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Sample records for plasma nicotine concentration

  1. Prenatal cigarette smoke exposure: Pregnancy outcome and gestational changes in plasma nicotine concentration, hematocrit, and carboxyhemoglobin in a newly standardized rat model

    SciTech Connect

    Farkas, Svetlana; Hussein, Jabeen; Ariano, Robert E.; Sitar, Daniel S.; Hasan, Shabih U. . E-mail: hasans@ucalgary.ca

    2006-07-15

    Epidemiological studies support an association between perinatal cigarette smoke (CS) exposure and a number of severe pre- and postnatal complications. However, the mechanisms through which CS enhances such risks largely remain unknown. One of the reasons for our inability to discover such mechanisms has been the unavailability of a clinically relevant and physiologically concordant animal model. A number of studies have previously used nicotine (Nic) as surrogate for CS. We sought to (1) establish the amount of CS exposure to achieve plasma Nic concentrations observed among moderate to heavy smokers (20-60 ng/ml) (2) investigate the temporal changes in plasma Nic concentrations, carboxyhemoglobin, and hematocrit with advancing pregnancy, and (3) elucidate the effects of CS exposure on pregnancy outcome. Pregnant Sprague-Dawley rats were exposed to various doses of CS or room air (Sham) from days 6 to 21 of gestation. Exposure to 6000 ml/day of CS led to very high plasma Nic concentrations and increased maternal and fetal mortality (P < 0.001). The plasma Nic concentrations remained higher than those observed in moderate smokers until the CS dose was reduced to 1000 ml/day and showed dose-dependent temporal changes with advancing gestational age. Significant increases in carboxyhemoglobin and hematocrit were observed in the CS group as compared with the Sham group (P < 0.001). In addition, prenatally CS exposed fetuses had lower birth weight as compared with the Sham group (P = 0.04). Our current study establishes a newly standardized and physiologically relevant model to investigate the mechanisms of CS-mediated adverse effects during the critical period of fetal development.

  2. Effects of User Puff Topography, Device Voltage, and Liquid Nicotine Concentration on Electronic Cigarette Nicotine Yield: Measurements and Model Predictions

    PubMed Central

    Talih, Soha; Balhas, Zainab; Eissenberg, Thomas; Salman, Rola; Karaoghlanian, Nareg; El Hellani, Ahmad; Baalbaki, Rima; Saliba, Najat

    2015-01-01

    Introduction: Some electronic cigarette (ECIG) users attain tobacco cigarette–like plasma nicotine concentrations while others do not. Understanding the factors that influence ECIG aerosol nicotine delivery is relevant to regulation, including product labeling and abuse liability. These factors may include user puff topography, ECIG liquid composition, and ECIG design features. This study addresses how these factors can influence ECIG nicotine yield. Methods: Aerosols were machine generated with 1 type of ECIG cartridge (V4L CoolCart) using 5 distinct puff profiles representing a tobacco cigarette smoker (2-s puff duration, 33-ml/s puff velocity), a slow average ECIG user (4 s, 17 ml/s), a fast average user (4 s, 33 ml/s), a slow extreme user (8 s, 17 ml/s), and a fast extreme user (8 s, 33 ml/s). Output voltage (3.3–5.2 V or 3.0–7.5 W) and e-liquid nicotine concentration (18–36 mg/ml labeled concentration) were varied. A theoretical model was also developed to simulate the ECIG aerosol production process and to provide insight into the empirical observations. Results: Nicotine yields from 15 puffs varied by more than 50-fold across conditions. Experienced ECIG user profiles (longer puffs) resulted in higher nicotine yields relative to the tobacco smoker (shorter puffs). Puff velocity had no effect on nicotine yield. Higher nicotine concentration and higher voltages resulted in higher nicotine yields. These results were predicted well by the theoretical model (R 2 = 0.99). Conclusions: Depending on puff conditions and product features, 15 puffs from an ECIG can provide far less or far more nicotine than a single tobacco cigarette. ECIG emissions can be predicted using physical principles, with knowledge of puff topography and a few ECIG device design parameters. PMID:25187061

  3. Chewing nicotine gum for 3 months: what happens to plasma nicotine levels?

    PubMed Central

    McNabb, M E

    1984-01-01

    Techniques that help patients stop smoking should also reduce their exposure to agents such as nicotine. The mean plasma nicotine levels in 50 subjects while they were still smoking and then while they were chewing pieces of gum containing either 2 or 4 mg of nicotine over a 12-week period of abstinence were 35, 9 and 23 ng/mL (217, 56 and 143 nmol/L) respectively. A small number of subjects given an unlimited supply of gum used 14 to 24 pieces of 4-mg gum daily and had plasma nicotine levels exceeding the levels achieved while smoking. There were no acute symptoms necessitating medical intervention associated with these excessive levels. Side effects were uncommon and usually controllable. When simple dosage rules are followed people who chew nicotine gum for a few months to stop smoking lower their exposure to nicotine. PMID:6478344

  4. Simultaneous determination of nicotine, cotinine, and nicotine N-oxide in human plasma, semen, and sperm by LC-Orbitrap MS.

    PubMed

    Abu-Awwad, Ahmad; Arafat, Tawfiq; Schmitz, Oliver J

    2016-09-01

    Nicotine (Nic) distribution in human fluids and tissues has a deleterious effect on human health. In addition to its poisoning profile, Nic may contribute to the particular impact of smoking on human reproduction. Although present in seminal fluid, still nobody knows whether nicotine is available in sperm or not. Herein, we developed and validated a new bioanalytical method, for simultaneous determination of Nic, cotinine (Cot), and nicotine N'-oxide (Nox) in human plasma, semen, and sperm by LC-ESI-orbitrap-MS. Blood and semen samples were collected from 12 healthy smoking volunteers in this study. Sperm bodies were then separated quantitatively from 1 mL of semen samples by centrifugation. The developed method was fully validated for plasma following European and American guidelines for bioanalytical method validation, and partial validation was applied to semen analysis. Plasma, semen, and sperm samples were treated by trichloroacetic acid solution for protein direct precipitation in single extraction step. The established calibration range for Nic and Nox in plasma and semen was linear between 5 and 250 ng/mL, and for Cot between 10 and 500 ng/mL. Nic and Cot were detected in human sperm at concentrations as high as in plasma. In addition, Nox was present in semen and sperm but not in plasma. Graphical abstract Nicotine correlation between plasma and semen a; Nicotine correlation between semen and sperm c; Cotinine correlation between plasma and semen b; Cotinine correlation between semen and sperm d.

  5. Simultaneous determination of nicotine, cotinine, and nicotine N-oxide in human plasma, semen, and sperm by LC-Orbitrap MS.

    PubMed

    Abu-Awwad, Ahmad; Arafat, Tawfiq; Schmitz, Oliver J

    2016-09-01

    Nicotine (Nic) distribution in human fluids and tissues has a deleterious effect on human health. In addition to its poisoning profile, Nic may contribute to the particular impact of smoking on human reproduction. Although present in seminal fluid, still nobody knows whether nicotine is available in sperm or not. Herein, we developed and validated a new bioanalytical method, for simultaneous determination of Nic, cotinine (Cot), and nicotine N'-oxide (Nox) in human plasma, semen, and sperm by LC-ESI-orbitrap-MS. Blood and semen samples were collected from 12 healthy smoking volunteers in this study. Sperm bodies were then separated quantitatively from 1 mL of semen samples by centrifugation. The developed method was fully validated for plasma following European and American guidelines for bioanalytical method validation, and partial validation was applied to semen analysis. Plasma, semen, and sperm samples were treated by trichloroacetic acid solution for protein direct precipitation in single extraction step. The established calibration range for Nic and Nox in plasma and semen was linear between 5 and 250 ng/mL, and for Cot between 10 and 500 ng/mL. Nic and Cot were detected in human sperm at concentrations as high as in plasma. In addition, Nox was present in semen and sperm but not in plasma. Graphical abstract Nicotine correlation between plasma and semen a; Nicotine correlation between semen and sperm c; Cotinine correlation between plasma and semen b; Cotinine correlation between semen and sperm d. PMID:27422648

  6. Concentration of Nicotine and Glycols in 27 Electronic Cigarette Formulations.

    PubMed

    Peace, Michelle R; Baird, Tyson R; Smith, Nathaniel; Wolf, Carl E; Poklis, Justin L; Poklis, Alphonse

    2016-07-01

    Personal battery-powered vaporizers or electronic cigarettes were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. Electronic cigarettes and their e-cigarette liquid formulations are virtually unregulated. These formulations are typically composed of propylene glycol and/or glycerin, flavoring components and an active drug, such as nicotine. Twenty-seven e-cigarette liquid formulations that contain nicotine between 6 and 22 mg/L were acquired within the USA and analyzed by various methods to determine their contents. They were screened by Direct Analysis in Real Time™ Mass Spectrometry (DART-MS). Nicotine was confirmed and quantitated by high-performance liquid chromatography-tandem mass spectrometry, and the glycol composition was confirmed and quantitated by gas chromatography-mass spectrometry. The DART-MS screening method was able to consistently identify the exact mass peaks resulting from the protonated molecular ion of nicotine, glycol and a number of flavor additives within 5 mmu. Nicotine concentrations were determined to range from 45 to 131% of the stated label concentration, with 18 of the 27 have >10% variance. Glycol composition was generally accurate to the product description, with only one exception where the propylene glycol to glycerin percentage ratio was stated as 50:50 and the determined concentration of propylene glycol to glycerin was 81:19 (% v/v). No unlabeled glycols were detected in these formulations.

  7. Smoking-Relevant Nicotine Concentration Attenuates the Unfolded Protein Response in Dopaminergic Neurons

    PubMed Central

    Srinivasan, Rahul; Henley, Beverley M.; Henderson, Brandon J.; Indersmitten, Tim; Cohen, Bruce N.; Kim, Charlene H.; McKinney, Sheri; Deshpande, Purnima; Xiao, Cheng

    2016-01-01

    Retrospective epidemiological studies show an inverse correlation between susceptibility to Parkinson's disease and a person's history of tobacco use. Animal model studies suggest nicotine as a neuroprotective agent and nicotinic acetylcholine (ACh) receptors (nAChRs) as targets for neuroprotection, but the underlying neuroprotective mechanism(s) are unknown. We cultured mouse ventral midbrain neurons for 3 weeks. Ten to 20% of neurons were dopaminergic (DA), revealed by tyrosine hydroxylase (TH) immunoreactivity. We evoked mild endoplasmic reticulum (ER) stress with tunicamycin (Tu), producing modest increases in the level of nuclear ATF6, phosphorylated eukaryotic initiation factor 2α, nuclear XBP1, and the downstream proapoptotic effector nuclear C/EBP homologous protein. We incubated cultures for 2 weeks with 200 nm nicotine, the approximate steady-state concentration between cigarette smoking or vaping, or during nicotine patch use. Nicotine incubation suppressed Tu-induced ER stress and the unfolded protein response (UPR). Study of mice with fluorescent nAChR subunits showed that the cultured TH+ neurons displayed α4, α6, and β3 nAChR subunit expression and ACh-evoked currents. Gene expression profile in cultures from TH-eGFP mice showed that the TH+ neurons also express several other genes associated with DA release. Nicotine also upregulated ACh-induced currents in DA neurons by ∼2.5-fold. Thus, nicotine, at a concentration too low to activate an appreciable fraction of plasma membrane nAChRs, induces two sequelae of pharmacological chaperoning in the ER: UPR suppression and nAChR upregulation. Therefore, one mechanism of neuroprotection by nicotine is pharmacological chaperoning, leading to UPR suppression. Measuring this pathway may help in assessing neuroprotection. SIGNIFICANCE STATEMENT Parkinson's disease (PD) cannot yet be cured or prevented. However, many retrospective epidemiological studies reveal that PD is diagnosed less frequently in

  8. Nicotine dose-concentration relationship and pregnancy outcomes in rat: Biologic plausibility and implications for future research

    SciTech Connect

    Hussein, Jabeen; Farkas, Svetlana; MacKinnon, Yolanda; Ariano, Robert E.; Sitar, Daniel S.; Hasan, Shabih U. . E-mail: hasans@ucalgary.ca

    2007-01-01

    Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderate to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers.

  9. Nicotinic infertility: assessing DNA and plasma membrane integrity of human spermatozoa.

    PubMed

    Arabi, M

    2004-10-01

    Infertility remains a major problem in society, with recent data suggesting its presence in one of four couples. The objective of the present study was to evaluate the impact of nicotine (0.25, 0.5 and 0.75 mm), as a major component of cigarette smoke, in vitro, on sperm membrane [by spermatocrit and lipoperoxidation (LPO) tests], DNA integrity (by Comet assay), and viability of spermatozoa (by eosin staining) from normozoospermic men. Sperm samples were washed and diluted with phosphate-buffered saline. A drop in spermatocrit values and an increase in thiobarbituric acid-reactive substances/LPO rate was observed with the addition of nicotine, predominantly at a concentration of 0.75 mm, indicating a deleterious effect of nicotine on sperm membrane intactness. There was also a strong negative correlation between LPO rate and percentage viable sperm cell (r = -0.990). Data obtained from Comet assay technique revealed that nicotine could induce double-stranded DNA breaks (11% in 0.75 mm concentration) in the sperm nuclei. The value of r between LPO rate and percentage Comets was found to be +0.976. Taken together, nicotine proved to be a potential oxidant agent in the category of environmental factors to the integrity of sperm plasma membrane and DNA. PMID:15458549

  10. Nicotine Concentrations in Electronic Cigarette Refill and Do-It-Yourself Fluids

    PubMed Central

    Davis, Barbara; Dang, Michael; Kim, Jisoo

    2015-01-01

    Introduction: We evaluated the accuracy of nicotine concentration labeling on electronic cigarette refill products. Methods: The nicotine concentration of 71 electronic cigarette refill fluid products and 1 related do-it-yourself (DIY) product was quantified using high-performance liquid chromatography. Quantified data were compared with manufacturers labeled concentrations. Duplicate refill fluid products purchased at different times were evaluated by visual comparison of fluid coloration and quantified nicotine concentration. Results: Thirty-five of the 54 nicotine-containing fluids had quantified nicotine concentrations that deviated by more than ±10% from the manufacturer labels, with 46 of 50 being in excess of labeled values. Refill fluids labeled as 0 nicotine had no detectable nicotine. Of the 5 products that were unlabeled for nicotine concentration, 3 contained no detectable nicotine, whereas the remaining 2 contained nicotine in excess of 100mg/ml and may have been intended for DIY use. Sixteen of the 18 duplicate bottles of refill fluid varied greatly in their nicotine concentrations. One of the 5 companies showed significant improvement in labeling accuracy among the most recently purchased products. Of the 23 total duplicate pairs, 15 of 23 varied in coloration from their mates. Conclusions: Nicotine concentration labeling on electronic cigarette refill products was often inaccurate but showed improvement recently in products from 1 company. To ensure the safety of refill fluids and DIY products, it is necessary to establish quality control guidelines for the manufacturing and labeling and to monitor products longitudinally. PMID:24862971

  11. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    SciTech Connect

    Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  12. Nicotine concentrations in urine and saliva of smokers and non-smokers.

    PubMed Central

    Feyerabend, C; Higenbottam, T; Russell, M A

    1982-01-01

    Nicotine concentrations were measured in saliva and urine samples collected from 82 smokers and 56 non-smokers after a morning at work. Each subject answered a series of questions related to their recent intentional or passive exposure to tobacco smoke. All non-smokers had measurable amounts of nicotine in both saliva and urine. Those non-smokers who reported recent exposure to tobacco smoke had significantly higher nicotine concentrations (p less than 0.001) than those who had not been exposed; their concentrations overlapped those of smokers who had smoked up to three cigarettes before sampling had the greatest influence on nicotine concentrations (r=0.62 for saliva and r=0.51 for urine). Neither the nicotine for yield of cigarettes nor the self-reported degree of inhalation had any significant effect on nicotine concentrations. PMID:6802384

  13. Layer-specific interference with cholinergic signaling in the prefrontal cortex by smoking concentrations of nicotine.

    PubMed

    Poorthuis, Rogier B; Bloem, Bernard; Verhoog, Matthijs B; Mansvelder, Huibert D

    2013-03-13

    Adolescence is a period in which the developing prefrontal cortex (PFC) is sensitive to maladaptive changes when exposed to nicotine. Nicotine affects PFC function and repeated exposure to nicotine during adolescence impairs attention performance and impulse control during adulthood. Nicotine concentrations experienced by smokers are known to desensitize nicotinic acetylcholine receptors (nAChRs), but the impact thereof on PFC circuits is poorly understood. Here, we investigated how smoking concentrations of nicotine (100-300 nm) interfere with cholinergic signaling in the mouse PFC. nAChR desensitization depends on subunit composition. Since nAChR subunits are differentially expressed across layers of the PFC neuronal network, we hypothesized that cholinergic signaling through nAChRs across layers would suffer differentially from exposure to nicotine. Throughout the PFC, nicotine strongly desensitized responses to ACh in neurons expressing β2* nAChRs, whereas ACh responses mediated by α7 nAChRs were not hampered. The amount of desensitization of β2* nAChR currents depended on neuron type and cortical layer. β2*-mediated responses of interneurons in LII-III and LVI completely desensitized, while cholinergic responses in LV interneurons and LVI pyramidal cells showed less desensitization. This discrepancy depended on α5 subunit expression. Two-photon imaging of neuronal population activity showed that prolonged exposure to nicotine limited cholinergic signaling through β2* nAChRs to deep PFC layers where α5 subunits were expressed. Together, our results demonstrate a layer-dependent decrease in cholinergic activation of the PFC through nAChRs by nicotine. These mechanisms may be one of the first steps leading up to the pathophysiological changes associated with nicotine exposure during adolescence.

  14. Establishing a minimal erythema concentration of methyl nicotinate for optimum evaluation of anti-inflammatories.

    PubMed

    Jumbelic, L C; Liebel, F T; Southall, M D

    2006-01-01

    Topical administration of chemicals such as methyl nicotinate that induce erythema have been employed to measure the effectiveness of formulations containing anti-inflammatory agents. Prior studies have utilized a single concentration of methyl nicotinate, between 36.5 and 100 mM, for all test subjects in evaluations of topical formulations. However, individuals have different thresholds of response to methyl nicotinate; thus, a single concentration may not be appropriate for all individuals and could result in the apparent lack of anti-inflammatory activity of the formulation being evaluated. In the current study, we evaluated the use of a minimal erythema concentration (MEC) of methyl nicotinate, defined as the lowest concentration that produces a complete and even erythema at the test site, compared with a 36.5-mM concentration of methyl nicotinate. Hydroalcoholic gels containing the nonsteroidal anti-inflammatory drug ibuprofen were compared with placebo. Diffuse reflectance spectroscopy was employed to measure differences in cutaneous inflammatory response between the control (placebo)-treated group and the ibuprofen-treated group. When chemical erythema was induced using an MEC of methyl nicotinate, greater reductions in erythema were seen in ibuprofen-treated sites compared with sites treated with a 36.5-mM concentration of methyl nicotinate. In conclusion, for an accurate assessment method of erythema induced by methyl nicotinate, consideration should be given to determining the extent of response of an erythema-producing agent on an individual basis. An MEC of methyl nicotinate should be determined and employed for each individual to obtain more consistent and reliable efficacy results of anti-inflammatory activity.

  15. Preliminary Results of an Examination of Electronic Cigarette User Puff Topography: The Effect of a Mouthpiece-Based Topography Measurement Device on Plasma Nicotine and Subjective Effects

    PubMed Central

    Spindle, Tory R.; Breland, Alison B.; Karaoghlanian, Nareg V.; Shihadeh, Alan L.

    2015-01-01

    Introduction: Electronic cigarettes (ECIGs) heat a nicotine-containing solution; the resulting aerosol is inhaled by the user. Nicotine delivery may be affected by users’ puffing behavior (puff topography), and little is known about the puff topography of ECIG users. Puff topography can be measured using mouthpiece-based computerized systems. However, the extent to which a mouthpiece influences nicotine delivery and subjective effects in ECIG users is unknown. Methods: Plasma nicotine concentration, heart rate, and subjective effects were measured in 13 experienced ECIG users who used their preferred ECIG and liquid (≥12mg/ml nicotine) during 2 sessions (with or without a mouthpiece). In both sessions, participants completed an ECIG use session in which they were instructed to take 10 puffs with 30-second inter-puff intervals. Puff topography was recorded in the mouthpiece condition. Results: Almost all measures of the effects of ECIG use were independent of topography measurement. Collapsed across session, mean plasma nicotine concentration increased by 16.8ng/ml, and mean heart rate increased by 8.5 bpm (ps < .05). Withdrawal symptoms decreased significantly after ECIG use. Participants reported that the mouthpiece affected awareness and made ECIG use more difficult. Relative to previously reported data for tobacco cigarette smokers using similar topography measurement equipment, ECIG-using participants took larger and longer puffs with lower flow rates. Conclusions: In experienced ECIG users, measuring ECIG topography did not influence ECIG-associated nicotine delivery or most measures of withdrawal suppression. Topography measurement systems will need to account for the low flow rates observed for ECIG users. PMID:25239957

  16. Effects of chronic nicotine administration on body weight, food intake and nitric oxide concentration in female and male rats.

    PubMed

    Ijomone, Omamuyovwi Meashack; Olaibi, Olayemi Kafilat; Nwoha, Polycarp Umunna

    2014-09-01

    Nicotine is readily consumed through cigarettes; however it is also easily consumed through the various forms of non-prescription nicotine replacement therapy. It has been shown to possess potential therapeutic value for the management of neurologic and neurodegenerative diseases in the last decade. Hence, this study examined the effects of chronic subcutaneous nicotine administration on food intake and body weight as well as on nitric oxide concentrations and total antioxidant capacity in female and male rats. Nicotine was administered to rats via subcutaneous injections at doses of 0.25, 2 and 4mg/kg body weight for 28 days. Control groups received normal saline; the vehicle for nicotine. Food intake by each group was monitored daily and body weight of the animals was measured twice weekly. At the end of drug administration, blood was obtained from each animal via cardiac puncture for biochemical determination of serum total antioxidant capacity (TAC) and nitric (NO) concentrations using standard assay kits. Results show significant loss (p<0.05) of body weight in all nicotine treated female rats. In contrast, male rats showed weight gain, though this was significantly lower (p<0.001) in nicotine treated groups compared to control. Nicotine significantly reduced (p<0.001) food consumed in both female and male rats; however dose related changes were observed in only male rats. No significant difference was observed in TAC following nicotine treatments for both female and male rats. Furthermore, only males exhibited changes in NO concentrations following nicotine treatment, as it significantly increased (p<0.01) NO concentrations in all male treated groups. In conclusion, this study has shown that modulation of body weight, food consumption and nitric oxide formation by nicotine is sexually dimorphic. Also, the study suggests that nicotine modulation of food intake and body weight and its modulation of NO may be independent of each other.

  17. Nicotine from cigarette smoking enhances clonidine-induced increase of serum growth hormone concentrations in men.

    PubMed Central

    Coiro, V; d'Amato, L; Borciani, E; Rossi, G; Camellini, L; Maffei, M L; Pignatti, D; Chiodera, P

    1984-01-01

    In order to determine whether nicotine exerts its stimulant effect on serum concentrations of growth hormone (GH) by interacting with an adrenergic pathway, we evaluated the effect of cigarette smoking on the response of GH to the administration of clonidine, a specific alpha-adrenoceptor agonist. In six normal volunteers, clonidine significantly increased serum levels of GH. When subjects smoked two non-filter cigarettes, GH response to the alpha-adrenoceptor agonist was greatly enhanced. These findings suggest that in man nicotinic cholinergic and adrenergic mechanisms might interact in the stimulation of GH secretion. PMID:6508989

  18. Simultaneous determination of myristyl nicotinate, nicotinic acid, and nicotinamide in rabbit plasma by liquid chromatography-tandem mass spectrometry using methyl ethyl ketone as a deproteinization solvent.

    PubMed

    Catz, Paul; Shinn, Walter; Kapetanovic, Izet M; Kim, Hyuntae; Kim, Moonsun; Jacobson, Elaine L; Jacobson, Myron K; Green, Carol E

    2005-12-27

    Myristyl nicotinate (Nia-114) is an ester prodrug being developed for delivery of nicotinic acid (NIC) into the skin for prevention of actinic keratosis and its progression to skin cancer. To facilitate dermal studies of Nia-114, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using methyl ethyl ketone (MEK) as a deproteinization solvent was developed and validated for the simultaneous determination of Nia-114, NIC, and nicotinamide (NAM) in rabbit plasma. NAM is the principal metabolite of NIC, which is also expected to have chemopreventive properties. The analytes were chromatographically separated using a Spherisorb Cyano column under isocratic conditions, and detected by multiple reaction monitoring (MRM) in positive-ion electrospray ionization mode with a run time of 9 min. The method utilized a plasma sample volume of 0.2 ml and isotope-labeled D4 forms of each analyte as internal standards. The method was linear over the concentration range of 2-1000, 8-1000, and 75-1000 ng/ml, for Nia-114, NIC, and NAM, respectively. The intra- and inter-day assay accuracy and precision were within +/-15% for all analytes at low, medium, and high quality control standard levels. The relatively high value for the lower limit of quantitation (LLOQ) of NAM was demonstrated to be due to the high level of endogenous NAM in the rabbit plasma (about 350 ng/ml). Endogenous levels of NIC and NAM in human, dog, rat, and mouse plasma were also determined, and mean values ranged from <2 ng/ml NIC and 38.3 ng/ml NAM in human, to 233 ng/ml NIC and 622 ng/ml NAM in mouse. Nia-114 was generally unstable in rabbit plasma, as evidenced by loss of 44-50% at room temperature by 2 h, and loss of 64-70% upon storage at -20 degrees C for 1 week, whereas it was stable (<7% loss) upon storage at -80 degrees C for 1 month.

  19. Simultaneous and Sensitive Measurement of Nicotine, Cotinine, trans-3’-Hydroxycotinine and Norcotinine in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry

    PubMed Central

    Shakleya, Diaa M.; Huestis, Marilyn A.

    2009-01-01

    An LCMSMS method for the simultaneous quantification of nicotine, cotinine, trans-3’-hydroxycotinine and norcotinine in human plasma was developed and fully validated. Potential endogenous and exogenous interferences were extensively evaluated and limits of quantification were determined by decreasing analyte concentration. Analytical ranges were 1–500 ng/mL for nicotine and cotinine, 5–500 ng/mL for trans-3’-hydroxycotinine and norcotinine. Mean intra- and inter-assay analytical recovery were between 101.9 and 116.8%, and intra- and inter-assay imprecision were less than 11% RSD for all analytes: parameters were evaluated at three different concentrations across the linear range of the assay. Extraction efficiency was ≥ 70% for all analytes. This validated method is useful for determination of nicotine and metabolites in human plasma to support research on the role of nicotine biomarkers on neuronal systems mediating cognitive and affective processes and to differentiate active, passive and environmental exposure. PMID:19748838

  20. Nicotine Metabolite Ratio (3-hydroxycotinine/cotinine) in Plasma and Urine by Different Analytical Methods and Laboratories: Implications for Clinical Implementation

    PubMed Central

    Tanner, Julie-Anne; Novalen, Maria; Jatlow, Peter; Huestis, Marilyn A.; Murphy, Sharon E.; Kaprio, Jaakko; Kankaanpää, Aino; Galanti, Laurence; Stefan, Cristiana; George, Tony P.; Benowitz, Neal L.; Lerman, Caryn; Tyndale, Rachel F.

    2015-01-01

    Background The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) and COT to trans-3′-hydroxycotinine (3HC). The nicotine metabolite ratio (NMR, 3HC/COT) is commonly used as a biomarker of CYP2A6 enzymatic activity, rate of nicotine metabolism, and total nicotine clearance; NMR is associated with numerous smoking phenotypes, including smoking cessation. Our objective was to investigate the impact of different measurement methods, at different sites, on plasma and urinary NMR measures from ad libitum smokers. Methods Plasma (n=35) and urine (n=35) samples were sent to eight different laboratories, which employed similar and different methods of COT and 3HC measurements to derive the NMR. We used Bland-Altman analysis to assess agreement, and Pearson correlations to evaluate associations, between NMR measured by different methods. Results Measures of plasma NMR were in strong agreement between methods according to Bland-Altman analysis (ratios 0.82–1.16) and were highly correlated (all Pearson r>0.96, P<0.0001). Measures of urinary NMR were in relatively weaker agreement (ratios 0.62–1.71) and less strongly correlated (Pearson r values of 0.66–0.98, P<0.0001) between different methods. Plasma and urinary COT and 3HC concentrations, while weaker than NMR, also showed good agreement in plasma, which was better than in urine, as was observed for NMR. Conclusions Plasma is a very reliable biological source for the determination of NMR, robust to differences in these analytical protocols or assessment site. Impact Together this indicates a reduced need for differential interpretation of plasma NMR results based on the approach used, allowing for direct comparison of different studies. PMID:26014804

  1. Nicotinic receptors on rat alveolar macrophages dampen ATP-induced increase in cytosolic calcium concentration

    PubMed Central

    2010-01-01

    Background Nicotinic acetylcholine receptors (nAChR) have been identified on a variety of cells of the immune system and are generally considered to trigger anti-inflammatory events. In the present study, we determine the nAChR inventory of rat alveolar macrophages (AM), and investigate the cellular events evoked by stimulation with nicotine. Methods Rat AM were isolated freshly by bronchoalveolar lavage. The expression of nAChR subunits was analyzed by RT-PCR, immunohistochemistry, and Western blotting. To evaluate function of nAChR subunits, electrophysiological recordings and measurements of intracellular calcium concentration ([Ca2+]i) were conducted. Results Positive RT-PCR results were obtained for nAChR subunits α3, α5, α9, α10, β1, and β2, with most stable expression being noted for subunits α9, α10, β1, and β2. Notably, mRNA coding for subunit α7 which is proposed to convey the nicotinic anti-inflammatory response of macrophages from other sources than the lung was not detected. RT-PCR data were supported by immunohistochemistry on AM isolated by lavage, as well as in lung tissue sections and by Western blotting. Neither whole-cell patch clamp recordings nor measurements of [Ca2+]i revealed changes in membrane current in response to ACh and in [Ca2+]i in response to nicotine, respectively. However, nicotine (100 μM), given 2 min prior to ATP, significantly reduced the ATP-induced rise in [Ca2+]i by 30%. This effect was blocked by α-bungarotoxin and did not depend on the presence of extracellular calcium. Conclusions Rat AM are equipped with modulatory nAChR with properties distinct from ionotropic nAChR mediating synaptic transmission in the nervous system. Their stimulation with nicotine dampens ATP-induced Ca2+-release from intracellular stores. Thus, the present study identifies the first acute receptor-mediated nicotinic effect on AM with anti-inflammatory potential. PMID:20920278

  2. Nicotine and metabolites determination in human plasma by ultra performance liquid chromatography-tandem mass spectrometry: a simple approach for solving contamination problem and clinical application.

