubMed

    Rose, J E; Behm, F M

    1991-02-01

    The interactive effects of caffeine and nicotine were studied in twelve subjects. Mood and physiologic responses to the pharmacologic components nicotine and caffeine were measured, while controlling for the sensory/behavioral aspects of smoking and coffee drinking. Two experimental sessions presented a caffeine x nicotine design, with caffeinated or decaffeinated coffee followed at thirty-minute intervals by controlled inhalations of nicotine and nonnicotine smoke. Results showed that there was a significant interactive effect of caffeine and nicotine on subjective arousal such that nicotine decreased arousal only in the presence of caffeine. These findings extend previous work showing interactive effects of caffeine and self-titrated doses of cigarette smoke in affecting subjective arousal. The effects of nicotine on subjective arousal may, therefore, depend not only on nicotine dose, but also on the presence of caffeine. Heart rate was increased by nicotine and both systolic and diastolic blood pressures were elevated by caffeine. Caffeine also potentiated the increase in diastolic blood pressure resulting from smoke inhalations, but this occurred irrespective of nicotine dose. PMID:2057503

  12. Effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of carbamazepine in healthy volunteers.

    PubMed

    Malhotra, S; Dixit, R K; Garg, S K

    2002-01-01

    The effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of a single dose of carbamazepine was studied. In a two-way cross-over design with a 1 week washout period, 10 healthy volunteers were randomized to received 200 mg carbamazepine orally with 300 ml of Coca-Cola or water. Blood samples were collected at 0, 0.5, 1, 2, 3, 6, 9, 12, 24, 48 and 72 h after drug administration. Plasma carbamazepine levels were higher with Coca-Cola as compared to water. The AUC0-infinity and Cmax of carbamazepine were significantly enhanced after Coca-Cola while tmax was achieved earlier with Coca-Cola. The results of the study indicate that concomitant administration of Coca-Cola enhances the rate and extent of absorption of carbamazepine.

  13. Acetaminophen overdose associated with double serum concentration peaks.

    PubMed

    Papazoglu, Cristian; Ang, Jonathan R; Mandel, Michael; Basak, Prasanta; Jesmajian, Stephen

    2015-01-01

    Acetaminophen is the most commonly used analgesic-antipyretic medication in the United States. Acetaminophen overdose, a frequent cause of drug toxicity, has been recognized as the leading cause of fatal and non-fatal hepatic necrosis. N-Acetylcysteine is the recommended antidote for acetaminophen poisoning. Despite evidence on the efficacy of N-acetylcysteine for prevention of hepatic injury, controversy persists about the optimal duration of the therapy. Here, we describe the case of a 65-year-old male with acetaminophen overdose and opioid co-ingestion who developed a second peak in acetaminophen serum levels after completing the recommended 21-hour intravenous N-acetylcysteine protocol and when the standard criteria for monitoring drug levels was achieved. Prolongation of N-acetylcysteine infusion beyond the standard protocol, despite a significant gap in treatment, was critical for successful avoidance of hepatotoxicity. Delay in acetaminophen absorption may be associated with a second peak in serum concentration following an initial declining trend, especially in cases of concomitant ingestion of opioids. In patients with acetaminophen toxicity who co-ingest other medications that may potentially delay gastric emptying or in those with risk factors for delayed absorption of acetaminophen, we recommend close monitoring of aminotransferase enzyme levels, as well as trending acetaminophen concentrations until undetectable before discontinuing the antidote therapy. PMID:26653695

  14. [A Case of Acetaminophen Poisoning Associated with Tramcet Overdose].

    PubMed

    Urabe, Shigehiko; Terao, Yoshiaki; Tuji, Tikako; Egashira, Takashi; Goto, Shino; Fukusaki, Makoto

    2016-06-01

    Tramcet is a mixture of tramadol and acetaminophen. Acetaminophen poisoning may be caused by excessive intake of Tramcet. A 17-year-old female took excessive quantity of Tramcet before noon. She reported it herself in the emergency room. Her main complaint was nausea and dizziness. Acetaminophen may cause liver damage with dose-dependent manner. Because there was a possibility of acetaminophen poisoning, we started oral acetylcysteine. She was discharged from hospital 5 days later without side effects of acetylecysteine and liver damage. PMID:27483669

  15. Acetaminophen overdose associated with double serum concentration peaks

    PubMed Central

    Papazoglu, Cristian; Ang, Jonathan R.; Mandel, Michael; Basak, Prasanta; Jesmajian, Stephen

    2015-01-01

    Acetaminophen is the most commonly used analgesic–antipyretic medication in the United States. Acetaminophen overdose, a frequent cause of drug toxicity, has been recognized as the leading cause of fatal and non-fatal hepatic necrosis. N-Acetylcysteine is the recommended antidote for acetaminophen poisoning. Despite evidence on the efficacy of N-acetylcysteine for prevention of hepatic injury, controversy persists about the optimal duration of the therapy. Here, we describe the case of a 65-year-old male with acetaminophen overdose and opioid co-ingestion who developed a second peak in acetaminophen serum levels after completing the recommended 21-hour intravenous N-acetylcysteine protocol and when the standard criteria for monitoring drug levels was achieved. Prolongation of N-acetylcysteine infusion beyond the standard protocol, despite a significant gap in treatment, was critical for successful avoidance of hepatotoxicity. Delay in acetaminophen absorption may be associated with a second peak in serum concentration following an initial declining trend, especially in cases of concomitant ingestion of opioids. In patients with acetaminophen toxicity who co-ingest other medications that may potentially delay gastric emptying or in those with risk factors for delayed absorption of acetaminophen, we recommend close monitoring of aminotransferase enzyme levels, as well as trending acetaminophen concentrations until undetectable before discontinuing the antidote therapy. PMID:26653695

  16. [A Case of Acetaminophen Poisoning Associated with Tramcet Overdose].

    PubMed

    Urabe, Shigehiko; Terao, Yoshiaki; Tuji, Tikako; Egashira, Takashi; Goto, Shino; Fukusaki, Makoto

    2016-06-01

    Tramcet is a mixture of tramadol and acetaminophen. Acetaminophen poisoning may be caused by excessive intake of Tramcet. A 17-year-old female took excessive quantity of Tramcet before noon. She reported it herself in the emergency room. Her main complaint was nausea and dizziness. Acetaminophen may cause liver damage with dose-dependent manner. Because there was a possibility of acetaminophen poisoning, we started oral acetylcysteine. She was discharged from hospital 5 days later without side effects of acetylecysteine and liver damage.

  17. Effects of the antiepileptic drug carbamazepine on human erythrocytes.

    PubMed

    Suwalsky, Mario; Mennickent, Sigrid; Norris, Beryl; Villena, Fernando; Sotomayor, Carlos P

    2006-12-01

    The structural effects of the antiepileptic drug carbamazepine (CBZ) on the human erythrocyte membrane and molecular models have been investigated in the present work. This report presents the following evidence that CBZ interacts with red cell membranes: (a) X-ray diffraction and fluorescence spectroscopy of phospholipid bilayers showed that CBZ perturbed a class of lipids found in the outer moiety of the erythrocyte membrane; (b) in isolated unsealed human erythrocytes (IUM) the drug induced a disordering effect on the polar head groups and acyl chains of the membrane lipid bilayer; (c) in scanning electron microscopy (SEM) studies on human erythrocytes the formation of echinocytes was observed, due to the preferential insertion of CBZ in the outer monolayer of the red cell membrane. The effects of the drug detected in the present work were observed at concentrations of the order of those currently appearing in serum when it is therapeutically administered. This is the first time that toxic effects of carbamazepine on the human erythrocyte membrane have been described. PMID:16844339

  18. Degradation kinetics and metabolites of carbamazepine in soil.

    PubMed

    Li, Juying; Dodgen, Laurel; Ye, Qingfu; Gan, Jay

    2013-04-16

    The antiepileptic drug carbamazepine (CBZ) is one of the most frequently detected human pharmaceuticals in wastewater effluents and biosolids. Soil is a primary environmental compartment receiving CBZ through wastewater irrigation and biosolid application. In this study, we explored the transformation of CBZ to biologically active intermediates in soil. Both (14)C labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to track transformation kinetics and identify major degradation intermediates. Through 120 days of incubation under aerobic conditions, mineralization of CBZ did not exceed 2% of the spiked rate in different soils. Amendment of biosolids further suppressed mineralization. The fraction of non-extractable (i.e., bound) residue also remained negligible (<5%). On the other hand, CBZ was transformed to a range of degradation intermediates, including 10,11-dihydro-10-hydroxycarbamazepine, carbamazepine-10,11-epoxide, acridone-N-carbaldehyde, 4-aldehyde-9-acridone, and acridine, of which acridone-N-carbaldehyde was formed in a large fraction and appeared to be recalcitrant to further degradation. Electrocyclization, ring cleavage, hydrogen shift, carbonylation, and decarbonylation contributed to CBZ transformative reactions in soil, producing biologically active products. The persistence of the parent compound and formation of incomplete intermediates suggest that CBZ has a high risk for off-site transport from soil, such as accumulation into plants and contamination of groundwater.

  19. Transformation Pathways of the Recalcitrant Pharmaceutical Compound Carbamazepine by the White-Rot Fungus Pleurotus ostreatus: Effects of Growth Conditions.

    PubMed

    Golan-Rozen, Naama; Seiwert, Bettina; Riemenschneider, Christina; Reemtsma, Thorsten; Chefetz, Benny; Hadar, Yitzhak

    2015-10-20

    The widely used anticonvulsant pharmaceutical carbamazepine is recalcitrant in many environmental niches and thus poses a challenge in wastewater treatment. We followed the decomposition of carbamazepine by the white-rot fungus Pleurotus ostreatus in liquid culture compared to solid-state fermentation on lignocellulosic substrate where different enzymatic systems are active. Carbamazepine metabolites were identified using liquid chromatography-high-resolution mass spectrometry (LC-Q-TOF-MS). In liquid culture, carbamazepine was only transformed to 10,11-epoxy carbamazepine and 10,11-dihydroxy carbamazepine as a dead-end product. During solid-state fermentation, carbamazepine metabolism resulted in the generation of an additional 22 transformation products, some of which are toxic. Under solid-state-fermentation conditions, 10,11-epoxy carbamazepine was further metabolized via acridine and 10,11-dihydroxy carbamazepine pathways. The latter was further metabolized via five subpathways. When (14)C-carbonyl-labeled carbamazepine was used as the substrate, (14)C-CO2 release amounted to 17.4% of the initial radioactivity after 63 days of incubation. The proposed pathways were validated using metabolites (10,11-epoxy carbamazepine, 10,11-dihydroxy carbamazepine, and acridine) as primary substrates and following their fate at different time points. This work highlights the effect of growth conditions on the transformation pathways of xenobiotics. A better understanding of the fate of pollutants during bioremediation treatments is important for establishment of such technologies. PMID:26418858

  20. Acute effects of caffeine on heart rate variability in habitual caffeine consumers.

    PubMed

    Rauh, Robert; Burkert, Michaela; Siepmann, Martin; Mueck-Weymann, Michael

    2006-05-01

    During the last years, heart rate variability (HRV) has become a promising risk factor for cardiovascular events. However, the effect of caffeine on HRV in habitual caffeine consumers has barely been investigated. Therefore, we treated 30 male habitual caffeine users in a randomized double-blinded crossover study design with either placebo, 100 or 200 mg caffeine orally and determined parameters of HRV under resting conditions and metronomic breathing. As result, we could not detect significant differences in HRV parameters up to 90 min after drug ingestion. We conclude that modest amounts of caffeine do not reveal negative nor positive effects on HRV within the first 90 min after drug ingestion in young and healthy habitual caffeine consumers. However, further research is necessary to determine the effects of caffeine on HRV in habitual caffeine users, healthy as well as suffering from diabetes, hypertension and postmyocardial infarction.

  1. Carbamazepine, carbamazepine epoxide and dihydroxycarbamazepine sorption to soil and occurrence in a wastewater reuse site in Tunisia.

    PubMed

    Fenet, Hélène; Mathieu, Olivier; Mahjoub, Olfa; Li, Zhi; Hillaire-Buys, Dominique; Casellas, Claude; Gomez, Elena

    2012-06-01

    Treated wastewater is being increasingly used for irrigation and aquifer replenishment through artificial recharge. However, wastewater reuse can result in contamination of exposed soil and groundwater by chemicals such as some pharmaceuticals and their metabolites. The fate of these molecules depends largely on their capacity to sorb onto soil and aquifer materials during infiltration. In this study, the sorption isotherm of carbamazepine (CBZ), an anti-seizure medication, and two of its metabolites, i.e. carbamazepine-10,11-epoxide (CBZ-EP) and 10,11-dihydro-10,11-dihydroxycarbamazepine (DiOH-CBZ), were determined in two soils in laboratory assays. In the field, the presence of CBZ and its metabolites were investigated in soil and in groundwater underlying an irrigated area with treated wastewater. The results showed that CBZ had the highest carbon normalised sorption coefficients in the two tested soils (irrigated soil and a Lufa SP2.4 reference soil) followed by CBZ-EP and DiOH-CBZ, indicating the relatively higher mobility of CBZ metabolites compared to CBZ. The chromatographic analysis revealed that CBZ and its two metabolites were present in treated wastewater used for irrigation and in groundwater. In soil samples, CBZ concentrations showed a build-up taking place with irrigation. The mobility of metabolites in soil and their potential biodegradation require further investigation.

  2. Caffeine reduces myocardial blood flow during exercise.

    PubMed

    Higgins, John P; Babu, Kavita M

    2013-08-01

    Caffeine consumption has been receiving increased interest from both the medical and lay press, especially given the increased amounts now available in energy products. Acute ingestion of caffeine usually increases cardiac work; however, caffeine impairs the expected proportional increase in myocardial blood flow to match this increased work of the heart, most notably during exercise. This appears to be mainly due to caffeine's effect on blocking adenosine-induced vasodilatation in the coronary arteries in normal healthy subjects. This review summarizes the available medical literature specifically relating to pure caffeine tablet ingestion and reduced exercise coronary blood flow, and suggests possible mechanisms. Further studies are needed to evaluate this effect for other common caffeine-delivery systems, including coffee, energy beverages, and energy gels, which are often used for exercise performance enhancement, especially in teenagers and young athletes.

  3. Evaluating the Validity of Caffeine Use Disorder.

    PubMed

    Budney, Alan J; Lee, Dustin C; Juliano, Laura M

    2015-09-01

    Caffeine use disorder is included in the conditions for further study section of the DSM-5. Caffeine's profile of neurobiological, behavioral, and clinical effects is similar to other common substances that humans use recreationally. Extant data suggest that a clinically meaningful addictive disorder develops in some regular caffeine users, but this literature is incomplete and not yet sufficient to determine if and how best to define and treat caffeine use disorder. An overview of the literature relevant to determining the clinical importance of problematic caffeine use is followed by discussion of potential concerns and benefits associated with its classification as a mental disorder. Concerns about overdiagnosis and trivialization of other psychiatric syndromes are weighed against the public health benefits of increased awareness and development of interventions targeting problematic caffeine use. This discussion includes consideration of alternative diagnostic approaches, improvement of assessment practices, and the need for additional clinical and epidemiological research.

  4. Caffeine reduces myocardial blood flow during exercise.

    PubMed

    Higgins, John P; Babu, Kavita M

    2013-08-01

    Caffeine consumption has been receiving increased interest from both the medical and lay press, especially given the increased amounts now available in energy products. Acute ingestion of caffeine usually increases cardiac work; however, caffeine impairs the expected proportional increase in myocardial blood flow to match this increased work of the heart, most notably during exercise. This appears to be mainly due to caffeine's effect on blocking adenosine-induced vasodilatation in the coronary arteries in normal healthy subjects. This review summarizes the available medical literature specifically relating to pure caffeine tablet ingestion and reduced exercise coronary blood flow, and suggests possible mechanisms. Further studies are needed to evaluate this effect for other common caffeine-delivery systems, including coffee, energy beverages, and energy gels, which are often used for exercise performance enhancement, especially in teenagers and young athletes. PMID:23764265

  5. Optimization in development of acetaminophen syrup formulation.

    PubMed

    Worakul, Nimit; Wongpoowarak, Wibul; Boonme, Prapaporn

    2002-03-01

    Formulation of acetaminophen syrup could be developed by an optimization technique to reduce the time and cost of study. Cosolvents were used in the formulation because of the low solubility of acetaminophen in water. They were composed of polyethylene glycol 4000, propylene glycol, sorbitol solution, and glycerin. Their effects on the solubility of acetaminophen and the pH of formulations were investigated. Effects on taste and price were calculated based on their properties. Simulation study of the effect of cosolvents upon the formulation scores was performed, using an algorithm based upon a simulated annealing concept to achieve the global optima and heuristic optimization concept to accelerate convergence. The program written as a Visual Basic module within Microsoft Access 97 was used to simulate and assess the optimal cosolvent amounts to achieve the most desirable formulations automatically according to the specified criteria. Formulators could customize the optimal formulation according to their needs and cost constraints by redefining the desirable outcomes in the source code of the program. PMID:12026227

  6. Exacerbation of Acetaminophen Hepatotoxicity by the Anthelmentic Drug Fenbendazole

    PubMed Central

    Gardner, Carol R.; Mishin, Vladimir; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-01-01

    Fenbendazole is a broad-spectrum anthelmintic drug widely used to prevent or treat nematode infections in laboratory rodent colonies. Potential interactions between fenbendazole and hepatotoxicants such as acetaminophen are unknown, and this was investigated in this study. Mice were fed a control diet or a diet containing fenbendazole (8–12 mg/kg/day) for 7 days prior to treatment with acetaminophen (300 mg/kg) or phosphate buffered saline. In mice fed a control diet, acetaminophen administration resulted in centrilobular hepatic necrosis and increases in serum transaminases, which were evident within 12 h. Acetaminophen-induced hepatotoxicity was markedly increased in mice fed the fenbendazole-containing diet, as measured histologically and by significant increases in serum transaminase levels. Moreover, in mice fed the fenbendazole-containing diet, but not the control diet, 63% mortality was observed within 24 h of acetaminophen administration. Fenbendazole by itself had no effect on liver histology or serum transaminases. To determine if exaggerated hepatotoxicity was due to alterations in acetaminophen metabolism, we analyzed sera for the presence of free acetaminophen and acetaminophen-glucuronide. We found that there were no differences in acetaminophen turnover. We also measured cytochrome P450 (cyp) 2e1, cyp3a, and cyp1a2 activity. Whereas fenbendazole had no effect on the activity of cyp2e1 or cyp3a, cyp1a2 was suppressed. A prolonged suppression of hepatic glutathione (GSH) was also observed in acetaminophen-treated mice fed the fenbendazole-containing diet when compared with the control diet. These data demonstrate that fenbendazole exacerbates the hepatotoxicity of acetaminophen, an effect that is related to persistent GSH depletion. These findings are novel and suggest a potential drug-drug interaction that should be considered in experimental protocols evaluating mechanisms of hepatotoxicity in rodent colonies treated with fenbendazole. PMID

  7. Exacerbation of acetaminophen hepatotoxicity by the anthelmentic drug fenbendazole.

    PubMed

    Gardner, Carol R; Mishin, Vladimir; Laskin, Jeffrey D; Laskin, Debra L

    2012-02-01

    Fenbendazole is a broad-spectrum anthelmintic drug widely used to prevent or treat nematode infections in laboratory rodent colonies. Potential interactions between fenbendazole and hepatotoxicants such as acetaminophen are unknown, and this was investigated in this study. Mice were fed a control diet or a diet containing fenbendazole (8-12 mg/kg/day) for 7 days prior to treatment with acetaminophen (300 mg/kg) or phosphate buffered saline. In mice fed a control diet, acetaminophen administration resulted in centrilobular hepatic necrosis and increases in serum transaminases, which were evident within 12 h. Acetaminophen-induced hepatotoxicity was markedly increased in mice fed the fenbendazole-containing diet, as measured histologically and by significant increases in serum transaminase levels. Moreover, in mice fed the fenbendazole-containing diet, but not the control diet, 63% mortality was observed within 24 h of acetaminophen administration. Fenbendazole by itself had no effect on liver histology or serum transaminases. To determine if exaggerated hepatotoxicity was due to alterations in acetaminophen metabolism, we analyzed sera for the presence of free acetaminophen and acetaminophen-glucuronide. We found that there were no differences in acetaminophen turnover. We also measured cytochrome P450 (cyp) 2e1, cyp3a, and cyp1a2 activity. Whereas fenbendazole had no effect on the activity of cyp2e1 or cyp3a, cyp1a2 was suppressed. A prolonged suppression of hepatic glutathione (GSH) was also observed in acetaminophen-treated mice fed the fenbendazole-containing diet when compared with the control diet. These data demonstrate that fenbendazole exacerbates the hepatotoxicity of acetaminophen, an effect that is related to persistent GSH depletion. These findings are novel and suggest a potential drug-drug interaction that should be considered in experimental protocols evaluating mechanisms of hepatotoxicity in rodent colonies treated with fenbendazole.

  8. Role of adenosine receptors in caffeine tolerance

    SciTech Connect

    Holtzman, S.G.; Mante, S.; Minneman, K.P. )

    1991-01-01

    Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity.

  9. The effects of caffeine on wound healing.

    PubMed

    Ojeh, Nkemcho; Stojadinovic, Olivera; Pastar, Irena; Sawaya, Andrew; Yin, Natalie; Tomic-Canic, Marjana

    2016-10-01

    The purine alkaloid caffeine is a major component of many beverages such as coffee and tea. Caffeine and its metabolites theobromine and xanthine have been shown to have antioxidant properties. Caffeine can also act as adenosine-receptor antagonist. Although it has been shown that adenosine and antioxidants promote wound healing, the effect of caffeine on wound healing is currently unknown. To investigate the effects of caffeine on processes involved in epithelialisation, we used primary human keratinocytes, HaCaT cell line and ex vivo model of human skin. First, we tested the effects of caffeine on cell proliferation, differentiation, adhesion and migration, processes essential for normal wound epithelialisation and closure. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) proliferation assay to test the effects of seven different caffeine doses ranging from 0·1 to 5 mM. We found that caffeine restricted cell proliferation of keratinocytes in a dose-dependent manner. Furthermore, scratch wound assays performed on keratinocyte monolayers indicated dose-dependent delays in cell migration. Interestingly, adhesion and differentiation remained unaffected in monolayer cultures treated with various doses of caffeine. Using a human ex vivo wound healing model, we tested topical application of caffeine and found that it impedes epithelialisation, confirming in vitro data. We conclude that caffeine, which is known to have antioxidant properties, impedes keratinocyte proliferation and migration, suggesting that it may have an inhibitory effect on wound healing and epithelialisation. Therefore, our findings are more in support of a role for caffeine as adenosine-receptor antagonist that would negate the effect of adenosine in promoting wound healing.

  10. Caffeinated energy drinks in children

    PubMed Central

    Goldman, Ran D.

    2013-01-01

    Abstract Question A 14-year-old boy came to my office to discuss his frequent consumption of energy drinks to enhance his performance at school and while playing soccer. What is the recommended use of energy drinks in children and is there any harm in consuming them? Answer Energy drinks are beverages with a high concentration of caffeine and additional stimulants. They are sold in numerous places and are easily accessed by children, adolescents, and young adults. Many reports warn about potential adverse effects associated with their consumption, especially in combination with alcohol among adolescents, and in combination with stimulant medications among children treated for attention deficit hyperactivity disorder. Children and adolescents should avoid energy drinks, and health care providers should educate youth and their parents about the risks of caffeinated drinks. PMID:24029508

  11. Caffeine fostering of mycoparasitic fungi against phytopathogens.

    PubMed

    Sugiyama, Akifumi; Sano, Cecile M; Yazaki, Kazufumi; Sano, Hiroshi

    2016-01-01

    Caffeine (1,3,7-trimethixanthine) is a typical purine alkaloid produced in more than 80 plant species. Its biological role is considered to strengthen plant's defense capabilities, directly as a toxicant to biotic attackers (allelopathy) and indirectly as an activator of defense system (priming). Caffeine is actively secreted into rhizosphere through primary root, and possibly affects the structure of microbe community nearby. The fungal community in coffee plant rhizosphere is enriched with particular species, including Trichoderma family, a mycoparasite that attacks and kills phytopathogens by coiling and destroying their hyphae. In the present study, the caffeine response of 8 filamentous fungi, 4 mycoparasitic Trichoderma, and 4 prey phytopathogens, was examined. Results showed that allelopathic effect of caffeine on fungal growth and development was differential, being stronger on pathogens than on Trichoderma species. Upon confronting, the prey immediately ceased the growth, whereas the predator continued to grow, indicating active mycoparasitism to have occurred. Caffeine enhanced mycoparasitism up to 1.7-fold. Caffeine thus functions in a double-track manner against fungal pathogens: first by direct suppression of growth and development, and second by assisting their natural enemy. These observations suggest that caffeine is a powerful weapon in the arms race between plants and pathogens by fostering enemy's enemy, and we propose the idea of "caffeine fostering" as the third role of caffeine.

  12. Caffeine fostering of mycoparasitic fungi against phytopathogens.

    PubMed

    Sugiyama, Akifumi; Sano, Cecile M; Yazaki, Kazufumi; Sano, Hiroshi

    2016-01-01

    Caffeine (1,3,7-trimethixanthine) is a typical purine alkaloid produced in more than 80 plant species. Its biological role is considered to strengthen plant's defense capabilities, directly as a toxicant to biotic attackers (allelopathy) and indirectly as an activator of defense system (priming). Caffeine is actively secreted into rhizosphere through primary root, and possibly affects the structure of microbe community nearby. The fungal community in coffee plant rhizosphere is enriched with particular species, including Trichoderma family, a mycoparasite that attacks and kills phytopathogens by coiling and destroying their hyphae. In the present study, the caffeine response of 8 filamentous fungi, 4 mycoparasitic Trichoderma, and 4 prey phytopathogens, was examined. Results showed that allelopathic effect of caffeine on fungal growth and development was differential, being stronger on pathogens than on Trichoderma species. Upon confronting, the prey immediately ceased the growth, whereas the predator continued to grow, indicating active mycoparasitism to have occurred. Caffeine enhanced mycoparasitism up to 1.7-fold. Caffeine thus functions in a double-track manner against fungal pathogens: first by direct suppression of growth and development, and second by assisting their natural enemy. These observations suggest that caffeine is a powerful weapon in the arms race between plants and pathogens by fostering enemy's enemy, and we propose the idea of "caffeine fostering" as the third role of caffeine. PMID:26529400

  13. Caffeine fostering of mycoparasitic fungi against phytopathogens

    PubMed Central

    Sugiyama, Akifumi; Sano, Cecile M.; Yazaki, Kazufumi; Sano, Hiroshi

    2016-01-01

    Caffeine (1,3,7-trimethixanthine) is a typical purine alkaloid produced in more than 80 plant species. Its biological role is considered to strengthen plant's defense capabilities, directly as a toxicant to biotic attackers (allelopathy) and indirectly as an activator of defense system (priming). Caffeine is actively secreted into rhizosphere through primary root, and possibly affects the structure of microbe community nearby. The fungal community in coffee plant rhizosphere is enriched with particular species, including Trichoderma family, a mycoparasite that attacks and kills phytopathogens by coiling and destroying their hyphae. In the present study, the caffeine response of 8 filamentous fungi, 4 mycoparasitic Trichoderma, and 4 prey phytopathogens, was examined. Results showed that allelopathic effect of caffeine on fungal growth and development was differential, being stronger on pathogens than on Trichoderma species. Upon confronting, the prey immediately ceased the growth, whereas the predator continued to grow, indicating active mycoparasitism to have occurred. Caffeine enhanced mycoparasitism up to 1.7-fold. Caffeine thus functions in a double-track manner against fungal pathogens: first by direct suppression of growth and development, and second by assisting their natural enemy. These observations suggest that caffeine is a powerful weapon in the arms race between plants and pathogens by fostering enemy's enemy, and we propose the idea of "caffeine fostering" as the third role of caffeine. PMID:26529400

  14. Caffeine Expectancy Questionnaire (CaffEQ): construction, psychometric properties, and associations with caffeine use, caffeine dependence, and other related variables.

    PubMed

    Huntley, Edward D; Juliano, Laura M

    2012-09-01

    Expectancies for drug effects predict drug initiation, use, cessation, and relapse, and may play a causal role in drug effects (i.e., placebo effects). Surprisingly little is known about expectancies for caffeine even though it is the most widely used psychoactive drug in the world. In a series of independent studies, the nature and scope of caffeine expectancies among caffeine consumers and nonconsumers were assessed, and a comprehensive and psychometrically sound Caffeine Expectancy Questionnaire (CaffEQ) was developed. After 2 preliminary studies, the CaffEQ was administered to 1,046 individuals from the general population along with other measures of interest (e.g., caffeine use history, anxiety). Exploratory factor analysis of the CaffEQ yielded a 7-factor solution. Subsequently, an independent sample of 665 individuals completed the CaffEQ and other measures, and a subset (n = 440) completed the CaffEQ again approximately 2 weeks later. Confirmatory factor analysis revealed good model fit, and test-retest reliability was very good. The frequency and quantity of caffeine use were associated with greater expectancies for withdrawal/dependence, energy/work enhancement, appetite suppression, social/mood enhancement, and physical performance enhancement and lower expectancies for anxiety/negative physical effects and sleep disturbance. Caffeine expectancies predicted various caffeine- associated features of substance dependence (e.g., use despite harm, withdrawal incidence and severity, perceived difficulty stopping use, tolerance). Expectancies for caffeine consumed via coffee were stronger than for caffeine consumed via soft drinks or tea. The CaffEQ should facilitate the advancement of our knowledge of caffeine and drug use in general. PMID:22149323

  15. Carbamazepine breakthrough as indicator for specific vulnerability of karst springs: application on the Jeita spring, Lebanon

    NASA Astrophysics Data System (ADS)

    Doummar, J.; Geyer, T.; Noedler, K.; Sauter, M.

    2014-12-01

    The pharmaceutical drug carbamazepine is considered an effective wastewater marker. The varying concentration of this drug was analyzed in a mature karst spring following a precipitation event. The results show that carbamazepine is an indicator of wastewater entering the system through a fast flow pathway, leading to an increase of the drug concentrations in spring water shortly after a strong rainfall event. The analysis of the breakthrough curve of carbamazepine along with the electrical conductivity signal and major ions chemograph allowed the development of a conceptual model for precipitation event-based flow and transport in the investigated karst system. Furthermore the amount of newly recharged water and the mass of carbamazepine reaching the aquifer system during the event could be estimated using a simple mixing approach. The distance between the karst spring and the potential carbamazepine source was estimated by the combination of results from artificial tracer tests and the carbamazepine breakthrough curve. The assessment of spring responses to precipitation event using persistent drugs like carbamazepine helps assess the effect of waste water contamination at a spring and gives therefore insights to the specific vulnerability of a karst spring.

  16. Double-peaked Acetaminophen Concentration Secondary to Intestinal Trauma.

    PubMed

    Alyahya, B; Tamur, S; Aljenedil, S; Larocuque, A; Holody, E; Gosselin, S

    2016-01-01

    BackgroundReduced gastrointestinal motility can alter the toxicokinetics of acetaminophen poisoning. We report a case of altered acetaminophen toxicokinetics due to delayed gastrointestinal absorption, likely secondary to intestinal trauma/surgery.  Case ReportA 37-year-old woman ingested an unknown amount of acetaminophen and ethanol then stabbed herself in the abdomen. The initial acetaminophen was 1,285.9 μmol/L and the time of ingestion was not known. Intravenous acetylcysteine protocol was started. She developed an ileus post-surgery for the stab wounds. At 31 hours post-presentation, the acetaminophen returned undetectable, and the transaminases were normal. After the resolution of the ileus, repeated acetaminophen peaked at 363.3 μmol/L 52 hours post-admission. At 76 hours post-admission, the acetaminophen was undetectable, and transaminases and coagulation parameters were normal. ConclusionsReduction in gastrointestinal motility secondary to trauma and/or surgery must be considered when determining when to initiate or discontinue treatment as well as how long to monitor acetaminophen concentrations. PMID:27463118

  17. Adolescents' Misperceptions of the Dangerousness of Acetaminophen in Overdose.

    ERIC Educational Resources Information Center

    Harris, Hope Elaine; Myers, Wade C.

    1997-01-01

    Assesses the generality and strength of nonclinical youths' (N=569) perceptions of the harmfulness and lethality of acetaminophen in overdose. Findings indicate that adolescents have ready access to acetaminophen and use it in suicide attempts but underestimate its potential for toxicity, lacking knowledge regarding side effects of overdose. (RJM)

  18. Acetaminophen hepatotoxicity: studies on the mechanism of cysteamine protection

    SciTech Connect

    Miller, M.G.; Jollow, D.J.

    1986-03-30

    Inhibition of the cytochrome P-450-dependent formation of the acetaminophen-reactive metabolite was investigated as a possible mechanism for cysteamine protection against acetaminophen hepatotoxicity. Studies in isolated hamster hepatocytes indicated that cysteamine competitively inhibited the cytochrome P-450 enzyme system as represented by formation of the acetaminophen-glutathione conjugate. However, cysteamine was not a potent inhibitor of glutathione conjugate formation (Ki = 1.17 mM). Cysteamine also weakly inhibited the glucuronidation of acetaminophen (Ki = 2.44 mM). In vivo studies were in agreement with the results obtained in isolated hepatocytes; cysteamine moderately inhibited both glucuronidation and the cytochrome P-450-dependent formation of acetaminophen mercapturate. The overall elimination rate constant (beta) for acetaminophen was correspondingly decreased. Since cysteamine decreased both beta and the apparent rate constant for mercapturate formation (K'MA), the proportion of the dose of acetaminophen which is converted to the toxic metabolite (K'MA/beta) was not significantly decreased in the presence of cysteamine. Apparently, cysteamine does inhibit the cytochrome P-450-dependent formation of the acetaminophen-reactive metabolite, but this effect is not sufficient to explain antidotal protection.

  19. Electronic Spectra of the Jet-Cooled Acetaminophen

    NASA Astrophysics Data System (ADS)

    Lee, Seung Jun; Min, Ahreum; Kim, Yusic; Choi, Myong Yong; Chang, Jinyoung; Lee, Sang Hak; Kim, Seong Keun

    2010-06-01

    Resonant two-photon ionization (R2PI), laser induced fluorescence (LIF) and UV-UV double resonance spectra of the jet-cooled acetaminophen, widely used as a pain reliever and fever reducer, were obtained in the gas phase. Conformational characterizations for acetaminophen will be presented with an aid of spectroscopic techniques and DFT B3LYP calculations.

  20. Acetaminophen prevents oxidative burst and delays apoptosis in human neutrophils.

    PubMed

    Freitas, Marisa; Costa, Vera M; Ribeiro, Daniela; Couto, Diana; Porto, Graça; Carvalho, Félix; Fernandes, Eduarda

    2013-05-23

    Acetaminophen is a frequently prescribed over-the-counter drug to reduce fever and pain in the event of inflammatory process. As neutrophils are relevant cells in inflammatory processes, the putative interaction of acetaminophen with these cells, if present, would be of paramount importance. The present study was undertaken to evaluate the effect of acetaminophen in human neutrophils' oxidative burst and lifespan in vitro. The obtained results demonstrate that acetaminophen efficiently modulates neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils, in a concentration-dependent manner, at in vivo relevant concentrations. It was clearly demonstrated that acetaminophen is a strong scavenger of HOCl and H2O2, which probably contributed to the effect observed in neutrophils. Acetaminophen also induced the depletion of glutathione in stimulated neutrophils, suggesting its transformation into a reactive intermediate. Obtained results further revealed that acetaminophen affects programmed cell death of human neutrophils, resulting in a delay of previously stimulated neutrophils-mediated apoptosis. Overall, our data suggested that acetaminophen has considerable potential to be included in anti-inflammatory therapeutic strategies, by preventing biological damage induced by an excessive production of reactive species generated in activated neutrophils and by extending the lifespan of neutrophils, favoring the elimination of pathogens, thus contributing to tissue healing and resolution of inflammation. PMID:23518321

  1. Decrease of plasma and urinary oxidative metabolites of acetaminophen after consumption of watercress by human volunteers.

    PubMed

    Chen, L; Mohr, S N; Yang, C S

    1996-12-01

    To investigate the effect of the consumption of watercress (Nasturtium officinale R. Br.), a cruciferous vegetable, on acetaminophen metabolism, the pharmacokinetics of acetaminophen and its metabolites were studied in a crossover trial of human volunteers. A single oral dose of acetaminophen (1 gm) was given 10 hours after ingestion of watercress homogenates (50 gm). In comparison with acetaminophen only, the ingestion of watercress resulted in a significant reduction in the area under the plasma cysteine acetaminophen (Cys-acetaminophen) concentration-time curve and in the peak plasma Cys-acetaminophen concentration by 28% +/- 3% and by 21% +/- 4% (mean +/- SE; n = 7; p < 0.005), respectively. Correspondingly, the Cys-acetaminophen formation rate constant and Cys-acetaminophen formation fraction were decreased by 55% +/- 9% and 52% +/- 7% (p < 0.01), respectively. Consistent with the results obtained from the plasma, the total urinary excretion of Cys-acetaminophen in 24 hours was also reduced. A decrease of mercapturate acetaminophen, a Cys-acetaminophen metabolite, was also shown in the plasma and urine samples. However, the plasma pharmacokinetic processes and the urinary excretions of acetaminophen, acetaminophen glucuronide, and acetaminophen sulfate were not altered significantly by the watercress treatment. These results suggest that the consumption of watercress causes a decrease in the levels of oxidative metabolites of acetaminophen, probably due to inhibition of oxidative metabolism of this drug.

  2. Electrochemical degradation of carbamazepine using modified electrode with graphene-AuAg composite

    NASA Astrophysics Data System (ADS)

    Pogacean, F.; Biris, A. R.; Socaci, C.; Floare-Avram, V.; Rosu, M. C.; Coros, M.; Pruneanu, S.

    2015-12-01

    Carbamazepine is a pharmaceutical drug which has been detected in surface and drinking water primarily due to human usage but also from the accidental disposal of pharmaceuticals into sewers. We have developed a graphene-modified electrode which was tested at the detection and degradation of carbamazepine. The oxidation process was studied by cyclic voltammetry in aqueous and organic solutions. The electrochemical degradation of carbamazepine was performed by polarizing the working electrode at a certain potential, for different times (from 5 to 60 minutes). The degradation efficiency was highly dependent on the type of solution and on the supporting electrolyte.

  3. Caffeine and exercise: metabolism, endurance and performance.

    PubMed

    Graham, T E

    2001-01-01

    Caffeine is a common substance in the diets of most athletes and it is now appearing in many new products, including energy drinks, sport gels, alcoholic beverages and diet aids. It can be a powerful ergogenic aid at levels that are considerably lower than the acceptable limit of the International Olympic Committee and could be beneficial in training and in competition. Caffeine does not improve maximal oxygen capacity directly, but could permit the athlete to train at a greater power output and/or to train longer. It has also been shown to increase speed and/or power output in simulated race conditions. These effects have been found in activities that last as little as 60 seconds or as long as 2 hours. There is less information about the effects of caffeine on strength; however, recent work suggests no effect on maximal ability, but enhanced endurance or resistance to fatigue. There is no evidence that caffeine ingestion before exercise leads to dehydration, ion imbalance, or any other adverse effects. The ingestion of caffeine as coffee appears to be ineffective compared to doping with pure caffeine. Related compounds such as theophylline are also potent ergogenic aids. Caffeine may act synergistically with other drugs including ephedrine and anti-inflammatory agents. It appears that male and female athletes have similar caffeine pharmacokinetics, i.e., for a given dose of caffeine, the time course and absolute plasma concentrations of caffeine and its metabolites are the same. In addition, exercise or dehydration does not affect caffeine pharmacokinetics. The limited information available suggests that caffeine non-users and users respond similarly and that withdrawal from caffeine may not be important. The mechanism(s) by which caffeine elicits its ergogenic effects are unknown, but the popular theory that it enhances fat oxidation and spares muscle glycogen has very little support and is an incomplete explanation at best. Caffeine may work, in part, by

  4. Caffeine and exercise: metabolism, endurance and performance.

    PubMed

    Graham, T E

    2001-01-01

    Caffeine is a common substance in the diets of most athletes and it is now appearing in many new products, including energy drinks, sport gels, alcoholic beverages and diet aids. It can be a powerful ergogenic aid at levels that are considerably lower than the acceptable limit of the International Olympic Committee and could be beneficial in training and in competition. Caffeine does not improve maximal oxygen capacity directly, but could permit the athlete to train at a greater power output and/or to train longer. It has also been shown to increase speed and/or power output in simulated race conditions. These effects have been found in activities that last as little as 60 seconds or as long as 2 hours. There is less information about the effects of caffeine on strength; however, recent work suggests no effect on maximal ability, but enhanced endurance or resistance to fatigue. There is no evidence that caffeine ingestion before exercise leads to dehydration, ion imbalance, or any other adverse effects. The ingestion of caffeine as coffee appears to be ineffective compared to doping with pure caffeine. Related compounds such as theophylline are also potent ergogenic aids. Caffeine may act synergistically with other drugs including ephedrine and anti-inflammatory agents. It appears that male and female athletes have similar caffeine pharmacokinetics, i.e., for a given dose of caffeine, the time course and absolute plasma concentrations of caffeine and its metabolites are the same. In addition, exercise or dehydration does not affect caffeine pharmacokinetics. The limited information available suggests that caffeine non-users and users respond similarly and that withdrawal from caffeine may not be important. The mechanism(s) by which caffeine elicits its ergogenic effects are unknown, but the popular theory that it enhances fat oxidation and spares muscle glycogen has very little support and is an incomplete explanation at best. Caffeine may work, in part, by

  5. Alcohol and Caffeine: The Perfect Storm

    PubMed Central

    O'Brien, Mary Claire

    2011-01-01

    Although it is widely believed that caffeine antagonizes the intoxicating effects of alcohol, the molecular mechanisms underlying their interaction are incompletely understood. It is known that both caffeine and alcohol alter adenosine neurotransmission, but the relationship is complex, and may be dose dependent. In this article, we review the available literature on combining caffeine and alcohol. Ethical constraints prohibit laboratory studies that would mimic the high levels of alcohol intoxication achieved by many young people in real-world settings, with or without the addition of caffeine. We propose a possible neurochemical mechanism for the increase in alcohol consumption and alcohol-related consequences that have been observed in persons who simultaneously consume caffeine. Caffeine is a nonselective adenosine receptor antagonist. During acute alcohol intake, caffeine antagonizes the “unwanted” effects of alcohol by blocking the adenosine A1 receptors that mediate alcohol's somnogenic and ataxic effects. The A1 receptor–mediated “unwanted” anxiogenic effects of caffeine may be ameliorated by alcohol-induced increase in the extracellular concentration of adenosine. Moreover, by means of interactions between adenosine A2A and dopamine D2 receptors, caffeine-mediated blockade of adenosine A2A receptors can potentiate the effects of alcohol-induced dopamine release. Chronic alcohol intake decreases adenosine tone. Caffeine may provide a “treatment” for the withdrawal effects of alcohol by blocking the effects of upregulated A1 receptors. Finally, blockade of A2A receptors by caffeine may contribute to the reinforcing effects of alcohol. PMID:24761263

  6. Caffeine withdrawal and high-intensity endurance cycling performance.

    PubMed

    Irwin, Christopher; Desbrow, Ben; Ellis, Aleisha; O'Keeffe, Brooke; Grant, Gary; Leveritt, Michael

    2011-03-01

    In this study, we investigated the impact of a controlled 4-day caffeine withdrawal period on the effect of an acute caffeine dose on endurance exercise performance. Twelve well-trained and familiarized male cyclists, who were caffeine consumers (from coffee and a range of other sources), were recruited for the study. A double-blind placebo-controlled cross-over design was employed, involving four experimental trials. Participants abstained from dietary caffeine sources for 4 days before the trials and ingested capsules (one in the morning and one in the afternoon) containing either placebo or caffeine (1.5 mg · kg(-1) body weight · day(-1)). On day 5, capsules containing placebo or caffeine (3 mg · kg(-1) body weight) were ingested 90 min before completing a time trial, equivalent to one hour of cycling at 75% peak sustainable power output. Hence the study was designed to incorporate placebo-placebo, placebo-caffeine, caffeine-placebo, and caffeine-caffeine conditions. Performance time was significantly improved after acute caffeine ingestion by 1:49 ± 1:41 min (3.0%, P = 0.021) following a withdrawal period (placebo-placebo vs. placebo-caffeine), and by 2:07 ± 1:28 min (3.6%, P = 0.002) following the non-withdrawal period (caffeine-placebo vs. caffeine-caffeine). No significant difference was detected between the two acute caffeine trials (placebo-caffeine vs. caffeine-caffeine). Average heart rate throughout exercise was significantly higher following acute caffeine administration compared with placebo. No differences were observed in ratings of perceived exertion between trials. A 3 mg · kg(-1) dose of caffeine significantly improves exercise performance irrespective of whether a 4-day withdrawal period is imposed on habitual caffeine users. PMID:21279864

  7. Ibuprofen versus acetaminophen with codeine for the relief of perineal pain after childbirth: a randomized controlled trial

    PubMed Central

    Peter, Elizabeth A.; Janssen, Patricia A.; Grange, Caroline S.; Douglas, M. Joanne

    2001-01-01

    Background Pain from episiotomy or tearing of perineal tissues during childbirth is often poorly treated and may be severe. This randomized double-blind controlled trial was performed to compare the effectiveness, side effects and cost of, and patient preference for, 2 analgesics for the management of postpartum perineal pain. Methods A total of 237 women who gave birth vaginally with episiotomy or a third- or fourth-degree tear between August 1995 and November 1996 at a tertiary-level teaching and referral centre for obstetric care in Vancouver were randomly assigned to receive either ibuprofen (400 mg) (n = 127) or acetaminophen (600 mg) with codeine (60 mg) and caffeine (15 mg) (Tylenol No. 3) (n = 110), both given orally every 4 hours as necessary. Pain ratings were recorded before the first dose and at 1, 2, 3, 4, 12 and 24 hours after the first dose on a 10-cm visual analogue scale. Side effects and overall opinion were assessed at 24 hours. Results Ibuprofen and acetaminophen with codeine had similar analgesic properties in the first 24 hours post partum (mean pain rating 3.4 and 3.3, mean number of doses in 24 hours 3.4 and 3.3, and proportion of treatment failures 13.8% [16/116] and 16.0% [16/100] respectively). Significantly fewer subjects in the ibuprofen group than in the acetaminophen with codeine group experienced side effects (52.4% v. 71.7%) (p = 0.006). There were no significant differences in overall patient satisfaction between the 2 groups. The major determinant of pain intensity was forceps-assisted delivery. Overall, 78% of the treatment failures were in women with forceps-assisted deliveries. Interpretation Since the 2 analgesics were rated similarly, ibuprofen may be the preferred choice because it is less expensive and requires less nursing time to dispense. Further studies need to address improved analgesia for women with forceps-assisted deliveries. PMID:11706909

  8. Caffeinated Energy Drinks -- A Growing Problem

    PubMed Central

    Reissig, Chad J.; Strain, Eric C.; Griffiths, Roland R.

    2009-01-01

    Since the introduction of Red Bull in Austria in 1987 and in the United States in 1997, the energy drink market has grown exponentially. Hundreds of different brands are now marketed, with caffeine content ranging from a modest 50 mg to an alarming 505 mg per can or bottle. Regulation of energy drinks, including content labeling and health warnings differs across countries, with some of the most lax regulatory requirements in the U.S. The absence of regulatory oversight has resulted in aggressive marketing of energy drinks, targeted primarily toward young males, for psychoactive, performance-enhancing and stimulant drug effects. There are increasing reports of caffeine intoxication from energy drinks, and it seems likely that problems with caffeine dependence and withdrawal will also increase. In children and adolescents who are not habitual caffeine users, vulnerability to caffeine intoxication may be markedly increased due to an absence of pharmacological tolerance. Genetic factors may also contribute to an individual’s vulnerability to caffeine related disorders including caffeine intoxication, dependence, and withdrawal. The combined use of caffeine and alcohol is increasing sharply, and studies suggest that such combined use may increase the rate of alcohol-related injury. Several studies suggest that energy drinks may serve as a gateway to other forms of drug dependence. Regulatory implications concerning labeling and advertising, and the clinical implications for children and adolescents are discussed. PMID:18809264

  9. Extraction of Caffeine--A Modern Experiment

    ERIC Educational Resources Information Center

    Cohen, Paul Shea; Smith, Eileen Patricia

    1969-01-01

    Describes an organic chemistry experiment suitable for high school students in second year or an advanced chemistry course. The techniques for the extraction and purification of caffeine from various household materials are described. Further experimentation with the extracted caffeine is suggested. (LC)

  10. Creatine and Caffeine: Considerations for Concurrent Supplementation.

    PubMed

    Trexler, Eric T; Smith-Ryan, Abbie E

    2015-12-01

    Nutritional supplementation is a common practice among athletes, with creatine and caffeine among the most commonly used ergogenic aids. Hundreds of studies have investigated the ergogenic potential of creatine supplementation, with consistent improvements in strength and power reported for exercise bouts of short duration (≤ 30 s) and high intensity. Caffeine has been shown to improve endurance exercise performance, but results are mixed in the context of strength and sprint performance. Further, there is conflicting evidence from studies comparing the ergogenic effects of coffee and caffeine anhydrous supplementation. Previous research has identified independent mechanisms by which creatine and caffeine may improve strength and sprint performance, leading to the formulation of multi-ingredient supplements containing both ingredients. Although scarce, research has suggested that caffeine ingestion may blunt the ergogenic effect of creatine. While a pharmacokinetic interaction is unlikely, authors have suggested that this effect may be explained by opposing effects on muscle relaxation time or gastrointestinal side effects from simultaneous consumption. The current review aims to evaluate the ergogenic potential of creatine and caffeine in the context of high-intensity exercise. Research directly comparing coffee and caffeine anhydrous is discussed, along with previous studies evaluating the concurrent supplementation of creatine and caffeine.

  11. Effects of Caffeine on Crayfish Muscle Fibers

    PubMed Central

    Chiarandini, Dante J.; Reuben, John P.; Brandt, Philip W.; Grundfest, Harry

    1970-01-01

    Contractions are evoked in single muscle fibers of crayfish by intracellular as well as extracellular applications of caffeine. Responses to external applications in concentrations above 2 mM could be induced indefinitely. With concentrations above 5 mM the caffeine-induced responses were highly repeatable. Tensions were transient even when the caffeine remained in the bath. There was no change in resting potential, but during the contraction the effective resistance decreased about 10%. A number of factors (change in pH, Ca, K, and Cl) modified the responses. The time course of the tension was greatly prolonged when the transverse tubular system (TTS) was s swollen and was again shortened when the TTS was caused to shrink. An increased permeability to Ca induced by caffeine was evidenced by the transformation of the normally graded electrical responses to Ca spikes, which are insensitive to tetrodotoxin. The overshoot is a function of both external Ca and caffeine. A 10-fold change in Ca changed the overshoot by 19 mv in the presence of 10 mM caffeine and by 29 mv in 80 mM caffeine. The role of the increased permeability to Ca for caffeine-induced contractions will be analyzed in the accompanying paper. PMID:5443468

  12. Caffeinated energy drinks--a growing problem.

    PubMed

    Reissig, Chad J; Strain, Eric C; Griffiths, Roland R

    2009-01-01

    Since the introduction of Red Bull in Austria in 1987 and in the United States in 1997, the energy drink market has grown exponentially. Hundreds of different brands are now marketed, with caffeine content ranging from a modest 50 mg to an alarming 505 mg per can or bottle. Regulation of energy drinks, including content labeling and health warnings differs across countries, with some of the most lax regulatory requirements in the U.S. The absence of regulatory oversight has resulted in aggressive marketing of energy drinks, targeted primarily toward young males, for psychoactive, performance-enhancing and stimulant drug effects. There are increasing reports of caffeine intoxication from energy drinks, and it seems likely that problems with caffeine dependence and withdrawal will also increase. In children and adolescents who are not habitual caffeine users, vulnerability to caffeine intoxication may be markedly increased due to an absence of pharmacological tolerance. Genetic factors may also contribute to an individual's vulnerability to caffeine-related disorders including caffeine intoxication, dependence, and withdrawal. The combined use of caffeine and alcohol is increasing sharply, and studies suggest that such combined use may increase the rate of alcohol-related injury. Several studies suggest that energy drinks may serve as a gateway to other forms of drug dependence. Regulatory implications concerning labeling and advertising, and the clinical implications for children and adolescents are discussed. PMID:18809264

  13. Caffeine reduces dipyridamole-induced myocardial ischemia

    SciTech Connect

    Smits, P.; Aengevaeren, W.R.; Corstens, F.H.; Thien, T. )

    1989-10-01

    The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-{sup 201}Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed nodepressions, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging.

  14. Caffeine lengthens circadian rhythms in mice.

    PubMed

    Oike, Hideaki; Kobori, Masuko; Suzuki, Takahiro; Ishida, Norio

    2011-07-01

    Although caffeine alters sleep in many animals, whether or not it affects mammalian circadian clocks remains unknown. Here, we found that incubating cultured mammalian cell lines, human osteosarcoma U2OS cells and mouse fibroblast NIH3T3 cells, with caffeine lengthened the period of circadian rhythms. Adding caffeine to ex vivo cultures also lengthened the circadian period in mouse liver explants from Per2::Luciferase reporter gene knockin mice, and caused a phase delay in brain slices containing the suprachiasmatic nucleus (SCN), where the central circadian clock in mammals is located. Furthermore, chronic caffeine consumption ad libitum for a week delayed the phase of the mouse liver clock in vivo under 12 h light-dark conditions and lengthened the period of circadian locomotor rhythms in mice under constant darkness. Our results showed that caffeine alters circadian clocks in mammalian cells in vitro and in the mouse ex vivo and in vivo. PMID:21684260

  15. Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity in CD-1 mice: I. Enhancement of acetaminophen nephrotoxicity by acetaminophen-cysteine

    SciTech Connect

    Stern, Stephan T.; Bruno, Mary K.; Hennig, Gayle E.; Horton, Robert A.; Roberts, Jeanette C.; Cohen, Steven D. . E-mail: scohen@mcp.edu

    2005-01-15

    Acetaminophen (APAP) nephrotoxicity has been observed both in humans and research animals. Recent studies suggest a contributory role for glutathione (GSH)-derived conjugates of APAP in the development of nephrotoxicity. Inhibitors of either {gamma}-glutamyl transpeptidase ({gamma}-GT) or the probenecid-sensitive organic anion transporter ameliorate APAP-induced nephrotoxicity but not hepatotoxicity in mice and inhibition of {gamma}-GT similarly protected rats from APAP nephrotoxicity. Protection against APAP nephrotoxicity by disruption of these GSH conjugate transport and metabolism pathways suggests that GSH conjugates are involved. APAP-induced renal injury may involve the acetaminophen-glutathione (APAP-GSH) conjugate or a metabolite derived from APAP-GSH. Acetaminophen-cysteine (APAP-CYS) is a likely candidate for involvement in APAP nephrotoxicity because it is both a product of the {gamma}-GT pathway and a probable substrate for the organic anion transporter. The present experiments demonstrated that APAP-CYS treatment alone depleted renal but not hepatic glutathione (GSH) in a dose-responsive manner. This depletion of renal GSH may predispose the kidney to APAP nephrotoxicity by diminishing GSH-mediated detoxification mechanisms. Indeed, pretreatment of male CD-1 mice with APAP-CYS before challenge with a threshold toxic dose of APAP resulted in significant enhancement of APAP-induced nephrotoxicity. This was evidenced by histopathology and plasma blood urea nitrogen (BUN) levels at 24 h after APAP challenge. APAP alone was minimally nephrotoxic and APAP-CYS alone produced no detectable injury. By contrast, APAP-CYS pretreatment did not alter the liver injury induced by APAP challenge. These data are consistent with there being a selective, contributory role for APAP-GSH-derived metabolites in APAP-induced renal injury that may involve renal-selective GSH depletion.

  16. Effect of polyethylene glycol 400 on the intestinal permeability of carbamazepine in the rabbit

    SciTech Connect

    Riad, L.E.; Sawchuk, R.J. )

    1991-04-01

    Because of the limited solubility of carbamazepine, aqueous solutions are usually prepared using glycols as cosolvents. This research focuses on the effect of varying the composition of polyethylene glycol 400 (PEG-400) in aqueous solutions in rabbit intestinal permeability of carbamazepine in the duodenojejunum and the ascending colon using an in situ perfusion technique. In both segments the intestinal permeability varied inversely with the percentage of PEG-400, when the concentration of carbamazepine in the perfusing solution was maintained constant. The decreased permeability may be explained by a reduction in the thermodynamic activity of carbamazepine with increased concentrations of PEG-400, as well as by reverse solvent drag because of the hyperosmolarity of the perfusing solutions.

  17. Behavioral Management of Excessive Caffeine Consumption: Three Case Studies.

    ERIC Educational Resources Information Center

    Johnson-Greene, Douglas; And Others

    Although caffeine is seemingly harmless in ordinary daily intake, there has been increasing concern about the possible side effects of habitual caffeine ingestion. The excessive daily ingestion of caffeine in the form of coffee, soda pop, tea, and various medications may lead to a chronic disorder known as caffeinism. This study tested the…

  18. Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats.