    PubMed

    Liachenko, Natalia; Boulamery, Audrey; Simon, Nicolas

    2015-10-01

    A quantitative method using ultra performance liquid chromatography-tandem mass spectrometry is described for simultaneous determination of nicotine and its metabolites (cotinine and trans-3'- hydroxycotinine) in human plasma. Aliquots of 0.25 mL of plasma specimens were used for analysis, and 3 analytes were extracted by liquid-liquid extraction. The main problem was blank plasma contamination with environmental nicotine. Activated charcoal was used to avoid this analytical interference. For optimized chromatographic performance, a basic mobile phase consisting of 0.2% ammonia in water (mobile phase A, pH10.6) and acetonitrile (mobile phase B) was selected. The analytes were separated on a 50 mm × 2.1 mm BEH C18 column, 1.7 μm particle size, and quantified by MS/MS using multiple-reaction monitoring (MRM) in positive mode. The chromatographic separation was achieved in 3 min followed by 1.2 min of column equilibration. The calibration curves were linear in the concentration range of 10-1000 ng/mL with correlation coefficients exceeding 0.99. Within-day precisions and between-day precisions (CV, %) were <15 %. The accuracy expressed as bias was within ±15% for all analytes. The recovery values ranged from 50% to 97%. The ions used for quantification of nicotine, cotinine and 3-OH-cotinine were 166.9 > 129.7; 176.9 > 79.7; 192.9 > 79.7 m/z, respectively. The original blank sample preparation solved the problem of contamination in a cost-effective and efficient way. The validated method has been routinely used for analysis of nicotine and metabolites and determination of hydroxycotinine/cotinine metabolic ratio. This biomarker seems to be interesting at predicting response of nicotine patch replacement therapies.

  3. Nicotine concentration in leaves of flue-cured tobacco plants as affected by removal of the shoot apex and lateral buds.

    PubMed

    Wang, Shu-Sheng; Shi, Qiu-Mei; Li, Wen-Qing; Niu, Jun-Fang; Li, Chun-Jian; Zhang, Fu-Suo

    2008-08-01

    It is believed that the nicotine concentration in tobacco is closely correlated with the amount of nitrogen (N) supplied. On the other hand, N uptake mainly occurs at the early growth stage, whereas nicotine concentration increases at the late growth stage, especially after removing the shoot apex. To identify the causes of the increased nicotine concentration in tobacco plants, and to compare the effects of different ways of mechanical wounding on nicotine concentration, field experiments were carried out in Fuzhou, Fujian Province in 2003 and 2004. Excision of the shoot apex had almost no influence on N content in the plant; however, it caused dramatic increases in nicotine concentration in leaves, especially in the middle and upper leaves. An additional increase of the nicotine concentration was obtained by removal of axillary buds. The wounding caused by routine leaf harvests, however, did not change the leaf nicotine concentration, and neither did reducing leaf harvest times. The present results revealed no direct relationship between N supply and nicotine concentration in tobacco leaves, and indicate that not all kinds of mechanical wounding were capable of stimulating nicotine synthesis in tobacco plants. Since nicotine production is highly dependent on the removal of apical meristems and hence on the major sources of auxin in the plant, and application of 1-naphthylacetic acid onto the cut surface of the stem after removing the shoot apex markedly decreased the nicotine concentration in different leaves and the total nicotine content in the plant, the results suggest that decreased auxin supply caused by removal of the shoot apex as a kind of mechanical wounding might regulate nicotine synthesis in the roots of tobacco plants.

  4. Nicotine is Chemotactic for Neutrophils and Enhances Neutrophil Responsiveness to Chemotactic Peptides

    NASA Astrophysics Data System (ADS)

    Totti, Noel; McCusker, Kevin T.; Campbell, Edward J.; Griffin, Gail L.; Senior, Robert M.

    1984-01-01

    Neutrophils contribute to chronic bronchitis and pulmonary emphysema associated with cigarette smoking. Nicotine was found to be chemotactic for human neutrophils but not monocytes, with a peak activity at ~ 31 micromolar. In lower concentrations (comparable to those in smokers' plasma), nicotine enhanced the response of neutrophils to two chemotactic peptides. In contrast to most other chemoattractants for neutrophils, however, nicotine did not affect degranulation or superoxide production. Nicotine thus may promote inflammation and consequent lung injury in smokers.

  5. Plasma concentrations of voriconazole in falcons.

    PubMed

    Schmidt, V; Demiraj, F; Di Somma, A; Bailey, T; Ungemach, F R; Krautwald-Junghanns, M-E

    2007-08-25

    Doses of 12.5 mg voriconazole/kg bodyweight administered every 12 hours by crop gavage to six falcons for 14 days provided peak plasma concentrations of more than 1 microg/ml, but the trough concentrations were lower and sometimes undetectable. Administering the same doses incorporated into meat that was fed to one falcon for seven days and to three falcons for up to 91 days provided similar plasma concentrations.

  6. Plasma lipid concentrations for some Brazilian lizards.

    PubMed

    Gillett, M P; Lima, V L; Costa, J C; Sibrian, A M

    1979-01-01

    1. Plasma concentrations of cholesterol, cholesteryl esters, phospholipids and triglycerides were determined for ten species of Brazilian lizards, Iguana iguana, Tropidurus torquatos and T. semitaeniatus (Iguanidae), Tupinambis teguixin, Ameiva ameiva and Cnemidophorus ocellifer (Teiidae), Mabuya maculata (Scincidae), Hemidactylus mabouia (Gekkonidae), Amphisbaenia vermicularis and Leposternon polystegum (Amphisbaenidae). 2. Considerable inter- and intra-species variations in plasma lipid concentrations were observed. 3. The percentage of total cholesterol esterified and the individual phospholipid composition of plasma were relatively constant for each species. 4. Over 60% of the cholesteryl esters present in plasma from three species each of iguanid and teiid lizards were polyenoic. PMID:318307

  7. [Enrichment of nicotine in plasma with three-phase hollow fiber based liquid phase microextraction].

    PubMed

    Yang, Xinlei; Luo, Mingbiao; Tang, Yuping

    2006-11-01

    A novel method for fast determination of nicotine in plasma was established by using high performance liquid chromatography (HPLC) coupled with a three-phase hollow fiber based liquid phase microextraction (TP-HF-LPME) technique for sample preparation. The microextraction was mediated by the pH difference between the environment inside and outside of an organic phase immobilized in the pores formed in the wall of a polypropylene hollow fiber. The pH value of the medium outside the organic phase was adjusted by adding a dilute KOH solution to form a basic donor phase while the pH value of the inner media was set to pH 3 to form an acceptor phase using a 10 mmol/L KH2PO4 solution. On working conditions, neutral nicotine molecules were firstly extracted from the original sample solution to the organic phase, and then the analyte was extracted from the organic phase to the acceptor phase. After described extraction time, 4 microL of acceptor phase was withdrawn and directly injected into HPLC system for analysis. Parameters related to TP-HF-LPME (organic solvent, pH of acceptor and donor phase, stirring rate, salt effect, methanol content in acceptor phase and extraction time) were also optimized experimentally. The proposed method integrates extraction, enrichment and clean-up into a single step, dramatically simplifying the traditional procedure to prepare a liquid sample with complex matrices such as plasma. It has been demonstrated to be a very fast, effective and virtually "green" sample preparation technique, which provided a good linear range (0.1 - 50 mg/L) with Nu of 0.999 6, a low detection limit (0.05 mg/L, S/N = 3) and a satisfactory relative standard deviation (< 5%).

  8. Flattening plasma corticosterone levels increases the prevalence of serotonergic dorsal raphe neurons inhibitory responses to nicotine in adrenalectomised rats.

    PubMed

    Frías-Domínguez, Carmen; Garduño, Julieta; Hernández, Salvador; Drucker-Colin, René; Mihailescu, Stefan

    2013-09-01

    Major depression is characterized by a diminished activity of the brain serotonergic system as well as by the flattening of plasma cortisol levels. Nicotine improves mood in patients with major depression and in experimentally depressed animals by increasing brain serotonin (5-HT), noradrenaline and dopamine levels. The present study was directed to determine if flattening plasma glucocorticoid levels changes nicotine's stimulatory effects upon 5-HT DRN neurons. The experiments were performed in brain slices obtained from rats previously (14 days) adrenalectomised and implanted subcutaneously with one pellet containing 75mg of corticosterone (Adx+CSR rats). Whole cell voltage and current clamp techniques were used to study the activity of immunocitochemically identified 5-HT DRN neurons. Administration of nicotine (1μM) in sham-operated animals produced stimulatory effects in all 5-HT DRN neurons studied. In Adx+CSR rats however, nicotine inhibited 75% of 5-HT DRN neurons and increased the potassium-dependent inward rectifying current. The inhibitory effect of nicotine upon 5-HT DRN neurons was dependent on serotonin release inside the DRN, since it was converted into a stimulatory response by the selective antagonist of 5-HT1A receptors N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY100635, 25nM). Adx+CSR rats also presented an increased function of 5-HT1A autoreceptors, since, in these rats, serotonin (1-10μM) produced a higher increase in the potassium dependent inward rectifying current in comparison with sham-operated animals. Serotonin release inside DRN was mediated by α4β2 nicotinic acetylcholine receptors since the selective antagonist of these receptors dihydro-β-erytroidine hydrobromide (DHβE, 100nM) blocked the inhibitory effects of nicotine 5-HT DRN neurons. These data indicate that, in the experimental model of adrenalectomised rats implanted with corticosterone pellets, nicotine increases the function of

  9. Decreased plasma motilin concentrations in pregnancy.

    PubMed Central

    Christofides, N D; Ghatei, M A; Bloom, S R; Borberg, C; Gillmer, M D

    1982-01-01

    Plasma motilin concentrations were measured in 37 women during the second and third trimester of pregnancy and one week after delivery. The mean plasma motilin concentrations, both fasting and after a glucose load and a mixed meal, were significantly (p less than 0.001) reduced during pregnancy, returning to the normal range one week post partum. Pregnancy appears to have a profound inhibitory effect on plasma motilin, and this may in part be responsible for the gastrointestinal hypomotility associated with pregnancy. PMID:6814598

  10. Plasma Glutamine Concentrations in Liver Failure

    PubMed Central

    Helling, Gunnel; Wahlin, Staffan; Smedberg, Marie; Pettersson, Linn; Tjäder, Inga; Norberg, Åke; Rooyackers, Olav; Wernerman, Jan

    2016-01-01

    Background Higher than normal plasma glutamine concentration at admission to an intensive care unit is associated with an unfavorable outcome. Very high plasma glutamine levels are sometimes seen in both acute and chronic liver failure. We aimed to systematically explore the relation between different types of liver failure and plasma glutamine concentrations. Methods Four different groups of patients were studies; chronic liver failure (n = 40), acute on chronic liver failure (n = 20), acute fulminant liver failure (n = 20), and post-hepatectomy liver failure (n = 20). Child-Pugh and Model for End-stage Liver Disease (MELD) scores were assessed as indices of liver function. All groups except the chronic liver failure group were followed longitudinally during hospitalisation. Outcomes were recorded up to 48 months after study inclusion. Results All groups had individuals with very high plasma glutamine concentrations. In the total group of patients (n = 100), severity of liver failure correlated significantly with plasma glutamine concentration, but the correlation was not strong. Conclusion Liver failure, regardless of severity and course of illness, may be associated with a high plasma glutamine concentration. Further studies are needed to understand whether high glutamine levels should be regarded as a biomarker or as a contributor to symptomatology in liver failure. PMID:26938452

  11. Plasma interactions with biased concentrator solar cells

    NASA Astrophysics Data System (ADS)

    Stillwell, R. P.; Stevens, N. J.

    1986-12-01

    Concentrator solar arrays are being proposed for future space missions as replacements for less efficient (power/mass) planar arrays. While planar solar arrays have been used in space and their characteristics evaluated, concentrator cell interactions have not. This study investigates the possible interactions between a biased concentrator cell and a plasma environment. This study involved experimental and preliminary analytical work. It has been found that the electric fields associated with the biased cell are confined to the light collector region of the cell configuration, and that the cell arcs in dense plasma environments, at negative voltages of less than -200 volts, in a way similar to the arcing experienced by planar cells.

  12. Plasma Efavirenz Concentrations Are Associated With Lipid and Glucose Concentrations.

    PubMed

    Sinxadi, Phumla Zuleika; McIlleron, Helen Margaret; Dave, Joel Alex; Smith, Peter John; Levitt, Naomi Sharlene; Haas, David William; Maartens, Gary

    2016-01-01

    Efavirenz-based antiretroviral therapy (ART) has been associated with dyslipidemia and dysglycemia, risk factors for cardiovascular disease. However, the pathogenesis is not well understood. We characterized relationships between plasma efavirenz concentrations and lipid and glucose concentrations in HIV-infected South Africans.Participants on efavirenz-based ART were enrolled into a cross-sectional study. The oral glucose tolerance test was performed after an overnight fast, and plasma drawn for mid-dosing interval efavirenz, fasting total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglycerides concentrations.Among 106 participants (77 women), median age was 38 years, median CD4 + T-cell count was 322 cells/μL, median duration on ART was 18 months, and median (interquartile range) efavirenz concentration was 2.23 (1.66 to 4.10) μg/mL. On multivariable analyses (adjusting for age, sex, body mass index, and ART duration) doubling of efavirenz concentrations resulted in mean changes in mmol/L (95%CI) of: total cholesterol (0.40 [0.22 to 0.59]), LDL cholesterol (0.19 [0.04 to 0.30]), HDL cholesterol (0.14 [0.07 to 0.20]), triglycerides (0.17 [0.03 to 0.33]), fasting glucose (0.18 [0.03 to 0.33]), and 2-h glucose concentrations (0.33 [0.08 to 0.60]). Among 57 participants with CYP2B6 genotype data, associations between slow metabolizer genotypes and metabolic profiles were generally consistent with those for measured efavirenz concentrations.Higher plasma efavirenz concentrations are associated with higher plasma lipid and glucose concentrations. This may have implications for long-term cardiovascular complications of efavirenz-based ART, particularly among populations with high prevalence of CYP2B6 slow metabolizer genotypes. PMID:26765416

  13. Nicotine poisoning

    MedlinePlus

    Nicotine is found in: Chewing tobacco Cigarettes E-cigarettes Liquid nicotine Nicotine gum (Nicorette) Nicotine patches (Habitrol, Nicoderm) Pipe tobacco Some insecticides Tobacco leaves Note: This list may not be all-inclusive.

  14. Behavioral alteration of plasma phenylalanine concentration.

    PubMed

    Jevning, R; Pirkle, H C; Wilson, A F

    1977-11-01

    The concentration of 13 neutral and acidic plasma amino acids was measured before, during and after either 40 min of control relaxation or 40 min of the process known as transcendental meditation (TM). An electro-oculogram, electroencephalogram, and electromyogram were simultaneously monitored in these subjects. Increased phenylalanine concentration was noted during TM practice with no change during control relaxation; no difference between the groups of total time slept or sleep stage percent was observed. The stability of phenylalanine concentration in controls and lack of correlation of increased phenylalanine with sleep in the long-term practitioners seem to suggest a relationship of the phenylalanine increase to TM practice.

  15. Comparison of nicotine pharmacokinetics in healthy Japanese male smokers following application of the transdermal nicotine patch and cigarette smoking.

    PubMed

    Sobue, Satoshi; Sekiguchi, Kaneo; Kikkawa, Hironori; Akasaki, Moriaki; Irie, Shin

    2006-05-01

    Transdermal nicotine patch (TNP) contains approximately 16.6 and 24.9 mg of nicotine per 20 and 30 cm2 (TNP-20 and TNP-30). The aims of the study are to investigate linearity of nicotine pharmacokinetics after single application of different strengths of TNP and to directly compare plasma nicotine concentrations with those during cigarette smoking. Twelve healthy Japanese male smokers were randomly allocated to 1 of 2 cohorts consisting of 6 subjects each. Cohort 1 subjects received 1 sheet of TNP-20 (TNP-20x1) in period 1, and 2 sheets of TNP-20 (TNP-20x2) in period 3. Cohort 2 subjects were received 1 sheet of TNP-30 (TNP-30x1) in period 2, and smoked a total of 12 cigarettes at 1 h intervals in period 4. Each TNP was applied to the upper arm for 16 h. After TNP-20x1 or TNP-20x2 treatment in cohort 1, the amount of nicotine delivered from TNP (Dose) was proportional to surface area of TNP. Cmax and AUC of nicotine increased with the surface area (Dose), and tmax, t(1/2), CL/F and percentage of dose excreted in urine were almost the same between both treatments. These suggest the linear pharmacokinetics of nicotine in proportion to the surface area and Dose following single application of TNP in identical subjects. In cohort 2, the plasma nicotine concentrations after TNP-30x1 treatment were approximately half those just before each smoking.

  16. Factors influencing lopinavir and atazanavir plasma concentration

    PubMed Central

    Stöhr, Wolfgang; Back, David; Dunn, David; Sabin, Caroline; Winston, Alan; Gilson, Richard; Pillay, Deenan; Hill, Teresa; Ainsworth, Jonathan; Gazzard, Brian; Leen, Clifford; Bansi, Loveleen; Fisher, Martin; Orkin, Chloe; Anderson, Jane; Johnson, Margaret; Easterbrook, Philippa; Gibbons, Sara; Khoo, Saye

    2010-01-01

    Background The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in plasma concentration has been observed for both drugs. The aim of this study was to evaluate which demographic factors and concomitant drugs are associated with lopinavir and atazanavir plasma concentration. Methods Data from the Liverpool TDM (therapeutic drug monitoring) Registry were linked with the UK Collaborative HIV Cohort (CHIC) study. For each patient, the first measurement of lopinavir (twice daily) or atazanavir [once daily, ritonavir boosted (/r) or unboosted] plasma concentration was included. Linear regression was used to evaluate the association of dose, gender, age, weight, ethnicity and concomitant antiretroviral drugs or rifabutin with log-transformed drug concentration, adjusted for time since last intake. Results Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 on atazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors for lopinavir concentration: weight (11% decrease per additional 10 kg; P = 0.001); dose (25% increase for 533 mg/r; P = 0.024); and rifabutin (116% increase; P < 0.001). For atazanavir the predictors were dose (compared with 300 mg/r: 40% increase for 400 mg/r, 67% decrease for 400 mg; overall P < 0.001) and efavirenz (32% decrease; P = 0.016) but not tenofovir (P = 0.54). Conclusions This analysis confirms that efavirenz decreases atazanavir concentrations, and there was a negative association of weight and lopinavir concentrations. The strong impact of rifabutin on lopinavir concentration should be studied further. PMID:19897506

  17. Nicotine causes genotoxic damage but is not metabolized during long-term exposure of human nasal miniorgan cultures.

    PubMed

    Ginzkey, Christian; Steussloff, Gudrun; Koehler, Christian; Hackenberg, Stephan; Richter, Elmar; Hagen, Rudolf; Kleinsasser, Norbert H

    2014-08-17

    Human nasal miniorgan cultures (MOC) are a useful tool in ecogenotoxicology. Repetitive exposure to nicotine showed reversible DNA damage, and stable CYP2A6 expression was demonstrated in nasal MOC in previous investigations. The aim of the present study was to evaluate the genotoxic effect of nicotine in nasal MOC after chronic nicotine exposure, and to monitor possible metabolism capacities. MOC were dissected from human nasal mucosa and cultured under standard cell culture conditions. MOC were exposed to nicotine for 3 weeks at concentrations of 1 μM and 1 mM. The concentrations were chosen based on nicotine plasma levels in heavy smokers, and possible concentrations used in topical application of nicotine nasal spray. DNA damage was assessed by the comet assay at days 7, 14 and 21. Concentrations of nicotine and cotinine were analyzed in cell culture medium by gas chromatography/mass spectrometry to determine a possible metabolism of nicotine by MOC. Distinct DNA damage in MOC could be demonstrated after 1 week of exposure to 1 μM and 1 mM nicotine. This effect decreased after 2 and 3 weeks with no statistically relevant DNA migration. No nicotine metabolism could be detected by changes in nicotine and cotinine concentrations in the supernatants. This is the first time genotoxic effects have been evaluated in nasal MOC after chronic nicotine exposure for up to 3 weeks. Genotoxic effects were present after 1 week of culture with a decrease over time. Down-regulation of nicotinic acetylcholine receptors, which are expressed in nasal mucosa, may be a possible explanation. The lack of nicotine metabolism in this model could be explained by the functional loss of CYP2A6 during chronic nicotine exposure. Further investigations are necessary to provide a more detailed description of the underlying mechanisms involved in DNA damage by nicotine. PMID:24983901

  18. Do plasma melatonin concentrations decline with age?

    NASA Technical Reports Server (NTRS)

    Zeitzer, J. M.; Daniels, J. E.; Duffy, J. F.; Klerman, E. B.; Shanahan, T. L.; Dijk, D. J.; Czeisler, C. A.

    1999-01-01

    PURPOSE: Numerous reports that secretion of the putative sleep-promoting hormone melatonin declines with age have led to suggestions that melatonin replacement therapy be used to treat sleep problems in older patients. We sought to reassess whether the endogenous circadian rhythm of plasma melatonin concentration changes with age in healthy drug-free adults. METHODS: We analyzed the amplitude of plasma melatonin profiles during a constant routine in 34 healthy drug-free older subjects (20 women and 14 men, aged 65 to 81 years) and compared them with 98 healthy drug-free young men (aged 18 to 30 years). RESULTS: We could detect no significant difference between a healthy and drug-free group of older men and women as compared to one of young men in the endogenous circadian amplitude of the plasma melatonin rhythm, as described by mean 24-hour average melatonin concentration (70 pmol/liter vs 73 pmol/liter, P = 0.97), or the duration (9.3 hours vs 9.1 hours, P = 0.43), mean (162 pmol/liter vs 161 pmol/liter, P = 0.63), or integrated area (85,800 pmol x min/liter vs 86,700 pmol x min/liter, P = 0.66) of the nocturnal peak of plasma melatonin. CONCLUSION: These results do not support the hypothesis that reduction of plasma melatonin concentration is a general characteristic of healthy aging. Should melatonin replacement therapy or melatonin supplementation prove to be clinically useful, we recommend that an assessment of endogenous melatonin be carried out before such treatment is used in older patients.

  19. Bimodal concentration-response of nicotine involves the nicotinic acetylcholine receptor, transient receptor potential vanilloid type 1, and transient receptor potential ankyrin 1 channels in mouse trachea and sensory neurons.

    PubMed

    Kichko, Tatjana I; Lennerz, Jochen; Eberhardt, Mirjam; Babes, Ramona M; Neuhuber, Winfried; Kobal, Gerd; Reeh, Peter W

    2013-11-01

    High concentrations of nicotine, as in the saliva of oral tobacco consumers or in smoking cessation aids, have been shown to sensitize/activate recombinant transient receptor potential vanilloid type 1 (rTRPV1) and mouse TRPA1 (mTRPA1) channels. By measuring stimulated calcitonin gene-related peptide (CGRP) release from the isolated mouse trachea, we established a bimodal concentration-response relationship with a threshold below 10 µM (-)-nicotine, a maximum at 100 µM, an apparent nadir between 0.5 and 10 mM, and a renewed increase at 20 mM. The first peak was unchanged in TRPV1/A1 double-null mutants as compared with wild-types and was abolished by specific nicotinic acetylcholine receptor (nAChR) inhibitors and by camphor, discovered to act as nicotinic antagonist. The nicotine response at 20 mM was strongly pHe-dependent, - five times greater at pH 9.0 than 7.4, indicating that intracellular permeation of the (uncharged) alkaloid was required to reach the TRPV1/A1 binding sites. The response was strongly reduced in both null mutants, and more so in double-null mutants. Upon measuring calcium transients in nodose/jugular and dorsal root ganglion neurons in response to 100 µM nicotine, 48% of the vagal (but only 14% of the somatic) sensory neurons were activated, the latter very weakly. However, nicotine 20 mM at pH 9.0 repeatedly activated almost every single cultured neuron, partly by releasing intracellular calcium and independent of TRPV1/A1 and nAChRs. In conclusion, in mouse tracheal sensory nerves nAChRs are 200-fold more sensitive to nicotine than TRPV1/A1; they are widely coexpressed with the capsaicin receptor among vagal sensory neurons and twice as abundant as TRPA1. Nicotine is the major stimulant in tobacco, and its sensory impact through nAChRs should not be disregarded.

  20. Plasma prolactin concentrations in lead exposed workers.

    PubMed

    Govoni, S; Battaini, F; Fernicola, C; Castelletti, L; Trabucchi, M

    1987-01-01

    Plasma Prolactin (Prl) Zinc protoporphyrin (Zpp) and blood lead concentrations (PbB) were measured in 76 exposed male workers. All of them were employed in small (not more than 30 persons) pewter factories and were randomly selected from those regularly controlled by the National Health Service, Occupational Health Unit of Brescia (USSL 41). Although all plasma Prl values were within the normal range, the mean value of the subgroup having Zpp and PbB higher than 40 micrograms/dl was significantly higher (+47%) than that observed in the group of workers having Zpp and PbB less than 40 micrograms/dl. The data indicate the possibility of a lead-induced Prl secretion dysfunction, probably mediated by a decrease in dopaminergic inhibitory control.

  1. Plasma prolactin concentrations in lead exposed workers.

    PubMed

    Govoni, S; Battaini, F; Fernicola, C; Castelletti, L; Trabucchi, M

    1987-01-01

    Plasma Prolactin (Prl) Zinc protoporphyrin (Zpp) and blood lead concentrations (PbB) were measured in 76 exposed male workers. All of them were employed in small (not more than 30 persons) pewter factories and were randomly selected from those regularly controlled by the National Health Service, Occupational Health Unit of Brescia (USSL 41). Although all plasma Prl values were within the normal range, the mean value of the subgroup having Zpp and PbB higher than 40 micrograms/dl was significantly higher (+47%) than that observed in the group of workers having Zpp and PbB less than 40 micrograms/dl. The data indicate the possibility of a lead-induced Prl secretion dysfunction, probably mediated by a decrease in dopaminergic inhibitory control. PMID:3598878

  2. Increased hepatic nicotine elimination after phenobarbital induction in the conscious rat

    SciTech Connect

    Foth, H.; Walther, U.I.; Kahl, G.F. )

    1990-09-15

    Elimination parameters of (14C)nicotine in conscious rats receiving nicotine (0.3 mg/kg) either intravenously or orally were studied. The oral availability of unchanged nicotine, derived by comparison of the respective areas under the concentration vs time curves (AUC), was 89%, indicating low hepatic extraction ratios of about 10%. Pretreatment of rats with phenobarbital (PB) markedly increased hepatic first-pass extraction of nicotine. The oral availability of unchanged nicotine in plasma dropped to 1.4% of the corresponding values obtained from PB-treated rats receiving nicotine iv. After PB pretreatment, the clearance of iv nicotine was increased approximately twofold over controls, much less than the observed more than ninefold increase of hepatic first-pass extraction. It is assumed that extrahepatic metabolism contributed significantly to the rapid removal of nicotine from the plasma. The elimination of cotinine, originating from nicotine administered either po or iv, was significantly increased by PB pretreatment, as determined by the ratio of corresponding AUCs. The pattern of nicotine metabolites in urine also indicated an increase in the rate of cotinine metabolic turnover. The amount of norcotinine in the organic extract of urine paralleled PB microsomal enzyme induction. The ratio between urinary concentrations of the normetabolite and cotinine correlated strongly with the PB-induced state of rat liver. This may be a suitable indicator of PB-inducible hepatic cytochrome P450 isoenzyme(s). Since smoking habits in man are feedback-regulated by nicotine plasma concentrations, a similar increase of nicotine elimination by microsomal enzyme induction in man may be of relevance for tobacco consumption.

  3. Nicotine Lozenges

    MedlinePlus

    Nicotine lozenges are used to help people stop smoking. Nicotine lozenges are in a class of medications called smoking cessation aids. They work by providing nicotine to your body to decrease the withdrawal symptoms ...

  4. Effects of chronic nicotine ingestion on pressor response to Nomega-Nitro-L-arginine methyl ester and ex vivo concentration and relaxation response of aorta to L-arginine.

    PubMed

    Hui, S; Mei, Q; Qiu, B

    1997-12-01

    Effects of nitric oxide synthase inhibition on blood vessels were studied in nicotine-treated rats. Male Sprague-Dawley rats drank a nicotine solution with a concentration of 25 or 50 microg/ml for 15 days. The blood pressure and heart rate of chloralose-anaesthetized rats and isolated aortic strip contractions were measured. NomegaNitro-L-arginine methyl ester (L-NAME)-induced hypertension was significantly reduced after chronic nicotine treatment. The Emax of contractions of isolated aortic strips to noradrenaline were dose-dependently enhanced by nicotine and the potentiation was abolished by L-arginine. The relaxation of aortic strips to acetylcholine was significantly decreased in nicotine-treated rats, whereas L-arginine, but not D-arginine, reversed this action. Neither nicotine nor L-NAME affected the heart rate. The results show that chronic nicotine treatment reduced the pressor response of L-NAME.