    PubMed

    Hidaka, Muneaki; Okumura, Manabu; Fujita, Ken-Ichi; Ogikubo, Tetsuya; Yamasaki, Keishi; Iwakiri, Tomomi; Setoguchi, Nao; Arimori, Kazuhiko

    2005-05-01

    In this study, we investigated whether components of pomegranate could inhibit CYP3A-mediated drug metabolism. The ability of pomegranate to inhibit the carbamazepine 10,11-epoxidase activity of CYP3A was examined using human liver microsomes, and pomegranate juice was shown to be a potent inhibitor of human CYP3A. Addition of 25 microl (5.0% v/v) of pomegranate juice resulted in almost complete inhibition of the carbamazepine 10,11-epoxidase activity of human CYP3A (1.8%). The inhibition potency of pomegranate juice was similar to that of grapefruit juice. In addition, we investigated the in vivo interaction between pomegranate juice and carbamazepine pharmacokinetics using rats. In comparison with water, the area under the concentration-time curve (AUC) of carbamazepine was approximately 1.5-fold higher when pomegranate juice (2 ml) was orally injected 1 h before the oral administration of the carbamazepine (50 mg/kg). On the other hand, the elimination half-life of carbamazepine and the AUC ratio of carbamazepine 10,11-epoxide to carbamazepine were not altered by the injection of pomegranate juice. These data suggest that pomegranate juice component(s) impairs the function of enteric but not hepatic CYP3A. Thus, we discovered that a component(s) of pomegranate inhibits the human CYP3A-mediated metabolism of carbamazepine. Furthermore, pomegranate juice alters the carbamazepine pharmacokinetics in rats.

  19. Effects of short-term exposure to fluoxetine and carbamazepine to the collembolan Folsomia candida.

    PubMed

    Oliveira, M; Cardoso, D N; Soares, A M V M; Loureiro, S

    2015-02-01

    Pharmaceuticals, emerging environmental contaminants, have their ecotoxicological effects to non-target organisms in soil largely unknown. This study assessed short-term effects of two human pharmaceuticals, carbamazepine and fluoxetine, to Folsomia candida. Avoidance to spiked soils was assessed after 48 and 96 h exposure and biochemical changes (acetylcholinesterase and glutathione S-transferase activities, and lipid peroxidation levels) after 96 h. F. candida avoided soils spiked with 0.04, 0.4 and 4 mg carbamazepine kg(-1) after 48 h. However, higher number of organisms were found in soils with 40 mg carbamazepine kg(-1), a behavior also displayed for 40 mg fluoxetine kg(-1) spiked soils. After 96 h, F. candida showed avoidance behavior to soils with 4 and 40 mg carbamazepine kg(-1). Acetylcholinesterase activity decreased in 0.4 mg fluoxetine kg(-1) exposed organisms. Peroxidative damages were detected in organisms exposed to 4 and 40 mg kg(-1) carbamazepine and glutathione S-transferase inhibition was observed at 40 mg kg(-1). Data suggests that carbamazepine and fluoxetine may pose risk to soil collembolan. PMID:25010847

  20. Pharmacokinetic interaction studies of fenugreek with CYP3A substrates cyclosporine and carbamazepine.

    PubMed

    Al-Jenoobi, Fahad I; Alam, Mohd Aftab; Alkharfy, Khalid M; Al-Suwayeh, Saleh A; Korashy, Hesham M; Al-Mohizea, Abdullah M; Iqbal, Muzaffar; Ahad, Abdul; Raish, Mohammad

    2014-06-01

    The present study investigated the effect of fenugreek seed powder on disposition of CYP3A substrates, cyclosporine and carbamazepine. Rabbits were treated with fenugreek seed powder (300 mg/kg p.o.) for 8 days and on 8th day the single dose of cyclosporine (30 mg/kg, p.o.) and carbamazepine (40 mg/kg, p.o.) were administered to the corresponding group after 1 h of fenugreek administration. Blood samples were drawn at several time points and analyzed by using UPLC-MS (cyclosporine) and HPLC (carbamazepine). Pharmacokinetic parameters were calculated by using PK Solver. The present investigation reveals that there was no statistically significant difference between pre- and post-treated pharmacokinetic parameters such as AUC(o-t), AUC(o-∞), C(max), T(max), T(1/2), K(el), MRT(o-∞) , V(z/F), and Cl/F for cyclosporine and carbamazepine. Two tailed "P" values for all these pharmacokinetic parameters were more than 0.05, indicating insignificant impact of fenugreek treatment on the disposition of cyclosporine and carbamazepine. Further, fenugreek may also not have any significant effect on the functionality of P-glycoprotein as cyclosporine is a substrate to P-glycoprotein. The outcomes of present study suggested that fenugreek may not likely to interfere cyclosporine and carbamazepine pharmacokinetics, when co-administered with these drugs. PMID:24022709

  1. Tipepidine enhances the antinociceptive-like action of carbamazepine in the acetic acid writhing test.

    PubMed

    Kawaura, Kazuaki; Miki, Risa; Urashima, Yuri; Honda, Sokichi; Shehata, Ahmed M; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2011-01-25

    Several antidepressants have been used to treat severe pain in clinics. Recently, we reported that the centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test, although the mechanism of action appears to be quite different from that of known antidepressants. In the present study, we investigated whether a combination of tipepidine and carbamazepine acts synergistically to induce an antinociceptive effect in the acetic acid-induced writhing test in mice. Prior to studying the combination of tipepidine and carbamazepine, the analgesic action of tipepidine alone was also examined in mice. Tipepidine at 5-40mg/kg i.p. significantly reduced the number of writhes induced by acetic acid in mice. Carbamazepine at 20mg/kg i.p. also significantly reduced the writhing reaction. Furthermore, co-administration of carbamazepine (5 and 10mg/kg, i.p.) and tipepidine (2.5mg/kg i.p.) significantly decreased the number of writhes induced by acetic acid. This finding suggests that a combination of carbamazepine and tipepidine may be a new strategy for the treatment of neuropathic pain such as what occurs in trigeminal neuralgia, because the use of carbamazepine is often limited by its adverse effects and by reduction of its analgesic efficacy by microsomal enzyme induction. PMID:21114989

  2. Crystallization of Carbamazepine in Proximity to Its Precursor Iminostilbene and a Silica Surface

    PubMed Central

    2016-01-01

    Amorphous films of the anticonvulsant drug carbamazepine are easily accessible by various methods, while the crystallization into specific polymorphs represents a challenging and time-consuming task. In this work, the crystallization of drop cast carbamazepine at silica surfaces is investigated by atomic force microscopy and both in situ and ex situ grazing incidence X-ray diffraction. The pristine films grow with low crystallization rates into a triclinic polymorph, exhibiting poor orientational order within films. However, if iminostilbene, a chemical precursor of carbamazepine, is added to the solution, enhanced crystallization rates result. The individual components crystallize phase-separated upon solvent evaporation without the formation of cocrystals. Iminostilbene reduces the time scale of carbamazepine crystallization from several hours to minutes. Besides the change in crystallization dynamics, iminostilbene induces order to the carbamazepine crystallites, evident as a 110 texture. In situ data of intermixed solutions demonstrate that iminostilbene crystallization occurs first. The iminostilbene crystals then act as templates for carbamazepine growth, whereby fully epitaxial growth is suggested from the results. The findings motivate such an approach for other systems, as this solution-processed, intrinsic epitaxial behavior might be employed in up-scaled manufacturing processes. PMID:27175105

  3. Potential role of caveolin-1 in acetaminophen-induced hepatotoxicity

    SciTech Connect

    Gardner, Carol R.; Gray, Joshua P.; Joseph, Laurie B.; Cervelli, Jessica; Bremer, Nicole; Kim, Yunjung; Mishin, Vladimir; Laskin, Jeffrey D.; Laskin, Debra L.

    2010-05-15

    Caveolin-1 (Cav-1) is a membrane scaffolding protein, which functions to regulate intracellular compartmentalization of various signaling molecules. In the present studies, transgenic mice with a targeted disruption of the Cav-1 gene (Cav-1{sup -/-}) were used to assess the role of Cav-1 in acetaminophen-induced hepatotoxicity. Treatment of wild-type mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis and increases in serum transaminases. This was correlated with decreased expression of Cav-1 in the liver. Acetaminophen-induced hepatotoxicity was significantly attenuated in Cav-1{sup -/-} mice, an effect that was independent of acetaminophen metabolism. Acetaminophen administration resulted in increased hepatic expression of the oxidative stress marker, lipocalin 24p3, as well as hemeoxygenase-1, but decreased glutathione and superoxide dismutase-1; no differences were noted between the genotypes suggesting that reduced toxicity in Cav-1{sup -/-} mice is not due to alterations in antioxidant defense. In wild-type mice, acetaminophen increased mRNA expression of the pro-inflammatory cytokines, interleukin-1beta, and monocyte chemoattractant protein-1 (MCP-1), as well as cyclooxygenase-2, while 15-lipoxygenase (15-LOX), which generates anti-inflammatory lipoxins, decreased. Acetaminophen-induced changes in MCP-1 and 15-LOX expression were greater in Cav-1{sup -/-} mice. Although expression of tumor necrosis factor-alpha, a potent hepatocyte mitogen, was up-regulated in the liver of Cav-1{sup -/-} mice after acetaminophen, expression of proliferating cell nuclear antigen and survivin, markers of cellular proliferation, were delayed, which may reflect the reduced need for tissue repair. Taken together, these data demonstrate that Cav-1 plays a role in promoting inflammation and toxicity during the pathogenesis of acetaminophen-induced injury.

  4. Acetaminophen-induced acute liver injury in HCV transgenic mice

    SciTech Connect

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  5. Rationale for Use of Intravenous Acetaminophen in Special Operations Medicine.

    PubMed

    Vokoun, Edward Scott

    2015-01-01

    Use of intravenous acetaminophen has increased recently as an opioid-sparing strategy for patients undergoing major surgery. Its characteristics and efficacy suggest that it would a useful adjunct in combat trauma medicine. This article reviews those characteristics, which include rapid onset, high peak plasma concentration, and favorable side-effect profile. Also discussed is the hepatotoxicity risk of acetaminophen in a combat trauma patient. It concludes that intravenous acetaminophen should be considered as an addition to the US Special Operations Command Tactical Trauma Protocols and supplied to medics for use in field care.

  6. Mechanisms of Acetaminophen-Induced Liver Necrosis

    PubMed Central

    Roberts, Dean W.; James, Laura P.

    2010-01-01

    Although considered safe at therapeutic doses, at higher doses, acetaminophen produces a centrilobular hepatic necrosis that can be fatal. Acetaminophen poisoning accounts for approximately one-half of all cases of acute liver failure in the United States and Great Britain today. The mechanism occurs by a complex sequence of events. These events include: (1) CYP metabolism to a reactive metabolite which depletes glutathione and covalently binds to proteins; (2) loss of glutathione with an increased formation of reactive oxygen and nitrogen species in hepatocytes undergoing necrotic changes; (3) increased oxidative stress, associated with alterations in calcium homeostasis and initiation of signal transduction responses, causing mitochondrial permeability transition; (4) mitochondrial permeability transition occurring with additional oxidative stress, loss of mitochondrial membrane potential, and loss of the ability of the mitochondria to synthesize ATP; and (5) loss of ATP which leads to necrosis. Associated with these essential events there appear to be a number of inflammatory mediators such as certain cytokines and chemokines that can modify the toxicity. Some have been shown to alter oxidative stress, but the relationship of these modulators to other critical mechanistic events has not been well delineated. In addition, existing data support the involvement of cytokines, chemokines, and growth factors in the initiation of regenerative processes leading to the reestablishment of hepatic structure and function. PMID:20020268

  7. Catabolism of caffeine in plants and microorganisms.

    PubMed

    Mazzafera, Paulo

    2004-05-01

    Caffeine has been found in tissues of several plants. Because of its stimulating effect on the central nervous system, a great number of reports have been published on its content in beverages and foodstuffs. However, a much more restricted number of reports have dealt specifically with caffeine metabolism in plants. This review presents, in chronological manner, the contribution of these reports to the vast knowledge accumulated on caffeine catabolism in plants and microorganisms over the last 40 years. In plants, the accumulated data indicate the operation of a main catabolic pathway: caffeine --> theophylline --> 3-methylxantine --> xanthine --> uric acid --> allantoin --> allantoic acid --> glyoxylic acid + urea --> NH3 + CO2. Some studies have shown that, depending on the plant species, other minor routes may operate with the formation of theobromine and 7-methylxantine, which are salvaged for caffeine formation since they also appear in the biosynthetic pathway. A specific group of coffee known as liberio-excelsioides has the ability to convert caffeine to the corresponding methyluric acid, which is methylated to other uric acid derivatives. In bacteria caffeine is either degraded to theobromine or paraxanthine. Both dimethylxanthines are demethylated to 7-methylxantine which in turn is demethylated to xanthine and then enters the catabolic pathway of purines. In bacteria, theobromine, paraxanthine and 7-methylxantine may also be oxidized to their corresponding methyluric acids.

  8. Caffeine and sports activity: a review.

    PubMed

    Nehlig, A; Debry, G

    1994-07-01

    Potential ergogenic effects of caffeine at the cellular level are mediated by three main mechanisms of action which are: intracellular mobilization of calcium from sarcoplasmic reticulum and increased sensitivity of myofibrilles to calcium; inhibition of phosphodiesterases leading to an increase in cyclic-3',5'-adenosine monophosphate (cAMP) in various tissues including muscle; and the antagonism at the level of adenosine receptors, mainly in the central nervous system. The main mechanism of action of caffeine at the level usually encountered in vivo after the ingestion of a few cups of coffee is undoubtedly linked to the antagonism of caffeine at adenosine receptors. Caffeine also increases production of plasma catecholamines that allow the body to adapt to the stress created by physical exercise. Catecholamine production increases probably, in turn, the availability of free fatty acids as muscle substrates during work, thus allowing glycogen sparing. Caffeine is able to increase muscle contractility, has no ergogenic effect on intense exercise of brief duration, but can improve the time before exhaustion. Caffeine is also able to improve physical performance and endurance during prolonged activity of submaximal intensity. Glycogen sparing resulting from increased rate of lipolysis could contribute to the prolonged time to exhaustion. Finally, tolerance to the methylxanthine should be taken into account when an athlete wants to draw any benefit from caffeine absorption prior to a sports event. PMID:7960313

  9. Adenosine A1 receptors determine effects of caffeine on total fluid intake but not caffeine appetite.

    PubMed

    Rieg, Timo; Schnermann, Jürgen; Vallon, Volker

    2007-01-26

    Adenosine A1 receptor wild-type (+/+) and knockout (-/-) mice were used to elucidate the role of adenosine A1 receptors in caffeine self-administration in a two-bottle choice test and in the effect of caffeine on total fluid intake and plasma renin concentration. With access to water only, adenosine A1 receptor -/- mice showed greater basal fluid intake and greater plasma renin concentration than +/+ mice. Free access to both water and a caffeinated solution (30 mg/100 ml) for 14 days increased total fluid intake only in adenosine A1 receptor +/+ mice (by 23+/-3%), and both total fluid intake and plasma renin concentration were no longer different between genotypes. Mean intake of water and caffeinated solution was not different between adenosine A1 receptor +/+ and -/- mice. These data reveal that adenosine A1 receptors do not contribute to caffeine consumption, but determine the effects of caffeine on fluid intake and plasma renin concentration. PMID:17126319

  10. Pulsed corona discharge oxidation of aqueous carbamazepine micropollutant.

    PubMed

    Ajo, Petri; Krzymyk, Ewelina; Preis, Sergei; Kornev, Iakov; Kronberg, Leif; Louhi-Kultanen, Marjatta

    2016-08-01

    The anti-epileptic drug carbamazepine (CBZ) receives growing attention due to slow biodegradation and inherent accumulation in the aquatic environment. The application of a gas-phase pulsed corona discharge (PCD) was investigated to remove CBZ from synthetic solutions and spiked wastewater effluent from a municipal wastewater treatment facility. The treated water was showered between high voltage (HV) wires and grounded plate electrodes, to which ultra-short HV pulses were applied. CBZ was readily oxidized and 1-(2-benzaldehyde)-4-hydroquinazoline-2-one (BQM) and 1-(2-benzaldehyde)-4-hydro-quinazoline-2,4-dione (BQD) were identified as the most abundant primary transformation products, which, contrary to CBZ ozonation data available in the literature, were further easily oxidized with PCD: BQM and BQD attributed to only a minor portion of the target compound oxidized. In concentrations commonly found in wastewater treatment plant effluents (around 5 µg L(-1)), up to 97% reduction in CBZ concentration was achieved at mere 0.3 kW h m(-3) energy consumption, and over 99.9% was removed at 1 kW h m(-3). The PCD application proved to be efficient in the removal of both the parent substance and its known transformation products, even with the competing reactions in the complex composition of wastewater. PMID:26758812

  11. Carbamazepine damage to rat spermatogenesis in different sexual developmental phases.

    PubMed

    de Oliva, Samara Urban; Miraglia, Sandra Maria

    2009-10-01

    Carbamazepine (CBZ) is a first-line antiepileptic drug (AED), although it is also utilized for treatment of psychiatric disorders and neuropathic pain. The utilization of CBZ has been associated with damage to male reproduction including hormonal alterations, sexual dysfunction and reduction of sperm quality. Wide and long-term use of CBZ has been a common schedule for children and adolescents, despite the fact it alters the testosterone level in adult rats and humans. In addition, hypothalamic-pituitary-gonadal (HPG) axis during pre-puberty and puberty is more susceptible to toxic agents than in adult phase. The objective of this work was to evaluate the side effects of CBZ on the spermatogenic process of rats from pre-puberty to puberty and sexual maturation. Damage on the seminiferous epithelium, testicular interstitial oedema, reductions of testosterone levels and an increase in oestradiol levels were observed in rats, which were CBZ-treated since the weaning. The results suggest that CBZ, when administered from pre-puberty, provokes specific side effects on rat testes, resulting in more severe damage in the adult phase.

  12. Pulsed corona discharge oxidation of aqueous carbamazepine micropollutant.

    PubMed

    Ajo, Petri; Krzymyk, Ewelina; Preis, Sergei; Kornev, Iakov; Kronberg, Leif; Louhi-Kultanen, Marjatta

    2016-08-01

    The anti-epileptic drug carbamazepine (CBZ) receives growing attention due to slow biodegradation and inherent accumulation in the aquatic environment. The application of a gas-phase pulsed corona discharge (PCD) was investigated to remove CBZ from synthetic solutions and spiked wastewater effluent from a municipal wastewater treatment facility. The treated water was showered between high voltage (HV) wires and grounded plate electrodes, to which ultra-short HV pulses were applied. CBZ was readily oxidized and 1-(2-benzaldehyde)-4-hydroquinazoline-2-one (BQM) and 1-(2-benzaldehyde)-4-hydro-quinazoline-2,4-dione (BQD) were identified as the most abundant primary transformation products, which, contrary to CBZ ozonation data available in the literature, were further easily oxidized with PCD: BQM and BQD attributed to only a minor portion of the target compound oxidized. In concentrations commonly found in wastewater treatment plant effluents (around 5 µg L(-1)), up to 97% reduction in CBZ concentration was achieved at mere 0.3 kW h m(-3) energy consumption, and over 99.9% was removed at 1 kW h m(-3). The PCD application proved to be efficient in the removal of both the parent substance and its known transformation products, even with the competing reactions in the complex composition of wastewater.

  13. The antiepileptic drug carbamazepine affects sodium transport in toad epithelium.

    PubMed

    Suwalsky, Mario; Mennickent, Sigrid; Norris, Beryl; Cardenas, Hernán

    2006-09-01

    The present work investigates the effects of the antiepileptic drug carbamazepine (CBZ) on sodium transport in the isolated skin of the toad Pleurodema thaul. A submaximal concentration of the drug (0.2 mM) applied to the outer surface of the epithelium increased the electrical parameters short-circuit current (Isc) and potential difference (PD) by over 28%, whereas only a higher concentration (1 mM) induced over a 45% decrease in these parameters when applied to the inner surface. The amiloride test showed that the outer surface stimulatory effect was accompanied by an increase and the inner surface inhibitory effect by a decrease in the sodium electromotive force (ENa). Exploration of these effects of CBZ on the outer surface showed that 0.2 mM increased net Na+ (22Na) influx by 20% and 0.6 mM CBZ decreased Na+ mucosa-serosa flux by 19%, a result in agreement with the finding that higher concentrations of CBZ applied to the inner surface not only decreased ENa but also sodium conductance (GNa). PMID:16542818

  14. Reductive transformation of carbamazepine by abiotic and biotic processes.

    PubMed

    König, Anne; Weidauer, Cindy; Seiwert, Bettina; Reemtsma, Thorsten; Unger, Tina; Jekel, Martin

    2016-09-15

    The antiepileptic drug carbamazepine (CBZ) is ubiquitously present in the anthropogenic water cycle and is therefore of concern regarding the potable water supply. Despite of its persistent behavior in the aquatic environment, a redox dependent removal at bank filtration sites with anaerobic aquifer passage was reported repeatedly but not elucidated in detail yet. The reductive transformation of CBZ was studied, using abiotic systems (catalytic hydrogenation, electrochemistry) as well as biologically active systems (column systems, batch degradation tests). In catalytic hydrogenation CBZ is gradually hydrogenated and nine transformation products (TPs) were detected by liquid chromatography high-resolution mass spectrometry. 10,11-Dihydro-CBZ ((2H)-CBZ) was the major stable product in these abiotic, surface catalyzed reduction processes and turned out to be not a precursor of the more hydrogenated TPs. In the biotic reduction processes the formation of (2H)-CBZ alone could not explain the observed CBZ decline. There, also traces of (6H)-CBZ and (8H)-CBZ were formed by microbes under anaerobic conditions and four phase-II metabolites of reduced CBZ could be detected and tentatively identified. Thus, the spectrum of reduction products of CBZ is more diverse than previously thought. In environmental samples CBZ removal along an anaerobic soil passage was confirmed and (2H)-CBZ was determined at one of the sites.

  15. Caffeine relaxes smooth muscle through actin depolymerization.

    PubMed

    Tazzeo, Tracy; Bates, Genevieve; Roman, Horia Nicolae; Lauzon, Anne-Marie; Khasnis, Mukta D; Eto, Masumi; Janssen, Luke J

    2012-08-15

    Caffeine is sometimes used in cell physiological studies to release internally stored Ca(2+). We obtained evidence that caffeine may also act through a different mechanism that has not been previously described and sought to examine this in greater detail. We ruled out a role for phosphodiesterase (PDE) inhibition, since the effect was 1) not reversed by inhibiting PKA or adenylate cyclase; 2) not exacerbated by inhibiting PDE4; and 3) not mimicked by submillimolar caffeine nor theophylline, both of which are sufficient to inhibit PDE. Although caffeine is an agonist of bitter taste receptors, which in turn mediate bronchodilation, its relaxant effect was not mimicked by quinine. After permeabilizing the membrane using β-escin and depleting the internal Ca(2+) store using A23187, we found that 10 mM caffeine reversed tone evoked by direct application of Ca(2+), suggesting it functionally antagonizes the contractile apparatus. Using a variety of molecular techniques, we found that caffeine did not affect phosphorylation of myosin light chain (MLC) by MLC kinase, actin-filament motility catalyzed by MLC kinase, phosphorylation of CPI-17 by either protein kinase C or RhoA kinase, nor the activity of MLC-phosphatase. However, we did obtain evidence that caffeine decreased actin filament binding to phosphorylated myosin heads and increased the ratio of globular to filamentous actin in precontracted tissues. We conclude that, in addition to its other non-RyR targets, caffeine also interferes with actin function (decreased binding by myosin, possibly with depolymerization), an effect that should be borne in mind in studies using caffeine to probe excitation-contraction coupling in smooth muscle.

  16. Caffeine in your drink: natural or synthetic?

    PubMed

    Zhang, Lijun; Kujawinski, Dorothea M; Federherr, Eugen; Schmidt, Torsten C; Jochmann, Maik A

    2012-03-20

    Owing to possible adulteration and health concerns, it is important to discriminate between natural and synthetic food ingredients. A new method for compound-specific isotope analysis (CSIA) by coupling high-temperature reversed-phase liquid chromatography to isotope ratio mass spectrometry (HT-RPLC/IRMS) was developed for discrimination of natural and synthetic caffeine contained in all types of drinks. The analytical parameters such as stationary phase, column inner diameter, and column temperature were optimized for the separation of caffeine directly from drinks (without extraction). On the basis of the carbon isotope analysis of 42 natural caffeine samples including coffee beans, tea leaves, guaraná powder, and maté leaves, and 20 synthetic caffeine samples from different sources by high-temperature reversed-phase liquid chromatography coupled to isotope ratio mass spectrometry, it is concluded that there are two distinguishable groups of caffeine δ(13)C-values: one between -25 and -32‰ for natural caffeine, and the other between -33 and -38‰ for synthetic caffeine. Isotope analysis by HT-RPLC/IRMS has been applied to identify the caffeine source in 38 drinks. Four mislabeled products were detected due to added but nonlabeled synthetic caffeine with δ(13)C-values lower than -33‰. This work is the first application of HT-RPLC/IRMS to real-world food samples, which showed several advantages: simple sample preparation (only dilution), high throughput, long-term column stability, and high precision of δ(13)C-value. Thus, HT-RPLC/IRMS can be a very promising tool in stable isotope analysis of nonvolatile compounds. PMID:22339647

  17. Presence and fate of carbamazepine, oxcarbazepine, and seven of their metabolites at wastewater treatment plants.

    PubMed

    Leclercq, Marie; Mathieu, Olivier; Gomez, Elena; Casellas, Claude; Fenet, Hélène; Hillaire-Buys, Dominique

    2009-04-01

    Many pharmaceuticals are excreted in wastewater as parent substances or metabolites subsequent to therapeutic or diagnostic application in medical care. This includes the antiepileptic carbamazepine, which is not removed during conventional wastewater treatment and was found to be ubiquitous in the aquatic environment. Some carbamazepine metabolites have also been found in treated wastewater, but only five of them have been studied to date. However, at least 30 carbamazepine metabolites have been identified in humans, including some pharmacologically active or genotoxic compounds. Oxcarbazepine, an antiepileptic which is increasingly used, generates metabolites common to those of carbamazepine. The present work focuses on the presence of carbamazepine, oxcarbazepine, and seven of their metabolites (carbamazepine-10,11-epoxide, 10-hydroxy-10,11-dihydrocarbamazepine, 10,11-dihydro-10,11-trans-dihydroxycarbamazepine, 2-hydroxy-carbamazepine, iminostilbene, acridine, and acridone) at three different treatment plants (conventional activated sludge, trickling filter, and stabilization ponds) selected in France. The main aim of this work was to identify selected compounds in wastewater after therapeutic use and to measure concentrations in influents and effluents at the three wastewater treatment plants. Except for iminostilbene, all of these compounds were detected in wastewater. The metabolite common to carbamazepine and oxcarbazepine, i.e., 10,11-dihydro-10,11-trans-dihydroxycarbamazepine, was detected at a higher concentration than the parent substances in wastewater. The presence of parent molecules was noted in inlet and outlet water samples. Carbamazepine, as expected, was not removed by conventional activated sludge treatment. Nevertheless, in a wastewater treatment plant with a 78-day hydraulic retention time, a 73% decrease in carbamazepine concentration was observed. For the first time, oxcarbazepine was found in environmental samples. A decrease in

  18. Caffeine Promotes Global Spatial Processing in Habitual and Non-Habitual Caffeine Consumers

    PubMed Central

    Giles, Grace E.; Mahoney, Caroline R.; Brunyé, Tad T.; Taylor, Holly A.; Kanarek, Robin B.

    2013-01-01

    Information processing is generally biased toward global cues, often at the expense of local information. Equivocal extant data suggests that arousal states may accentuate either a local or global processing bias, at least partially dependent on the nature of the manipulation, task, and stimuli. To further differentiate the conditions responsible for such equivocal results we varied caffeine doses to alter physiological arousal states and measured their effect on tasks requiring the retrieval of local versus global spatial knowledge. In a double-blind, repeated-measures design, non-habitual (Experiment 1; N = 36, M = 42.5 ± 28.7 mg/day caffeine) and habitual (Experiment 2; N = 34, M = 579.5 ± 311.5 mg/day caffeine) caffeine consumers completed four test sessions corresponding to each of four caffeine doses (0, 100, 200, 400 mg). During each test session, participants consumed a capsule containing one of the three doses of caffeine or placebo, waited 60 min, and then completed two spatial tasks, one involving memorizing maps and one spatial descriptions. A spatial statement verification task tested local versus global spatial knowledge by differentially probing memory for proximal versus distal landmark relationships. On the map learning task, results indicated that caffeine enhanced memory for distal (i.e., global) compared to proximal (i.e., local) comparisons at 100 (marginal), 200, and 400 mg caffeine in non-habitual consumers, and marginally beginning at 200 mg caffeine in habitual consumers. On the spatial descriptions task, caffeine enhanced memory for distal compared to proximal comparisons beginning at 100 mg in non-habitual but not habitual consumers. We thus provide evidence that caffeine-induced physiological arousal amplifies global spatial processing biases, and these effects are at least partially driven by habitual caffeine consumption. PMID:24146646

  19. Caffeine induced changes in cerebral circulation

    SciTech Connect

    Mathew, R.J.; Wilson, W.H.

    1985-09-01

    While the caffeine induced cerebral vasoconstriction is well documented, the effects of oral ingestion of the drug in a dose range comparable to the quantities in which it is usually consumed and the intensity and duration of the associated reduction in cerebral circulation are unknown. Cerebral blood flow was measured via the TTXenon inhalation technique before and thirty and ninety minutes after the oral administration of 250 mg of caffeine or a placebo, under double-blind conditions. Caffeine ingestion was found to be associated with significant reductions in cerebral perfusion thirty and ninety minutes later. The placebo group showed no differences between the three sets of cerebral blood flow values.

  20. Performance effects and metabolic consequences of caffeine and caffeinated energy drink consumption on glucose disposal.

    PubMed

    Shearer, Jane; Graham, Terry E

    2014-10-01

    This review documents two opposing effects of caffeine and caffeine-containing energy drinks, i.e., their positive effects on athletic performance and their negative impacts on glucose tolerance in the sedentary state. Analysis of studies examining caffeine administration prior to performance-based exercise showed caffeine improved completion time by 3.6%. Similar analyses following consumption of caffeine-containing energy drinks yielded positive, but more varied, benefits, which were likely due to the diverse nature of the studies performed, the highly variable composition of the beverages consumed, and the range of caffeine doses administered. Conversely, analyses of studies administering caffeine prior to either an oral glucose tolerance test or insulin clamp showed a decline in whole-body glucose disposal of ~30%. The consequences of this resistance are unknown, but there may be implications for the development of a number of chronic diseases. Both caffeine-induced performance enhancement and insulin resistance converge with the primary actions of caffeine on skeletal muscle.

  1. How habitual caffeine consumption and dose influence flavour preference conditioning with caffeine.

    PubMed

    Tinley, Elizabeth M; Durlach, Paula J; Yeomans, Martin R

    2004-09-15

    This study investigated the effects of both habitual caffeine use and dose administered in determining the ability of caffeine to reinforce conditioned changes in flavour preference. Thirty overnight-withdrawn moderate caffeine consumers and 30 non or low-dose caffeine (non/low) consumers evaluated five novel-flavoured fruit teas. Subsequently, their median-rated tea was used in four ensuing conditioning sessions. Either placebo, 1 or 2 mg/kg of caffeine (n=10 consumers, 10 non/low consumers in each condition), was added to the target tea, and all five teas were reevaluated at a final tasting. Pleasantness ratings over the four conditioning sessions indicated that non/low consumers' liking increased for the noncaffeinated fruit tea with no change for the tea containing either 1 or 2 mg/kg of caffeine. Among consumers, pleasantness ratings tended to decrease for the noncaffeinated fruit tea but increased significantly at the 1-mg dose and showed a tendency to increase at the 2-mg dose. Similar effects were shown in the evaluations made before and after conditioning, with no change in the nonexposed drinks. These results show that 1.0 mg/kg of caffeine reinforces changes in flavour pleasantness in acutely withdrawn habitual consumers but not in nonconsumers or nondependent low-caffeine consumers, further endorsing the negative-reinforcement theory of conditioning with caffeine.

  2. Caffeine metabolites not caffeine protect against riboflavin photosensitized oxidative damage related to skin and eye health.

    PubMed

    Scurachio, R S; Mattiucci, F; Santos, W G; Skibsted, L H; Cardoso, D R

    2016-10-01

    Caffeine metabolites were found to bind riboflavin with dissociation constant in the millimolar region by an exothermic process with positive entropy of reaction, which was found by (1)H NMR and fluorescence spectroscopy to occur predominantly by hydrogen bonding with water being released from riboflavin solvation shell upon caffeine metabolite binding to riboflavin. The caffeine metabolites 1-methyl uric acid and 1,7-dimethyl uric acid were shown by transient absorption laser flash photolysis to be efficient as quenchers of triplet riboflavin with second-order rate constant of 1.4 10(8)Lmol(-1)s(-1) and 1.0 10(8)Lmol(-1)s(-1), respectively, in aqueous solution of pH6.4 at 25°C and more efficient than the other caffeine metabolite 1,7-dimethyl xanthine with second-order rate constant of 4.2 10(7)Lmol(-1)s(-1). Caffeine was in contrast found to be non-reactive towards triplet riboflavin. Caffeine metabolites rather than caffeine seem accordingly important for the observed protective effect against cutaneous melanoma identified for drinkers of regular but not of decaffeinated coffee. The caffeine metabolites, but not caffeine, were by time resolved single photon counting found to quench singlet excited riboflavin through exothermic formation of ground-state precursor complexes indicating importance of hydrogen bounding through keto-enol tautomer's for protection of oxidizable substrates and sensitive structures against riboflavin photosensitization.

  3. Caffeine metabolites not caffeine protect against riboflavin photosensitized oxidative damage related to skin and eye health.

    PubMed

    Scurachio, R S; Mattiucci, F; Santos, W G; Skibsted, L H; Cardoso, D R

    2016-10-01

    Caffeine metabolites were found to bind riboflavin with dissociation constant in the millimolar region by an exothermic process with positive entropy of reaction, which was found by (1)H NMR and fluorescence spectroscopy to occur predominantly by hydrogen bonding with water being released from riboflavin solvation shell upon caffeine metabolite binding to riboflavin. The caffeine metabolites 1-methyl uric acid and 1,7-dimethyl uric acid were shown by transient absorption laser flash photolysis to be efficient as quenchers of triplet riboflavin with second-order rate constant of 1.4 10(8)Lmol(-1)s(-1) and 1.0 10(8)Lmol(-1)s(-1), respectively, in aqueous solution of pH6.4 at 25°C and more efficient than the other caffeine metabolite 1,7-dimethyl xanthine with second-order rate constant of 4.2 10(7)Lmol(-1)s(-1). Caffeine was in contrast found to be non-reactive towards triplet riboflavin. Caffeine metabolites rather than caffeine seem accordingly important for the observed protective effect against cutaneous melanoma identified for drinkers of regular but not of decaffeinated coffee. The caffeine metabolites, but not caffeine, were by time resolved single photon counting found to quench singlet excited riboflavin through exothermic formation of ground-state precursor complexes indicating importance of hydrogen bounding through keto-enol tautomer's for protection of oxidizable substrates and sensitive structures against riboflavin photosensitization. PMID:27611451

  4. Performance effects and metabolic consequences of caffeine and caffeinated energy drink consumption on glucose disposal.

    PubMed

    Shearer, Jane; Graham, Terry E

    2014-10-01

    This review documents two opposing effects of caffeine and caffeine-containing energy drinks, i.e., their positive effects on athletic performance and their negative impacts on glucose tolerance in the sedentary state. Analysis of studies examining caffeine administration prior to performance-based exercise showed caffeine improved completion time by 3.6%. Similar analyses following consumption of caffeine-containing energy drinks yielded positive, but more varied, benefits, which were likely due to the diverse nature of the studies performed, the highly variable composition of the beverages consumed, and the range of caffeine doses administered. Conversely, analyses of studies administering caffeine prior to either an oral glucose tolerance test or insulin clamp showed a decline in whole-body glucose disposal of ~30%. The consequences of this resistance are unknown, but there may be implications for the development of a number of chronic diseases. Both caffeine-induced performance enhancement and insulin resistance converge with the primary actions of caffeine on skeletal muscle. PMID:25293551

  5. Careful: Acetaminophen in Pain Relief Medicines Can Cause Liver Damage

    MedlinePlus

    ... Careful: Acetaminophen in pain relief medicines can cause liver damage Share Tweet Linkedin Pin it More sharing ... word or may have the abbreviation "APAP." Severe liver damage may occur and may lead to death ...

  6. NQO2 is a reactive oxygen species generating off-target for acetaminophen.

    PubMed

    Miettinen, Teemu P; Björklund, Mikael

    2014-12-01

    The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity.

  7. NQO2 Is a Reactive Oxygen Species Generating Off-Target for Acetaminophen

    PubMed Central

    2014-01-01

    The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity. PMID:25313982

  8. Uptake of carbamazepine by rhizomes and endophytic bacteria of Phragmites australis

    PubMed Central

    Sauvêtre, Andrés; Schröder, Peter

    2015-01-01

    Carbamazepine is an antiepileptic and mood-stabilizing drug which is used widely in Europe and North America. In the environment, it is found as a persistent and recalcitrant contaminant, being one of the most prominent hazardous pharmaceuticals and personal care products in effluents of wastewater treatment plants. Phragmites australis is one of the species with both, the highest potential of detoxification and phytoremediation. It has been used successfully in the treatment of industrial and municipal wastewater. Recently, the identification of endophytic microorganisms from different plant species growing in contaminated sites has provided a list of candidates which could be used as bio-inoculants for bioremediation of difficult compounds. In this study, Phragmites australis plants were exposed to 5 mg/L of carbamazepine. After 9 days the plants had removed 90% of the initial concentration. Endophytic bacteria were isolated from these plants and further characterized. Phylogenetic analysis based on 16S rDNA sequencing revealed that the majority of these isolates belong to three groups: Proteobacteria, Actinobacteria, and Bacteroidetes. Carbamazepine uptake and plant growth promoting (PGP) traits were analyzed among the isolates. Ninety percent of the isolates produce indole acetic acid (IAA) and all of them possess at least one of the PGP traits tested. One isolate identified as Chryseobacterium taeanense combines good carbamazepine uptake and all of the PGP traits. Rhizobium daejeonense can remove carbamazepine and produces 23 μg/mL of IAA. Diaphorobacter nitroreducens and Achromobacter mucicolens are suitable for carbamazepine removal while both, Pseudomonas veronii and Pseudomonas lini show high siderophore production and phosphate solubilization. Alone or in combination, these isolates might be applied as inoculates in constructed wetlands in order to enhance the phytoremediation of carbamazepine during wastewater treatment. PMID:25750647

  9. Uptake of carbamazepine by rhizomes and endophytic bacteria of Phragmites australis.

    PubMed

    Sauvêtre, Andrés; Schröder, Peter

    2015-01-01

    Carbamazepine is an antiepileptic and mood-stabilizing drug which is used widely in Europe and North America. In the environment, it is found as a persistent and recalcitrant contaminant, being one of the most prominent hazardous pharmaceuticals and personal care products in effluents of wastewater treatment plants. Phragmites australis is one of the species with both, the highest potential of detoxification and phytoremediation. It has been used successfully in the treatment of industrial and municipal wastewater. Recently, the identification of endophytic microorganisms from different plant species growing in contaminated sites has provided a list of candidates which could be used as bio-inoculants for bioremediation of difficult compounds. In this study, Phragmites australis plants were exposed to 5 mg/L of carbamazepine. After 9 days the plants had removed 90% of the initial concentration. Endophytic bacteria were isolated from these plants and further characterized. Phylogenetic analysis based on 16S rDNA sequencing revealed that the majority of these isolates belong to three groups: Proteobacteria, Actinobacteria, and Bacteroidetes. Carbamazepine uptake and plant growth promoting (PGP) traits were analyzed among the isolates. Ninety percent of the isolates produce indole acetic acid (IAA) and all of them possess at least one of the PGP traits tested. One isolate identified as Chryseobacterium taeanense combines good carbamazepine uptake and all of the PGP traits. Rhizobium daejeonense can remove carbamazepine and produces 23 μg/mL of IAA. Diaphorobacter nitroreducens and Achromobacter mucicolens are suitable for carbamazepine removal while both, Pseudomonas veronii and Pseudomonas lini show high siderophore production and phosphate solubilization. Alone or in combination, these isolates might be applied as inoculates in constructed wetlands in order to enhance the phytoremediation of carbamazepine during wastewater treatment.

  10. Interactions between carbamazepine and polyethylene glycol (PEG) 6000: characterisations of the physical, solid dispersed and eutectic mixtures.

    PubMed

    Naima, Z; Siro, T; Juan-Manuel, G D; Chantal, C; René, C; Jerome, D

    2001-02-01

    The influence of a hydrophilic carrier (PEG 6000) on the polymorphism of carbamazepine, an antiepileptic drug, was investigated in binary physical mixtures and solid dispersions by means of differential scanning calorimetry (DSC), thermal gravimetry, hot-stage microscopy (HSM), and X-ray diffractometry, respectively. This study provides also an attempt to develop a method to calculate more precisely the eutectic composition. In rather ideal physical mixtures, carbamazepine was found as monoclinic Form III. In solid dispersions, the drug was found to crystallize as trigonal Form II; a eutectic invariant in the PEG 6000-rich composition domain (6% of carbamazepine mass) was evidenced by DSC experiments and confirmed by HSM observations. In the binary phase diagram the ideal carbamazepine liquidus curve was located at temperatures higher than the respective experimental ones. This suggests that drug can be maintained in the liquid state in the temperature-mass fraction (T--x) region between the two carbamazepine liquidus curves. This indicates in turn that attractive interactions occur between carbamazepine and PEG 6000-chains. These interactions have been also claimed to prevent carbamazepine from degradation into iminostilbene (a compound resulting from the chemical degradation of carbamazepine which is postulated to be responsible for the idiosyncratic toxicity of the drug) and thought to lead to the crystallization of metastable Carbamazepine II from melt. The negative excess entropy for eutectic mixtures indicated that the drug crystals are finely dispersed in the bulk of polymer chains.

  11. Reversal of acetaminophen toxicity in isolated hamster hepatocytes by dithiothreitol

    SciTech Connect

    Tee, L.B.; Boobis, A.R.; Huggett, A.C.; Davies, D.S.

    1986-04-01

    The toxicity of acetaminophen in freshly isolated hamster hepatocytes was investigated. Cells exposed to 2.5 mM acetaminophen for 90 min, followed by washing to completely remove unbound acetaminophen, and resuspension in fresh buffer, showed a dramatic decrease in viability over the ensuing 4.5 hr by which time only 4% of the cells could still exclude trypan blue. During the initial 90-min incubation, there was a substantial depletion of glutathione, to 19% of control values, covalent binding of (/sup 14/C)acetaminophen to cellular proteins, and evidence of morphological changes consistent with some disturbance of the plasma membrane. During subsequent incubation of these cells, covalent binding did not change nor did lipid peroxidation, despite the decrease in viability that occurred. Subsequent incubation of cells exposed to acetaminophen for 90 min in buffer containing 1.5 mM dithiothreitol (DTT), a disulfide-reducing agent, largely prevented the decrease in cell viability and reversed the morphological changes that occurred during the first 90-min incubation. However, there was no change in lipid peroxidation, glutathione content, or covalent binding. It is concluded that acetaminophen interacted with some critical target in the cell, and that this left unchecked, led eventually to the death of the cell. DTT prevented and reversed this effect. The toxicity of acetaminophen, and its reversal by DTT, appear independent of either covalent binding of acetaminophen or lipid peroxidation. In addition, the effect of DTT was independent of the concentration of glutathione, most probably acting by directly reducing oxidized SH-groups in critical enzymes, possibly membrane-bound ATP-dependent Ca2+ translocases.

  12. Caffeine in surface and wastewaters in Barbados, West Indies.

    PubMed

    Edwards, Quincy A; Kulikov, Sergei M; Garner-O'Neale, Leah D

    2015-01-01

    Caffeine, a purine alkaloid drug, has been recognized as a contaminant of water bodies in various climatic regions, however, these environmental caffeine concentrations are the first to be reported in the tropical Caribbean. The major objective of this study was to develop an improved method to extract caffeine from surface and wastewaters in the warm Caribbean environment and measure caffeine concentrations in highly populated areas in Barbados. Caffeine was extracted from water via solid phase extraction (SPE); the acidified water samples were loaded onto C-18 cartridges and eluted with pure chloroform. The extracted caffeine was quantified using gas chromatography - mass spectroscopy - multiple reaction monitoring (GC-MS/MS-MRM). Method detection limits of 0.2 ng L(-1) from 1 L water samples were achieved. Caffeine was detected in all environmental water samples investigated. The concentrations of caffeine in surface waters were detected in the range 0.1 - 6.9 μg L(-1). The two wastewater treatment plants, primary and secondary treatment systems, significantly differed in their ability to eliminate caffeine in the raw sewage (38% and 99% caffeine removal efficiencies respectively). Thus, it may be essential to employ secondary treatment to effectively remove caffeine from wastewater systems in Barbados. Caffeine in water bodies are principally attributed to anthropogenic sources as caffeine-producing plants are not commonly grown on the island of Barbados. The study also shows the recalcitrance of caffeine to hydrolytic degradation. PMID:25729634

  13. Caffeine in surface and wastewaters in Barbados, West Indies.

    PubMed

    Edwards, Quincy A; Kulikov, Sergei M; Garner-O'Neale, Leah D

    2015-01-01

    Caffeine, a purine alkaloid drug, has been recognized as a contaminant of water bodies in various climatic regions, however, these environmental caffeine concentrations are the first to be reported in the tropical Caribbean. The major objective of this study was to develop an improved method to extract caffeine from surface and wastewaters in the warm Caribbean environment and measure caffeine concentrations in highly populated areas in Barbados. Caffeine was extracted from water via solid phase extraction (SPE); the acidified water samples were loaded onto C-18 cartridges and eluted with pure chloroform. The extracted caffeine was quantified using gas chromatography - mass spectroscopy - multiple reaction monitoring (GC-MS/MS-MRM). Method detection limits of 0.2 ng L(-1) from 1 L water samples were achieved. Caffeine was detected in all environmental water samples investigated. The concentrations of caffeine in surface waters were detected in the range 0.1 - 6.9 μg L(-1). The two wastewater treatment plants, primary and secondary treatment systems, significantly differed in their ability to eliminate caffeine in the raw sewage (38% and 99% caffeine removal efficiencies respectively). Thus, it may be essential to employ secondary treatment to effectively remove caffeine from wastewater systems in Barbados. Caffeine in water bodies are principally attributed to anthropogenic sources as caffeine-producing plants are not commonly grown on the island of Barbados. The study also shows the recalcitrance of caffeine to hydrolytic degradation.

  14. The Effects of Caffeine on Hyperactive Children

    ERIC Educational Resources Information Center

    Firestone, Philip; And Others

    1978-01-01

    The psychological, physiological, and behavioral effects of a 2-week regimen of 300 mg of caffeine on 20 hyperactive males between the ages of 5 and 12 years were examined, using a double-blind crossover format. (Author)

  15. Caffeinated alcohol beverages: a public health concern.

    PubMed

    Attwood, Angela S

    2012-01-01

    Consumption of alcohol mixed with caffeinated energy drinks is becoming popular, and the number of pre-mixed caffeinated alcohol products on the worldwide market is increasing. There is public health concern and even occasional legal restriction relating to these drinks, due to associations with increased intoxication and harms. The precise nature and degree of the pharmacological relationship between caffeine and alcohol is not yet elucidated, but it is proposed that caffeine attenuates the sedative effects of alcohol intoxication while leaving motor and cognitive impairment unaffected. This creates a potentially precarious scenario for users who may underestimate their level of intoxication and impairment. While legislation in some countries has restricted production or marketing of pre-mixed products, many individuals mix their own energy drink-alcohol 'cocktails'. Wider dissemination of the risks might help balance marketing strategies that over-emphasize putative positive effects. PMID:22645036

  16. Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity.

    PubMed

    Wang, Kun-Peng; Bai, Yu; Wang, Jian; Zhang, Jin-Zhen

    2014-05-01

    Schisandra chinensis is a well-known traditional medicinal herb. Acetaminophen is a commonly used over-the-counter analgesic and overdose of acetaminophen was the most frequent cause of acute liver failure. However, no studies have demonstrated the role of Schisandra chinensis in acetaminophen-induced acute liver failure to the best of our knowledge. In this study, an acute liver injury model was established in mice using acetaminophen. The protective role of Schisandra chinensis was detected by histopathological analysis, and measurement of the serum transaminase levels and hepatic Cyp activity levels in the mouse model. Subsequently, hepatocytes were isolated from the livers of the mouse model. The cell cycle, apoptosis, mitochondrial membrane potential and reactive oxygen species were determined using flow cytometry. Cell proliferation and 26S proteasome activity were determined using spectrophotometry. Schisandra chinensis was found to resist acetaminophen-induced hepatotoxicity by protecting mitochondria and lysosomes and inhibiting the phosphor-c-Jun N-terminal kinase signaling pathway. These findings provide a novel application of Schisandra chinensis against acetaminophen-induced acute liver failure.

  17. Effect of acetaminophen on sulfamethazine acetylation in male volunteers.

    PubMed

    Tahir, I M; Iqbal, T; Saleem, S; Mehboob, H; Akhter, N; Riaz, M

    2016-03-01

    The effect of acetaminophen on sulfamethazine N-acetylation by human N-acetyltrasferase-2 (NAT2) was studied in 19 (n=19) healthy male volunteers in two different phases. In the first phase of the study the volunteers were given an oral dose of sulfamethazine 500 mg alone and blood and urine samples were collected. After the 10-day washout period the same selected volunteers were again administered sulfamethazine 500 mg along with 1000 mg acetaminophen. The acetylation of sulfamethazine by human NAT2 in both phases with and without acetaminophen was determined by HPLC to establish their respective phenotypes. In conclusion obtained statistics of present study revealed that acetaminophen significantly (P<0.0001) decreased sulfamethazine acetylation in plasma of both slow and fast acetylator male volunteers. A highly significant (P<0.0001) decrease in plasma-free and total sulfamethazine concentration was also observed when acetaminophen was co-administered. Urine acetylation status in both phases of the study was found not to be in complete concordance with that of plasma. Acetaminophen significantly (P<0.0001) increased the acetyl, free and total sulfamethazine concentration in urine of both slow and fast acetylators. Urine acetylation analysis has not been found to be a suitable approach for phenotypic studies.

  18. Ferroptosis is Involved in Acetaminophen Induced Cell Death.

    PubMed

    Lőrincz, Tamás; Jemnitz, Katalin; Kardon, Tamás; Mandl, József; Szarka, András

    2015-09-01

    The recently described form of programmed cell death, ferroptosis can be induced by agents causing GSH depletion or the inhibition of GPX4. Ferroptosis clearly shows distinct morphologic, biochemical and genetic features from apoptosis, necrosis and autophagy. Since NAPQI the highly reactive metabolite of the widely applied analgesic and antipyretic, acetaminophen induces a cell death which can be characterized by GSH depletion, GPX inhibition and caspase independency the involvement of ferroptosis in acetaminophen induced cell death has been investigated. The specific ferroptosis inhibitor ferrostatin-1 failed to elevate the viability of acetaminophen treated HepG2 cells. It should be noticed that these cells do not form NAPQI due to the lack of phase I enzyme expression therefore GSH depletion cannot be observed. However in the case of acetaminophen treated primary mouse hepatocytes the significant elevation of cell viability could be observed upon ferrostatin-1 treatment. Similar to ferrostatin-1 treatment, the addition of the RIP1 kinase inhibitor necrostatin-1 could also elevate the viability of acetaminophen treated primary hepatocytes. Ferrostatin-1 has no influence on the expression of CYP2E1 or on the cellular GSH level which suggest that the protective effect of ferrostatin-1 in APAP induced cell death is not based on the reduced metabolism of APAP to NAPQI or on altered NAPQI conjugation by cellular GSH. Our results suggest that beyond necroptosis and apoptosis a third programmed cell death, ferroptosis is also involved in acetaminophen induced cell death in primary hepatocytes.

  19. Ferroptosis is Involved in Acetaminophen Induced Cell Death.

    PubMed

    Lőrincz, Tamás; Jemnitz, Katalin; Kardon, Tamás; Mandl, József; Szarka, András

    2015-09-01

    The recently described form of programmed cell death, ferroptosis can be induced by agents causing GSH depletion or the inhibition of GPX4. Ferroptosis clearly shows distinct morphologic, biochemical and genetic features from apoptosis, necrosis and autophagy. Since NAPQI the highly reactive metabolite of the widely applied analgesic and antipyretic, acetaminophen induces a cell death which can be characterized by GSH depletion, GPX inhibition and caspase independency the involvement of ferroptosis in acetaminophen induced cell death has been investigated. The specific ferroptosis inhibitor ferrostatin-1 failed to elevate the viability of acetaminophen treated HepG2 cells. It should be noticed that these cells do not form NAPQI due to the lack of phase I enzyme expression therefore GSH depletion cannot be observed. However in the case of acetaminophen treated primary mouse hepatocytes the significant elevation of cell viability could be observed upon ferrostatin-1 treatment. Similar to ferrostatin-1 treatment, the addition of the RIP1 kinase inhibitor necrostatin-1 could also elevate the viability of acetaminophen treated primary hepatocytes. Ferrostatin-1 has no influence on the expression of CYP2E1 or on the cellular GSH level which suggest that the protective effect of ferrostatin-1 in APAP induced cell death is not based on the reduced metabolism of APAP to NAPQI or on altered NAPQI conjugation by cellular GSH. Our results suggest that beyond necroptosis and apoptosis a third programmed cell death, ferroptosis is also involved in acetaminophen induced cell death in primary hepatocytes. PMID:25962350

  20. Caffeine supplementation and peak anaerobic power output.

    PubMed

    Glaister, Mark; Muniz-Pumares, Daniel; Patterson, Stephen D; Foley, Paul; McInnes, Gillian

    2015-01-01

    The aim of this study was to investigate the effects of caffeine supplementation on peak anaerobic power output (Wmax). Using a counterbalanced, randomised, double-blind, placebo-controlled design, 14 well-trained men completed three trials of a protocol consisting of a series of 6-s cycle ergometer sprints, separated by 5-min passive recovery periods. Sprints were performed at progressively increasing torque factors to determine the peak power/torque relationship and Wmax. Apart from Trial 1 (familiarisation), participants ingested a capsule containing 5 mg·kg(-1) of caffeine or placebo, one hour before each trial. The effects of caffeine on blood lactate were investigated using capillary samples taken after each sprint. The torque factor which produced Wmax was not significantly different (p ≥ 0.05) between the caffeine (1.15 ± 0.08 N·m·kg(-1)) and placebo (1.13 ± 0.10 N·m·kg(-1)) trials. There was, however, a significant effect (p < 0.05) of supplementation on Wmax, with caffeine producing a higher value (1885 ± 303 W) than placebo (1835 ± 290 W). Analysis of the blood lactate data revealed a significant (p < 0.05) torque factor × supplement interaction with values being significantly higher from the sixth sprint (torque factor 1.0 N·m·kg(-1)) onwards following caffeine supplementation. The results of this study confirm previous reports that caffeine supplementation significantly increases blood lactate and Wmax. These findings may explain why the majority of previous studies, which have used fixed-torque factors of around 0.75 N·m·kg(-1) and thereby failing to elicit Wmax, have failed to find an effect of caffeine on sprinting performance.

  1. Caffeine intake reduces sleep duration in adolescents.

    PubMed

    Lodato, Francesca; Araújo, Joana; Barros, Henrique; Lopes, Carla; Agodi, Antonella; Barchitta, Martina; Ramos, Elisabete

    2013-09-01

    In our study, we hypothesized that higher caffeine intake would be associated with lower sleep duration among 13-year-old adolescents. In addition, we aimed to identify food sources of caffeine intake in this sample. Eligible participants were adolescents who were born in 1990 and attended school in Porto, Portugal, in 2003/2004. Self-administered questionnaires were used, and diet was evaluated using a food frequency questionnaire. From the 2160 eligible participants, only 1522 with valid information regarding their diet were included in this study. In our sample, the median intake of caffeine was 23.1 mg/d, with soft drinks being the major source. Ice tea presented the highest median (25th-75th percentiles) contribution (33.1% [14.0-52.1]), followed by cola (21.1% [6.4-37.6]). Regarding cocoa products, chocolate bars presented a median contribution of 5.1% (1.0-14.0), and snacks containing chocolate had a contribution of 3.0% (0.5-7.2). Coffee and tea presented a negligible contribution. Adolescents who reported less sleep duration and those who spent more time watching TV during the weekend had a significantly higher caffeine intake. Overall, boys had higher intakes of caffeine from soft drinks, and private school attendees, those who had parents with more education, who reported less television viewing time and had lower body mass index presented higher intakes of caffeine from chocolate. Considering sleeping more than 9.5 hours as a reference class, for each increase of 10 mg/d in caffeine intake, we found that the odds ratio of sleeping 8.5 hours or less was 1.12 (95% confidence interval, 1.06-1.19). Our results support the hypothesis that caffeine intake was inversely associated with sleep duration in adolescents.

  2. Characterization of individuals seeking treatment for caffeine dependence.

    PubMed

    Juliano, Laura M; Evatt, Daniel P; Richards, Brian D; Griffiths, Roland R

    2012-12-01

    Previous investigations have identified individuals who meet criteria for Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000) substance dependence as applied to caffeine, but there is little research on treatments for caffeine dependence. This study aimed to thoroughly characterize individuals who are seeking treatment for problematic caffeine use. Ninety-four individuals who identified as being psychologically or physically dependent on caffeine, or who had tried unsuccessfully to modify caffeine consumption participated in a face-to-face diagnostic clinical interview. They also completed measures concerning caffeine use and quitting history, reasons for seeking treatment, and standardized self-report measures of psychological functioning. Caffeine treatment seekers (mean age 41 years, 55% women) consumed an average of 548 mg caffeine per day. The primary source of caffeine was coffee for 50% of the sample and soft drinks for 37%. Eighty-eight percent reported prior serious attempts to modify caffeine use (mean 2.7 prior attempts), and 43% reported being advised by a medical professional to reduce or eliminate caffeine. Ninety-three percent met criteria for caffeine dependence when generic DSM-IV-TR substance dependence criteria were applied to caffeine use. The most commonly endorsed criteria were withdrawal (96%), persistent desire or unsuccessful efforts to control use (89%), and use despite knowledge of physical or psychological problems caused by caffeine (87%). The most common reasons for wanting to modify caffeine use were health-related (59%) and not wanting to be dependent on caffeine (35%). This investigation reveals that there are individuals with problematic caffeine use who are seeking treatment and suggests that there is a need for effective caffeine dependence treatments. PMID:22369218

  3. Acute Liver Failure including Acetaminophen Overdose

    PubMed Central

    Fontana, Robert J.

    2008-01-01

    Synopsis Acute liver failure (ALF) is a dramatic and highly unpredictable clinical syndrome defined by the sudden onset of coagulopathy and encephalopathy. Although many disease processes can cause ALF, acetaminophen overdose is the leading cause in the United States, and has a 66% chance of recovery with early N-acetylcysteine treatment and supportive care. Cerebral edema and infectious complications are notoriously difficult to detect and treat in ALF patients and may lead to irreversible brain damage and multi-organ failure. Emergency liver transplantation is associated with a 70% 1-year patient survival but 20% of listed patients die, highlighting the importance of early referral of ALF patients with a poor prognosis to a liver transplant center. PMID:18570942

  4. Pharmacokinetics: time-dependent changes--autoinduction of carbamazepine epoxidation

    SciTech Connect

    Bertilsson, L.; Tomson, T.; Tybring, G.

    1986-07-01

    Drugs labeled with stable isotopes have been useful to study time-dependent changes in kinetics. Early studies suggested that carbamazepine (CBZ) may induce its own metabolism, but this could not be proved until tetradeuterium-labeled CBZ (CBZ-D4) was synthesized and then given to patients. CBZ-D4 was administered to three children during long-term treatment of epilepsy with CBZ. After 17 to 32 days of treatment, the plasma clearance of CBZ-D4 was doubled, but during the next four months, there was no further increase, indicating that autoinduction was complete within one month. Two patients with chronic alcoholism were treated with CBZ for five days. Half of the first dose of 600 mg was comprised of CBZ-D4. The half-life of this CBZ-D4 dose in the two patients (20 and 26 hr, respectively) was similar to the post-steady-state half-life of CBZ (23 hr in both patients) measured later. A single dose of CBZ given one week after the last maintenance dose had a longer half-life (46 and 45 hr, respectively), which probably is close to the disposition of the drug before starting the treatment with CBZ. This shows that autoinduction of CBZ metabolism was completed during the very first doses of CBZ. Autoinduction also disappeared rapidly after stopping the treatment. We have shown that it is mainly the epoxide-diol pathway that is induced, both during autoinduction and after induction with other antiepileptic agents.

  5. Carbamazepine population pharmacokinetics in children: mixed-effect models.

    PubMed

    Delgado Iribarnegaray, M F; Santo Bueldga, D; García Sánchez, M J; Otero, M J; Falcão, A C; Domínguez-Gil, A

    1997-04-01

    The aim of the authors' study was to investigate the factors affecting carbamazepine (CBZ) clearance (CL) in children with epilepsy. The factors evaluated were total body weight (TBW), age, dose, sex, and phenobarbital (PB) and valproic acid (VA) comedication. A total of 387 steady-state serum concentration samples was analyzed. These were collected during CBZ therapy from 201 children, aged 1-14 years and weighting 9-78 kg. Population CL was calculated by using NONMEM, with a one-compartment model with first-order absorption and elimination. The absorption rate, bioavailability, and volume of distribution were set at values found in the literature. The model found best to describe the data was CL = (0.0122 TBW + 0.0467 Dose) Age0.331 (1.289 PB). The interindividual variability in CL had a variation coefficient (CV) of 11.8%, and the residual error, described by using an additive model, was 1.5 mg/l. The results show that CL increases linearly with TBW and nonlinearly with age; thus older children have a lower CL with respect to TBW than do younger ones. Likewise CL was seen to increase with the increase in the CBZ dose, suggesting a dose-dependent autoinduction of CBZ metabolism. Concomitant PB administration affected CL: however, sex and VA comedication did not affect it significantly. The final regression model for CL, was validated in a different group of 74 children. The standarized prediction error (SPE) was not significantly different from zero (SPE = 0.028), indicating that the model proposed for CL can be used to make accurate dosage recommendations. With these population estimates, CBZ doses that would be suitable for pediatric patients of different ages are proposed.

  6. Anti-solvent co-crystallization of carbamazepine and saccharin.

    PubMed

    Wang, In-Chun; Lee, Min-Jeong; Sim, Sang-Jun; Kim, Woo-Sik; Chun, Nan-Hee; Choi, Guang J

    2013-06-25

    The co-crystal approach has been investigated extensively over the past decade as one of the most promising methods to enhance the dissolution properties of insoluble drug substances. Co-crystal powders are typically produced by mechanical grinding (neat or wet) or a solution method (evaporation or cooling). In this study, high-purity carbamazepine-saccharin (CBZ-SAC) co-crystals were manufactured by a novel method, anti-solvent addition. Among various solvents, methanol was found to perform well with water as the anti-solvent for the co-crystallization of CBZ and SAC. When water was added to the methanol solution of CBZ and SAC at room temperature under agitation, nucleation of CBZ-SAC co-crystals occurred within 2-3 min. Co-crystallization was complete after 30 min, giving a solid yield as high as 84.5% on a CBZ basis. The effects of initial concentrations, focusing on the SAC/CBZ ratio, were examined to establish optimal conditions. The whole anti-solvent co-crystallization process was monitored at-line via ATR-FTIR analysis of regularly sampled solutions. The nucleation and crystal growth of CBZ-SAC co-crystals were detected by a significant increase in absorption in the range of 2400-2260 cm(-1), associated with the formation of hydrogen bonds between the carbonyl group in CBZ and the N-H of SAC. When CBZ hydrates were formed as impurities during anti-solvent co-crystallization, the hydrogen bonding between methanol and water was reduced greatly, primarily due to the incorporation of water molecules into the CBZ crystal lattice. In conclusion, an anti-solvent approach can be used to produce highly pure CBZ-SAC co-crystal powders with a high solid yield. PMID:23598078

  7. Anti-solvent co-crystallization of carbamazepine and saccharin.

    PubMed

    Wang, In-Chun; Lee, Min-Jeong; Sim, Sang-Jun; Kim, Woo-Sik; Chun, Nan-Hee; Choi, Guang J

    2013-06-25

    The co-crystal approach has been investigated extensively over the past decade as one of the most promising methods to enhance the dissolution properties of insoluble drug substances. Co-crystal powders are typically produced by mechanical grinding (neat or wet) or a solution method (evaporation or cooling). In this study, high-purity carbamazepine-saccharin (CBZ-SAC) co-crystals were manufactured by a novel method, anti-solvent addition. Among various solvents, methanol was found to perform well with water as the anti-solvent for the co-crystallization of CBZ and SAC. When water was added to the methanol solution of CBZ and SAC at room temperature under agitation, nucleation of CBZ-SAC co-crystals occurred within 2-3 min. Co-crystallization was complete after 30 min, giving a solid yield as high as 84.5% on a CBZ basis. The effects of initial concentrations, focusing on the SAC/CBZ ratio, were examined to establish optimal conditions. The whole anti-solvent co-crystallization process was monitored at-line via ATR-FTIR analysis of regularly sampled solutions. The nucleation and crystal growth of CBZ-SAC co-crystals were detected by a significant increase in absorption in the range of 2400-2260 cm(-1), associated with the formation of hydrogen bonds between the carbonyl group in CBZ and the N-H of SAC. When CBZ hydrates were formed as impurities during anti-solvent co-crystallization, the hydrogen bonding between methanol and water was reduced greatly, primarily due to the incorporation of water molecules into the CBZ crystal lattice. In conclusion, an anti-solvent approach can be used to produce highly pure CBZ-SAC co-crystal powders with a high solid yield.

  8. Acetaminophen Induces Apoptosis in Rat Cortical Neurons

    PubMed Central

    Posadas, Inmaculada; Santos, Pablo; Blanco, Almudena; Muñoz-Fernández, Maríangeles; Ceña, Valentín

    2010-01-01

    Background Acetaminophen (AAP) is widely prescribed for treatment of mild pain and fever in western countries. It is generally considered a safe drug and the most frequently reported adverse effect associated with acetaminophen is hepatotoxicity, which generally occurs after acute overdose. During AAP overdose, encephalopathy might develop and contribute to morbidity and mortality. Our hypothesis is that AAP causes direct neuronal toxicity contributing to the general AAP toxicity syndrome. Methodology/Principal Findings We report that AAP causes direct toxicity on rat cortical neurons both in vitro and in vivo as measured by LDH release. We have found that AAP causes concentration-dependent neuronal death in vitro at concentrations (1 and 2 mM) that are reached in human plasma during AAP overdose, and that are also reached in the cerebrospinal fluid of rats for 3 hours following i.p injection of AAP doses (250 and 500 mg/Kg) that are below those required to induce acute hepatic failure in rats. AAP also increases both neuronal cytochrome P450 isoform CYP2E1 enzymatic activity and protein levels as determined by Western blot, leading to neuronal death through mitochondrial–mediated mechanisms that involve cytochrome c release and caspase 3 activation. In addition, in vivo experiments show that i.p. AAP (250 and 500 mg/Kg) injection induces neuronal death in the rat cortex as measured by TUNEL, validating the in vitro data. Conclusions/Significance The data presented here establish, for the first time, a direct neurotoxic action by AAP both in vivo and in vitro in rats at doses below those required to produce hepatotoxicity and suggest that this neurotoxicity might be involved in the general toxic syndrome observed during patient APP overdose and, possibly, also when AAP doses in the upper dosing schedule are used, especially if other risk factors (moderate drinking, fasting, nutritional impairment) are present. PMID:21170329

  9. Psychophysiological effects of habitual caffeine consumption.

    PubMed

    James, J E

    1994-01-01

    Caffeine is the most widely consumed pharmacologically active substance in the world, and a key issue concerning its possible implications for human health is whether it has persistent (i.e., chronic) physiological effects on habitual consumers. This study examined blood pressure, heart rate (HR), electromyogram (EMG), and skin conductance level (SCL) in 36 healthy men and women exposed to a pattern of moderate intake. A double-blind placebo-controlled crossover design with counterbalancing was used in which all subjects participated in four experimental conditions involving the ingestion of placebo or caffeine three times daily for 6 days followed by a seventh ("challenge") day of placebo or caffeine ingestion. Results confirmed that caffeine has significant pressor effects, and these were found to he additive to the pressor action of a laboratory stressor. Following habitual consumption of the drug. pressor effects were diminished (indicative of tolerance) but not eliminated. Effects of caffeine on other parameters were either modest (HR and EMG) or negligible (SCL). Considering (he near-universal use of caffeine. the persistent pressor effects observed in this study have important implications for clinical practice and public health. PMID:16250800

  10. Environmental concentration of carbamazepine accelerates fish embryonic development and disturbs larvae behavior.

    PubMed

    Qiang, Liyuan; Cheng, Jinping; Yi, Jun; Rotchell, Jeanette M; Zhu, Xiaotong; Zhou, Junliang

    2016-09-01

    Environmental pollution caused by pharmaceuticals has been recognized as a major threat to the aquatic ecosystems. Carbamazepine, as the widely prescribed antiepileptic drug, has been frequently detected in the aquatic environment and has created concerns about its potential impacts in the aquatic organisms. The effects of carbamazepine on zebrafish embryos were studied by examining their phenotype, behavior and molecular responses. The results showed that carbamazepine disturbed the normal growth and development of exposed zebrafish embryos and larvae. Upon exposure to carbamazepine at 1 μg/L, the hatching rate, body length, swim bladder appearance and yolk sac absorption rate were significantly increased. Embryos in treatment groups were more sensitive to touch and light stimulation. At molecular level, exposure to an environmentally relevant concentration (1 μg/L) of carbamazepine disturbed the expression pattern of neural-related genes of zebrafish embryos and larvae. This study suggests that the exposure of fish embryo to antiepileptic drugs, at environmentally relevant concentrations, affects their early development and impairs their behavior. Such impacts may have future repercussions by affecting fish population structure. PMID:27386877

  11. Nonconvulsive status epilepticus precipitated by carbamazepine presenting as dissociative and affective disorders in adolescents.

    PubMed

    Marini, Carla; Parmeggiani, Lucio; Masi, Gabriele; D'Arcangelo, Gianluca; Guerrini, Renzo

    2005-08-01

    Nonconvulsive status epilepticus can be confused with psychiatric disorders. Inappropriate drug treatment can represent a precipitating factor. We describe two patients with idiopathic generalized epilepsy in whom nonconvulsive status epilepticus, aggravated by carbamazepine, was misdiagnosed as psychiatric disorder. A 14-year-old girl experienced a tonic-clonic seizure at age 12 years preceded by monthly episodes of confusion with awkward behavior since age 9 years. She was treated with carbamazepine, and the episodes of confusion became more frequent, leading to a diagnosis of dissociative disorder. An electroencephalogram during one of these episodes revealed nonconvulsive status epilepticus. Substitution of carbamazepine with valproic acid controlled the episodes of status epilepticus. A 23-year-old woman presented at age 16 years with a tonic-clonic seizure. Since early adolescence, she had had episodes of depressive mood, worsening of school performances, and facial tics. Carbamazepine treatment caused worsening of the depressive episodes and facial tics. An electroencephalogram during a typical episode revealed nonconvulsive status epilepticus. Carbamazepine substitution with valproate led to seizure freedom and behavioral improvement. Nonconvulsive status epilepticus should be suspected and searched for in patients with epileptic seizures and ictal or fluctuating behavioral disorders.

  12. Inhibitory effects of caffeine on hippocampal neurogenesis and function.

    PubMed

    Han, Myoung-Eun; Park, Kyu-Hyun; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Kim, Hak-Jin; Oh, Sae-Ock

    2007-05-18

    Caffeine is one of the most extensively consumed psychostimulants in the world. However, compared to short-term effects of caffeine, the long-term effects of caffeine consumption on learning and memory are poorly characterized. The present study found that long-term consumption of low dose caffeine (0.3 g/L) slowed hippocampus-dependent learning and impaired long-term memory. Caffeine consumption for 4 weeks also significantly reduced hippocampal neurogenesis compared to controls. From these results, we concluded that long-term consumption of caffeine could inhibit hippocampus-dependent learning and memory partially through inhibition of hippocampal neurogenesis.

  13. The effects of caffeine on the cholinergic system.

    PubMed

    Pohanka, Miroslav

    2014-01-01

    Caffeine is a secondary metabolite of tea and coffee plants. It is the active psychostimulant ingredient of widely consumed beverages, chocolate and some drugs as well. The major pathways for caffeine including interaction with adenosine receptors have been identified but caffeine has several minor pathways as well that remain poorly understood including the cholinergic system. Given the role of caffeine in the cholinergic system, some molecular targets have been tracked and a mechanism of its action has been proposed in research studies. However, the biological effect of caffeine on the cholinergic system is not completely understood. The present review focuses on the role of caffeine in the cholinergic system.

  14. [Caffeine in nutrition. Article 1. Consumption with food and regulation].

    PubMed

    Bessonov, V V; Khanferyan, R A

    2015-01-01

    The article presents a review of the literature data on the effect of caffeine contained in a variety of foods on the functions of human, it presents the modern international legal regulatory rules in the consumption of caffeine, and caffeine consumption rules corresponding to the technical regulations of the Customs Union (Russian Federation, Kazakhstan, Belaruss). It describes the sources of caffeine in the traditional diet and its consumption, safety evaluation in connection with the acute and chronic caffeine consumption and the value of caffeine as an ingredient in soft drinks tonic. PMID:26852540

  15. Determination of human pharmaceuticals in pre- and post-sewage treatment

    NASA Astrophysics Data System (ADS)

    Tahrim, Nurfaizah Abu; Abdullah, Md. Pauzi; Aziz, Yang Farina Abdul

    2013-11-01

    In this present work, an analytical method based on solid phase extraction (SPE) followed by liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS) in positive electrospray ionisation mode was successfully applied to real samples for the determination of human pharmaceuticals in pre- and post-sewage treatment samples. The ten target compounds selected in this study include acetaminophen, theophylline, caffeine, metoprolol, sulfamethoxazole, carbamazepine, prednisolone, ketoprofen, norgestrel and simvastatin. Acetaminophen, theophylline and caffeine were present at all five raw sewage samples. In addition, this work provides the first report on the investigation and detection of theophylline in sewage treatment plant (STP) samples in Malaysia.

  16. Degradation of exogenous caffeine by Populus alba and its effects on endogenous caffeine metabolism.

    PubMed

    Pierattini, Erika C; Francini, Alessandra; Raffaelli, Andrea; Sebastiani, Luca

    2016-04-01

    This is the first study reporting the presence of endogenous caffeine, theobromine, and theophylline in all organs of poplar plants. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used in order to evaluate the uptake, translocation, and metabolism of caffeine-(trimethyl-(13)C) in Populus alba L. Villafranca clone grown in hydroponic conditions. We investigated the remediation of caffeine since it is one of the most widely consumed drugs and it is frequently detected in wastewater treatment plant effluents, surface water, and groundwater worldwide. Our results demonstrated that poplar can absorb and degrade exogenous caffeine without negative effects on plant health. Data showed that concentrations of all endogenous compounds varied depending on caffeine-(trimethyl-(13)C) treatments. In particular, in control conditions, endogenous caffeine, theobromine, and theophylline were mainly distributed in roots. On the other hand, once caffeine-(trimethyl-(13)C) was provided, this compound and its dimethy-(13)C metabolites are mainly localized at leaf level. In conclusion, our results support the possible use of Villafranca clone in association with other water treatment systems in order to complete the process of caffeine remediation. PMID:26681326

  17. Degradation of exogenous caffeine by Populus alba and its effects on endogenous caffeine metabolism.

    PubMed

    Pierattini, Erika C; Francini, Alessandra; Raffaelli, Andrea; Sebastiani, Luca

    2016-04-01

    This is the first study reporting the presence of endogenous caffeine, theobromine, and theophylline in all organs of poplar plants. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used in order to evaluate the uptake, translocation, and metabolism of caffeine-(trimethyl-(13)C) in Populus alba L. Villafranca clone grown in hydroponic conditions. We investigated the remediation of caffeine since it is one of the most widely consumed drugs and it is frequently detected in wastewater treatment plant effluents, surface water, and groundwater worldwide. Our results demonstrated that poplar can absorb and degrade exogenous caffeine without negative effects on plant health. Data showed that concentrations of all endogenous compounds varied depending on caffeine-(trimethyl-(13)C) treatments. In particular, in control conditions, endogenous caffeine, theobromine, and theophylline were mainly distributed in roots. On the other hand, once caffeine-(trimethyl-(13)C) was provided, this compound and its dimethy-(13)C metabolites are mainly localized at leaf level. In conclusion, our results support the possible use of Villafranca clone in association with other water treatment systems in order to complete the process of caffeine remediation.

  18. A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States.

    PubMed

    Blieden, Marissa; Paramore, L Clark; Shah, Dhvani; Ben-Joseph, Rami

    2014-05-01

    Acetaminophen is a commonly-used analgesic in the US and, at doses of more than 4 g/day, can lead to serious hepatotoxicity. Recent FDA and CMS decisions serve to limit and monitor exposure to high-dose acetaminophen. This literature review aims to describe the exposure to and consequences of high-dose acetaminophen among chronic pain patients in the US. Each year in the US, approximately 6% of adults are prescribed acetaminophen doses of more than 4 g/day and 30,000 patients are hospitalized for acetaminophen toxicity. Up to half of acetaminophen overdoses are unintentional, largely related to opioid-acetaminophen combinations and attempts to achieve better symptom relief. Liver injury occurs in 17% of adults with unintentional acetaminophen overdose.

  19. The identification of carbamazepine biodegrading phylotypes and phylotypes sensitive to carbamazepine exposure in two soil microbial communities.

    PubMed

    Thelusmond, Jean-Rene; Strathmann, Timothy J; Cupples, Alison M

    2016-11-15

    Carbamazepine (CBZ), an antiepileptic drug, has been introduced into agricultural soils via irrigation with treated wastewater and biosolids application. Such contamination is problematic because CBZ is persistent and the risks to ecosystems or human health are unknown. The current study examined CBZ biodegradation in two agricultural soils (soil 1 and 2) and the effects on the soil microbial communities during CBZ exposure. The experimental design involved three CBZ concentrations (50, 500, 5000ng/g), under aerobic as well as anaerobic conditions. CBZ concentrations were determined using solid phase extraction and LC MS/MS. The effect of CBZ on the soil microbial community was investigated using high throughput sequencing and a computational approach to predict functional composition of the metagenomes (phylogenetic investigation of communities by reconstruction of unobserved states, PICRUSt). The most significant CBZ biodegradation occurred in soil 1 under aerobic conditions. In contrast, CBZ biodegradation was limited under anaerobic conditions in soil 1 and under both conditions in soil 2. For soil 1, several phylotypes were enriched following CBZ degradation compared to the controls, including unclassified Sphingomonadaceae, Xanthomonadaceae and Rhodobacteraceae, as well as Sphingomonas, Aquicella and Microvirga. These phylotypes are considered putative CBZ degraders as they appear to be benefiting from CBZ biodegradation. PICRUSt revealed that soil 1 contained a greater abundance of xenobiotic degrading genes compared to soil 2, and thus, this analysis method offers a potential valuable approach for predicting CBZ attenuation in soils. PICRUSt analysis also implicated Sphingomonadaceae and Xanthomonadaceae in drug metabolism. Interestingly, numerous phylotypes decreased in abundance following CBZ exposure and these varied with soil type, concentration, duration of exposure, and the availability of oxygen. For three phylotypes (Flavobacterium, 3 genus incertae

  20. Caffeine intake by patients with autosomal dominant polycystic kidney disease.

    PubMed

    Vendramini, L C; Nishiura, J L; Baxmann, A C; Heilberg, I P

    2012-09-01

    Because caffeine may induce cyst and kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD), we evaluated caffeine intake and renal volume using renal ultrasound in ADPKD patients. Caffeine intake was estimated by the average of 24-h dietary recalls obtained on 3 nonconsecutive days in 102 ADPKD patients (68 females, 34 males; 39 ± 12 years) and compared to that of 102 healthy volunteers (74 females, 28 males; 38 ± 14 years). The awareness of the need for caffeine restriction was assessed. Clinical and laboratory data were obtained from the medical records of the patients. Mean caffeine intake was significantly lower in ADPKD patients versus controls (86 vs 134 mg/day), and 63% of the ADPKD patients had been previously aware of caffeine restriction. Caffeine intake did not correlate with renal volume in ADPKD patients. There were no significant differences between the renal volumes of patients in the highest and lowest tertiles of caffeine consumption. Finally, age-adjusted multiple linear regression revealed that renal volume was associated with hypertension, chronic kidney disease stage 3 and the time since diagnosis, but not with caffeine intake. The present small cross-sectional study indicated a low level of caffeine consumption by ADPKD patients when compared to healthy volunteers, which was most likely due to prior awareness of the need for caffeine restriction. Within the range of caffeine intake observed by ADPKD patients in this study (0-471 mg/day), the renal volume was not directly associated with caffeine intake.

  1. Quantification of sewer exfiltration using the anti-epileptic drug carbamazepine as marker species for wastewater.

    PubMed

    Fenz, R; Blaschke, A P; Clara, M; Kroiss, H; Mascher, D; Zessner, M

    2005-01-01

    The anti-epileptic drug carbamazepine was used as marker species in wastewater to identify and quantify sewer exfiltration. In several studies carbamazepine turned out to be hardly removed in wastewater treatment and not or just slightly attenuated during bank infiltration. Concentrations in wastewater are generally 1000 times higher than the limit of quantification. In contrast to many other marker species a "young" drug as carbamazepine is discharged to the environment only by wastewater. The results from this study carried out in Linz, Austria indicate an average exfiltration rate, expressed as percentage of the dry weather flow that is lost on the city-wide scale, of 1%. This rate is lower than sewage losses reported in most other studies which attempted to quantify exfiltration on the basis of groundwater pollution. However, it was also possible to identify one area with significant higher sewage losses.

  2. HLA-A★3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans

    PubMed Central

    McCormack, Mark; Alfirevic, Ana; Bourgeois, Stephane; Farrell, John J.; Kasperavičiūtė, Dalia; Carrington, Mary; Sills, Graeme J.; Marson, Tony; Jia, Xiaoming; de Bakker, Paul I.W.; Chinthapalli, Krishna; Molokhia, Mariam; Johnson, Michael R.; O’Connor, Gerard D.; Chaila, Elijah; Alhusaini, Saud; Shianna, Kevin V.; Radtke, Rodney A.; Heinzen, Erin L.; Walley, Nicole; Pandolfo, Massimo; Pichler, Werner; Park, B. Kevin; Depondt, Chantal; Sisodiya, Sanjay M.; Goldstein, David B.; Deloukas, Panos; Delanty, Norman; Cavalleri, Gianpiero L.; Pirmohamed, Munir

    2011-01-01

    BACKGROUND Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B★1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations. METHODS We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3987 control subjects, all of European descent. We tested for an association between disease and HLA alleles through proxy single-nucleotide polymorphisms and imputation, confirming associations by high-resolution sequence-based HLA typing. We replicated the associations in samples from 145 subjects with carbamazepine-induced hypersensitivity reactions. RESULTS The HLA-A★3101 allele, which has a prevalence of 2 to 5% in Northern European populations, was significantly associated with the hypersensitivity syndrome (P = 3.5×10−8). An independent genomewide association study of samples from subjects with maculopapular exanthema also showed an association with the HLA-A★3101 allele (P = 1.1×10−6). Follow-up genotyping confirmed the variant as a risk factor for the hypersensitivity syndrome (odds ratio, 12.41; 95% confidence interval [CI], 1.27 to 121.03), maculopapular exanthema (odds ratio, 8.33; 95% CI, 3.59 to 19.36), and SJS–TEN (odds ratio, 25.93; 95% CI, 4.93 to 116.18). CONCLUSIONS The presence of the HLA-A★3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry. The presence of the allele increased the risk from 5.0% to 26.0%, whereas its absence reduced the risk from 5.0% to 3.8%. (Funded by the U.K. Department of Health and others.) PMID:21428769

  3. Dissolution and mechanical behaviors of recrystallized carbamazepine from alcohol solution in the presence of additives

    NASA Astrophysics Data System (ADS)

    Nokhodchi, A.; Bolourtchian, N.; Dinarvand, R.

    2005-02-01

    Carbamazepine (CBZ) crystals were grown from pure ethanol solutions containing various additives (PEG 4000, PVP K30 or Tween 80). Physical characteristics of the crystals were studied for the morphology of crystals using scanning electron microscope, for the identification of polymorphism by X-ray powder diffraction (XRPD) and FT-IR, and for thermodynamic properties using differential scanning calorimetery (DSC). The dissolution behaviour of various carbamazepine crystals was also studied by dissolution apparatus II at pH 7.4 containing 1% sodium lauryl sulphate (SLS). The scanning electron micrograph (SEM) studies showed that the presence of the additives in the solutions growth medium affected the morphology and size of carbamazepine crystals. SEMs of untreated and treated carbamazepine crystals obtained from alcohol containing PEG 4000, PVP K30 or Tween 80 showed that the crystal shape of untreated carbamazepine is flaky or thin plate-like, whereas the crystals obtained from alcohol containing no additive, PEG 4000, PVP K30 or Tween 80 are polyhedral prismatic, block-shaped, polyhedral or hexagonal, respectively. XRPD, FT-IR and DSC results showed that the untreated CBZ was form III and recrystallization of CBZ in the absence or presence of the additives did not cause any polymorphic changes. The results showed that the higher dissolution rate and compact strength were observed for the crystals obtained in the presence of PVP K30. The presence of the additives in crystallization medium alters crystal morphology of carbamazepine, but only the samples crystallized in the presence of PVP K30 showed an improvement in dissolution rate and tensile strength.

  4. Carbamazepine and naproxen: fate in wetland mesocosms planted with Scirpus validus.

    PubMed

    Zhang, Dong Qing; Hua, Tao; Gersberg, Richard M; Zhu, Junfei; Ng, Wun Jern; Tan, Soon Keat

    2013-03-01

    Scirpus validus was grown hydroponically and exposed to the pharmaceuticals, carbamazepine and naproxen at concentrations of 0.5-2.0 mg L(-1) for an exposure duration of up to 21 d. By the end of experiment, carbamazepine elimination from the nutrient solution reached to 74%, while nearly complete removal (>98%) was observed for naproxen. Photodegradation and biodegradation played only minor roles for carbamazepine elimination, while naproxen showed a high potential for both photodegradation and biodegradation. Levels of carbamazepine ranged from 3.3 to19.0 μg g(-1) (fresh weight) in the roots and 0.3-0.7 μg g(-1) (fresh weight) in the shoots, while naproxen concentrations were 0.2-2.4 μg g(-1) (fresh weight) in the roots and 0.2-2.8 μg g(-1) (fresh weight) in the shoots. Bioaccumulation factors (BAFs) for carbamazepine ranged from 5.5 to 13.0 for roots and 0.3-1.0 for shoots, and uptake by S. validus accounted for up to 22% of the total mass loss of carbamazepine in the nutrient solutions. All BAFs for naproxen were less than 4.2 and plant uptake accounted for less than 5% of the total mass loss of naproxen, implying that plant uptake was not significant in naproxen elimination. The rather limited plant uptake of naproxen was not surprising despite the fact that its log K(ow) is close to the optimal range (1.8-3.1) for maximal potential for plant uptake. Apparently, for ionizable compounds such as naproxen, the effects of pK(a) and pH partitioning might be more important than lipophilicity. PMID:23267729

  5. Neurobehavioral hazard identification and characterization for caffeine.

    PubMed

    Turnbull, Duncan; Rodricks, Joseph V; Mariano, Gregory F

    2016-02-01

    This report evaluates the scientific literature on caffeine with respect to potential central nervous system (CNS) effects, specifically effects on sleep, anxiety, and aggression/risk-taking. Caffeine has been the subject of more scientific safety studies than any other food ingredient. It is important, therefore, to evaluate new studies in the context of this large existing body of knowledge. The safety of caffeine can best be described in a narrative form, and is not usefully expressed in terms of a "bright line" numerical value like an "acceptable daily intake" (ADI). Caffeine intake has been associated with a range of reversible physiological effects, in a few studies at levels of less than 100 mg in sensitive individuals. It is also clear that many people can tolerate much greater levels - perhaps up to 600-800 mg/day or more - without experiencing such effects. The reasons for this type of variability in response are described in this report. Based on all the available evidence, there is no reason to believe that experiencing such effects from caffeine intake has any significant or lasting effect on health. The point at which caffeine intake may cause harm to the CNS is not readily identifiable, in part because data on the effects of daily intakes greater than 600 mg is limited. Effects of caffeine on risk-taking and aggressive behavior in young people have received considerable publicity, yet are the most difficult to study because of ethical concerns and limitations in the ability to design appropriate studies. At present, the weight of available evidence does not support these concerns, yet this should not preclude ongoing careful monitoring of the scientific literature.

  6. Neurobehavioral hazard identification and characterization for caffeine.

    PubMed

    Turnbull, Duncan; Rodricks, Joseph V; Mariano, Gregory F

    2016-02-01

    This report evaluates the scientific literature on caffeine with respect to potential central nervous system (CNS) effects, specifically effects on sleep, anxiety, and aggression/risk-taking. Caffeine has been the subject of more scientific safety studies than any other food ingredient. It is important, therefore, to evaluate new studies in the context of this large existing body of knowledge. The safety of caffeine can best be described in a narrative form, and is not usefully expressed in terms of a "bright line" numerical value like an "acceptable daily intake" (ADI). Caffeine intake has been associated with a range of reversible physiological effects, in a few studies at levels of less than 100 mg in sensitive individuals. It is also clear that many people can tolerate much greater levels - perhaps up to 600-800 mg/day or more - without experiencing such effects. The reasons for this type of variability in response are described in this report. Based on all the available evidence, there is no reason to believe that experiencing such effects from caffeine intake has any significant or lasting effect on health. The point at which caffeine intake may cause harm to the CNS is not readily identifiable, in part because data on the effects of daily intakes greater than 600 mg is limited. Effects of caffeine on risk-taking and aggressive behavior in young people have received considerable publicity, yet are the most difficult to study because of ethical concerns and limitations in the ability to design appropriate studies. At present, the weight of available evidence does not support these concerns, yet this should not preclude ongoing careful monitoring of the scientific literature. PMID:26702789

  7. MODULATION OF ACETAMINOPHEN-INDUCED HEPATOTOXICITY BY THE XENOBIOTIC RECEPTOR CAR

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have identified the xenobiotic receptor CAR (constitutive androstane receptor) as a key regulator of acetaminophen metabolism and hepatotoxicity. Known CAR activators as well as high doses of acetaminophen induced expression of three acetaminophen-metabolizing enzymes in wild-type but not in CAR-...

  8. Use of Arctium lappa Extract Against Acetaminophen-Induced Hepatotoxicity in Rats

    PubMed Central

    El-Kott, Attalla Farag; Bin-Meferij, Mashael Mohammed

    2015-01-01

    Background Severe destructive hepatic injuries can be induced by acetaminophen overdose and may lead to acute hepatic failure. Objective To investigate the ameliorative effects of Arctium lappa root extract on acetaminophen-induced hepatotoxicity. Methods Rats were divided into 4 groups: normal control group, Arctium lappa extract group, acetaminophen-injected group, and acetaminophen treated with Arctium lappa extract group. Results The treatment with Arctium lappa extract reduced serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase in the acetaminophen group when compared with the control group. DNA fragments in the acetaminophen-injected group were also significantly increased (P < 0.05). The comet assay revealed increased detaching tail length and DNA concentration during the hepatic toxicity in the acetaminophen group. The malondialdehyde content was inhibited by Arctium lappa treatment (12.97±0.89 nmol/mg) when compared with the acetaminophen-treated-only group (12.97±0.89 nmol/mg). Histopathologic examination revealed that acetaminophen administration produced hepatic cell necrosis, infiltrate of lymphocytes, and vacuolation that were associated with the acetaminophen-treated animal group, but the degree of acetaminophen-induced hepatotoxicity was mediated by treatment with Arctium lappa extract. Conclusions Arctium lappa can prevent most of the hepatic tissue damage caused by acetaminophen overdose in rats. PMID:26543508

  9. Caffeine's Jolt Can Sometimes Be Short-Lived

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159413.html Caffeine's Jolt Can Sometimes Be Short-Lived Stimulant effect ... 17, 2016 THURSDAY, June 16, 2016 (HealthDay News) -- Caffeine no longer improves alertness or mental performance after ...

  10. Mediterranean Diet, Caffeine May Be Good for Your Eyes

    MedlinePlus

    ... medlineplus.gov/news/fullstory_161598.html Mediterranean Diet, Caffeine May Be Good for Your Eyes Study found ... HealthDay News) -- Eating a Mediterranean diet and consuming caffeine may lower your chances of developing age-related ...

  11. Caffeine use among active duty US Army soldiers.

    PubMed

    Lieberman, Harris R; Stavinoha, Trisha; McGraw, Susan; White, Alan; Hadden, Louise; Marriott, Bernadette P

    2012-06-01

    Eighty-percent of the US adult population regularly consumes caffeine, but limited information is available on the extent and patterns of use. Caffeine use is a public health issue and its risks and benefits are regularly considered in scientific literature and the lay media. Recently, new caffeine-containing products have been introduced and are widely available on Army bases and are added to rations to maintain cognitive performance. This study surveyed caffeine consumption and demographic characteristics in 990 US Army soldiers. Data were weighted by age, sex, rank, and Special Forces status. Total caffeine intake and intake from specific products were estimated. Logistic regression was used to examine relationships between caffeine use and soldier demographic and lifestyle characteristics. Eighty-two percent of soldiers consumed caffeine at least once a week. Mean daily caffeine consumption was 285 mg/day (347 mg/day among regular caffeine consumers). Male soldiers consumed, on average, 303 mg/day and females 163 mg/day (regular consumers: 365 mg/day for male soldiers, 216 mg/day for female soldiers). Coffee was the main source of caffeine intake. Among young males, energy drinks were the largest source of caffeine intake, but their intake was not greater than older males. Regression analysis indicated an association of higher caffeine intake with male sex, white race, and tobacco use (P<0.01). Most soldiers consume caffeine in levels accepted as safe, but some consume greater quantities than recommended, although definitive information on safe upper limits of caffeine intake is not available. Labels of caffeine-containing products should provide caffeine content so individuals can make informed decisions.

  12. Caffeine use among active duty US Army soldiers.

    PubMed

    Lieberman, Harris R; Stavinoha, Trisha; McGraw, Susan; White, Alan; Hadden, Louise; Marriott, Bernadette P

    2012-06-01

    Eighty-percent of the US adult population regularly consumes caffeine, but limited information is available on the extent and patterns of use. Caffeine use is a public health issue and its risks and benefits are regularly considered in scientific literature and the lay media. Recently, new caffeine-containing products have been introduced and are widely available on Army bases and are added to rations to maintain cognitive performance. This study surveyed caffeine consumption and demographic characteristics in 990 US Army soldiers. Data were weighted by age, sex, rank, and Special Forces status. Total caffeine intake and intake from specific products were estimated. Logistic regression was used to examine relationships between caffeine use and soldier demographic and lifestyle characteristics. Eighty-two percent of soldiers consumed caffeine at least once a week. Mean daily caffeine consumption was 285 mg/day (347 mg/day among regular caffeine consumers). Male soldiers consumed, on average, 303 mg/day and females 163 mg/day (regular consumers: 365 mg/day for male soldiers, 216 mg/day for female soldiers). Coffee was the main source of caffeine intake. Among young males, energy drinks were the largest source of caffeine intake, but their intake was not greater than older males. Regression analysis indicated an association of higher caffeine intake with male sex, white race, and tobacco use (P<0.01). Most soldiers consume caffeine in levels accepted as safe, but some consume greater quantities than recommended, although definitive information on safe upper limits of caffeine intake is not available. Labels of caffeine-containing products should provide caffeine content so individuals can make informed decisions. PMID:22709816

  13. Tramadol and acetaminophen tablets for dental pain.

    PubMed Central

    Medve, R. A.; Wang, J.; Karim, R.

    2001-01-01

    The purpose of this work was to compare the efficacy and time to analgesia of a new tramadol/acetaminophen combination tablet to those of tramadol or acetaminophen (APAP) alone. A meta-analysis was performed of 3 separate single-dose, double-blind, parallel-group trials in patients with moderate or severe pain following extraction of 2 or more third molars. Patients in each study were evenly randomized to a single dose of tramadol/APAP (75 mg/650 mg), tramadol 75 mg, APAP 650 mg, ibuprofen 400 mg, or placebo. Active control with ibuprofen was used to determine model sensitivity. Pain relief (scale, 0-4) and pain intensity (scale, 0-3) were reported at 30 minutes after the dose and then hourly for 8 hours. Total pain relief over 8 hours (TOTPAR8) and the sum of pain intensity differences (SPID8) were calculated from the hourly scores. Time to onset of pain relief was determined by the double-stopwatch technique, and patients were advised to wait at least 2 hours before taking supplemental analgesia. Patients assessed overall efficacy (scale, 1-5) upon completion. In all, 1197 patients (age range, 16-46 years) were evaluable for efficacy; treatment groups in each study were similar at baseline. Pain relief was superior to placebo (P < or = .0001) for all treatments. Pain relief provided by tramadol/ APAP was superior to that of tramadol or APAP alone, as shown by mean TOT-PAR8 (12.1 vs 6.7 and 8.6, respectively, P < or = .0001) and SPID8 (4.7 vs 0.9 and 2.7, respectively, P < or = .0001). Estimated onset of pain relief was 17 minutes (95% CI, 15-20 minutes) for tramadol/APAP compared with 51 minutes (95% CI, 40-70 minutes) for tramadol, 18 minutes (95% CI, 16-21 minutes) for APAP, and 34 minutes (95% CI, 28-44 minutes) for ibuprofen. Median time to supplemental analgesia and mean overall assessment of efficacy were greater (P < .05) for the tramadol/APAP group (302 minutes and 3.0, respectively) than for the tramadol (122 minutes and 2.0) or APAP (183 minutes and 2

  14. The effect of moderate hemodilution with fluosol-DA or normal saline on acetaminophen disposition in the rat.

    PubMed

    Shrewsbury, R P; White, L G

    1990-02-15

    Hemodilution with 40 ml/kg of Fluosol or saline reduced the acetaminophen Vd and the acetaminophen sulfate ClM at 48 or 72 h, respectively. Fluosol hemodilution increased the acetaminophen renal excretion at 24 and 72 h. But at 48 h, Fluosol hemodilution either inhibited the renal secretion of acetaminophen or enhanced its reabsorption.

  15. Caffeine Taste Signaling in Drosophila Larvae

    PubMed Central

    Apostolopoulou, Anthi A.; Köhn, Saskia; Stehle, Bernhard; Lutz, Michael; Wüst, Alexander; Mazija, Lorena; Rist, Anna; Galizia, C. Giovanni; Lüdke, Alja; Thum, Andreas S.

    2016-01-01

    The Drosophila larva has a simple peripheral nervous system with a comparably small number of sensory neurons located externally at the head or internally along the pharynx to assess its chemical environment. It is assumed that larval taste coding occurs mainly via external organs (the dorsal, terminal, and ventral organ). However, the contribution of the internal pharyngeal sensory organs has not been explored. Here we find that larvae require a single pharyngeal gustatory receptor neuron pair called D1, which is located in the dorsal pharyngeal sensilla, in order to avoid caffeine and to associate an odor with caffeine punishment. In contrast, caffeine-driven reduction in feeding in non-choice situations does not require D1. Hence, this work provides data on taste coding via different receptor neurons, depending on the behavioral context. Furthermore, we show that the larval pharyngeal system is involved in bitter tasting. Using ectopic expressions, we show that the caffeine receptor in neuron D1 requires the function of at least four receptor genes: the putative co-receptors Gr33a, Gr66a, the putative caffeine-specific receptor Gr93a, and yet unknown additional molecular component(s). This suggests that larval taste perception is more complex than previously assumed already at the sensory level. Taste information from different sensory organs located outside at the head or inside along the pharynx of the larva is assembled to trigger taste guided behaviors. PMID:27555807

  16. Caffeine Taste Signaling in Drosophila Larvae.

    PubMed

    Apostolopoulou, Anthi A; Köhn, Saskia; Stehle, Bernhard; Lutz, Michael; Wüst, Alexander; Mazija, Lorena; Rist, Anna; Galizia, C Giovanni; Lüdke, Alja; Thum, Andreas S

    2016-01-01

    The Drosophila larva has a simple peripheral nervous system with a comparably small number of sensory neurons located externally at the head or internally along the pharynx to assess its chemical environment. It is assumed that larval taste coding occurs mainly via external organs (the dorsal, terminal, and ventral organ). However, the contribution of the internal pharyngeal sensory organs has not been explored. Here we find that larvae require a single pharyngeal gustatory receptor neuron pair called D1, which is located in the dorsal pharyngeal sensilla, in order to avoid caffeine and to associate an odor with caffeine punishment. In contrast, caffeine-driven reduction in feeding in non-choice situations does not require D1. Hence, this work provides data on taste coding via different receptor neurons, depending on the behavioral context. Furthermore, we show that the larval pharyngeal system is involved in bitter tasting. Using ectopic expressions, we show that the caffeine receptor in neuron D1 requires the function of at least four receptor genes: the putative co-receptors Gr33a, Gr66a, the putative caffeine-specific receptor Gr93a, and yet unknown additional molecular component(s). This suggests that larval taste perception is more complex than previously assumed already at the sensory level. Taste information from different sensory organs located outside at the head or inside along the pharynx of the larva is assembled to trigger taste guided behaviors.

  17. Caffeine accelerates recovery from general anesthesia.

    PubMed

    Wang, Qiang; Fong, Robert; Mason, Peggy; Fox, Aaron P; Xie, Zheng

    2014-03-01

    General anesthetics inhibit neurotransmitter release from both neurons and secretory cells. If inhibition of neurotransmitter release is part of an anesthetic mechanism of action, then drugs that facilitate neurotransmitter release may aid in reversing general anesthesia. Drugs that elevate intracellular cAMP levels are known to facilitate neurotransmitter release. Three cAMP elevating drugs (forskolin, theophylline, and caffeine) were tested; all three drugs reversed the inhibition of neurotransmitter release produced by isoflurane in PC12 cells in vitro. The drugs were tested in isoflurane-anesthetized rats. Animals were injected with either saline or saline containing drug. All three drugs dramatically accelerated recovery from isoflurane anesthesia, but caffeine was most effective. None of the drugs, at the concentrations tested, had significant effects on breathing rates, O2 saturation, heart rate, or blood pressure in anesthetized animals. Caffeine alone was tested on propofol-anesthetized rats where it dramatically accelerated recovery from anesthesia. The ability of caffeine to accelerate recovery from anesthesia for different chemical classes of anesthetics, isoflurane and propofol, opens the possibility that it will do so for all commonly used general anesthetics, although additional studies will be required to determine whether this is in fact the case. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in human patients. PMID:24375022

  18. Caffeine use in sports. A pharmacological review.

    PubMed

    Sinclair, C J; Geiger, J D

    2000-03-01

    Caffeine is the most widely ingested psychoactive drug in the world. As many know, chronic use of caffeine leads to dependence, tolerance, drug craving, and upon abrupt cessation unpleasant withdrawal symptoms. Thus, caffeine fulfills pharmacological criteria by which agents are classified as drugs of abuse. Nevertheless, its use is legal and only at high, but readily attainable, levels is it banned from sport. Its use is widespread by athletes as young as 11 years of age who are seeking athletic advantage over fellow competitors. It is likely that its use will not decline any time soon because it is inexpensive, readily available, medically quite safe, socially acceptable, and by most measures legal. However, at levels allowed in sport, caffeine through its wide-ranging physiological and psychological effects increases endurance in well-trained athletes. If the goal of drug-testing and education programs in sport is to protect the health of athletes, prevent unfair advantage (cheating) and encourage ethical behavior then it seems obvious that the allowable levels of caffeine ingestion should be decreased. The alternative is to continue with policies designed largely to punish only those that get caught.

  19. Caffeine accelerates recovery from general anesthesia.

    PubMed

    Wang, Qiang; Fong, Robert; Mason, Peggy; Fox, Aaron P; Xie, Zheng

    2014-03-01

    General anesthetics inhibit neurotransmitter release from both neurons and secretory cells. If inhibition of neurotransmitter release is part of an anesthetic mechanism of action, then drugs that facilitate neurotransmitter release may aid in reversing general anesthesia. Drugs that elevate intracellular cAMP levels are known to facilitate neurotransmitter release. Three cAMP elevating drugs (forskolin, theophylline, and caffeine) were tested; all three drugs reversed the inhibition of neurotransmitter release produced by isoflurane in PC12 cells in vitro. The drugs were tested in isoflurane-anesthetized rats. Animals were injected with either saline or saline containing drug. All three drugs dramatically accelerated recovery from isoflurane anesthesia, but caffeine was most effective. None of the drugs, at the concentrations tested, had significant effects on breathing rates, O2 saturation, heart rate, or blood pressure in anesthetized animals. Caffeine alone was tested on propofol-anesthetized rats where it dramatically accelerated recovery from anesthesia. The ability of caffeine to accelerate recovery from anesthesia for different chemical classes of anesthetics, isoflurane and propofol, opens the possibility that it will do so for all commonly used general anesthetics, although additional studies will be required to determine whether this is in fact the case. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in human patients.

  20. Caffeine Taste Signaling in Drosophila Larvae.

    PubMed

    Apostolopoulou, Anthi A; Köhn, Saskia; Stehle, Bernhard; Lutz, Michael; Wüst, Alexander; Mazija, Lorena; Rist, Anna; Galizia, C Giovanni; Lüdke, Alja; Thum, Andreas S

    2016-01-01

    The Drosophila larva has a simple peripheral nervous system with a comparably small number of sensory neurons located externally at the head or internally along the pharynx to assess its chemical environment. It is assumed that larval taste coding occurs mainly via external organs (the dorsal, terminal, and ventral organ). However, the contribution of the internal pharyngeal sensory organs has not been explored. Here we find that larvae require a single pharyngeal gustatory receptor neuron pair called D1, which is located in the dorsal pharyngeal sensilla, in order to avoid caffeine and to associate an odor with caffeine punishment. In contrast, caffeine-driven reduction in feeding in non-choice situations does not require D1. Hence, this work provides data on taste coding via different receptor neurons, depending on the behavioral context. Furthermore, we show that the larval pharyngeal system is involved in bitter tasting. Using ectopic expressions, we show that the caffeine receptor in neuron D1 requires the function of at least four receptor genes: the putative co-receptors Gr33a, Gr66a, the putative caffeine-specific receptor Gr93a, and yet unknown additional molecular component(s). This suggests that larval taste perception is more complex than previously assumed already at the sensory level. Taste information from different sensory organs located outside at the head or inside along the pharynx of the larva is assembled to trigger taste guided behaviors. PMID:27555807

  1. Luminescence characteristics of caffeine and theophylline1

    NASA Astrophysics Data System (ADS)

    Andino, M. M.; De Lima, C. G.; Winefordner, J. D.

    The luminescence properties of solutions of caffeine and theophylline in methanol are observed. The effects of the solvent pH, the presence of a heavy atom and the matrix or substrate on the fluorescence and phosphorescence properties of the compounds are evaluated. Caffeine and theophylline fluorescence can be observed at room temperature from dilute methanolic solutions and strong phosphorescence is observed at low temperature when the matrix is in a polycrystalline state. Acidic and basic media cause spectral changes and reduce the intensity of the low temperature phosphorescence. Iodide is a good heavy-atom enhancer of both the low temperature and room temperature phosphorescence of caffeine and theophylline. The intensity of the phosphorescence at room temperature and when spotted on filter paper depends on the type of filter paper and the pH of the spotting solution and/or the pH of the wet surface at the moment of spotting. Theophylline is more sensitive than caffeine to the microenvironment. Under the appropriate experimental conditions, both low temperature and room temperature phosphorescence could be used as analytical tools for the determination of caffeine and theophylline.

  2. Is caffeine consumption a risk factor for osteoporosis?

    PubMed

    Cooper, C; Atkinson, E J; Wahner, H W; O'Fallon, W M; Riggs, B L; Judd, H L; Melton, L J

    1992-04-01

    High caffeine consumption has been proposed as a risk factor for osteoporotic fracture, but the evidence associating high caffeine intake with low bone density is inconsistent. We therefore examined the influence of caffeine consumption on bone mineral at six skeletal sites in an age-stratified random sample of white women residing in Rochester, Minnesota. After age adjustment, there was no association between overall caffeine consumption and bone mineral at five of the six sites. In the femoral shaft, however, there was a statistically significant interaction between age and caffeine consumption so that high caffeine intake was associated with slight reductions in bone mineral among elderly subjects but with modestly increased bone mineral at younger ages. When caffeine intake was categorized by source, no consistent influence of coffee, tea, or other caffeinated beverage consumption could be detected on bone mineral. Caffeine intake was, however, positively associated with cigarette smoking and alcohol consumption. After adjusting for age, caffeine consumption was not correlated with biochemical indices of bone turnover, circulating concentrations of estradiol and estrone, or other dietary and musculoskeletal variables. These data suggest that caffeine intake in the range consumed by a representative sample of white women is not an important risk factor for osteoporosis. Among elderly women, however, in whom calcium balance performance is impaired, high caffeine intake may predispose to cortical bone loss from the proximal femur.

  3. Caffeine Consumption Patterns and Beliefs of College Freshmen

    ERIC Educational Resources Information Center

    McIlvain, Gary E.; Noland, Melody P.; Bickel, Robert

    2011-01-01

    Background: Caffeine consumption by young people has increased dramatically over the last decade through increased coffee consumption and "energy drinks." In higher amounts, caffeine causes many adverse effects that are cause for concern. Purpose: Purposes of this study were to determine: (1) the amount of caffeine consumed by a sample of college…

  4. Caffeine Use Disorder: A Comprehensive Review and Research Agenda.

    PubMed

    Meredith, Steven E; Juliano, Laura M; Hughes, John R; Griffiths, Roland R

    2013-09-01

    Caffeine is the most commonly used drug in the world. Although consumption of low to moderate doses of caffeine is generally safe, an increasing number of clinical studies are showing that some caffeine users become dependent on the drug and are unable to reduce consumption despite knowledge of recurrent health problems associated with continued use. Thus, the World Health Organization and some health care professionals recognize caffeine dependence as a clinical disorder. In this comprehensive literature review, we summarize published research on the biological evidence for caffeine dependence; we provide a systematic review of the prevalence of caffeine dependence and rates of endorsement of clinically meaningful indicators of distress and functional impairment among habitual caffeine users; we discuss the diagnostic criteria for Caffeine Use Disorder-a condition for further study included in the Diagnostic and Statistical Manual of Mental Disorders (5(th) ed.); and we outline a research agenda to help guide future clinical, epidemiological, and genetic investigations of caffeine dependence. Numerous controlled laboratory investigations reviewed in this article show that caffeine produces behavioral and physiological effects similar to other drugs of dependence. Moreover, several recent clinical studies indicate that caffeine dependence is a clinically meaningful disorder that affects a nontrivial proportion of caffeine users. Nevertheless, more research is needed to determine the reliability, validity, and prevalence of this clinically important health problem. PMID:24761279

  5. Beverage caffeine intakes in the U.S.

    PubMed

    Mitchell, Diane C; Knight, Carol A; Hockenberry, Jon; Teplansky, Robyn; Hartman, Terryl J

    2014-01-01

    Caffeine is one of the most researched food components, with the vast majority of dietary contributions coming from beverage consumption; however, there is little population-level data on caffeine intakes in the U.S. This study estimated the caffeine intakes of the U.S. population using a comprehensive beverage survey, the Kantar Worldpanel Beverage Consumption Panel. A nationally representative sample of 37,602 consumers (aged ≥ 2 years) of caffeinated beverages completed 7-day diaries which facilitated the development of a detailed database of caffeine values to assess intakes. Results showed that 85% of the U.S. population consumes at least one caffeinated beverage per day. The mean (±SE) daily caffeine intake from all beverages was 165±1 mg for all ages combined. Caffeine intake was highest in consumers aged 50-64 years (226±2 mg/day). The 90th percentile intake was 380 mg/day for all ages combined. Coffee was the primary contributor to caffeine intakes in all age groups. Carbonated soft drinks and tea provided a greater percentage of caffeine in the younger (<18 years) age groups. The percentage of energy drink consumers across all age groups was low (≤10%). These data provide a current perspective on caffeinated beverage consumption patterns and caffeine intakes in the U.S. population.

  6. Caffeine Use Disorder: A Comprehensive Review and Research Agenda

    PubMed Central

    Meredith, Steven E.; Juliano, Laura M.; Hughes, John R.

    2013-01-01

    Caffeine is the most commonly used drug in the world. Although consumption of low to moderate doses of caffeine is generally safe, an increasing number of clinical studies are showing that some caffeine users become dependent on the drug and are unable to reduce consumption despite knowledge of recurrent health problems associated with continued use. Thus, the World Health Organization and some health care professionals recognize caffeine dependence as a clinical disorder. In this comprehensive literature review, we summarize published research on the biological evidence for caffeine dependence; we provide a systematic review of the prevalence of caffeine dependence and rates of endorsement of clinically meaningful indicators of distress and functional impairment among habitual caffeine users; we discuss the diagnostic criteria for Caffeine Use Disorder—a condition for further study included in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.); and we outline a research agenda to help guide future clinical, epidemiological, and genetic investigations of caffeine dependence. Numerous controlled laboratory investigations reviewed in this article show that caffeine produces behavioral and physiological effects similar to other drugs of dependence. Moreover, several recent clinical studies indicate that caffeine dependence is a clinically meaningful disorder that affects a nontrivial proportion of caffeine users. Nevertheless, more research is needed to determine the reliability, validity, and prevalence of this clinically important health problem. PMID:24761279

  7. Caffeine as a flavor additive in soft-drinks.

    PubMed

    Keast, Russell S J; Riddell, Lynnette J

    2007-07-01

    Over 60% of soft-drinks sold in the United States contain caffeine, a mildly addictive psycho-active chemical, as a flavor additive. Using sweeteners as controls, we assessed whether caffeine has flavor activity in a cola soft-drink. A forced-choice triangle discrimination methodology was used to determine detection thresholds of caffeine in sweeteners and a cola beverage. The subjects (n=30, 28 female, 23+/-4 years old) were trained tasters and completed over 1600 discrimination tests during the study. The mean detection thresholds for caffeine in the sweet solutions were: 0.333+/-0.1mM sucrose; 0.467+/-0.29 mM aspartame; 0.462+/-0.3mM sucralose, well below the concentration in common cola beverages (0.55-0.67 mM). A fixed concentration of caffeine, corresponding to the concentration of caffeine in a common cola beverage (0.67 mM) was added to the sweeteners and a non-caffeinated cola beverage. Subjects could distinguish between caffeinated and non-caffeinated sweeteners (p<0.001), but all subjects failed to distinguish between caffeinated and non-caffeinated cola beverage (p=1.0). Caffeine has no flavor activity in soft-drinks yet will induce a physiologic and psychologic desire to consume the drink.

  8. Caffeine levels in beverages from Argentina's market: application to caffeine dietary intake assessment.

    PubMed

    Olmos, V; Bardoni, N; Ridolfi, A S; Villaamil Lepori, E C

    2009-03-01

    The caffeine content of different beverages from Argentina's market was measured. Several brands of coffees, teas, mates, chocolate milks, soft and energy drinks were analysed by high-performance liquid chromatography (HPLC) with ultraviolet detection. The highest concentration level was found in short coffee (1.38 mg ml(-1)) and the highest amount per serving was found in instant coffee (95 mg per serving). A consumption study was also carried out among 471 people from 2 to 93 years of age to evaluate caffeine total dietary intake by age and to identify the sources of caffeine intake. The mean caffeine intake among adults was 288 mg day(-1) and mate was the main contributor to that intake. The mean caffeine intake among children of 10 years of age and under was 35 mg day(-1) and soft drinks were the major contributors to that intake. Children between 11 and 15 years old and teenagers (between 16 and 20 years) had caffeine mean intakes of 120 and 240 mg day(-1), respectively, and mate was the major contributor to those intakes. Drinking mate is a deep-rooted habit among Argentine people and it might be the reason for their elevated caffeine mean daily intake.