  5. Cigarette nicotine yields and nicotine intake among Japanese male workers

    PubMed Central

    Ueda, K; Kawachi, I; Nakamura, M; Nogami, H; Shirokawa, N; Masui, S; Okayama, A; Oshima, A

    2002-01-01

    Objectives: To analyse brand nicotine yield including "ultra low" brands (that is, cigarettes yielding ≤ 0.1 mg of nicotine by Federal Trade Commission (FTC) methods) in relation to nicotine intake (urinary nicotine, cotinine and trans-3'-hydroxycotinine) among 246 Japanese male smokers. Design: Cross sectional study. Setting: Two companies in Osaka, Japan. Subjects: 130 Japanese male workers selected randomly during their annual regular health check up and 116 Japanese male volunteers taking part in a smoking cessation programme. Main outcome measurements: Subjects answered a questionnaire about smoking habits. Following the interview, each participant was asked to smoke his own cigarette and, after extinguishing it, to blow expired air into an apparatus for measuring carbon monoxide concentration. Urine was also collected for the assays of nicotine metabolites. Results: We found wide variation in urinary nicotine metabolite concentrations at any given nicotine yield. Based on one way analysis of variance (ANOVA), the urinary nicotine metabolite concentrations of ultra low yield cigarette smokers were significantly lower compared to smokers of high (p = 0.002) and medium yield cigarettes (p = 0.017). On the other hand, the estimated nicotine intake per ultra low yield cigarette smoked (0.59 mg) was much higher than the 0.1 mg indicated by machine. Conclusions: In this study of Japanese male smokers, actual levels of nicotine intake bore little relation to advertised nicotine yield levels. Our study reinforces the need to warn consumers of inappropriate advertisements of nicotine yields, especially low yield brands. PMID:11891369

  6. Waterpipe tobacco products: nicotine labelling versus nicotine delivery

    PubMed Central

    Vansickel, Andrea R; Shihadeh, Alan; Eissenberg, Thomas

    2013-01-01

    Background Waterpipe tobacco package labelling typically indicates “0.0% tar” and “0.05% or 0.5% nicotine”. Objective To determine the extent to which nicotine labeling is related to nicotine delivery. Methods 110 waterpipe smokers engaged in a 45-minute waterpipe smoking session. Puff topography and plasma nicotine were measured. Three waterpipe tobacco brands were used: Nakhla (0.5% nicotine), Starbuzz (0.05% nicotine), and Al Fakher (0.05% nicotine). Data were analyzed by one-way ANOVA. Results Topography did not differ across brands. Peak plasma nicotine varied significantly across brands. Al Fakher had the highest nicotine delivery (11.4 ng/ml) followed by Nakhla (9.8 ng/ml) and Starbuzz (5.8 ng/ml). Conclusions Nicotine labelling on waterpipe tobacco products does not reflect delivery; smoking a brand with a “0.05% nicotine” label led to greater plasma nicotine levels than smoking a brand with a “0.5% nicotine” label. Waterpipe tobacco products should be labelled in a manner that does not mislead consumers. PMID:21636612

  7. Clinical outcome of smoking-cessation trial of nicotine chewing gum evaluated by analysis of nicotine in hair.

    PubMed

    Mizuno, A; Uematsu, T; Ishikawa, T; Yoshimine, N; Nakashima, M

    1997-08-01

    The axial distribution of nicotine along the hair shafts was examined in 21 subjects enrolled in a placebo-controlled, double-blind trial of nicotine chewing gum (Nicorette) for validating their self-reported smoking behavior and their physicians' assessments. Hair samples obtained from the subjects once during the 3-month follow-up period (n = 10 for placebo and n = 11 for Nicorette ad libitum) were analyzed for the cm x cm distribution of nicotine along the hair shafts. Hair analysis results were compared with the monthly self-reports and with the plasma concentrations of thiocyanate (SCN-) measured at 1-month intervals. A gradual decrease in nicotine content along the hair shafts generally corresponded to the decrease in self-reported number of cigarettes smoked daily by the subjects who reported that they abstained from smoking or decreased the number of daily cigarettes in placebo and nicotine chewing gum groups. Because nicotine may dissociate slowly from hair follicle cells, nicotine in the hair did not mark a sudden decrease or cessation of smoking and, therefore, hair analysis tended to underestimate the real decrease of smoking. However, physician assessment seemed to depend solely on self-reporting because the time profile of changes in serum SCN- concentration did not correspond necessarily to the changes in the self-reported number of cigarettes used daily.

  8. Nicotine and sympathetic neurotransmission.

    PubMed

    Haass, M; Kübler, W

    1997-01-01

    Nicotine increases heart rate, myocardial contractility, and blood pressure. These nicotine-induced cardiovascular effects are mainly due to stimulation of sympathetic neurotransmission, as nicotine stimulates catecholamine release by an activation of nicotine acetylcholine receptors localized on peripheral postganglionic sympathetic nerve endings and the adrenal medulla. The nicotinic acetylcholine receptor is a ligand-gated cation channel with a pentameric structure and a central pore with a cation gate, which is essential for ion selectivity and permeability. Binding of nicotine to its extracellular binding site leads to a conformational change of the central pore, which results in the influx of sodium and calcium ions. The resulting depolarization of the sympathetic nerve ending stimulates calcium influx through voltage-dependent N-type calcium channels, which triggers the nicotine-evoked exocytotic catecholamine release. In the isolated perfused guinea-pig heart, cardiac energy depletion sensitizes cardiac sympathetic nerves to the norepinephrine-releasing effect of nicotine, as indicated by a leftward shift of the concentration-response curve, a potentiation of maximum transmitter release, and a delay of the tachyphylaxis of nicotine-evoked catecholamine release. This sensitization was also shown to occur in the human heart under in vitro conditions. Through the intracardiac release of norepinephrine, nicotine induces a beta-adrenoceptor-mediated increase in heart rate and contractility, and an alpha-adrenoceptor-mediated increase in coronary vasomotor tone. The resulting simultaneous increase in oxygen demand and coronary resistance has a detrimental effect on the oxygen balance of the heart, especially in patients with coronary artery disease. Sensitization of the ischemic heart to the norepinephrine-releasing effect of nicotine may be a trigger for acute cardiovascular events in humans, such as acute myocardial infarction and/or life

  9. Nicotine enantiomers and oxidative stress.

    PubMed

    Yildiz, D; Ercal, N; Armstrong, D W

    1998-09-15

    Nicotine affects a variety of cellular processes ranging from induction of gene expression to secretion of hormones and modulation of enzymatic activities. The objective of this study was to characterize the toxicity of nicotine enantiomers as well as their ability to induce oxidative stress in an in vitro model using Chinese hamster ovary (CHO) cells. Colony formation assay has demonstrated that (-)-nicotine is the more toxic of the enantiomers. At 6 mM concentrations, (-)-nicotine was found to be approximately 28- and 19-fold more potent than (+)-, and (+/-)-nicotine (racemic), respectively. Results also indicated that the toxicity of (+/-)-nicotine is higher than that of (+)-nicotine. (-)-Nicotine at a 10 mM concentration substantially decreased glutathione (GSH) levels (46% decrease). In addition, a 3-fold increase in malondialdehyde (MDA) level was evident in cells after exposure to 10 mM (-)-nicotine. Increased lactate dehydrogenase (LDH) activities in the media demonstrated that cellular membrane integrity was disturbed in nicotine treated cells. In the presence of superoxide dismutase (SOD) and catalase (CAT), the LDH activities returned to control value in 24 h with all concentrations of (-)-, (+)-, and (+/-)-nicotine. The decreases in LDH activities in the presence of the radical scavenging enzymes SOD and CAT suggest that membrane damage may be due to free radical generation. PMID:9865482

  10. Assessment of nicotine-induced DNA damage in a genotoxicological test battery.

    PubMed

    Ginzkey, Christian; Friehs, Gudrun; Koehler, Christian; Hackenberg, Stephan; Hagen, Rudolf; Kleinsasser, Norbert H

    2013-02-18

    The role of the tobacco-alkaloid nicotine in tumour biology is widely discussed in the literature. Due to a strong capacity to induce angiogenesis, a pro-mutagenic potential in non-tumour and cancer cells, and a pro- and anti-apoptotic influence, nicotine seems to promote the growth of established tumours. However, results indicating DNA damage and genetic instability associated with nicotine have been contradictory thus far. A variety of markers and endpoints of genotoxicity are required to characterize the genotoxic potential of nicotine. Induction of DNA single- and double-strand breaks, the formation of micronuclei, and the induction of sister chromatid exchange and chromosome aberrations represent possible genotoxicological endpoints at different cellular levels. Human lymphocytes were exposed to nicotine concentrations between 1μM and 1mM for 24h in vitro. The comet assay, the cytokinesis-block micronucleus test, the chromosome aberration (CA) test, and the sister chromatid exchange (SCE) test were then applied. Viability and apoptosis were measured by flow cytometry in combination with the annexin V-propidium iodide staining test. In this test setting, no enhanced DNA migration was measured by the comet assay. An increase in the micronucleus frequency was detected at a concentration of 100μM nicotine without affecting the frequency of apoptotic cells. A distinct genotoxic effect was determined by the CA test and the SCE test, with a significant increase in CA and SCE at a concentration of 1μM. In the annexin V test, nicotine did not influence the proportion of apoptotic or necrotic cells. The current data indicating the induction of CA by nicotine underscore the necessity of ongoing investigations on the potential of nicotine to initiate mutagenesis and tumour promotion. Taking into account the physiological nicotine plasma levels in smokers or in nicotine-replacement therapy, particularly the long-term use of nicotine should be critically discussed. PMID

  11. Ameliorative effect of sesame lignans on nicotine toxicity in rats.

    PubMed

    Chattopadhyay, Krishna; Mondal, Srinath; Chattopadhyay, Brajadulal; Ghosh, Santinath

    2010-11-01

    Nicotine causes oxidative and genotoxic damages in the tissues leading to several diseases. Any strategy through natural diet that prevents or slows the progression and severity of nicotine toxicity has a significant health impact. This work is designed to investigate natural antioxidants that play effective protective role against nicotine-induced toxicity. Experiments were conducted on male albino rats by injecting nicotine tartrate (3.5 mg/kg body wt./day for 15 days) subcutaneously and thereby supplementing sesame lignans (0.1 g/100g diet and 0.2 g/100g diet) orally to them. Significant (P<0.01) increase of total cholesterol, triglyceride, LDL-cholesterol, VLDL-cholesterol, decrease of HDL-cholesterol, decrease in antioxidant enzymes and increase in concentration of lipid peroxidative product has been observed in plasma due to nicotine toxicity. Significant (P<0.01) decrease of total DNA contents and highly significant (P<0.001) DNA damage of liver tissue is also observed on nicotine treatment. Sesame lignans minimizes the above mentioned effects. The nicotine-induced oxidative and genotoxic damages on the tissues can be effectively attenuated by sesame lignans supplemented diet. PMID:20804815

  12. SEASONAL VARIATION IN PLASMA SEX STEROID CONCENTRATION IN JUVENILE ALLIGATORS

    EPA Science Inventory

    Seasonal variation in plasma sex steroid concentrations is common in mature vertebrates, and is occasionally seen in juvenile animals. In this study, we examine the seasonal pattern of sex hormone concentration in juvenile American alligators (Alligator mississippiensis) and make...

  13. Effect of charge and lipid concentration on in-vivo percutaneous absorption of methyl nicotinate from liposomal vesicles.

    PubMed

    Puglia, Carmelo; Esposito, Elisabetta; Menegatti, Enea; Nastruzzi, Claudio; Rizza, Luisa; Cortesi, Rita; Bonina, Francesco

    2005-09-01

    We have investigated the influence of charge and lipid concentration on the in-vivo percutaneous absorption of a model compound, methyl nicotinate (MN), from liposomal vesicles. MN-loaded liposomes were produced by the reverse-phase evaporation method (REV) using different concentrations of phosphatidyl choline (PC), in association with surfactants such as dioctadecyl dimethyl ammonium bromide (DDAB18) and dicetyl phosphate (DCP), which impart a positive or negative charge to the systems, respectively. The liposomal suspensions were then processed to hydrogels and used to study in-vivo the MN permeation profile. MN was chosen as the model compound since it was capable of causing cutaneous erythema, the intensity and duration of which was proportional to the amount entering the living epidermis over time. The extent of the erythema was monitored by reflectance spectrophotometry, a non-invasive technique. In-vivo findings showed an interesting MN delayed release, which was proportional to the amount of phospholipids in each liposomal formulation. Furthermore, it could be noted that the erythematous effect was more prolonged when MN was delivered from neutral or negatively-charged liposomal forms.

  14. Continuous nicotine infusion reduces nicotine self-administration in rats with 23-h/day access to nicotine.

    PubMed

    LeSage, Mark G; Keyler, Dan E; Shoeman, Don; Raphael, Donna; Collins, Gregory; Pentel, Paul R

    2002-05-01

    The effects of continuous nicotine infusion on nicotine self-administration (NSA) were studied in rats as a model of nicotine replacement therapy (NRT) in humans. A NSA model in which rats had 23-h/day access to nicotine was used to approximate nicotine access conditions in cigarette smokers. In order to estimate serum nicotine concentrations associated with NSA, arterial and venous serum nicotine concentrations were measured during a simulation of NSA. Nicotine was noncontingently administered as 30 doses/12 h of 0.03 mg/kg/i.n.f. or 60 doses/12 h of 0.01 mg/kg/i.n.f. daily. Venous serum nicotine concentrations were measured after the first nicotine dose of the day, and arterial and venous concentrations were measured after doses in the middle of the day. The range of mean concentrations measured was similar to those reported in cigarette smokers (venous concentrations 6-59 ng/ml, arterial concentrations 42-96 ng/ml). The effects of continuous nicotine infusion on NSA were studied by noncontingently administering nicotine at various rates via osmotic pump to animals self-administering nicotine (0.01 or 0.03 mg/kg/i.n.f.) during 23-h/day sessions. Continuous nicotine infusion at all infusion rates substantially suppressed NSA, but suppression was rate-related only for the 0.01-mg/kg/inf NSA unit dose. Nicotine infusion rates producing venous serum nicotine concentrations equaling or exceeding the peak venous levels associated with simulated NSA were more effective than lower infusion rates only at the lower NSA unit dose. The highest nicotine infusion rate had no sustained effect on food-maintained responding, demonstrating its specificity for suppression of NSA. These data provide a model for studying NRT in the rat.

  15. [Plasma lipid concentration in smoking and nonsmoking male adults treated from alcohol addiction].

    PubMed

    Słodczyk, Ewa; Szołtysek-Bołdys, Izabela; Kozar-Konieczna, Aleksandra; Goniewicz, Jerzy; Ptak, Małgorzata; Olszowy, Zofia; Kośmider, Leon; Goniewicz, Maciej Łukasz; Sobczak, Andrzej

    2013-01-01

    Alcohol drinking and tobacco smoking affect plasma lipid levels and are both independent risk factors of cardiovascular diseases. Alcohol and nicotine addictions are more common among man than women in Poland. The aim of the study was to evaluate changes in plasma lipid levels after cessation of heavy drinking in smoking and nonsmoking Polish male adults. Subjects were recruited from individuals who participated in an inpatient addiction program following alcohol detoxification. We recruited 119 male adults: 48 non-smokers in age between 31 and 60 years (mean 48.7 +/- 8.8) and 71 smokers in age between 30 and 60 years (mean 46.1 +/- 7.8). Each subjects provided three blood samples: at baseline, after 3 weeks, and after 6 weeks of treatment. Plasma samples were analyzed for lipids by manual precipitation and automatic enzymatic methods. Changes in plasma lipid concentrations were analyzed using two-way analysis of variances with repeated measures with smoking status as between subjects factor and time post alcohol cessation as within-subject factors. All analyses were adjusted for age, and BMI. We found that plasma levels of HDL decreased in smoking and nonsmoking subjects by 30% and 24%, respectively (p < 0.001). In smoking subjects, plasma levels of triglycerides and LDL increased significantly after 6 weeks post cessation of heavy drinking cessation by 17% and 16%, respectively (p = 0.001). We also found that total cholesterol levels remained high in smoking subjects, but decreased significantly by 7% (p = 0.022) in nonsmoking subjects after 6 weeks post cessation of heavy drinking. We concluded that cigarette smoking increased LDL and inhibited the decline in plasma cholesterol among subjects addicted to alcohol following cessation of heavy drinking. Alcohol addiction therapy should be complemented with smoking cessation to prevent increase in cardiovascular risk.

  16. [Nicotine dependence].

    PubMed

    Kawazoe, Shingo; Shinkai, Takahiro

    2015-09-01

    Smoking is the most widespread addictive behavior in the world, and it causes physical and psychological dependence on nicotine. As for physical nicotine dependence, nicotine produces rewarding effects by interacting with nicotinic acetylcholine receptors on neurons in the brain's reward system. Psychological dependence on nicotine comes with a complex psychological procedure that is based on distorted cognition which justifies their smoking behavior. Clinicians should support smokers with willingness to quit smoking comprehensively with this knowledge, although the success rate of smoking cessation is no ideal in general. PMID:26394514

  17. Secondhand smoke exposure and risk following the Irish smoking ban: an assessment of salivary cotinine concentrations in hotel workers and air nicotine levels in bars

    PubMed Central

    Mulcahy, M; Evans, D; Hammond, S; Repace, J; Byrne, M

    2005-01-01

    Objective: To investigate whether the Irish smoking ban has had an impact on secondhand smoke (SHS) exposures for hospitality workers. Design, setting, and participants: Before and after the smoking ban a cohort of workers (n = 35) from a sample of city hotels (n = 15) were tested for saliva cotinine concentrations and completed questionnaires. Additionally, a random sample (n = 20) of city centre bars stratified by size (range 400–5000 square feet), were tested for air nicotine concentrations using passive samplers before and after the ban. Main outcome measures: Salivary cotinine concentrations (ng/ml), duration of self reported exposures to secondhand smoke, air nicotine (µg/cubic metre). Results: Cotinine concentrations reduced by 69%, from 1.6 ng/ml to 0.5 ng/ml median (SD 1.29; p < 0.005). Overall 74% of subjects experienced decreases (range 16–99%), with 60% showing a halving of exposure levels at follow up. Self reported exposure to SHS at work showed a significant reduction from a median 30 hours a week to zero (p < 0.001). There was an 83% reduction in air nicotine concentrations from median 35.5 µg/m3 to 5.95 µg/m3 (p < 0.001). At baseline, three bars (16%) were below the 6.8 µg/m3 air nicotine significant risk level for lung cancer alone; at follow up this increased to 10 (53%). Conclusions: Passive smoking and associated risks were significantly reduced but not totally eliminated. Exposure to SHS is still possible for those working where smoking is still allowed and those working where smoke may migrate from outdoor areas. Further research is required to assess the true extent and magnitude of these exposures. PMID:16319361

  18. Intracellular accumulation of boceprevir according to plasma concentrations and pharmacogenetics.

    PubMed

    Cusato, Jessica; Allegra, Sarah; De Nicolò, Amedeo; Boglione, Lucio; Fatiguso, Giovanna; Abdi, Adnan Mohamed; Cariti, Giuseppe; Di Perri, Giovanni; D'Avolio, Antonio

    2015-06-01

    Boceprevir (BOC) is a directly-acting antiviral agent for the treatment of hepatitis C virus genotype 1 (HCV-1) infection. It is a mixture of two stereoisomers, the inactive R and the active S isomers. No data have previously been published on BOC intracellular accumulation. In this study, BOC isomer concentrations in peripheral blood mononuclear cells (PBMCs) and plasma were determined. The influence of various single nucleotide polymorphisms (SNPs) on plasma and intracellular drug exposure at Week 4 of triple therapy were also evaluated. Plasma and intracellular BOC concentrations were determined at the end of the dosing interval (C(trough)) using a UPLC-MS/MS validated method. Allelic discrimination was performed through real-time PCR. Median plasma concentrations were 65.97 ng/mL for the S isomer and 36.31 ng/mL for the R isomer; the median S/R plasma concentration ratio was 1.66. The median PBMC concentration was 2285.88 ng/mL for the S isomer; the R isomer was undetectable within PBMCs. The median S isomer PBMC/plasma concentration ratio was 28.59. A significant positive correlation was found between plasma and PBMC S isomer concentrations. ABCB1 1236, SLC28A2 124 and IL28B rs12979860 SNPs were associated with the S isomer PBMC/plasma concentration ratio. In regression models, S isomer plasma levels and FokI polymorphism were able to predict S isomer intracellular exposure, whereas SNPs in AKR1, BCRP1 and SLC28A2 predicted the S isomer PBMC/plasma concentration ratio. No similar data regarding BOC pharmacogenetics and pharmacokinetics have been published previously. This study adds a novel and useful overview of the pharmacological properties of this drug. PMID:25836019

  19. Intracellular accumulation of boceprevir according to plasma concentrations and pharmacogenetics.

    PubMed

    Cusato, Jessica; Allegra, Sarah; De Nicolò, Amedeo; Boglione, Lucio; Fatiguso, Giovanna; Abdi, Adnan Mohamed; Cariti, Giuseppe; Di Perri, Giovanni; D'Avolio, Antonio

    2015-06-01

    Boceprevir (BOC) is a directly-acting antiviral agent for the treatment of hepatitis C virus genotype 1 (HCV-1) infection. It is a mixture of two stereoisomers, the inactive R and the active S isomers. No data have previously been published on BOC intracellular accumulation. In this study, BOC isomer concentrations in peripheral blood mononuclear cells (PBMCs) and plasma were determined. The influence of various single nucleotide polymorphisms (SNPs) on plasma and intracellular drug exposure at Week 4 of triple therapy were also evaluated. Plasma and intracellular BOC concentrations were determined at the end of the dosing interval (C(trough)) using a UPLC-MS/MS validated method. Allelic discrimination was performed through real-time PCR. Median plasma concentrations were 65.97 ng/mL for the S isomer and 36.31 ng/mL for the R isomer; the median S/R plasma concentration ratio was 1.66. The median PBMC concentration was 2285.88 ng/mL for the S isomer; the R isomer was undetectable within PBMCs. The median S isomer PBMC/plasma concentration ratio was 28.59. A significant positive correlation was found between plasma and PBMC S isomer concentrations. ABCB1 1236, SLC28A2 124 and IL28B rs12979860 SNPs were associated with the S isomer PBMC/plasma concentration ratio. In regression models, S isomer plasma levels and FokI polymorphism were able to predict S isomer intracellular exposure, whereas SNPs in AKR1, BCRP1 and SLC28A2 predicted the S isomer PBMC/plasma concentration ratio. No similar data regarding BOC pharmacogenetics and pharmacokinetics have been published previously. This study adds a novel and useful overview of the pharmacological properties of this drug.

  20. Evaluation of a Novel Nicotine Inhaler Device: Part 1—Arterial and Venous Pharmacokinetics

    PubMed Central

    Hearn, Alex; Redfern, Andrew

    2015-01-01

    Introduction: In the United Kingdom, licensed nicotine-containing products can be recommended to reduce the harm associated with smoking. Many smokers find currently available nicotine replacement products unsatisfactory. The arterial and venous pharmacokinetics (PK) of nicotine delivered via a novel inhaler device were determined. Methods: Results are reported for Parts A (N = 18) and C (N = 18) of a 4-part (A–D) Phase I study. Participants (18–55 years, ≥10 cigarettes/day, smoking within 1hr of waking, expired carbon monoxide >10 ppm on screening) orally inhaled 2 single doses of nicotine (2 of 3 dose levels [0.22, 0.45, and 0.67 mg]) (Part A) and repeated hourly doses of 0.67mg nicotine for 12hr (Part C), via the novel device. Arterial and venous PK and tolerability were assessed. Results: In Part A, mean arterial plasma nicotine concentrations at 2min after the start of inhalation were 1.10, 2.06, and 2.59ng/mL for the 0.22, 0.45, and 0.67mg doses, respectively. Mean maximum arterial plasma nicotine concentrations (C max) were 2.11, 3.73, and 4.38ng/mL and mean times to C max were 10.2, 7.3, and 6.5min after the start of inhalation for the 0.22, 0.45, and 0.67mg doses, respectively. In Part C, the mean pre- and postdose venous plasma nicotine concentration increased steadily and fluctuated in the range 8–10mg/mL after 9hr. The novel device was well tolerated; most adverse events were mild. Conclusion: The novel inhaler device delivers nicotine rapidly into the systemic circulation and offers a viable alternative to cigarettes for those finding it difficult to quit the behavioral and sensorial aspects of smoking. PMID:25385878

  1. Plasma amylin and insulin concentrations in normoglycemic and hyperglycemic cats.

    PubMed Central

    Lutz, T A; Rand, J S

    1996-01-01

    The recently discovered pancreatic peptide amylin is postulated to be involved in the pathogenesis of feline diabetes mellitus. However, plasma amylin concentrations in normal and diabetic cats have not yet been published. The aim of the present study was to validate a commercial amylin radioimmunoassay kit for the measurement of feline amylin in unextracted plasma, and to measure plasma amylin concentrations in normal and diabetic cats. The kit had satisfactory specificity, sensitivity, accuracy, and precision, and can be recommended for measurement of feline amylin in unextracted EDTA plasma, when nonspecific binding of plasma samples is used in the calculation of measured amylin concentration. Fasting amylin concentration in cats with normal glucose tolerance was 97 +/- 4 pmol/L. Plasma amylin increased in parallel with insulin after glucose administration in cats with normal and impaired glucose tolerance. In contrast to cats with normal glucose tolerance, cats with impaired glucose tolerance had markedly delayed amylin and insulin secretion. Diabetic cats had basal hypoinsulinemia combined with hyperamylinemia. Hyperamylinemia may lead to reduced insulin secretion and insulin resistance, and contribute to the development of feline diabetes. In conclusion, feline amylin can be measured in unextracted EDTA plasma. Fasting amylin concentrations are approximately 100 pmol/L, and amylin and insulin are cosecreted in cats with normal and impaired glucose tolerance. Increased amylin concentrations may contribute to the development of feline diabetes mellitus. PMID:8746416

  2. Partition functions and concentrations in plasmas out of thermal equilibrium

    SciTech Connect

    Andre, P.

    1995-06-01

    Taking into account the disequilibrium between the temperatures (electronic, rotational, vibrational, translational) in a nitrogen-plasma out of thermal equilibrium, different partition function and chemical potential calculation method are described and applied. From the variation of the temperature hypotheses, their influence on the plasma concentration is shown.

  3. Dietary determinants of plasma homocysteine concentrations.

    PubMed

    Verhoef, Petra; de Groot, Lisette C P G M

    2005-05-01

    Severe hyperhomocysteinemia is typically caused by rare enzymatic defects or by renal failure. In contrast, mild to moderate hyperhomocysteinemia chiefly results from suboptimal status of nutritional factors involved in homocysteine metabolism. Low dietary intake of folate is the most important nutritional cause of elevated homocysteine (tHcy) concentrations. Folic acid is more effective than dietary folate in lowering tHcy concentrations, and a daily dose of 400 mug of folic acid is the minimum daily dose associated with the maximum tHcy-lowering effect ( approximately 20-25% reduction). Mean fasting tHcy concentrations have dropped substantially in populations with mandatory folic acid fortification, and other B-vitamins, such as vitamin B (12), are important determinants of tHcy levels in this setting. Vitamins B (2) and B (6) have little influence on fasting tHcy concentrations, although the former may be relevant in individuals with the MTHFR 677 TT-genotype, and the latter may improve tHcy catabolism in elderly individuals. Betaine and choline can lower fasting tHcy concentrations to a similar extent as folic acid, particularly in the setting of a high intake of methionine. Consumption of tea and coffee increase tHcy concentrations by up to 20%. A high-protein meal also increases tHcy, but these changes are transient, and levels return to normal after an overnight fast. Serine and cystine also influence the methionine-induced postprandial rise in tHcy concentrations. In conclusion, alteration in dietary intake or use of folic acid supplements can substantially lower tHcy concentrations. However, it is not known whether lowering tHcy levels can reduce the risk of cardiovascular disease or cognitive decline or prevent pregnancy complications or osteoporosis. PMID:16047264

  4. Prospective determination of plasma imipenem concentrations in critically ill children.

    PubMed

    Giannoni, Eric; Moreillon, Philippe; Cotting, Jacques; Moessinger, Adrien; Bille, Jacques; Décosterd, Laurent; Zanetti, Giorgio; Majcherczyk, Paul; Bugnon, Denis

    2006-07-01

    Plasma imipenem concentrations were measured in 19 critically ill children (median age, 0.8 year; range, 0.02 to 12.9 years). Wide interindividual variations (2 to 4x at peak and >10x at trough concentrations) resulted in unpredictable plasma levels in several children. To avoid subtherapeutic drug levels, we recommend treatment with at least 100 mg/kg of body weight/day of imipenem-cilastatin for critically ill children requiring such therapy.

  5. Simultaneous determination of nicotinic acid and its four metabolites in rat plasma using high performance liquid chromatography with tandem mass spectrometric detection (LC/MS/MS).

    PubMed

    Szafarz, Malgorzata; Lomnicka, Magdalena; Sternak, Magdalena; Chlopicki, Stefan; Szymura-Oleksiak, Joanna

    2010-04-01

    A sensitive and specific liquid chromatography electrospray ionization-tandem mass spectrometry method for the simultaneous quantitation of nicotinic acid (NicA) and its metabolites nicotinamide (NA), 1-methylnicotinamide (MNA), 1-methyl-2-pyridone-5-carboxamide (M2PY) and 1-methyl-4-pyridone-5-carboxamide (M4PY) in rat plasma has been developed and validated. As an internal standard, 6-chloronicotinamide was used. The samples (100 microL) were subjected to deproteinization with acetonitrile (200 microL) and then, after centrifugation, 150 microL of the supernatant was transferred into conical vial and evaporated. Dry residue was reconstituted in 100 microL of the ACN/water (10:90, v/v) mixture. Chromatography was performed on a Waters Spherisorb 5 microm CNRP 4.6 x 150 mm analytical column with gradient elution using a mobile phase containing acetonitrile and water with 0.1% of formic acid. The full separation of all compounds was achieved within 15 min of analysis. Detection was performed by an Applied Biosystems MDS Sciex API 2000 triple quadrupole mass spectrometer set at unit resolution. The mass spectrometer was operated in the selected reactions monitoring mode (SRM), monitoring the transition of the protonated molecular ions m/z 153-110 for M2PY, 153-136 for M4PY, 124-80 for NicA, 123-80 for NA and 137-94 for MNA. The mass spectrometric conditions were optimized for each compound by continuously infusing the standard solution at the rate of 5 microL/min using a Harvard infusion pump. Electrospray ionization (ESI) was used for ion production. The instrument was coupled to an Agilent 1100 LC system. The precision and accuracy for both intra- and inter-day determination of all analytes ranged from 1.3% to 13.3% and from 94.43% to 110.88%. No significant matrix effect (ME) was observed. Stability of compounds was established in a battery of stability studies, i.e. bench-top, autosampler and long-term storage stability as well as freeze/thaw cycles. The method

  6. Measurement of plasma adenosine concentration: methodological and physiological considerations

    SciTech Connect

    Gewirtz, H.; Brown, P.; Most, A.S.