  9. Associations of ambulatory blood pressure with urinary caffeine and caffeine metabolite excretions.

    PubMed

    Guessous, Idris; Pruijm, Menno; Ponte, Belén; Ackermann, Daniel; Ehret, Georg; Ansermot, Nicolas; Vuistiner, Philippe; Staessen, Jan; Gu, Yumei; Paccaud, Fred; Mohaupt, Markus; Vogt, Bruno; Pechère-Bertschi, Antoinette; Pechère-Berstchi, Antoinette; Martin, Pierre-Yves; Burnier, Michel; Eap, Chin B; Bochud, Murielle

    2015-03-01

    Intake of caffeinated beverages might be associated with reduced cardiovascular mortality possibly via the lowering of blood pressure. We estimated the association of ambulatory blood pressure with urinary caffeine and caffeine metabolites in a population-based sample. Families were randomly selected from the general population of Swiss cities. Ambulatory blood pressure monitoring was conducted using validated devices. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24 hours urine using ultrahigh performance liquid chromatography tandem mass spectrometry. We used mixed models to explore the associations of urinary excretions with blood pressure although adjusting for major confounders. The 836 participants (48.9% men) included in this analysis had mean age of 47.8 and mean 24-hour systolic and diastolic blood pressure of 120.1 and 78.0 mm Hg. For each doubling of caffeine excretion, 24-hour and night-time systolic blood pressure decreased by 0.642 and 1.107 mm Hg (both P values <0.040). Similar inverse associations were observed for paraxanthine and theophylline. Adjusted night-time systolic blood pressure in the first (lowest), second, third, and fourth (highest) quartile of paraxanthine urinary excretions were 110.3, 107.3, 107.3, and 105.1 mm Hg, respectively (P trend <0.05). No associations of urinary excretions with diastolic blood pressure were generally found, and theobromine excretion was not associated with blood pressure. Anti-hypertensive therapy, diabetes mellitus, and alcohol consumption modify the association of caffeine urinary excretion with systolic blood pressure. Ambulatory systolic blood pressure was inversely associated with urinary excretions of caffeine and other caffeine metabolites. Our results are compatible with a potential protective effect of caffeine on blood pressure. PMID:25489060

  10. Associations of ambulatory blood pressure with urinary caffeine and caffeine metabolite excretions.

    PubMed

    Guessous, Idris; Pruijm, Menno; Ponte, Belén; Ackermann, Daniel; Ehret, Georg; Ansermot, Nicolas; Vuistiner, Philippe; Staessen, Jan; Gu, Yumei; Paccaud, Fred; Mohaupt, Markus; Vogt, Bruno; Pechère-Bertschi, Antoinette; Pechère-Berstchi, Antoinette; Martin, Pierre-Yves; Burnier, Michel; Eap, Chin B; Bochud, Murielle

    2015-03-01

    Intake of caffeinated beverages might be associated with reduced cardiovascular mortality possibly via the lowering of blood pressure. We estimated the association of ambulatory blood pressure with urinary caffeine and caffeine metabolites in a population-based sample. Families were randomly selected from the general population of Swiss cities. Ambulatory blood pressure monitoring was conducted using validated devices. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24 hours urine using ultrahigh performance liquid chromatography tandem mass spectrometry. We used mixed models to explore the associations of urinary excretions with blood pressure although adjusting for major confounders. The 836 participants (48.9% men) included in this analysis had mean age of 47.8 and mean 24-hour systolic and diastolic blood pressure of 120.1 and 78.0 mm Hg. For each doubling of caffeine excretion, 24-hour and night-time systolic blood pressure decreased by 0.642 and 1.107 mm Hg (both P values <0.040). Similar inverse associations were observed for paraxanthine and theophylline. Adjusted night-time systolic blood pressure in the first (lowest), second, third, and fourth (highest) quartile of paraxanthine urinary excretions were 110.3, 107.3, 107.3, and 105.1 mm Hg, respectively (P trend <0.05). No associations of urinary excretions with diastolic blood pressure were generally found, and theobromine excretion was not associated with blood pressure. Anti-hypertensive therapy, diabetes mellitus, and alcohol consumption modify the association of caffeine urinary excretion with systolic blood pressure. Ambulatory systolic blood pressure was inversely associated with urinary excretions of caffeine and other caffeine metabolites. Our results are compatible with a potential protective effect of caffeine on blood pressure.

  11. Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update.

    PubMed

    Yoon, Eric; Babar, Arooj; Choudhary, Moaz; Kutner, Matthew; Pyrsopoulos, Nikolaos

    2016-06-28

    Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes. APAP hepatotoxicity remains a global issue; in the United States, in particular, it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases. The pathophysiology, disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated, and adverse patient outcomes with increased morbidity and mortality continue to occur. Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients. Future research focus in this field may benefit from shifting towards obtaining antidotal knowledge at the molecular level, with focus on the underlying molecular signaling pathways. PMID:27350943

  12. Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update

    PubMed Central

    Yoon, Eric; Babar, Arooj; Choudhary, Moaz; Kutner, Matthew; Pyrsopoulos, Nikolaos

    2016-01-01

    Abstract Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes. APAP hepatotoxicity remains a global issue; in the United States, in particular, it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases. The pathophysiology, disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated, and adverse patient outcomes with increased morbidity and mortality continue to occur. Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients. Future research focus in this field may benefit from shifting towards obtaining antidotal knowledge at the molecular level, with focus on the underlying molecular signaling pathways. PMID:27350943

  13. Plastic and glassy crystal states of caffeine.

    PubMed

    Descamps, Marc; Correia, Natalia T; Derollez, Patrick; Danede, Florence; Capet, Frédéric

    2005-08-25

    The present paper focuses on the high temperature form I of caffeine and on its low temperature metastable form. Structural, dynamic, and kinetic information has been obtained by X-ray, dielectric, and calorimetric investigations. This study shows the following features: (1) The high temperature phase (I) of caffeine is in a state of dynamically orientationally disordered crystalline state (so-called "plastic, or rotator, phase"). (2) This high-symmetry hexagonal phase can be maintained at low temperature in a metastable situation. (3) Under deep undercooling of form I a glass transition occurs in the disordered crystalline state near room temperature. It is associated with the orientational freezing in of the molecular motions. Otherwise stated, the metastable state I enters into a nonergodic unstable state, so-called "glassy crystal" state. These findings rationalize the difficulties seen with caffeine in pharmaceutical science.

  14. Xenobiotics and Autoimmunity: Does Acetaminophen Cause Primary Biliary Cirrhosis?

    PubMed Central

    Leung, Patrick S.C.; Lam, Kit; Kurth, Mark J.; Coppel, Ross L.; Gershwin, M. Eric

    2012-01-01

    The serologic hallmark of primary biliary cirrhosis (PBC) is the presence of antimitochondrial autoantibodies (AMA) directed against the E2 subunit of PDC-E2. The PBC-related autoepitope of PDC-E2 contains lipoic acid, and previous work has demonstrated that mimics of lipoic acid following immunization of mice lead to a PBC-like disease. Furthermore, approximately one third of patients who have ingested excessive amounts of acetaminophen (paracetamol) develop AMA of the same specificity as patients with PBC. Quantitative structure-activity relationship (QSAR) data indicates that acetaminophen metabolites are particularly immunoreactive with AMA, and we submit that in genetically susceptible hosts, electrophilic modification of lipoic acid in PDC-E2 by acetaminophen or similar drugs can facilitate a loss of tolerance and lead to the development of PBC. PMID:22920894

  15. Acetylsalicylic acid and acetaminophen protect against oxidative neurotoxicity.

    PubMed

    Maharaj, H; Maharaj, D S; Daya, S

    2006-09-01

    Due to the implication of oxidative stress in neurodegenerative disorders we decided to investigate the antioxidant properties of acetylsalicylic acid and acetaminophen either alone or in combination. The thiobarbituric acid assay (TBA) and the nitroblue tetrazolium (NBT) assay were used to investigate quinolinic acid (QA)-induced: lipid peroxidation and superoxide anion generation in the rat hippocampus, in vivo. The study also shows, using cresyl violet staining, the preservation of structural integrity of neuronal cells following treatment with acetylsalicylic acid and acetaminophen in QA-lesioned rat hippocampus. Furthermore the study sought to determine whether these agents have any effect on endogenous (QA) formation. This study shows that acetylsalicylic acid and acetaminophen inhibit QA-induced superoxide anion generation, lipid peroxidation and cell damage, in vivo, in the rat hippocampus. In addition these agents inhibit the enzyme, 3-hydroxyanthranilic acid oxygenase (3-HAO), responsible for the synthesis of endogenous QA.

  16. Fate of caffeine in mesocosms wetland planted with Scirpus validus.

    PubMed

    Zhang, Dong Qing; Hua, Tao; Gersberg, Richard M; Zhu, Junfei; Ng, Wun Jern; Tan, Soon Keat

    2013-01-01

    Uptake, accumulation and translocation of caffeine by Scirpus validus grown in hydroponic condition were investigated. The plants were cultivated in Hoagland's nutrient solution spiked with caffeine at concentrations of 0.5-2.0 mg L(-1). The effect of photodegradation on caffeine elimination was determined in dark controls and proved to be negligible. Removal of caffeine in mesocosms without plants showed however that biodegradation could account for about 15-19% of the caffeine lost from solutions after 3 and 7 d. Plant uptake played a significant role in caffeine elimination. Caffeine was detected in both roots and shoots of S. validus. Root concentrations of caffeine were 0.1-6.1 μg g(-1), while the concentrations for shoots were 6.4-13.7 μg g(-1). A significant (p<0.05) positive correlation between the concentration in the root and the initial concentrations in the nutrient solution was observed. The bioaccumulation factors (BAFs) of caffeine for roots ranged from 0.2 to 3.1, while BAFs for shoots ranged from 3.2 to 16.9. Translocation from roots to shoots was the major pathway of shoot accumulation. The fraction of caffeine in the roots as a percentage of the total caffeine mass in solution was limited to 0.2-4.4% throughout the whole experiment, while shoot uptake percentage ranged from 12% to 25% for caffeine at the initial concentration of 2.0 mg L(-1) to 50-62% for caffeine at the initial concentration of 0.5 mg L(-1). However, a marked decrease in the concentration of caffeine in the shoots between d-14 and d-21 suggests that caffeine may have been catabolized in the plant tissues subsequent to plant uptake and translocation.

  17. Caffeine and coffee as therapeutics against Alzheimer's disease.

    PubMed

    Arendash, Gary W; Cao, Chuanhai

    2010-01-01

    Epidemiologic studies have increasingly suggested that caffeine/coffee could be an effective therapeutic against Alzheimer's disease (AD). We have utilized a transgenic mouse model for AD in well-controlled studies to determine if caffeine and/or coffee have beneficial actions to protect against or reverse AD-like cognitive impairment and AD pathology. AD mice given caffeine in their drinking water from young adulthood into older age showed protection against memory impairment and lower brain levels of the abnormal protein (amyloid-beta; Abeta) thought to be central to AD pathogenesis. Moreover, "aged" cognitively-impaired AD mice exhibited memory restoration and lower brain Abeta levels following only 1-2 months of caffeine treatment. We believe that the cognitive benefits of chronic caffeine administration in AD mice are due to caffeine itself, and not metabolites of caffeine; this, because our long-term administration of theophylline to AD mice provided no cognitive benefits. In acute studies involving AD mice, one oral caffeine treatment quickly reduced both brain and plasma Abeta levels - similarly rapid alterations in plasma Abeta levels were seen in humans following acute caffeine administration. "Caffeinated" coffee provided to AD mice also quickly decreased plasma Abeta levels, but not "decaffeinated" coffee, suggesting that caffeine is critical to decreasing blood Abeta levels. Caffeine appears to provide its disease-modifying effects through multiple mechanisms, including a direct reduction of Abeta production through suppression of both beta- and gamma-secretase levels. These results indicate a surprising ability of moderate caffeine intake (the human equivalent of 500 mg caffeine or 5 cups of coffee per day) to protect against or treat AD in a mouse model for the disease and a therapeutic potential for caffeine against AD in humans.

  18. Mobility of pharmaceuticals carbamazepine, diclofenac, ibuprofen, and propyphenazone in miscible-displacement experiments

    NASA Astrophysics Data System (ADS)

    Scheytt, Traugott J.; Mersmann, Petra; Heberer, Thomas

    2006-02-01

    Many pharmaceuticals pass the unsaturated zone before reaching an aquifer. Therefore, laboratory sand column transport experiments were conducted to study the transport behavior of carbamazepine, diclofenac, ibuprofen, and propyphenazone under unsaturated conditions. The test water was artificial sewage effluent to simulate the infiltration of reused wastewater. The test water was spiked with the pharmaceutically active compounds and the tracer LiCl. Afterwards it was passed through laboratory sand columns, one experiment for each pharmaceutical. The physical and chemical parameters were recorded and general ions measured. Pharmaceuticals were measured using solid phase extraction, derivatization, and detection with GC-MS. The column experiments indicate a significant elimination of ibuprofen (54%), propyphenazone (55%), and diclofenac (35%), whereas carbamazepine was not eliminated. Retardation factors varied between 1.84 for carbamazepine, 2.51 for propyphenazone, 3.00 for ibuprofen, and 4.80 for diclofenac. These results show that mobility and elimination of diclofenac, ibuprofen, and propyphenazone is about in the same range as for experiments under saturated conditions whereas carbamazepine had a significantly lower sorption and elimination under unsaturated conditions.

  19. Genetic screening for human leukocyte antigen alleles prior to carbamazepine treatment.

    PubMed

    Tan, Jeremy C K; Murrell, Dedee F; Hersch, Mark I

    2015-12-01

    We describe a 28-year-old Malaysian Australian man of Han Chinese descent with toxic epidermal necrolysis (TEN), occurring 2 weeks after commencing carbamazepine. He was subsequently found to be positive for human leukocyte antigen (HLA)-B*1502. Carbamazepine-induced Stevens-Johnson syndrome/TEN is strongly associated with the HLA-B*1502 allele, which is highly prevalent in Han Chinese, Malay, Thai and Indian populations. Prospective screening for the allele may prevent this cutaneous adverse drug reaction from occurring, but many neurologists and other medical practitioners are still unaware of the medico-legal risks of prescribing carbamazepine in susceptible populations and the availability of HLA-B*1502 testing. Performing HLA-B*1502 genotyping and avoiding carbamazepine in at-risk individuals has been proven to decrease incidences of drug-induced TEN. This test is widely available at most large pathology services in Australia, with results available within 2 weeks. The recommendation by regulatory bodies should be strengthened to ensure that the broad medical community is made more aware of this pertinent issue.

  20. Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

    PubMed Central

    Govindasamy, Parthasarathy; Kesavan, Bhaskar Reddy; Narasimha, Jayaveera Korlakunta

    2013-01-01

    Objective To achieve transbuccal release of carbamazepine by loading in unidirectional release mucoadhesive buccal patches. Methods Buccal patches of carbamazepine with unidirectional drug release were prepared using hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and ethyl cellulose by solvent casting method. Water impermeable backing layer (Pidilite® Biaxially-oriented polypropylene film) of patches provided unidirectional drug release. They were evaluated for thickness, mass uniformity, surface pH and folding endurance. Six formulations FA2, FA8, FA10, FB1, FB14 and FB16 (folding endurance above 250) were evaluated further for swelling studies, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, ex vivo permeation, accelerated stability studies and FTIR and XRD spectral studies. Results The ex vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 kg/m/s. The in vitro drug release studies revealed that formulation FA8 released 84% and FB16 released 99.01% of drug in 140 min. Conclusions The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic delivery of carbamazepine. PMID:24093793

  1. Caffeine inhibits acetylcholinesterase, but not butyrylcholinesterase.

    PubMed

    Pohanka, Miroslav; Dobes, Petr

    2013-05-08

    Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE) and/or, butyrylcholinesterase (BChE), the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon's plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, Ki, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as Ki was found to be 175 ± 9 µmol/L. The predicted free energy of binding was -6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed.

  2. Patient perception and knowledge of acetaminophen in a large family medicine service.

    PubMed

    Herndon, Christopher M; Dankenbring, Dawn M

    2014-06-01

    The use of acetaminophen is currently under increased scrutiny by the US Food and Drug Administration (FDA) due to the risk of intentional and more concerning, unintentional overdose-related hepatotoxicity. Acetaminophen is responsible for an estimated 48% of all acute liver failure diagnoses. The purpose of this study is to evaluate patient perception and knowledge of the safe use and potential toxicity of acetaminophen-containing products. The authors conducted a descriptive, 2-week study using a convenience sample from a large family medicine clinic waiting room. Survey questions assessed ability to identify acetaminophen, knowledge of the current recommended maximum daily dose, respondent acetaminophen use patterns, common adverse effects associated with acetaminophen, and respondent self-reported alcohol consumption. Acetaminophen safety information was provided to all persons regardless of participation in the study. Of the 102 patients who chose to participate, 79% recognized acetaminophen as a synonym of Tylenol, whereas only 9% identified APAP as a frequently used abbreviation. One third of respondents thought acetaminophen was synonymous with ibuprofen and naproxen. Approximately one fourth of patients correctly identified the then maximum recommended daily acetaminophen dose of 4 g. Seventy-eight percent of patients correctly identified hepatotoxicity as the most common serious adverse effect. We conclude that patient deficiencies in knowledge of acetaminophen recognition, dosing, and toxicity warrant public education by health professionals at all levels of interaction. Current initiatives are promising; however, further efforts are required.

  3. Extracorporeal treatment for carbamazepine poisoning: Systematic review and recommendations from the EXTRIP workgroup

    PubMed Central

    Ghannoum, Marc; Yates, Christopher; Galvao, Tais F.; Sowinski, Kevin M.; Vo, Thi Hai Vân; Coogan, Andrew; Gosselin, Sophie; Lavergne, Valery; Nolin, Thomas D.; Hoffman, Robert S.

    2014-01-01

    Abstract Context. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence and consensus-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning. Objectives. To perform a systematic review and provide clinical recommendations for ECTR in carbamazepine poisoning. Methods. After a systematic literature search, the subgroup extracted the data and summarized the findings following a pre-determined format. The entire workgroup voted via a two-round modified Delphi method to reach a consensus on voting statements, using a RAND/UCLA Appropriateness Method to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote determined the final recommendations. Results. Seventy-four articles met inclusion criteria. Articles included case reports, case series, descriptive cohorts, pharmacokinetic studies, and in-vitro studies; two poor-quality observational studies were identified, yielding a very low quality of evidence for all recommendations. Data on 173 patients, including 6 fatalities, were reviewed. The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D) or if significant toxicity persists, particularly when carbamazepine concentrations rise or remain elevated, despite using multiple-dose activated charcoal (MDAC) and supportive measures (2D). ECTR should be continued until clinical improvement is apparent (1D) or the serum carbamazepine concentration is below 10 mg/L (42 the μ in μmol/L looks weird.) (2D). Intermittent hemodialysis is the preferred ECTR (1D), but both intermittent hemoperfusion (1D) or continuous

  4. Potentiation of morphine analgesia by caffeine.

    PubMed Central

    Misra, A. L.; Pontani, R. B.; Vadlamani, N. L.

    1985-01-01

    Significant potentiation of morphine (5 mg kg-1 s.c. or 1 mg kg-1 i.v.) analgesia (tail-withdrawal reflex at 55 degrees C) was observed in caffeine-treated (100 mg kg-1 i.p.) rats as compared to the control group and lower doses of caffeine (2mg kg-1 i.p.) did not show this effect. Potentiated analgesia was reversed by naloxone. Pharmacokinetic or dispositional factors appear to be involved in part in this potentiation. PMID:4005485

  5. Potentiation of morphine analgesia by caffeine.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1985-04-01

    Significant potentiation of morphine (5 mg kg-1 s.c. or 1 mg kg-1 i.v.) analgesia (tail-withdrawal reflex at 55 degrees C) was observed in caffeine-treated (100 mg kg-1 i.p.) rats as compared to the control group and lower doses of caffeine (2mg kg-1 i.p.) did not show this effect. Potentiated analgesia was reversed by naloxone. Pharmacokinetic or dispositional factors appear to be involved in part in this potentiation. PMID:4005485

  6. Antagonism of acetaminophen-induced hepatocellular destruction by trifluoperazine in mice.

    PubMed

    Yamamoto, H

    1990-08-01

    The effect of trifluoperazine, a specific calmodulin inhibitor, on hepatocellular destruction induced by acetaminophen was investigated in mice. Trifluoperazine 30 mg/kg administered intraperitoneally 30 min. or 0 min. before acetaminophen blocked hepatocellular destruction induced by the hepatotoxin, as evidenced by the determination of plasma GPT activity. Trifluoperazine also completely inhibited an increase of calcium contents in liver induced by acetaminophen administration. Furthermore, the increase of hepatic phosphorylase a activity induced by acetaminophen administration was completely abolished by pretreatment with trifluoperazine. However, hepatic glutathione depletion induced by acetaminophen was not prevented by pretreatment with trifluoperazine. Trifluoperazine administration caused a marked decrease in the body temperature of acetaminophen-treated animals. However, when the trifluoperazine-treated acetaminophen-poisoned animals were kept normothermic, the preventive effects were abolished. These findings suggest that this protective effect may be mediated by the trifluoperazine blockade of the deleterious effects of calcium accumulation in liver or the trifluoperazine decreasing effects on body temperature.

  7. Impact of caffeine and coffee on our health.

    PubMed

    Gonzalez de Mejia, Elvira; Ramirez-Mares, Marco Vinicio

    2014-10-01

    Coffee is the most frequently consumed caffeine-containing beverage. The caffeine in coffee is a bioactive compound with stimulatory effects on the central nervous system and a positive effect on long-term memory. Although coffee consumption has been historically linked to adverse health effects, new research indicates that coffee consumption may be beneficial. Here we discuss the impact of coffee and caffeine on health and bring attention to the changing caffeine landscape that includes new caffeine-containing energy drinks and supplements, often targeting children and adolescents.

  8. Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers.

    PubMed

    Kaushik, Gaurav; Huber, David P; Aho, Ken; Finney, Bruce; Bearden, Shawn; Zarbalis, Konstantinos S; Thomas, Michael A

    2016-05-27

    Psychoactive pharmaceuticals have been found as teratogens at clinical dosage during pregnancy. These pharmaceuticals have also been detected in minute (ppb) concentrations in drinking water in the US, and are environmental contaminants that may be complicit in triggering neurological disorders in genetically susceptible individuals. Previous studies have determined that psychoactive pharmaceuticals (fluoxetine, venlafaxine and carbamazepine) at environmentally relevant concentrations enriched sets of genes regulating development and function of the nervous system in fathead minnows. Altered gene sets were also associated with potential neurological disorders, including autism spectrum disorders (ASD). Subsequent in vitro studies indicated that psychoactive pharmaceuticals altered ASD-associated synaptic protein expression and gene expression in human neuronal cells. However, it is unknown if environmentally relevant concentrations of these pharmaceuticals are able to cross biological barriers from mother to fetus, thus potentially posing risks to nervous system development. The main objective of this study was to test whether psychoactive pharmaceuticals (fluoxetine, venlafaxine, and carbamazepine) administered through the drinking water at environmental concentrations to pregnant mice could reach the brain of the developing embryo by crossing intestinal and placental barriers. We addressed this question by adding (2)H-isotope labeled pharmaceuticals to the drinking water of female mice for 20 days (10 pre-and 10 post-conception days), and quantifying (2)H-isotope enrichment signals in the dam liver and brain of developing embryos using isotope ratio mass spectrometry. Significant levels of (2)H enrichment was detected in the brain of embryos and livers of carbamazepine-treated mice but not in those of control dams, or for fluoxetine or venlafaxine application. These results provide the first evidence that carbamazepine in drinking water and at typical

  9. Reinforcing and subjective effects of caffeine in normal human volunteers.

    PubMed

    Stern, K N; Chait, L D; Johanson, C E

    1989-01-01

    The reinforcing and subjective effects of caffeine (100 and 300 mg, PO) were determined in a group of 18 normal, healthy adults. Subjects (eight females, ten males) were light to moderate users of caffeine, and had no history of drug abuse. A discrete-trial choice procedure was used in which subjects were allowed to choose between the self-administration of color-coded capsules containing either placebo or caffeine. The number of times caffeine was chosen over placebo was used as the primary index of reinforcing efficacy. Subjective effects were measured before and several times after capsule ingestion. The low dose of caffeine was chosen on 42.6% of occasions, not significantly different from chance (50%). The high dose of caffeine was chosen on 38.9% of occasions, significantly less than expected by chance, indicating that this dose served as a punisher. Both doses of caffeine produced stimulant-like subjective effects, with aversive effects such as increased anxiety predominating after the high dose. When subjects were divided into groups of caffeine-sensitive choosers and nonchoosers, a consistent relationship emerged between caffeine choice and subjective effects; nonchoosers reported primarily aversive effects after caffeine (increased anxiety and dysphoria), whereas choosers reported stimulant and "positive" mood effects. When compared with previous findings, these results demonstrate that caffeine is less reinforcing than amphetamine and related psychomotor stimulants. PMID:2498963

  10. Caffeine promotes wakefulness via dopamine signaling in Drosophila.

    PubMed

    Nall, Aleksandra H; Shakhmantsir, Iryna; Cichewicz, Karol; Birman, Serge; Hirsh, Jay; Sehgal, Amita

    2016-01-01

    Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly Drosophila melanogaster, which shows a robust diurnal pattern of sleep/wake activity, caffeine reduces nighttime sleep behavior independently of the one known adenosine receptor. Here, we show that dopamine is required for the wake-promoting effect of caffeine in the fly, and that caffeine likely acts presynaptically to increase dopamine signaling. We identify a cluster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones relevant for the caffeine response. PAM neurons show increased activity following caffeine administration, and promote wake when activated. Also, inhibition of these neurons abrogates sleep suppression by caffeine. While previous studies have focused on adenosine-receptor mediated mechanisms for caffeine action, we have identified a role for dopaminergic neurons in the arousal-promoting effect of caffeine.

  11. Caffeine promotes wakefulness via dopamine signaling in Drosophila

    PubMed Central

    Nall, Aleksandra H.; Shakhmantsir, Iryna; Cichewicz, Karol; Birman, Serge; Hirsh, Jay; Sehgal, Amita

    2016-01-01

    Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly Drosophila melanogaster, which shows a robust diurnal pattern of sleep/wake activity, caffeine reduces nighttime sleep behavior independently of the one known adenosine receptor. Here, we show that dopamine is required for the wake-promoting effect of caffeine in the fly, and that caffeine likely acts presynaptically to increase dopamine signaling. We identify a cluster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones relevant for the caffeine response. PAM neurons show increased activity following caffeine administration, and promote wake when activated. Also, inhibition of these neurons abrogates sleep suppression by caffeine. While previous studies have focused on adenosine-receptor mediated mechanisms for caffeine action, we have identified a role for dopaminergic neurons in the arousal-promoting effect of caffeine. PMID:26868675

  12. Pharmacokinetics for topically applied caffeine in the rat.

    PubMed

    Kronschläger, Martin; Forsman, Erik; Yu, Zhaohua; Talebizadeh, Nooshin; Löfgren, Stefan; Meyer, Linda M; Bergquist, Jonas; Söderberg, Per

    2014-05-01

    Topically applied caffeine was recently identified as a promising candidate molecule for cataract prevention. Little is known about the pharmacokinetics for topically applied caffeine. Potential toxicity of 72 mM caffeine on the ocular surface and the lens was qualitatively monitored and no toxic effects were observed. The concentration of caffeine was measured in the lens and the blood after topical application of 72 mM caffeine to groups of 10 animals sacrificed at 30, 60, 90 and 120 min after topical application. The lens concentration decreased throughout the observation period while the blood concentration increased up to 120 min. Further, the concentration of caffeine in the lens and blood was measured 30 min after topical application of caffeine, the concentration of caffeine being 0.72, 3.34, 15.51 and 72 mM depending on group belonging, in groups of 10 animals. The caffeine concentration in lens and blood, respectively, increased proportionally to the caffeine concentration topically applied. The rat blood concentrations achieved were far below the equivalent threshold dose of FDA recommended daily dose for humans. This information is important for further development of caffeine eye drops for cataract prevention.

  13. Caffeine Expectancy Questionnaire (CaffEQ): Construction, Psychometric Properties, and Associations with Caffeine Use, Caffeine Dependence, and Other Related Variables

    ERIC Educational Resources Information Center

    Huntley, Edward D.; Juliano, Laura M.

    2012-01-01

    Expectancies for drug effects predict drug initiation, use, cessation, and relapse, and may play a causal role in drug effects (i.e., placebo effects). Surprisingly little is known about expectancies for caffeine even though it is the most widely used psychoactive drug in the world. In a series of independent studies, the nature and scope of…

  14. Effect of microbial fermentation on caffeine content of tea leaves.

    PubMed

    Wang, Xiaogang; Hu, Shuxia; Wan, Xiaochun; Pan, Caiyuan

    2005-09-01

    Caffeine is widely used in the food and pharmaceutical industries. For safety concerns, natural caffeine is preferred over synthetic products despite of its high cost. To explore more economical methods of acquiring natural caffeine, we adopted a microbial fermentation technique to increase the caffeine content of tea leaves. Our studies showed that the caffeine content in tea leaves increased reasonably after treating leaves with microorganisms for a period of time (i.e. orthodox pile-fermentation), and the amount of caffeine content increase varied significantly between black and green teas (27.57% and 86.41%). These results suggested that the change of caffeine content in tea leaves during the pile-fermentation depended not only on the growth and reproduction of microorganisms, but also on the tea composition.

  15. The pH dependent Raman spectroscopic study of caffeine

    NASA Astrophysics Data System (ADS)

    Kang, Jian; Gu, Huaimin; Zhong, Liang; Hu, Yongjun; Liu, Fang

    2011-02-01

    First of all the surface enhanced Raman spectroscopy (SERS) and normal Raman spectra of caffeine aqueous solution were obtained at different pH values. In order to obtain the detailed vibrational assignments of the Raman spectroscopy, the geometry of caffeine molecule was optimized by density functional theory (DFT) calculation. By comparing the SERS of caffeine with its normal spectra at different pH values; it is concluded that pH value can dramatically affect the SERS of caffeine, but barely affect the normal Raman spectrum of caffeine aqueous solution. It can essentially affect the reorientation of caffeine molecule to the Ag colloid surface, but cannot impact the vibration of functional groups and chemical bonds in caffeine molecule.

  16. Neuroendocrine responses to caffeine in the work environment.

    PubMed

    Lane, J D

    1994-01-01

    The effect of caffeine on neuroendocrine stress responses in the workplace was studied in 14 habitual coffee drinkers. Urinary catecholamine and cortisol levels were measured on 2 study days, in a 4-hour interval from morning until noon, while participants performed their normal work-related activities. Caffeine (300 mg) or placebo was administered blind at the beginning of study intervals, after overnight caffeine abstinence. Retrospective mood and symptom ratings were collected at the end of each morning. Caffeine elevated urinary epinephrine levels during work by 37% but did not affect norepinephrine or cortisol levels. Subjective reports suggest that caffeine abstinence was associated with symptoms of caffeine withdrawal by the end of the morning. Effects included higher ratings of sleepiness, lethargy, and headache and a reduced desire to socialize. Results suggest caffeine may increase the activity of the sympathetic adrenal-medullary system during everyday activities in the work environment. This action may potentiate psychophysiological responses elicited by occupational stressors.

  17. Transfer of Nicotine, Cotinine and Caffeine Into Breast Milk in a Smoker Mother Consuming Caffeinated Drinks.

    PubMed

    Calvaresi, Valeria; Escuder, Diana; Minutillo, Adele; Bastons-Compta, Adriana; García-Algar, Oscar; Pallás Alonso, Carmen Rosa; Pacifici, Roberta; Pichini, Simona

    2016-07-01

    Although the habits of cigarette smoking and associated coffee drinking are generally ceased during pregnancy, they are often reinitiated after delivery when the breastfeeding period starts. This is a case report of a 32-year-old lactating smoker mother who consumed caffeinated drinks and who agreed to donate breast milk after smoking one cigarette (containing 0.6 mg of nicotine) and drinking one cup of espresso (containing 80 mg of caffeine) for an investigation of the excretion of nicotine, its major metabolite cotinine and caffeine into the breast milk and subsequent transfer to the infant. Nicotine and its metabolite cotinine peaked in the breast milk at 0.5 h after the cigarette smoking, and caffeine peaked 2 h after drinking coffee. Moreover, the nicotine disappeared from the milk by 3 h, the caffeine required 24 h and the cotinine required 72 h. The relative infant doses of caffeine, nicotine and cotinine were found to be 8.9, 12.8 and 77.6%, respectively. In the light of these results obtained after the mother smoked only one cigarette and consumed one cup of espresso, if a lactating mother cannot refrain from smoking cigarettes, she should extend the time between the last smoked cigarette and breastfeeding to at least 3 h when the nicotine has been completely eliminated from the milk. Similarly, nursing mothers should also drink coffee sparingly and immediately after nursing and avoid coffee or caffeinated beverages for at least 4 h prior to breastfeeding to minimize the infant's exposure to caffeine.

  18. Caffeine Does Not Modulate Inhibitory Control

    ERIC Educational Resources Information Center

    Tieges, Zoe; Snel, Jan; Kok, Albert; Ridderinkhof, K. Richard

    2009-01-01

    The effects of a 3 mg/kg body weight (BW) dose of caffeine were assessed on behavioral indices of response inhibition. To meet these aims, we selected a modified AX version of the Continuous Performance Test (CPT), the stop task, and the flanker task. In three double-blind, placebo-controlled, within-subjects experiments, these tasks were…

  19. Soxhlet Extraction of Caffeine from Beverage Plants

    NASA Astrophysics Data System (ADS)

    Adam, D. J.; Mainwaring, J.; Quigley, Michael N.

    1996-12-01

    A simple procedure is described for the extraction of caffeine from coffee beans or granules, tea leaves, mat leaves, etc. Since dichloromethane and several other hazardous substances are used, the procedure is best performed in a fume hood. Following extraction, melting point determination of the crystalline precipitate establishes its positive identity. Includes 33 references.

  20. Effects of Caffeine on Crayfish Muscle Fibers

    PubMed Central

    Chiarandini, Dante J.; Reuben, John P.; Girardier, Lucien; Katz, George M.; Grundfest, Harry

    1970-01-01

    When caffeine evokes a contraction, and only then, crayfish muscle fibers become refractory to a second challenge with caffeine for up to 20 min in the standard saline (5 mM Ko). However, the fibers still respond with contraction to an increase in Ko, though with diminished tension. Addition of Mn slows recovery, but the latter is greatly accelerated during exposure of the fiber to high Ko, or after a brief challenge with high Ko. Neither the depolarization induced by the K, nor the repolarization after its removal accounts for the acceleration, which occurs only if the challenge with K had itself activated the contractile system; acceleration is blocked when contractile responses to K are blocked by reducing the Ca in the bath or by adding Mn. Recovery is accelerated by redistribution of intracellular Cl and by trains of intracellularly applied depolarizing pulses, but not by hyperpolarization. The findings indicate that two sources of Ca can be mobilized to activate the contractile system. Caffeine mobilizes principally the Ca store of the SR. Depolarizations that are induced by high Ko, by transient efflux of Cl, or by intracellularly applied currents mobilize another source of Ca which is strongly dependent upon the entry of Ca from the bathing medium. The sequestering mechanism of the SR apparently can utilize this second source of Ca to replenish its own store so as to accelerate recovery of responsiveness to a new challenge with caffeine. PMID:5443469

  1. Psychostimulant and Other Effects of Caffeine in 9- to 11-Year-Old Children

    ERIC Educational Resources Information Center

    Heatherley, Susan V.; Hancock, Katie M. F.; Rogers, Peter J.

    2006-01-01

    Background: Recent research on adults suggests that "beneficial" psychostimulant effects of caffeine are found only in the context of caffeine deprivation; that is, caffeine improves psychomotor and cognitive performance in habitual caffeine consumers following caffeine withdrawal. Furthermore, no net benefit is gained because performance is…

  2. A Survey of Caffeine Use and Associated Side Effects in a College Population.

    ERIC Educational Resources Information Center

    Johnson-Greene, Douglas; And Others

    1988-01-01

    Surveyed 270 college students concerning their caffeine consumption. Results suggest there is identifiable group using excessive amounts of caffeine. Identified several deleterious effects possibly related to caffeine use. Approximately 75 percent of caffeine users surveyed rarely sought information on caffeine content of products or avoided…

  3. Postsurgical pain: zomepirac sodium, propoxyphene/-acetaminophen combination, and placebo.

    PubMed

    Honig, S; Murray, K A

    1981-10-01

    Zomepirac sodium, a new, nonnarcotic analgesic agent, was compared with the combination of propoxyphene/acetaminophen in a placebo-controlled, double-blind, single-dose study in 196 hospitalized postsurgical patients with pain severe enough to require a prescription analgesic. Patients received 100 mg zomepirac sodium, 50 mg zomepirac sodium, 100 mg propoxyphene napsylate with 650 mg acetaminophen, or placebo. Total pain relief during the 6-hour observation period showed that 100 mg zomepirac sodium was significantly more effective than the propoxyphene combination. All active drugs were superior to placebo. Percentages of patients requiring remedication before the end of the study were: 77 per cent for placebo, 48 per cent for propoxyphene/acetaminophen, 43 per cent for 50 mg zomepirac sodium, and 29 per cent for 100 mg zomepirac sodium. The numbers of patients reporting side effects were not significantly different among the treatment groups. These results confirm those of other single-dose pain studies which showed 100 mg zomepirac sodium significantly more efficacious than the propoxyphene/acetaminophen combination.

  4. Acetaminophen-induced Liver Injury: from Animal Models to Humans.

    PubMed

    Jaeschke, Hartmut; Xie, Yuchao; McGill, Mitchell R

    2014-09-01

    Drug-induced liver injury is an important clinical problem and a challenge for drug development. Whereas progress in understanding rare and unpredictable (idiosyncratic) drug hepatotoxicity is severely hampered by the lack of relevant animal models, enormous insight has been gained in the area of predictable hepatotoxins, in particular acetaminophen-induced liver injury, from a broad range of experimental models. Importantly, mechanisms of toxicity obtained with certain experimental systems, such as in vivo mouse models, primary mouse hepatocytes, and metabolically competent cell lines, are being confirmed in translational studies in patients and in primary human hepatocytes. Despite this progress, suboptimal models are still being used and experimental data can be confusing, leading to controversial conclusions. Therefore, this review attempts to discuss mechanisms of drug hepatotoxicity using the most studied drug acetaminophen as an example. We compare the various experimental models that are used to investigate mechanisms of acetaminophen hepatotoxicity, discuss controversial topics in the mechanisms, and assess how these experimental findings can be translated to the clinic. The success with acetaminophen in demonstrating the clinical relevance of experimental findings could serve as an example for the study of other drug toxicities. PMID:26355817

  5. Analgesic efficacy of acetaminophen for controlling postextraction dental pain

    PubMed Central

    Deshpande, Ashwini; Bhargava, Darpan; Gupta, Manas

    2014-01-01

    Background: Considering the clinical safety of acetaminophen over other nonsteroidal anti-inflammatory drugs, this clinical trial was formulated to assess the analgesic efficacy of acetaminophen for controlling postextraction dental pain when compared to commonly prescribed ibuprofen. Aim: The aim was to assess the analgesic efficacy of paracetamol/acetaminophen in postextraction dental pain. Settings and Design: Double-blind, randomized prospective clinical trial. Materials and Methods: A total of 30 patients requiring bilateral maxillary and mandibular premolar extraction for their orthodontic treatment were included in the study to evaluate the efficacy of acetaminophen in controlling postextraction dental pain. Statistical Analysis Used: Unpaired t-test. Results and Conclusions: Clinically, both the postoperative analgesics exerted similar pain control with minor variations of recorded visual analog scale scores by the patients in both the groups. It may be concluded from the findings of this study that paracetamol at a dosage of 500 mg thrice a day (1.5 g) is sufficient to achieve reliable pain control following exodontia provided the surgical trauma caused to the investing tissues is minimal. PMID:25593867

  6. Connexin32: a mediator of acetaminophen-induced liver injury?

    PubMed

    Maes, Michaël; McGill, Mitchell R; da Silva, Tereza Cristina; Lebofsky, Margitta; Maria Monteiro de Araújo, Cintia; Tiburcio, Taynã; Veloso Alves Pereira, Isabel; Willebrords, Joost; Crespo Yanguas, Sara; Farhood, Anwar; Zaidan Dagli, Maria Lucia; Jaeschke, Hartmut; Cogliati, Bruno; Vinken, Mathieu

    2016-02-01

    Connexin32 is the building block of hepatocellular gap junctions, which control direct intercellular communication and thereby act as goalkeepers of liver homeostasis. This study was set up to investigate whether connexin32 is involved in hepatotoxicity induced by the analgesic and antipyretic drug acetaminophen. To this end, whole body connexin32 knock-out mice were overdosed with acetaminophen followed by sampling at different time points within a 24-h time frame. Evaluation was done based upon a series of clinically and mechanistically relevant read-outs, including protein adduct formation, histopathological examination, measurement of alanine aminotransferase activity, cytokine production, levels of reduced and oxidized glutathione and hepatic protein amounts of proliferating cell nuclear antigen. In essence, it was found that genetic ablation of connexin32 has no influence on several key events in acetaminophen-induced hepatotoxicity, including cell death, inflammation or oxidative stress, yet it does affect production of protein adducts as well as proliferating cell nuclear antigen steady-state protein levels. This outcome is not in line with previous studies, which are contradicting on their own, as both amplification and alleviation of this toxicological process by connexin32 have been described. This could question the suitability of the currently available models and tools to investigate the role of connexin32 in acetaminophen-triggered hepatotoxicity. PMID:26739117

  7. A Dog Model for Acetaminophen-Induced Fulminant Hepatic Failure

    PubMed Central

    FRANCAVILLA, A.; MAKOWKA, L.; POLIMENO, L.; BARONE, M.; DEMETRIS, J.; PRELICH, J.; Van THIEL, D. H.; STARZL, T. E.

    2010-01-01

    The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure. PMID:2910762

  8. Bioaccumulation and bioconcentration of carbamazepine and other pharmaceuticals in fish under field and controlled laboratory experiments. Evidences of carbamazepine metabolization by fish.

    PubMed

    Valdés, M E; Huerta, B; Wunderlin, D A; Bistoni, M A; Barceló, D; Rodriguez-Mozaz, S

    2016-07-01

    There is a growing interest in evaluating the presence of pharmaceutical residues and their metabolites in aquatic biota. In this study, twenty pharmaceuticals, including carbamazepine (CBZ) and two metabolites, were analyzed in homogenates of two fish species (Gambusia affinis and Jenynsia multidentata) captured in polluted areas of the Suquía River (Córdoba, Argentina). The twenty target pharmaceuticals were found in G. affinis, while only fifteen were detected in J. multidentata. We observed a noticeable difference in the accumulation pattern of both fish species, suggesting different pathways for the bioaccumulation of polar pharmaceuticals in each fish. In order to investigate uptake and tissue distribution of pharmaceuticals, a detailed study was performed under controlled laboratory conditions in J. multidentata, exposed to CBZ. CBZ and two of its metabolites (carbamazepine-10,11-epoxide - CBZ-EP and 2-hydroxycarbamazepine - 2-OH-CBZ) were monitored in five organs of fish under laboratory exposure. To our knowledge, this is the first report on the presence of CBZ and its metabolite 2-OH-CBZ in gills, intestine, liver, brain and muscle of fish, while the metabolite carbamazepine-10,11-epoxide (CBZ-EP) was detected in gills and muscle. A ratio CBZ-EP/CBZ close to 0.1 suggests that gills and muscle of J. multidentata could metabolize CBZ through the CBZ-EP pathway. Our results reinforce the need of analyzing multiple species to account for the environmental impact of pollutants, negating the simplification of a single, "representative model" during ecotoxicological biomonitoring. To our knowledge, the biotransformation of CBZ to its metabolites (CBZ-EP, 2-OH-CBZ) in fish, under controlled laboratory in vivo exposures, is reported for the first time.

  9. Caffeine Awareness in Children: Insights from a Pilot Study

    PubMed Central

    Thakre, Tushar P.; Deoras, Ketan; Griffin, Catherine; Vemana, Aarthi; Podmore, Petra; Krishna, Jyoti

    2015-01-01

    Study Objectives: Caffeine, a commonly consumed psychoactive substance, can have significant effects on sleep. Caffeine intake among children is increasing, mainly in the form of sodas. However, adolescent caffeine consumers may lack knowledge about the caffeine content in common beverages. If true, this very fact may hamper the assessment of the effects of caffeine consumption on sleep in children if such assessments are a priori dependent on responders being able to reliably distinguish between caffeinated and noncaffeinated beverages. This preliminary study investigated adolescents' caffeine knowledge and intake at a Cleveland-area public middle school. Methods: Seventh- and eighth-grade students were surveyed using: (1) the Caffeine Literacy and Sleep Study (CLASS), a 15-question pilot instrument designed to assess caffeine knowledge and intake by type, quantity and timing, as well as sleep habits; and (2) the Cleveland Adolescent Sleepiness Questionnaire (CASQ), a validated survey measuring excessive daytime sleepiness in adolescents. These questionnaires were distributed and collected during a specified class period. Results: Of the 635 seventh- and eighth-grade students who attended school on the day of the study, 555 (87%) participated. Lack of knowledge about caffeine content of particular drinks was noted in seventh and eighth graders of both sexes with nearly 29% unaware that their favorite drinks contain caffeine and more than 50% unable to correctly identify the drinks with the most caffeine. A low percentage of students correctly identified light-colored sodas lacking caffeine: 7-Up (24.1%), Sierra Mist (38.9%), ginger ale (39.8%), Sprite (39.8%), and Fresca (53.7%). The percentages of students correctly identifying caffeinated light-colored beverages were: Arizona Green Tea (43.5%), Mello Yellow (50.9%), and A&W cream soda (67.6%). However, Mountain Dew was correctly identified by most (93.5%) as caffeinated. Conclusions: Students were not

  10. Legitimacy of concerns about caffeine and energy drink consumption.

    PubMed

    Wesensten, Nancy J

    2014-10-01

    Whether caffeine and energy drink consumption presents a critical emerging health problem is not currently known. Available evidence suggests that energy drink consumption represents a change in the ways in which individuals in the United States consume caffeine but that the amount of caffeine consumed daily has not appreciably increased. In the present review, the question of whether Americans are sleep deprived (a potential reason for using caffeine) is briefly explored. Reported rates of daily caffeine consumption (based on beverage formulation) and data obtained from both civilian and military populations in the United States are examined, the efficacy of ingredients other than caffeine in energy drinks is discussed, and the safety and side effects of caffeine are addressed, including whether evidence supports the contention that excessive caffeine/energy drink consumption induces risky behavior. The available evidence suggests that the main legitimate concern regarding caffeine and energy drink use is the potential negative impact on sleep but that, otherwise, there is no cause for concern regarding caffeine use in the general population.

  11. Pharmacologic immunosuppression of mononuclear phagocyte phagocytosis by caffeine.

    PubMed

    Steck, Ryan P; Hill, Spencer L; Weagel, Evita G; Weber, K Scott; Robison, Richard A; O'Neill, Kim L

    2015-12-01

    Caffeine is the most widely used neurostimulant in the world. There is considerable debate on its effect on immune cells as it has been shown to antagonize adenosine receptors (ARs), which mediate an anti-inflammatory switch in activated immune cells. A second target is phosphodiesterase, where it acts as an inhibitor. If the primary effect of caffeine on mononuclear phagocytes were to antagonize ARs we would expect cells exposed to caffeine to have a prolonged proinflammatory response. The aim of this study was to investigate the effects and mechanism of action of caffeine in mononuclear phagocytes. Human mononuclear phagocytes were separated from whole blood and pretreated with protein kinase A inhibitor (PKA) and then exposed to micromolar physiological concentrations of caffeine. Phagocytosis and phagocytosis exhaustion were quantified using flow cytometry. Treatments were analyzed and compared to controls, using a beta regression controlling for factors of age, gender, caffeine intake, and exercise. We found that caffeine suppresses phagocytosis at micromolar physiological concentrations. This suppression was prevented when mononuclear phagocytes were pretreated with PKA inhibitor, suggesting that caffeine's phagocytic suppression may be due to its function as a phosphodiesterase inhibitor, pushing cells towards an anti-inflammatory response. Additionally, these effects are altered by regular caffeine intake and fitness level, emphasizing that tolerance and immune robustness are important factors in mononuclear phagocyte activation. These results demonstrate that caffeine may be acting as a phosphodiesterase inhibitor and suppressing phagocytosis in mononuclear phagocytes by promoting an anti-inflammatory response.

  12. Self-report reliability and symptomatology of habitual caffeine consumption.

    PubMed Central

    James, J E; Bruce, M S; Lader, M H; Scott, N R

    1989-01-01

    1. A large body of research on the demography of caffeine use and its potential health consequences has been undermined by the absence of empirical data on the reliability of retrospective self-reports of caffeine consumption. 2. The principal aim of the present study was to use standard bioanalytic method to assess the reliability of subjects' self-reported caffeine use. Saliva samples were obtained from 142 first-and second-year medical students and assayed for caffeine and paraxanthine. 3. Self-reported caffeine use was found to be significantly correlated with salivary caffeine (r = 0.31, P less than 0.001) and paraxanthine (r = 0.42, P less than 0.001), thereby providing qualified support for use of questionnaires to estimate patterns of caffeine consumption. 4. A secondary aim of the study was to extend previous research concerning the symptomatology of caffeine use by examining the association between caffeine exposure and a variety of measures of somatic and psychological health. Caffeine consumption was reliably associated with the self-reported occurrence of somatic symptoms, but not psychological well-being. PMID:2719904

  13. Caffeine increases food intake while reducing anxiety-related behaviors.

    PubMed

    Sweeney, Patrick; Levack, Russell; Watters, Jared; Xu, Zhenping; Yang, Yunlei

    2016-06-01

    The objective of this study was to determine the effects of different doses of caffeine on appetite and anxiety-related behavior. Additionally, we sought to determine if withdrawal from chronic caffeine administration promotes anxiety. In this study, we utilized rodent open field testing and feeding behavior assays to determine the effects of caffeine on feeding and anxiety-related behavior (n = 8 mice; 4-8 weeks old). We also measured 2 h and 24 h food intake and body-weight during daily administration of caffeine (n = 12 mice; 4-8 weeks old). To test for caffeine withdrawal induced anxiety, anxiety-related behavior in rodents was quantified following withdrawal from four consecutive days of caffeine administration (n = 12 mice; 4-8 weeks old). We find that acute caffeine administration increases food intake in a dose-dependent manner with lower doses of caffeine more significantly increasing food intake than higher doses. Acute caffeine administration also reduced anxiety-related behaviors in mice without significantly altering locomotor activity. However, we did not observe any differences in 24 h food intake or body weight following chronic caffeine administration and there were no observable differences in anxiety-related behaviors during caffeine withdrawal. In conclusion, we find that caffeine can both increase appetite and decrease anxiety-related behaviors in a dose dependent fashion. Given the complex relationship between appetite and anxiety, the present study provides additional insights into potential caffeine-based pharmacological mechanisms governing appetite and anxiety disorders, such as bulimia nervosa. PMID:26972351

  14. Efficacy of Intravenous Infusion of Acetaminophen for Intrapartum Analgesia

    PubMed Central

    Zutshi, Vijay; Rani, Kumari Usha; Patel, Madhumita

    2016-01-01

    Introduction The intensity of pain experienced by women in labour, has been found to affect the progress of labour, foetal well-being and maternal psychology. Adverse effects associated with commonly used opioids for providing intrapartum analgesia have created a need for an alternative non-opioid drug. Aim To evaluate the efficacy of an intravenous infusion of 1000 mg of acetaminophen as an intrapartum analgesic. Materials and Methods The present prospective single-centre, single blind, placebo-controlled randomized interventional study was conducted in Department of Obstetrics and Gynaecology in Vardhaman Mahavir Medical College & Safdarjung Hospital over a period of six months from September 2014 to March 2015. After receiving the ethical clearance and written informed consent. The first 200 consecutive parturients fulfilling the inclusion criteria were recruited into the study. Women were then randomised to receive either intravenous 1000 mg (100ml) of acetaminophen (Group A, n=100) or 100 ml normal saline (Group B, n=100). Primary outcome assessed was effectiveness of acetaminophen to provide an adequate amount of analgesia, as measured by a change in Visual Analogue Scale (VAS) pain intensity score at various times after drug administration. Secondary outcomes measured were duration of labour, need for additional rescue analgesia and presence of adverse maternal or foetal effect. Results There was pain reduction at 1 and 2 hours in both groups (p<0.001). However, it was more significant in the acetaminophen group, especially at 1 hour. Duration of labour was shortened in both the groups, without any maternal and foetal adverse effects. Conclusion Intravenous acetaminophen is an efficacious non-opioid drug for relieving labour pain without any significant maternal and foetal adverse effects. PMID:27656511

  15. Effect of diethyl ether on the biliary excretion of acetaminophen.

    PubMed

    Watkins, J B; Siegers, C P; Klaassen, C D

    1984-10-01

    The biliary and renal excretion of acetaminophen and its metabolites over 8 hr was determined in rats exposed to diethyl ether by inhalation for 1 hr. Additional rats were anesthetized with urethane (1 g/kg ip) while control animals were conscious throughout the experiment (surgery was performed under hexobarbital narcosis: 150 mg/kg ip; 30-min duration). The concentration of UDP-glucuronic acid was decreased 80% in livers from ether-anesthetized rats but was not reduced in urethane-treated animals when compared to that in control rats. The concentration of reduced glutathione was not affected by either urethane or diethyl ether. Basal bile flow was not altered by the anesthetic agents. Bile flow rate after acetaminophen injection (100 mg/kg iv) was increased slightly over basal levels for 2 hr in hexobarbital-treated control rats, was unaltered in urethane-anesthetized animals, and was decreased throughout the 8-hr experiment in rats exposed to diethyl ether for 1 hr. In control and urethane-anesthetized animals, approximately 30-35% of the total acetaminophen dose (100 mg/kg iv) was excreted into bile in 8 hr, while only 16% was excreted in rats anesthetized with diethyl ether. Urinary elimination (60-70% of the dose) was not altered by exposure to ether. Separation of metabolites by reverse-phase high-pressure liquid chromatography showed that ether decreased the biliary elimination of unchanged acetaminophen and its glucuronide, sulfate, and glutathione conjugates by 47, 40, 49, and 73%, respectively, as compared to control rats. Excretion of unchanged acetaminophen and the glutathione conjugate into bile was depressed in urethane-anesthetized animals by 45 and 66%, respectively, whereas elimination of the glucuronide and sulfate conjugates was increased by 27 and 50%, respectively. These results indicate that biliary excretion is influenced by the anesthetic agent and that diethyl ether depresses conjugation with sulfate and glutathione as well as glucuronic

  16. Quantitative Analysis by Isotopic Dilution Using Mass Spectroscopy: The Determination of Caffeine by GC-MS.

    ERIC Educational Resources Information Center

    Hill, Devon W.; And Others

    1988-01-01

    Describes a laboratory technique for quantitative analysis of caffeine by an isotopic dilution method for coupled gas chromatography-mass spectroscopy. Discusses caffeine analysis and experimental methodology. Lists sample caffeine concentrations found in common products. (MVL)

  17. Withdrawal syndrome and hypomagnesaemia and in a newborn exposed to valproic acid and carbamazepine during pregnancy.

    PubMed

    Satar, Mehmet; Ortaköylü, Kadir; Batun, İnci; Yıldızdaş, Hacer Y; Özlü, Ferda; Demir, Hüsnü; Topaloğlu, Ali Kemal

    2016-06-01

    The usage of drugs during pregnancy affect the fetus and the newborn. In this report, we present findings from a newborn baby, whose mother was epileptic, and was under the treatment of valproic acid and carbamazepine during pregnancy. We have found symptoms of withdrawal syndrome, hyponatremia and feeding problem, which was most probably related to exposure to the mentioned drugs. We have also diagnosed hypomagnesaemia and atrial septal defect 4 milimeters in diameter. There are already many reports about the side effects of valproic acid and carbamazepine usage during pregnancy. To the best of our knowledge, hypomagnesaemia has not yet been reported as a side effect. We think that hypomagnesaemia is also related to the usage of antiepileptics. PMID:27489470

  18. Characterization and biodegradation kinetics of a new cold-adapted carbamazepine-degrading bacterium, Pseudomonas sp. CBZ-4.

    PubMed

    Li, Ang; Cai, Rui; Di, Cui; Qiu, Tian; Pang, Changlong; Yang, Jixian; Ma, Fang; Ren, Nanqi

    2013-11-01

    Carbamazepine is frequently detected in waters and hardly eliminated during conventional wastewater treatment processes due to its complicated chemical structure and resistance to biodegradation. A carbamazepine-degrading bacterium named CBZ-4 was isolated at a low temperature (10 degreeC) from activated sludge in a municipal wastewater treatment plant. Strain CBZ-4, which can use carbamazepine as its sole source of carbon and energy, was identified as Pseudomonas sp. by the 16S rRNA gene sequence. The composition and percentage of fatty acids, which can reveal the cold-adaptation mechanism of strain CBZ-4, were determined. Strain CBZ-4 can effectively degrade carbamazepine at optimal conditions: pH 7.0, 10 degreeC, 150 r/min rotation speed, and 13% inoculation volume. The average removal rate of carbamazepine was 46.6% after 144 hr of incubation. The biodegradation kinetics of carbamazepine by CBZ-4 was fitted via the Monod model. Vmax and Ks were found to be 0.0094 hr-1 and 32.5 mg/L, respectively. PMID:24552057

  19. Solid-vapor interactions: influence of environmental conditions on the dehydration of carbamazepine dihydrate.

    PubMed

    Surana, Rahul; Pyne, Abira; Suryanarayanan, Raj

    2003-12-31

    The goal of this research was a phenomenological study of the effect of environmental factors on the dehydration behavior of carbamazepine dihydrate. Dehydration experiments were performed in an automated vapor sorption apparatus under a variety of conditions, and weight loss was monitored as a function of time. In addition to lattice water, carbamazepine dihydrate contained a significant amount of physically bound water. Based on the kinetics of water loss, it was possible to differentiate between the removal of physically bound water and the lattice water. The activation energy for the 2 processes was 44 and 88 kJ/mol, respectively. As expected, the dehydration rate of carbamazepine dihydrate decreased with an increase in water vapor pressure. While dehydration at 0% relative humidity (RH) resulted in an amorphous anhydrate, the crystallinity of the anhydrate increased as a function of the RH of dehydration. A method was developed for in situ crystallinity determination of the anhydrate formed. Dehydration in the presence of the ethanol vapor was a 2-step process, and the fraction dehydrated at each step was a function of the ethanol vapor pressure. We hypothesize the formation of an intermediate lower hydrate phase with unknown water stoichiometry. An increase in the ethanol vapor pressure first led to a decrease in the dehydration rate followed by an increase. In summary, the dehydration behavior of carbamazepine dihydrate was evaluated at different vapor pressures of water and ethanol. Using the water sorption apparatus, it was possible to (1) differentiate between the removal of physically bound and lattice water, and (2) develop a method for quantifying, in situ, the crystallinity of the product (anhydrate) phase. PMID:15198563

  20. Adaptation to acetaminophen exposure elicits major changes in expression and distribution of the hepatic proteome.

    PubMed

    Eakins, R; Walsh, J; Randle, L; Jenkins, R E; Schuppe-Koistinen, I; Rowe, C; Starkey Lewis, P; Vasieva, O; Prats, N; Brillant, N; Auli, M; Bayliss, M; Webb, S; Rees, J A; Kitteringham, N R; Goldring, C E; Park, B K

    2015-01-01

    Acetaminophen overdose is the leading cause of acute liver failure. One dose of 10-15 g causes severe liver damage in humans, whereas repeated exposure to acetaminophen in humans and animal models results in autoprotection. Insight of this process is limited to select proteins implicated in acetaminophen toxicity and cellular defence. Here we investigate hepatic adaptation to acetaminophen toxicity from a whole proteome perspective, using quantitative mass spectrometry. In a rat model, we show the response to acetaminophen involves the expression of 30% of all proteins detected in the liver. Genetic ablation of a master regulator of cellular defence, NFE2L2, has little effect, suggesting redundancy in the regulation of adaptation. We show that adaptation to acetaminophen has a spatial component, involving a shift in regionalisation of CYP2E1, which may prevent toxicity thresholds being reached. These data reveal unexpected complexity and dynamic behaviour in the biological response to drug-induced liver injury. PMID:26607827

  1. Adaptation to acetaminophen exposure elicits major changes in expression and distribution of the hepatic proteome

    PubMed Central

    Eakins, R.; Walsh, J.; Randle, L.; Jenkins, R. E.; Schuppe-Koistinen, I.; Rowe, C.; Starkey Lewis, P.; Vasieva, O.; Prats, N.; Brillant, N.; Auli, M.; Bayliss, M.; Webb, S.; Rees, J. A.; Kitteringham, N. R.; Goldring, C. E.; Park, B. K.

    2015-01-01

    Acetaminophen overdose is the leading cause of acute liver failure. One dose of 10–15 g causes severe liver damage in humans, whereas repeated exposure to acetaminophen in humans and animal models results in autoprotection. Insight of this process is limited to select proteins implicated in acetaminophen toxicity and cellular defence. Here we investigate hepatic adaptation to acetaminophen toxicity from a whole proteome perspective, using quantitative mass spectrometry. In a rat model, we show the response to acetaminophen involves the expression of 30% of all proteins detected in the liver. Genetic ablation of a master regulator of cellular defence, NFE2L2, has little effect, suggesting redundancy in the regulation of adaptation. We show that adaptation to acetaminophen has a spatial component, involving a shift in regionalisation of CYP2E1, which may prevent toxicity thresholds being reached. These data reveal unexpected complexity and dynamic behaviour in the biological response to drug-induced liver injury. PMID:26607827

  2. Adaptation to acetaminophen exposure elicits major changes in expression and distribution of the hepatic proteome.

    PubMed

    Eakins, R; Walsh, J; Randle, L; Jenkins, R E; Schuppe-Koistinen, I; Rowe, C; Starkey Lewis, P; Vasieva, O; Prats, N; Brillant, N; Auli, M; Bayliss, M; Webb, S; Rees, J A; Kitteringham, N R; Goldring, C E; Park, B K

    2015-11-26

    Acetaminophen overdose is the leading cause of acute liver failure. One dose of 10-15 g causes severe liver damage in humans, whereas repeated exposure to acetaminophen in humans and animal models results in autoprotection. Insight of this process is limited to select proteins implicated in acetaminophen toxicity and cellular defence. Here we investigate hepatic adaptation to acetaminophen toxicity from a whole proteome perspective, using quantitative mass spectrometry. In a rat model, we show the response to acetaminophen involves the expression of 30% of all proteins detected in the liver. Genetic ablation of a master regulator of cellular defence, NFE2L2, has little effect, suggesting redundancy in the regulation of adaptation. We show that adaptation to acetaminophen has a spatial component, involving a shift in regionalisation of CYP2E1, which may prevent toxicity thresholds being reached. These data reveal unexpected complexity and dynamic behaviour in the biological response to drug-induced liver injury.

  3. Oral pharmacokinetics of acetaminophen to evaluate gastric emptying profiles of Shiba goats.

    PubMed

    Elbadawy, Mohamed; Sasaki, Kazuaki; Miyazaki, Yuji; Aboubakr, Mohamed; Khalil, Waleed Fathy; Shimoda, Minoru

    2015-10-01

    The pharmacokinetics of acetaminophen was investigated following oral dosing to Shiba goats in order to evaluate the properties of gastric emptying. Acetaminophen was intravenously and orally administered at 30 mg/kg body weight to goats using a crossover design with a 3-week washout period. The stability of acetaminophen in rumen juice was also assessed. Acetaminophen concentrations were measured by HPLC. Since acetaminophen was stable in rumen juice for 24 hr, the extremely low bioavailability (16%) was attributed to its hepatic extensive first-pass effect. The mean absorption time and absorption half-life were unexpectedly short (4.93 and 3.35 hr, respectively), indicating its marked absorption from the forestomach, which may have been due to its smaller molecular weight. Therefore, acetaminophen was considered to be unsuitable for evaluating gastric emptying in Shiba goats.

  4. Caffeine potentiates the enhancement by choline of striatal acetylcholine release

    NASA Technical Reports Server (NTRS)

    Johnson, D. A.; Ulus, I. H.; Wurtman, R. J.

    1992-01-01

    We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect.

  5. Effect of caffeine on cocaine locomotor stimulant activity in rats.

    PubMed

    Misra, A L; Vadlamani, N L; Pontani, R B

    1986-03-01

    The effect of caffeine on the locomotor stimulant activity induced by intravenous cocaine in rats was investigated. Low doses of caffeine (20 mg/kg IP) potentiated the locomotor activity induced by 1, 2.5 mg/kg intravenous doses of cocaine and higher doses of caffeine (50, 100 mg/kg IP) had no significant effect. The locomotor stimulant effect of 20 mg/kg IP dose of caffeine per se in vehicle was significantly higher and that with 100 mg/kg dose significantly lower than that of the vehicle control. Thus caffeine produced dose-dependent effects on cocaine-induced locomotor stimulant activity, with low dose potentiating and higher doses having no significant effect on such activity. Pharmacokinetic or dispositional factors did not appear to play a role in potentiation of cocaine locomotor stimulant activity by caffeine. PMID:3703910

  6. Performance comparison of a co-crystal of carbamazepine with marketed product.

    PubMed

    Hickey, Magali B; Peterson, Matthew L; Scoppettuolo, Lisa A; Morrisette, Sherry L; Vetter, Anna; Guzmán, Hector; Remenar, Julius F; Zhang, Zhong; Tawa, Mark D; Haley, Sean; Zaworotko, Michael J; Almarsson, Orn

    2007-08-01

    The carbamazepine: saccharin co-crystal (1) was studied in terms of a series of attributes, including suitability for multi-gram scale-up, propensity for crystal polymorphism, physical stability, in vitro dissolution and oral bioavailability, with the goal of comparing 1 with the marketed form of carbamazepine (Tegretol). Preparation of 1 was achieved on a 30g scale with a conventional cooling crystallization process from alcohol solution without seeding. The compound is not overtly polymorphic. This finding is in contrast to the form diversity of pure carbamazepine, which has four known polymorphs and a host of solvates, including a dihydrate, which is the stable form in the presence of water. Physical and chemical stability of the co-crystal is also shown to be quantitatively similar to the pure drug in the marketed product (Tegretol). Finally, comparison of oral bioavailability of 1 with Tegretol tablets in dogs shows the co-crystal to be a viable alternative to the anhydrous polymorph in formulated solid oral products. The balance of properties and performance of 1 as a model co-crystal is discussed. PMID:17292592

  7. Monitoring of carbamazepine concentrations in wastewater and groundwater to quantify sewer leakage.

    PubMed

    Fenz, R; Blaschke, A P; Clara, M; Kroiss, H; Mascher, D; Zessner, M

    2005-01-01

    Monitoring of carbamazepine concentrations in wastewater and groundwater enables us to identify and quantify sewer exfiltration. The antiepileptic drug carbamazepine is hardly removed in wastewater treatment plants and not or just slightly attenuated during bank infiltration and subsoil flow. Concentrations in wastewater are generally 1000 times higher than the limit of quantification. In contrast to . many other wastewater tracers carbamazepine is discharged to the environment only via domestic wastewater. The results from this study carried out in Linz, Austria indicate an average exfiltration rate of 1%, expressed as percentage of the dry weather flow that is lost to the groundwater on the city-wide scale. This rate is lower than sewage losses reported in most other studies which attempted to quantify exfiltration on the basis of groundwater pollution. However, it was also possible to identify one area with significantly higher sewage losses. This method seems to be very suitable for the verification of leakage models used to assess sewer exfiltration on a regional scale.

  8. Biosynthesis of caffeine underlying the diversity of motif B' methyltransferase.

    PubMed

    Nakayama, Fumiyo; Mizuno, Kouichi; Kato, Misako

    2015-05-01

    Caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine) are well-known purine alkaloids in Camellia, Coffea, Cola, Paullinia, Ilex, and Theobroma spp. The caffeine biosynthetic pathway depends on the substrate specificity of N-methyltransferases, which are members of the motif B' methyl-transferase family. The caffeine biosynthetic pathways in purine alkaloid-containing plants might have evolved in parallel with one another, consistent with different catalytic properties of the enzymes involved in these pathways. PMID:26058161

  9. Biosynthesis of caffeine underlying the diversity of motif B' methyltransferase.

    PubMed

    Nakayama, Fumiyo; Mizuno, Kouichi; Kato, Misako

    2015-05-01

    Caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine) are well-known purine alkaloids in Camellia, Coffea, Cola, Paullinia, Ilex, and Theobroma spp. The caffeine biosynthetic pathway depends on the substrate specificity of N-methyltransferases, which are members of the motif B' methyl-transferase family. The caffeine biosynthetic pathways in purine alkaloid-containing plants might have evolved in parallel with one another, consistent with different catalytic properties of the enzymes involved in these pathways.

  10. Acetaminophen hepatotoxicity and sterile inflammation: The mechanism of protection of Chlorogenic acid.

    PubMed

    Jaeschke, Hartmut

    2016-01-01

    Acetaminophen hepatotoxicity is characterized by extensive necrotic cell death and a sterile inflammatory response. A recent report suggested that a therapeutic intervention with chlorogenic acid, a dietary polyphenolic compound, protects against acetaminophen-induced liver injury by inhibiting the inflammatory injury. The purpose of this letter is to discuss a number of reasons why the protective mechanism of chlorogenic acid against acetaminophen hepatotoxicity does not involve an anti-inflammatory effect and provides an alternative explanation for the observed protection. PMID:26363200

  11. Acetaminophen hepatotoxicity and sterile inflammation: The mechanism of protection of Chlorogenic acid.

    PubMed

    Jaeschke, Hartmut

    2016-01-01

    Acetaminophen hepatotoxicity is characterized by extensive necrotic cell death and a sterile inflammatory response. A recent report suggested that a therapeutic intervention with chlorogenic acid, a dietary polyphenolic compound, protects against acetaminophen-induced liver injury by inhibiting the inflammatory injury. The purpose of this letter is to discuss a number of reasons why the protective mechanism of chlorogenic acid against acetaminophen hepatotoxicity does not involve an anti-inflammatory effect and provides an alternative explanation for the observed protection.

  12. [Acetaminophen-induced hypothermia, an AIDS related side-effect? About 4 cases].

    PubMed

    Denes, Eric; Amaniou, Monique; Rogez, Jean-Philippe; Weinbreck, Pierre; Merle, Louis

    2002-10-01

    Hypothermia is an uncommon side effect of acetaminophen. We report 4 cases of HIV-infected patients who developed hypothermia after intravenous injection of propacetamol (the parenteral formulation of acetaminophen). The mechanism of this hypothermia is unknown. AIDS-induced changes in the metabolism of acetaminophen, could be an explanation. AIDS-associated opportunistic diseases may account for part of the mechanism. These hypothermias occur within 6 hours after the injection, are well tolerated and regress spontaneously. PMID:12486392

  13. Drug Utilization, Dosing, and Costs After Implementation of Intravenous Acetaminophen Guidelines for Pediatric Patients

    PubMed Central

    Fusco, Nicholas M.; Parbuoni, Kristine; Morgan, Jill A.

    2014-01-01

    OBJECTIVES The objectives of this evaluation of medication use were to characterize the use of intravenous acetaminophen at our institution and to determine if acetaminophen was prescribed at age-appropriate dosages per institutional guidelines, as well as to evaluate compliance with restrictions for use. Total acquisition costs associated with intravenous acetaminophen usage is described as well. METHODS This retrospective study evaluated the use of acetaminophen in pediatric patients younger than 18 years of age, admitted to a tertiary care hospital, who received at least 1 dose of intravenous acet-aminophen between August 1, 2011, and January 31, 2012. RESULTS A total of 52 doses of intravenous acetaminophen were administered to 31 patients during the 6-month study period. Most patients were admitted to the otorhinolaryngology service (55%), and the majority of doses were administered either in the operating room (46%) or in the intensive care unit (46%). Nineteen doses (37%) of intravenous acetaminophen were administered to patients who did not meet institutional guidelines' eligibility criteria. Three patients received single doses of intravenous acetaminophen that were greater than the dose recommended for their age. One patient during the study period received more than the recommended 24-hour maximum cumulative dose for acetaminophen. Total acquisition cost of intravenous acetaminophen therapy over the 6-month study period was $530.40. CONCLUSIONS Intravenous acetaminophen was used most frequently among pediatric patients admitted to the otorhinolaryngology service during the perioperative period. Nineteen doses (37%) were administered to patients who did not meet the institutional guidelines' eligibility criteria. Our data support reinforcing the availability of institutional guidelines to promote cost-effective use of intravenous acetaminophen while minimizing the prescription of inappropriate doses. PMID:24782690

  14. Caffeine reduction in coffee pulp through silage.

    PubMed

    Porres, C; Alvarez, D; Calzada, J

    1993-01-01

    Silage tests to study reductions of antiphysiological compounds (caffeine and polyphenols) of fresh coffee pulp during the anaerobic fermentation were done. A concrete silo divided in compartments, with a total capacity of 9 tons of fresh material was utilized. The silage periods ranged between 99-224 days and the following materials were ensiled: 1) coffee pulp, 2) coffee pulp with sugar cane molasses, 3) coffee pulp with a mixture of molasses and ammonia and 4) screw pressed coffee pulp with molasses. Reductions in caffeine, total polyphenols and condensed polyphenols ranged between 13-63%, 28-70% and 51-81% respectively. It was concluded that in the case of coffee pulp, silage presents and ideal method to preserve the material and partially reduce the contents of antiphysiological compounds.

  15. Modulation of the hypothalamo-pituitary-adrenocortical axis by caffeine

    PubMed Central

    Patz, Michael D.; Day, Heidi E.W.; Burow, Andrew; Campeau, Serge

    2008-01-01

    Summary Although caffeine is the most consumed psychoactive substance in the world, the extents of many of its effects are unknown. High doses of caffeine have been shown to activate the HPA axis while the effects of low to moderate doses have usually not been described in detail. Moreover, although several lines of evidence suggest that low doses of caffeine may restrain some negative affective states, the possible modulatory role of caffeine on HPA axis activation induced by a stressful stimulus has not been described. Thus, the present studies investigated the possible modulatory effects of low to moderate doses of caffeine on moderate to high HPA axis activation induced by different intensities of loud noise. First, in order to test this modulation, time courses for adrenocorticotropic hormone (ACTH) and corticosterone responses to loud noise stress and to caffeine were defined, in rats. Plasma ACTH and corticosterone levels peaked 30 min from the onset of noise presentation, and rapidly declined after noise termination. A low caffeine dose of 2 mg/kg significantly increased plasma corticosterone and ACTH levels 30 min following injections, but levels returned to baseline 60 min following injections. Caffeine doses of 30 mg/kg and higher elevated plasma hormone levels for at least 2 h. Doses of 2 or 10 mg/kg, however, did not modulate endocrine responses to loud noise presentation. It is concluded that although caffeine activates the HPA axis, low to moderate doses do not modulate HPA axis responses to stressful stimuli. PMID:16413973

  16. Caffeine enhances micturition through neuronal activation in micturition centers.

    PubMed

    Cho, Young-Sam; Ko, Il-Gyu; Kim, Sung-Eun; Hwan, Lakkyong; Shin, Mal-Soon; Kim, Chang-Ju; Kim, Sang-Hoon; Jin, Jun-Jang; Chung, Jun-Young; Kim, Khae-Hawn

    2014-12-01

    Caffeine may promote incontinence through its diuretic effect, particularly in individuals with underlying detrusor overactivity, in addition to increasing muscle contraction of the bladder smooth muscle. Caffeine may also affect bladder function via central micturition centers, including the medial preoptic area, ventrolateral periaqueductal gray, and pontine micturition center. However, the biochemical mechanisms of caffeine in central micturition centers affecting bladder function remain unclear. In the present study, the effects of caffeine on the central micturition reflex were investigated by measuring the degree of neuronal activation, and by quantifying nerve growth factor (NGF) expression in rats. Following caffeine administration for 14 days, a urodynamic study was performed to assess the changes to bladder function. Subsequently, immunohistochemical staining to identify the expression of c‑Fos and NGF in the central micturition areas was performed. Ingestion of caffeine increased bladder smooth muscle contraction pressure and time as determined by cystometry. Expression levels of c‑Fos and NGF in all central micturition areas were significantly increased following the administration of caffeine. The effects on contraction pressure and time were the most potent and expression levels of c‑Fos and NGF were greatest at the lowest dose of caffeine. These results suggest that caffeine facilitates bladder instability through enhancing neuronal activation in the central micturition areas.

  17. Caffeine Content in Popular Energy Drinks and Energy Shots.

    PubMed

    Attipoe, Selasi; Leggit, Jeffrey; Deuster, Patricia A

    2016-09-01

    The use of energy beverages is high among the general population and military personnel. Previous studies have reported discrepancies between the actual amount of caffeine in products and the amount of caffeine on stated labels. Thus, the purpose of this study was to examine the content of caffeine listed on the labels of various energy drinks and energy shots. Top-selling energy drinks (n = 9) and energy shots (n = 5) were purchased from retail stores. Three of each of the 14 products were purchased and analyzed for caffeine content by an independent laboratory. Of the 14 products tested, 5 did not provide caffeine amounts on their facts panel-of those, 3 listed caffeine as an ingredient and 2 listed caffeine as part of a proprietary blend. The remaining 9 (of 14) products stated the amounts of caffeine on their labels, all of which were within 15% of the amount indicated on the label. In this study, although the energy beverages that indicated the amount of caffeine it contained had values within ±15% of the amount listed on the label, a potentially acceptable range, this finding is not acceptable with regard to current labeling regulations, which require added ingredients to total 100%. PMID:27612347

  18. Caffeine Consumption and Sleep Quality in Australian Adults.

    PubMed

    Watson, Emily J; Coates, Alison M; Kohler, Mark; Banks, Siobhan

    2016-01-01

    Caffeine is commonly consumed to help offset fatigue, however, it can have several negative effects on sleep quality and quantity. The aim of this study was to determine the relationship between caffeine consumption and sleep quality in adults using a newly validated caffeine food frequency questionnaire (C-FFQ). In this cross sectional study, 80 adults (M ± SD: 38.9 ± 19.3 years) attended the University of South Australia to complete a C-FFQ and the Pittsburgh Sleep Quality Index (PSQI). Caffeine consumption remained stable across age groups while the source of caffeine varied. Higher total caffeine consumption was associated with decreased time in bed, as an estimate of sleep time (r = -0.229, p = 0.041), but other PSQI variables were not. Participants who reported poor sleep (PSQI global score ≥ 5) consumed 192.1 ± 122.5 mg (M ± SD) of caffeine which was significantly more than those who reported good sleep quality (PSQI global score < 5; 125.2 ± 62.6 mg; p = 0.008). The C-FFQ was found to be a quick but detailed way to collect population based caffeine consumption data. The data suggests that shorter sleep is associated with greater caffeine consumption, and that consumption is greater in adults with reduced sleep quality. PMID:27527212

  19. Caffeine Content in Popular Energy Drinks and Energy Shots.

    PubMed

    Attipoe, Selasi; Leggit, Jeffrey; Deuster, Patricia A

    2016-09-01

    The use of energy beverages is high among the general population and military personnel. Previous studies have reported discrepancies between the actual amount of caffeine in products and the amount of caffeine on stated labels. Thus, the purpose of this study was to examine the content of caffeine listed on the labels of various energy drinks and energy shots. Top-selling energy drinks (n = 9) and energy shots (n = 5) were purchased from retail stores. Three of each of the 14 products were purchased and analyzed for caffeine content by an independent laboratory. Of the 14 products tested, 5 did not provide caffeine amounts on their facts panel-of those, 3 listed caffeine as an ingredient and 2 listed caffeine as part of a proprietary blend. The remaining 9 (of 14) products stated the amounts of caffeine on their labels, all of which were within 15% of the amount indicated on the label. In this study, although the energy beverages that indicated the amount of caffeine it contained had values within ±15% of the amount listed on the label, a potentially acceptable range, this finding is not acceptable with regard to current labeling regulations, which require added ingredients to total 100%.

  20. Caffeine Consumption and Sleep Quality in Australian Adults

    PubMed Central

    Watson, Emily J.; Coates, Alison M.; Kohler, Mark; Banks, Siobhan

    2016-01-01

    Caffeine is commonly consumed to help offset fatigue, however, it can have several negative effects on sleep quality and quantity. The aim of this study was to determine the relationship between caffeine consumption and sleep quality in adults using a newly validated caffeine food frequency questionnaire (C-FFQ). In this cross sectional study, 80 adults (M ± SD: 38.9 ± 19.3 years) attended the University of South Australia to complete a C-FFQ and the Pittsburgh Sleep Quality Index (PSQI). Caffeine consumption remained stable across age groups while the source of caffeine varied. Higher total caffeine consumption was associated with decreased time in bed, as an estimate of sleep time (r = −0.229, p = 0.041), but other PSQI variables were not. Participants who reported poor sleep (PSQI global score ≥ 5) consumed 192.1 ± 122.5 mg (M ± SD) of caffeine which was significantly more than those who reported good sleep quality (PSQI global score < 5; 125.2 ± 62.6 mg; p = 0.008). The C-FFQ was found to be a quick but detailed way to collect population based caffeine consumption data. The data suggests that shorter sleep is associated with greater caffeine consumption, and that consumption is greater in adults with reduced sleep quality. PMID:27527212

  1. Antibacterial activity of caffeine against plant pathogenic bacteria.

    PubMed

    Sledz, Wojciech; Los, Emilia; Paczek, Agnieszka; Rischka, Jacek; Motyka, Agata; Zoledowska, Sabina; Piosik, Jacek; Lojkowska, Ewa

    2015-01-01

    The objective of the present study was to evaluate the antibacterial properties of a plant secondary metabolite - caffeine. Caffeine is present in over 100 plant species. Antibacterial activity of caffeine was examined against the following plant-pathogenic bacteria: Ralstonia solanacearum (Rsol), Clavibacter michiganesis subsp. sepedonicus (Cms), Dickeya solani (Dsol), Pectobacterium atrosepticum (Pba), Pectobacterium carotovorum subsp. carotovorum (Pcc), Pseudomonas syringae pv. tomato (Pst), and Xanthomonas campestris subsp. campestris (Xcc). MIC and MBC values ranged from 5 to 20 mM and from 43 to 100 mM, respectively. Caffeine increased the bacterial generation time of all tested species and caused changes in cell morphology. The influence of caffeine on the synthesis of DNA, RNA and proteins was investigated in cultures of plant pathogenic bacteria with labelled precursors: [(3)H]thymidine, [(3)H]uridine or (14)C leucine, respectively. RNA biosynthesis was more affected than DNA or protein biosynthesis in bacterial cells treated with caffeine. Treatment of Pba with caffeine for 336 h did not induce resistance to this compound. Caffeine application reduced disease symptoms caused by Dsol on chicory leaves, potato slices, and whole potato tubers. The data presented indicate caffeine as a potential tool for the control of diseases caused by plant-pathogenic bacteria, especially under storage conditions. PMID:26307771

  2. Exercise and sport performance with low doses of caffeine.

    PubMed

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (<3 mg/kg body mass, ~200 mg) are also ergogenic in some exercise and sport situations, although this has been less well studied. Lower caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis. PMID:25355191

  3. Caffeine Consumption and Sleep Quality in Australian Adults.

    PubMed

    Watson, Emily J; Coates, Alison M; Kohler, Mark; Banks, Siobhan

    2016-08-04

    Caffeine is commonly consumed to help offset fatigue, however, it can have several negative effects on sleep quality and quantity. The aim of this study was to determine the relationship between caffeine consumption and sleep quality in adults using a newly validated caffeine food frequency questionnaire (C-FFQ). In this cross sectional study, 80 adults (M ± SD: 38.9 ± 19.3 years) attended the University of South Australia to complete a C-FFQ and the Pittsburgh Sleep Quality Index (PSQI). Caffeine consumption remained stable across age groups while the source of caffeine varied. Higher total caffeine consumption was associated with decreased time in bed, as an estimate of sleep time (r = -0.229, p = 0.041), but other PSQI variables were not. Participants who reported poor sleep (PSQI global score ≥ 5) consumed 192.1 ± 122.5 mg (M ± SD) of caffeine which was significantly more than those who reported good sleep quality (PSQI global score < 5; 125.2 ± 62.6 mg; p = 0.008). The C-FFQ was found to be a quick but detailed way to collect population based caffeine consumption data. The data suggests that shorter sleep is associated with greater caffeine consumption, and that consumption is greater in adults with reduced sleep quality.

  4. Caffeine and anaerobic performance: ergogenic value and mechanisms of action.

    PubMed

    Davis, J K; Green, J Matt

    2009-01-01

    The effect caffeine elicits on endurance performance is well founded. However, comparatively less research has been conducted on the ergogenic potential of anaerobic performance. Some studies showing no effect of caffeine on performance used untrained subjects and designs often not conducive to observing an ergogenic effect. Recent studies incorporating trained subjects and paradigms specific to intermittent sports activity support the notion that caffeine is ergogenic to an extent with anaerobic exercise. Caffeine seems highly ergogenic for speed endurance exercise ranging in duration from 60 to 180 seconds. However, other traditional models examining power output (i.e. 30-second Wingate test) have shown minimal effect of caffeine on performance. Conversely, studies employing sport-specific methodologies (i.e. hockey, rugby, soccer) with shorter duration (i.e. 4-6 seconds) show caffeine to be ergogenic during high-intensity intermittent exercise. Recent studies show caffeine affects isometric maximal force and offers introductory evidence for enhanced muscle endurance for lower body musculature. However, isokinetic peak torque, one-repetition maximum and muscular endurance for upper body musculature are less clear. Since relatively few studies exist with resistance training, a definite conclusion cannot be reached on the extent caffeine affects performance. It was previously thought that caffeine mechanisms were associated with adrenaline (epinephrine)-induced enhanced free-fatty acid oxidation and consequent glycogen sparing, which is the leading hypothesis for the ergogenic effect. It would seem unlikely that the proposed theory would result in improved anaerobic performance, since exercise is dominated by oxygen-independent metabolic pathways. Other mechanisms for caffeine have been suggested, such as enhanced calcium mobilization and phosphodiesterase inhibition. However, a normal physiological dose of caffeine in vivo does not indicate this mechanism plays a

  5. Antibacterial activity of caffeine against plant pathogenic bacteria.

    PubMed

    Sledz, Wojciech; Los, Emilia; Paczek, Agnieszka; Rischka, Jacek; Motyka, Agata; Zoledowska, Sabina; Piosik, Jacek; Lojkowska, Ewa

    2015-01-01

    The objective of the present study was to evaluate the antibacterial properties of a plant secondary metabolite - caffeine. Caffeine is present in over 100 plant species. Antibacterial activity of caffeine was examined against the following plant-pathogenic bacteria: Ralstonia solanacearum (Rsol), Clavibacter michiganesis subsp. sepedonicus (Cms), Dickeya solani (Dsol), Pectobacterium atrosepticum (Pba), Pectobacterium carotovorum subsp. carotovorum (Pcc), Pseudomonas syringae pv. tomato (Pst), and Xanthomonas campestris subsp. campestris (Xcc). MIC and MBC values ranged from 5 to 20 mM and from 43 to 100 mM, respectively. Caffeine increased the bacterial generation time of all tested species and caused changes in cell morphology. The influence of caffeine on the synthesis of DNA, RNA and proteins was investigated in cultures of plant pathogenic bacteria with labelled precursors: [(3)H]thymidine, [(3)H]uridine or (14)C leucine, respectively. RNA biosynthesis was more affected than DNA or protein biosynthesis in bacterial cells treated with caffeine. Treatment of Pba with caffeine for 336 h did not induce resistance to this compound. Caffeine application reduced disease symptoms caused by Dsol on chicory leaves, potato slices, and whole potato tubers. The data presented indicate caffeine as a potential tool for the control of diseases caused by plant-pathogenic bacteria, especially under storage conditions.

  6. Cytokinesis in Impatiens balsamina and the effect of caffeine.

    PubMed

    Jones, M G; Payne, H L

    1978-01-01

    A description of cytokinesis in cells of roots of Impatiens balsamina is given, and the effect of caffeine on this process. The disposition of organelles, microtubules and vesicles which form the new cell plate is similar in normal and caffeine treated roots. In sections cut in the plane of the developing cell plate, membranous arms radiating from common centres appear to play an important role in promoting efficient fusion of the vesicles, and caffeine reduces their occurrence. The possible presence of callose in the newly formed cell plate, and the formation of plasmodesmata, are discussed. Mechanisms of membrane fusion and effects of caffeine on this event are also considered.

  7. Exercise and sport performance with low doses of caffeine.

    PubMed

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (<3 mg/kg body mass, ~200 mg) are also ergogenic in some exercise and sport situations, although this has been less well studied. Lower caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis.

  8. Severe anion gap metabolic acidosis from acetaminophen use secondary to 5-oxoproline (pyroglutamic acid) accumulation.

    PubMed

    Zand, Ladan; Muriithi, Angela; Nelsen, Eric; Franco, Pablo M; Greene, Eddie L; Qian, Qi; El-Zoghby, Ziad M

    2012-12-01

    Anion gap metabolic acidosis (AGMA) is commonly encountered in medical practice. Acetaminophen-induced AGMA is, however, not widely recognized. We report 2 cases of high anion gap metabolic acidosis secondary to 5-oxoproline accumulation resulting from acetaminophen consumption: the first case caused by acute one-time ingestion of large quantities of acetaminophen and the second case caused by chronic repeated ingestion in a patient with chronic liver disease. Recognition of this entity facilitated timely diagnosis and effective treatment. Given acetaminophen is commonly used over the counter medication, increased recognition of this adverse effect is of important clinical significance.

  9. Inhibition of acetaminophen activation by ethanol and acetaldehyde in liver microsomes

    SciTech Connect

    Chifumi Sato; Jian Liu; Happei Miyakawa; Toshihiko Nouchi; Yujiro Tanaka; Masakatsu Uchihara; Fumiaki Marumo Tokyo Medical and Dental Univ. )

    1991-01-01

    Mechanisms of the inhibitory effect of ethanol on acetaminophen hepatotoxicity are controversial. The authors studied the effects of ethanol and acetaldehyde, and oxidative metabolite of ethanol, on NADHP-dependent acetaminophen-glutathione conjugate production in liver microsomes. Ethanol at concentrations as low as 2mM prevented the conjugate production noncompetitively. Acetaldehyde also inhibited acetaminophen-glutathione conjugate production at concentrations as low as 0.1 mM that is comparable with those observed in vivo after social drinking. Acetaldehyde may be involved in ethanol-induced inhibition of acetaminophen hepatotoxicity.

  10. Acetaminophen Poisoning and Risk of Acute Pancreatitis: A Population-Based Cohort Study.

    PubMed

    Chen, Sy-Jou; Lin, Chin-Sheng; Hsu, Chin-Wang; Lin, Cheng-Li; Kao, Chia-Hung

    2015-07-01

    The aim of this study was to assess whether acetaminophen poisoning is associated with a higher risk of acute pancreatitis. We conducted a retrospective cohort study by using the longitudinal population-based database of Taiwan's National Health Insurance (NHI) program between 2000 and 2011. The acetaminophen cohort comprised patients aged ≥ 20 years with newly identified acetaminophen poisoning (N = 2958). The comparison cohort comprised randomly selected patients with no history of acetaminophen poisoning. The acetaminophen and comparison cohorts were frequency matched by age, sex, and index year (N = 11,832) at a 1:4 ratio. Each patient was followed up from the index date until the date an acute pancreatitis diagnosis was made, withdrawal from the NHI program, or December 31, 2011. Cox proportional hazard regression models were used to determine the effects of acetaminophen on the risk of acute pancreatitis.The risk of acute pancreatitis was 3.11-fold higher in the acetaminophen cohort than in the comparison cohort (11.2 vs 3.61 per 10,000 person-years), with an adjusted hazard ratio of 2.40 (95% confidence interval, 1.29-4.47). The incidence rate was considerably high in patients who were aged 35 to 49 years, men, those who had comorbidities, and within the first year of follow-up.Acetaminophen poisoning is associated with an increased risk of acute pancreatitis. Additional prospective studies are necessary to verify how acetaminophen poisoning affects the risk of acute pancreatitis.

  11. Combining boron isotopes and carbamazepine to monitor artificial recharge (southern Mediterranean)

    NASA Astrophysics Data System (ADS)

    Cary, Lise; Guerrot, Catherine; Casanova, Joël

    2014-05-01

    The groundwater resources of coastal areas are highly vulnerable, being located either in complex hydrogeological structures or in local shallow aquifers where water stress and salt water intrusion occur under the multiple constraints governed by increasing anthropogenic pressures and climatic conditions. Yet, recent integrated water resource planning often relies on alternative water supplies. In order to limit seawater intrusion in an agricultural overexploited watershed and to ensure water availability, managed aquifer recharge with treated wastewater was settled in the Korba aquifer on the east coast of Tunisia. Water quality monitoring was implemented in order to determine the different system components and to trace the effectiveness of the artificial recharge. Groundwater samples taken from recharge control piezometers and surrounding farm wells were analyzed for their chemical contents, for their boron isotopes, a proven tracer of groundwater salinization and domestic sewage, and their carbamazepine content, an anti-epileptic known to pass through wastewater treatment and so recognized as a pertinent tracer of wastewater contamination. The aquifer system is constituted by the superficial and shallow Plio-Quaternary formations and by the deeper Miocene units which constitute its basement. Marine Pliocene sediments display interbedded sandstone-sand-marl topped with variably clayey sandstone. Quaternary deposits are mainly made of fossiliferous carbonated sandstones. The system equilibrium was permanently disturbed by the different temporal dynamics of continuous processes such as cation exchange, and by threshold processes linked to oxidation-reductive conditions. The boron isotopic compositions of groundwaters displayed a significant variability (10 - 45 ) and significantly shifted back-and-forth due to mixing with end-members of various origins. Under the variable contribution of meteoric recharge, the Plio-Quaternary groundwater was subject to seawater

  12. Interpretation of hair findings in children: about a case involving carbamazepine.

    PubMed

    Kintz, Pascal

    2014-06-01

    This office has been recently involved in a case dealing with child custody, where the final outcome was difficult to establish. The following concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the hair of a 21-month-old girl: 154 (0-1 cm), 198 (1-2 cm), 247 (2-3 cm), and 368 pg/mg (3-4 cm) after decontamination. Obviously, the concentrations measured in the hair were much lower than those observed in patients under daily treatment. In this sense, the frequency of exposures appears as infrequent (low level of exposure), with marked decrease in the more recent period. However, the girl was never prescribed carbamazepine and the mother, who was under carbamazepine therapy, denied any administration. The Judge asked if this could result from a single exposure and at which period. At least, three possible interpretations of the measured carbamazepine concentrations were addressed: (1) decrease in administration in the more recent period; (2) increase of body weight due to growing, so the same dosage will result in lower concentrations in hair; and (3) sweat contamination from the mother at the time the girl is with her in bed, the older hair being in contact longer with the bedding. In this case, it was impossible to conclude that the child was deliberately administered carbamazepine. The results of the analysis of hair could indicate that she was in an environment where carbamazepine was being used and where the drug was not being handled and stored with appropriate care. There are many differences between the hair from children and those from adults: hair from children is thinner and more porous, the ratio anagen and catagen phases are not maintained, and the growth rate can be different, at some periods, from the usual 1 cm/month. These differences, together with the influence of PK-PD parameters are reviewed in this paper, as a basis for suitable interpretation. In view of these results it is proposed that a single hair

  13. Effects of Smoking Cues on Caffeine Urges in Heavy Smokers and Caffeine Consumers with and without Schizophrenia

    PubMed Central

    Adolfo, Amy B.; AhnAllen, Christopher G.; Tidey, Jennifer W.

    2009-01-01

    Cigarette smoking and caffeine use are established and problematic drug-use behaviors in people with schizophrenia. Associative links between drugs of abuse may occur but the relationship between caffeine use and cigarette smoking has received little attention in schizophrenia. In this cross-cue reactivity laboratory study, we examined the effects of neutral and smoking cues on craving for caffeinated beverages in participants with schizophrenia or schizoaffective disorder (SS; n = 15) and non-psychiatric controls (CS; n = 18) all of whom were heavy smokers and daily caffeine users. Participants were tested under non-abstinent and 5-hour abstinent conditions. SS tended to report greater daily levels of caffeine use than CS. Although this difference was not significant, that may be due to the small sample sizes as the size of this effect was large. Daily caffeine intake was significantly correlated with daily smoking rate in SS but not CS. A significant interaction between group and cue type after controlling for caffeine intake indicated that exposure to smoking cues increased urge for caffeinated beverages in SS but not CS. These results indicate support for associative connections between cigarette smoking cues and craving for caffeine in smokers with schizophrenia. PMID:19006656

  14. Co-administration of N-Acetylcysteine and Acetaminophen Efficiently Blocks Acetaminophen Toxicity.

    PubMed

    Owumi, Solomon E; Andrus, James P; Herzenberg, Leonard A; Herzenberg, Leonore A

    2015-08-01

    Preclinical Research Although acetaminophen (APAP) is an effective analgesic and anti-pyretic, APAP overdose is the most frequent cause of serious, often lethal, drug-induced hepatotoxicity. Administration of N-acetyl cysteine (NAC) within 8 hours of APAP overdose effectively mitigates APAP-induced hepatotoxicity. Thus, preventing APAP toxicity before it occurs by formulating APAP with NAC is logical and, as we show here in a mouse model, is effective in preventing APAP toxicity. Thus, toxic oral APAP doses sufficient to cause severe widespread liver damage do not cause significant damage when administered concurrently with equal amounts of NAC, that is, in the NAC-APAP treated animals, hepatic transaminases increase only marginally and liver architecture remains fully intact. Thus, we conclude that concomitant oral dosing with APAP and NAC can provide a convenient and effective way of preventing toxicity associated with large dosage of APAP. From a public health perspective, these findings support the concept that a co-formulation of APAP plus NAC is a viable over-the-counter (OTC) alternative to the current practice of providing APAP OTC and treating APAP toxicity if/when it occurs. In essence, our findings indicate that replacing the current OTC APAP with a safe and functional APAP/NAC formulation could prevent the accidental and intentional APAP toxicity that occurs today. PMID:26250417

  15. Co-administration of N-Acetylcysteine and Acetaminophen Efficiently Blocks Acetaminophen Toxicity.

    PubMed

    Owumi, Solomon E; Andrus, James P; Herzenberg, Leonard A; Herzenberg, Leonore A

    2015-08-01

    Preclinical Research Although acetaminophen (APAP) is an effective analgesic and anti-pyretic, APAP overdose is the most frequent cause of serious, often lethal, drug-induced hepatotoxicity. Administration of N-acetyl cysteine (NAC) within 8 hours of APAP overdose effectively mitigates APAP-induced hepatotoxicity. Thus, preventing APAP toxicity before it occurs by formulating APAP with NAC is logical and, as we show here in a mouse model, is effective in preventing APAP toxicity. Thus, toxic oral APAP doses sufficient to cause severe widespread liver damage do not cause significant damage when administered concurrently with equal amounts of NAC, that is, in the NAC-APAP treated animals, hepatic transaminases increase only marginally and liver architecture remains fully intact. Thus, we conclude that concomitant oral dosing with APAP and NAC can provide a convenient and effective way of preventing toxicity associated with large dosage of APAP. From a public health perspective, these findings support the concept that a co-formulation of APAP plus NAC is a viable over-the-counter (OTC) alternative to the current practice of providing APAP OTC and treating APAP toxicity if/when it occurs. In essence, our findings indicate that replacing the current OTC APAP with a safe and functional APAP/NAC formulation could prevent the accidental and intentional APAP toxicity that occurs today.

  16. What's in a teaspoon? Underdosing with acetaminophen in family practice.

    PubMed

    Hyam, E; Brawer, M; Herman, J; Zvieli, S

    1989-09-01

    A study was made of 100 paediatric encounters in which an accompanying parent stated that the child had been given acetaminophen syrup during the preceding 24 hours. In 80% of cases a household teaspoon had been used to determine the amount of medication required. The volumes of these spoons were measured using a syringe. The range was from 1.5 to 5 cm3 with 79% containing 2 to 3 cm3. The mean volume was 2.95 cm3 (SD 0.79) and the median was 2.5 cm3. The mean dose administered was 62% of that recommended when the calculation was made according to age and 64% according to body weight. Much of the underdosing observed was due to parents' assumption that a household teaspoon contains 5 cm3 of acetaminophen syrup and also to a failure to correct for advancing age and increasing weight. PMID:2792624

  17. Role of nicotinamide (vitamin B3) in acetaminophen-induced changes in rat liver: Nicotinamide effect in acetaminophen-damged liver.

    PubMed

    Mahmoud, Yomna I; Mahmoud, Asmaa A

    2016-06-01

    Acetaminophen is a widely used analgesic and antipyretic agent, which is safe at therapeutic doses. However, overdoses of acetaminophen induce severe oxidative stress, which leads to acute liver failure. Nicotinamide has proven effective in ameliorating many pathological conditions that occur due to oxidative stress. This study verifies the prophylactic and therapeutic effects of nicotinamide against the hepatic pathophysiological and ultrastructural alterations induced by acetaminophen. Wistar rats intoxicated with an acute overdose of acetaminophen (5g/kg b.wt) were given a single dose of nicotinamide (500mg/kg b.wt) either before or after intoxication. Acetaminophen caused significant elevation in the liver functions and lipid peroxidation marker, and decline in the activities of the hepatic antioxidant enzymes. This oxidative injury was associated with hepatic centrilobular necrosis, hemorrage, vacuolar degeneration, lipid accumulation and mitochondrial alterations. Treating intoxicated rats with nicotinamide (500mg/kg) significantly ameliorated acetaminophen-induced biochemical changes and pathological injuries. However, administering the same dose of nicotinamide to healthy animals or prior to acetaminophen-intoxication induced hepatotoxicity. Caution should be taken when administering high doses of NAM because of its possible hepatotoxicity. Considering the wide use of nicotinamide, there is an important need for monitoring nicotinamide tolerance, safety and efficacy in healthy and diseased subjects. PMID:27211843

  18. The influence of CYP2C8*3 on carbamazepine serum concentration in epileptic pediatric patients

    PubMed Central

    Milovanovic, DD; Milovanovic, JR; Radovanovic, M; Radosavljevic, I; Obradovic, S; Jankovic, S; Milovanovic, D

    2016-01-01

    Abstract The aim of the present study was to investigate the distribution of CYP2C8 variants *3 and *5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). The CYP2C8 *3 and *5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8*3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8*3 (mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL, p = 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in CYP2C8*3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 *3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that the CYP2C8*3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.

  19. Increased caffeine consumption is associated with reduced hepatic fibrosis

    PubMed Central

    Modi, Apurva A; Feld, Jordan J; Park, Yoon; Kleiner, David E; Everhart, James E.; Liang, T. Jake; Hoofnagle, Jay H.

    2009-01-01

    Background Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. Aim To use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Methods Patients undergoing liver biopsy completed a detailed caffeine questionnaire on 3 occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis. Results 177 patients (99 male, 104 Caucasian, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions. Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75th percentile for the cohort (308 mg ~2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (OR 0.33, 95% CI: 0.14-0.80, p=0.015) and the protective association persisted after controlling for age, sex, race, liver disease, body mass index and alcohol intake in all patients (OR 0.25, 95% CI: 0.09-0.67, p=0.006), as well as the subset with HCV infection (OR 0.19, 95% CI: 0.05-0.66, p=0.009). Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis. Conclusion A reliable tool for measurement of caffeine consumption demonstrated that caffeine consumption, particularly from regular coffee, above a threshold of approximately 2 coffee-cup equivalents per day, was associated with less severe hepatic fibrosis. PMID:20034049

  20. Cytochrome P450-Dependent Metabolism of Caffeine in Drosophila melanogaster

    PubMed Central

    Coelho, Alexandra; Fraichard, Stephane; Le Goff, Gaëlle; Faure, Philippe; Artur, Yves; Ferveur, Jean-François; Heydel, Jean-Marie

    2015-01-01

    Caffeine (1, 3, 7-trimethylxanthine), an alkaloid produced by plants, has antioxidant and insecticide properties that can affect metabolism and cognition. In vertebrates, the metabolites derived from caffeine have been identified, and their functions have been characterized. However, the metabolites of caffeine in insects remain unknown. Thus, using radiolabelled caffeine, we have identified some of the primary caffeine metabolites produced in the body of Drosophila melanogaster males, including theobromine, paraxanthine and theophylline. In contrast to mammals, theobromine was the predominant metabolite (paraxanthine in humans; theophylline in monkeys; 1, 3, 7-trimethyluric acid in rodents). A transcriptomic screen of Drosophila flies exposed to caffeine revealed the coordinated variation of a large set of genes that encode xenobiotic-metabolizing proteins, including several cytochromes P450s (CYPs) that were highly overexpressed. Flies treated with metyrapone—an inhibitor of CYP enzymes—showed dramatically decreased caffeine metabolism, indicating that CYPs are involved in this process. Using interference RNA genetic silencing, we measured the metabolic and transcriptomic effect of three candidate CYPs. Silencing of CYP6d5 completely abolished theobromine synthesis, whereas CYP6a8 and CYP12d1 silencing induced different consequences on metabolism and gene expression. Therefore, we characterized several metabolic products and some enzymes potentially involved in the degradation of caffeine. In conclusion, this pioneer approach to caffeine metabolism in insects opens novel perspectives for the investigation of the physiological effects of caffeine metabolites. It also indicates that caffeine could be used as a biomarker to evaluate CYP phenotypes in Drosophila and other insects. PMID:25671424

  1. Cytochrome P450-dependent metabolism of caffeine in Drosophila melanogaster.

    PubMed

    Coelho, Alexandra; Fraichard, Stephane; Le Goff, Gaëlle; Faure, Philippe; Artur, Yves; Ferveur, Jean-François; Heydel, Jean-Marie

    2015-01-01

    Caffeine (1, 3, 7-trimethylxanthine), an alkaloid produced by plants, has antioxidant and insecticide properties that can affect metabolism and cognition. In vertebrates, the metabolites derived from caffeine have been identified, and their functions have been characterized. However, the metabolites of caffeine in insects remain unknown. Thus, using radiolabelled caffeine, we have identified some of the primary caffeine metabolites produced in the body of Drosophila melanogaster males, including theobromine, paraxanthine and theophylline. In contrast to mammals, theobromine was the predominant metabolite (paraxanthine in humans; theophylline in monkeys; 1, 3, 7-trimethyluric acid in rodents). A transcriptomic screen of Drosophila flies exposed to caffeine revealed the coordinated variation of a large set of genes that encode xenobiotic-metabolizing proteins, including several cytochromes P450s (CYPs) that were highly overexpressed. Flies treated with metyrapone--an inhibitor of CYP enzymes--showed dramatically decreased caffeine metabolism, indicating that CYPs are involved in this process. Using interference RNA genetic silencing, we measured the metabolic and transcriptomic effect of three candidate CYPs. Silencing of CYP6d5 completely abolished theobromine synthesis, whereas CYP6a8 and CYP12d1 silencing induced different consequences on metabolism and gene expression. Therefore, we characterized several metabolic products and some enzymes potentially involved in the degradation of caffeine. In conclusion, this pioneer approach to caffeine metabolism in insects opens novel perspectives for the investigation of the physiological effects of caffeine metabolites. It also indicates that caffeine could be used as a biomarker to evaluate CYP phenotypes in Drosophila and other insects. PMID:25671424

  2. Caffeine triggers behavioral and neurochemical alterations in adolescent rats.

    PubMed

    Ardais, A P; Borges, M F; Rocha, A S; Sallaberry, C; Cunha, R A; Porciúncula, L O

    2014-06-13

    Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions.

  3. Cytochrome P450-dependent metabolism of caffeine in Drosophila melanogaster.

    PubMed

    Coelho, Alexandra; Fraichard, Stephane; Le Goff, Gaëlle; Faure, Philippe; Artur, Yves; Ferveur, Jean-François; Heydel, Jean-Marie

    2015-01-01

    Caffeine (1, 3, 7-trimethylxanthine), an alkaloid produced by plants, has antioxidant and insecticide properties that can affect metabolism and cognition. In vertebrates, the metabolites derived from caffeine have been identified, and their functions have been characterized. However, the metabolites of caffeine in insects remain unknown. Thus, using radiolabelled caffeine, we have identified some of the primary caffeine metabolites produced in the body of Drosophila melanogaster males, including theobromine, paraxanthine and theophylline. In contrast to mammals, theobromine was the predominant metabolite (paraxanthine in humans; theophylline in monkeys; 1, 3, 7-trimethyluric acid in rodents). A transcriptomic screen of Drosophila flies exposed to caffeine revealed the coordinated variation of a large set of genes that encode xenobiotic-metabolizing proteins, including several cytochromes P450s (CYPs) that were highly overexpressed. Flies treated with metyrapone--an inhibitor of CYP enzymes--showed dramatically decreased caffeine metabolism, indicating that CYPs are involved in this process. Using interference RNA genetic silencing, we measured the metabolic and transcriptomic effect of three candidate CYPs. Silencing of CYP6d5 completely abolished theobromine synthesis, whereas CYP6a8 and CYP12d1 silencing induced different consequences on metabolism and gene expression. Therefore, we characterized several metabolic products and some enzymes potentially involved in the degradation of caffeine. In conclusion, this pioneer approach to caffeine metabolism in insects opens novel perspectives for the investigation of the physiological effects of caffeine metabolites. It also indicates that caffeine could be used as a biomarker to evaluate CYP phenotypes in Drosophila and other insects.

  4. Fennel and raspberry leaf as possible inhibitors of acetaminophen oxidation.

    PubMed

    Langhammer, Astrid Jordet; Nilsen, Odd Georg

    2014-10-01

    In addition to CYP2E1, several CYP isoenzymes, notably CYP1A2, 2D6, and 3A4, are suggested to contribute in acetaminophen oxidation and formation of the hepatotoxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). The in vitro CYP2E1 inhibitory potentials of fennel and raspberry leaf, herbs previously found to inhibit CYP1A2, 2D6, and 3A4 activities in vitro, were investigated. Extracts from commercially available herbal products were incubated with recombinant cDNA-expressed human CYP2E1. A validated LC/MS/MS methodology was applied for determination of 6-hydroxychlorzoxazone formation with disulfiram used as a positive inhibitory control. CYP2E1 IC50 inhibition constants were found to be 23 ± 4 and 27 ± 5 µg/ml for fennel and raspberry leaf, respectively, constants significantly lower than those presented in the literature for other herbal extracts. Together with previous findings, the presented in vitro data for CYP2E1 inhibition suggest that fennel and raspberry leaf have a significant potential of inhibiting all the major metabolic pathways for acetaminophen oxidation and NAPQI formation. Both herbs should be further investigated for their in vivo ability of inhibiting acetaminophen oxidation and NAPQI formation.

  5. Acetaminophen-induced acute liver injury in mice.

    PubMed

    Mossanen, J C; Tacke, F

    2015-04-01

    The induction of acute hepatic damage by acetaminophen (N-acetyl-p-aminophenol [APAP]), also termed paracetamol, is one of the most commonly used experimental models of acute liver injury in mice. The specific values of this model are the highly reproducible, dose-dependent hepatotoxicity of APAP and its outstanding translational importance, because acetaminophen overdose is one of the most frequent reasons for acute liver failure (ALF) in humans. However, preparation of concentrated APAP working solutions, application routes, fasting period and variability due to sex, genetic background or barrier environment represent important considerations to be taken into account before implementing this model. This standard operating procedure (SOP) provides a detailed protocol for APAP preparation and application in mice, aimed at facilitating comparability between research groups as well as minimizing animal numbers and distress. The mouse model of acetaminophen poisoning therefore helps to unravel the pathogenesis of APAP-induced toxicity or subsequent immune responses in order to explore new therapeutic interventions for improving the prognosis of ALF in patients.

  6. [Analgesic/Antipyretic treatment: ibuprofen or acetaminophen? An update].

    PubMed

    Olive, Georges

    2006-01-01

    Because of the adverse effects associated with aspirin, especially Reye's syndrome in children, practitioners currently use as first line therapy drugs such as ibuprofen or acetaminophen. Their pharmacokinetic characteristics are not quite identical: both are absorbed rapidly and have high bioavailability, however, unlike acetaminophen, ibuprofen is characterized by high plasma protein binding and a limited distribution volume. Both drugs are metabolized essentially in the liver into inactive hydroxylated or glucoronidated metabolites by conjugation but acetaminophen is also transformed into an oxidation compound--normally reduced by glutathione--which, in the case of acute overdosing with depletion of endogenous glutathione stores, may lead to severe hepatotoxicity. Old age and light to moderate renal or hepatic failure do not significantly modify their pharmacokinetic parameters, and thus do not call for dose adjustment. Clinical trials have shown both drugs to have comparable efficacy on pain and fever, with perhaps a slight advantage for ibuprofen. In practice, the choice will depend on the prescription habits of the practitioner, patient's (or parents') preferences and, above all, the pathological context and possible contra-indications. PMID:16886709

  7. Formulation and characterization of acetaminophen nanoparticles in orally disintegrating films.

    PubMed

    Al-Nemrawi, Nusaiba K; Dave, Rutesh H

    2016-01-01

    The purpose of this study was to prepare orally disintegrating films containing nanoparticles loaded with acetaminophen. Nanoparticles were prepared by the emulsion-solvent evaporation method where acetone phase containing acetaminophen and poly(lactide-co-glycolide acid) (PLGA) was added to water phase containing hydroxypropyl methyl cellulose, poly ethylene glycol, polyvinyl alcohol (PVA) and aspartame in a rate of 1.5 drop s(-1) and agitated at 1200 rpm. The size, polydispersity index (PI) and drug entrapment (DE) were measured. The emulsions were cast to form films, which were evaluated physico-mechanically. The effect of different degrees of hydrolization of PVA and polymerization of PLGA and the effect of different ratios of PVA to PLGA was studied. Films with acceptable physico-mechanical properties were further studied. The size and PI of the nanoparticles was dependent on PVA hydrolization, PLGA polymerization and the ratio of PVA to PLGA. All films disintegrated in less than one minute, but acetaminophen was not free in the dissolution media even after six days. These results may indicate that although the nanoparticles released from the films immediately when impressed in solution the drug is sustained in the nanoparticles for longer time, which is to be clarified in future work.