    1987-05-01

    This study tested the hypothesis that measurements of plasma adenosine concentration made on samples of blood obtained in dipyridamole and EHNA (i.e., stopping solution) may be falsely elevated as a result of ongoing in vitro production and accumulation of adenosine during sample processing. Studies were performed with samples of anticoagulated blood obtained from anesthesized domestic swine. Adenosine concentration of ultra filtrated plasma was determined by HPLC. The following parameters were evaluated: (i) rate of clearance of (/sup 3/H)adenosine added to plasma, (ii) endogenous adenosine concentration of matched blood samples obtained in stopping solution alone, stopping solution plus EDTA, and perchloric acid (PCA), (iii) plasma and erythrocyte endogenous adenosine concentration in nonhemolyzed samples, and (iv) plasma adenosine concentration of samples hemolyzed in the presence of stopping solution alone or stopping solution plus EDTA. We observed that (i) greater than or equal to 95% of (/sup 3/H)adenosine added to plasma is removed from it by formed elements of the blood in less than 20 s, (ii) plasma adenosine concentration of samples obtained in stopping solution alone is generally 10-fold greater than that of matched samples obtained in stopping solution plus EDTA, (iii) deliberate mechanical hemolysis of blood samples obtained in stopping solution alone resulted in substantial augmentation of plasma adenosine levels in comparison with matched nonhemolyzed specimens--addition of EDTA to stopping solution prevented this, and (iv) adenosine content of blood samples obtained in PCA agreed closely with the sum of plasma and erythrocyte adenosine content of samples obtained in stopping solution plus EDTA.

  7. Nicotine dependence and psychiatric disorders.

    PubMed

    Salín-Pascual, Rafael J; Alcocer-Castillejos, Natasha V; Alejo-Galarza, Gabriel

    2003-01-01

    , concentration, and memory. Finally there are several strategies to deal with nicotine dependence, Nicotine Replacement Therapy (NRT), which are nicotine chewing-gum, transdermal nicotine patches, and nicotine inhalators device. Also some antidepressants like bupropion has shown to be effective in smoking cessation treatment. To know more about nicotine phenomenon would be important, because that will allow a more mature perspective about the damage and beneficial effects of that substance. PMID:15011738

  8. Plasma concentrations of endothelin in patients with abnormal vascular reactivity

    SciTech Connect

    Predel, H.G.; Meyer-Lehnert, H.; Baecker, A.; Stelkens, H.; Kramer, H.J. )

    1990-01-01

    We measured circulating concentrations of endothelin in healthy subjects and in patients with abnormal vascular reactivity. Endothelin concentrations were determined by radioimmunoassay after extraction of plasma using Sep-Pak C-18 cartridges in healthy subjects, in patients with diabetes mellitus type I, in patients with mild to moderate essential hypertension and in non-dialyzed patients with stable chronic renal failure. Plasma concentrations were similar in healthy controls, in diabetics and in hypertensive patients averaging 5.0{plus minus}0.6 pg/ml, 4.7{plus minus}0.2 pg/ml and 6.5{plus minus}1.0 pg/ml, respectively. In contrast, plasma concentrations of endothelin were markedly elevated in patients with chronic renal failure averaging 16.6{plus minus}2.9 pg/ml. No correlations were observed between serum creatinine concentrations ranging from 124 to 850 {mu}mol/l or blood pressure and plasma concentrations of endothelin. Bicycle ergometric exercise in six healthy subjects and an acute modest i.v. saline load of 1,000 ml of 0.45% NaCl administered within 60 min in six patients with mild essential hypertension did not affect plasma concentrations of endothelin.

  9. A randomised, crossover study on an electronic vapour product, a nicotine inhalator and a conventional cigarette. Part A: Pharmacokinetics.

    PubMed

    Walele, Tanvir; Sharma, Girish; Savioz, Rebecca; Martin, Claire; Williams, Josie

    2016-02-01

    The pharmacokinetic (PK) profile of nicotine delivered by an Electronic Vapour Product (EVP) was characterised in a 2-part study in smokers. The study was designed as a randomised, controlled, four-way crossover trial. Part 1 compared an unflavoured e-liquid (UF2.0%) and a flavoured e-liquid (FL2.0%) to a conventional cigarette (CC; JPS Silver King Size, 0.6 mg) and a licensed nicotine inhalator (Nicorette(®); 15 mg). Part 2 compared e-liquids with increasing nicotine concentrations (0%, 0.4%, 0.9%, 2.0%). Subjects used each different product for a daily use session. In Part 1, maximum plasma nicotine concentration (Cmax) for UF2.0%, FL2.0%, Nicorette(®) and CC was 3.6, 2.5, 2.5 and 21.2 ng/mL, respectively. The time to maximum plasma nicotine concentration (Tmax) was longer for the EVP (UF2.0%, 9.0 min; FL2.0%, 10.0 min) and the nicotine inhalator (13.0 min) compared to CC (3.0 min). In Part 2, EVP with 0%, 0.4%, 0.9% and 2.0% nicotine produced Cmax values of 0.6, 1.0, 1.9 and 3.6 ng/mL, respectively. At the maximum nicotine concentration of 2% as prescribed by the European Tobacco Directive, the EVP achieved nicotine delivery that was comparable to the inhalator. EVPs thus offer a potential alternative to nicotine inhalator devices for those finding it difficult to quit smoking.

  10. Nicotine replacement therapy

    MedlinePlus

    Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012 Nov 14;11: ...

  11. Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos

    SciTech Connect

    Qiao, Dan; Seidler, Frederic J.; Slotkin, Theodore A. . E-mail: t.slotkin@duke.edu

    2005-08-01

    Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their differences in structure and mechanism of action, share many aspects for damage to the developing brain. Both are thought to generate oxidative radicals; in the current study, we evaluated their ability to produce lipid peroxidation in two in vitro models of neural cell development (PC12 and SH-SY5Y cells) and for nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos, in concentrations relevant to human exposures, elicited an increase in thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect that was prevented by addition of the antioxidant, Vitamin E. Initiating differentiation with nerve growth factor, which enhances nicotinic acetylcholine receptor expression, increased the TBARS response to nicotine but not chlorpyrifos, suggesting that the two agents act by different originating mechanisms to converge on the endpoint of oxidative damage. Furthermore, nicotine protected the cells from oxidative damage evoked by chlorpyrifos and similarly blocked the antimitotic effect of chlorpyrifos. Treatment of adolescent rats with nicotine elicited increases in TBARS in multiple brain regions when given in doses that simulate plasma nicotine concentrations found in smokers or at one-tenth the dose. Our results indicate that nicotine and chlorpyrifos elicit oxidative damage to developing neural cells both in vitro and in vivo, a mechanism that explains some of the neurodevelopmental endpoints that are common to the two agents. The balance between neuroprotectant and neurotoxicant actions of nicotine may be particularly important in situations where exposure to tobacco smoke is combined with other prooxidant insults.

  12. Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.

    PubMed

    Qiao, Dan; Seidler, Frederic J; Slotkin, Theodore A

    2005-08-01

    Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their differences in structure and mechanism of action, share many aspects for damage to the developing brain. Both are thought to generate oxidative radicals; in the current study, we evaluated their ability to produce lipid peroxidation in two in vitro models of neural cell development (PC12 and SH-SY5Y cells) and for nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos, in concentrations relevant to human exposures, elicited an increase in thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect that was prevented by addition of the antioxidant, Vitamin E. Initiating differentiation with nerve growth factor, which enhances nicotinic acetylcholine receptor expression, increased the TBARS response to nicotine but not chlorpyrifos, suggesting that the two agents act by different originating mechanisms to converge on the endpoint of oxidative damage. Furthermore, nicotine protected the cells from oxidative damage evoked by chlorpyrifos and similarly blocked the antimitotic effect of chlorpyrifos. Treatment of adolescent rats with nicotine elicited increases in TBARS in multiple brain regions when given in doses that simulate plasma nicotine concentrations found in smokers or at one-tenth the dose. Our results indicate that nicotine and chlorpyrifos elicit oxidative damage to developing neural cells both in vitro and in vivo, a mechanism that explains some of the neurodevelopmental endpoints that are common to the two agents. The balance between neuroprotectant and neurotoxicant actions of nicotine may be particularly important in situations where exposure to tobacco smoke is combined with other prooxidant insults. PMID:15963341

  13. Plasma glutamine concentration in spinal cord injured patients.

    PubMed

    Rogeri, P S; Costa Rosa, L F B P

    2005-09-23

    Glutamine, a non-essential amino acid, is the most important source of energy for macrophages and lymphocytes. Reduction in its plasma concentration is related with loss of immune function, as leukocyte proliferation and cytokine production. It is well known that glutamine is largely produced by the skeletal muscle which is severely compromised as a consequence of the paralysis due to the damage of the spinal cord. In spinal cord injury (SCI) patients, infections, such as pneumonia and sepsis in general, are a major cause of morbidity and mortality. In comparison with the control group, a 54% decrease in plasma glutamine concentration was observed as well as a decrease in the production of TNF and IL-1 by peripheral blood mononuclear cells cultivated for 48 h in SCI patients. Therefore, we propose that a decrease in plasma glutamine concentration is an important contributor to the immunosuppression seen in SCI patients. PMID:16024049

  14. Nicotine Withdrawal

    PubMed Central

    McLaughlin, Ian; Dani, John A.; De Biasi, Mariella

    2015-01-01

    An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks. While the severity of withdrawal symptoms is largely determined by how nicotine is consumed, certain short nucleotide polymorphisms (SNPs) have been shown to predispose individuals to consume larger amounts of nicotine more frequently—as well as to more severe symptoms of withdrawal when trying to quit. Additionally, rodent behavioral models and transgenic mouse models have revealed that specific nicotinic acetylcholine receptor (nAChR) subunits, cellular components, and neuronal circuits are critical to the expression of withdrawal symptoms. Consequently, by continuing to map neuronal circuits and nAChR subpopulations that underlie the nicotine withdrawal syndrome—and by continuing to enumerate genes that predispose carriers to nicotine addiction and exacerbated withdrawal symptoms—it will be possible to pursue personalized therapeutics that more effectively treat nicotine addiction. PMID:25638335

  15. Photovoltaic concentrator pointing dynamics and plasma interaction study

    SciTech Connect

    Stern, T.G.

    1984-01-01

    The objectives of this experiment are to use the Space Technology Experiments Platform (STEP) system to demonstrate the viability of concentrator photovoltaic arrays by: (1) configuring a deployable mast on the STEP pallet with concentrator mass models and some active photovoltaic modules (2) measuring the array pointing dynamics under normal rotation as well as disturbance conditions (3) performing an array plasma interaction experiment to determine the steady-state plasma losses under various voltage conditions and (4) providing active distributed control of the support truss to determine the improvement in dynamic response. Experiment approach and test control and instrumentation are described.

  16. Chronic oral nicotine administration affects the circadian rhythm of dopamine and 5-hydroxytryptamine metabolism in the striata of mice.

    PubMed

    Pietila, K; Laakso, I; Ahtee, L

    1995-12-01

    The effect of chronic oral administration of nicotine on the circadian rhythm of striatal dopamine (DA) and 5-hydroxytryptamine (5-HT) was studied in mice. Mice receiving nicotine in their drinking water and control mice drinking tap water were killed at 05:00, 11:00, 15:00 or 21:00 hours on the 50th day of chronic administration. The plasma concentrations of nicotine and cotinine, as well the striatal concentrations of DA, 5-HT and their metabolites 3,4 dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), homovanilic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated. The largest plasma concentrations of nicotine and cotinine were found at 05:00, when they were more than double the concentrations found at the other times studied. This indicates that the mice, typically for nocturnal animals, consumed most of their daily drinking water at night. In the control mice, the striatal DA and 3-MT concentrations showed circadian variation and were lowest at 11:00. The 5-HIAA concentrations also varied, being highest at 11:00. In the nicotine-treated mice the circadian variations in striatal monoamines were altered and more pronounced than in the controls. The concentrations of DA, DOPAC, HVA and 5-HIAA were highest at 11:00 and that of 5-HT at 21:00. The striatal DA, DOPAC, HVA and 5-HIAA concentrations in the nicotine-treated mice were significantly higher at 11:00 and the 5-HT concentrations at 21:00 than in the control mice, and, in contrast to the control mice, in the mice treated with chronic nicotine no circadian rhythm was observed in the 3-MT. No elevation of striatal DA metabolites occurred in the nicotine-treated mice compared with the controls when the plasma nicotine concentration was at its peak at 05:00. This finding suggests development of tolerance to the nicotine-induced changes in striatal DA metabolism. Further, our findings suggest that the chronic administration of nicotine in the drinking water of mice alters the circadian

  17. Nicotine Gum

    MedlinePlus

    ... program, which may include support groups, counseling, or specific behavioral change techniques. Nicotine gum is in a ... at room temperature and away from light, excess heat and moisture (not in the bathroom). Throw away ...

  18. Pharmacokinetics of nicotine in rats after multiple-cigarette smoke exposure

    SciTech Connect

    Rotenberg, K.S.; Adir, J.

    1983-06-15

    The pharmacokinetics of nicotine and its major metabolites was evaluated in male rats after multiple-cigarette smoke exposure. A smoke-exposure apparatus was used to deliver cigarette smoke to the exposure chamber. The rats were exposed to smoke from a single cigarette every 8 hr for 14 days and to the smoke of a cigarette spiked with radiolabeled nicotine on the 15th day. Blood and urine samples were collected at timed intervals during the 10-min smoke-exposure period of the last cigarette and up to 48 hr thereafter. Nicotine, cotinine, and other polar metabolites were separated by thin-layer chromatography and quantified by liquid scintillation counting. The data were analyzed by computer fitting, and the derived pharmacokinetic parameters were compared to those observed after a single iv injection of nicotine and after a single-cigarette smoke exposure. The results indicated that the amount of nicotine absorbed from multiple-cigarette smoke was approximately 10-fold greater than that absorbed from a single cigarette. Also, unlike the single-cigarette smoke exposure experiment, nicotine plasma levels did not decay monotonically but increased after the 5th hr, and high plasma concentrations persisted for 30 hr. The rate and extent of the formation of cotinine, the major metabolite of nicotine, were decreased as compared with their values following a single-cigarette smoke exposure. It was concluded that nicotine or a constituent of tobacco smoke inhibits the formation of cotinine and may affect the biotransformation of other metabolites. Urinary excretion tended to support the conclusions that the pharmacokinetic parameters of nicotine and its metabolites were altered upon multiple as compared to single dose exposure.

  19. Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats

    PubMed Central

    Pravetoni, M; Keyler, DE; Raleigh, MD; Harris, AC; LeSage, MG; Mattson, CK; Pettersson, S; Pentel, PR

    2011-01-01

    Preclinical models of nicotine vaccine pharmacology have relied on i.v. or s.c. administration of nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. Nicotine vaccine effects were examined in rats using two cigarette smoke exposure models: a 10 minute nose-only exposure (NSE) producing serum nicotine levels equivalent to the nicotine boost from 1 cigarette in a smoker, and a two hour whole-body exposure (WBE) producing serum nicotine levels similar to those associated with regular midday smoking. Vaccination prior to 10 min smoke NSE reduced nicotine distribution to brain by 90%, comparable to its effect on nicotine administered i.v. Vaccination prior to 2 hr smoke WBE reduced nicotine distribution to brain by 35%. The nicotine concentration in broncheoalveolar lavage (BAL) fluid obtained after 2 hr WBE was increased by 230% in vaccinated rats but was also increased in rats passively immunized with a nicotine-specific monoclonal antibody, and so was likely due to transfer of antibody from serum rather than local production at the pulmonary mucosa. Nicotine-specific IgA was not detectable in BAL fluid, but titers in serum were appreciable at 21–25% of the IgG titer and could contribute to vaccine efficacy. Both vaccination and passive immunization are effective in reducing nicotine distribution to brain in rats when nicotine is delivered via inhaled cigarette smoke. These data validate results previously obtained in rodents for nicotine vaccines using i.v. or s.c. nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation. PMID:21333633

  20. Nicotine levels in indoor athletic centres.

    PubMed

    Michael, C M; Demetriou, E; Kosmas, V; Krashia, A; Akkelidou, D

    1996-12-01

    The levels of nicotine during athletic events were measured at six indoor athletic centres in Cyprus. Samples of air were pumped through a tube containing XAD-4 resin. Quantitation of nicotine was carried out by GC with a method detection limit of 0.03 microgram of nicotine, recovery ranged between 99.5 and 100.5%. Confirmation of the nicotine presence was carried out by GC/MS. The concentrations of nicotine measured were between 3.6 and 39.0 micrograms/Nm3 with a geometric mean range 6.5-28.3 micrograms/Nm3.

  1. Plasma homocysteine concentration changes after renal transplantation in children.

    PubMed

    Merouani, Aicha; Delvin, Edgar E; Genest, Jacques; Rozen, Rima; Lambert, Marie

    2002-07-01

    Hyperhomocysteinemia, a risk factor for vascular disease, is found in children as well as in 80% of adult patients with end-stage renal disease. The aim of this study was to assess the changes in plasma homocysteine concentrations after renal transplantation (RT). Plasma homocysteine, vitamin B(12), and folate concentrations were prospectively measured in six patients at three points, before and post transplantation (6 months, 4 years), and compared with controls using standardized scores (Z score) for each of these parameters. Folic acid supplementation was introduced after the evaluation at 6 months. Patients had elevated median plasma homocysteine Z scores during dialysis (4.12). When assessed at 6 months and 4 years, median plasma homocysteine Z scores were, respectively, 2.35 and 0.29. Median folate Z scores were 1.89 during dialysis, -0.26 at 6 months, and 3.26 at 4 years post RT. Median vitamin B(12) Z score was 2.12 during dialysis, 0.58 at 6 months, and -0.07 at 4 years post RT. Glomerular filtration rate (GFR) improved after RT, with median GFR of 84.5 ml/min per 1.73 m(2) at 6 months. This stabilized to a value of 70.5 ml/min per 1.73 m(2) at 4 years. When comparing values before and after RT at 6 months, changes were observed only for GFR ( P<0.03) and vitamin B(12) ( P<0.05). There were no changes in plasma homocysteine, folate, and serum albumin. At 4 years, a significant decrease in plasma homocysteine was observed ( P<0.05) with increased GFR ( P<0.03). No significant changes were observed in plasma albumin, folate, and vitamin B(12) concentrations. In conclusion, elevated plasma homocysteine in children during dialysis persists after RT despite a significant improvement in renal function. However, normalization was attained when patients were supplemented with folic acid. Further controlled studies are required to evaluate the determinants and treatment of elevated plasma homocysteine in pediatric transplant patients. PMID:12172766

  2. Drug-dependent behaviors and nicotinic acetylcholine receptor expressions in Caenorhabditis elegans following chronic nicotine exposure.

    PubMed

    Polli, Joseph R; Dobbins, Dorothy L; Kobet, Robert A; Farwell, Mary A; Zhang, Baohong; Lee, Myon-Hee; Pan, Xiaoping

    2015-03-01

    Nicotine, the major psychoactive compound in tobacco, targets nicotinic acetylcholine receptors (nAChRs) and results in drug dependence. The nematode Caenorhabditis elegans' (C. elegans) genome encodes conserved and extensive nicotinic receptor subunits, representing a useful system to investigate nicotine-induced nAChR expressions in the context of drug dependence. However, the in vivo expression pattern of nAChR genes under chronic nicotine exposure has not been fully investigated. To define the role of nAChR genes involved in nicotine-induced locomotion changes and the development of tolerance to these effects, we characterized the locomotion behavior combining the use of two systems: the Worm Tracker hardware and the WormLab software. Our results indicate that the combined system is an advantageous alternative to define drug-dependent locomotion behavior in C. elegans. Chronic (24-h dosing) nicotine exposure at 6.17 and 61.7μM induced nicotine-dependent behaviors, including drug stimulation, tolerance/adaption, and withdrawal responses. Specifically, the movement speed of naïve worms on nicotine-containing environments was significantly higher than on nicotine-free environments, suggesting locomotion stimulation by nicotine. In contrast, the 24-h 6.17μM nicotine-treated worms exhibited significantly higher speeds on nicotine-free plates than on nicotine-containing plates. Furthermore significantly increased locomotion behavior during nicotine cessation was observed in worms treated with a higher nicotine concentration of 61.7μM. The relatively low locomotion speed of nicotine-treated worms on nicotine-containing environments also indicates adaption/tolerance of worms to nicotine following chronic nicotine exposure. In addition, this study provides useful information regarding the comprehensive in vivo expression profile of the 28 "core" nAChRs following different dosages of chronic nicotine treatments. Eleven genes (lev-1, acr-6, acr-7, acr-11, lev-8, acr

  3. Vagal branches involved in inhibition of bradykinin-induced synovial plasma extravasation by intrathecal nicotine and noxious stimulation in the rat.

    PubMed Central

    Miao, F J; Jänig, W; Levine, J D

    1997-01-01

    1. Stimulation of cutaneous and spinal visceral nociceptive afferents and intrathecal nicotine reduces bradykinin-induced plasma extravasation (BK-induced PE) in the knee joint of the rat. This depression is mediated by the hypothalamo-pituitary-adrenal (HPA) axis and is potentiated by subdiaphragmatic vagotomy. It is believed that activity in vagal afferents tonically inhibits ascending impulse transmission in the neuraxis projecting to the hypothalamus. Vagotomy, by removing such inhibition, allows greater depression of BK-induced PE. In this study we determined whether the vagal afferents which negatively regulate activities of the HPA axis are present in all branches of the abdominal vagus nerves or only in specific branches. 2. We measured the depression of BK-induced PE elicited by graded stimulation of spinal visceral afferents with intraperitoneal capsaicin and by intrathecal nicotine in vagus-intact rats and in rats in which specific vagal branches were selectively interrupted. (i) Interruption of the coeliac branches mimicked the effect of total subdiaphragmatic vagotomy in potentiating the depression of BK-induced PE generated by intrathecal nicotine and by stimulation of spinal visceral afferents. (ii) Interruption of the gastric and hepatic branches of the abdominal vagus nerves together or individually did not affect the depression of BK-induced PE generated by the two stimuli. 3. These results indicate that afferent activity in coeliac and accessory coeliac vagal branches is involved in the regulation of the nociceptive system-initiated depression of BK-induced PE. The afferent fibres in these vagal branches involved probably monitor physiological events in abdominal visceral organs. Images Figure 4 PMID:9032694

  4. Urinary oxalate and glycolate excretion and plasma oxalate concentration.

    PubMed Central

    Barratt, T M; Kasidas, G P; Murdoch, I; Rose, G A

    1991-01-01

    The diagnosis of primary hyperoxaluria in young children is hampered by the lack of a reliable reference range for urinary oxalate excretion, especially in infants. We present data on urinary oxalate and glycolate excretion in 137 normal children, on the plasma oxalate concentration in 33 normal children and 53 with chronic renal failure, and on amniotic fluid oxalate concentration in 63 uncomplicated pregnancies. The urinary oxalate:creatinine molar ratios were log normally distributed: mean (range) values were less than 1 year 0.061 (0.015-0.26), 1-5 years 0.036 (0.011-0.12), 5-12 years 0.030 (0.0059-0.15), and greater than 12 years 0.013 (0.0021-0.083). Geometric mean (range) plasma oxalate concentration in the normal children was 1.53 (0.78-3.02) mumols/l and was independent of age. The mean (SD) plasma oxalate: creatinine molar ratio in these normal children and 50 with chronic renal failure was 0.033 (0.013), and was independent of age and renal function. Mean (SD) amniotic fluid oxalate concentration was 19.0 (4.3) mumols/l. PMID:2031609

  5. Effect of gaseous ammonia on nicotine sorption

    SciTech Connect

    Webb, A.M.; Singer, B.C.; Nazaroff, W.W.

    2002-06-01

    Nicotine is a major constituent of environmental tobacco smoke. Sorptive interactions of nicotine with indoor surfaces can substantially alter indoor concentrations. The phenomenon is poorly understood, including whether sorption is fully reversible or partially irreversible. They hypothesize that acid-base chemistry on indoor surfaces might contribute to the apparent irreversibility of nicotine sorption under some circumstances. Specifically, they suggest that nicotine may become protonated on surfaces, markedly reducing its vapor pressure. If so, subsequent exposure of the surface to gaseous ammonia, a common base, could raise the surface pH, causing deprotonation and desorption of nicotine from surfaces. A series of experiments was conducted to explore the effect of ammonia on nicotine sorption to and reemission from surfaces. The results indicate that, under some conditions, exposure to gaseous ammonia can substantially increase the rate of desorption of previously sorbed nicotine from common indoor surface materials.

  6. Plasma bevantolol concentration and heart rate in rabbits.

    PubMed

    Liu, X Q; Ye, X L; Zhu, H Q; Huang, S K

    1993-05-01

    Bevantolol (Bev, 5, 10 mg.kg-1) was injected i.v. to rabbits. A measure the lag time of heart rate (HR) response behind the changes in plasma Bev concentration (K(eo)), and the sensitivity of the site of action of Bev (EC50) were determined. The K(eo) were 0.03 +/- 0.02 and 0.029 +/- 0.009 min-1 and the EC50 were 0.2 +/- 0.1 and 0.27 +/- 0.14 microgram.ml-1 respectively for the 2 dosages. The peak changes in HR lagged behind the changes in plasma Bev concentration. There were no significant changes in both pharmacokinetic and pharmacodynamic parameters between the dosages.

  7. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours

    PubMed Central

    Haouala, Amina; Widmer, Nicolas; Guidi, Monia; Montemurro, Michael; Leyvraz, Serge; Buclin, Thierry; Eap, Chin B; Decosterd, Laurent A; Csajka, Chantal

    2013-01-01

    Aim Total imatinib concentrations are currently measured for the therapeutic drug monitoring of imatinib, whereas only free drug equilibrates with cells for pharmacological action. Due to technical and cost limitations, routine measurement of free concentrations is generally not performed. In this study, free and total imatinib concentrations were measured to establish a model allowing the confident prediction of imatinib free concentrations based on total concentrations and plasma proteins measurements. Methods One hundred and fifty total and free plasma concentrations of imatinib were measured in 49 patients with gastrointestinal stromal tumours. A population pharmacokinetic model was built up to characterize mean total and free concentrations with inter-patient and intrapatient variability, while taking into account α1-acid glycoprotein (AGP) and human serum albumin (HSA) concentrations, in addition to other demographic and environmental covariates. Results A one compartment model with first order absorption was used to characterize total and free imatinib concentrations. Only AGP influenced imatinib total clearance. Imatinib free concentrations were best predicted using a non-linear binding model to AGP, with a dissociation constant Kd of 319 ng ml−1, assuming a 1:1 molar binding ratio. The addition of HSA in the equation did not improve the prediction of imatinib unbound concentrations. Conclusion Although free concentration monitoring is probably more appropriate than total concentrations, it requires an additional ultrafiltration step and sensitive analytical technology, not always available in clinical laboratories. The model proposed might represent a convenient approach to estimate imatinib free concentrations. However, therapeutic ranges for free imatinib concentrations remain to be established before it enters into routine practice. PMID:22891806

  8. Low plasma concentrations of adrenaline and physiological tremor in man.

    PubMed Central

    Fellows, I W; Macdonald, I A; Wharrad, H J; Birmingham, A T

    1986-01-01

    Finger tremor was measured in six normal subjects during intravenous infusions of adrenaline (10 ngkg-1min-1 and 50 ngkg-1min-1) resulting in venous plasma adrenaline concentrations within the physiological range (0.77 +/- 0.08 and 2.28 +/- 0.18 nmoll-1). Tremor amplitude significantly increased after 15 and 25 minutes infusion at the higher dose of adrenaline. The lower dose of adrenaline increased tremor in three of the six subjects. PMID:3701348

  9. Pharmacokinetics of a nicotine polacrilex lozenge.

    PubMed

    Choi, Jae H; Dresler, Carolyn M; Norton, Michele R; Strahs, Kenneth R

    2003-10-01

    To evaluate the pharmacokinetic characteristics of the 2-mg and 4-mg nicotine polacrilex lozenges, the following four separate studies were conducted in healthy adult smokers: (a) A single-dose, four-way crossover (replicate design) study to compare the 4-mg lozenge and the 4-mg nicotine polacrilex gum, (b) a single-dose, two-way crossover study to compare the 2-mg lozenge and the 2-mg gum, (c) a multiple-dose, four-way crossover study to compare the lozenges administered every 90 min and the gums administered every 60 min at 2- and 4-mg dose levels, and (d) a single-dose, three-way crossover study to compare the pharmacokinetic profiles of the 4-mg lozenge when administered in three different ways: (i) Used as directed, (ii) chewed and immediately swallowed, and (iii) chewed, retained in the mouth for 5 min, and then swallowed. The single-dose studies consistently demonstrated 8%-10% higher maximal plasma concentrations and 25%-27% higher AUC values (area under the concentration-time curve) from the lozenges compared with the gums at the 2- and 4-mg dose levels, probably owing to the residual nicotine retained in the gum. The multiple-dose study applying different dosing intervals (i.e., every 90 min for the lozenges and every 60 min for the gums) resulted in approximately 30% lower AUC(0-t) values for the lozenges compared with those for the gums. Administration of the lozenge contrary to the label-specified instructions for use did not lead to a faster or higher absorption of nicotine. These pharmacokinetic characteristics should allow the lozenge to become an effective and safe therapeutic alternative for smoking cessation.