  8. Developmental exposure to acetaminophen does not induce hyperactivity in zebrafish larvae.

    PubMed

    Reuter, Isabel; Knaup, Sabine; Romanos, Marcel; Lesch, Klaus-Peter; Drepper, Carsten; Lillesaar, Christina

    2016-08-01

    First line pain relief medication during pregnancy relies nearly entirely on the over-the-counter analgesic acetaminophen, which is generally considered safe to use during gestation. However, recent epidemiological studies suggest a risk of developing attention-deficit/hyperactivity disorder (ADHD)-like symptoms in children if mothers use acetaminophen during pregnancy. Currently, there are no experimental proofs that prenatal acetaminophen exposure causes developmental brain alterations of progeny. Exposure to high acetaminophen concentrations causes liver toxicity, which is well investigated in different model organisms. However, sub-liver-toxic concentrations have not been experimentally investigated with respect to ADHD endophenotypes such as hyperactivity. We used zebrafish to investigate the potential impact of acetaminophen exposure on locomotor activity levels, and compared it to the established zebrafish Latrophilin 3 (Lphn3) ADHD-model. We determined the sub-liver-toxic concentration of acetaminophen in zebrafish larvae and treated wild-type and lphn3.1 knockdown larvae with increasing concentrations of acetaminophen. We were able to confirm that lphn3.1 knockdown alone causes hyperactivity, strengthening the implication of Lphn3 dysfunction as an ADHD risk factor. Neither acute nor chronic exposure to acetaminophen at sub-liver-toxic concentrations in wild-type or lphn3.1 knock-downs increases locomotor activity levels. Together our findings show that embryonic to larval exposure to acetaminophen does not cause hyperactivity in zebrafish larvae. Furthermore, there are no additive and/or synergistic effects of acetaminophen exposure in a susceptible background induced by knock-down of lphn3.1. Our experimental study suggests that there is, at least in zebrafish larvae, no direct link between embryonic acetaminophen exposure and hyperactivity. Further work is necessary to clarify this issue in humans. PMID:27116683

  9. Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the {gamma}-glutamyl cycle

    SciTech Connect

    Stern, Stephan T.; Bruno, Mary K.; Horton, Robert A.; Hill, Dennis W.; Roberts, Jeanette C.; Cohen, Steven D. . E-mail: scohen@mcp.edu

    2005-01-15

    Acetaminophen (APAP) nephrotoxicity has been observed both in humans and research animals. Our recent investigations have focused on the possible involvement of glutathione-derived APAP metabolites in APAP nephrotoxicity and have demonstrated that administration of acetaminophen-cysteine (APAP-CYS) potentiated APAP-induced renal injury with no effects on APAP-induced liver injury. Additionally, APAP-CYS treatment alone resulted in a dose-responsive renal GSH depletion. This APAP-CYS-induced renal GSH depletion could interfere with intrarenal detoxification of APAP or its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) and may be the mechanism responsible for the potentiation of APAP nephrotoxicity. Renal-specific GSH depletion has been demonstrated in mice and rats following administration of amino acid {gamma}-glutamyl acceptor substrates for {gamma}-glutamyl transpeptidase ({gamma}-GT). The present study sought to determine if APAP-CYS-induced renal glutathione depletion is the result of disruption of the {gamma}-glutamyl cycle through interaction with {gamma}-GT. The results confirmed that APAP-CYS-induced renal GSH depletion was antagonized by the {gamma}-glutamyl transpeptidase ({gamma}-GT) inhibitor acivicin. In vitro analysis demonstrated that APAP-CYS is a {gamma}-glutamyl acceptor for both murine and bovine renal {gamma}-GT. Analysis of urine from mice pretreated with acivicin and then treated with APAP, APAP-CYS, or acetaminophen-glutathione identified a {gamma}-glutamyl-cysteinyl-acetaminophen metabolite. These findings are consistent with the hypothesis that APAP-CYS contributes to APAP nephrotoxicity by depletion of renal GSH stores through interaction with the {gamma}-glutamyl cycle.

  10. Caffeine and the risk of hip fracture: the Framingham Study.

    PubMed

    Kiel, D P; Felson, D T; Hannan, M T; Anderson, J J; Wilson, P W

    1990-10-01

    Caffeine increases urinary calcium output and has been implicated as a risk factor for osteoporosis. The authors examined the effect of caffeine on hip fracture risk in 3,170 individuals attending the 12th (1971-1973) Framingham Study examination. Coffee and tea consumption, age, Framingham examination number, weight, smoking, alcohol consumption, and estrogen use were used to evaluate hip fracture risk according to caffeine intake. Hip fractures occurred in 135 subjects during 12 years of follow-up. Fracture risk over each 2-year period increased with increasing caffeine intake (one cup of coffee = one unit of caffeine, one cup of tea = 1/2 unit of caffeine). For intake of 1.5-2.0 units per day, the adjusted relative risk (RR) of fracture was not significantly elevated compared with intake of one or less units per day. Consumption of greater than or equal to 2.5 units per day significantly increased the risk of fracture. Overall, intake of greater than two cups of coffee per day (four cups of tea) increased the risk of fracture. In summary, hip fracture risk was modestly increased with heavy caffeine use, but not for intake equivalent to one cup of coffee per day. Since caffeine use may be associated with other behaviors that are, themselves, risk factors for fracture, the association may be indirect. Further studies should be performed to confirm these findings.

  11. Human coffee drinking: manipulation of concentration and caffeine dose.

    PubMed Central

    Griffiths, R R; Bigelow, G E; Liebson, I A; O'Keeffe, M; O'Leary, D; Russ, N

    1986-01-01

    In a residential research ward coffee drinking was studied in 9 volunteer human subjects with histories of heavy coffee drinking. A series of five experiments was undertaken to characterize adlibitum coffee consumption and to investigate the effects of manipulating coffee concentration, caffeine dose per cup, and caffeine preloads prior to coffee drinking. Manipulations were double-blind and scheduled in randomized sequences across days. When cups of coffee were freely available, coffee drinking tended to be rather regularly spaced during the day with intercup intervals becoming progressively longer throughout the day; experimental manipulations showed that this lengthening of intercup intervals was not due to accumulating caffeine levels. Number of cups of coffee consumed was an inverted U-shaped function of both coffee concentration and caffeine dose per cup; however, coffee-concentration and dose-per-cup manipulations did not produce similar effects on other measures of coffee drinking (intercup interval, time to drink a cup, within-day distribution of cups). Caffeine preload produced dose-related decreases in number of cups consumed. As a whole, these experiments provide some limited evidence for both the suppressive and the reinforcing effects of caffeine on coffee consumption. Examination of total daily coffee and caffeine intake across experiments, however, provides no evidence for precise regulation (i.e., titration) of coffee or caffeine intake. PMID:3958660

  12. Caffeine Use among Active Duty Navy and Marine Corps Personnel

    PubMed Central

    Knapik, Joseph J.; Trone, Daniel W.; McGraw, Susan; Steelman, Ryan A.; Austin, Krista G.; Lieberman, Harris R.

    2016-01-01

    Data from the National Health and Nutrition Examination Survey (NHANES) indicate 89% of Americans regularly consume caffeine, but these data do not include military personnel. This cross-sectional study examined caffeine use in Navy and Marine Corps personnel, including prevalence, amount of daily consumption, and factors associated with use. A random sample of Navy and Marine Corps personnel was contacted and asked to complete a detailed questionnaire describing their use of caffeine-containing substances, in addition to their demographic, military, and lifestyle characteristics. A total of 1708 service members (SMs) completed the questionnaire. Overall, 87% reported using caffeinated beverages ≥1 time/week, with caffeine users consuming a mean ± standard error of 226 ± 5 mg/day (242 ± 7 mg/day for men, 183 ± 8 mg/day for women). The most commonly consumed caffeinated beverages (% users) were coffee (65%), colas (54%), teas (40%), and energy drinks (28%). Multivariable logistic regression modeling indicated that characteristics independently associated with caffeine use (≥1 time/week) included older age, white race/ethnicity, higher alcohol consumption, and participating in less resistance training. Prevalence of caffeine use in these SMs was similar to that reported in civilian investigations, but daily consumption (mg/day) was higher. PMID:27735834

  13. Maternal Caffeine Consumption and Risk of Congenital Limb Deficiencies

    PubMed Central

    Chen, Lei; Bell, Erin M.; Browne, Marilyn L.; Druschel, Charlotte M.; Romitti, Paul A.; Schmidt, Rebecca J.; Burns, Trudy L.; Moslehi, Roxana; Olney, Richard S.

    2015-01-01

    BACKGROUND Animal studies have shown that high doses of caffeine might cause congenital limb deficiencies (LDs); however, no epidemiologic studies have explored this relation. METHODS This case-control study assessed associations between maternal dietary caffeine and congenital LDs using data from the National Birth Defects Prevention Study (NBDPS), with 844 LD cases and 8069 controls from 1997 to 2007. Caffeine intakes from beverages (coffee, tea, and soda) and chocolate combined and by beverage type were examined. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated for subtypes of isolated LDs (no additional major anomalies) and LDs with other major anomalies separately, comparing the odds of 10 to <100, 100 to <200, 200 to <300, and 300+ mg/day total caffeine intake to 0 to <10 mg/day. RESULTS All total dietary caffeine intake categories of 10 mg/day and above were marginally associated with odds of all isolated LDs combined (aOR, 1.4–1.7), isolated longitudinal LDs (aOR, 1.2–1.6), and isolated transverse LDs (aOR, 1.3–1.8) compared to the lowest intake category. A dose-response pattern for total dietary caffeine intake was not observed. CONCLUSIONS A weak increased risk of congenital LDs associated with maternal dietary caffeine consumption was observed in this study; however, risk did not vary by amount of caffeine consumed. PMID:22903936

  14. The Effects of Caffeine on Memory for Word Lists.

    ERIC Educational Resources Information Center

    Erikson, George; And Others

    Research has suggested that behavioral differences may account for the effects of caffeine on information processing. To investigate the effects of caffeine on memory for supraspan word lists, 107 college students (47 males, 60 females), divided into 12 groups by high and low impulsivity scores on the Eysenck Personality Inventory, participated in…

  15. Caffeine. Courseware Evaluation for Vocational and Technical Education.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. National Center for Research in Vocational Education.

    This courseware evaluation rates the "Caffeine" program developed by Lane Community College and sold by the Oregon Department of Education. (The program--not included in this document--is part of a computer-assisted instruction project with nursing applications.) Part A describes "Caffeine" in terms of topics (food and nutrition, allied health)…

  16. The Effects of Caffeine and Provocation on Aggression.

    ERIC Educational Resources Information Center

    Ferguson, Tamara J.; And Others

    1982-01-01

    Administered caffeine to males (N=39) who were provoked or not provoked by a partner. Provoked participants attributed their feelings to both the drug and their partner's behavior. Angered subjects were more aversive when thinking they had taken caffeine but reduced their aggression when told the drug was a placebo. (Author/JAC)

  17. Effects of Pre- and Postnatal Caffeine Exposure on Human Infants.

    ERIC Educational Resources Information Center

    Jacobson, Sandra W.; Dowler, Jeffrey K.

    An investigation was made of the behavioral effects of caffeine in a sample of 313 newborns and their mothers. A weighted measure of caffeine based on daily ingestion of coffee, tea, and cola was derived from a maternal interview. The majority of mothers consumed the equivalent of about 1.3 cups of coffee per day. Infant outcome measures included…

  18. Subjective and objective effects of coffee consumption - caffeine or expectations?

    PubMed

    Dömötör, Zs; Szemerszky, R; Köteles, F

    2015-03-01

    Impact of 5 mg/kg caffeine, chance of receiving caffeine (stimulus expectancies), and expectations of effects of caffeine (response expectancies) on objective (heart rate (HR), systolic/diastolic blood pressure (SBP/DBP), measures of heart rate variability (HRV), and reaction time (RT)) and subjective variables were investigated in a double-blind, placebo-controlled experiment with a no-treatment group. Participants were 107 undergraduate university students (mean age 22.3 ± 3.96 years). Consumption of 5 mg/kg caffeine had an impact on participants' SBP, standard deviation of normal heartbeat intervals, HR (decrease), and subjective experience 40 minutes later even after controlling for respective baseline values, stimulus and response expectancies, and habitual caffeine consumption. No effects on DBP, high frequency component of HRV, the ratio of low- and high-frequency, and RT were found. Beyond actual caffeine intake, response expectancy score was also a determinant of subjective experience which refers to a placebo component in the total effect. Actual autonomic (SBP, HR) changes and somatosensory amplification tendency, however, had no significant impact on subjective experience. Placebo reaction plays a role in the subjective changes caused by caffeine consumption but it has no impact on objective variables. Conditional vs deceptive administration of caffeine (i.e. stimulus expectancies) had no impact on any assessed variable. PMID:25481367

  19. Subjective and objective effects of coffee consumption - caffeine or expectations?

    PubMed

    Dömötör, Zs; Szemerszky, R; Köteles, F

    2015-03-01

    Impact of 5 mg/kg caffeine, chance of receiving caffeine (stimulus expectancies), and expectations of effects of caffeine (response expectancies) on objective (heart rate (HR), systolic/diastolic blood pressure (SBP/DBP), measures of heart rate variability (HRV), and reaction time (RT)) and subjective variables were investigated in a double-blind, placebo-controlled experiment with a no-treatment group. Participants were 107 undergraduate university students (mean age 22.3 ± 3.96 years). Consumption of 5 mg/kg caffeine had an impact on participants' SBP, standard deviation of normal heartbeat intervals, HR (decrease), and subjective experience 40 minutes later even after controlling for respective baseline values, stimulus and response expectancies, and habitual caffeine consumption. No effects on DBP, high frequency component of HRV, the ratio of low- and high-frequency, and RT were found. Beyond actual caffeine intake, response expectancy score was also a determinant of subjective experience which refers to a placebo component in the total effect. Actual autonomic (SBP, HR) changes and somatosensory amplification tendency, however, had no significant impact on subjective experience. Placebo reaction plays a role in the subjective changes caused by caffeine consumption but it has no impact on objective variables. Conditional vs deceptive administration of caffeine (i.e. stimulus expectancies) had no impact on any assessed variable.

  20. Assessing caffeine intake in the United Kingdom diet.

    PubMed

    Fitt, Emily; Pell, David; Cole, Darren

    2013-10-01

    Caffeine occurs naturally in the leaves and seeds of many plants and is artificially added to some beverages. Consumption of caffeine has been linked to both positive and adverse health outcomes. We incorporated estimates of caffeine content (mg/100g or ml) of foods and drinks, taken from the published literature, to provide a preliminary estimate of caffeine intake for the UK population, based on data collected in the National Diet and Nutrition Survey 2008-10. Among consumers mean total caffeine intakes of adult men 19+ y were significantly greater than intakes by boys 4-10y and 11-18y (p<0.05), with the same age-related differences seen for females. 4.1% of men 19+ y and 3.8% of women 19+ y had caffeine intakes in excess of 300mg/d. The addition of caffeine to UK food composition databases will allow more detailed study of the health effects of caffeine consumption.

  1. Structural features of DNA interaction with caffeine and theophylline

    NASA Astrophysics Data System (ADS)

    Nafisi, Shohreh; Manouchehri, Firouzeh; Tajmir-Riahi, Heidar-Ali; Varavipour, Maryam

    2008-03-01

    Caffeine and theophylline are strong antioxidants that prevent DNA damage. The anticancer and antiviral activities of these natural products are implicated in their mechanism of actions. However, there has been no information on the interactions of these xanthine derivatives with individual DNA at molecular level. The aim of this study was to examine the stability and structural features of calf-thymus DNA complexes with caffeine and theophylline in aqueous solution, using constant DNA concentration (6.25 mM) and various caffeine or theophylline/DNA(P) ratios of 1/80, 1/40, 1/20, 1/10, 1/5, 1/2 and 1/1. FTIR, UV-visible spectroscopic methods were used to determine the ligand external binding modes, the binding constant and the stability of caffeine, theophylline-DNA complexes in aqueous solution. Spectroscopic evidence showed that the complexation of caffeine and theophylline with DNA occurred via G-C and A-T and PO 2 group with overall binding constants of K(caffeine-DNA) = 9.7 × 10 3 M -1 and K(theophylline-DNA) = 1.7 × 10 4 M -1. The affinity of ligand-DNA binding is in the order of theophylline > caffeine. A partial B to A-DNA transition occurs upon caffeine and theophylline complexation.

  2. International society of sports nutrition position stand: caffeine and performance

    PubMed Central

    2010-01-01

    Position Statement: The position of The Society regarding caffeine supplementation and sport performance is summarized by the following seven points: 1.) Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg/kg) and overall does not result in further enhancement in performance when consumed in higher dosages (≥ 9 mg/kg). 2.) Caffeine exerts a greater ergogenic effect when consumed in an anhydrous state as compared to coffee. 3.) It has been shown that caffeine can enhance vigilance during bouts of extended exhaustive exercise, as well as periods of sustained sleep deprivation. 4.) Caffeine is ergogenic for sustained maximal endurance exercise, and has been shown to be highly effective for time-trial performance. 5.) Caffeine supplementation is beneficial for high-intensity exercise, including team sports such as soccer and rugby, both of which are categorized by intermittent activity within a period of prolonged duration. 6.) The literature is equivocal when considering the effects of caffeine supplementation on strength-power performance, and additional research in this area is warranted. 7.) The scientific literature does not support caffeine-induced diuresis during exercise, or any harmful change in fluid balance that would negatively affect performance. PMID:20205813

  3. International society of sports nutrition position stand: caffeine and performance.

    PubMed

    Goldstein, Erica R; Ziegenfuss, Tim; Kalman, Doug; Kreider, Richard; Campbell, Bill; Wilborn, Colin; Taylor, Lem; Willoughby, Darryn; Stout, Jeff; Graves, B Sue; Wildman, Robert; Ivy, John L; Spano, Marie; Smith, Abbie E; Antonio, Jose

    2010-01-01

    Position Statement: The position of The Society regarding caffeine supplementation and sport performance is summarized by the following seven points: 1.) Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg/kg) and overall does not result in further enhancement in performance when consumed in higher dosages (>/= 9 mg/kg). 2.) Caffeine exerts a greater ergogenic effect when consumed in an anhydrous state as compared to coffee. 3.) It has been shown that caffeine can enhance vigilance during bouts of extended exhaustive exercise, as well as periods of sustained sleep deprivation. 4.) Caffeine is ergogenic for sustained maximal endurance exercise, and has been shown to be highly effective for time-trial performance. 5.) Caffeine supplementation is beneficial for high-intensity exercise, including team sports such as soccer and rugby, both of which are categorized by intermittent activity within a period of prolonged duration. 6.) The literature is equivocal when considering the effects of caffeine supplementation on strength-power performance, and additional research in this area is warranted. 7.) The scientific literature does not support caffeine-induced diuresis during exercise, or any harmful change in fluid balance that would negatively affect performance. PMID:20205813

  4. Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial

    PubMed Central

    Gerami, Hooshang; Nemati, Shadman; Kazemnejad, Ehsan; Aghajanpour, Mohammad

    2012-01-01

    Background It is still a challenge to find an effective treatment for tinnitus. The aim of this study was the evaluation of carbamazepine and oxcarbazepine effects on tinnitus. Methods In a randomized double–blind clinical trial, 57 patients who were visited in a university hospital due to chronic non-pulsatile tinnitus, were randomized in three groups and treated with carbamazepine (300-600 mg/day), oxcarbazepine (450-900 mg/day) and placebo for 12 weeks. Visual analogue scale (VAS) and tinnitus severity index (TSI) were measured in all subjects in the beginning and at the end of the 8th and 12th weeks of the trial. Data was analyzed by repeated measure analysis, paired and independent t-test. Results Among 51 participants who completed the trial course (28 men, 23 women), carbamazepine, oxcarbazepine and placebo decreased tinnitus severity in 56.6%, 46.2% and 38.5% of patients according to VAS, and in 61.1%, 58.8% and 50% of patients according to TSI, respectively. The effects of carbamazepine and oxcarbazepine were better in the first 8 weeks of treatment. However, their effect on tinnitus did not show any statistical difference in comparison with placebo (P = 0.34, P = 0.28). Conclusion Carbamazepine and oxcarbazepine are not more effective than placebo in decreasing tinnitus severity. PMID:24250874

  5. CAFFEINE IMPROVES HEART RATE WITHOUT IMPROVING SEPSIS SURVIVAL

    PubMed Central

    Bauzá, Gustavo; Remick, Daniel

    2015-01-01

    Introduction Caffeine is consumed on a daily basis for its nervous system stimulant properties and is a global adenosine receptor antagonist. Since adenosine receptors have been found to play a major role in regulating the immune response to a septic insult, we investigated if caffeine consumption prior to a septic insult would alter immunological and physiological responses, as well as survival. Methods Two separate experimental designs were employed, both using outbred female ICR mice. In the first experiment mice were administered 20mg/kg of caffeine (equal to 2–3 cups of coffee for a human) or normal saline intraperitoneally at the time of cecal ligation and puncture (CLP). Immunological parameters including cytokines and local cell recruitment measured. In the second experiment caffeine (10mg/kg/hr) was delivered continuously for 24 hours via a subcutaneous infusion pump placed the day prior to CLP and hemodynamic parameters were examined. In both experiments survival was followed for five days. Results A single dose of caffeine at the initiation of sepsis did not alter survival. This single dose of caffeine did significantly increase in plasma levels of the chemokine KC six hours after the onset of sepsis compared to septic mice given normal saline. There were no changes in IL-6 or IL-10 levels in the caffeine groups. Peritoneal lavages performed 24 hours post-CLP showed no difference in the levels of IL-6, TNF, KC, MIP-1, IL-10 or the IL-1 receptor antagonist between caffeine and normal saline treated mice. Additionally, the lavages yielded similar numbers of cells (4.1×106 vehicle vs. 6.9×106 caffeine) and bacterial colony forming units (CFU, 4.1 million CFU vehicle vs. 2.8 million CFU caffeine). In the infusion group, caffeine also did not alter survival. However, caffeine infusion did increase heart rate prior to CLP, and prevented the decline in heart rate after CLP. Conclusion Caffeine increased heart rate in mice but does not impact cytokine

  6. Caffeine dimerization: effects of sugar, salts, and water structure.

    PubMed

    Shimizu, Seishi

    2015-10-01

    Sugars and salts strongly affect the dimerization of caffeine in water. Such a change of dimerization, considered to be crucial for bitter taste suppression, has long been rationalized by the change of "water structure" induced by the additives; "kosmotropic" (water structure enhancing) salts and sugars promote dimerization, whereas "chaotropic" (water structure breaking) salts suppress dimerization. Based on statistical thermodynamics, here we challenge this consensus; we combine the rigorous Kirkwood-Buff theory of solution with the classical isodesmic model of caffeine association. Instead of the change of water structure, we show that the enhancement of caffeine dimerization is due to the exclusion of additives from caffeine, and that the weakening of dimerization is due to the binding of additives on caffeine.

  7. Dimer excision in Escherichia coli in the presence of caffeine

    SciTech Connect

    Rothman, R.H.

    1980-07-01

    The observation that polA1 and recL152 mutations result in both slow pyrimidine dimer excision and large repair patch size leads to the hypothesis that patch size is directly related to the rate of excision. In this study caffeine, a known inhibitor of excision repair, was used to examine the extent of correlation between excision rate and patch size by measuring patch size in the presence of several concentrations of caffeine. Both the rate of excision and the resistance to ultraviolet radiation were reduced with increasing concentrations of caffeine after irradiation. Caffeine also inhibited the rate at which incisions were made and prolonged the time required to rejoin the discontinuities. Patch size, however, was unaffected by caffeine treatment.

  8. Acute caffeine administration affects zebrafish response to a robotic stimulus.

    PubMed

    Ladu, Fabrizio; Mwaffo, Violet; Li, Jasmine; Macrì, Simone; Porfiri, Maurizio

    2015-08-01

    Zebrafish has been recently proposed as a valid animal model to investigate the fundamental mechanisms regulating emotional behavior and evaluate the modulatory effects exerted by psychoactive compounds. In this study, we propose a novel methodological framework based on robotics and information theory to investigate the behavioral response of zebrafish exposed to acute caffeine treatment. In a binary preference test, we studied the response of caffeine-treated zebrafish to a replica of a shoal of conspecifics moving in the tank. A purely data-driven information theoretic approach was used to infer the influence of the replica on zebrafish behavior as a function of caffeine concentration. Our results demonstrate that acute caffeine administration modulates both the average speed and the interaction with the replica. Specifically, zebrafish exposed to elevated doses of caffeine show reduced locomotion and increased sensitivity to the motion of the replica. The methodology developed in this study may complement traditional experimental paradigms developed in the field of behavioral pharmacology.

  9. Caffeine challenge test and panic disorder: a systematic literature review.

    PubMed

    Vilarim, Marina Machado; Rocha Araujo, Daniele Marano; Nardi, Antonio Egidio

    2011-08-01

    This systematic review aimed to examine the results of studies that have investigated the induction of panic attacks and/or the anxiogenic effect of the caffeine challenge test in patients with panic disorder. The literature search was performed in PubMed, Biblioteca Virtual em Saúde and the ISI Web of Knowledge. The words used for the search were caffeine, caffeine challenge test, panic disorder, panic attacks and anxiety disorder. In total, we selected eight randomized, double-blind studies where caffeine was administered orally, and none of them controlled for confounding factors in the analysis. The percentage of loss during follow-up ranged between 14.3% and 73.1%. The eight studies all showed a positive association between caffeine and anxiogenic effects and/or panic disorder.

  10. [Impact factors and degradation mechanism for the ozonation of acetaminophen in aqueous solution].

    PubMed

    Cao, Fei; Yuan, Shou-Jun; Zhang, Meng-Tao; Wang, Wei; Hu, Zhen-Hu

    2014-11-01

    The effect and mechanism of O3 on the degradation of acetaminophen in aqueous solution were studied by the batch experiment. The results showed that acetaminophen could be degraded effectively by ozone and degradation of acetaminophen fitted well with the pseudo-first-order kinetics model (R2 > 0.992). The degradation of acetaminophen was promoted with the increase of pH, the concentration of bicarbonate and ozone. The results of gas chromatography-mass spectrometry (GC-MS) and ion chromatography analysis showed that degradation products such as hydroquinone and a series of carboxylic acids were firstly formed during ozonation of acetaminophen. Then, the products were further oxidized. The degradation pathways of acetaminophen were also discussed by the identified products. The result of TOC showed that the mineralization of acetaminophen was ultimately lower. When the initial concentration of acetaminophen was 20 mg x L(-1) and the concentration of ozone was 9.10 mg x L(-1), the mineralization was only 16.42% after 130 min.

  11. Protective effects of (-)-epigallocatechin-3-gallate against acetaminophen-induced liver injury in rats).

    PubMed

    Yao, Hsien-Tsung; Yang, Yu-Chi; Chang, Chen-Hui; Yang, Hui-Ting; Yin, Mei-Chin

    2015-09-01

    (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin with various biological activities found in tea. In this study, the effects of EGCG on the metabolism and toxicity of acetaminophen in rat liver were investigated. Male Sprague-Dawley rats were fed a controlled diet without or with EGCG (0.54 %, w/w) for 1 week and were then intraperitoneally injected with acetaminophen (1 g/kg body weight) and killed after 12 h. Concentrations of acetaminophen and its conjugates in plasma and liver were then determined. The cytochrome P450 (CYP) and phase II enzymes activities were also evaluated. Rats fed the EGCG diet had lower plasma alanine aminotransferase and aspartate aminotransferase activities, as indices of hepatotoxicity, after acetaminophen treatment. Morphological damage by acetaminophen was lower in rats fed the EGCG diet. In addition, EGCG significantly reduced hepatic activities of midazolam 1-hydroxylation (CYP3A), nitrophenol 6-hydroxylase (CYP2E1), UDP-glucurosyltransferase, and sulfotransferase. Finally, EGCG feeding reduced acetaminophen-glucuronate and acetaminophen-glutathione contents in plasma and liver. These results indicate that EGCG feeding may reduce the metabolism and toxicity of acetaminophen in rats. PMID:26264479

  12. Sulphation of acetaminophen by the human cytosolic sulfotransferases: a systematic analysis.

    PubMed

    Yamamoto, Akihiro; Liu, Ming-Yih; Kurogi, Katsuhisa; Sakakibara, Yoichi; Saeki, Yuichi; Suiko, Masahito; Liu, Ming-Cheh

    2015-12-01

    Sulphation is known to be critically involved in the metabolism of acetaminophen in vivo. This study aimed to systematically identify the major human cytosolic sulfotransferase (SULT) enzyme(s) responsible for the sulphation of acetaminophen. A systematic analysis showed that three of the twelve human SULTs, SULT1A1, SULT1A3 and SULT1C4, displayed the strongest sulphating activity towards acetaminophen. The pH dependence of the sulphation of acetaminophen by each of these three SULTs was examined. Kinetic parameters of these three SULTs in catalysing acetaminophen sulphation were determined. Moreover, sulphation of acetaminophen was shown to occur in HepG2 human hepatoma cells and Caco-2 human intestinal epithelial cells under the metabolic setting. Of the four human organ samples tested, liver and intestine cytosols displayed considerably higher acetaminophen-sulphating activity than those of lung and kidney. Collectively, these results provided useful information concerning the biochemical basis underlying the metabolism of acetaminophen in vivo previously reported.

  13. The effect of aging on acetaminophen pharmacokinetics, toxicity and Nrf2 in Fischer 344 rats.

    PubMed

    Mach, John; Huizer-Pajkos, Aniko; Cogger, Victoria C; McKenzie, Catriona; Le Couteur, David G; Jones, Brett E; de Cabo, Rafael; Hilmer, Sarah N

    2014-04-01

    We investigated the effect of aging on hepatic pharmacokinetics and the degree of hepatotoxicity following a toxic dose of acetaminophen. Young and old male Fischer 344 rats were treated with 800 mg/kg acetaminophen (young n = 8, old n = 5) or saline (young n = 9, old n = 9). Serum measurements showed old rats treated with acetaminophen had significantly lower serum alanine aminotransferase and higher acetaminophen and acetaminophen glucuronide levels and creatinine, compared with acetaminophen treated young rats (p < .05). Immunoblotting and activity assays showed old saline-treated rats had twofold lower cytochrome P450 2E1 activity and threefold higher NAD(P)H quinone oxireductase 1 protein expression and activity than young saline-treated rats (p < .05), although Nrf2, glutathione cysteine ligase-modulatory subunit, glutathione cysteine ligase-catalytic subunit, and cytochrome P450 2E1 protein expressions were unchanged. Primary hepatocytes isolated from young rats treated with 10 mM acetaminophen had lower survival than those from old rats (52.4% ± 5.8%, young; 83.6% ± 1.7%, old, p < .05). The pharmacokinetic changes described may decrease susceptibility to acetaminophen-induced hepatotoxicity but may increase risk of nephrotoxicity in old age.

  14. Impact of Intraoperative Acetaminophen Administration on Postoperative Opioid Consumption in Patients Undergoing Hip or Knee Replacement

    PubMed Central

    Vaughan, Cathy; McGee, Ann

    2014-01-01

    Abstract Background: Opioid utilization for acute pain has been associated with numerous adverse events, potentially resulting in longer inpatient stays and increased costs. Objective: To examine the effect of intravenous (IV) acetaminophen administered intraoperatively on postoperative opioid consumption in adult subjects who underwent hip or knee replacement. Methods: This retrospective cohort study evaluated postoperative opioid consumption in 176 randomly selected adult subjects who underwent hip or knee replacement at Duke University Hospital (DUH). Eighty-eight subjects received a single, intraoperative, 1 g dose of IV acetaminophen. The other subjects did not receive any IV acetaminophen. This study evaluated mean opioid consumption (in oral morphine equivalents) during the 24-hour postoperative period in the 2 groups. Other endpoints included length of stay in the postanesthesia care unit (PACU), incidence of oversedation, need for acute opioid reversal, and adjunctive analgesic utilization. Results: Subjects who were given a single dose of intraoperative acetaminophen received an average of 149.3 mg of oral morphine equivalents during the 24 hours following surgery compared to 147.2 mg in participants who were not exposed to IV acetaminophen (P = .904). The difference in average length of PACU stay between the IV acetaminophen group (163 minutes) and those subjects not exposed to IV acetaminophen (169 minutes) was not statistically significant (P = .588). No subjects in the study experienced oversedation or required acute opioid reversal. Conclusion: There was not a statistically significant difference in postoperative opioid consumption between patients receiving and not receiving IV acetaminophen intraoperatively. PMID:25673891

  15. Acetaminophen hepatotoxicity and HIF-1{alpha} induction in acetaminophen toxicity in mice occurs without hypoxia

    SciTech Connect

    Chaudhuri, Shubhra; McCullough, Sandra S.; Hennings, Leah; Letzig, Lynda; Simpson, Pippa M.; Hinson, Jack A.; James, Laura P.

    2011-05-01

    HIF-1{alpha} is a nuclear factor important in the transcription of genes controlling angiogenesis including vascular endothelial growth factor (VEGF). Both hypoxia and oxidative stress are known mechanisms for the induction of HIF-1{alpha}. Oxidative stress and mitochondrial permeability transition (MPT) are mechanistically important in acetaminophen (APAP) toxicity in the mouse. MPT may occur as a result of oxidative stress and leads to a large increase in oxidative stress. We previously reported the induction of HIF-1{alpha} in mice with APAP toxicity and have shown that VEGF is important in hepatocyte regeneration following APAP toxicity. The following study was performed to examine the relative contribution of hypoxia versus oxidative stress to the induction of HIF-1{alpha} in APAP toxicity in the mouse. Time course studies using the hypoxia marker pimonidazole showed no staining for pimonidazole at 1 or 2 h in B6C3F1 mice treated with APAP. Staining for pimonidazole was present in the midzonal to periportal regions at 4, 8, 24 and 48 h and no staining was observed in centrilobular hepatocytes, the sites of the toxicity. Subsequent studies with the MPT inhibitor cyclosporine A showed that cyclosporine A (CYC; 10 mg/kg) reduced HIF-1{alpha} induction in APAP treated mice at 1 and 4 h and did not inhibit the metabolism of APAP (depletion of hepatic non-protein sulfhydryls and hepatic protein adduct levels). The data suggest that HIF-1{alpha} induction in the early stages of APAP toxicity is secondary to oxidative stress via a mechanism involving MPT. In addition, APAP toxicity is not mediated by a hypoxia mechanism.

  16. Acetaminophen hepatotoxicity and HIF-1α induction in acetaminophen toxicity in mice occurs without hypoxia.

    PubMed

    Chaudhuri, Shubhra; McCullough, Sandra S; Hennings, Leah; Letzig, Lynda; Simpson, Pippa M; Hinson, Jack A; James, Laura P

    2011-05-01

    HIF-1α is a nuclear factor important in the transcription of genes controlling angiogenesis including vascular endothelial growth factor (VEGF). Both hypoxia and oxidative stress are known mechanisms for the induction of HIF-1α. Oxidative stress and mitochondrial permeability transition (MPT) are mechanistically important in acetaminophen (APAP) toxicity in the mouse. MPT may occur as a result of oxidative stress and leads to a large increase in oxidative stress. We previously reported the induction of HIF-1α in mice with APAP toxicity and have shown that VEGF is important in hepatocyte regeneration following APAP toxicity. The following study was performed to examine the relative contribution of hypoxia versus oxidative stress to the induction of HIF-1α in APAP toxicity in the mouse. Time course studies using the hypoxia marker pimonidazole showed no staining for pimonidazole at 1 or 2h in B6C3F1 mice treated with APAP. Staining for pimonidazole was present in the midzonal to periportal regions at 4, 8, 24 and 48h and no staining was observed in centrilobular hepatocytes, the sites of the toxicity. Subsequent studies with the MPT inhibitor cyclosporine A showed that cyclosporine A (CYC; 10mg/kg) reduced HIF-1α induction in APAP treated mice at 1 and 4h and did not inhibit the metabolism of APAP (depletion of hepatic non-protein sulfhydryls and hepatic protein adduct levels). The data suggest that HIF-1α induction in the early stages of APAP toxicity is secondary to oxidative stress via a mechanism involving MPT. In addition, APAP toxicity is not mediated by a hypoxia mechanism.

  17. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes.

    PubMed

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B; Rivkees, Scott A; Wendler, Christopher C

    2014-12-15

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20-60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3-65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes.

  18. The effect of caffeine ingestion on delayed onset muscle soreness.

    PubMed

    Hurley, Caitlin F; Hatfield, Disa L; Riebe, Deborah A

    2013-11-01

    The beneficial effects of caffeine on aerobic activity and resistance training performance are well documented. However, less is known concerning caffeine's potential role in reducing perception of pain and soreness during exercise. In addition, there is no information regarding the effects of caffeine on delayed onset muscle soreness (DOMS). The primary purpose of this study was to examine the effect of caffeine ingestion on muscle soreness, blood enzyme activity, and performance after a bout of elbow flexion/extension exercise. Nine low-caffeine-consuming males (body mass: 76.68 ± 8.13 kg; height: 179.18 ± 9.35 cm; age: 20 ± 1 year) were randomly assigned to ingest either caffeine or placebo 1 hour before completing 4 sets of 10 bicep curls on a preacher bench, followed by a fifth set in which subjects completed as many repetitions as possible. Soreness and soreness on palpation intensity were measured using three 0-10 visual analog scales before exercise, and 24, 48, 72, 96, and 120 hours after exercise. After a washout period, subjects crossed over to the other treatment group. Caffeine ingestion resulted in significantly (p ≤ 0.05) lower levels of soreness on day 2 and day 3 compared with placebo. Total repetitions in the final set of exercise increased with caffeine ingestion compared with placebo. This study demonstrates that caffeine ingestion immediately before an upper-body resistance training out enhances performance. A further beneficial effect of sustained caffeine ingestion in the days after the exercise bout is an attenuation of DOMS. This decreased perception of soreness in the days after a strenuous resistance training workout may allow individuals to increase the number of training sessions in a given time period.

  19. Caffeine causes pulmonary hypertension syndrome (ascites) in broilers.

    PubMed

    Kamely, M; Torshizi, M A Karimi; Rahimi, S; Wideman, R F

    2016-04-01

    Pulmonary hypertension syndrome (PHS), or ascites, is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance accompanied by right ventricular hypertrophy (RVH) and fluid accumulation in the abdominal cavity. Experimental models are required for triggering PHS to study the pathogenesis of this syndrome and to select resistant genetic lines. Caffeine increases vascular resistance and promotes systemic hypertension in mammals, but a similar effect of caffeine on the pulmonary circulation had not previously been demonstrated. Two experiments were conducted to evaluate the impact of caffeine alone (Exp. 1) or in combination with cold temperature (Exp. 2) on parameters associated with PHS in young broiler chicks. In Exp. 1, 288 chicks were distributed among 24 pens and brooded at standard environmental temperatures, and on d 3 through 42 caffeine was added to the water at doses of 0 (control), 6.25, 12.5, 25, 50, and 100 mg/(kg BW·d). In Exp. 2, 192 chicks were distributed among 16 pens and brooded at cool environmental temperatures, and on d 3 through 42 caffeine was added to the water at doses of 0 (control), 15, 30, and 45 mg/(kg BW·d). In Exp. 1 caffeine administered at or above 12.5 mg/(kg BW·d) induced severe PHS and resulted in acute mortality and RVH ( < 0.05). Hematocrit also slightly increased by caffeine supplementation ( = 0.07). In Exp. 2 caffeine-treated broilers exposed to cold temperatures remarkably exhibited PHS incidences and developed RVH with right ventricular to total ventricular weight ratios of 30% or greater. Moreover, hematocrit significantly increased because of caffeine supplementation in cool ambient temperature ( = 0.002). Our data demonstrate that caffeine induces high incidences of PHS in broilers, which is exacerbated by exposure to low temperatures. PMID:27136008

  20. Variation in caffeine concentration in single coffee beans.

    PubMed

    Fox, Glen P; Wu, Alex; Yiran, Liang; Force, Lesleigh

    2013-11-13

    Twenty-eight coffee samples from around the world were tested for caffeine levels to develop near-infrared reflectance spectroscopy (NIRS) calibrations for whole and ground coffee. Twenty-five individual beans from five of those coffees were used to develop a NIRS calibration for caffeine concentration in single beans. An international standard high-performance liquid chromatography method was used to analyze for caffeine content. Coffee is a legal stimulant and possesses a number of heath properties. However, there is variation in the level of caffeine in brewed coffee and other caffeinated beverages. Being able to sort beans on the basis of caffeine concentration will improve quality control in the level of caffeine in those beverages. The range in caffeine concentration was from 0.01 mg/g (decaffeinated coffee) to 19.9 mg/g (Italian coffee). The majority of coffees were around 10.0-12.0 mg/g. The NIRS results showed r(2) values for bulk unground and ground coffees were >0.90 with standard errors <2 mg/g. For the single-bean calibration the r(2) values were between 0.85 and 0.93 with standard errors of cross validation of 0.8-1.6 mg/g depending upon calibration. The results showed it was possible to develop NIRS calibrations to estimate the caffeine concentration of individual coffee beans. One application of this calibration could be sorting beans on caffeine concentration to provide greater quality control for high-end markets. Furthermore, bean sorting may open new markets for novel coffee products. PMID:24070227

  1. Effect of Caffeine on Oxidative Stress During Maximum Incremental Exercise

    PubMed Central

    Olcina, Guillermo J.; Muñoz, Diego; Timón, Rafael; Caballero, M. Jesús; Maynar, Juan I.; Córdova, Alfredo; Maynar, Marcos

    2006-01-01

    Caffeine (1,3,7-trimethylxanthine) is an habitual substance present in a wide variety of beverages and in chocolate-based foods and it is also used as adjuvant in some drugs. The antioxidant ability of caffeine has been reported in contrast with its pro- oxidant effects derived from its action mechanism such as the systemic release of catecholamines. The aim of this work was to evaluate the effect of caffeine on exercise oxidative stress, measuring plasma vitamins A, E, C and malonaldehyde (MDA) as markers of non enzymatic antioxidant status and lipid peroxidation respectively. Twenty young males participated in a double blind (caffeine 5mg·kg- 1 body weight or placebo) cycling test until exhaustion. In the exercise test, where caffeine was ingested prior to the test, exercise time to exhaustion, maximum heart rate, and oxygen uptake significantly increased, whereas respiratory exchange ratio (RER) decreased. Vitamins A and E decreased with exercise and vitamin C and MDA increased after both the caffeine and placebo tests but, regarding these particular variables, there were no significant differences between the two test conditions. The results obtained support the conclusion that this dose of caffeine enhances the ergospirometric response to cycling and has no effect on lipid peroxidation or on the antioxidant vitamins A, E and C. Key Points Caffeine ingestion may improve maximal aerobic performance in non trained men. Cellular oxidative damage is not altered by caffeine ingestion in maximal aerobic exercises. Antioxidant response to exercise, vitamins A, E and C, is not modified by caffeine action in maximal aerobic efforts. PMID:24357958

  2. Variation in caffeine concentration in single coffee beans.

    PubMed

    Fox, Glen P; Wu, Alex; Yiran, Liang; Force, Lesleigh

    2013-11-13

    Twenty-eight coffee samples from around the world were tested for caffeine levels to develop near-infrared reflectance spectroscopy (NIRS) calibrations for whole and ground coffee. Twenty-five individual beans from five of those coffees were used to develop a NIRS calibration for caffeine concentration in single beans. An international standard high-performance liquid chromatography method was used to analyze for caffeine content. Coffee is a legal stimulant and possesses a number of heath properties. However, there is variation in the level of caffeine in brewed coffee and other caffeinated beverages. Being able to sort beans on the basis of caffeine concentration will improve quality control in the level of caffeine in those beverages. The range in caffeine concentration was from 0.01 mg/g (decaffeinated coffee) to 19.9 mg/g (Italian coffee). The majority of coffees were around 10.0-12.0 mg/g. The NIRS results showed r(2) values for bulk unground and ground coffees were >0.90 with standard errors <2 mg/g. For the single-bean calibration the r(2) values were between 0.85 and 0.93 with standard errors of cross validation of 0.8-1.6 mg/g depending upon calibration. The results showed it was possible to develop NIRS calibrations to estimate the caffeine concentration of individual coffee beans. One application of this calibration could be sorting beans on caffeine concentration to provide greater quality control for high-end markets. Furthermore, bean sorting may open new markets for novel coffee products.

  3. Understanding Adolescent Caffeine Use: Connecting Use Patterns with Expectancies, Reasons, and Sleep

    ERIC Educational Resources Information Center

    Ludden, Alison Bryant; Wolfson, Amy R.

    2010-01-01

    Little is known about adolescents' caffeine use, yet caffeinated soda, and more recently coffee and energy drinks, are part of youth culture. This study examines adolescents' caffeine use and, using cluster analysis, identifies three groups of caffeine users who differed in their reasons for use, expectancies, and sleep behaviors. In this high…

  4. 'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

    SciTech Connect

    Jetten, Marlon J.A.; Gaj, Stan; Ruiz-Aracama, Ainhoa; Kok, Theo M. de; Delft, Joost H.M. van; Lommen, Arjen; Someren, Eugene P. van; Jennen, Danyel G.J.; Claessen, Sandra M.; Peijnenburg, Ad A.C.M.; Stierum, Rob H.; Kleinjans, Jos C.S.

    2012-03-15

    Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, 'omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. 'Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites. -- Highlights: ► 'Omics techniques outperformed

  5. 5-oxoproline-induced anion gap metabolic acidosis after an acute acetaminophen overdose.

    PubMed

    Lawrence, David T; Bechtel, Laura K; Charlton, Nathan P; Holstege, Christopher P

    2010-09-01

    Metabolic acidosis after acute acetaminophen overdose is typically attributed to either transient lactic acidosis without evidence of hepatic injury or hepatic failure. High levels of the organic acid 5-oxoprolinuria are usually reported in patients with predisposing conditions, such as sepsis, who are treated in a subacute or chronic fashion with acetaminophen. The authors report a case of a 40-year-old woman who developed anion gap metabolic acidosis and somnolence after an acute acetaminophen overdose. Substantial hepatic damage did not occur, which ruled out acetaminophen-induced hepatic insufficiency as a cause of the patient's acidosis or altered mental status. Urinalysis revealed elevated levels of 5-oxoproline, suggesting that the patient's acute acetaminophen overdose was associated with marked anion gap metabolic acidosis due solely to 5-oxoproline without hepatic complications. The acidosis fully resolved with N-acetylcysteine treatment and supportive care including hydration.

  6. [Human herpes virus 6 infection in an inmunocompetent patient with carbamazepine-induced DRESS syndrome].

    PubMed

    Álvarez, Sergio; Delama, Ignacio; Navajas-Galimany, Lucas; Eymin, Gonzalo; Ceballos, M Elena; Andino-Navarrete, Romina

    2016-06-01

    DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is an adverse life-threatening drug reaction characterized by a polymorphous rash associated with fever, lymphadenopathy and multiorgan involvement with eosinophilia. We present the case of an immunocompetent man with DRESS syndrome secondary to carbamazepine, that developed concomitantly meningoencephalitis caused by human herpes virus 6 (HHV-6), and a review of literature. The pathogenic role of HHV-6 in DRESS syndrome remains controversial. Given the diagnostic and possibly prognostic significance of HHV-6, the screening seems to be a good measure to use in the clinical management of these patients. PMID:27598287

  7. Determination of association constant of host-guest supramolecular complex (molecular recognition of carbamazepine, antiseizure drug, with calix(4)arene).

    PubMed

    Meenakshi, C; Jayabal, P; Ramakrishnan, V

    2015-12-01

    The thermodynamic property of the host-guest, inclusion complex formed between p-t-butyl calix(4)arene which is a supramolecule, and the antiseizure drug, carbamazepine was studied. p-t-Butyl calix(4)arene has been used as a host molecule and carbamazepine as a guest molecule. Optical absorption spectral studies were carried out to investigate the molecular recognition properties of p-t-butyl calix(4)arene with carbamazepine. The stochiometry of the host-guest complexes formed and the association constant were determined. An interesting 1:2 stochiometric host-guest complex was formed. Job's continuous method of variation and Benesi-Hildebrand expression were used for the determination of binding constant and the stochiometry of the host-guest complex formed. Molecular dimension of the host molecule plays a vital role in the formation of the host-guest stochiometric complexes.

  8. Caffeine Use Disorder: A Review of the Evidence and Future Implications.

    PubMed

    Addicott, Merideth A

    2014-09-01

    The latest edition of the Diagnostic and Statistical Manual (DSM-5) has introduced new provisions for caffeine-related disorders. Caffeine Withdrawal is now an officially recognized diagnosis, and criteria for caffeine use disorder have been proposed for additional study. caffeine use disorder is intended to be characterized by cognitive, behavioral, and physiological symptoms indicative of caffeine use despite significant caffeine-related problems, similar to other Substance Use Disorders. However, since nonproblematic caffeine use is so common and widespread, it may be difficult for some health professionals to accept that caffeine use can result in the same types of pathological behaviors caused by alcohol, cocaine, opiates, or other drugs of abuse. Yet there is evidence that some individuals are psychologically and physiologically dependent on caffeine, although the prevalence and severity of these problems is unknown. This article reviews the recent changes to the DSM, the concerns regarding these changes, and some potential impacts these changes could have on caffeine consumers. PMID:25089257

  9. Caffeine Content Labeling: A Missed Opportunity for Promoting Personal and Public Health

    PubMed Central

    Kole, Jon

    2013-01-01

    Current regulation of caffeine-containing products is incoherent, fails to protect consumers' interests, and should be modified in multiple ways. We make the case for one of the regulatory reforms that are needed: all consumable products containing added caffeine should be required by the Food and Drug Administration (FDA) to include caffeine quantity on their labels. Currently, no foods or beverages that contain caffeine are required to include caffeine content on their labels. Strengthening these lax labeling requirements could prevent direct caffeine-induced harm, protect those most vulnerable to caffeine-related side effects, and enhance consumer autonomy and effective caffeine use. Consumers have an interest in regulating their intake of caffeine and thus, ought to know how much caffeine their foods and beverages contain. PMID:24761278

  10. Acetaminophen hepatotoxicity in mice: Effect of age, frailty and exposure type.

    PubMed

    Kane, Alice E; Mitchell, Sarah J; Mach, John; Huizer-Pajkos, Aniko; McKenzie, Catriona; Jones, Brett; Cogger, Victoria; Le Couteur, David G; de Cabo, Rafael; Hilmer, Sarah N

    2016-01-01

    Acetaminophen is a commonly used analgesic that can cause severe hepatotoxicity in overdose. Despite old age and frailty being associated with extensive and long-term utilization of acetaminophen and a high prevalence of adverse drug reactions, there is limited information on the risks of toxicity from acetaminophen in old age and frailty. This study aimed to assess changes in the risk and mechanisms of hepatotoxicity from acute, chronic and sub-acute acetaminophen exposure with old age and frailty in mice. Young and old male C57BL/6 mice were exposed to either acute (300 mg/kg via oral gavage), chronic (100 mg/kg/day in diet for six weeks) or sub-acute (250 mg/kg, t.i.d., for three days) acetaminophen, or saline control. Pre-dosing mice were scored for the mouse clinical frailty index, and after dosing serum and liver tissue were collected for assessment of toxicity and mechanisms. There were no differences with old age or frailty in the degree of hepatotoxicity induced by acute, chronic or subacute acetaminophen exposure as assessed by serum liver enzymes and histology. Age-related changes in the acetaminophen toxicity pathways included increased liver GSH concentrations, increased NQO1 activity and an increased pro- and anti-inflammatory response to acetaminophen in old age. Frailty-related changes included a negative correlation between frailty index and serum protein, albumin and ALP concentrations for some mouse groups. In conclusion, although there were changes in some pathways that would be expected to influence susceptibility to acetaminophen toxicity, there was no overall increase in acetaminophen hepatotoxicity with old age or frailty in mice. PMID:26615879

  11. Toxicity from repeated doses of acetaminophen in children: assessment of causality and dose in reported cases.

    PubMed

    Heard, Kennon; Bui, Alison; Mlynarchek, Sara L; Green, Jody L; Bond, G Randall; Clark, Richard F; Kozer, Eran; Koff, Raymond S; Dart, Richard C

    2014-01-01

    Liver injury has been reported in children treated with repeated doses of acetaminophen. The objective of this study was to identify and validate reports of liver injury or death in children younger than 6 years who were administered repeated therapeutic doses of acetaminophen. We reviewed US Poison Center data, peer-reviewed literature, US Food and Drug Administration Adverse Event Reports, and US Manufacturer Safety Reports describing adverse effects after acetaminophen administration. Reports that described hepatic abnormalities (description of liver injury or abnormal laboratory testing) or death after acetaminophen administration to children younger than 6 years were included. The identified reports were double abstracted and then reviewed by an expert panel to determine if the hepatic injury was related to acetaminophen and whether the dose of acetaminophen was therapeutic (≤75 mg/kg) or supratherapeutic. Our search yielded 2531 reports of adverse events associated with acetaminophen use. From these cases, we identified 76 cases of hepatic injury and 26 deaths associated with repeated acetaminophen administration. There were 6 cases of hepatic abnormalities and no deaths associated with what our panel determined to be therapeutic doses. A large proportion of cases could not be fully evaluated due to incomplete case reporting. Although we identified numerous examples of liver injury and death after repeated doses of acetaminophen, all the deaths and all but 6 cases of hepatic abnormalities involved doses more than 75 mg/kg per day. This study suggests that the doses of less than 75 mg/kg per day of acetaminophen are safe for children younger than 6 years.

  12. Candidate Gene Polymorphisms in Patients with Acetaminophen-Induced Acute Liver Failure

    PubMed Central

    Peter, Inga; Hazarika, Suwagmani; Vasiadi, Magdalini; Greenblatt, David J.; Lee, William M.

    2014-01-01

    Acetaminophen is a leading cause of acute liver failure (ALF). Genetic differences might predispose some individuals to develop ALF. In this exploratory study, we evaluated genotype frequency differences among patients enrolled by the ALF Study Group who had developed ALF either intentionally from a single-time-point overdose of acetaminophen (n = 78), unintentionally after chronic high doses of acetaminophen (n = 79), or from causes other than acetaminophen (n = 103). The polymorphisms evaluated included those in genes encoding putative acetaminophen-metabolizing enzymes (UGT1A1, UGT1A6, UGT1A9, UGT2B15, SULT1A1, CYP2E1, and CYP3A5) as well as CD44 and BHMT1. Individuals carrying the CYP3A5 rs776746 A allele were overrepresented among ALF patients who had intentionally overdosed with acetaminophen, with an odds ratio of 2.3 (95% confidence interval, 1.1–4.9; P = 0.034) compared with all other ALF patients. This finding is consistent with the enhanced bioactivation of acetaminophen by the CYP3A5 enzyme. Persons homozygous for the CD44 rs1467558 A allele were also overrepresented among patients who had unintentionally developed ALF from chronic acetaminophen use, with an odds ratio of 4.0 (1.0–17.2, P = 0.045) compared with all other ALF subjects. This finding confirms a prior study that found elevated serum liver enzyme levels in healthy volunteers with the CD44 rs1467558 AA genotype who had consumed high doses of acetaminophen for up to 2 weeks. However, both genetic associations were considered relatively weak, and they were not statistically significant after adjustment for multiple comparisons testing. Nevertheless, both CYP3A5 rs776746 and CD44 rs1467558 warrant further investigation as potential genomic markers of enhanced risk of acetaminophen-induced ALF. PMID:24104197

  13. Acetaminophen and meloxicam inhibit platelet aggregation and coagulation in blood samples from humans.

    PubMed

    Martini, Angela K; Rodriguez, Cassandra M; Cap, Andrew P; Martini, Wenjun Z; Dubick, Michael A

    2014-12-01

    Acetaminophen (Ace) and meloxicam (Mel) are the two types of analgesic and antipyretic medications. This study investigated the dose responses of acetaminophen and meloxicam on platelet aggregation and coagulation function in human blood samples. Blood samples were collected from six healthy humans and processed to make platelet-adjusted (100 × 10 cells/μl) blood samples. Acetaminophen (Tylenol, Q-PAP, 100 mg/ml) was added at the doses of 0 μg/ml (control), 214 μg/ml (the standard dose, 1 ×), 4 ×, 8 ×, 10 ×, 12 ×, 16 ×, and 20 ×. Similarly, meloxicam (Metacam, 5 mg/ml) was added at doses of 0 μg/ml (control), 2.85 μg/ml (the standard dose, 1 ×), 4 ×, 8 ×, 10 ×, 12 ×, 16 ×, and 20 ×. Fifteen minutes after the addition of acetaminophen and/or meloxicam, platelet aggregation was stimulated with collagen (2 μg/ml) or arachidonic acid (0.5 mmol/l) and assessed using a Chrono-Log 700 aggregometer. Coagulation function was assessed by prothrombin time (PT), activated partial thromboplastin time (aPTT), and using Rotem thrombelastogram. A robust inhibition by acetaminophen and/or meloxicam was observed in arachidonic acid-stimulated platelet aggregation starting at 1 × dose. Collagen-stimulated platelet aggregation was inhibited by ACE starting at 1 × (78 ± 10% of control), and by meloxicam starting at 4 × (72 ± 5% of control, both P < 0.05). The inhibitions by acetaminophen and meloxicam combined were similar to those by acetaminophen or meloxicam. aPTT was prolonged by meloxicam starting at 4 ×. No changes were observed in PT or any of Rotem measurements by acetaminophen and/or meloxicam. Acetaminophen and meloxicam compromised platelet aggregation and aPTT. Further effort is warranted to characterize the effects of acetaminophen and meloxicam on bleeding in vivo.

  14. Hydroxyzine and metabolites as a source of interference in carbamazepine particle-enhanced turbidimetric inhibition immunoassay (PETINIA).

    PubMed

    Parant, François; Moulsma, Mustapha; Gagnieu, Marie Claude; Lardet, Gisèle

    2005-08-01

    A 32-year-old epileptic patient with a lengthy history of multiple-drug abuse and psychotic disorders was found to have an elevated serum carbamazepine concentration of 40.5 mg/L (therapeutic range 4-12 mg/L) using particle-enhanced turbidimetric inhibition immunoassay (PETINIA). Serum reanalysis by LC-DAD revealed only high hydroxyzine (HDZ) concentration (HDZ = 0.55 mg/L; therapeutic range <0.1 mg/L), suggesting cross-reactivity between HDZ and PETINIA. To confirm this hypothesis, the authors tested 2 commercially available carbamazepine immunoassays, PETINIA and EMIT 2000, for in vitro cross-reactivity with HDZ and 2 HDZ metabolites (cetirizine and norchlorcyclizine). To determine the frequency of this interaction in a clinical setting, 40 sera of 39 patients taking HDZ without carbamazepine were tested by both immunoassays. For some samples, LC-ESI-MS analysis of HDZ metabolites was performed. Additionally, cross-reactivities produced by other benzhydrylpiperazine drugs were evaluated. in vitro, 5 mg of HDZ, cetirizine, and norchlorcyclizine cross-reacted with PETINIA at 85%, 125%, and 66%, respectively. Conversely, EMIT 2000 showed no cross-reactivity. For PETINIA, erroneous carbamazepine concentrations were detected in 35 out of 40 sera of patients taking HDZ. The magnitude of interference correlated moderately with serum HDZ concentrations (Spearman rho coefficient 0.58, P < 0.001), suggesting a major role for the multiple HDZ metabolites (4 serum metabolites were detected by LC-ESI-MS). Furthermore, other benzhydrylpiperazine drugs (eg, oxatomide) showed in vitro cross-reactivity with PETINIA. In conclusion, HDZ and its metabolites cross-react with carbamazepine PETINIA immunoassay, which could significantly affect the correct interpretation of serum carbamazepine concentrations in patients treated with HDZ.

  15. The Combined Effects of Alcohol, Caffeine and Expectancies on Subjective Experience, Impulsivity and Risk-Taking

    PubMed Central

    Heinz, Adrienne J.; de Wit, Harriet; Lilje, Todd C.; Kassel, Jon D.

    2013-01-01

    Caffeinated alcoholic beverage (CAB) consumption is a rapidly growing phenomenon among young adults and is associated with a variety of health-risk behaviors. The current study examined whether either caffeinated alcohol or the expectation of receiving caffeinated alcohol altered affective, cognitive and behavioral outcomes hypothesized to contribute to risk behavior. Young adult social drinkers (N=146) participated in a single session where they received alcohol (peak Breath Alcohol Content = .088 g/dL, SD = .019; equivalent to about 4 standard drinks) and were randomly assigned to one of four further conditions 1) no caffeine, no caffeine expectancy, 2) caffeine and caffeine expectancy, 3) no caffeine but caffeine expectancy, 4) caffeine but no caffeine expectancy. Participants’ habitual CAB consumption was positively correlated with measures of impulsivity and risky behavior, independently of study drugs. Administration of caffeine (mean dose = 220 mg, SD = 38; equivalent to about 2.75 Red Bulls) in the study reduced subjective ratings of intoxication and reversed the decrease in desire to continue drinking, regardless of expectancy. Caffeine also reduced the effect of alcohol on inhibitory reaction time (faster incorrect responses). Participants not expecting caffeine were less attentive after alcohol, whereas participants expecting caffeine were not, regardless of caffeine administration. Alcohol decreased response accuracy in all participants except those who both expected and received caffeine. Findings suggest that CABs may elevate risk for continued drinking by reducing perceived intoxication, and by maintaining the desire to continue drinking. Simply expecting to consume caffeine may reduce the effects of alcohol on inattention, and either expecting or consuming caffeine may protect against other alcohol-related performance decrements. Caffeine, when combined with alcohol, has both beneficial and detrimental effects on mechanisms known to contribute to

  16. Association of different zinc concentrations combined with a fixed caffeine dose on plasma and tissue caffeine and zinc levels in the rat.

    PubMed

    Yazdani, Malektaj; Gottschalk, Sheila; Ide, Kazuya; Nakamoto, Tetsuo

    2002-01-01

    Because caffeine and tissue levels of Zn are closely related, the objectives of this study were to determine the changes in plasma caffeine levels over a period of 5 h when different concentrations of Zn combined with a fixed concentration of caffeine were injected into the femoral vein of rats and to determine the relationship between tissue levels of caffeine and Zn at 5 h postinjection. Rats were divided into three groups: group 1, 220 microg caffeine; group 2, 220 microg caffeine + 8 microg Zn/g body weight (BW); group 3, 220 microg caffeine + 16 microg Zn/g BW. Blood from groups 1 and 3 was collected at 3 min, 30 min, 1 h, 3 h, and 5 h to determine the pharmacokinetics of caffeine. All groups were killed at 5 h. Caffeine and Zn concentrations of the brain, kidney, heart, and liver of all groups were determined. The plasma-caffeine curve in group 3 showed a lower concentration at 3 min and a slower caffeine-elimination rate during the first 3 h. Brain and kidney caffeine levels remained constant in all groups, whereas caffeine levels were increased in the heart in group 2 and in the liver in group 3. Zn concentrations in the brain and kidney were lower in group 2 compared with groups 1 and 3 and higher in group 3 compared to groups 1 and 2. Zn concentration in the heart was the same among the three groups but was increased in the liver in group 3 compared to groups 1 and 2. Therefore, we concluded that caffeine combined with Zn affects caffeine pharmacokinetics. With caffeine intake, levels of Zn (16 microg/g BW) that are slightly higher than the daily requirements (12 microg/g BW) may prevent a reduction of Zn in tissue. In addition, caffeine's effects on Zn concentration among organs are different.

  17. Physiology, biochemistry and possible applications of microbial caffeine degradation.

    PubMed

    Gummadi, Sathyanarayana N; Bhavya, B; Ashok, Nandhini

    2012-01-01

    Caffeine, a purine alkaloid is a constituent of widely consumed beverages. The scientific evidence which has proved the harm of this alkaloid has paved the way for innumerable research in the area of caffeine degradation. In addition to this, the fact that the by-products of the coffee and tea industry pollute the environment has called for the need of decaffeinating coffee and tea industry's by-products. Though physical and chemical methods for decaffeination are available, the lack of specificity for removal of caffeine in these techniques and their non-eco-friendly nature has opened the area of microbial and enzymatic degradation of caffeine. Another important application of microbial caffeine degradation apart from its advantages like specificity, eco-friendliness and cost-effectiveness is the fact that this process will enable the production of industrially and medically useful components of the caffeine degradation pathway like theobromine and theophylline. This is a comprehensive review which mainly focuses on caffeine degradation, large-scale degradation of the same and its applications in the industrial world.

  18. Reversible neuronal and muscular toxicity of caffeine in developing vertebrates.

    PubMed

    Rodriguez, Rufino S; Haugen, Rebecca; Rueber, Alexandra; Huang, Cheng-Chen

    2014-06-01

    This study utilizes zebrafish embryos to understand the cellular and molecular mechanisms of caffeine toxicity in developing vertebrate embryos. By using a high concentration of caffeine, we observed almost all the phenotypes that have been described in humans and/or in other animal models, including neural tube closure defect, jittery, touch insensitivity, and growth retardation as well as a drastic coiled body phenotype. Zebrafish embryos exposed to 5mM caffeine exhibited high frequent movement, 10 moves/min comparing with around 3 moves/min in control embryos, within half an hour post exposure (HPE). They later showed twitching, uncoordinated movement, and eventually severe body curvature by 6HPE. Exposure at later stages resulted in the same phenotypes but more posteriorly. Surprisingly, when caffeine was removed before 6HPE, the embryos were capable of recovering but still exhibited mild curvature and shorter bodies. Longer exposure caused irreversible body curvature and lethality. These results suggest that caffeine likely targets the neuro-muscular physiology in developing embryos. Immunohistochemistry revealed that the motorneurons in treated embryos developed shorter axons, abnormal branching, and excessive synaptic vesicles. Developing skeletal muscles also appeared smaller and lacked the well-defined boundaries seen in control embryos. Finally, caffeine increases the expression of genes involved in synaptic vesicle migration. In summary, our results provide molecular understanding of caffeine toxicity on developing vertebrate embryos.

  19. Caffeine promotes glutamate and histamine release in the posterior hypothalamus

    PubMed Central

    Kodama, Tohru; Siegel, Jerome M.

    2014-01-01

    Histamine neurons are active during waking and largely inactive during sleep, with minimal activity during rapid-eye movement (REM) sleep. Caffeine, the most widely used stimulant, causes a significant increase of sleep onset latency in rats and humans. We hypothesized that caffeine increases glutamate release in the posterior hypothalamus (PH) and produces increased activity of wake-active histamine neurons. Using in vivo microdialysis, we collected samples from the PH after caffeine administration in freely behaving rats. HPLC analysis and biosensor measurements showed a significant increase in glutamate levels beginning 30 min after caffeine administration. Glutamate levels remained elevated for at least 140 min. GABA levels did not significantly change over the same time period. Histamine level significantly increased beginning 30 min after caffeine administration and remained elevated for at least 140 min. Immunostaining showed a significantly elevated number of c-Fos-labeled histamine neurons in caffeine-treated rats compared with saline-treated animals. We conclude that increased glutamate levels in the PH activate histamine neurons and contribute to caffeine-induced waking and alertness. PMID:25031227

  20. Assessment of caffeine intake in the Korean population.

    PubMed

    Lim, Ho Soo; Hwang, Ju Young; Choi, Jae Chon; Kim, Meehye

    2015-01-01

    An improved method for the analysis of caffeine in foods by HPLC was validated by measuring several analytical parameters. The caffeine contents of 1202 products available from Korean markets were analysed. A consumption study was conducted by using data from the Korea National Health and Nutrition Examination Survey (KNHANES), 2010-12, to estimate the caffeine intakes of the Korean population. The mean intakes of caffeine from all sources in the general population and consumers were 67.8 and 102.6 mg day(-1) for all age groups, respectively. The 95th percentile intakes of the general population and consumers were 250.7 and 313.7 mg day(-1), respectively. In those aged 30-49 years, the caffeine intakes of the general population and consumers were highest at 25.5% (101.8 mg kg(-1) day(-1)) and 36.6% (0.9 mg kg(-1) day(-1)), respectively, compared with the maximum recommended daily intake (400 mg day(-1)) for adults. In the general population, the main contributors to the total caffeine intake were carbonated beverage for the younger age groups and coffee for the adults. These data provide a current perspective on caffeine intake in the Korean population.

  1. Caffeinated Alcoholic Beverages - An Emerging Trend in Alcohol Abuse.

    PubMed

    Franklin, Kelle M; Hauser, Sheketha R; Bell, Richard L; Engleman, Eric A

    2013-08-20

    Alcohol use disorders are pervasive in society and their impact affects quality of life, morbidity and mortality, as well as individual productivity. Alcohol has detrimental effects on an individual's physiology and nervous system, and is associated with disorders of many organ and endocrine systems impacting an individual's health, behavior, and ability to interact with others. Youth are particularly affected. Unfortunately, adolescent usage also increases the probability for a progression to dependence. Several areas of research indicate that the deleterious effects of alcohol abuse may be exacerbated by mixing caffeine with alcohol. Some behavioral evidence suggests that caffeine increases alcohol drinking and binge drinking episodes, which in turn can foster the development of alcohol dependence. As a relatively new public health concern, the epidemiological focus has been to establish a need for investigating the effects of caffeinated alcohol. While the trend of co-consuming these substances is growing, knowledge of the central mechanisms associated with caffeinated ethanol has been lacking. Research suggests that caffeine and ethanol can have additive or synergistic pharmacological actions and neuroadaptations, with the adenosine and dopamine systems in particular implicated. However, the limited literature on the central effects of caffeinated ethanol provides an impetus to increase our knowledge of the neuroadaptive effects of this combination and their impact on cognition and behavior. Research from our laboratories indicates that an established rodent animal model of alcoholism can be extended to investigate the acute and chronic effects of caffeinated ethanol. PMID:25419478

  2. Caffeine as a cause of urticaria-angioedema

    PubMed Central

    Tognetti, Linda; Murdaca, Francesco; Fimiani, Michele

    2014-01-01

    We report the case of a young woman presenting with recurrent urticaria. The episodes occurred both in and out of the workplace. On three occasions it presented as urticaria-angioedema, requiring emergency care on one occassion. A thorough clinical history along with serological and allergological tests allowed a diagnosis of caffeine-induced urticaria-angioedema. We advised the patient to follow a caffeine-free diet and to avoid all caffeine or methylxanthine-containing drugs. After two years of caffeine abstinence, she had not experienced any further episodes of urticaria-angioedema. Only a few cases of caffeine-induced urticaria and/or anaphylaxis have been reported till date, with varying outcomes in allergologic investigations. Moreover, several cases are probably undiagnosed or misdiagnosed as idiopathic urticaria or as occupational allergy. We speculate that hypersensitivity to caffeine rather than autoimmine reaction may be the probable cause of urticaria. Caffeine should considered as a potential urticaria-inducing agent and should be included in the allergological test series. PMID:25593798

  3. Reversible neuronal and muscular toxicity of caffeine in developing vertebrates.

    PubMed

    Rodriguez, Rufino S; Haugen, Rebecca; Rueber, Alexandra; Huang, Cheng-Chen

    2014-06-01

    This study utilizes zebrafish embryos to understand the cellular and molecular mechanisms of caffeine toxicity in developing vertebrate embryos. By using a high concentration of caffeine, we observed almost all the phenotypes that have been described in humans and/or in other animal models, including neural tube closure defect, jittery, touch insensitivity, and growth retardation as well as a drastic coiled body phenotype. Zebrafish embryos exposed to 5mM caffeine exhibited high frequent movement, 10 moves/min comparing with around 3 moves/min in control embryos, within half an hour post exposure (HPE). They later showed twitching, uncoordinated movement, and eventually severe body curvature by 6HPE. Exposure at later stages resulted in the same phenotypes but more posteriorly. Surprisingly, when caffeine was removed before 6HPE, the embryos were capable of recovering but still exhibited mild curvature and shorter bodies. Longer exposure caused irreversible body curvature and lethality. These results suggest that caffeine likely targets the neuro-muscular physiology in developing embryos. Immunohistochemistry revealed that the motorneurons in treated embryos developed shorter axons, abnormal branching, and excessive synaptic vesicles. Developing skeletal muscles also appeared smaller and lacked the well-defined boundaries seen in control embryos. Finally, caffeine increases the expression of genes involved in synaptic vesicle migration. In summary, our results provide molecular understanding of caffeine toxicity on developing vertebrate embryos. PMID:24667760

  4. Caffeine use in sports: considerations for the athlete.

    PubMed

    Sökmen, Bülent; Armstrong, Lawrence E; Kraemer, William J; Casa, Douglas J; Dias, Joao C; Judelson, Daniel A; Maresh, Carl M

    2008-05-01

    The ergogenic effects of caffeine on athletic performance have been shown in many studies, and its broad range of metabolic, hormonal, and physiologic effects has been recorded, as this review of the literature shows. However, few caffeine studies have been published to include cognitive and physiologic considerations for the athlete. The following practical recommendations consider the global effects of caffeine on the body: Lower doses can be as effective as higher doses during exercise performance without any negative coincidence; after a period of cessation, restarting caffeine intake at a low amount before performance can provide the same ergogenic effects as acute intake; caffeine can be taken gradually at low doses to avoid tolerance during the course of 3 or 4 days, just before intense training to sustain exercise intensity; and caffeine can improve cognitive aspects of performance, such as concentration, when an athlete has not slept well. Athletes and coaches also must consider how a person's body size, age, gender, previous use, level of tolerance, and the dose itself all influence the ergogenic effects of caffeine on sports performance.

  5. Physiology, biochemistry and possible applications of microbial caffeine degradation.

    PubMed

    Gummadi, Sathyanarayana N; Bhavya, B; Ashok, Nandhini

    2012-01-01

    Caffeine, a purine alkaloid is a constituent of widely consumed beverages. The scientific evidence which has proved the harm of this alkaloid has paved the way for innumerable research in the area of caffeine degradation. In addition to this, the fact that the by-products of the coffee and tea industry pollute the environment has called for the need of decaffeinating coffee and tea industry's by-products. Though physical and chemical methods for decaffeination are available, the lack of specificity for removal of caffeine in these techniques and their non-eco-friendly nature has opened the area of microbial and enzymatic degradation of caffeine. Another important application of microbial caffeine degradation apart from its advantages like specificity, eco-friendliness and cost-effectiveness is the fact that this process will enable the production of industrially and medically useful components of the caffeine degradation pathway like theobromine and theophylline. This is a comprehensive review which mainly focuses on caffeine degradation, large-scale degradation of the same and its applications in the industrial world. PMID:22139018

  6. Complex Behavior of Caffeine Crystallites on Muscovite Mica Surfaces

    PubMed Central

    2015-01-01

    Defined fabrication of organic thin films is highly desired in technological, as well as pharmaceutical, applications since morphology and crystal structure are directly linked to physical, electrical, and optical properties. Within this work, the directed growth of caffeine deposited by hot wall epitaxy (HWE) on muscovite mica is studied. Optical and atomic force microscopy measurements reveal the presence of caffeine needles exhibiting a preferable alignment in the azimuthal directions with respect to the orientation of the defined mica surface. Specular X-ray diffraction and X-ray diffraction pole figure measurements give evidence that the β-polymorphic form of caffeine forms on the mica surface. All results consent that caffeine molecules have an edge-on conformation i.e. minimizing their interaction area with the surface. Furthermore, the azimuthal alignment of the long caffeine needle axis takes place along the [11̅0], [100], and [110] real space directions of mica; needles are observed every 60° azimuthally. While mica has a complex surface structure with mirror planes and lowered oxygen rows, the slightly disturbed 3-fold symmetry dictates the crystal alignment. This is different to previous findings for solution cast caffeine growth on mica. For HWE the needles align solely along the mica main directions whereby solution cast needles show an additional needle splitting due to a different alignment of caffeine with respect to the surface. PMID:26366127

  7. Caffeinated Alcoholic Beverages – An Emerging Trend in Alcohol Abuse

    PubMed Central

    Franklin, Kelle M; Hauser, Sheketha R; Bell, Richard L.; Engleman, Eric A

    2014-01-01

    Alcohol use disorders are pervasive in society and their impact affects quality of life, morbidity and mortality, as well as individual productivity. Alcohol has detrimental effects on an individual’s physiology and nervous system, and is associated with disorders of many organ and endocrine systems impacting an individual’s health, behavior, and ability to interact with others. Youth are particularly affected. Unfortunately, adolescent usage also increases the probability for a progression to dependence. Several areas of research indicate that the deleterious effects of alcohol abuse may be exacerbated by mixing caffeine with alcohol. Some behavioral evidence suggests that caffeine increases alcohol drinking and binge drinking episodes, which in turn can foster the development of alcohol dependence. As a relatively new public health concern, the epidemiological focus has been to establish a need for investigating the effects of caffeinated alcohol. While the trend of co-consuming these substances is growing, knowledge of the central mechanisms associated with caffeinated ethanol has been lacking. Research suggests that caffeine and ethanol can have additive or synergistic pharmacological actions and neuroadaptations, with the adenosine and dopamine systems in particular implicated. However, the limited literature on the central effects of caffeinated ethanol provides an impetus to increase our knowledge of the neuroadaptive effects of this combination and their impact on cognition and behavior. Research from our laboratories indicates that an established rodent animal model of alcoholism can be extended to investigate the acute and chronic effects of caffeinated ethanol. PMID:25419478

  8. Uptake of carbamazepine by cucumber plants--a case study related to irrigation with reclaimed wastewater.

    PubMed

    Shenker, Moshe; Harush, Daniella; Ben-Ari, Julius; Chefetz, Benny

    2011-02-01

    Reclaimed wastewater is an important source of irrigation in semiarid and arid zones. Here we report data on carbamazepine (CBZ) uptake by cucumber plants in hydroponic culture and greenhouse experiments using different soil types irrigated with fresh water or reclaimed wastewater. Data obtained from the hydroponic culture experiments suggest that CBZ is mainly translocated by water mass flow, and thus it is concentrated and accumulated to the largest extent in the mature/older leaves. Carbamazepine concentration in cucumber fruits and leaves was negatively correlated with soil organic matter content. The concentrations of CBZ in the roots and stems were relatively low, and most CBZ in the plant (76-84% of total uptake) was detected in the leaves. A greenhouse experiment using fresh water and reclaimed wastewater spiked, or not, with CBZ at 1 μg L(-1) (typical concentration in effluents) revealed that CBZ can be taken up and bioaccumulated from its background concentration in reclaimed wastewater. Bioaccumulation factor (calculated as the ratio of CBZ concentration in the plant to that in the soil solution) for the fruits (0.8-1) was significantly lower than the value calculated for the leaves (17-20). This study emphasizes the potential uptake of active pharmaceutical compounds by crops in organic-matter-poor soils irrigated with reclaimed wastewater and highlights the potential risks associated with this agricultural practice. PMID:21071061

  9. Structure prediction, disorder and dynamics in a DMSO solvate of carbamazepine.

    PubMed

    Cruz-Cabeza, Aurora J; Day, Graeme M; Jones, William

    2011-07-28

    We have applied crystal structure prediction methods to understand and predict the formation of a DMSO solvate of the anti-convulsant drug carbamazepine (CBZ), in which the DMSO molecules are disordered. Crystal structure prediction calculations on the 1:1 CBZ:DMSO solvate revealed the generation of two similar low energy structures which differ only in the orientation of the DMSO molecules. Analysis of crystal energy landscapes generated at 0 K suggests the possibility of solvent disorder. A combined computational and experimental study of the changes in the orientation of the DMSO within the crystal structure revealed that the nature of the disorder changes with temperature. At low temperature, the DMSO disorder is static whilst at high temperature the DMSO configurations can interconvert by a 180° rotation of the DMSO molecules within the lattice. This 180° rotation of the DMSO molecules drives a phase change from a high temperature dynamically disordered phase to a low temperature phase with static disorder. Crystallisation of a DMSO solvate of the related molecule epoxycarbamazepine resulted in a different degree of DMSO disorder in the crystal structure, despite the similarity of the carbamazepine and epoxycarbamazepine molecules. We believe consideration of disorder and its contribution to entropy and crystal free energies at temperature other than 0 K is fundamental for the accuracy of future energy rankings in crystal structure prediction calculations of similar solvated structures. PMID:21670828

  10. Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods.

    PubMed

    Sethia, S; Squillante, E

    2004-03-19

    This study compares the physicochemical properties of carbamazepine (CBZ) solid dispersions prepared by either a conventional solvent evaporation versus a supercritical fluid process. Solid dispersions of carbamazepine in polyvinylpyrrolidone (PVP) K30 with either Gelucire 44/14 or Vitamin E TPGS, NF (d-alpha-tocopheryl polyethylene glycol 1000 succinate) were prepared and characterized by intrinsic dissolution, differential scanning calorimetry, powder X-ray diffraction and Fourier transform infrared spectroscopy. CBZ/PVP K30 and CBZ/PVP K30/TPGS solid dispersions showed increased dissolution rate. The best intrinsic dissolution rate (IDR) was obtained for supercritically processed CBZ/PVP K30 that was four-fold higher than pure CBZ. Thermograms of various solid dispersions did not show the melting peak of CBZ, indicating that CBZ was in amorphous form inside the carrier system. This was further confirmed by X-ray diffraction studies. Infrared spectroscopic studies showed interaction between CBZ and PVP K30 in solid dispersions. The amorphous state of CBZ coupled with presence of interaction between drug and PVP K30 suggests fewer, if any, stability problems. Because the supercritical-based process produced solid dispersions with IDR better than conventional solid dispersions augmented with amphiphilic carriers, stability issues associated with lipid carriers do not apply, which, in turn, implies easier scale up under current Good Manufacturing Practice for this technique.

  11. Timing of Caffeine Therapy and Neonatal Outcomes in Preterm Infants: A Retrospective Study.

    PubMed

    Hand, Ivan; Zaghloul, Nahla; Barash, Lily; Parris, Rudolph; Aden, Ulrika; Li, Hsiu-Ling

    2016-01-01

    Background. Caffeine is widely used to treat apnea of prematurity. Here, we evaluated the efficacy of early caffeine (1-2 DOL) in decreasing the incidence of adverse neonatal outcomes. Methods. A retrospective cohort was used to compare the neonatal morbidity of 150 preterm neonates with gestational age ≤29 weeks. Infants were divided into 3 groups based on the initiation timing of caffeine therapy; (1) early caffeine (1-2 DOL), (2) late caffeine (3-7 DOL), and (3) very late caffeine (≥8 DOL). Results. The neonatal outcomes of early caffeine were comparable with those of the late caffeine group. Moreover, when comparing the neonatal morbidity of the very late caffeine group with that of the early caffeine group, multivariable logistic regression analyses were performed. We found that the timing of caffeine did not influence the risk of BPD (OR, 0.393; CI, 0.126-1.223; p = 0.107), but birthweight did (OR, 0.996; CI, 0.993-0.999; p = 0.018) in these infants. Conclusion. Neonatal outcomes of preterm infants were comparable whether caffeine was administered early or late in the first 7 DOL. The risk of BPD in infants receiving caffeine after 8 DOL was irrespective of delayed treatment with caffeine. Our results clearly demonstrate the need for further studies before caffeine prophylaxis can be universally recommended.

  12. Timing of Caffeine Therapy and Neonatal Outcomes in Preterm Infants: A Retrospective Study

    PubMed Central

    Hand, Ivan; Zaghloul, Nahla; Barash, Lily; Parris, Rudolph; Aden, Ulrika; Li, Hsiu-Ling

    2016-01-01

    Background. Caffeine is widely used to treat apnea of prematurity. Here, we evaluated the efficacy of early caffeine (1-2 DOL) in decreasing the incidence of adverse neonatal outcomes. Methods. A retrospective cohort was used to compare the neonatal morbidity of 150 preterm neonates with gestational age ≤29 weeks. Infants were divided into 3 groups based on the initiation timing of caffeine therapy; (1) early caffeine (1-2 DOL), (2) late caffeine (3–7 DOL), and (3) very late caffeine (≥8 DOL). Results. The neonatal outcomes of early caffeine were comparable with those of the late caffeine group. Moreover, when comparing the neonatal morbidity of the very late caffeine group with that of the early caffeine group, multivariable logistic regression analyses were performed. We found that the timing of caffeine did not influence the risk of BPD (OR, 0.393; CI, 0.126–1.223; p = 0.107), but birthweight did (OR, 0.996; CI, 0.993–0.999; p = 0.018) in these infants. Conclusion. Neonatal outcomes of preterm infants were comparable whether caffeine was administered early or late in the first 7 DOL. The risk of BPD in infants receiving caffeine after 8 DOL was irrespective of delayed treatment with caffeine. Our results clearly demonstrate the need for further studies before caffeine prophylaxis can be universally recommended. PMID:27242907

  13. Mechanisms of Caffeine-Induced Inhibition of UVB Carcinogenesis.

    PubMed

    Conney, Allan H; Lu, Yao-Ping; Lou, You-Rong; Kawasumi, Masaoki; Nghiem, Paul

    2013-01-01

    Sunlight-induced non-melanoma skin cancer is the most prevalent cancer in the United States with more than two million cases per year. Several studies have shown an inhibitory effect of caffeine administration on UVB-induced skin cancer in mice, and these studies are paralleled by epidemiology studies that indicate an inhibitory effect of coffee drinking on non-melanoma skin cancer in humans. Strikingly, decaffeinated coffee consumption had no such inhibitory effect. Mechanism studies indicate that caffeine has a sunscreen effect that inhibits UVB-induced formation of thymine dimers and sunburn lesions in the epidermis of mice. In addition, caffeine administration has a biological effect that enhances UVB-induced apoptosis thereby enhancing the elimination of damaged precancerous cells, and caffeine administration also enhances apoptosis in tumors. Caffeine administration enhances UVB-induced apoptosis by p53-dependent and p53-independent mechanisms. Exploration of the p53-independent effect indicated that caffeine administration enhanced UVB-induced apoptosis by inhibiting the UVB-induced increase in ATR-mediated formation of phospho-Chk1 (Ser345) and abolishing the UVB-induced decrease in cyclin B1 which resulted in caffeine-induced premature and lethal mitosis in mouse skin. In studies with cultured primary human keratinocytes, inhibition of ATR with siRNA against ATR inhibited Chk1 phosphorylation and enhanced UVB-induced apoptosis. Transgenic mice with decreased epidermal ATR function that were irradiated chronically with UVB had 69% fewer tumors at the end of the study compared with irradiated littermate controls with normal ATR function. These results, which indicate that genetic inhibition of ATR (like pharmacologic inhibition of ATR via caffeine) inhibits UVB-induced carcinogenesis support the concept that ATR-mediated phosphorylation of Chk1 is an important target for caffeine's inhibitory effect on UVB-induced carcinogenesis. PMID:23785666

  14. Evaluation of the Reproductive and Developmental Risks of Caffeine

    PubMed Central

    Brent, Robert L; Christian, Mildred S; Diener, Robert M

    2011-01-01

    A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the “pregnancy signal,” which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine is an abortafacient for the wide range of human caffeine exposures. Almost all the congenital malformation epidemiology studies were negative. Animal pharmacokinetic studies indicate that the teratogenic plasma level of caffeine has to reach or exceed 60 µg/ml, which is not attainable from ingesting large amounts of caffeine in foods and beverages. No epidemiological study described the “caffeine teratogenic syndrome.” Six of the 17 recent epidemiology studies dealing with the risk of caffeine and fetal weight reduction were negative. Seven of the positive studies had growth reductions that were clinically insignificant and none of the studies cited the animal literature. Analysis of caffeine's reproductive toxicity considers reproducibility and plausibility of clinical, epidemiological, and animal data. Moderate or even high amounts of beverages and foods containing caffeine do not increase the risks of congenital malformations, miscarriage or growth retardation. Pharmacokinetic studies markedly improve the ability to perform the risk analyses. Birth Defects Res (Part B) 92:152–187, 2011. © 2011 Wiley-Liss, Inc. PMID:21370398

  15. Selective crystallization of metastable phase of acetaminophen by ultrasonic irradiation

    NASA Astrophysics Data System (ADS)

    Mori, Yoichiro; Maruyama, Mihoko; Takahashi, Yoshinori; Ikeda, Kenji; Fukukita, Suguru; Yoshikawa, Hiroshi Y.; Okada, Shino; Adachi, Hiroaki; Sugiyama, Shigeru; Takano, Kazufumi; Murakami, Satoshi; Matsumura, Hiroyoshi; Inoue, Tsuyoshi; Yoshimura, Masashi; Mori, Yusuke

    2015-06-01

    A new method for selective crystallization of the metastable phase (form II) of acetaminophen is described. To obtain form II, we prepared a highly supersaturated solution (σI = 3.7) and then applied ultrasonic irradiation at different frequencies. Without ultrasonic irradiation, spontaneous crystallization did not occur within one month in the highly supersaturated condition (σI = 3.7). When ultrasonic irradiation at 28 kHz was applied, form II preferentially crystallized. Therefore, we conclude that ultrasonic irradiation can be an effective technique for selectively crystallizing the metastable phase.

  16. Translational biomarkers of acetaminophen-induced acute liver injury.

    PubMed

    Beger, Richard D; Bhattacharyya, Sudeepa; Yang, Xi; Gill, Pritmohinder S; Schnackenberg, Laura K; Sun, Jinchun; James, Laura P

    2015-09-01

    Acetaminophen (APAP) is a commonly used analgesic drug that can cause liver injury, liver necrosis and liver failure. APAP-induced liver injury is associated with glutathione depletion, the formation of APAP protein adducts, the generation of reactive oxygen and nitrogen species and mitochondrial injury. The systems biology omics technologies (transcriptomics, proteomics and metabolomics) have been used to discover potential translational biomarkers of liver injury. The following review provides a summary of the systems biology discovery process, analytical validation of biomarkers and translation of omics biomarkers from the nonclinical to clinical setting in APAP-induced liver injury.

  17. Implications of Sensorineural Hearing Loss With Hydrocodone/Acetaminophen Abuse

    PubMed Central

    Novac, Andrei; Iosif, Anamaria M.; Groysman, Regina; Bota, Robert G.

    2015-01-01

    Sensorineural hearing loss is an infrequently recognized side effect of pain medication abuse. Chronic pain patients treated with opiates develop different degrees of tolerance to pain medications. In many cases, the tolerance becomes the gateway to a variety of cycles of overuse and unmasking of significant psychiatric morbidity and mortality. An individualized approach utilizing combined treatment modalities (including nonopiate pharmaceuticals) is expected to become the norm. Patients can now be provided with multidisciplinary care that addresses an individual’s psychiatric, social, and medical needs, which requires close cooperation between physicians of varying specialties. This report describes a patient who experienced hearing loss from hydrocodone/acetaminophen abuse. PMID:26835162

  18. Implications of Sensorineural Hearing Loss With Hydrocodone/Acetaminophen Abuse.

    PubMed

    Novac, Andrei; Iosif, Anamaria M; Groysman, Regina; Bota, Robert G

    2015-01-01

    Sensorineural hearing loss is an infrequently recognized side effect of pain medication abuse. Chronic pain patients treated with opiates develop different degrees of tolerance to pain medications. In many cases, the tolerance becomes the gateway to a variety of cycles of overuse and unmasking of significant psychiatric morbidity and mortality. An individualized approach utilizing combined treatment modalities (including nonopiate pharmaceuticals) is expected to become the norm. Patients can now be provided with multidisciplinary care that addresses an individual's psychiatric, social, and medical needs, which requires close cooperation between physicians of varying specialties. This report describes a patient who experienced hearing loss from hydrocodone/acetaminophen abuse. PMID:26835162

  19. [Caffeine as adjuvant analgeticum for treating acute pain].

    PubMed

    Nikolajsen, Lone; Haroutiunian, Simon

    2013-10-14

    Based on 19 studies (7,238 participants) a Cochrane review concludes that the addition of caffeine to an analgesic drug provides superior analgesia compared with the analgesic drug alone. The benefit is small, with a number needed to treat of approx. 16. The use of analgesics containing caffeine is associated with an increased risk of the development of physical dependence, overuse headache, and withdrawal symptoms upon abrupt discontinuation. Combination analgesics with caffeine should only be used temporarily and exclusively for the treatment of acute pain conditions. PMID:24629115

  20. The use of O, H and Sr isotopes and carbamazepine to identify the origin of water bodies supplying a shallow alluvial aquifer

    NASA Astrophysics Data System (ADS)

    Sassine, Lara; Le Gal La Salle, Corinne; Lancelot, Joël; Verdoux, Patrick

    2014-05-01

    Alluvial aquifers are of great socio-economic importance in France since they supply 82% of drinking water production, though they reveal to be very vulnerable to pesticides and emerging organic contaminants. The aim of this work is to identify the origin of water bodies which contribute to the recharge of an alluvial aquifer for a better understanding of its hydrochemistry and transfer of contaminants therein. The study is based on an isotopic and geochemical tracers approach, including major elements, trace elements (Br, Sr),and isotopes (δ18O, δ2H, 87Sr/86Sr), as well as organic molecules. Indeed, organic molecules such as pharmaceutical compounds, more precisely carbamazepine and caffeine, have shown their use as indicators of surface water in groundwater. The study area is a partially-confined shallow alluvial aquifer, the so-called Vistrenque aquifer, located at 15 km from the Mediterranean Sea, in the Quaternary alluviums deposited by an ancient arm of the Rhône River, in Southern France. This aquifer constitutes a shallow alluvial layer in a NE-SW graben structure. It is situated between a karst aquifer in lower Cretaceous limestones, on the NW border, and the Costières Plateau, on the SE border, having a similar geology as the Vistrenque. The alluvial plain is crossed by a surface water network with the Vistre as the main stream, and a canal used for irrigation essentially, the BRL canal, which is fed by the Rhône River. δ18O and δ2H allowed to differentiate the BRL canal water, depleted in heavy isotopes (δ2H = -71.5o vs V-SMOW), and the more enriched local rainwater (δ2H = -35.5o vs V-SMOW). In the Vistre surface water a binary mixing were evidenced with the BRL canal water and the rainwater, as end members. Then, in the Vistrenque groundwater both the BRL and the Vistre contributions could be identified, as they still show contrasting signature with local recharge. This allows to highlight the surface water contribution to a heavily exploited

  1. Prophylactic and Therapeutic Potential of Acetyl-L-carnitine against Acetaminophen-Induced Hepatotoxicity in Mice.

    PubMed

    Alotaibi, Salman A; Alanazi, Abdulrazaq; Bakheet, Saleh A; Alharbi, Naif O; Nagi, Mahmoud N

    2016-01-01

    Prophylactic and therapeutic effects of acetylcarnitine against acetaminophen-induced hepatotoxicity were studied in mice. To evaluate the prophylactic effects of acetylcarnitine, mice were supplemented with acetylcarnitine (2 mmol/kg/day per oral (p.o.) for 5 days) before a single dose of acetaminophen (350 mg/kg intraperitoneal (i.p.)). Animals were sacrificed 6 h after acetaminophen injection. Acetaminophen significantly increased the markers of liver injury, hepatic reactive oxygen species, and nitrate/nitrite, and decreased hepatic glutathione (GSH) and the antioxidant enzymes. Acetylcarnitine supplementation resulted in reversal of all biochemical parameters toward the control values. To explore the therapeutic effects of acetylcarnitine, mice were given a single dose of acetylcarnitine (0.5, 1, and 2 mmol/kg p.o.) 1.5 h after acetaminophen. Animals were sacrificed 6 h after acetaminophen. Acetylcarnitine administration resulted in partial reversal of liver injury only at 2 mmol/kg p.o. At equimolar doses, N-acetylcystiene was superior as therapeutic agent to acetylcarnitine. However, acetylcarnitine potentiated the effect of N-acetylcystiene in the treatment of acetaminophen toxicity. PMID:26265018

  2. Association between recent acetaminophen use and asthma: modification by polymorphism at TLR4.

    PubMed

    Lee, Seung-Hwa; Kang, Mi-Jin; Yu, Ho-Sung; Hong, Kyungmo; Jung, Young-Ho; Kim, Hyung-Young; Seo, Ju-Hee; Kwon, Ji-Won; Kim, Byoung-Ju; Kim, Ha-Jung; Kim, Young-Joon; Kim, Hee-Suk; Kim, Hyo Bin; Park, Kang Seo; Lee, So-Yeon; Hong, Soo-Jong

    2014-05-01

    The risk of asthma has been increasing in parallel with use of acetaminophen, which is a potential source of oxidative stress. Toll-like receptor 4 (TLR4) plays a critical role not only in innate immunity, but also in mediating reactive oxygen species induced inflammation. Therefore, we investigated associations between acetaminophen usage and TLR4 polymorphism on asthma and bronchial hyperresponsiveness (BHR). The number of 2,428 elementary school children in Seoul and Jeongeup cities was recruited. Subjects who used acetaminophen with a family history of asthma had an increased risk of both asthma diagnosis ever and current asthma. Individuals with CT+TT genotypes at the TLR4 polymorphism, in combination with acetaminophen usage, also demonstrated an increased risk of asthma diagnosis ever (aOR, 2.08; 95% confidence interval [CI], 1.10-3.92). Family history of asthma and acetaminophen usage were risk factors for BHR. Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT genotypes at the TLR4 polymorphism had an increased risk of BHR when combined with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94). In conclusion, acetaminophen usage may be associated with asthma and BHR in genetically susceptible subjects. This effect may be modified by polymorphism at TLR4.

  3. Acetaminophen for analgesia following pyloromyotomy: does the route of administration make a difference?

    PubMed Central

    Yung, Arvid; Thung, Arlyne; Tobias, Joseph D

    2016-01-01

    Background During the perioperative care of infants with hypertrophic pyloric stenosis, an opioid-sparing technique is often advocated due to concerns such as postoperative hypoventilation and apnea. Although the rectal administration of acetaminophen is commonly employed, an intravenous (IV) preparation is also currently available, but only limited data are available regarding IV acetaminophen use for infants undergoing pyloromyotomy. The objective of the current study was to compare the efficacy of IV and rectal acetaminophen for postoperative analgesia in infants undergoing laparoscopic pyloromyotomy. Methods A retrospective review of the use of IV and rectal acetaminophen in infants undergoing laparoscopic pyloromyotomy was performed. The efficacy was assessed by evaluating the perioperative need for supplemental analgesic agents, postoperative pain scores, tracheal extubation time, time in the postanesthesia care unit, time to oral feeding, and time to hospital discharge. Results The study cohort included 68 patients, of whom 34 patients received IV acetaminophen and 34 received rectal acetaminophen. All patients also received local infiltration of the surgical site with 0.25% bupivacaine. No intraoperative opioids were administered. There was no difference between the two groups with regard to postoperative pain scores, need for supplemental analgesic agents, time in the postanesthesia care unit, or time in the hospital. There was no difference in the number of children who tolerated oral feeds on the day of surgery or in postoperative complications. Conclusion Our preliminary data suggest that there is no clinical difference or advantage with the use of IV versus rectal acetaminophen in infants undergoing laparoscopic pyloromyotomy. PMID:27022299

  4. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model.

    PubMed

    van den Driesche, Sander; Macdonald, Joni; Anderson, Richard A; Johnston, Zoe C; Chetty, Tarini; Smith, Lee B; McKinnell, Chris; Dean, Afshan; Homer, Natalie Z; Jorgensen, Anne; Camacho-Moll, Maria E; Sharpe, Richard M; Mitchell, Rod T

    2015-05-20

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; P = 0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; P = 0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect.

  5. Prophylactic and Therapeutic Potential of Acetyl-L-carnitine against Acetaminophen-Induced Hepatotoxicity in Mice.

    PubMed

    Alotaibi, Salman A; Alanazi, Abdulrazaq; Bakheet, Saleh A; Alharbi, Naif O; Nagi, Mahmoud N

    2016-01-01

    Prophylactic and therapeutic effects of acetylcarnitine against acetaminophen-induced hepatotoxicity were studied in mice. To evaluate the prophylactic effects of acetylcarnitine, mice were supplemented with acetylcarnitine (2 mmol/kg/day per oral (p.o.) for 5 days) before a single dose of acetaminophen (350 mg/kg intraperitoneal (i.p.)). Animals were sacrificed 6 h after acetaminophen injection. Acetaminophen significantly increased the markers of liver injury, hepatic reactive oxygen species, and nitrate/nitrite, and decreased hepatic glutathione (GSH) and the antioxidant enzymes. Acetylcarnitine supplementation resulted in reversal of all biochemical parameters toward the control values. To explore the therapeutic effects of acetylcarnitine, mice were given a single dose of acetylcarnitine (0.5, 1, and 2 mmol/kg p.o.) 1.5 h after acetaminophen. Animals were sacrificed 6 h after acetaminophen. Acetylcarnitine administration resulted in partial reversal of liver injury only at 2 mmol/kg p.o. At equimolar doses, N-acetylcystiene was superior as therapeutic agent to acetylcarnitine. However, acetylcarnitine potentiated the effect of N-acetylcystiene in the treatment of acetaminophen toxicity.

  6. BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury

    SciTech Connect

    Nagy, Gabor; Szarka, Andras; Lotz, Gabor; Doczi, Judit; Wunderlich, Livius; Kiss, Andras; Jemnitz, Katalin; Veres, Zsuzsa; Banhegyi, Gabor; Schaff, Zsuzsa; Suemegi, Balazs; Mandl, Jozsef

    2010-02-15

    It has been recently shown that acute acetaminophen toxicity results in endoplasmic reticulum redox stress and an increase in cells with apoptotic phenotype in liver. Since activation of effector caspases was absent, the relevance of caspase-independent mechanisms in acetaminophen-induced programmed cell death was investigated. BGP-15, a drug with known protective actions in conditions involving redox imbalance, has been co-administered with a single sublethal dose of acetaminophen. Proapoptotic events and outcome of the injury were investigated. ER redox alterations and early ER-stress-related signaling events induced by acetaminophen, such as ER glutathione depletion, phosphorylation of eIF2alpha and JNK and induction of the transcription factor GADD153, were not counteracted by co-treatment with BGP-15. However, BGP-15 prevented AIF mitochondria-to-nucleus translocation and mitochondrial depolarization. BGP-15 co-treatment attenuated the rate of acetaminophen-induced cell death as assessed by apoptotic index and enzyme serum release. These results reaffirm that acute acetaminophen toxicity involves oxidative stress-induced caspase-independent cell death. In addition, pharmacological inhibition of AIF translocation may effectively protect against or at least delay acetaminophen-induced programmed cell death.

  7. BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury.

    PubMed

    Nagy, Gábor; Szarka, András; Lotz, Gábor; Dóczi, Judit; Wunderlich, Lívius; Kiss, András; Jemnitz, Katalin; Veres, Zsuzsa; Bánhegyi, Gábor; Schaff, Zsuzsa; Sümegi, Balázs; Mandl, József

    2010-02-15

    It has been recently shown that acute acetaminophen toxicity results in endoplasmic reticulum redox stress and an increase in cells with apoptotic phenotype in liver. Since activation of effector caspases was absent, the relevance of caspase-independent mechanisms in acetaminophen-induced programmed cell death was investigated. BGP-15, a drug with known protective actions in conditions involving redox imbalance, has been co-administered with a single sublethal dose of acetaminophen. Proapoptotic events and outcome of the injury were investigated. ER redox alterations and early ER-stress-related signaling events induced by acetaminophen, such as ER glutathione depletion, phosphorylation of eIF2alpha and JNK and induction of the transcription factor GADD153, were not counteracted by co-treatment with BGP-15. However, BGP-15 prevented AIF mitochondria-to-nucleus translocation and mitochondrial depolarization. BGP-15 co-treatment attenuated the rate of acetaminophen-induced cell death as assessed by apoptotic index and enzyme serum release. These results reaffirm that acute acetaminophen toxicity involves oxidative stress-induced caspase-independent cell death. In addition, pharmacological inhibition of AIF translocation may effectively protect against or at least delay acetaminophen-induced programmed cell death.

  8. Comparing the Efficacy of Intravenous Acetaminophen and Intravenous Meperidine in Pain Relief After Outpatient Urological Surgery

    PubMed Central

    Kolahdouzan, Khosro; Eydi, Mahmood; Mohammadipour Anvari, Hassan; Golzari, Samad EJ; Abri, Reyhaneh; Ghojazadeh, Morteza; Ojaghihaghighi, Seyed Hossein

    2014-01-01

    Background: Pain relief after surgery is an essential component of postoperative care. Objectives: The purpose of this study was to compare the efficacy of intravenous acetaminophen and intravenous meperidine in pain relief after outpatient urological surgery. Patients and Methods: In a prospective, randomized, double-blind clinical trial, 100 outpatients of urological surgery were studied in two groups of acetaminophen (A) and meperidine (M). Patients in group A received 1g of acetaminophen in 100 mL saline within 15 minutes and patients in group M received a single intravenous injection of meperidine 0.5 mg/kg, 15 minutes prior to the end of operation. Postoperative pain was recorded using visual analog scale (VAS). Vital signs, nausea, vomiting, dizziness and respiratory depressions were compared between the two groups. Results: Pain severity in patients treated with intravenous acetaminophen six hours after the operation within one-hour interval was significantly lower than meperidine group (P < 0.0001). Ninety patients in the meperidine group and five patients in the acetaminophen group required additional doses of analgesics. Nausea was significantly lower in acetaminophen group than meperidine group. Conclusions: Intravenous acetaminophen reduced pain following outpatient urological surgery more significantly than meperidine. PMID:25798377

  9. Association of the Anxiogenic and Alerting Effects of Caffeine with ADORA2A and ADORA1 Polymorphisms and Habitual Level of Caffeine Consumption

    PubMed Central

    Rogers, Peter J; Hohoff, Christa; Heatherley, Susan V; Mullings, Emma L; Maxfield, Peter J; Evershed, Richard P; Deckert, Jürgen; Nutt, David J

    2010-01-01

    Caffeine, a widely consumed adenosine A1 and A2A receptor antagonist, is valued as a psychostimulant, but it is also anxiogenic. An association between a variant within the ADORA2A gene (rs5751876) and caffeine-induced anxiety has been reported for individuals who habitually consume little caffeine. This study investigated whether this single nucleotide polymorphism (SNP) might also affect habitual caffeine intake, and whether habitual intake might moderate the anxiogenic effect of caffeine. Participants were 162 non-/low (NL) and 217 medium/high (MH) caffeine consumers. In a randomized, double-blind, parallel groups design they rated anxiety, alertness, and headache before and after 100 mg caffeine and again after another 150 mg caffeine given 90 min later, or after placebo on both occasions. Caffeine intake was prohibited for 16 h before the first dose of caffeine/placebo. Results showed greater susceptibility to caffeine-induced anxiety, but not lower habitual caffeine intake (indeed coffee intake was higher), in the rs5751876 TT genotype group, and a reduced anxiety response in MH vs NL participants irrespective of genotype. Apart from the almost completely linked ADORA2A SNP rs3761422, no other of eight ADORA2A and seven ADORA1 SNPs studied were found to be clearly associated with effects of caffeine on anxiety, alertness, or headache. Placebo administration in MH participants decreased alertness and increased headache. Caffeine did not increase alertness in NL participants. With frequent consumption, substantial tolerance develops to the anxiogenic effect of caffeine, even in genetically susceptible individuals, but no net benefit for alertness is gained, as caffeine abstinence reduces alertness and consumption merely returns it to baseline. PMID:20520601

  10. Variability in Acetaminophen Labeling Practices: a Missed Opportunity to Enhance Patient Safety.

    PubMed

    King, Jennifer P; McCarthy, Danielle M; Serper, Marina; Jacobson, Kara L; Mullen, Rebecca J; Parker, Ruth M; Wolf, Michael S

    2015-12-01

    Confusion regarding a drug's active ingredient may lead to simultaneous use of multiple acetaminophen-containing prescriptions and increase the risk of unintentional overdose. The objective of this study was to examine prescription labeling practices for commonly prescribed acetaminophen-containing analgesics, specifically focusing on how active ingredient information and concomitant use warnings were conveyed. Patients with new acetaminophen-containing prescriptions were recruited upon discharge from an emergency department in Chicago or at an outpatient, hospital-based pharmacy in Atlanta. Label information was transcribed from prescription bottles and patients' knowledge of active ingredient was assessed by in-person interviews. Among the 245 acetaminophen-containing prescriptions, hydrocodone was the most common second active ingredient (n = 208, 84.8 %) followed by oxycodone (n = 28, 11.4 %). Acetaminophen was identified by its full name on 6.9 % (n = 17) of labels; various abbreviations were used in 93.1 % of cases. One hundred forty-seven bottles used auxiliary warning labels with the majority of labels (n = 130, 88.4 %) warning about maximum dose and 11.5 % (n = 17) about concomitant use. Most of the study participants (n = 177, 72.2 %) were not able to identify acetaminophen as an active ingredient in their prescription. There was no significant association between the use of unabbreviated labels including warning information and patients' awareness of acetaminophen as an active ingredient (36.4 vs. 27.3 %, p = 0.50). We noted high variability in labeling practices and warning information conveyed to patients receiving acetaminophen-containing prescriptions. Missed opportunities to adequately convey risk information may contribute to the burden of acetaminophen-related liver injury.

  11. Relationship between serum acetaminophen concentration and N-acetylcysteine-induced adverse drug reactions.

    PubMed

    Zyoud, Sa'ed H; Awang, Rahmat; Sulaiman, Syed Azhar Syed; Khan, Halilol Rahman Mohamed; Sawalha, Ansam F; Sweileh, Waleed M; Al-Jabi, Samah W

    2010-09-01

    Intravenous N-acetylcysteine is usually regarded as a safe antidote. However, during the infusion of the loading dose, different types of adverse drug reactions (ADR) may occur. The objective of this study was to investigate the relation between the incidence of different types of ADR and serum acetaminophen concentration in patients presenting to the hospital with acetaminophen overdose. This is a retrospective study of patients admitted to the hospital for acute acetaminophen overdose over a period of 5 years (1 January 2004 to 31 December 2008). Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. SPSS 15 was used for data analysis. Of 305 patients with acetaminophen overdose, 146 (47.9%) were treated with intravenous N-acetylcysteine and 139 (45.6%) were included in this study. Different types of ADR were observed in 94 (67.6%) patients. Low serum acetaminophen concentrations were significantly associated with cutaneous anaphylactoid reactions but not other types of ADR. Low serum acetaminophen concentration was significantly associated with flushing (p < 0.001), rash (p < 0.001) and pruritus (p < 0.001). However, there were no significant differences in serum acetaminophen concentrations between patients with and without the following ADR: gastrointestinal reactions (p = 0.77), respiratory reactions (p = 0.96), central nervous reactions (p = 0.82) and cardiovascular reactions (p = 0.37). In conclusion, low serum acetaminophen concentrations were associated with higher cutaneous anaphylactoid reactions. Such high serum acetaminophen concentrations may be protective against N-acetylcysteine-induced cutaneous ADR. PMID:20374238

  12. Use of acetaminophen (paracetamol) during pregnancy and the risk of autism spectrum disorder in the offspring.

    PubMed

    Andrade, Chittaranjan

    2016-02-01

    Acetaminophen (paracetamol) is available over the counter in most countries and is widely considered to be safe for use during pregnancy; studies report gestational exposures to acetaminophen that lie in the 46%-65% range. Acetaminophen influences inflammatory and immunologic mechanisms and may predispose to oxidative stress; these and other effects are hypothesized to have the potential to compromise neurodevelopment in the fetal and infant brain. Two ecological studies suggested that population-level trends in the use of acetaminophen were associated with trends in the incidence/prevalence of autism; one of these studies specifically examined acetaminophen use during pregnancy. One large prospective observational cohort study found that gestational exposure to acetaminophen (especially when the duration of exposure was 28 days or more) was associated with motor milestone delay, gross and fine motor impairments, communication impairment, impairments in internalizing and externalizing behaviors, and hyperactivity, all at age 3 years; however, social and emotional developmental behaviors were mostly unaffected. A very recent large cohort study with a 12.7-year follow-up found that gestational exposure to acetaminophen was associated with an increased risk of autism spectrum disorder, but only when a hyperkinetic disorder was also present. In the light of existing data associating acetaminophen use during pregnancy and subsequent risk of attention-deficit/hyperactivity disorder, this new finding suggests that the predisposition, if any, is toward the hyperkinetic syndrome rather than to autism. In summary, the empirical data are very limited, but whatever empirical data exist do not support the suggestion that the use of acetaminophen during pregnancy increases the risk of autism in the offspring.

  13. Use of acetaminophen (paracetamol) during pregnancy and the risk of autism spectrum disorder in the offspring.

    PubMed

    Andrade, Chittaranjan

    2016-02-01

    Acetaminophen (paracetamol) is available over the counter in most countries and is widely considered to be safe for use during pregnancy; studies report gestational exposures to acetaminophen that lie in the 46%-65% range. Acetaminophen influences inflammatory and immunologic mechanisms and may predispose to oxidative stress; these and other effects are hypothesized to have the potential to compromise neurodevelopment in the fetal and infant brain. Two ecological studies suggested that population-level trends in the use of acetaminophen were associated with trends in the incidence/prevalence of autism; one of these studies specifically examined acetaminophen use during pregnancy. One large prospective observational cohort study found that gestational exposure to acetaminophen (especially when the duration of exposure was 28 days or more) was associated with motor milestone delay, gross and fine motor impairments, communication impairment, impairments in internalizing and externalizing behaviors, and hyperactivity, all at age 3 years; however, social and emotional developmental behaviors were mostly unaffected. A very recent large cohort study with a 12.7-year follow-up found that gestational exposure to acetaminophen was associated with an increased risk of autism spectrum disorder, but only when a hyperkinetic disorder was also present. In the light of existing data associating acetaminophen use during pregnancy and subsequent risk of attention-deficit/hyperactivity disorder, this new finding suggests that the predisposition, if any, is toward the hyperkinetic syndrome rather than to autism. In summary, the empirical data are very limited, but whatever empirical data exist do not support the suggestion that the use of acetaminophen during pregnancy increases the risk of autism in the offspring. PMID:26930528

  14. Study on the reaction mechanism and the static injection chemiluminescence method for detection of acetaminophen.

    PubMed

    Wu, Yongjun; Zhang, Huili; Yu, Songcheng; Yu, Fei; Li, Yanqiang; Zhang, Hongquan; Qu, Lingbo; Harrington, Peter de B

    2013-01-01

    Acetaminophen, also called paracetamol, is found in Tylenol, Excedrin and other products as over-the-counter medicines. In this study, acetaminophen as a luminol signal enhancer was used in the chemiluminescence (CL) substrate solution of horseradish peroxidase (HRP) for the first time. The use of acetaminophen in the luminol-HRP-H2O2 system affected not only the intensity of the obtained signal, but also its kinetics. It was shown that acetaminophen was to be a potent enhancer of the luminol-HRP-H2O2 system. A putative enhancement mechanism for the luminol-H2O2-HRP-acetaminophen system is presented. The resonance of the nucleophilic amide group and the benzene ring of acetaminophen structure have a great effect on O-H bond dissociation energy of the phenol group and therefore on phenoxyl radical stabilization. These radicals act as mediators between HRP and luminol in an electron transfer reaction that generates luminol radicals and subsequently light emission, in which the intensity of CL is enhanced in the presence of acetaminophen. In addition, a simple method was developed to detect acetaminophen by static injection CL based on the enhanced CL system of luminol-H2O2-HRP by acetaminophen. Experimental conditions, such as pH and concentrations of substrates, have been examined and optimized. The proposed method exhibited good performance, the linear range was from 0.30 to 7.5 mM, the relative standard deviation was 1.86% (n = 10), limit of detection was 0.16 mM and recovery was 99 ± 4%.