  10. Pharmacokinetics of a nicotine polacrilex lozenge.

    PubMed

    Choi, Jae H; Dresler, Carolyn M; Norton, Michele R; Strahs, Kenneth R

    2003-10-01

    To evaluate the pharmacokinetic characteristics of the 2-mg and 4-mg nicotine polacrilex lozenges, the following four separate studies were conducted in healthy adult smokers: (a) A single-dose, four-way crossover (replicate design) study to compare the 4-mg lozenge and the 4-mg nicotine polacrilex gum, (b) a single-dose, two-way crossover study to compare the 2-mg lozenge and the 2-mg gum, (c) a multiple-dose, four-way crossover study to compare the lozenges administered every 90 min and the gums administered every 60 min at 2- and 4-mg dose levels, and (d) a single-dose, three-way crossover study to compare the pharmacokinetic profiles of the 4-mg lozenge when administered in three different ways: (i) Used as directed, (ii) chewed and immediately swallowed, and (iii) chewed, retained in the mouth for 5 min, and then swallowed. The single-dose studies consistently demonstrated 8%-10% higher maximal plasma concentrations and 25%-27% higher AUC values (area under the concentration-time curve) from the lozenges compared with the gums at the 2- and 4-mg dose levels, probably owing to the residual nicotine retained in the gum. The multiple-dose study applying different dosing intervals (i.e., every 90 min for the lozenges and every 60 min for the gums) resulted in approximately 30% lower AUC(0-t) values for the lozenges compared with those for the gums. Administration of the lozenge contrary to the label-specified instructions for use did not lead to a faster or higher absorption of nicotine. These pharmacokinetic characteristics should allow the lozenge to become an effective and safe therapeutic alternative for smoking cessation. PMID:14577980

  11. Time controlled pulsatile transdermal delivery of nicotine: A phase I feasibility trial in male smokers.

    PubMed

    Hammann, Felix; Kummer, Oliver; Guercioni, Stefania; Imanidis, Georgios; Drewe, Juergen

    2016-06-28

    Nicotine substitution is a mainstay component in smoking cessation schemes. Current products including patches are poorly effective mainly because they do not give smokers the same pharmacokinetic profile of nicotine as cigarette consumption. This work evaluates a new computer operated delivery system for time controlled pulsatile transdermal administration of nicotine in a phase I clinical trial with twelve heavy smoking male volunteers. The device was affixed to the ventral side of the leading lower arm of the subjects and was programmed to deliver two pulses of drug within 16h with three delivery rates in a consecutive dose escalation study. Tolerability of the three increasing doses of nicotine was established. Plasma concentration of nicotine exhibited two peaks and one trough and reached therapeutically effective levels that behaved linearly with the drug load concentration of the device. In vivo input rate, delivered amount and elimination kinetics were deduced by pharmacokinetic modeling to analyze device performance. Timing, dose and duration of delivery were controlled by system operation parameters. Hence, feasibility of controlled pulsatile delivery of nicotine at predetermined intervals was demonstrated. After additional optimization, preprogrammed or on demand administration to meet individualized and circadian replacement needs should improve smoking cessation efficacy. PMID:27090163

  12. Plasma D-dimer concentration in patients with systemic sclerosis

    PubMed Central

    Lippi, Giuseppe; Volpe, Alessandro; Caramaschi, Paola; Salvagno, Gian Luca; Montagnana, Martina; Guidi, Gian Cesare

    2006-01-01

    Background Systemic sclerosis (SSc) is an autoimmune disorder of the connective tissue characterized by widespread vascular lesions and fibrosis. Little is known so far on the activation of the hemostatic and fibrinolytic systems in SSc, and most preliminary evidences are discordant. Methods To verify whether SSc patients might display a prothrombotic condition, plasma D-dimer was assessed in 28 consecutive SSc patients and in 33 control subjects, matched for age, sex and environmental habit. Results and discussion When compared to healthy controls, geometric mean and 95% confidence interval (IC95%) of plasma D-dimer were significantly increased in SSc patients (362 ng/mL, IC 95%: 361–363 ng/mL vs 229 ng/mL, IC95%: 228–231 ng/mL, p = 0.005). After stratifying SSc patients according to disease subset, no significant differences were observed between those with limited cutaneous pattern and controls, whereas patients with diffuse cutaneous pattern displayed substantially increased values. No correlation was found between plasma D-dimer concentration and age, sex, autoantibody pattern, serum creatinine, erythrosedimentation rate, nailfold videocapillaroscopic pattern and pulmonary involvement. Conclusion We demonstrated that SSc patients with diffuse subset are characterized by increased plasma D-dimer values, reflecting a potential activation of both the hemostatic and fibrinolytic cascades, which might finally predispose these patients to thrombotic complications. PMID:16420700

  13. Plasma polychlorinated biphenyl concentrations and immune function in postmenopausal women

    SciTech Connect

    Spector, June T.; De Roos, Anneclaire J.; Ulrich, Cornelia M.; Sheppard, Lianne; Sjoedin, Andreas; Wener, Mark H.; Wood, Brent; and others

    2014-05-01

    Background: Polychlorinated biphenyl (PCB) exposure has been associated with non-Hodgkin lymphoma in several studies, and the immune system is a potential mediator. Objectives: We analyzed associations of plasma PCBs with immune function measures. We hypothesized that higher plasma PCB concentrations are associated with lower immune function cross-sectionally, and that increases in PCB concentrations over a one year period are associated with decreases in immune function. Methods: Plasma PCB concentrations and immune function [natural killer (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were measured at baseline and one year in 109 postmenopausal overweight women participating in an exercise intervention study in the Seattle, Washington (USA) area. Mixed models, with adjustment for body mass index and other potential confounders, were used to estimate associations of PCBs with immune function cross-sectionally and longitudinally. Results: Associations of PCBs with immune function measures differed across groups of PCBs (e.g., medium- and high-chlorinated and dioxin-like [mono-ortho-substituted]) and by the time frame for the comparison (cross-sectional vs. longitudinal). Higher concentrations of medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross-sectionally but not longitudinally. The mean decrease in 0.5 µg/mL PHA-TLP/50.0 pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and NK cytotoxicity. Conclusions: These results do not provide strong evidence of impaired cellular immunity from PCB exposure. Larger longitudinal studies with greater variability in PCB exposures are needed to further examine temporal associations of PCBs with immune function. - Highlights: • Plasma PCBs and immune function were measured in 109 women at baseline and one year. • Immune measures included T lymphocyte proliferation

  14. Plasma concentrations of coffee polyphenols and plasma biomarkers of diabetes risk in healthy Japanese women

    PubMed Central

    Lee, A H; Tan, L 'B; Hiramatsu, N; Ishisaka, A; Alfonso, H; Tanaka, A; Uemura, N; Fujiwara, Y; Takechi, R

    2016-01-01

    Coffee consumption has been reported to reduce the risk of type 2 diabetes in experimental and epidemiological studies. This anti-diabetic effect of coffee may be attributed to its high content in polyphenols especially caffeic acid and chlorogenic acid. However, the association between plasma coffee polyphenols and diabetic risks has never been investigated in the literature. In this study, fasting plasma samples were collected from 57 generally healthy females aged 38–73 (mean 52, s.d. 8) years recruited in Himeji, Japan. The concentrations of plasma coffee polyphenols were determined by liquid chromatography coupled with mass tandem spectrometer. Diabetes biomarkers in the plasma/serum samples were analysed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman's correlation coefficients. The results showed that plasma chlorogenic acid exhibited negative associations with fasting blood glucose, glycated hemoglobin and C-reactive protein, whereas plasma total coffee polyphenol and plasma caffeic acid were weakly associated with these biomarkers. Our preliminary data support previous findings that coffee polyphenols have anti-diabetic effects but further replications with large samples of both genders are recommended. PMID:27270110

  15. Plasma concentrations of coffee polyphenols and plasma biomarkers of diabetes risk in healthy Japanese women.

    PubMed

    Lee, A H; Tan, L 'b; Hiramatsu, N; Ishisaka, A; Alfonso, H; Tanaka, A; Uemura, N; Fujiwara, Y; Takechi, R

    2016-06-06

    Coffee consumption has been reported to reduce the risk of type 2 diabetes in experimental and epidemiological studies. This anti-diabetic effect of coffee may be attributed to its high content in polyphenols especially caffeic acid and chlorogenic acid. However, the association between plasma coffee polyphenols and diabetic risks has never been investigated in the literature. In this study, fasting plasma samples were collected from 57 generally healthy females aged 38-73 (mean 52, s.d. 8) years recruited in Himeji, Japan. The concentrations of plasma coffee polyphenols were determined by liquid chromatography coupled with mass tandem spectrometer. Diabetes biomarkers in the plasma/serum samples were analysed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman's correlation coefficients. The results showed that plasma chlorogenic acid exhibited negative associations with fasting blood glucose, glycated hemoglobin and C-reactive protein, whereas plasma total coffee polyphenol and plasma caffeic acid were weakly associated with these biomarkers. Our preliminary data support previous findings that coffee polyphenols have anti-diabetic effects but further replications with large samples of both genders are recommended.

  16. Factors affecting plasma aluminum concentrations in nonexposed workers.

    PubMed

    House, R A

    1992-10-01

    In this study, the distribution and determinants of plasma aluminum concentrations were examined in 71 office employees not occupationally exposed to aluminum. The samples were analyzed by Zeeman graphite furnace atomic absorption spectroscopy and were found to be log normally distributed. After using the International Federation of Clinical Chemistry (IFCC) recommended procedure for removal of likely aberrant values, the 95th percentile value was 198 nmol/L (90% CI:165-238); when those using antacids were also excluded, the 95th percentile value fell to 175 nmol/L (90% CI:147-208). Multiple regression analysis indicated that the factors most predictive of log plasma aluminum were the batch in which the sample was analyzed and the use of antacids containing aluminum. The statistical significance of the batch variable likely indicates the well-recognized problem of contamination in sampling and analyzing aluminum. PMID:1403189

  17. Factors affecting plasma aluminum concentrations in nonexposed workers

    SciTech Connect

    House, R.A. )

    1992-10-01

    In this study, the distribution and determinants of plasma aluminum concentrations were examined in 71 office employees not occupationally exposed to aluminum. The samples were analyzed by Zeeman graphite furnace atomic absorption spectroscopy and were found to be log normally distributed. After using the International Federation of Clinical Chemistry (IFCC) recommended procedure for removal of likely aberrant values, the 95th percentile value was 198 nmol/L (90% CI:165-238); when those using antacids were also excluded, the 95th percentile value fell to 175 nmol/L (90% CI:147-208). Multiple regression analysis indicated that the factors most predictive of log plasma aluminum were the batch in which the sample was analyzed and the use of antacids containing aluminum. The statistical significance of the batch variable likely indicates the well-recognized problem of contamination in sampling and analyzing aluminum.35 references.

  18. Combination induction plasma tube and current concentrator for introducing a sample into a plasma

    DOEpatents

    Hull, Donald E.; Bieniewski, Thomas M.

    1988-01-01

    An induction plasma tube in combination with a current concentrator. The rent concentrator has a substantially cylindrical body having an open end and a partially closed end which defines an aperture. A first slot extends the longitudinal length of the cylindrical body and a second slot extends radially outward from the aperture. Together the first and second slots form a single L-shaped slot. The current concentrator is disposed within a volume bounded by an induction coil substantially along the axis thereof, and when power is applied to the induction coil a concentrated current is induced within the current concentrator aperture. The concentrator is moveable relative to the coil along the longitudinal axis of the coil to control the amount of current which is concentrated at the aperture.

  19. Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans.

    PubMed

    Kirkpatrick, Matthew G; Francis, Sunday M; Lee, Royce; de Wit, Harriet; Jacob, Suma

    2014-08-01

    MDMA (±3,4-methylenedioxymethamphetamine, 'ecstasy') is reportedly used recreationally because it increases feelings of sociability and interpersonal closeness. Prior work suggests that the pro-social effects of MDMA may be mediated by release of oxytocin. A direct examination of plasma levels of oxytocin after acute doses of oxytocin and MDMA, in the same individuals, would provide further evidence for the idea that MDMA produces its pro-social effects by increasing oxytocin. Fourteen healthy MDMA users participated in a 4-session, double-blind study in which they received oral MDMA (0.75 and 1.5mg/kg), intranasal oxytocin (20IU or 40IU), and placebo. Plasma oxytocin concentrations, as well as cardiovascular and subjective effects were assessed before and at several time points after drug administration. MDMA (1.5mg/kg only) increased plasma oxytocin levels to a mean peak of 83.7pg/ml at approximately 90-120min, compared to 18.6pg/ml after placebo. Intranasal oxytocin (40IU, but not 20IU) increased plasma oxytocin levels to 48.0pg/ml, 30-60min after nasal spray administration. MDMA dose-dependently increased heart rate, blood pressure, feelings of euphoria (e.g., 'High' and 'Like Drug'), and feelings of sociability, whereas oxytocin had no cardiovascular or subjective effects. The subjective and cardiovascular responses to MDMA were not related to plasma oxytocin levels, although the N was small for this analysis. Future studies examining the effects of oxytocin antagonists on responses to MDMA will help to determine the mechanism by which MDMA produces pro-social effects.

  20. Effects of running the Bostom Marathon on plasma concentrations of large neutral amino acids

    NASA Technical Reports Server (NTRS)

    Conlay, L. A.; Wurtman, R. J.; Lopez G-Coviella, I.; Blusztajn, J. K.; Vacanti, C. A.; Logue, M.; During, M.; Caballero, B.; Maher, T. J.; Evoniuk, G.

    1989-01-01

    Plasma large neutral amino acid concentrations were measured in thirty-seven subjects before and after completing the Boston Marathon. Concentrations of tyrosine, phenylalanine, and methionine increased, as did their 'plasma ratios' (i.e., the ratio of each amino acid's concentration to the summed plasma concentrations of the other large neutral amino acids which compete with it for brain uptake). No changes were noted in the plasma concentrations of tryptophan, leucine, isoleucine, nor valine; however, the 'plasma ratios' of valine, leucine, and isoleucine all decreased. These changes in plasma amino acid patterns may influence neurotransmitter synthesis.

  1. Plasma homocysteine concentration in children with chronic renal failure.

    PubMed

    Merouani, A; Lambert, M; Delvin, E E; Genest, J; Robitaille, P; Rozen, R

    2001-10-01

    Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 micromol/l vs 6.8 micromol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 micromol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B12 was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 micromol/l) than nondialyzed patients with the mutation (10.7 micromol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B12 less than 522 pmol/l. Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B12 status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are particularly at risk for hyperhomocysteinemia. Further studies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients. PMID:11605787

  2. Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: Investigation of nicotinic acid receptor agonists

    SciTech Connect

    Zgoda-Pols, Joanna R.; Chowdhury, Swapan; Wirth, Mark; Milburn, Michael V.; Alexander, Danny C.; Alton, Kevin B.

    2011-08-15

    An investigative renal toxicity study using metabolomics was conducted with a potent nicotinic acid receptor (NAR) agonist, SCH 900424. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques were used to identify small molecule biomarkers of acute kidney injury (AKI) that could aid in a better mechanistic understanding of SCH 900424-induced AKI in mice. The metabolomics study revealed 3-indoxyl sulfate (3IS) as a more sensitive marker of SCH 900424-induced renal toxicity than creatinine or urea. An LC-MS assay for quantitative determination of 3IS in mouse matrices was also developed. Following treatment with SCH 900424, 3IS levels were markedly increased in murine plasma and brain, thereby potentially contributing to renal- and central nervous system (CNS)-related rapid onset of toxicities. Furthermore, significant decrease in urinary excretion of 3IS in those animals due to compromised renal function may be associated with the elevation of 3IS in plasma and brain. These data suggest that 3IS has a potential to be a marker of renal and CNS toxicities during chemically-induced AKI in mice. In addition, based on the metabolomic analysis other statistically significant plasma markers including p-cresol-sulfate and tryptophan catabolites (kynurenate, kynurenine, 3-indole-lactate) might be of toxicological importance but have not been studied in detail. This comprehensive approach that includes untargeted metabolomic and targeted bioanalytical sample analyses could be used to investigate toxicity of other compounds that pose preclinical or clinical development challenges in a pharmaceutical discovery and development. - Research Highlights: > Nicotinic acid receptor agonist, SCH 900424, caused acute kidney injury in mice. > MS-based metabolomics was conducted to identify potential small molecule markers of renal toxicity. > 3-indoxyl-sulfate was found to be as a more sensitive marker of renal toxicity than creatinine

  3. Plasma leptin concentrations are increased in women with premenstrual syndrome.

    PubMed

    Anim-Nyame, N; Domoney, C; Panay, N; Jones, J; Alaghband-Zadeh, J; Studd, J W

    2000-11-01

    Leptin is a metabolic regulator of the hypothalamic- pituitary-gonadal axis, and plays an important role in human reproduction. Its neuro-endocrine effects are mediated by interactions with receptors in the hypothalamus, where emotional drive is also controlled. We postulated that circulating leptin concentrations are increased in premenstrual syndrome (PMS), and that this may be associated with the psychological symptoms of the disease. We obtained fasting venous samples from 32 women with PMS and 28 women with asymptomatic menstrual cycles, matched for age, body mass index and menstrual cycle length. Leptin concentrations were measured by radioimmunoassay. Leptin concentrations increased significantly during the luteal phases of the menstrual cycles of the control and PMS groups as compared with the follicular phase, having excluded the 11 women with PMS and six controls found to be anovulatory on the basis of mid-luteal plasma progesterone concentrations from the analysis. A greater increase was observed in women with PMS than the controls (P: = 0.00006 and 0.003 respectively). Although leptin concentrations in the follicular and luteal phases were higher in PMS than the controls, the difference was only statistically significant between the follicular phases (P: = 0.001). There was no clear relationship between leptin and oestradiol or progesterone in this study. These findings suggest that leptin may play a role in the pathophysiology of the disease, and requires further evaluation.

  4. Nicotine delivery and pharmacologic response from Verve, an oral nicotine delivery product.

    PubMed

    Koszowski, Bartosz; Viray, Lauren C; Stanfill, Stephen B; Lisko, Joseph G; Rosenberry, Zach R; Potts, Jennifer L; Pickworth, Wallace B

    2015-09-01

    Verve, an oral nicotine delivery product (ONDP), was introduced by Nu Mark (Altria Client Group, Richmond VA) for smokers to use in places where smoking is prohibited. This study assessed the effect of this ONDP on plasma nicotine levels, heart rate, product satisfaction, and ability to suppress smoking urge and cigarette cravings. Thirteen daily cigarette smokers [8 men and 5 women; average age 33.4years] attended two laboratory sessions, one occurred after overnight tobacco abstinence. Plasma samples were collected before and after ONDP use and measured for nicotine. In non-abstinent smokers, mean plasma nicotine levels increased from 18.3 to 21.0ng/mL. In abstinent smokers, average nicotine levels increased from 3.1 to 4.5ng/mL. After overnight tobacco abstinence, ONDP use significantly (p<0.01) increased heart rate from 69beats per minute (bpm) to 75bpm; while urge to smoke decreased significantly (p<0.01) from a score of 8.6 to 4.9. Participants indicated moderate product satisfaction that was not changed by tobacco abstinence. Analysis of unused ONDP revealed total nicotine levels of 1.68±0.09mg/disc. Spent ONDP discs were also analyzed to determine % nicotine liberated during chewing; results were 80% in the non-abstinent and 82% in the abstinent conditions (ns). Our study results indicate that ONDP use can increase plasma nicotine levels and heart rate and reduce cigarette cravings in abstinent smokers.

  5. Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants

    PubMed Central

    Mupfudze, Tatenda G.; Stoltzfus, Rebecca J.; Rukobo, Sandra; Moulton, Lawrence H.; Humphrey, Jean H.; Prendergast, Andrew J.

    2015-01-01

    Objective Anemia in infancy is a global public health problem. We evaluated the relative contributions of iron deficiency and inflammation to infant anemia. Methods We measured plasma hepcidin, ferritin, soluble transferrin receptor (sTfR), alpha-1-acid glycoprotein and C-reactive protein (CRP) by ELISA on archived plasma from 289 HIV-unexposed anemic or non-anemic Zimbabwean infants at ages 3mo, 6mo and 12mo. Among anemic infants, we determined the proportion with iron-deficiency anemia (IDA) and anemia of inflammation (AI). We undertook regression analyses of plasma hepcidin and anemia status, adjusting for sex, age and birthweight. Results Anemic infants at 3mo were more stunted and had higher CRP (median 0.45 vs 0.21mg/L; P = 0.037) and hepcidin (median 14.7 vs 9.7ng/mL; P = 0.022) than non-anemic infants, but similar levels of ferritin and sTfR; 11% infants had IDA and 15% had AI. Anemic infants at 6mo had higher hepcidin (median 7.9 vs 4.5ng/mL; P = 0.016) and CRP (median 2.33 vs 0.32mg/L; P<0.001), but lower ferritin (median 13.2 vs 25.1μg/L; P<0.001) than non-anemic infants; 56% infants had IDA and 12% had AI. Anemic infants at 12mo had lower ferritin (median 3.2 vs 22.2μg/L; P<0.001) and hepcidin (median 0.9 vs 1.9ng/mL; P = 0.019), but similar CRP levels; 48% infants had IDA and 8% had AI. Comparing anemic with non-anemic infants, plasma hepcidin was 568% higher, 405% higher and 64% lower at 3mo, 6mo and 12mo, respectively, after adjusting for sex and birthweight (all p<0.01). Plasma hepcidin declined significantly with age among anemic but not non-anemic infants. Girls had 61% higher hepcidin than boys, after adjusting for age, anemia and birthweight (p<0.001). Conclusion Anemia is driven partly by inflammation early in infancy, and by iron deficiency later in infancy, with plasma hepcidin concentrations reflecting the relative contribution of each. However, there is need to better characterize the drivers of hepcidin during infancy in developing

  6. Influence of moderate alcohol intake on wakening plasma thiopental concentration.

    PubMed

    Loft, S; Jensen, V; Rørsgaard, S

    1983-06-01

    In an earlier study, an inverse correlation between thiopental-induced sleeping time and alcohol intake in the preceding week was demonstrated in women undergoing termination of pregnancy. In order to investigate the mechanism behind the apparent cross-tolerance, the relationship between alcohol consumption in the week preceding thiopental/nitrous oxide/oxygen anesthesia and wakening plasma thiopental concentration on one hand and sleeping time on the other was examined in 68 women scheduled for termination of pregnancy and in 37 women scheduled for diagnostic uterine dilatation and curettage. In terms of pure alcohol, the weekly intake (mean +/- s.d.) was 1.17 +/- 2.07 ml . kg-1 in the former and 1.49 +/- 1.70 ml . kg-1 in the latter group. A positive correlation between alcohol consumption and wakening plasma thiopental concentration was found in both groups, reaching statistical significance (P less than 0.05) in the group undergoing termination of pregnancy, but not in the other. The inverse correlation found earlier between alcohol intake and sleeping time was not reproduced significantly in any of the groups. The results indicate that moderate alcohol intake may induce cerebral tolerance to thiopental.

  7. Good relationship between saliva cotinine kinetics and plasma cotinine kinetics after smoking one cigarette.

    PubMed

    Yuki, Dai; Kikuchi, Akira; Miura, Naoki; Kakehi, Aoi; Onozawa, Masahiro

    2013-11-01

    This study investigated the relationship between plasma and saliva cotinine kinetics after smoking one cigarette and the relationship between cotinine kinetics and estimated nicotine intake, which was calculated as mouth level exposure (MLE) of nicotine, from smoking two test cigarettes with different nicotine yields. This study was conducted in 16 healthy adult Japanese smokers, who did not have null nor reduced-activity alleles of CYP2A6, with a quasi-randomized crossover design of smoking a low-tar cigarette or a high-tar cigarette. Saliva cotinine showed similar concentration profiles to plasma cotinine, and all of the calculated pharmacokinetic parameters of cotinine showed the same values in plasma and saliva. The Cmax and AUC of cotinine showed almost the same dose-responsiveness to the estimated MLE of nicotine between plasma and saliva, but the tmax and t1/2 of cotinine were not affected by the estimated MLE of nicotine in either plasma or saliva. The results show that saliva cotinine kinetics reflects plasma cotinine kinetics, and measurement of saliva cotinine concentration gives the same information as plasma cotinine on the nicotine intake. Thus, saliva cotinine would be a good and less-invasive exposure marker of cigarette smoke, reflecting the plasma cotinine concentration and kinetics.

  8. Evaluation of plasma inflammatory cytokine concentrations in racing sled dogs

    PubMed Central

    von Pfeil, Dirsko J. F.; Cummings, Bethany P.; Loftus, John P.; Levine, Corri B.; Mann, Sabine; Downey, Robert L.; Griffitts, Caroline; Wakshlag, Joseph J.

    2015-01-01

    In human athletes significant changes in cytokine concentrations secondary to exercise have been observed. This prospective study evaluated the effect of a multi-day stage sled dog race on plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). Samples from 20 dogs were harvested prior to and on days 2 and 8 of an 8-day race. Exercise resulted in significantly decreased TNF-α and IL-8 as well as increases of MCP-1, IL-6, and IL-10 concentrations (P-value between 0.01 and < 0.0001 for all parameters). The proportion of values for IL-2 that were below the detection limit increased from 40% on day 0 to 75% on day 2 and decreased on day 8 to 40% (P = 0.04). Racing sled dogs show cytokine-concentration changes that are different from those in humans. PMID:26663920

  9. Coexistence of passive and proton antiporter-mediated processes in nicotine transport at the mouse blood-brain barrier.

    PubMed

    Cisternino, Salvatore; Chapy, Hélène; André, Pascal; Smirnova, Maria; Debray, Marcel; Scherrmann, Jean-Michel

    2013-04-01

    Nicotine, the main tobacco alkaloid leading to smoking dependence, rapidly crosses the blood-brain barrier (BBB) to become concentrated in the brain. Recently, it has been shown that nicotine interacts with some organic cation transporters (OCT), but their influence at the BBB has not yet been assessed in vivo. In this study, we characterized the transport of nicotine at the mouse luminal BBB by in situ brain perfusion. Its influx was saturable and followed the Michaelis-Menten kinetics (K(m)=2.60 mM, V(max)=37.60 nmol/s/g at pH 7.40). At its usual micromolar concentrations in the plasma, most (79%) of the net transport of nicotine at the BBB was carrier-mediated, while passive diffusion accounted for 21%. Studies on knockout mice showed that the OCT Oct1-3, P-gp, and Bcrp did not alter [(3)H]-nicotine transport at the BBB. Neither did inhibiting the transporters Mate1, Octn, or Pmat. The in vivo manipulation of intracellular and/or extracellular pH, the chemical inhibition profile, and the trans-stimulation experiments demonstrated that the nicotine transporter at the BBB shared the properties of the clonidine/proton antiporter. The molecular features of this proton-coupled antiporter have not yet been identified, but it also transports diphenhydramine and tramadol and helps nicotine cross the BBB at a faster rate and to a greater extent. The pharmacological inhibition of this nicotine/proton antiporter could represent a new strategy to reduce nicotine uptake by the brain and thus help curb addiction to smoking. PMID:23212563

  10. Coexistence of passive and proton antiporter-mediated processes in nicotine transport at the mouse blood-brain barrier.

    PubMed

    Cisternino, Salvatore; Chapy, Hélène; André, Pascal; Smirnova, Maria; Debray, Marcel; Scherrmann, Jean-Michel

    2013-04-01

    Nicotine, the main tobacco alkaloid leading to smoking dependence, rapidly crosses the blood-brain barrier (BBB) to become concentrated in the brain. Recently, it has been shown that nicotine interacts with some organic cation transporters (OCT), but their influence at the BBB has not yet been assessed in vivo. In this study, we characterized the transport of nicotine at the mouse luminal BBB by in situ brain perfusion. Its influx was saturable and followed the Michaelis-Menten kinetics (K(m)=2.60 mM, V(max)=37.60 nmol/s/g at pH 7.40). At its usual micromolar concentrations in the plasma, most (79%) of the net transport of nicotine at the BBB was carrier-mediated, while passive diffusion accounted for 21%. Studies on knockout mice showed that the OCT Oct1-3, P-gp, and Bcrp did not alter [(3)H]-nicotine transport at the BBB. Neither did inhibiting the transporters Mate1, Octn, or Pmat. The in vivo manipulation of intracellular and/or extracellular pH, the chemical inhibition profile, and the trans-stimulation experiments demonstrated that the nicotine transporter at the BBB shared the properties of the clonidine/proton antiporter. The molecular features of this proton-coupled antiporter have not yet been identified, but it also transports diphenhydramine and tramadol and helps nicotine cross the BBB at a faster rate and to a greater extent. The pharmacological inhibition of this nicotine/proton antiporter could represent a new strategy to reduce nicotine uptake by the brain and thus help curb addiction to smoking.

  11. Measurement of nicotine in household dust

    SciTech Connect

    Kim, Sungroul Aung, Ther; Berkeley, Emily; Diette, Gregory B.; Breysse, Patrick N.

    2008-11-15

    An analytical method of measuring nicotine in house dust was optimized and associations among three secondhand smoking exposure markers were evaluated, i.e., nicotine concentrations of both house dust and indoor air, and the self-reported number of cigarettes smoked daily in a household. We obtained seven house dust samples from self-reported nonsmoking homes and 30 samples from smoking homes along with the information on indoor air nicotine concentrations and the number of cigarettes smoked daily from an asthma cohort study conducted by the Johns Hopkins Center for Childhood Asthma in the Urban Environment. House dust nicotine was analyzed by isotope dilution gas chromatography-mass spectrometry (GC/MS). Using our optimized method, the median concentration of nicotine in the dust of self-reported nonsmoking homes was 11.7 ng/mg while that of smoking homes was 43.4 ng/mg. We found a substantially positive association (r=0.67, P<0.0001) between house dust nicotine concentrations and the numbers of cigarettes smoked daily. Optimized analytical methods showed a feasibility to detect nicotine in house dust. Our results indicated that the measurement of nicotine in house dust can be used potentially as a marker of longer term SHS exposure.

  12. Adolescent nicotine treatment changes the response of acetylcholine systems to subsequent nicotine administration in adulthood.

    PubMed

    Slotkin, Theodore A; Bodwell, Bethany E; Ryde, Ian T; Seidler, Frederic J

    2008-05-15

    Nicotine alters the developmental trajectory of acetylcholine (ACh) systems in the immature brain, with vulnerability extending from fetal stages through adolescence. We administered nicotine to adolescent rats (postnatal days PN30-47) and then examined the subsequent response to nicotine given in adulthood (PN90-107), simulating plasma levels in smokers, and performing evaluations during nicotine treatment (PN105) and withdrawal (PN110, PN120 and PN130), as well as assessing persistent changes at 6 months of age (PN180). We measured nicotinic acetylcholine receptor (nAChR) binding, choline acetyltransferase (ChAT) activity, a marker for ACh terminals, and hemicholinium-3 (HC3) binding to the choline transporter, an index of ACh presynaptic activity. By itself, adolescent nicotine exposure evoked sex-selective deficits in cerebrocortical HC3 binding while elevating ChAT in young adulthood in striatum and midbrain. Nicotine given in adulthood produced profound nAChR upregulation lasting 2 weeks after discontinuing treatment, and decrements in cerebrocortical and striatal HC3 binding emerged during withdrawal, indicative of reduced ACh synaptic activity. For all three parameters, adolescent nicotine altered the responses to nicotine given in adulthood, producing both sensitization and desensitization that depended on sex and brain region, effects that parallel the disparate behavioral outcomes reported for these treatments. The interaction seen here for the impact of adolescent nicotine exposure on adult nicotine responses was substantially greater than that found previously for the effects of prenatal nicotine exposure on adult responses. Our findings thus reinforce the importance of adolescence as a critical period in which the future responsiveness to nicotine is programmed.