  15. Variability in Acetaminophen Labeling Practices: a Missed Opportunity to Enhance Patient Safety.

    PubMed

    King, Jennifer P; McCarthy, Danielle M; Serper, Marina; Jacobson, Kara L; Mullen, Rebecca J; Parker, Ruth M; Wolf, Michael S

    2015-12-01

    Confusion regarding a drug's active ingredient may lead to simultaneous use of multiple acetaminophen-containing prescriptions and increase the risk of unintentional overdose. The objective of this study was to examine prescription labeling practices for commonly prescribed acetaminophen-containing analgesics, specifically focusing on how active ingredient information and concomitant use warnings were conveyed. Patients with new acetaminophen-containing prescriptions were recruited upon discharge from an emergency department in Chicago or at an outpatient, hospital-based pharmacy in Atlanta. Label information was transcribed from prescription bottles and patients' knowledge of active ingredient was assessed by in-person interviews. Among the 245 acetaminophen-containing prescriptions, hydrocodone was the most common second active ingredient (n = 208, 84.8 %) followed by oxycodone (n = 28, 11.4 %). Acetaminophen was identified by its full name on 6.9 % (n = 17) of labels; various abbreviations were used in 93.1 % of cases. One hundred forty-seven bottles used auxiliary warning labels with the majority of labels (n = 130, 88.4 %) warning about maximum dose and 11.5 % (n = 17) about concomitant use. Most of the study participants (n = 177, 72.2 %) were not able to identify acetaminophen as an active ingredient in their prescription. There was no significant association between the use of unabbreviated labels including warning information and patients' awareness of acetaminophen as an active ingredient (36.4 vs. 27.3 %, p = 0.50). We noted high variability in labeling practices and warning information conveyed to patients receiving acetaminophen-containing prescriptions. Missed opportunities to adequately convey risk information may contribute to the burden of acetaminophen-related liver injury. PMID:25697756

  16. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Associated with Acetaminophen Use during Viral Infections.

    PubMed

    Ban, Ga-Young; Ahn, Seun-Joo; Yoo, Hye-Soo; Park, Hae-Sim; Ye, Young-Min

    2016-08-01

    An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN. PMID:27574505

  17. Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans

    PubMed Central

    Foster, Josh; Mauger, Alexis; Thomasson, Katie; White, Stephanie; Taylor, Lee

    2016-01-01

    In non-febrile mouse models, high dose acetaminophen administration causes profound hypothermia. However, this potentially hazardous side-effect has not been confirmed in non-febrile humans. Thus, we sought to ascertain whether an acute therapeutic dose (20 mg⋅kg lean body mass) of acetaminophen would reduce non-febrile human core temperature in a sub-neutral environment. Ten apparently healthy (normal core temperature, no musculoskeletal injury, no evidence of acute illness) Caucasian males participated in a preliminary study (Study 1) to determine plasma acetaminophen concentration following oral ingestion of 20 mg⋅kg lean body mass acetaminophen. Plasma samples (every 20 min up to 2-hours post ingestion) were analyzed via enzyme linked immunosorbent assay. Thirteen (eight recruited from Study 1) apparently healthy Caucasian males participated in Study 2, and were passively exposed to 20°C, 40% r.h. for 120 min on two occasions in a randomized, repeated measures, crossover design. In a double blind manner, participants ingested acetaminophen (20 mg⋅kg lean body mass) or a placebo (dextrose) immediately prior to entering the environmental chamber. Rectal temperature, skin temperature, heart rate, and thermal sensation were monitored continuously and recorded every 10 min. In Study 1, the peak concentration of acetaminophen (14 ± 4 μg/ml) in plasma arose between 80 and 100 min following oral ingestion. In Study 2, acetaminophen ingestion reduced the core temperature of all participants, whereas there was no significant change in core temperature over time in the placebo trial. Mean core temperature was significantly lower in the acetaminophen trial compared with that of a placebo (p < 0.05). The peak reduction in core temperature in the acetaminophen trial was reached at 120 min in six of the thirteen participants, and ranged from 0.1 to 0.39°C (average peak reduction from baseline = 0.19 ± 0.09°C). There was no significant difference in skin

  18. Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans.

    PubMed

    Foster, Josh; Mauger, Alexis; Thomasson, Katie; White, Stephanie; Taylor, Lee

    2016-01-01

    In non-febrile mouse models, high dose acetaminophen administration causes profound hypothermia. However, this potentially hazardous side-effect has not been confirmed in non-febrile humans. Thus, we sought to ascertain whether an acute therapeutic dose (20 mg⋅kg lean body mass) of acetaminophen would reduce non-febrile human core temperature in a sub-neutral environment. Ten apparently healthy (normal core temperature, no musculoskeletal injury, no evidence of acute illness) Caucasian males participated in a preliminary study (Study 1) to determine plasma acetaminophen concentration following oral ingestion of 20 mg⋅kg lean body mass acetaminophen. Plasma samples (every 20 min up to 2-hours post ingestion) were analyzed via enzyme linked immunosorbent assay. Thirteen (eight recruited from Study 1) apparently healthy Caucasian males participated in Study 2, and were passively exposed to 20°C, 40% r.h. for 120 min on two occasions in a randomized, repeated measures, crossover design. In a double blind manner, participants ingested acetaminophen (20 mg⋅kg lean body mass) or a placebo (dextrose) immediately prior to entering the environmental chamber. Rectal temperature, skin temperature, heart rate, and thermal sensation were monitored continuously and recorded every 10 min. In Study 1, the peak concentration of acetaminophen (14 ± 4 μg/ml) in plasma arose between 80 and 100 min following oral ingestion. In Study 2, acetaminophen ingestion reduced the core temperature of all participants, whereas there was no significant change in core temperature over time in the placebo trial. Mean core temperature was significantly lower in the acetaminophen trial compared with that of a placebo (p < 0.05). The peak reduction in core temperature in the acetaminophen trial was reached at 120 min in six of the thirteen participants, and ranged from 0.1 to 0.39°C (average peak reduction from baseline = 0.19 ± 0.09°C). There was no significant difference in skin

  19. Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Associated with Acetaminophen Use during Viral Infections

    PubMed Central

    Ban, Ga-Young; Ahn, Seun-Joo; Yoo, Hye-Soo; Park, Hae-Sim

    2016-01-01

    An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN. PMID:27574505

  20. Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans.

    PubMed

    Foster, Josh; Mauger, Alexis; Thomasson, Katie; White, Stephanie; Taylor, Lee

    2016-01-01

    In non-febrile mouse models, high dose acetaminophen administration causes profound hypothermia. However, this potentially hazardous side-effect has not been confirmed in non-febrile humans. Thus, we sought to ascertain whether an acute therapeutic dose (20 mg⋅kg lean body mass) of acetaminophen would reduce non-febrile human core temperature in a sub-neutral environment. Ten apparently healthy (normal core temperature, no musculoskeletal injury, no evidence of acute illness) Caucasian males participated in a preliminary study (Study 1) to determine plasma acetaminophen concentration following oral ingestion of 20 mg⋅kg lean body mass acetaminophen. Plasma samples (every 20 min up to 2-hours post ingestion) were analyzed via enzyme linked immunosorbent assay. Thirteen (eight recruited from Study 1) apparently healthy Caucasian males participated in Study 2, and were passively exposed to 20°C, 40% r.h. for 120 min on two occasions in a randomized, repeated measures, crossover design. In a double blind manner, participants ingested acetaminophen (20 mg⋅kg lean body mass) or a placebo (dextrose) immediately prior to entering the environmental chamber. Rectal temperature, skin temperature, heart rate, and thermal sensation were monitored continuously and recorded every 10 min. In Study 1, the peak concentration of acetaminophen (14 ± 4 μg/ml) in plasma arose between 80 and 100 min following oral ingestion. In Study 2, acetaminophen ingestion reduced the core temperature of all participants, whereas there was no significant change in core temperature over time in the placebo trial. Mean core temperature was significantly lower in the acetaminophen trial compared with that of a placebo (p < 0.05). The peak reduction in core temperature in the acetaminophen trial was reached at 120 min in six of the thirteen participants, and ranged from 0.1 to 0.39°C (average peak reduction from baseline = 0.19 ± 0.09°C). There was no significant difference in skin

  1. [Caffeine--common ingredient in a diet and its influence on human health].

    PubMed

    Wierzejska, Regina

    2012-01-01

    Caffeine is widely consumed by people of all ages. In the last period a market of caffeine-containing products, particularly energy drinks and food supplements increased. Caffeine for years is under discussion, whether has positive whether adverse impact on health. Children are a group of special anxieties. Caffeine is a stimulant of central nervous system and therefore is probably the most commonly used psychoactive substance in the world. The physiological effect of caffeine and the lack of nutrition value causes a great interest its impact on health, especially with reference to the risk of cardiovascular diseases. Results of scientific research are not clear. The influence of caffeine on the human body is conditioned with the individual metabolism of caffeine which also depends on many endogenic and environmental factors. According to the current knowledge moderate caffeine intake by healthy adults at a dose level of 400 mg a day is not associated with adverse effects, but it also depends on other health determinants of a lifestyle. Excessive caffeine consumption can cause negative health consequences such as psychomotor agitation, insomnia, headache, gastrointestinal complaints. Adverse effect of caffeine intoxication is classified in World Health Organization's International Classification of Diseases (ICD-10). Metabolism of caffeine by pregnant woman is slowed down. Caffeine and its metabolites pass freely across the placenta into a fetus. For this reason pregnant women should limit caffeine intake. Children and adolescents should also limit daily caffeine consumption. It results from the influence of caffeine on the central nervous system in the period of rapid growth and the final stage of brain development, calcium balance and sleep duration. Average daily caffeine consumption in European countries ranging from 280-490 mg. The highest caffeine intake is in Scandinavian countries what results from the great consumption of the coffee. As far as caffeine

  2. [Caffeine--common ingredient in a diet and its influence on human health].

    PubMed

    Wierzejska, Regina

    2012-01-01

    Caffeine is widely consumed by people of all ages. In the last period a market of caffeine-containing products, particularly energy drinks and food supplements increased. Caffeine for years is under discussion, whether has positive whether adverse impact on health. Children are a group of special anxieties. Caffeine is a stimulant of central nervous system and therefore is probably the most commonly used psychoactive substance in the world. The physiological effect of caffeine and the lack of nutrition value causes a great interest its impact on health, especially with reference to the risk of cardiovascular diseases. Results of scientific research are not clear. The influence of caffeine on the human body is conditioned with the individual metabolism of caffeine which also depends on many endogenic and environmental factors. According to the current knowledge moderate caffeine intake by healthy adults at a dose level of 400 mg a day is not associated with adverse effects, but it also depends on other health determinants of a lifestyle. Excessive caffeine consumption can cause negative health consequences such as psychomotor agitation, insomnia, headache, gastrointestinal complaints. Adverse effect of caffeine intoxication is classified in World Health Organization's International Classification of Diseases (ICD-10). Metabolism of caffeine by pregnant woman is slowed down. Caffeine and its metabolites pass freely across the placenta into a fetus. For this reason pregnant women should limit caffeine intake. Children and adolescents should also limit daily caffeine consumption. It results from the influence of caffeine on the central nervous system in the period of rapid growth and the final stage of brain development, calcium balance and sleep duration. Average daily caffeine consumption in European countries ranging from 280-490 mg. The highest caffeine intake is in Scandinavian countries what results from the great consumption of the coffee. As far as caffeine

  3. A 3-D hydrologic transport model of a water recharge system using carbamazepine and chloride as tracers

    NASA Astrophysics Data System (ADS)

    Rona, Michael; Gasser, Guy; Negev, Ido; Pankratov, Irena; Elhanany, Sara; Lev, Ovadia; Gvirtzman, Haim

    2014-05-01

    Wastewater recharge facilities are often used as a final water treatment before the discharge to the sea or before water reclamation. These facilities are often located in active aquifers that supply drinking water. Thus, leakage from the water recharge facility and gradual expansion of the underground wastewater plume are of considerable health concern. Hydrological modeling of water recharge systems are widely used as operational and predictive tools. These models rely on distributed water head monitoring and at least one chemical or physical tracer to model solutes' transport. Refractory micropollutants have proven useful in qualitative identification of pollution leakages and for quantification of pollution to a specific site near water recharge facilities. However, their usefulness as tracers for hydrological modeling is still questionable. In this article, we describe a long term, 3-D hydraulic model of a large-scale wastewater effluents recharge system in which a combination of chloride and a refractory micropollutant, carbamazepine is used to trace the solute transport. The combination of the two tracers provides the model with the benefits of the high specificity of the carbamazepine and the extensive historic data base that is available for chloride. The model predicts westward expansion of the pollution plume, whereas a standing front is formed at the east. These trends can be confirmed by the time trace of the carbamazepine concentrations at specific locations. We show that the combination of two tracers accounts better (at least at some locations) for the evolution of the pollution plume than a model based on chloride or carbamazepine alone.

  4. Fate of carbamazepine, its metabolites, and lamotrigine in soils irrigated with reclaimed wastewater: Sorption, leaching and plant uptake.

    PubMed

    Paz, Anat; Tadmor, Galit; Malchi, Tomer; Blotevogel, Jens; Borch, Thomas; Polubesova, Tamara; Chefetz, Benny

    2016-10-01

    Irrigation with reclaimed wastewater may result in the ubiquitous presence of pharmaceutical compounds (PCs) and their metabolites in the agroecosystem. In this study, we focused on two highly persistent anticonvulsant drugs, lamotrigine and carbamazepine and two of its metabolites (EP-CBZ and DiOH-CBZ), aiming to elucidate their behavior in agricultural ecosystem using batch and lysimeter experiments. Sorption of the studied compounds by soils was found to be governed mainly by the soil organic matter level. Sorption affinity of compounds to soils followed the order lamotrigine > carbamazepine > EP-CBZ > DiOH-CBZ. Sorption was reversible, and no competition between sorbates in bi-solute systems was observed. The results of the lysimeter studies were in accordance with batch experiment findings, demonstrating accumulation of lamotrigine and carbamazepine in top soil layers enriched with organic matter. Detection of carbamazepine and one of its metabolites in rain-fed wheat previously irrigated with reclaimed wastewater, indicates reversibility of their sorption, resulting in their potential leaching and their availability for plant uptake. This study demonstrates the long-term implication of introduction of PCs to the agroecosystem. PMID:27351902

  5. Human Exposure to Wastewater-Derived Pharmaceuticals in Fresh Produce: A Randomized Controlled Trial Focusing on Carbamazepine.

    PubMed

    Paltiel, Ora; Fedorova, Ganna; Tadmor, Galit; Kleinstern, Geffen; Maor, Yehoshua; Chefetz, Benny

    2016-04-19

    Fresh water scarcity has led to increased use of reclaimed wastewater as an alternative and reliable source for crop irrigation. Beyond microbiological safety, concerns have been raised regarding contamination of reclaimed wastewater by xenobiotics including pharmaceuticals. This study focuses on carbamazepine, an anticonvulsant drug which is ubiquitously detected in reclaimed wastewater, highly persistent in soil, and taken up by crops. In a randomized controlled trial we demonstrate that healthy individuals consuming reclaimed wastewater-irrigated produce excreted carbamazepine and its metabolites in their urine, while subjects consuming fresh water-irrigated produce excreted undetectable or significantly lower levels of carbamazepine. We also report that the carbamazepine metabolite pattern at this low exposure level differed from that observed at therapeutic doses. This "proof of concept" study demonstrates that human exposure to xenobiotics occurs through ingestion of reclaimed wastewater-irrigated produce, providing real world data which could guide risk assessments and policy designed to ensure the safe use of wastewater for crop irrigation. PMID:27021726

  6. Fate of carbamazepine, its metabolites, and lamotrigine in soils irrigated with reclaimed wastewater: Sorption, leaching and plant uptake.

    PubMed

    Paz, Anat; Tadmor, Galit; Malchi, Tomer; Blotevogel, Jens; Borch, Thomas; Polubesova, Tamara; Chefetz, Benny

    2016-10-01

    Irrigation with reclaimed wastewater may result in the ubiquitous presence of pharmaceutical compounds (PCs) and their metabolites in the agroecosystem. In this study, we focused on two highly persistent anticonvulsant drugs, lamotrigine and carbamazepine and two of its metabolites (EP-CBZ and DiOH-CBZ), aiming to elucidate their behavior in agricultural ecosystem using batch and lysimeter experiments. Sorption of the studied compounds by soils was found to be governed mainly by the soil organic matter level. Sorption affinity of compounds to soils followed the order lamotrigine > carbamazepine > EP-CBZ > DiOH-CBZ. Sorption was reversible, and no competition between sorbates in bi-solute systems was observed. The results of the lysimeter studies were in accordance with batch experiment findings, demonstrating accumulation of lamotrigine and carbamazepine in top soil layers enriched with organic matter. Detection of carbamazepine and one of its metabolites in rain-fed wheat previously irrigated with reclaimed wastewater, indicates reversibility of their sorption, resulting in their potential leaching and their availability for plant uptake. This study demonstrates the long-term implication of introduction of PCs to the agroecosystem.

  7. Environmental fate of naproxen, carbamazepine and triclosan in wastewater, surface water and wastewater irrigated soil - Results of laboratory scale experiments.

    PubMed

    Durán-Álvarez, J C; Prado, B; González, D; Sánchez, Y; Jiménez-Cisneros, B

    2015-12-15

    Lab-scale photolysis, biodegradation and transport experiments were carried out for naproxen, carbamazepine and triclosan in soil, wastewater and surface water from a region where untreated wastewater is used for agricultural irrigation. Results showed that both photolysis and biodegradation occurred for the three emerging pollutants in the tested matrices as follows: triclosan>naproxen>carbamazepine. The highest photolysis rate for the three pollutants was obtained in experiments using surface water, while biodegradation rates were higher in wastewater and soil than in surface water. Carbamazepine showed to be recalcitrant to biodegradation both in soil and water; although photolysis occurred at a higher level than biodegradation, this compound was poorly degraded by natural processes. Transport experiments showed that naproxen was the most mobile compound through the first 30cm of the soil profile; conversely, the mobility of carbamazepine and triclosan through the soil was delayed. Biodegradation of target pollutants occurred within soil columns during transport experiments. Triclosan was not detected either in leachates or the soil in columns, suggesting its complete biodegradation. Data of these experiments can be used to develop more reliable fate-on-the-field and environmental risk assessment studies.

  8. Serotonin deficiency exacerbates acetaminophen-induced liver toxicity in mice.

    PubMed

    Zhang, Jingyao; Song, Sidong; Pang, Qing; Zhang, Ruiyao; Zhou, Lei; Liu, Sushun; Meng, Fandi; Wu, Qifei; Liu, Chang

    2015-01-29

    Acetaminophen (APAP) overdose is a major cause of acute liver failure. Peripheral 5-hydroxytryptamine (serotonin, 5-HT) is a cytoprotective neurotransmitter which is also involved in the hepatic physiological and pathological process. This study seeks to investigate the mechanisms involved in APAP-induced hepatotoxicity, as well as the role of 5-HT in the liver's response to APAP toxicity. We induced APAP hepatotoxicity in mice either sufficient of serotonin (wild-type mice and TPH1-/- plus 5- Hydroxytryptophan (5-HTP)) or lacking peripheral serotonin (Tph1-/- and wild-type mice plus p-chlorophenylalanine (PCPA)). Mice with sufficient 5-HT exposed to acetaminophen have a significantly lower mortality rate and a better outcome compared with mice deficient of 5-HT. This difference is at least partially attributable to a decreased level of inflammation, oxidative stress and endoplasmic reticulum (ER) stress, Glutathione (GSH) depletion, peroxynitrite formation, hepatocyte apoptosis, elevated hepatocyte proliferation, activation of 5-HT2B receptor, less activated c-Jun NH₂-terminal kinase (JNK) and hypoxia-inducible factor (HIF)-1α in the mice sufficient of 5-HT versus mice deficient of 5-HT. We thus propose a physiological function of serotonin that serotonin could ameliorate APAP-induced liver injury mainly through inhibiting hepatocyte apoptosis ER stress and promoting liver regeneration.

  9. Consumption and foraging behaviors for common stimulants (nicotine, caffeine).

    PubMed

    Phillips, James G; Currie, Jonathan; Ogeil, Rowan P

    2016-01-01

    Models are needed to understand the emerging capability to track consumers' movements. Therefore, we examined the use of legal and readily available stimulants that vary in their addictive potential (nicotine, caffeine). One hundred sixty-six participants answered the Kessler Psychological Distress Scale (K10), the Severity of Dependence Scale for nicotine and caffeine, and reported the number of times and locations stimulants were purchased and used. On average, nicotine dependent individuals made their purchases from 2 locations, while caffeine dependent individuals consumed caffeine at 2 locations, but some people exhibited a greater range and intensity of use. Stimulant foraging behavior could be described by power laws, and is exacerbated by dependency. The finding has implications for attempts to control substance use.

  10. Assessing Caffeine as an Emerging Environmental Concern Using Conventional Approaches

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Organic wastewater contaminants, including pharmaceuticals, caffeine, and nicotine, have received increased scrutiny because of their detection in water bodies receiving wastewater discharge. Despite recent measurement in US streams, caffeine’s effect on freshwater organisms is not well documented....

  11. Protonation of caffeine: A theoretical and experimental study

    NASA Astrophysics Data System (ADS)

    Bahrami, Hamed; Tabrizchi, Mahmoud; Farrokhpour, Hossein

    2013-03-01

    Protonation of caffeine was examined by ion mobility spectrometry equipped with two ionization sources, corona discharge (CD) and UV photoionization. Three peaks were observed in ion mobility spectrum by simultaneously running the two ionization sources. Experimental and theoretical evidence was collected to link the observed peaks to caffeine related ionic species. One peak was attributed to the M+ ion while the other two were assigned to different protonated isomers of caffeine. In the case of CD ionization source, it was observed that different sites of caffeine compete for protonation and their relative intensities, depends on the sample concentration as well as the nature of the reactant ions. The new concept of "internal proton affinity" (IPA) was defined to express the tendency of holding the added proton for each atom in a molecule.

  12. Removal of caffeine from industrial wastewater using Trichosporon asahii.

    PubMed

    Lakshmi, V; Das, Nilanjana

    2013-07-01

    Caffeine (1,3,7-trimethylxanthine), a natural alkaloid present mainly in tea and coffee products has been suggested as an environmental pollutant. Decaffeination is an important process for the removal of caffeine from coffee industrial wastes. In the present study, caffeine removal (through degradation) by yeast isolate, Trichosporon asahii immobilized on various conventional matrices (sodium alginate, carboxymethyl cellulose, chitosan, agar and agarose) was investigated using the method of entrapment. The biofilm forming ability of T. asahii was monitored by atomic force microscopy and scanning electron microscopy. Exopolysaccharide produced by T asahii biofilm was characterized by FT-IR spectroscopy and HPLC analysis. Caffeine removal from coffee processing industrial effluent was found to be 75 and 80 % by alginate immobilized yeast and yeast biofilm formed on gravels over a period of 48 hr in batch mode. Effectiveness of the process was also tested involving the continuous--flow column studies.

  13. Consumption and foraging behaviors for common stimulants (nicotine, caffeine).

    PubMed

    Phillips, James G; Currie, Jonathan; Ogeil, Rowan P

    2016-01-01

    Models are needed to understand the emerging capability to track consumers' movements. Therefore, we examined the use of legal and readily available stimulants that vary in their addictive potential (nicotine, caffeine). One hundred sixty-six participants answered the Kessler Psychological Distress Scale (K10), the Severity of Dependence Scale for nicotine and caffeine, and reported the number of times and locations stimulants were purchased and used. On average, nicotine dependent individuals made their purchases from 2 locations, while caffeine dependent individuals consumed caffeine at 2 locations, but some people exhibited a greater range and intensity of use. Stimulant foraging behavior could be described by power laws, and is exacerbated by dependency. The finding has implications for attempts to control substance use. PMID:26555360

  14. Removal of caffeine from industrial wastewater using Trichosporon asahii.

    PubMed

    Lakshmi, V; Das, Nilanjana

    2013-07-01

    Caffeine (1,3,7-trimethylxanthine), a natural alkaloid present mainly in tea and coffee products has been suggested as an environmental pollutant. Decaffeination is an important process for the removal of caffeine from coffee industrial wastes. In the present study, caffeine removal (through degradation) by yeast isolate, Trichosporon asahii immobilized on various conventional matrices (sodium alginate, carboxymethyl cellulose, chitosan, agar and agarose) was investigated using the method of entrapment. The biofilm forming ability of T. asahii was monitored by atomic force microscopy and scanning electron microscopy. Exopolysaccharide produced by T asahii biofilm was characterized by FT-IR spectroscopy and HPLC analysis. Caffeine removal from coffee processing industrial effluent was found to be 75 and 80 % by alginate immobilized yeast and yeast biofilm formed on gravels over a period of 48 hr in batch mode. Effectiveness of the process was also tested involving the continuous--flow column studies. PMID:24640246

  15. Caffeine and cardiovascular diseases: critical review of current research.

    PubMed

    Zulli, Anthony; Smith, Renee M; Kubatka, Peter; Novak, Jan; Uehara, Yoshio; Loftus, Hayley; Qaradakhi, Tawar; Pohanka, Miroslav; Kobyliak, Nazarii; Zagatina, Angela; Klimas, Jan; Hayes, Alan; La Rocca, Giampiero; Soucek, Miroslav; Kruzliak, Peter

    2016-06-01

    Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains "Which dose is safe?", as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistical power. This review will focus on comprehensive and critical review of the current literature and provide an avenue for further study. PMID:26932503

  16. ATP level and caffeine efficiency on cytokinesis inhibition in plants.

    PubMed

    López-Sáez, J F; Mingo, R; González-Fernández, A

    1982-06-01

    Plant cytokinesis appears to be a topographically organized process of exocytosis. Golgi vesicles which contain cell wall precursors are translocated during telophase, by interzonal microtubules, to the equatorial region of the mitotic apparatus where they fuse with each other giving rise to the new cell wall. Caffeine inhibits cytokinesis by hindering Golgi vesicle coalescence. The present results demonstrate that treatments which increase the cellular ATP level (adenosine, cycloheximide and anisomycin) counteract caffein-induced cytokinesis inhibition in meristem cells of onion root tips (Allium cepa L.), while treatments which decrease ATP level potentiate this caffeine effect (dinitrophenol, fluoroacetate, low oxygen tensions, etc.). We postulate that caffeine, in competition with the cellular ATP level, blocks cell plate formation by inhibiting a certain ATPase activity required for membrane fusion of Golgi vesicles.

  17. Carbamazepine as indicator for potential short-term contamination of karst springs

    NASA Astrophysics Data System (ADS)

    Doummar, J.; Baierl, M.; Noedler, K.; Licha, T.; Sauter, M.; Geyer, T.

    2012-04-01

    Karst aquifers are complex systems which vulnerability is very difficult to assess mainly because of the duality of recharge processes and duality of flow. Recharge to a karst aquifer occurs as diffuse or concentrated (sinkholes and dolines). Moreover, karst aquifers are formed by an unsaturated zone comprising soil, epikarst and unsaturated rock matrix, and a saturated zone formed of highly permeable conduits and low permeability matrix storage. In the case of contamination of groundwater by wastewater effluent polluted water can be either transported rapidly and have short term major risk on spring water quality or infiltrate into fractured rock matrix and therefore have a long term effect on the water quality. In order to identify the risk of wastewater infiltrating into an aquifer, researches have focused to date on the identification of indicative wastewater markers. Carbamazepine (CBZ) was frequently detected in surface water as well as in effluents of sewage treatment plants, as less than 10% of carbamazepine are usually eliminated during sewage treatment. Moreover, CBZ is not attenuated in aquifers (Heberer, 2002), is unlikely degradable or adsorbed, and can be detected in groundwater (Clara et al., 2004). Therefore, CBZ is considered to be fairly persistent in groundwater (Tixier et al., 2003), and is consequently regarded as an effective wastewater marker. In this case study, the Jeita spring in Lebanon (spring discharge: 1-20 m3/s) was monitored and sampled for major ions and micro-pollutants following a combined precipitation/snowmelt events. A total of 28 samples (major ions and micro-pollutants) were taken over a total sampling time of 16 days at interval varying between 4 and 24 hours. Based on the variation with time of discharge and electrical conductivity (monitored every 20 minutes) as well as the concentrations of the major ions, a conceptual model showing the response of the aquifer compartments to the precipitation event was generated. A

  18. Alcohol, nicotine, caffeine, and mental disorders

    PubMed Central

    Crocq, Marc-Antoine

    2003-01-01

    Alcohol, nicotine, and caffeine are the most widely consumed psychotropic drugs worldwide. They are largely consumed by normal individuals, but their use is even more frequent in psychiatric patients, Thus, patients with schizophrenia tend to abuse all three substances. The interrelationships between depression and alcohol are complex. These drugs can all create dependence, as understood in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Alcohol abuse is clearly deleterious to the brain, provoking acute and chronic mental disorders, ranging from intoxication with impairment of cognition, to delirium tremens, halluosis, and dementia. In contrast, the main health consequences of nicotine, notably cancer and cardiovascular disases, lie outside the realm of psychiatry However, the mes of nicotine dependence and motivation to smoke or quit are of concern to psychiatrists. PMID:22033899

  19. The effect of caffeine on cerebral asymmetry in rats.

    PubMed

    Voiculescu, M; Segarceanu, A; Negutu, M; Ghita, I; Fulga, I; Coman, O A

    2015-01-01

    EEG recordings reflect the gross electrical activity emanating from synaptic currents of individual neurons across large cortical areas. During periods of cortical activation, waking, and higher EEG frequencies, neurons display increased excitability and exhibit more asynchronous discharge. The activity of a number of subcortical neurotransmitter systems from several brain regions outside the thalamus can directly affect cortical activity patterns. These neurotransmitter systems are generally targets of pharmacological intervention or participate in neurological disease states. The EEG trace comprises 4 primary rhythms: alfa (α), beta (β), theta (θ) and delta (δ), which differ in frequency and amplitude. Caffeine effect on brain asymmetry will be studied in this work. The study was realized by means of Fourier spectral frequency analysis (Fast Fourier Transformation) of the EEG signal on anesthetized rats. All 3 doses of caffeine increased the global wave power of brain activity compared to the control group. All 3 doses of caffeine reduced the number of peaks for the 0.5-4 Hz frequency band, with the intermediate dose of caffeine having such an effect in the 4-7 Hz frequency band and the high dose of caffeine for the 23-33 Hz frequency band. The group that received high doses of caffeine showed an increase of the percentage of delta waves, with a concurrent decrease of the percentage of alpha1, alpha2, beta and theta 2 compared to the control group. Low-dose caffeine produced positive values of left-right difference in brain electrical activity (left predominance) for the 0.5-5 Hz and 7.8-10.3 Hz frequency intervals. The group that received high-dose caffeine exhibited a left hemisphere dominance for the 0.5-1.5 Hz; 13.9-14.1 Hz and 19-20 Hz frequency ranges while right dominance was present in the 1.7-13.9 Hz, 15-19 Hz and 21-25 Hz frequency ranges. In conclusion, all doses of caffeine modified the global power of the brain as well as the number of peaks on

  20. The effect of caffeine on cerebral asymmetry in rats

    PubMed Central

    Voiculescu, M; Segarceanu, A; Negutu, M; Ghita, I; Fulga, I; Coman, OA

    2015-01-01

    EEG recordings reflect the gross electrical activity emanating from synaptic currents of individual neurons across large cortical areas. During periods of cortical activation, waking, and higher EEG frequencies, neurons display increased excitability and exhibit more asynchronous discharge. The activity of a number of subcortical neurotransmitter systems from several brain regions outside the thalamus can directly affect cortical activity patterns. These neurotransmitter systems are generally targets of pharmacological intervention or participate in neurological disease states. The EEG trace comprises 4 primary rhythms: alfa (α), beta (β), theta (θ) and delta (δ), which differ in frequency and amplitude. Caffeine effect on brain asymmetry will be studied in this work. The study was realized by means of Fourier spectral frequency analysis (Fast Fourier Transformation) of the EEG signal on anesthetized rats. All 3 doses of caffeine increased the global wave power of brain activity compared to the control group. All 3 doses of caffeine reduced the number of peaks for the 0.5-4 Hz frequency band, with the intermediate dose of caffeine having such an effect in the 4-7 Hz frequency band and the high dose of caffeine for the 23-33 Hz frequency band. The group that received high doses of caffeine showed an increase of the percentage of delta waves, with a concurrent decrease of the percentage of alpha1, alpha2, beta and theta 2 compared to the control group. Low-dose caffeine produced positive values of left-right difference in brain electrical activity (left predominance) for the 0.5-5 Hz and 7.8-10.3 Hz frequency intervals. The group that received high-dose caffeine exhibited a left hemisphere dominance for the 0.5-1.5 Hz; 13.9-14.1 Hz and 19-20 Hz frequency ranges while right dominance was present in the 1.7-13.9 Hz, 15-19 Hz and 21-25 Hz frequency ranges. In conclusion, all doses of caffeine modified the global power of the brain as well as the number of peaks on

  1. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    SciTech Connect

    Flickinger, John C.; Kim, Hyun; Kano, Hideyuki; Greenberger, Joel S.; Arai, Yoshio; Niranjan, Ajay; Lunsford, L. Dade; Kondziolka, Douglas; Flickinger, John C.

    2012-07-15

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up {>=}6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age

  2. Formulation and Characterization of Acetaminophen Nanoparticles in Orally Disintegrating Films

    NASA Astrophysics Data System (ADS)

    AI-Nemrawi, Nusaiba K.

    The purpose of this study is to prepare acetaminophen loaded nanoparticles to be cast directly, while still in the emulsion form, into Orally Disintegrating Films (ODF). By casting the nanoparticles in the films, we expected to keep the particles in a stable form where the nanoparticles would be away from each other to prevent their aggregation. Once the films are applied on the buccal mucosa, they are supposed to dissolve within seconds, releasing the nanoparticles. Then the nanoparticles could be directly absorbed through the mucosa to the blood stream and deliver acetaminophen there. The oral cavity mucosa is one of the most attractive sites for systemic drug delivery due to its high permeability and blood supply. Furthermore, it is robust and shows short recovery times after stress or damage, and the drug bypasses first pass effect and avoids presystemic elimination in the GI tract. Nanoencapsulation increases drug efficacy, specificity, tolerability and therapeutic index. These Nanocapsules have several advantages in the protection of premature degradation and interaction with the biological environment, enhancement of absorption into a selected tissue, bioavailability, retention time and improvement of intracellular penetration. The most important characteristics of nanoparticles are their size, encapsulation efficiency (EE), zeta potential (surface charge), and the drug release profiles. Unfortunately, nanoparticles tend to precipitate or aggregate into larger particles within a short time after preparation or during storage. Some solutions for this problem were mentioned in literature including lyophilization and spray drying. These methods are usually expensive and give partial solutions that might have secondary problems; such as low re-dispersion efficacy of the lyophilized NPs. Furthermore, most of the formulations of NPs are invasive or topical. Few formulas are available to be given orally. Fast disintegrating films (ODFs) are rapidly gaining interest

  3. Electrochemical properties of the acetaminophen on the screen printed carbon electrode towards the high performance practical sensor applications.

    PubMed

    Karikalan, Natarajan; Karthik, Raj; Chen, Shen-Ming; Velmurugan, Murugan; Karuppiah, Chelladurai

    2016-12-01

    Acetaminophen is a non-steroidal anti-inflammatory drug used as an antipyretic agent for the alternative to aspirin. Conversely, the overdoses of acetaminophen can cause hepatic toxicity and kidney damage. Hence, the determination of acetaminophen receives much more attention in biological samples and also in pharmaceutical formulations. Here, we report a rapid and sensitive detection of the acetaminophen based on the bare (unmodified) screen printed carbon electrode (BSPCE) and its electrochemistry was studied in various pHs. From the observed results, the mechanism of the electro-oxidation of acetaminophen was derived for various pHs. The acetaminophen is not stable in strong acidic and strong alkaline media, which is hydrolyzed and hydroxylated. However, it is stable in intermediate pHs due to the dimerization of acetaminophen. The kinetics of the acetaminophen oxidation was briefly studied and documented in the schemes. In addition, the surface morphology and disorders of BSPCE was probed by scanning electron microscope (SEM) and Raman spectroscopy. Moreover, the BSPCE determined the acetaminophen with the linear concentration ranging from 0.05 to 190μM and the lower detection limit of 0.013μM. Besides that it reveals the good recoveries towards the pharmaceutical samples and shows the excellent selectivity, sensitivity and stability. To the best of our knowledge, this is the better performance compare to the previously reported unmodified acetaminophen sensors. PMID:27552419

  4. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors.

  5. Evaluation of the central effects of alcohol and caffeine interaction.

    PubMed Central

    Azcona, O; Barbanoj, M J; Torrent, J; Jané, F

    1995-01-01

    1. The dynamic and kinetic interactions of alcohol and caffeine were studied in a double-blind, placebo controlled, cross-over trial. Treatments were administered to eight healthy subjects in four experimental sessions, leaving a 1 week wash-out period between each, as follows: 1) placebo, 2) alcohol (0.8 g kg-1), 3) caffeine (400 mg) and 4) alcohol (0.8 g kg-1) + caffeine (400 mg). 2. Evaluations were performed by means of: 1) objective measures: a) psychomotor performance (critical flicker fusion frequency, simple reaction time and tapping test), b) long latency visual evoked potentials ('pattern reversal'); 2) subjective self-rated scales (visual analogue scales and profile of mood states); 3) caffeine and alcohol plasma concentration determinations. 3. The battery of pharmacodynamic tests was conducted at baseline and at +0.5 h, +1.5 h, +2.5 h, +4 h and +6 h. An analysis of variance was applied to the results, accepting a P < 0.05 as significant. The plasma-time curves for caffeine and alcohol were analysed by means of model-independent methods. 4. Results obtained with caffeine in the objective measures demonstrated a decrease in simple reaction time and an increase in the amplitude of the evoked potentials; the subjects' self-ratings showed a tendency to be more active. Alcohol increased simple reaction time and decreased amplitude of the evoked potentials, although the subjects rated themselves as being active. The combination of alcohol + caffeine showed no significant difference from placebo in the objective tests; nevertheless, the subjective feeling of drunkenness remained. The area under the curve (AUC) for caffeine was significantly higher when administered with alcohol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8554942

  6. Caffeinated forage tricks honeybees into increasing foraging and recruitment behaviors.

    PubMed

    Couvillon, Margaret J; Al Toufailia, Hasan; Butterfield, Thomas M; Schrell, Felix; Ratnieks, Francis L W; Schürch, Roger

    2015-11-01

    In pollination, plants provide food reward to pollinators who in turn enhance plant reproduction by transferring pollen, making the relationship largely cooperative; however, because the interests of plants and pollinators do not always align, there exists the potential for conflict, where it may benefit both to cheat the other [1, 2]. Plants may even resort to chemistry: caffeine, a naturally occurring, bitter-tasting, pharmacologically active secondary compound whose main purpose is to detract herbivores, is also found in lower concentrations in the nectar of some plants, even though nectar, unlike leaves, is made to be consumed by pollinators. [corrected]. A recent laboratory study showed that caffeine may lead to efficient and effective foraging by aiding honeybee memory of a learned olfactory association [4], suggesting that caffeine may enhance bee reward perception. However, without field data, the wider ecological significance of caffeinated nectar remains difficult to interpret. Here we demonstrate in the field that caffeine generates significant individual- and colony-level effects in free-flying worker honeybees. Compared to a control, a sucrose solution with field-realistic doses of caffeine caused honeybees to significantly increase their foraging frequency, waggle dancing probability and frequency, and persistency and specificity to the forage location, resulting in a quadrupling of colony-level recruitment. An agent-based model also demonstrates how caffeine-enhanced foraging may reduce honey storage. Overall, caffeine causes bees to overestimate forage quality, tempting the colony into sub-optimal foraging strategies, which makes the relationship between pollinator and plant less mutualistic and more exploitative. VIDEO ABSTRACT. PMID:26480843

  7. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  8. Coffee, Caffeine, and Risk of Depression Among Women

    PubMed Central

    Lucas, Michel; Mirzaei, Fariba; Pan, An; Okereke, Olivia I.; Willett, Walter C; O’Reilly, Éilis J; Koenen, Karestan; Ascherio, Alberto

    2012-01-01

    Background Caffeine is the world’s most widely used central nervous system stimulant, with about 80% consumed in form of coffee. However, studies that analyzed prospectively the relation of coffee or caffeine consumption and depression risk are scarce. Methods A total of 50,739 U.S. women (mean age=63 years) free from depressive symptoms at baseline (1996) were prospectively followed until 2006. Caffeine and coffee consumption, and other caffeinated and decaffeinated beverages, were obtained from validated questionnaires completed between 1980 through 2002 and computed as cumulative average of consumption with a 2-year latency applied. Clinical depression was defined as reporting both physician-diagnosed depression and antidepressant use. Relative risks of clinical depression were estimate using Cox proportional hazards regression models. Results During 10 years of follow-up (1996–2006), 2,607 incident cases of depression were identified. Compared to women consuming caffeinated coffee less frequently (≤1 cup/wk), multivariate relative risk of depression was 0.85 (95% confidence interval [CI], 0.75 to 0.95) for those consuming 2–3 cups/d and 0.80 (95%CI, 0.64 to 0.99; P trend <0.001) for those consuming ≥4 cups/d. Multivariate relative risk for depression was 0.80 (95%CI, 0.68 to 0.95; P trend=0.02) for women in the highest (≥550 mg/d) vs. lowest (<100 mg/d) of the 5 caffeine consumption categories. Decaffeinated coffee was not associated with depression risk. Conclusions In this large longitudinal study we found that depression risk decreases with increasing caffeinated coffee consumption. Further investigations are needed to confirm this finding and to determine whether usual caffeinated coffee consumption may contribute to depression prevention. PMID:21949167

  9. Caffeine intensifies taste of certain sweeteners: role of adenosine receptor.

    PubMed

    Schiffman, S S; Diaz, C; Beeker, T G

    1986-03-01

    Caffeine, a potent antagonist of adenosine receptors, potentiates the taste of some but not all sweeteners. It significantly enhances the taste of acesulfam-K, neohesperidin dihydrochalcone, d-tryptophan, thaumatin, stevioside, and sodium saccharin. Adenosine reverses the enhancement. Caffeine has no effect on aspartame, sucrose, fructose, and calcium cyclamate. These results suggest that the inhibitory A1 adenosine receptor plays an important local role in modulating the taste intensity of certain sweeteners and that several transduction mechanisms mediate sweet taste.

  10. Caffeinated forage tricks honeybees into increasing foraging and recruitment behaviors.

    PubMed

    Couvillon, Margaret J; Al Toufailia, Hasan; Butterfield, Thomas M; Schrell, Felix; Ratnieks, Francis L W; Schürch, Roger

    2015-11-01

    In pollination, plants provide food reward to pollinators who in turn enhance plant reproduction by transferring pollen, making the relationship largely cooperative; however, because the interests of plants and pollinators do not always align, there exists the potential for conflict, where it may benefit both to cheat the other [1, 2]. Plants may even resort to chemistry: caffeine, a naturally occurring, bitter-tasting, pharmacologically active secondary compound whose main purpose is to detract herbivores, is also found in lower concentrations in the nectar of some plants, even though nectar, unlike leaves, is made to be consumed by pollinators. [corrected]. A recent laboratory study showed that caffeine may lead to efficient and effective foraging by aiding honeybee memory of a learned olfactory association [4], suggesting that caffeine may enhance bee reward perception. However, without field data, the wider ecological significance of caffeinated nectar remains difficult to interpret. Here we demonstrate in the field that caffeine generates significant individual- and colony-level effects in free-flying worker honeybees. Compared to a control, a sucrose solution with field-realistic doses of caffeine caused honeybees to significantly increase their foraging frequency, waggle dancing probability and frequency, and persistency and specificity to the forage location, resulting in a quadrupling of colony-level recruitment. An agent-based model also demonstrates how caffeine-enhanced foraging may reduce honey storage. Overall, caffeine causes bees to overestimate forage quality, tempting the colony into sub-optimal foraging strategies, which makes the relationship between pollinator and plant less mutualistic and more exploitative. VIDEO ABSTRACT.

  11. The analgesic efficacy of intra-articular acetaminophen in an experimental model of carrageenan-induced arthritis

    PubMed Central

    Arun, Oguzhan; Canbay, Ozgur; Celebi, Nalan; Sahin, Altan; Konan, Ali; Atilla, Pergin; Aypar, Ulku

    2013-01-01

    BACKGROUND: Acetaminophen is one of the most common drugs used for the treatment of pain and fever. OBJECTIVES: To examine the effects of intra-articular (IA) acetaminophen on carrageenan-induced arthritic pain-related behaviour and spinal c-Fos expression in rats. METHODS: The present study was performed using 20 Sprague Dawley rats. Forty microlitres of IA 0.9% NaCl was injected in the control group, and 40 μL of IA carrageenan was injected in the carrageenan group. One hour after carrageenan injection, 400 μg of IA acetaminophen was injected in the IA acetaminophen group, and 400 μg of intraperitoneal (IP) acet-aminophen was injected in the IP acetaminophen group. One day before injection, and 4 h and 8 h after injection, diameters of both knee joints, motility of the rat, paw loading and joint mobility were assessed. After the rats were euthanized, L3 and L4 spinal segments were excised for c-Fos assessment. RESULTS: IA acetaminophen decreased both the severity and distribution of c-Fos expression. IP acetaminophen decreased only the distribution of c-Fos expression. IA acetaminophen decreased knee diameter at 8 h. IA and IP acetaminophen increased rat motility and paw loading scores. Joint mobility scores of IP acetaminophen were similar to saline at 8 h. CONCLUSIONS: Results of the present study indicate an analgesic and/or possible anti-inflammatory effect of IA acetaminophen and provide further evidence on the efficacy of systemic acetaminophen injection in reducing arthritic pain. PMID:24093120

  12. Differential cognitive effects of energy drink ingredients: caffeine, taurine, and glucose.

    PubMed

    Giles, Grace E; Mahoney, Caroline R; Brunyé, Tad T; Gardony, Aaron L; Taylor, Holly A; Kanarek, Robin B

    2012-10-01

    Energy drinks containing caffeine, taurine, and glucose may improve mood and cognitive performance. However, there are no studies assessing the individual and interactive effects of these ingredients. We evaluated the effects of caffeine, taurine, and glucose alone and in combination on cognitive performance and mood in 24-hour caffeine-abstained habitual caffeine consumers. Using a randomized, double-blind, mixed design, 48 habitual caffeine consumers (18 male, 30 female) who were 24-hour caffeine deprived received one of four treatments (200 mg caffeine/0 mg taurine, 0 mg caffeine/2000 mg taurine, 200 mg caffeine/2000 mg taurine, 0 mg caffeine/0 mg taurine), on each of four separate days, separated by a 3-day wash-out period. Between-participants treatment was a glucose drink (50 g glucose, placebo). Salivary cortisol, mood and heart rate were measured. An attention task was administered 30-minutes post-treatment, followed by a working memory and reaction time task 60-minutes post-treatment. Caffeine enhanced executive control and working memory, and reduced simple and choice reaction time. Taurine increased choice reaction time but reduced reaction time in the working memory tasks. Glucose alone slowed choice reaction time. Glucose in combination with caffeine, enhanced object working memory and in combination with taurine, enhanced orienting attention. Limited glucose effects may reflect low task difficulty relative to subjects' cognitive ability. Caffeine reduced feelings of fatigue and increased tension and vigor. Taurine reversed the effects of caffeine on vigor and caffeine-withdrawal symptoms. No effects were found for salivary cortisol or heart rate. Caffeine, not taurine or glucose, is likely responsible for reported changes in cognitive performance following consumption of energy drinks, especially in caffeine-withdrawn habitual caffeine consumers.

  13. Carbamazepine interacts with a slow inactivation state of NaV1.8-like sodium channels.

    PubMed

    Cardenas, Carlos A; Cardenas, Carla G; de Armendi, Alberto J; Scroggs, Reese S

    2006-11-13

    Carbamazepine was tested on high-threshold TTX-resistant Na+ currents (TTX-R-currents), evoked from acutely isolated rat dorsal root ganglion (DRG) cells. Under control conditions, the TTX-R-currents recorded from different DRG cells varied greatly regarding use-dependent inactivation (TTX-R-current UDI), measured as the percent decrease in current amplitude induced by changing the current activation rate from 0.1 Hz to 1.0 Hz. Also, when TTX-R-currents were evoked at 0.1 Hz from a holding potential (hp) of -60 mV, a larger fraction of TTX-R-channels resided tonically in a slow inactivation state in DRG cells with more TTX-R-current UDI versus those with less TTX-R-current UDI. The block of TTX-R-currents evoked from hp -60 mV by 100-microM carbamazepine and the EC50 for carbamazepine block was positively correlated with TTX-R-current UDI. The slope factors estimated for the concentration-response curves averaged 0.68, suggesting the presence of low and high affinity sites. Fitting the data with a two-site binding isotherm gave estimates of 30 microM and 760 microM for the EC50s of the high and low affinity sites, respectively. The fraction of the total fit attributed to the high affinity site was positively correlated with TTX-R-current UDI. Carbamazepine increased the fast and slow time constants for recovery from inactivation and the fraction of the fit attributed to the slow time constant. These data suggest that carbamazepine interacts with a slow inactivation state of TTX-R-channels. This particular mechanism might be exploited in future research aimed at developing pain medications that selectively block Na(V)1.8 channels or Na+ channels in general. PMID:16978779

  14. Caffeine and bone loss in healthy postmenopausal women.

    PubMed

    Harris, S S; Dawson-Hughes, B

    1994-10-01

    The effects of caffeine consumption on rates of change in bone mineral density (BMD) were examined in 205 healthy, nonsmoking, postmenopausal women. BMD of the spine and total body were measured by dual-energy x-ray absorptiometry, and dietary intakes by food-frequency questionnaire. Among women with calcium intakes above the median (744 mg/d), 1-y rates of bone change--adjusted for years since menopause, body mass index, physical activity, and baseline BMD--did not differ by caffeine intake. However, among women consuming less calcium, those with the highest caffeine intakes (> 450 mg/d) had significantly more bone loss (ANCOVA, P < 0.05) than did women consuming less caffeine (0-171 and 182-419 mg/d). Percent change in BMD by lowest to highest tertile of caffeine consumption was 0.26 +/- 2.74, 0.70 +/- 2.70, and -1.36 +/- 2.70 at the spine and -0.19 +/- 1.24, 0.23 +/- 1.23, and -0.68 +/- 1.25 at the total body. Daily consumption of caffeine in amounts equal to or greater than that obtained from about two to three servings of brewed coffee may accelerate bone loss from the spine and total body in women with calcium intakes below the recommended dietary allowance of 800 mg.

  15. Pathogen resistance of transgenic tobacco plants producing caffeine.

    PubMed

    Kim, Yun-Soo; Sano, Hiroshi

    2008-02-01

    Caffeine (1,3,7-trimethylxanthine) is a typical purine alkaloid, and produced by a variety of plants such as coffee and tea. Its physiological function, however, is not completely understood, but chemical defense against pathogens and herbivores, and allelopathic effects against competing plant species have been proposed. Previously, we constructed transgenic tobacco plants, which produced caffeine up to 5 microg per gram fresh weight of leaves, and showed them to repel caterpillars of tobacco cutworms (Spodoptera litura). In the present study, we found that these transgenic plants constitutively expressed defense-related genes encoding pathogenesis-related (PR)-1a and proteinase inhibitor II under non-stressed conditions. We also found that they were highly resistant against pathogens, tobacco mosaic virus and Pseudomonas syringae. Expression of PR-1a and PR-2 was higher in transgenic plants than in wild-type plants during infection. Exogenously applied caffeine to wild-type tobacco leaves exhibited the similar resistant activity. These results suggested that caffeine stimulated endogenous defense system of host plants through directly or indirectly activating gene expression. This assumption is essentially consistent with the idea of chemical defense, in which caffeine may act as one of signaling molecules to activate defense response. It is thus conceivable that the effect of caffeine is bifunctional; direct interference with pest metabolic pathways, and activation of host defense systems.

  16. The effects of stress and caffeine on hypertensives.

    PubMed

    Goldstein, I B; Shapiro, D

    1987-01-01

    Eighteen male hypertensives on diuretic medication between the ages of 37 and 60 were studied in a double-blind, randomized, crossover design under three conditions: 200 mg of caffeine and mental arithmetic; placebo and mental arithmetic; and 200 mg of caffeine alone. Systolic and diastolic blood pressure, heart rate, and skin conductance were recorded. During rest, caffeine compared to placebo increased blood pressure by 8/6 mm Hg, but had no effect on heart rate or skin conductance. During mental arithmetic, the combined effect of mental stress and caffeine led to a further increase of 17/7 mm Hg, reaching a pressure level of 163/100 mm Hg. Heart rate and skin conductance were increased above their prior caffeine levels. There were no significant differences between the blood pressure response to mental arithmetic with caffeine and that response to mental arithmetic with a placebo, which may have been due to the fact that the hypertensives were already responding at ceiling level during the mental stressor. PMID:3299441

  17. Effects of caffeine intake and smoking on neurocognition in schizophrenia.

    PubMed

    Núñez, Christian; Stephan-Otto, Christian; Cuevas-Esteban, Jorge; Maria Haro, Josep; Huerta-Ramos, Elena; Ochoa, Susana; Usall, Judith; Brébion, Gildas

    2015-12-30

    Although most studies support the beneficial effects of caffeine on neurocognition, its effects have never been assessed in psychiatric patients. In addition, results from studies in smokers are contradictory. Moreover, there are no data available about the neurocognitive effects of caffeine and tobacco together. We explored the concomitant effects of regular caffeine and tobacco intake on neurocognition in 52 schizophrenic patients and 61 healthy controls. Verbal fluency, processing speed, and working, visual and verbal memory were assessed. For each measurement, two tasks with two levels of complexity were administered. Our results showed that caffeine intake had beneficial effects on male schizophrenic patients only in complex tasks requiring deeper cognitive processing (semantic fluency, cognitive speed, working memory, and visual memory). Female patients and controls were unaffected. In contrast, smoking had a negative effect on male, but not on female, schizophrenic patients in semantic fluency. The effects of smoking in controls were inconsistent. In conclusion, our data showed, for the first time, beneficial effects of caffeine intake on neurocognition in male schizophrenic patients. These data suggest that further research of therapeutics based on caffeine is needed, as this could be beneficial for schizophrenic patients. In contrast, smoking appears to be detrimental. PMID:26614014

  18. Winning a Won Game: Caffeine Panacea for Obesity Syndemic

    PubMed Central

    Myslobodsky, M; Eldan, A

    2010-01-01

    Over the past decades, chronic sleep reduction and a concurrent development of obesity have been recognized as a common problem in the industrialized world. Among its numerous untoward effects, there is a possibility that insomnia is also a major contributor to obesity. This attribution poses a problem for caffeine, an inexpensive, “natural” agent that is purported to improve a number of conditions and is often indicated in a long-term pharmacotherapy in the context of weight management. The present study used the “common target” approach by exploring the tentative shared molecular networks of insomnia and adiposity. It discusses caffeine targets beyond those associated with adenosine signaling machinery, phosphodiesterases, and calcium release channels. Here, we provide a view suggesting that caffeine could exert some of its effects by acting on several signaling complexes composed of HIF-1α/VEGF/IL-8 along with NO, TNF-α, IL1, and GHRH, among others. Although the relevance of these targets to the reported therapeutic effects of caffeine has remained difficult to assess, the utilization of caffeine efficacies and potencies recommend its repurposing for development of novel therapeutic approaches. Among indications mentioned, are neuroprotective, nootropic, antioxidant, proliferative, anti-fibrotic, and anti-angiogenic that appear under a variety of dissimilar diagnostic labels comorbid with obesity. In the absence of safe and efficacious antiobesity agents, caffeine remains an attractive adjuvant. PMID:21119886

  19. Organoclays in water cause expansion that facilitates caffeine adsorption.

    PubMed

    Okada, Tomohiko; Oguchi, Junpei; Yamamoto, Ken-ichiro; Shiono, Takashi; Fujita, Masahiko; Iiyama, Taku

    2015-01-01

    This study investigates the adsorption of caffeine in water on organically modified clays (a natural montmorillonite and synthetic saponite, which are smectite group of layered clay minerals). The organoclays were prepared by cation-exchange reactions of benzylammonium and neostigmine with interlayer exchangeable cations in the clay minerals. Although less caffeine was uptaken on neostigmine-modified clays than on raw clay minerals, uptake was increased by adding benzylammonium to the clays. The adsorption equilibrium constant was considerably higher on benzylammonium-modified saponite (containing small quantities of intercalated benzylammonium) than on its montmorillonite counterpart. These observations suggest that decreasing the size and number of intercalated cations enlarges the siloxane surface area available for caffeine adsorption. When the benzylammonium-smectite powders were immersed in water, the intercalated water molecules expanded the interlayer space. Addition of caffeine to the aqueous dispersion further expanded the benzylammonium-montmorillonite system but showed no effect on benzylammonium-saponite. We assume that intercalated water molecules were exchanged with caffeine molecules. By intercalating benzylammonium into smectites, we have potentially created an adaptable two-dimensional nanospace that sequesters caffeine from aqueous media. PMID:25522121

  20. Effects of caffeine intake and smoking on neurocognition in schizophrenia.

    PubMed

    Núñez, Christian; Stephan-Otto, Christian; Cuevas-Esteban, Jorge; Maria Haro, Josep; Huerta-Ramos, Elena; Ochoa, Susana; Usall, Judith; Brébion, Gildas

    2015-12-30

    Although most studies support the beneficial effects of caffeine on neurocognition, its effects have never been assessed in psychiatric patients. In addition, results from studies in smokers are contradictory. Moreover, there are no data available about the neurocognitive effects of caffeine and tobacco together. We explored the concomitant effects of regular caffeine and tobacco intake on neurocognition in 52 schizophrenic patients and 61 healthy controls. Verbal fluency, processing speed, and working, visual and verbal memory were assessed. For each measurement, two tasks with two levels of complexity were administered. Our results showed that caffeine intake had beneficial effects on male schizophrenic patients only in complex tasks requiring deeper cognitive processing (semantic fluency, cognitive speed, working memory, and visual memory). Female patients and controls were unaffected. In contrast, smoking had a negative effect on male, but not on female, schizophrenic patients in semantic fluency. The effects of smoking in controls were inconsistent. In conclusion, our data showed, for the first time, beneficial effects of caffeine intake on neurocognition in male schizophrenic patients. These data suggest that further research of therapeutics based on caffeine is needed, as this could be beneficial for schizophrenic patients. In contrast, smoking appears to be detrimental.