  13. Adolescent nicotine treatment changes the response of acetylcholine systems to subsequent nicotine administration in adulthood.

    PubMed

    Slotkin, Theodore A; Bodwell, Bethany E; Ryde, Ian T; Seidler, Frederic J

    2008-05-15

    Nicotine alters the developmental trajectory of acetylcholine (ACh) systems in the immature brain, with vulnerability extending from fetal stages through adolescence. We administered nicotine to adolescent rats (postnatal days PN30-47) and then examined the subsequent response to nicotine given in adulthood (PN90-107), simulating plasma levels in smokers, and performing evaluations during nicotine treatment (PN105) and withdrawal (PN110, PN120 and PN130), as well as assessing persistent changes at 6 months of age (PN180). We measured nicotinic acetylcholine receptor (nAChR) binding, choline acetyltransferase (ChAT) activity, a marker for ACh terminals, and hemicholinium-3 (HC3) binding to the choline transporter, an index of ACh presynaptic activity. By itself, adolescent nicotine exposure evoked sex-selective deficits in cerebrocortical HC3 binding while elevating ChAT in young adulthood in striatum and midbrain. Nicotine given in adulthood produced profound nAChR upregulation lasting 2 weeks after discontinuing treatment, and decrements in cerebrocortical and striatal HC3 binding emerged during withdrawal, indicative of reduced ACh synaptic activity. For all three parameters, adolescent nicotine altered the responses to nicotine given in adulthood, producing both sensitization and desensitization that depended on sex and brain region, effects that parallel the disparate behavioral outcomes reported for these treatments. The interaction seen here for the impact of adolescent nicotine exposure on adult nicotine responses was substantially greater than that found previously for the effects of prenatal nicotine exposure on adult responses. Our findings thus reinforce the importance of adolescence as a critical period in which the future responsiveness to nicotine is programmed. PMID:18395624

  14. The nicotine metabolite, cotinine, alters the assembly and trafficking of a subset of nicotinic acetylcholine receptors.

    PubMed

    Fox, Ashley M; Moonschi, Faruk H; Richards, Christopher I

    2015-10-01

    Exposure to nicotine alters the trafficking and assembly of nicotinic receptors (nAChRs), leading to their up-regulation on the plasma membrane. Although the mechanism is not fully understood, nicotine-induced up-regulation is believed to contribute to nicotine addiction. The effect of cotinine, the primary metabolite of nicotine, on nAChR trafficking and assembly has not been extensively investigated. We utilize a pH-sensitive variant of GFP, super ecliptic pHluorin, to differentiate between intracellular nAChRs and those expressed on the plasma membrane to quantify changes resulting from cotinine and nicotine exposure. Similar to nicotine, exposure to cotinine increases the number of α4β2 receptors on the plasma membrane and causes a redistribution of intracellular receptors. In contrast to this, cotinine exposure down-regulates α6β2β3 receptors. We also used single molecule fluorescence studies to show that cotinine and nicotine both alter the assembly of α4β2 receptors to favor the high sensitivity (α4)2(β2)3 stoichiometry.

  15. The Nicotine Metabolite, Cotinine, Alters the Assembly and Trafficking of a Subset of Nicotinic Acetylcholine Receptors*

    PubMed Central

    Fox, Ashley M.; Moonschi, Faruk H.; Richards, Christopher I.

    2015-01-01

    Exposure to nicotine alters the trafficking and assembly of nicotinic receptors (nAChRs), leading to their up-regulation on the plasma membrane. Although the mechanism is not fully understood, nicotine-induced up-regulation is believed to contribute to nicotine addiction. The effect of cotinine, the primary metabolite of nicotine, on nAChR trafficking and assembly has not been extensively investigated. We utilize a pH-sensitive variant of GFP, super ecliptic pHluorin, to differentiate between intracellular nAChRs and those expressed on the plasma membrane to quantify changes resulting from cotinine and nicotine exposure. Similar to nicotine, exposure to cotinine increases the number of α4β2 receptors on the plasma membrane and causes a redistribution of intracellular receptors. In contrast to this, cotinine exposure down-regulates α6β2β3 receptors. We also used single molecule fluorescence studies to show that cotinine and nicotine both alter the assembly of α4β2 receptors to favor the high sensitivity (α4)2(β2)3 stoichiometry. PMID:26269589

  16. Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation.

    PubMed

    Miranda-Spooner, M; Paccola, C C; Neves, F M O; de Oliva, S U; Miraglia, S M

    2016-03-01

    We previously observed that nicotine, administered to rats (Wistar) during pregnancy and lactation periods, provokes, in the progeny, late morphofunctional alterations in Leydig cell, body weight increase in adulthood (90 days post partum, dpp) as well as seminiferous epithelium injury. Aiming to investigate whether the spermatogenic damage previously observed in adult progenies from pregnant and lactating nicotine-exposed rat dams are maintained or whether it is worsened in older rats, we analyzed the morphological testicular alterations after up to two complete periods of spermatogenesis (53 days each), spermatic parameters, and sperm DNA fragmentation. Pregnant and lactating rats were nicotine-exposed (2 mg/kg/day) through an osmotic minipump implanted on the first day of pregnancy and replaced after birth. Absolute Control (no minipump) and Sham Control (minipump without nicotine) groups were established. The offspring were killed at 90, 143, and 196 dpp. Significant alterations in morphometric and stereological testicular parameters, such as concentration of sperm number, daily sperm production, and plasma and intratesticular levels of cholesterol and testosterone were not observed in nicotine-exposed rats. Testicular histopathological analysis showed small intraepithelial vacuolization and an accentuated germ cell desquamation in exposed rats. However, the offspring from nicotine-exposed dams exhibited higher frequency of morphologically abnormal spermatozoa and lower sperm motility in comparison with control groups. In addition, nicotine-exposed groups showed a significant reduction in sperm mitochondrial activity and an increased sperm DNA fragmentation (Comet assay). These results indicate a late reproductive damage in the male progeny caused by maternal nicotine exposure, related to the decrease in sperm quality. PMID:26824756

  17. Spinal anaesthesia in newborns: total and free bupivacaine plasma concentration.

    PubMed

    Beauvoir, C; Rochette, A; Desch, G; D'Athis, F

    1996-01-01

    This study was designed to measure total and free bupivacaine (B) after spinal anaesthesia in newborns and to evaluate a possible influence of adrenaline on B absorption. Twenty-two newborns were randomly allocated to receive either plain B (group 1) or adrenaline added to B (group 2) for spinal anaesthesia. A single blood sample was collected ten min after spinal injection. Total B concentration was found 0.31 +/- 0.17 microgram ml-1 in group 1 and 0.25 +/- 0.09 microgram ml-1 in group 2. Bound B concentration was 0.27 +/- 0.17 microgram ml-1 in group 1 and 0.22 +/- 0.09 microgram ml-1 in group 2. No difference was found between the two groups for these parameters. Albumin but not alpha 1-acid-glyco-protein correlated to age and weight, bound B correlated to alpha 1-acid-glyco-protein but not to albumin. Despite the low plasma concentration of binding proteins in newborns, spinal anaesthesia with B does not result in a high level of free drug. Adrenaline does not have any pharmacological advantage in these patients.

  18. Acute changes in plasma renin activity, plasma aldosterone concentration and plasma electrolyte concentrations following furosemide administration in patients with congestive heart failure--interrelationships and diuretic response.

    PubMed

    Mulder, H; Schopman, W; van der Lely, A J; Schopman, W

    1987-02-01

    We studied the effects of furosemide on plasma renin and plasma aldosterone in 8 patients with mild to moderate congestive heart failure. In particular, we tried to correlate these effects with changes in plasma electrolyte concentrations and with the diuretic response on furosemide. We concluded that the diuretic response in patients with congestive heart failure is not dependent on the initial serum renin nor on the initial serum aldosterone concentration. The diuretic response did not correlate either with the changes in serum renin and/or serum aldosterone concentration. Serum renin and serum aldosterone correlated mutually before and after intravenous furosemide. We confirmed the inverse correlation between serum sodium and serum renin. SeNa and SeK correlated at all times with serum aldosterone; SeCl correlated with serum aldosterone only before intravenous furosemide administration. Indirect evidence could be provided that in patients with congestive heart failure a decreased renal blood flow is present, using the urinary beta 2-microglobulin concentration. Aldosterone has again, indirectly, proved to be integrated in the renal magnesium handling. PMID:3549504

  19. The Effect of Nicotine on HPA Axis Activity in Females is Modulated by the FKBP5 Genotype.

    PubMed

    Koopmann, Anne; Bez, Jennifer; Lemenager, Tagrid; Hermann, Derik; Dinter, Christina; Reinhard, Iris; Schuster, Rilana; Wiedemann, Klaus; Winterer, Georg; Kiefer, Falk

    2016-05-01

    Tobacco smoking modulates activity in the hypothalamic-pituitary-adrenal (HPA) axis and is used to cope with stress, especially by females. The single nucleotide polymorphism (SNP) rs1360780, linked to FK506-binding protein 51 (FKBP5), has been shown to affect HPA axis functioning, and has thus been suggested as a promising candidate for indicating vulnerability to stress-related disorders. The aim of this study was to investigate the interaction between nicotine consumption and rs1360780 on cortisol plasma levels in females. A total of 296 female smokers (assessed by the Fagerström Test for Nicotine Dependence; FTND) were genotyped for the SNP rs1360780. We measured participants' cortisol plasma concentration in blood plasma collected 3 h after standardized tobacco smoking exposure. In the 36 TT-homozygotes, we found a significant negative correlation between the FTND sum score and cortisol plasma concentrations. Using linear regression analysis, we found that the FTND sum score accounted for 12.4% of the variance of cortisol plasma levels. This association was not detected in C-allele carriers. Our results suggest that nicotine is an important confounder in the modulation of HPA axis activity by FKBP5. In light of these findings, future studies on FKBP5 should seek to include data on nicotine consumption as a covariate.

  20. Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs.

    PubMed

    Pieper, Korbinian; Schuster, Tibor; Levionnois, Olivier; Matis, Ulrike; Bergadano, Alessandra

    2011-03-01

    To assess the antinociceptive efficacy of transdermal (TD) buprenorphine (B) in dogs, a prospective, positive-controlled experimental study was performed in 10 healthy Beagles. In an open label crossover design, the dogs initially received intravenous B (IVB, 0.02 mg kg(-1)) as a positive control, followed by TDB (52.5 μg h(-1)) 4 months later. Blood was collected at regular intervals for determination of the plasma concentrations of B ([B]) and its metabolite norbuprenorphine. The antinociceptive efficacy was assessed using thermal and mechanical models of nociception. The peak concentration [B] was 1.54 ng mL(-1) (±1.98) 60 h after TDB application, although three dogs had no measurable [B] after TDB. Maximum thermal threshold (TT) was 52.6 °C (±0.48) at 1h after IVB administration and 51.63 °C (±1.01) 72 h after TDB application. The significant increase in TT indicated that effective antinociception was achieved beyond 36 h after the application of TDB, lasting until patch removal. There was hysteresis between [B] and the antinociceptive effect. PMID:20206560

  1. Effect of In Vivo Nicotine Exposure on Chlorpyrifos Pharmacokinetics and Pharmacodynamics in Rats

    SciTech Connect

    Lee, Sookwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

    2010-03-30

    Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1 mg nicotine/kg or saline (sc), and to either a single oral dose of 35 mg CPF/kg or a repeated dose of 5 mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. Physiologically based pharmacokinetic model simulations of CPF-oxon concentrations in blood and brain were predicted to be lower in nicotine treated groups, which were simulated by increasing the dearylation Vmax based upon previously conducted in vitro metabolism studies. These results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, further modulating brain AChE inhibition.

  2. UGT2B10 genotype influences nicotine glucuronidation, oxidation and consumption

    PubMed Central

    Berg, Jeannette Zinggeler; von Weymarn, Linda; Thompson, Elizabeth A.; Wickham, Katherine M.; Weisensel, Natalie A.; Hatsukami, Dorothy K.; Murphy, Sharon E.

    2010-01-01

    Background Tobacco exposure is routinely assessed by quantifying nicotine metabolites in plasma or urine. On average, 80% of nicotine undergoes C-oxidation to cotinine. However, interindividual variation in nicotine glucuronidation is substantial and glucuronidation accounts for from 0 to 40% of total nicotine metabolism. We report here the effect of a polymorphism in a UDP-glucuronsyl transferase, UGT2B10, on nicotine metabolism and consumption. Methods Nicotine, cotinine, their N-glucuronide conjugates, and total trans-3'-hydroxycotinine were quantified in the urine (n=327) and plasma (n =115) of smokers. Urinary nicotine N-oxide was quantified in 105 smokers. Nicotine equivalents, the sum of nicotine and all major metabolites, were calculated for each smoker. The relationship of the UGT2B10 Asp67Tyr allele to nicotine equivalents, N-glucuronidation, and C-oxidation was determined. Results Individuals heterozygous for the Asp67Tyr allele excreted less nicotine or cotinine as their glucuronide conjugates than wild-type, resulting in a 60% lower ratio of cotinine glucuronide:cotinine, a 50% lower ratio of nicotine glucuronide:nicotine and increased cotinine and trans-3'-hydroxycotinine. Nicotine equivalents, a robust biomarker of nicotine intake, were lower among Asp67Tyr heterozygotes compared to individuals without this allele; 58.2 nmol/ml (95% CI, 48.9 – 68.2) versus 69.2 nmol/ml (95% CI, 64.3 – 74.5). Conclusions Individuals heterozygous for UGT2B10 Asp67Tyr consume less nicotine than do wild type smokers. This striking observation suggests that variations in nicotine N-glucuronidation, as reported for nicotine C-oxidation, may influence smoking behavior. Impact UGT2B10 genotype influences nicotine metabolism and should be taken into account when characterizing the role of nicotine metabolism on smoking. PMID:20501767

  3. Nicotine activates and up-regulates nicotinic acetylcholine receptors in bronchial epithelial cells.

    PubMed

    Fu, Xiao Wen; Lindstrom, Jon; Spindel, Eliot R

    2009-07-01

    Prenatal nicotine exposure impairs normal lung development and leads to diminished pulmonary function after birth. Previous work from our laboratory has demonstrated that nicotine alters lung development by affecting a nonneuronal cholinergic autocrine loop that is expressed in lung. Bronchial epithelial cells (BECs) express choline acetyltransferase, the choline high-affinity transporter and nicotinic acetylcholine (ACh) receptor (nAChR) subunits. We now demonstrate through a combination of morphological and electrophysiological techniques that nicotine affects this autocrine loop by up-regulating and activating cholinergic signaling. RT-PCR showed the expression of alpha 3, alpha 4, alpha 7, alpha 9, alpha 10, beta2, and beta 4 nAChR mRNAs in rhesus monkey lung and cultured BECs. The expression of alpha 7, alpha 4, and beta2 nAChR was confirmed by immunofluorescence in the cultured BECs and lung. The electrophysiological characteristics of nAChR in BECs were determined using whole-cell patch-clamp on cultured BECs. Both ACh and nicotine evoked an inward current, with a rapid desensitizing current. Nicotine induced inward currents in a concentration-dependent manner, with an EC(50) of 26.7 microM. Nicotine-induced currents were reversibly blocked by the nicotinic antagonists, mecamylamine, dihydro-beta-erythroidine, and methyllcaconitine. Incubation of BECs with 1 microM nicotine for 48 hours enhanced nicotine-induced currents by roughly 26%. The protein tyrosine phosphorylation inhibitor, genistein, increased nicotine-induced currents by 58% and enhanced methyllcaconitine-sensitive currents (alpha 7 nAChR activities) 2.3-fold, whereas the protein tyrosine phosphatase inhibitor, pervanadate, decreased the effects of nicotine. These results demonstrate that chronic nicotine exposure up-regulates nAChR activity in developing lung, and that nAChR activity can be further modified by tyrosine phosphorylation.

  4. In vitro effects of nicotine on sperm motility and bio-functional flow cytometry sperm parameters.

    PubMed

    Condorelli, R A; La Vignera, S; Giacone, F; Iacoviello, L; Vicari, E; Mongioi', L; Calogero, A E

    2013-01-01

    The aim of this experimental study was to evaluate the effects of nicotine on sperm motility and on non-conventional sperm parameters in vitro. Capacitated spermatozoa isolated from 10 normozoospermic, healthy, non-smoker men were evaluated. Spermatozoa were exposed to increasing concentrations of nicotine (0, 1, 10, and 100 ng/ml) for 3 and 24 hours. Progressive motility and the following non-conventional sperm parameters, evaluated by flow cytometry, were assessed: mitochondrial membrane potential, viability, phosphatidylserine externalization, late apoptosis, degree of chromatin compactness, and DNA fragmentation. Nicotine suppressed, in a concentration-dependent manner, sperm progressive motility starting from the lowest concentration used (1 ng/ml). Similarly, it reduced the percentage of viable spermatozoa and increased the number of spermatozoa in late apoptosis, with altered chromatin compactness, or DNA fragmentation already after 3 hours of incubation. These effects were observed at a concentration similar (100 ng/ml) to that found in the seminal plasma of smokers (70 ng/ml), with the exception of the effects on sperm DNA fragmentation whose significant effect was detected also at a lower concentration (10 ng/ml). Nicotine may be regarded as a noxious component of cigarette smoke on the male reproductive function.

  5. Binding to plasma lipoproteins of chlorophenoxyisobutyric, tibric and nicotinic acids and their esters: its significance for the mechanism of lipid lowering by clofibrate and related drugs.

    PubMed

    Beaumont, J L; Dachet, C

    1976-01-01

    The binding of chlorophenoxyisobutyric (CPIB), tibric (TA) and nicotinic (NA) acids and CPIB ethyl ester (Clofibrate), TA and NA isopropyl esters (TAPE and NAPE) to human lipoproteins of low density of different classes (LDL2, LDL1 and VLDL) and high density (HDL) were studied by equilibrium dialysis and Sephadex gel filtration. Clofibrate and TAPE bound strongly to lipoproteins, but their acids, CPIB and TA and also NA and NAPE, did not bind. In the same experimental conditions, Clofibrate and TAPE bound only weakly to human serum albumin (HSA) and CPIB bound to HSA with a Ka of 3.3 X 10(5) M(-1) for 1 site of high affinity. The Clofibrate and TAPE bound to lipoproteins did not dissociate either during dialysis or during filtration on Sephadex G 25. The binding percentage remained constant for all drug concentrations studied, and the molar ratio of bound drug rose linearly with increasing concentrations. This suggests that the interaction may be irreversible, and there is some evidence that binding may induce irreversible changes in the lipoprotein molecules. These results, and those already found in experiments made with three other drugs related to Clofibrate, lead to the proposal that in their interaction with lipoproteins, the phenyl groups are necessary and the esterification is contributory. The possible role of this interaction in the lipid-lowering effect of the drugs is discussed with special reference to their possible implication in lipoprotein synthesis within the intestinal and hepatic cells.

  6. Lutein supplementation increases breast milk and plasma lutein concentrations in lactating women and infant plasma concentrations but does not affect other carotenoids.

    PubMed

    Sherry, Christina L; Oliver, Jeffery S; Renzi, Lisa M; Marriage, Barbara J

    2014-08-01

    Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2-3 mo postpartum. Lutein is the dominant carotenoid in the infant brain and the major carotenoid found in the retina of the eye. Eighty-nine lactating women 4-6 wk postpartum were randomly assigned to be administered either 0 mg/d of lutein (placebo), 6 mg/d of lutein (low-dose), or 12 mg/d of lutein (high-dose). The supplements were consumed for 6 wk while mothers followed their usual diets. Breast milk carotenoids were measured weekly by HPLC, and maternal plasma carotenoid concentrations were measured at the beginning and end of the study. Infant plasma carotenoid concentrations were assessed at the end of the study. No significant differences were found between dietary lutein + zeaxanthin intake and carotenoid concentrations in breast milk and plasma or body mass index at baseline. Total lutein + zeaxanthin concentrations were greater in the low- and high-dose-supplemented groups than in the placebo group in breast milk (140% and 250%, respectively; P < 0.0001), maternal plasma (170% and 250%, respectively; P < 0.0001), and infant plasma (180% and 330%, respectively; P < 0.05). Lutein supplementation did not affect other carotenoids in lactating women or their infants. Lactating women are highly responsive to lutein supplementation, which affects plasma lutein concentrations in the infant. This trial was registered at clinicaltrials.gov as NCT01747668.

  7. Genetic Factors for Enhancement of Nicotine Levels in Cultivated Tobacco.

    PubMed

    Wang, Bingwu; Lewis, Ramsey S; Shi, Junli; Song, Zhongbang; Gao, Yulong; Li, Wenzheng; Chen, Hongxia; Qu, Rongda

    2015-12-02

    Nicotine has practical applications relating to smoking cessation devices and alternative nicotine products. Genetic manipulation for increasing nicotine content in cultivated tobacco (Nicotiana tabacum L.) may be of value for industrial purposes, including the possibility of enhancing the efficiency of nicotine extraction. Biotechnological approaches have been evaluated in connection with this objective, but field-based results are few. Here, we report characterization of two genes encoding basic-helix-loop-helix (bHLH) transcription factors (TFs), NtMYC2a and NtMYC2b from tobacco. Overexpression of NtMYC2a increased leaf nicotine levels in T1 transgenic lines approximately 2.3-fold in greenhouse-grown plants of tobacco cultivar 'NC 95'. Subsequent field testing of T2 and T3 generations of transgenic NtMYC2a overexpression lines showed nicotine concentrations were 76% and 58% higher than control lines, respectively. These results demonstrated that the increased nicotine trait was stably inherited to the T2 and T3 generations, indicating the important role that NtMYC2a plays in regulating nicotine accumulation in N. tabacum and the great potential of NtMYC2a overexpression in tobacco plants for industrial nicotine production. Collected data in this study also indicated a negative feedback inhibition of nicotine biosynthesis. Further enhancement of nicotine accumulation in tobacco leaf may require modification of the processes of nicotine transport and deposition.

  8. Characterization of SPECTRUM Variable Nicotine Research Cigarettes

    PubMed Central

    Richter, Patricia; Steven, Pappas R.; Bravo, Roberto; Lisko, Joseph G.; Damian, Maria; Gonzalez-Jimenez, Nathalie; Gray, Naudia; Keong, Lisa M.; Kimbrell, Jacob B.; Kuklenyik, Peter; Lawler, Tameka S.; Lee, Grace E.; Mendez, Magaly; Perez, Jose; Smith, Shakia; Tran, Hang; Tyx, Robert; Watson, Clifford H.

    2016-01-01

    Objective To provide researchers an extensive characterization of the SPECTRUM variable nicotine research cigarettes. Methods Data on cigarette physical properties, nicotine content, harmful and potentially harmful constituents in the tobacco filler was compiled. Results Data on physical properties, concentrations of menthol, nicotine and minor alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, ammonia, and toxic metals in the filler tobacco for all available varieties of Spectrum research cigarettes are provided. The similarity in the chemistry and physical properties of SPECTRUM cigarettes to commercial cigarettes renders them acceptable for use in behavioral studies. Baseline information on harmful and potentially harmful constituents in research tobacco products, particularly constituent levels such as minor alkaloids that fall outside typical ranges reported for commercial, provide researchers with the opportunity to monitor smoking behavior and to identify biomarkers that will inform efforts to understand the role of nicotine in creating and sustaining addiction. Conclusions Well characterized research cigarettes suitable for human consumption are an important tool in clinical studies for investigating the physiological impacts of cigarettes delivering various levels of nicotine, the impact of reduced nicotine cigarettes on nicotine addiction, and the relationship between nicotine dose and smoking behavior. PMID:26779559

  9. Nicotine-motivated behavior in Caenorhabditis elegans requires the nicotinic acetylcholine receptor subunits acr-5 and acr-15.

    PubMed

    Sellings, Laurie; Pereira, Schreiber; Qian, Cheng; Dixon-McDougall, Thomas; Nowak, Christina; Zhao, Bin; Tyndale, Rachel F; van der Kooy, Derek

    2013-03-01

    Signaling at nicotinic acetylcholine receptors in Caenorhabditis elegans controls many behaviors, including egg-laying and locomotor activity. Here, we show that C. elegans approaches a point source of nicotine in a time-, concentration- and age-dependent manner. Additionally, nicotine paired with butanone under starvation conditions prevented the reduced approach to butanone that is observed when butanone is paired with starvation alone and pairing with nicotine generates a preference for the tastes of either sodium or chloride over baseline. These results suggest nicotine acts as a rewarding substance in C. elegans. Furthermore, the nicotinic receptor antagonist mecamylamine, the smoking cessation pharmacotherapy varenicline, mutation of the dop-1 and dop-2 dopamine receptors, and mutations of either acr-5 or acr-15, two nicotinic receptor subunit genes with sequence homology to the mammalian α7 subunit, all reduced the nicotine approach behavior. These two mutants also were defective at associating the presence of nicotine with butanone under starvation conditions and acr-5 mutation could obviate the effect of pairing nicotine with salts. Furthermore, the approach deficit in acr-15 mutants was rescued by selective re-expression in a subset of neurons, but not in muscle. Caenorhabditis elegans may therefore serve as a useful model organism for nicotine-motivated behaviors that could aid in the identification of novel nicotine motivational molecular pathways and consequently the development of novel cessation aids.

  10. Alteration in contractile G-protein coupled receptor expression by moist snus and nicotine in rat cerebral arteries

    SciTech Connect

    Sandhu, Hardip; Xu Cangbao; Edvinsson, Lars

    2011-04-15

    The cardiovascular risk for users of use of Swedish snus/American snuff (moist tobacco) has been debated for a long time. The present study was designed to examine the effects of water- or lipid-soluble (DMSO-soluble) snus and nicotine, the most important substance in tobacco, on the expression of vasocontractile G-protein coupled receptors (GPCR), such as endothelin ET{sub B}, serotonin 5-HT{sub 1B}, and thromboxane A{sub 2} TP receptors, in rat cerebral arteries. Studies show that these vasocontractile GPCR show alterations by lipid-soluble cigarette smoke particles via activation of mitogen-activated protein kinases (MAPK). However, the effects of moist tobacco on the expression of GPCR are less studied. Rat middle cerebral arteries were isolated and organ cultured in serum-free medium for 24 h in the presence of water-soluble snus (WSS), DMSO-soluble snus (DSS), or nicotine. The dose of snus and nicotine was kept at plasma level of snus users (25 ng nicotine/ml). A high dose (250 ng nicotine/ml) was also included due to the previous results showing alteration in the GPCR expression by nicotine at this concentration. Contractile responses to the ET{sub B} receptor agonist sarafotoxin 6c, 5-HT{sub 1B} receptor agonist 5-carboxamidotryptamine, and TP receptor agonist U46619 were investigated by a sensitive myograph. The expression of ET{sub B}, 5-HT{sub 1B}, and TP receptors was studied at mRNA and protein levels using quantitative real-time PCR and immunohistochemistry, respectively. Organ culture with WSS or DSS (25 ng nicotine/ml) lowered the 5-HT{sub 1B} receptor-mediated contraction. Furthermore, DSS shifted the TP receptor-mediated contraction curve left-wards with a stronger contraction. High dose of nicotine (250 ng nicotine/ml) increased the ET{sub B} receptor-mediated contraction. The combined 5-HT{sub 1B} and 5-HT{sub 2A} receptor-mediated contraction was increased, and both the 5-CT and TxA2 induced contractions were left-ward shifted by WSS, DSS, or

  11. Insulinotropic effect of high potassium concentration beyond plasma membrane depolarization.

    PubMed

    Belz, M; Willenborg, M; Görgler, N; Hamada, A; Schumacher, K; Rustenbeck, I

    2014-03-01

    The question whether K⁺ depolarization is an appropriate experimental substitute for the physiological nutrient-induced depolarization of the β-cell plasma membrane was investigated using primary mouse β-cells and islets. At basal glucose 40 mM K⁺ induced a massive monophasic response, whereas 15 mM K⁺ had only a minimal insulinotropic effect, even though the increase in the cytosolic Ca²⁺ concentration ([Ca²⁺]i) was not inferior to that by 20 mM glucose. In voltage-clamp experiments, Ca²⁺ influx appeared as nifedipine-inhibitable inward action currents in the presence of sulfonylurea plus TEA to block compensatory outward K⁺ currents. Under these conditions, 15 mM K⁺ induced prolonged action currents and 40 mM K⁺ transformed the action current pattern into a continuous inward current. Correspondingly, 15 mM K⁺ led to an oscillatory increase and 40 mM K⁺ to a plateau of [Ca²⁺]i superimposed on the [Ca²⁺]i elevated by sulfonylurea plus TEA. Raising K⁺ to 15 or 40 mM in the presence of sulfonylurea (±TEA) led to a fast further increase of insulin secretion. This was reduced to basal levels by nifedipine or CoCl₂. The effects of 15 mM K⁺ on depolarization, action currents, and insulin secretion were mimicked by adding 35 mM Cs⁺ and those of 40 mM K⁺ by adding 35 mM Rb⁺, in parallel with their ability to substitute for K⁺ as permeant cation. In conclusion, the alkali metals K⁺, Rb⁺, or Cs⁺ concentration-dependently transform the pattern of Ca²⁺ influx into the β-cell and may thus generate stimuli of supraphysiological strength for insulin secretion.

  12. Action of ethanol on responses to nicotine from cerebellar Purkinje neurons: relationship to methyllycaconitine (MLA) inhibition of nicotine responses.

    PubMed

    Yang, X; Criswell, H E; Breese, G R

    1999-08-01

    The effect of ethanol on responses to nicotine from rat cerebellar Purkinje neurons was investigated using extracellular single-unit recording. Systemic administration of ethanol initially enhanced the nicotine-induced inhibition from 50% of the Purkinje neurons. However, irrespective of whether there was an initial enhancement, systemic administration of ethanol antagonized the response to nicotine from the majority of Purkinje neurons. When varying ethanol concentrations were electro-osmotically applied to this neuronal cell type, the responses to nicotine (6/8) were enhanced when a low concentration of ethanol (40 mM) was in the pipette, whereas the majority of nicotine responses (10/11) were antagonized when a higher concentration of ethanol (160 mM) was applied to Purkinje neurons. Thus, the concentration of ethanol presented to the neuron seemed to explain the biphasic consequence of systemically administered ethanol on responses to nicotine. In order to determine whether ethanol affected a specific nACh receptor subtype containing the alpha-7 subunit, it was initially established that the nicotinic antagonists, alpha-bungarotoxin (alpha-BTX) and methyllycaconitine (MLA), which are associated with this subunit, had identical actions on responses to nicotine from Purkinje neurons. When MLA was tested against responses to nicotine from this cell type, MLA antagonized the response to nicotine from 45% (9/20) of the neurons tested. In a direct comparison of the action of ethanol to inhibit responses to nicotine with the action of MLA on the same Purkinje neuron, ethanol inhibited responses to nicotine on all neurons sensitive to MLA. However, ethanol also affected nicotine-induced neural changes from some Purkinje neurons not sensitive to MLA antagonism of nicotine. These data support the supposition that ethanol affects a nACh receptor subtype which has an alpha-7 subunit as well as other nACh receptor subtypes without this specific subunit.

  13. Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine: effects of route and ethanol coadministration

    PubMed Central

    Katner, Simon N.; Toalston, Jamie E.; Smoker, Michael P.; Rodd, Zachary A.; McBride, William J.

    2015-01-01

    Rationale Nicotine and ethanol are commonly coabused drugs, and nicotine-laced ethanol products are growing in popularity. However, little is known about time-course changes in extracellular nicotine and cotinine levels in rat models of ethanol and nicotine coabuse. Objectives The objective of the present study was to determine the time-course changes in brain levels of nicotine and cotinine following subcutaneous (SC) and intragastric (IG) nicotine administration in alcohol-preferring (P) and Wistar rats. Methods In vivo microdialysis was used to collect dialysate samples from the nucleus accumbens shell (NACsh) for nicotine and cotinine determinations, following SC administration of (−)-nicotine (0.18, 0.35, and 0.70 mg/kg) in female P and Wistar rats or IG administration of (−)-nicotine (0.35 and 0.70 mg/kg) in 15 % (v/v) ethanol or water in female P rats. Results SC nicotine produced nicotine and cotinine dialysate levels as high as 51 and 14 ng/ml, respectively. IG administration of 15 % EtOH + 0.70 mg/kg nicotine in P rats resulted in maximal nicotine and cotinine dialysate levels of 19 and 14 ng/ml, respectively, whereas administration of 0.70 mg/kg nicotine in water resulted in maximal nicotine and cotinine levels of 21 and 25 ng/ml, respectively. Nicotine and cotinine levels were detectable within the first 15 and 45 min, respectively, after IG administration. Conclusions Overall, the results of this study suggest that nicotine is rapidly adsorbed and produces relevant extracellular brain concentrations of nicotine and its pharmacologically active metabolite, cotinine. The persisting high brain concentrations of cotinine may contribute to nicotine addiction. PMID:25038869

  14. Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

    SciTech Connect

    Lee, Soo Kwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

    2010-03-30

    Chlorpyrifos (CPF) is one of the most studied and widely used broad spectrum organophosphorus (OP) insecticides. The neurotoxicity of CPF results from inhibition of cholinesterase (ChE) by its metabolite, chlorpyrifos-oxon (CPF-oxon), which subsequently leads to cholinergic hyperstimulation. The routine consumption of alcoholic beverages and tobacco products will modify a number of metabolic and physiological processes which may impact the metabolism and pharmacokinetics of other xenobiotics including pesticides. The objective of this study was to evaluate the influence of repeated ethanol and nicotine co-exposure on in vivo CPF pharmacokinetics and pharmacodynamics. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine along with changes in plasma and brain AChE activities were measured in male Sprague-Dawley (S-D) rats. Animals were repeatedly treated with either saline or ethanol (1 g/kg/day, po) and nicotine (1 mg/kg/day, sc) in addition to CPF (1 or 5 mg/kg/day, po) for 7 days. Rats were sacrificed at times from 1 to 24 hr post-last dosing of CPF. There were apparent differences in blood TCPy pharmacokinetics following ethanol and nicotine pretreatments in both CPF dose groups, which showed higher TCPy peak concentrations and increased blood TCPy AUC in ethanol and nicotine groups over CPF-only (~1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain acetylcholinesterase (AChE) activities from both ethanol and nicotine-treated groups showed substantially less inhibition following repeated 5 mg CPF/kg dosing compared to CPF-only controls (96 ± 13 and 66 ± 7% of naïve at 4 hr post-last CPF dosing, respectively). Inhibition of brain AChE activities was minimal in both 1 mg CPF/kg/day dosing groups, but a similar trend indicating less inhibition following ethanol/nicotine pretreatment was apparent. No differences were observed in plasma ChE activities due to the combined alcohol and nicotine treatments. In vitro, CPF

  15. Linkage between cholesterol 7alpha-hydroxylase and high plasma low-density lipoprotein cholesterol concentrations.

    PubMed Central

    Wang, J; Freeman, D J; Grundy, S M; Levine, D M; Guerra, R; Cohen, J C

    1998-01-01

    Interindividual differences in plasma low-density lipoprotein cholesterol (LDL-C) levels reflect both environmental variation and genetic polymorphism, but the specific genes involved and their relative contributions to the variance in LDL-C are not known. In this study we investigated the relationship between plasma LDL-C concentrations and three genes with pivotal roles in LDL metabolism: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and cholesterol 7alpha-hydroxylase (CYP7). Analysis of 150 nuclear families indicated statistically significant linkage between plasma LDL-C concentrations and CYP7, but not LDLR or APOB. Further sibling pair analyses using individuals with high plasma LDL-C concentrations as probands indicated that the CYP7 locus was linked to high plasma LDL-C, but not to low plasma LDL-C concentrations. This finding was replicated in an independent sample. DNA sequencing revealed two linked polymorphisms in the 5' flanking region of CYP7. The allele defined by these polymorphisms was associated with increased plasma LDL-C concentrations, both in sibling pairs and in unrelated individuals. Taken together, these findings indicate that polymorphism in CYP7 contributes to heritable variation in plasma LDL-C concentrations. Common polymorphisms in LDLR and APOB account for little of the heritable variation in plasma LDL-C concentrations in the general population. PMID:9502769

  16. Inside-out neuropharmacology of nicotinic drugs.

    PubMed

    Henderson, Brandon J; Lester, Henry A

    2015-09-01

    Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable AChR pentamers. These changes and stabilizations in turn lead to increases in both anterograde and retrograde traffic within the early secretory pathway. In addition to the eventual upregulation of AChRs at the plasma membrane, other effects of pharmacological chaperoning include modifications to endoplasmic reticulum stress and to the unfolded protein response. Because these processes depend on pharmacological chaperoning within intracellular organelles, we group them as "inside-out pharmacology". This term contrasts with the better-known, acute, "outside-in" effects of activating and desensitizing plasma membrane AChRs. We review current knowledge concerning the mechanisms and consequences of inside-out pharmacology. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. PMID:25660637

  17. Escalating doses of transdermal nicotine in heavy smokers: effects on smoking behavior and craving.

    PubMed

    Selby, Peter; Andriash, Katherine; Zawertailo, Laurie; Persad, Desmond; Zack, Martin; Busto, Usoa E

    2013-10-01

    Fixed-dose nicotine replacement therapy (NRT) is efficacious for smoking cessation in the general population of smokers. However, it is less effective in populations with psychiatric comorbidities and/or severe tobacco dependence where the percent nicotine replacement is suboptimal. The objective of this pilot study was to determine the effectiveness of nicotine patch dose titration in response to continued smoking in heavily dependent smokers with psychiatric comorbidity. In a single-arm, open-label study adult smokers (mean cigarettes per day, 25.4 ± 13.4; range, 14-43; n = 12) willing to quit were treated with escalating doses of transdermal nicotine and brief counseling intervention if they continued to smoke over a 9-week treatment period. Plasma nicotine and cotinine, along with expired carbon monoxide levels, and the subjective effects of smoking, urge to smoke, demand elasticity, and mood symptoms were also assessed. The mean NRT dose was 32.7 (SD, 16.4) mg/d (range, 7-56 mg/d). Smokers reported significant reductions in both cigarettes per day (mean decrease, 18.4 ± 11.5) confirmed by expired carbon monoxide (mean decrease, 13.5 ± 13.0) with no significant changes in plasma nicotine concentrations during the course of NRT dose titration. There were significant effects on the subjective effects of smoking and measures of smoking behavior. Most commonly reported adverse events were respiratory infections, skin irritation at patch site, nausea, and sleep disturbances, which were generally mild and transient. Titrating doses of NRT to effect with brief intervention hold promise as an effective clinical strategy to assist heavily dependent psychiatrically ill smokers to change their smoking behavior.

  18. Effect of chronic nicotine pre-treatment on phencyclidine (PCP) disposition in the rat.

    PubMed

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

    1983-09-01

    Disposition of [3H] phencyclidine (5 mg kg-1 i.p.) in brain, liver and plasma of rats treated chronically with 0.9% saline or nicotine (1 mg kg-1 s.c. twice a day for 11 days) was studied using a method possessing high sensitivity and specificity for PCP. No significant differences were observed in the values of PCP in plasma and tissues and in brain or liver to plasma PCP concentration ratios in the 2 groups 0.5, 1, 2 hr after [3H] PCP injection. With the exception of the value of PCP metabolites in plasma at 0.5 hr, the PCP metabolites concentrations were also not significantly different in the 2 groups. Data suggested that chronic nicotine pretreatment of rats did not affect the disposition of PCP and the potentiation of PCP-induced locomotor stimulant effects by nicotine possibly involves the additive pharmacodynamic interaction of 2 compounds at the level of the central nervous system. PMID:6651404

  19. Stress-induced changes in corticosteroid metabolism. [plasma and urine concentrations

    NASA Technical Reports Server (NTRS)

    Tacker, M. M.

    1975-01-01

    Because plasma and urine corticosteroid concentrations are influenced by several factors in addition to adrenal cortex secretion, the effect of stress on all of these factors was determined in order to interpret the plasma and urine concentrations. Progress on the investigation is reported.

  20. Plasma and Intracellular Antiretroviral Concentrations in HIV-Infected Patients under Short Cycles of Antiretroviral Therapy

    PubMed Central

    Zehnacker, Laura; Abe, Emuri; Mathez, Dominique; Alvarez, Jean-Claude; Leibowitch, Jacques; Azoulay, Stéphane

    2014-01-01

    Study of plasma and intracellular concentrations of atazanavir, lopinavir, nevirapine, and efavirenz was conducted on 48 patients under short cycles of antiretroviral therapy. Intracellular concentrations (IC) were still measurable for all drugs after 85 h or 110 h drug intake despite the absence of drug in plasma for atazanavir and lopinavir. A linear relationship between plasma and intracellular efavirenz was observed. Further studies to fully understand the impact of IC in the intermittent antiviral treatment are required. PMID:25431661

  1. Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans.

    PubMed

    Butler, Andrew A; St-Onge, Marie-Pierre; Siebert, Emily A; Medici, Valentina; Stanhope, Kimber L; Havel, Peter J

    2015-10-05

    Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations.

  2. Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans.

    PubMed

    Butler, Andrew A; St-Onge, Marie-Pierre; Siebert, Emily A; Medici, Valentina; Stanhope, Kimber L; Havel, Peter J

    2015-01-01

    Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations. PMID:26435060

  3. Elevated plasma and urinary concentrations of green tea catechins associated with improved plasma lipid profile in healthy Japanese women.

    PubMed

    Takechi, Ryusuke; Alfonso, Helman; Hiramatsu, Naoko; Ishisaka, Akari; Tanaka, Akira; Tan, La'Belle; Lee, Andy H

    2016-03-01

    This study investigated green tea catechins in plasma and urine and chronic disease biomarkers. We hypothesized that plasma and urinary concentration of green tea catechins are associated with cardiovascular disease and diabetes biomarkers. First void urine and fasting plasma samples were collected from 57 generally healthy females aged 38 to 73 years (mean, 52 ± 8 years) recruited in Himeji, Japan. The concentrations of plasma and urinary green tea catechins were determined by liquid chromatography coupled with mass tandem spectrometer. Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, glucose, insulin, glycated hemoglobin, and C-reactive protein in plasma/serum samples were analyzed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman correlation coefficients. The results showed weak associations between plasma total catechin and triglyceride (r = -0.30) and LDL cholesterol (r = -0.28), whereas plasma (-)-epigallocatechin-3-gallate, (-)-epigallocatechin, (-)-epicatechin-3-gallate, and (-)-epicatechin exhibited weak to moderate associations with triglyceride or LDL cholesterol, but little associations with HDL cholesterol, body fat, and body mass index were evident. Urinary total catechin was weakly associated with triglyceride (r = -0.19) and LDL cholesterol (r = -0.15), whereas urinary (-)-epigallocatechin-3-gallate (r = -0.33), (-)-epigallocatechin (r = -0.23), and (-)-epicatechin-3-gallate (r = -0.33) had weak to moderate correlations with triglyceride and similarly with body fat and body mass index. Both plasma (r = -0.24) and urinary (r = -0.24) total catechin, as well as individual catechins, were weakly associated with glycated hemoglobin. Plasma total and individual catechins were weakly to moderately associated with C-reactive protein, but not the case for urinary catechins. In conclusion, we found weak to moderate associations between plasma and urinary green tea

  4. Elevated plasma and urinary concentrations of green tea catechins associated with improved plasma lipid profile in healthy Japanese women.

    PubMed

    Takechi, Ryusuke; Alfonso, Helman; Hiramatsu, Naoko; Ishisaka, Akari; Tanaka, Akira; Tan, La'Belle; Lee, Andy H

    2016-03-01

    This study investigated green tea catechins in plasma and urine and chronic disease biomarkers. We hypothesized that plasma and urinary concentration of green tea catechins are associated with cardiovascular disease and diabetes biomarkers. First void urine and fasting plasma samples were collected from 57 generally healthy females aged 38 to 73 years (mean, 52 ± 8 years) recruited in Himeji, Japan. The concentrations of plasma and urinary green tea catechins were determined by liquid chromatography coupled with mass tandem spectrometer. Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, glucose, insulin, glycated hemoglobin, and C-reactive protein in plasma/serum samples were analyzed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman correlation coefficients. The results showed weak associations between plasma total catechin and triglyceride (r = -0.30) and LDL cholesterol (r = -0.28), whereas plasma (-)-epigallocatechin-3-gallate, (-)-epigallocatechin, (-)-epicatechin-3-gallate, and (-)-epicatechin exhibited weak to moderate associations with triglyceride or LDL cholesterol, but little associations with HDL cholesterol, body fat, and body mass index were evident. Urinary total catechin was weakly associated with triglyceride (r = -0.19) and LDL cholesterol (r = -0.15), whereas urinary (-)-epigallocatechin-3-gallate (r = -0.33), (-)-epigallocatechin (r = -0.23), and (-)-epicatechin-3-gallate (r = -0.33) had weak to moderate correlations with triglyceride and similarly with body fat and body mass index. Both plasma (r = -0.24) and urinary (r = -0.24) total catechin, as well as individual catechins, were weakly associated with glycated hemoglobin. Plasma total and individual catechins were weakly to moderately associated with C-reactive protein, but not the case for urinary catechins. In conclusion, we found weak to moderate associations between plasma and urinary green tea

  5. Transdermal nicotine absorption handling e-cigarette refill liquids.

    PubMed

    Maina, Giovanni; Castagnoli, Carlotta; Passini, Valter; Crosera, Matteo; Adami, Gianpiero; Mauro, Marcella; Filon, Francesca Larese

    2016-02-01

    The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids.

  6. Plasma steroid concentrations change in response to sexual behavior in Bufo marinus.

    PubMed

    Orchinik, M; Licht, P; Crews, D

    1988-09-01

    Steroid hormone concentrations change in response to social or environmental stimuli in many vertebrates. To test this phenomenon in an amphibian, we examined plasma androgen (A) and corticosterone (B) concentrations in male marine toads (Bufo marinus), a tropical species exhibiting intermale competition, amplectic clasping of females, and bouts of breeding behavior following rains. When males clasped females for 0, 1, 2, or 3 hr, plasma A concentrations were significantly and positively correlated with hours spent in amplexus. In field-sampled males, plasma A concentrations were higher in amplexing males than in single males. Among single males those found closer to breeding ponds had higher A concentrations than those more distant. These data support the hypothesis that sexual stimuli enhance plasma A concentrations in this amphibian. In 3-hr experimental tests and field-sampled males, B concentrations were higher in amplexing than in single males. Unlike some amphibians, short-term elevations of B apparently are not associated with decreased reproductive function. However, as in other amphibians in which high B concentrations are associated with stress-induced inhibition of reproduction, after 48-72 hr in captivity male toads showed high B concentrations and low plasma androgen concentrations. The bursts of sexual activities exhibited by B. marinus following heavy rains were associated with no changes in A concentration and with increased B concentration. PMID:3139541

  7. Plasma Concentration of Parasite DNA as a Measure of Disease Severity in Falciparum Malaria

    PubMed Central

    Imwong, Mallika; Woodrow, Charles J.; Hendriksen, Ilse C. E.; Veenemans, Jacobien; Verhoef, Hans; Faiz, M. Abul; Mohanty, Sanjib; Mishra, Saroj; Mtove, George; Gesase, Samwel; Seni, Amir; Chhaganlal, Kajal D.; Day, Nicholas P. J.; Dondorp, Arjen M.; White, Nicholas J.

    2015-01-01

    In malaria-endemic areas, Plasmodium falciparum parasitemia is common in apparently healthy children and severe malaria is commonly misdiagnosed in patients with incidental parasitemia. We assessed whether the plasma Plasmodium falciparum DNA concentration is a useful datum for distinguishing uncomplicated from severe malaria in African children and Asian adults. P. falciparum DNA concentrations were measured by real-time polymerase chain reaction (PCR) in 224 African children (111 with uncomplicated malaria and 113 with severe malaria) and 211 Asian adults (100 with uncomplicated malaria and 111 with severe malaria) presenting with acute falciparum malaria. The diagnostic accuracy of plasma P. falciparum DNA concentrations in identifying severe malaria was 0.834 for children and 0.788 for adults, similar to that of plasma P. falciparum HRP2 levels and substantially superior to that of parasite densities (P < .0001). The diagnostic accuracy of plasma P. falciparum DNA concentrations plus plasma P. falciparum HRP2 concentrations was significantly greater than that of plasma P. falciparum HRP2 concentrations alone (0.904 for children [P = .004] and 0.847 for adults [P = .003]). Quantitative real-time PCR measurement of parasite DNA in plasma is a useful method for diagnosing severe falciparum malaria on fresh or archived plasma samples. PMID:25344520

  8. A pilot study on nicotine residues in houses of electronic cigarette (e-cigarette) users, tobacco smokers, and non-users of nicotine-containing products

    PubMed Central

    Bush, Derek; Goniewicz, Maciej L.

    2015-01-01

    Background Nicotine deposited on the surfaces has been shown to react with airborne chemicals leading to formation of carcinogens and contributing to thirdhand exposure. While prior studies revealed nicotine residues in tobacco smokers' homes, none have examined the nicotine residue in electronic cigarette (e-cigarette) users' homes. Methods We measured nicotine on the surfaces in households of 8 e-cigarette users, 6 cigarette smokers, and 8 non-users of nicotine-containing products in Western New York, USA. Three surface wipe samples were taken from the floor, wall and window. Nicotine was extracted from the wipes and analyzed using gas chromatography. Results Half of the e-cigarette users' homes had detectable levels of nicotine on surfaces whereas nicotine was found in all of the tobacco cigarette smokers' homes. Trace amounts of nicotine were also detected in half of the homes of non-users of nicotine-containing products. Nicotine levels in e-cigarette users homes was significantly lower than that found in cigarette smokers homes (average concentration 7.7±17.2 vs. 1,303±2,676 μg/m2; p<0.05). There was no significant difference in the amount of nicotine in homes of e-cigarette users and non-users (p>0.05). Conclusions Nicotine is a common contaminant found on indoor surfaces. Using e-cigarettes indoors leads to significantly less thirdhand exposure to nicotine compared to smoking tobacco cigarettes. PMID:25869751

  9. Plane of nutrition affects plasma ghrelin concentrations in neonatal calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Investigating different planes of nutrition on appetite-related hormones could provide knowledge into the role of these hormones on growth performance in neonatal calves. The objective of the current study was to investigate the effects of feeding rates on ghrelin in plasma from preruminant calves....

  10. Comparison of the Pharmacokinetics of Nicotine Following Single and Ad Libitum Use of a Tobacco Heating System or Combustible Cigarettes

    PubMed Central

    Picavet, Patrick; Haziza, Christelle; Lama, Nicola; Weitkunat, Rolf

    2016-01-01

    Introduction: We aimed to compare the pharmacokinetics of nicotine between the heat-not-burn Tobacco Heating System 2.1 (THS 2.1) and combustible cigarettes (CCs). We also examined whether the subjective urge to smoke was associated with the pharmacokinetics of nicotine. Methods: This open-label, randomized, two-period, two-sequence crossover study conducted in 28 healthy smokers assessed the pharmacokinetics of nicotine after single and ad libitum use of the THS 2.1 or CCs. During the 7-day confinement period, blood samples were drawn for pharmacokinetic analysis. Subjective effects related to THS 2.1 or CC use were assessed using the Questionnaire of Smoking Urges (QSU-Brief). Results: The nicotine delivery rate was similar with the THS 2.1 and CCs after single and ad libitum use. The time to the maximum nicotine concentration was 8 minutes after single use of the THS 2.1 and CCs. The time to the peak concentration following ad libitum use was similar between the THS 2.1 and CCs. The maximum plasma nicotine concentration after single use of the THS 2.1 was 8.4ng/mL, 70.3% of that obtained with CCs. A transient reduction from baseline in the urge to smoke of 40% was observed 15 minutes after the single use of both the THS 2.1 and CCs. The mean QSU-Brief total scores following single and ad libitum use were similar for the THS 2.1 and CCs. Conclusions: These results suggest that the THS 2.1 effectively delivers nicotine and achieves similar pharmacokinetic profiles to CCs. The THS 2.1 also reduced the urge to smoke similarly to CCs. Implications: Reducing exposure to toxicants and safer delivery of nicotine are among the strategies that may reduce the harm of smoking-related diseases. In the present study, we investigated the pharmacokinetics of nicotine and their effects on the urge to smoke using the THS 2.1. It was developed to replicate the ritual of smoking as closely as possible by providing nicotine in a way that mimics CC smoking, but limits pyrolysis and

  11. Nicotine induces DNA damage in human salivary glands.

    PubMed

    Ginzkey, Christian; Kampfinger, Katja; Friehs, Gudrun; Köhler, Christian; Hagen, Rudolf; Richter, Elmar; Kleinsasser, Norbert H

    2009-01-10

    The tobacco alkaloid nicotine is responsible for addiction to tobacco and supposed to contribute to tobacco carcinogensis, too. Recently, genotoxic effects of nicotine have been reported in human cells from blood and upper aerodigestive tract. Because of nicotine accumulation in saliva, the study of possible in vitro genotoxic effects of nicotine have been extended to human salivary gland cells. Specimens of parotid glands of 10 tumor patients were obtained from tumor-free tissue. Single cells were prepared by enzymatic digestion immediately after surgery and exposed for 1h to 0.125-4.0mM of nicotine. Possible genotoxic effects were determined by the Comet assay using the % DNA in tail (DT) as a reliable indicator of DNA damage. Nicotine induced a significant dose-dependent increase of DNA migration in parotid gland single-cells. The mean DT was 1.12-fold (0.125mM) to 2.24-fold (4.0mM) higher compared to control. The lowest concentration eliciting significant DNA damage within 1h, 0.25mM nicotine, is only 10-fold higher than maximal concentrations of nicotine reported in saliva after unrestricted smoking. Although conclusive evidence for a carcinogenic potential of nicotine is still lacking, the safety of long-term nicotine replacement therapy should be carefully monitored. PMID:18852035

  12. Nicotine is a neurotoxin in the adolescent brain: critical periods, patterns of exposure, regional selectivity, and dose thresholds for macromolecular alterations.

    PubMed

    Abreu-Villaça, Yael; Seidler, Frederic J; Tate, Charlotte A; Slotkin, Theodore A

    2003-07-25

    In the fetus, nicotine is a neuroteratogen that elicits cell damage and loss and subsequent abnormalities of synaptic function. We explored whether these effects extend into adolescence, the period when most people begin smoking. Beginning on postnatal day 30, rats were given a 1 week regimen of nicotine infusions or twice-daily injections, at doses (0.6, 2 and 6 mg/kg/day) set to achieve plasma levels found in occasional to regular smokers. We assessed indices of cell packing density and cell number (DNA concentration and content), cell size (total protein/DNA ratio) and neuritic projections (membrane/total protein) in the midbrain, hippocampus and cerebral cortex, three regions known to be vulnerable to developmental effects of nicotine. With either route of administration, nicotine evoked shortfalls in DNA concentration and content, compensatory elevations of total protein/DNA, and reductions in the membrane/total protein ratio. Nearly all of the effects were apparent even at the lowest dose of nicotine and remained fully evident 1 month posttreatment. Although both males and females showed significant alterations, in general the effects were larger in females. Our results indicate that in adolescence, even a brief period of continuous or intermittent nicotine exposure, elicits lasting alterations in biomarkers associated with cellular and neuritic damage. As the effects are detected at exposures that produce plasma concentrations one-tenth of those in regular smokers, the exquisite sensitivity of the adolescent brain to nicotine neurotoxicity may contribute to lasting neurobehavioral damage even in occasional smokers. PMID:12850578

  13. Hormones, nicotine, and cocaine: clinical studies.

    PubMed

    Mello, Nancy K

    2010-06-01

    Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (2 min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine's sustained positive effects (<20 min), ratings of "high" and "rush" began to decrease within one or two puffs of a high-nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse and the implications for treatment of these addictive disorders are discussed.

  14. Nicotine Chemistry, Metabolism, Kinetics and Biomarkers

    PubMed Central

    Hukkanen, Janne; Jacob, Peyton

    2010-01-01

    Nicotine underlies tobacco addiction, influences tobacco use patterns, and is used as a pharmacological aid to smoking cessation. The absorption, distribution and disposition characteristics of nicotine from tobacco and medicinal products are reviewed. Nicotine is metabolized primarily by the liver enzymes CYP2A6, UDP-glucuronosyltransfease (UGT), and flavin-containing monooxygenase (FMO). In addition to genetic factors, nicotine metabolism is influenced by diet and meals, age, sex, use of estrogen-containing hormone preparations, pregnancy and kidney disease, other medications, and smoking itself. Substantial racial/ethnic differences are observed in nicotine metabolism, which are likely influenced by both genetic and environmental factors. The most widely used biomarker of nicotine intake is cotinine, which may be measured in blood, urine, saliva, hair, or nails. The current optimal plasma cotinine cut-point to distinguish smokers from non-smokers in the general US population is 3 ng ml−1. This cut-point is much lower than that established 20 years ago, reflecting less secondhand smoke exposure due to clear air policies and more light or occasional smoking. PMID:19184645

  15. Protein binding of prilocaine in human plasma: influence of concentration, pH and temperature.

    PubMed

    Bachmann, B; Biscoping, J; Sinning, E; Hempelmann, G

    1990-05-01

    Protein binding of prilocaine was investigated in vitro under various conditions of changing pH, temperature and total plasma concentration by means of HPLC with UV-detection and ultrafiltration. Whereas changes in temperature (25 degrees C-40 degrees C) and pH (pH 5-pH 10) influenced protein binding markedly, rising plasma concentrations up to 16 micrograms/ml did not affect plasma protein binding significantly. This may be a possible explanation for clinical evidence of low toxicity associated with the use of prilocaine. Discussions concerning protein binding of local anaesthetics should always be based on defined ambient conditions (pH, temperature, concentration).

  16. Nicotine-morphine interactions at α4β2, α7 and α3(⁎) nicotinic acetylcholine receptors.

    PubMed

    Talka, Reeta; Salminen, Outi; Whiteaker, Paul; Lukas, Ronald J; Tuominen, Raimo K

    2013-02-15

    Nicotine and opioids share several behavioral and rewarding properties. Although both opioids and nicotine have their own specific mechanism of action, there is empirical and experimental evidence of interactions between these drugs. We studied receptor-level interactions of nicotine and morphine at α4β2, α7 and α3(⁎) nicotinic acetylcholine receptors. [(3)H]epibatidine displacement was used to determine if morphine binds competitively to nicotinic acetylcholine receptors. Functional interactions of morphine and nicotine were studied with calcium fluorometry and (86)Rb(+) efflux assays. Morphine displaced [(3)H]epibatidine from nicotinic agonist binding sites in all cell lines studied. The Ki values for morphine were 13.2μM in SH-EP1-hα4β2 cells, 0.16μM and 126μM in SH-SY5Y cells and 43.7μM in SH-EP1-hα7 cells. In SH-EP1-hα4β2 cells expressing α4β2 nicotinic acetylcholine receptors, morphine acted as a partial agonist of (86)Rb(+) efflux comparable to cytisine (with EC50 values of 53.3μM for morphine and 5.38μM for cytisine). The effect of morphine was attenuated concentration-dependently by the nicotinic antagonist mecamylamine. In the SH-SY5Y cell line expressing several subtypes of nicotinic acetylcholine receptors morphine had an inhibitory effect on nicotine induced (86)Rb(+) ion efflux mediated by α3(⁎) nicotinic acetylcholine receptors. These results suggest that morphine acts as a partial agonist at α4β2 nicotinic acetylcholine receptors and as a weak antagonist at α3(⁎) nicotinic acetylcholine receptors.

  17. Plasma concentrations and cardiotoxic effects of desipramine and protriptyline in the rat

    PubMed Central

    Bianchetti, G.; Bonaccorsi, Aurora; Chiodaroli, A.; Franco, R.; Garattini, S.; Gomeni, R.; Morselli, P.L.

    1977-01-01

    1 Desipramine and protriptyline were administered to anaesthetized rats by two consecutive intravenous infusions in order to obtain a peak level (first infusion) followed by lower steady state concentrations (second infusion) (Wagner, 1974). Theoretical plasma level time courses were confirmed experimentally. 2 Desipramine and protriptyline were measured in atria and ventricles. Increasing infusion rates led to proportional increases in plasma and atrial concentrations. The tissue/medium ratio ranged from 57 to 21 for desipramine and from 43 to 11 for protriptyline according to the time of determination during infusions. 3 Heart rate changes, deviation of the electrical axis of the heart and prolongation of atrioventricular conduction were recorded at fixed times during infusion. 4 Positive chronotropic effects were noted at plasma concentrations ranging from 0.035 to 0.1 μg/ml for desipramine and from 0.04 to 1.2 μg/ml for protriptyline. At higher plasma concentrations the positive chronotropic effect decreased and bradycardia developed. Both drugs induced right rotation of the electrical axis of the heart. Threshold plasma levels giving 40° rotation were 1.35 μg/ml (desipramine) and 1.75 μg/ml (protriptyline). Atrioventricular conduction was prolonged at threshold plasma concentrations of 2.2 μg/ml for desipramine and 3.6 μg/ml for protriptyline. 5 Desipramine is more cardiotoxic than protriptyline. This difference is discussed in relation to the plasma and heart concentration of the two drugs. PMID:884382

  18. Biodegradation of nicotine by a newly isolated Pseudomonas stutzeri JZD

    NASA Astrophysics Data System (ADS)

    Petricevic, Jelena; Gujanicic, Vera; Radic, Danka; Jovicic Petrovic, Jelena; Jovic, Jelena; Raicevic, Vera

    2013-04-01

    The tobacco-manufacturing process and all activities that use tobacco, produce solid or liquid wastes with high concentrations of nicotine. Nicotine is a significant toxic waste product in tobacco industry. This waste is classified as 'toxic and hazardous' by European Union regulations when the nicotine content exceeds 500 milligrams per kilogram dry weight. Therefore, there is a major environmental requirement to remove nicotine from tobacco wastes. Bioremediation techniques which involve nicotine degradation by microorganisms have attracted attention during the last years, because microorganisms have the potential to reduce nicotine levels in tobacco and to detoxify tobacco wastes. The aim of this study is isolation and identification of nicotine degraded bacteria and optimization of nicotine degradation in laboratory conditions. An aerobic bacterial strain capable of effectively degrading nicotine was isolated from the tobacco industry waste, Serbia. After isolation, the liquid culture was spread onto the solid plates of the nicotine inorganic salt medium using the dilution plate method. Cell morphology of strain was observed by a light microscope and physiological characteristics were determined by Api technique and sequence analyzes of 16S rDNA. This isolate was identified as Pseudomonas stutzeri based on morphology, physiological characteristics, and Apiweb technique. Comparison with sequences available in data library showed the 99% similarity with 16S rDNA gene sequence of the species Pseudomonas stutzeri ( GenBank Acc. No. CP003725). We analyzed the effect of initial nicotine concentration (1g/L, 1.5 g/L, 2.5 g/L) on microbial activity in aim to optimize biodegradation. The effect of cultivation temperature (25°C; 30°C; 37°C) on nicotine degradation by P. stutzeri was evaluated after 24 h of cultivation, with 1.5 g/L nicotine added as the sole carbon source. Effect of biodegradation has depended on initial concentration. During incubation, number of

  19. Relation between plasma and saliva concentrations of enoxacin, ciprofloxacin, and theophylline.

    PubMed

    Zhai, S; Wei, X; Parker, B M; Kunze, K L; Vestal, R E

    1996-12-01

    To assess the reliability of predicting plasma concentrations of enoxacin, ciprofloxacin, and theophylline from drug concentrations in saliva, six healthy volunteers received single oral doses of enoxacin, ciprofloxacin, and theophylline administered in combination on each of four separate study days, with different, doses separated by at least 5 days. Drug concentrations were determined by a newly developed high-performance liquid chromatography (HPLC) assay, which could measure simultaneously all three drugs in plasma or saliva. Saliva data from the postabsorptive phase after drug administration were used to minimize the effects of variation in absorption. There were good correlations between saliva and plasma concentrations of enoxacin, ciprofloxacin, and theophylline (r = 0.91, 0.88, and 0.98, respectively). The mean (+/-SD) saliva-to-plasma (S/P) ratio for theophylline was 0.63 +/- 0.06 with a coefficient of variation (CV) of 7.9 +/- 2.7%. In contrast, the S/P ratios and CV values for enoxacin and ciprofloxacin were 0.72 +/- 0.21 and 28.9 +/- 11.1%, and 0.58 +/- 0.15 and 25.3 +/- 6.7%, respectively. Because of the large inter- and intraindividual variability, saliva concentrations of enoxacin and ciprofloxacin are not reliable for predicting plasma concentrations. However, saliva may be used reliably for predicting plasma concentrations of theophylline.

  20. Plasma bile acid concentrations in response to feeding in peregrine falcons (Falco peregrinus).

    PubMed

    Lumeij, J T; Remple, J D

    1992-01-01

    A significant post-prandial increase of plasma bile acid concentration (PBAC) was observed in peregrine falcons (Falco peregrinus). In order to avoid physiological food-induced elevations in PBAC, which can complicate interpretation of plasma chemistry results in birds of prey, it is recommended that blood samples be obtained after a fasting period of at least 24 hours.

  1. Nicotine induces chromatin changes and c-Jun up-regulation in HL-60 leukemia cells.

    PubMed

    Landais, Emilie; El-Khoury, Victoria; Prevost, Alain; Dufer, Jean; Liautaud-Roger, Françoise

    2005-12-01

    Although nicotine has been implicated as a potential factor in the pathogenesis of human cancer, its mechanisms of action regarding cancer development remain largely unknown. HL-60 cells were used to investigate the effects of a short-term treatment with nicotine at concentrations found in the blood of smokers. The findings show that nicotine induces chromatin decondensation, histone H3 acetylation and up-regulation of the c-Jun transcription factor mRNA. This increase is inhibited by mecamylamine, a nicotinic receptor antagonist, suggesting that nicotine alters cellular function directly via nicotinic acetylcholine receptors and may then play a role in cell physiology and tumor promotion.

  2. Inside-out neuropharmacology of nicotinic drugs

    PubMed Central

    Henderson, Brandon J.; Lester, Henry A.

    2015-01-01

    Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable AChR pentamers. These changes and stabilizations in turn lead to increases in both anterograde and retrograde traffic within the early secretory pathway. In addition to the eventual upregulation of AChRs at the plasma membrane, other effects of pharmacological chaperoning include modifications to endoplasmic reticulum stress and to the unfolded protein response. Because these processes depend on pharmacological chaperoning within intracellular organelles, we group them as “inside-out pharmacology”. This term contrasts with the better-known, acute, “outside-in” effects of activating and desensitizing plasma membrane AChRs. We review current knowledge concerning the mechanisms and consequences of inside-out pharmacology. PMID:25660637

  3. Amino acid concentrations in plasma and skeletal muscle after transurethral resection syndrome.

    PubMed

    Hahn, R; Essén, P; Wernerman, J

    1992-01-01

    The concentrations of amino acids in plasma and skeletal muscle were measured 1 and 4 hours after transurethral prostatic resection in three patients who developed symptoms of the transurethral resection syndrome. The irrigating solution contained 1.5% of glycine and 1% of ethanol. The concentrations of glycine in plasma and muscle were equal within an hour of the operation, and at four hours the abnormally high glycine concentration persisted in muscle, though it had decreased rapidly in plasma. Our data suggest that skeletal muscle is a quantitatively important reservoir for glycine when this amino acid is supplied in potentially toxic amounts, but that the plasma glycine concentration returns to normal as the patient's clinical condition improves. PMID:1279783

  4. High concentration of deuterium in palladium from plasma ion implantation

    SciTech Connect

    Uhm, H.S.; Lee, W.M. )

    1991-11-01

    Based on a theoretical calculation, a new scheme to increase deuterium density in palladium over its initial value is presented. This deuterium enrichment scheme makes use of plasma ion implantation. A cylindrical palladium rod (target) preloaded with deuterium atoms, coated with a diffusion-barrier material, is immersed in a deuterium plasma. The palladium rod is connected to a high-power modulator which provides a series of negative-voltage pulses. During these negative pulses, deuterium ions fall into the target, penetrate the diffusion barrier, and are implanted inside the palladium. For reasonable system parameters allowed by present technology, it is found from theoretical calculations that the saturation deuterium density after prolonged ion implantation can be several times the palladium atomic number density. Assuming an initial deuterium density, {ital n}{sub 0}=4{times}10{sup 22} cm{sup {minus}3}, it is also found that the deuterium density in palladium can triple its original value within a few days of the ion implantation for a reasonable target size. Because of the small diffusion coefficient in palladium, the incoming ions do not diffuse quickly inward, thereby accumulating near the target surface at the beginning of the implantation.

  5. Mechanisms of Nicotine Addiction

    SciTech Connect

    McGehee, Daniel

    2002-06-26

    Nicotine reinforces the use of tobacco products primarily through its interaction with specific receptor proteins within the brain's reward centers. A critical step in the process of addiction for many drugs, including nicotine, is the release of the neurotransmitter dopamine. A single nicotine exposure will enhance dopamine levels for hours, however, nicotinic receptors undergo both activation and then desensitization in minutes, which presents an important problem. How does the time course of receptor activity lead to the prolonged release of dopamine? We have found that persistent modulation of both inhibitory and excitatory synaptic connections by nicotine underlies the sustained increase in dopamine release. Because these inputs express different types of nicotinic receptors there is a coordinated shift in the balance of synaptic inputs toward excitation of the dopamine neurons. Excitatory inputs are turned on while inhibitory inputs are depressed, thereby boosting the brain's reward system.

  6. Mechanisms of Nicotine Addiction

    SciTech Connect

    McGehee, Daniel

    2009-06-26

    Nicotine reinforces the use of tobacco products primarily through its interaction with specific receptor proteins within the brain’s reward centers. A critical step in the process of addiction for many drugs, including nicotine, is the release of the neurotransmitter dopamine. A single nicotine exposure will enhance dopamine levels for hours, however, nicotinic receptors undergo both activation and then desensitization in minutes, which presents an important problem. How does the time course of receptor activity lead to the prolonged release of dopamine? We have found that persistent modulation of both inhibitory and excitatory synaptic connections by nicotine underlies the sustained increase in dopamine release. Because these inputs express different types of nicotinic receptors there is a coordinated shift in the balance of synaptic inputs toward excitation of the dopamine neurons. Excitatory inputs are turned on while inhibitory inputs are depressed, thereby boosting the brain’s reward system.

  7. Stable isotope studies of nicotine kinetics and bioavailability

    SciTech Connect

    Benowitz, N.L.; Jacob, P. 3d.; Denaro, C.; Jenkins, R. )

    1991-03-01

    The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine.

  8. [Plasma prolactin concentration and the effect of metergoline in pseudopregnant Afghan hounds].

    PubMed

    Okkens, A C; Dieleman, S J; Kooistra, H S; Bevers, M M

    2000-02-01

    The effects of metergoline, a 5-hydroxytryptamine (serotinin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-psueodopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentration of prolactine in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

  9. Plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and the effect of metergoline.

    PubMed

    Okkens, A C; Dieleman, S J; Kooistra, H S; Bevers, M M

    1997-01-01

    The effect of metergoline, a 5-hydroxytryptamine (serotonin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-pseudopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentrations of prolactin in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

  10. Pasteurized, monoclonal antibody factor VIII concentrate: establishing a new standard for purity and viral safety of plasma-derived concentrates.

    PubMed

    Goldsmith, J C

    2000-03-01

    A factor VIII concentrate (Monoclate-P) manufactured using a combination of pasteurization and immunoaffinity chromatography has been chosen to compare and contrast manufacturing aspects of plasma-derived factor VIII concentrates. Pasteurization is a virucidal method with a long safety record in clinical practice, while immuno-affinity chromatography selectively isolates and purifies the procoagulant protein of factor VIII, and partitions potential viral contaminants and nonessential proteins to the unbound fraction. The complete Monoclate-P production process reduces human immunodeficiency virus by > or = 10.5 log10, Sindbis (a model for hepatitis C virus) by > or = 6.5 log10, and murine encephalomyocarditis virus (a non-enveloped model virus) by 7.1 log10. The viral safety of Monoclate-P has been further demonstrated in clinical studies in patients not previously treated with blood or plasma-derived products. Additionally, the manufacture of Monoclate-P includes careful donor screening and plasma testing for antibodies to syphilis and human immunodeficiency, hepatitis B, and hepatitis C viruses to enhance source plasma safety. Combined with donor selection and plasma testing, multiple viral reduction steps effectively eliminate both lipid-enveloped viruses (e.g. human immunodeficiency, hepatitis B and C) and non-lipid-enveloped viruses (e.g. hepatitis A). In addition, polymerase chain reaction-based nucleic acid detection tests for hepatitis B and C viruses and for human immunodeficiency virus-1 have been introduced as part of an investigational new drug mechanism.

  11. Pasteurized, monoclonal antibody factor VIII concentrate: establishing a new standard for purity and viral safety of plasma-derived concentrates.

    PubMed

    Goldsmith, J C

    2000-03-01

    A factor VIII concentrate (Monoclate-P) manufactured using a combination of pasteurization and immunoaffinity chromatography has been chosen to compare and contrast manufacturing aspects of plasma-derived factor VIII concentrates. Pasteurization is a virucidal method with a long safety record in clinical practice, while immuno-affinity chromatography selectively isolates and purifies the procoagulant protein of factor VIII, and partitions potential viral contaminants and nonessential proteins to the unbound fraction. The complete Monoclate-P production process reduces human immunodeficiency virus by > or = 10.5 log10, Sindbis (a model for hepatitis C virus) by > or = 6.5 log10, and murine encephalomyocarditis virus (a non-enveloped model virus) by 7.1 log10. The viral safety of Monoclate-P has been further demonstrated in clinical studies in patients not previously treated with blood or plasma-derived products. Additionally, the manufacture of Monoclate-P includes careful donor screening and plasma testing for antibodies to syphilis and human immunodeficiency, hepatitis B, and hepatitis C viruses to enhance source plasma safety. Combined with donor selection and plasma testing, multiple viral reduction steps effectively eliminate both lipid-enveloped viruses (e.g. human immunodeficiency, hepatitis B and C) and non-lipid-enveloped viruses (e.g. hepatitis A). In addition, polymerase chain reaction-based nucleic acid detection tests for hepatitis B and C viruses and for human immunodeficiency virus-1 have been introduced as part of an investigational new drug mechanism. PMID:10759015

  12. Plasma clozapine concentration coefficients of variation in a long-term study.

    PubMed

    Diaz, Francisco J; de Leon, Jose; Josiassen, Richard C; Cooper, Thomas B; Simpson, George M

    2005-01-01

    Kurz et al. conducted the first study of the intra-individual variability of clozapine plasma concentrations but did not take into account the effect of smoking and co-medication. As patients were receiving varying doses, Kurz et al. standardized plasma levels by using a plasma level/dose/kg ratio. In 15 patients, the mean coefficient of variation (CV) was 53% (S.D. = 21). In this new study, plasma clozapine and norclozapine concentrations were measured every 2 weeks in 47 patients randomized to 100, 300, or 600 mg/day for 16-week double-blind clozapine trials under controlled conditions (stable smoking, limited co-medication and absence of caffeinated beverages). For 100, 300 and 600 mg/day, the respective mean CVs for plasma clozapine concentrations were 23% (S.D. = 14), 19% (S.D.= 11) and 18% (S.D. = 8). For the combined concentrations of clozapine and norclozapine, the respective mean CVs were 20% (S.D. = 13), 16% (S.D. = 9) and 15% (S.D. = 7). Under 100 mg/day, the mean CV for clozapine concentrations was significantly higher for heavy smokers than non-heavy smokers (32%, S.D. = 3 vs. 19%, S.D. = 8) (p = 0.03). Studies of CVs in other environments are needed. Clozapine CVs may be important in order to understand the importance of variations around the therapeutic range and to interpret drug interactions above the usual noise of measuring plasma concentrations.

  13. [Plasma haptoglobin concentration in cattle with surgically corrected torsio uteri intrapartum].

    PubMed

    Schönfelder, Axel; Schrödl, Wieland; Krüger, Monika; Richter, Andreas; Sobiraj, Axel

    2006-01-01

    In 26 cows with surgically corrected torsio uteri intra partum, severity of disease, wound healing and secondary diseases were correlated with plasma haptoglobin concentration. The objective of the investigation was to determine, if an increased plasma haptoglobin concentration indicates the severity of disease respectively expected wound healing disorders or secondary diseases. The degree of severity of disease was determined by rectally diagnosed elasticity of the uterus before the surgery. In the present investigation, the severity of a uterine torsion intra partum could not be evaluated by determining the plasma haptoglobin concentration. In 9 of 11 days of investigation there was no significant difference in the plasma haptoglobin concentration of animals with an elastic uterus (animals with good prognosis) in contrast to cows with tight uterus (patients with poor prognosis) found. The significant differences on the 6th and 7th day post surgery are related to secondary diseases in patients with poor prognosis, which develop evidently earlier and form stronger. The correlation of all cows with--to those without secondary illnesses shows, that 10 days post surgery patients with secondary diseases have a significant higher plasma haptoglobin concentration (p < 0.05) compared to animals without secondary illnesses. No correlations existed between plasma haptoglobin concentration and wound healing in the examined cattle. A postoperatively increase of haptoglobin indicates a higher risk of secondary illnesses and complications.

  14. Monitoring imatinib plasma concentrations in chronic myeloid leukemia

    PubMed Central

    Martins, Darlize Hübner; Wagner, Sandrine Comparsi; dos Santos, Tamyris Vianna; Lizot, Lilian de Lima Feltraco; Antunes, Marina Venzon; Capra, Marcelo; Linden, Rafael

    2011-01-01

    Imatinib has proved to be effective in the treatment of chronic myeloid leukemia, but plasma levels above 1,000 ng/mL must be achieved to optimize activity. Therapeutic drug monitoring of imatinib is useful for patients that do not present clinical response. There are several analytical methods to measure imatinib in biosamples, which are mainly based on liquid chromatography with mass spectrometric or diode array spectrophotometric detection. The former is preferred due to its lower cost and wider availability. The present manuscript presents a review of the clinical and analytical aspects of the therapeutic drug monitoring of imatinib in the treatment of chronic myeloid leukemia. The review includes references published over the last 10 years. There is evidence that the monitoring of plasmatic levels of imatinib is an useful alternative, especially considering the wide pharmacokinetic variability of this drug. PMID:23049322

  15. Platelet-rich plasma releasate differently stimulates cellular commitment toward the chondrogenic lineage according to concentration

    PubMed Central

    Matsiko, Amos; Tomazette, Marcel RP; Rocha, Wanessa KR; Cordeiro-Spinetti, Eric; Levingstone, Tanya J; Farina, Marcos; O’Brien, Fergal J; El-Cheikh, Marcia C; Balduino, Alex

    2015-01-01

    Platelet-rich plasma has been used to treat articular cartilage defects, with the expectations of anabolic and anti-inflammatory effects. However, its role on cellular chondrogenic or fibrogenic commitment is still a controversy. Herein, the role of platelet-rich plasma releasate, the product obtained following platelet-rich plasma activation, on cellular commitment toward the chondrogenic lineage was evaluated in vitro. Human nasoseptal chondrogenic cells and human bone marrow mesenchymal stromal cells were used as cell types already committed to the chondrogenic lineage and undifferentiated cells, respectively, as different concentrations of platelet-rich plasma releasate were tested in comparison to commonly used fetal bovine serum. Low concentration of platelet-rich plasma releasate (2.5%) presented similar effects on cellular growth compared to 10% fetal bovine serum, for both cell types. In a three-dimensional culture system, platelet-rich plasma releasate alone did not induce full nasoseptal chondrogenic cells cartilage-like pellet formation. Nonetheless, platelet-rich plasma releasate played a significant role on cell commitment as high-passage nasoseptal chondrogenic cells only originated cartilage-like pellets when expanded in the presence of platelet-rich plasma releasate rather than fetal bovine serum. Histological analyses and measurements of pellet area demonstrated that even low concentrations of platelet-rich plasma releasate were enough to prevent nasoseptal chondrogenic cells from losing their chondrogenic potential due to in vitro expansion thereby promoting their recommitment. Low concentration of platelet-rich plasma releasate supplemented in chondrogenic medium also increased the chondrogenic potential of mesenchymal stromal cells seeded on collagen-hyaluronic acid scaffolds, as observed by an increase in chondrogenic-related gene expression, sulfated glycosaminoglycan production, and compressive modulus following in vitro culture. On the

  16. Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans

    PubMed Central

    Butler, Andrew A.; St-Onge, Marie-Pierre; Siebert, Emily A.; Medici, Valentina; Stanhope, Kimber L.; Havel, Peter J.

    2015-01-01

    Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations. PMID:26435060

  17. Determination of chicken and turkey plasma and serum protein concentrations by refractometry and the biuret method.

    PubMed

    Andreasen, C B; Latimer, K S; Kircher, I M; Brown, J

    1989-01-01

    Plasma and serum protein concentrations were determined in chickens and turkeys by refractometry (with human and veterinary refractometers) and by the biuret method. Chicken and turkey serum protein values were significantly lower than respective plasma protein values according to both methods. Refractometer readings for both plasma and serum correlated closely with the results of the biuret test (r2 = 0.72 to 0.97). These findings indicate that plasma and serum protein values may be determined accurately in chickens and turkeys with a handheld refractometer.

  18. The role of nicotinic acid metabolites in flushing and hepatotoxicity.

    PubMed

    Stern, Ralph H

    2007-07-01

    Flushing and hepatotoxicity are important adverse effects of nicotinic acid. This article reviews the role of metabolism of nicotinic acid in the production of these side effects. The suggestion that nicotinic acid (NUA) formation produces flushing is traced to a correlation of flushing with NUA C(max) (maximal concentration) and the observation that aspirin inhibits NUA formation and flushing. The former does not establish causation and the latter can be explained by inhibition of prostaglandin formation. Recent characterization of the GPR109A receptor that mediates prostaglandin release by Langerhans cells to produce flushing has shown nicotinic acid, not NUA, is responsible. The suggestion that nicotinamide metabolites produce hepatotoxicity is not supported by any data. The mechanism of hepatotoxicity is unknown and a toxic metabolite of nicotinic acid has not been identified. Different nicotinic acid formulations produce different metabolite patterns due to nonlinear pharmacokinetics, but there is no evidence that these differences have any clinical importance. PMID:21291680

  19. Investigations of Enantiopure Nicotine Haptens Using an Adjuvanting Carrier in Anti-Nicotine Vaccine Development.

    PubMed

    Jacob, Nicholas T; Lockner, Jonathan W; Schlosburg, Joel E; Ellis, Beverly A; Eubanks, Lisa M; Janda, Kim D

    2016-03-24

    Despite efforts to produce suitable smoking cessation aids, addiction to nicotine continues to carry a substantive risk of recidivism. An attractive alternative to current therapies is the pharmacokinetic strategy of antinicotine vaccination. A major hurdle in the development of the strategy has been to elicit a sufficiently high antibody concentration to curb nicotine distribution to the brain. Herein, we detail investigations into a new hapten design, which was able to elicit an antibody response of significantly higher specificity for nicotine. We also explore the use of a mutant flagellin carrier protein with adjuvanting properties. These studies underlie the feasibility of improvement in antinicotine vaccine formulations to move toward clinical efficacy.

  20. Taurine concentrations in the diet, plasma, urine and breast milk of vegans compared with omnivores.

    PubMed

    Rana, S K; Sanders, T A

    1986-07-01

    1. The concentration of taurine in the diets, plasma, urine and breast milk were measured in vegans and age- and sex-matched omnivore controls. Plasma and urinary amino acid concentrations were also determined. 2. Taurine was absent from the vegan diet and occurred in variable amounts in the diets of the omnivores. Urinary taurine levels were less than half those of the omnivores but plasma and breast-milk levels were only slightly lower. 3. Dietary energy intakes were similar in the vegans and omnivores, but protein intakes tended to be lower in the vegans.

  1. Taurine concentrations in the diet, plasma, urine and breast milk of vegans compared with omnivores.

    PubMed

    Rana, S K; Sanders, T A

    1986-07-01

    1. The concentration of taurine in the diets, plasma, urine and breast milk were measured in vegans and age- and sex-matched omnivore controls. Plasma and urinary amino acid concentrations were also determined. 2. Taurine was absent from the vegan diet and occurred in variable amounts in the diets of the omnivores. Urinary taurine levels were less than half those of the omnivores but plasma and breast-milk levels were only slightly lower. 3. Dietary energy intakes were similar in the vegans and omnivores, but protein intakes tended to be lower in the vegans. PMID:3676193

  2. Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations

    SciTech Connect

    Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

    2003-08-15

    Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting ApoAV is a potent triglyceride modulator despite its low concentration. Together, these data indicate

  3. Plasma and synovial fluid meclofenamic acid concentrations in patients with rheumatoid arthritis of the knee.

    PubMed

    Koup, J R; Thomas, D; Tucker, E; Black, A; Ruderman, M; Dixon, J A; Kinkel, A

    1988-01-01

    We have measured plasma and synovial fluid concentrations of meclofenamic acid at 2, 4, 8, and 12 h during steady-state administration (100 mg three times daily for 4-7 days). Paired plasma and synovial samples were obtained pre-treatment and at one of the above times in twelve patients with a diagnosis of rheumatoid arthritis. In addition, the extent of protein binding of meclofenamic acid was assessed in vitro in the pre-treatment plasma and synovial fluid specimens. Peak total concentrations of 1.73 and 0.86 micrograms.ml-1 were observed in plasma (at 2 h) and synovial fluid (at 4 h) respectively. The extent of protein binding was 99.7 and 99.6% (not significantly different) in plasma and synovial fluid respectively. The results of this study are compared to those from similar reported studies of other nonsteroidal anti-inflamatory compounds.

  4. Effect of octreotide acetate on the plasma concentration and urinary excretion of uridine and purine bases.

    PubMed

    Yamamoto, Tetsuya; Moriwaki, Yuji; Takahashi, Sumio; Tsutsumi, Zenta; Ka, Tsuneyoshi; Hada, Toshikazu

    2002-04-01

    To determine the effect of octreotide acetate on urinary excretion of uric acid and plasma concentration of uridine, we subcutaneously administered octreotide acetate (1 microg/kg of body weight) to 5 healthy subjects. Ninety minutes after administration, octreotide acetate increased the plasma concentration of uridine by 15% and decreased the plasma concentration of glucagon by 24% and that of insulin to below the detection limits. In addition, octreotide acetate decreased the urinary excretion of uric acid, sodium, and chloride by 60%, 40%, and 38%, respectively, at 1 hour after administration. However, octreotide acetate did not affect the concentrations of hypoxanthine, xanthine, uric acid, cyclic AMP in plasma, lactic acid and pyruvic acid in blood, urinary excretion of hypoxanthine and xanthine, or creatinine clearance. From these results, we speculated that octreotide acetate decreases the urinary excretion of uric acid by decreasing the concentration of glucagon and/or urinary excretion of sodium, and increases the plasma concentration of uridine via decreased concentrations of glucagon and insulin.

  5. Depression of plasma luteinizing hormone concentration in quail by the anticholinesterase insecticide parathion

    USGS Publications Warehouse

    Rattner, B.A.; Clarke, R.N.; Ottinger, M.A.

    1986-01-01

    To examine the effects of parathion on basal plasma luteinizing hormone (LH) concentration, male Japanese quail (Coturnix japonica) were orally intubated with 0, 5 or 10 mg/kg parathion and sacrificed after 4, 8 and 24 hr. At the 5 mg/kg dose, plasma LH levels were reduced at 4 and 8 hr, but returned to control values by 24 hr. Brain acetylcholinesterase activity was substantially reduced by 10 mg/kg parathion (52, 75 and 37% inhibition at 4, 8 and 24 hr, respectively) and plasma LH concentration remained depressed through the 24-hr period. These findings suggest that the organophosphorus insecticide parathion may alter plasma LH concentration in a manner which might impair reproductive activity, and provide indirect evidence for a cholinergic component in the regulation of LH secretion in quail.

  6. Plasma glucocorticoid concentrations and body mass in ground squirrels: seasonal variation and circannual organization.

    PubMed

    Nunes, Scott; Pelz, Kimberly M; Muecke, Eva-Maria; Holekamp, Kay E; Zucker, Irving

    2006-04-01

    We examined variation in plasma glucocorticoid concentrations of free-living Belding's ground squirrels (Spermophilus beldingi) and captive golden-mantled ground squirrels (Spermophilus lateralis) housed in constant environmental conditions. Plasma corticosterone concentrations were not significantly correlated with time held captive in traps prior to collection of blood samples in males or non-breeding females, but these variables were significantly correlated in breeding females during the pre-mating, lactation, and post-lactation periods. Among male S. beldingi, plasma corticosterone concentrations increased over the course of the active season, and were significantly higher in non-breeding than breeding individuals. Corticosterone concentrations also increased in non-breeding females throughout the active period. In breeding females, baseline (non-stress) corticosterone concentrations, determined from blood samples collected within 3 min of capture, increased during gestation and declined during lactation, whereas stress values of corticosterone, determined from blood samples collected within 4-11 min of capture, increased during gestation and then again during the period after young emerged from the natal burrow. Changes in plasma corticosterone concentrations of S. beldingi paralleled changes in body mass. Among S. lateralis, plasma concentrations of cortisol were elevated when males and females were in reproductive condition and lower in reproductively quiescent squirrels. The annual peak in plasma cortisol concentrations occurred just prior to increases in body mass associated with pre-hibernation fattening. Collectively, these results suggest that concentrations of circulating glucocorticoids fluctuate with circannual rhythmicity in conjunction with annual cycles of change in body mass and activity; within these circannual cycles glucocorticoid concentrations are influenced by stress and breeding status. PMID:16360155

  7. Plasma cortisol and glucose concentrations in the striped mullet ( Mugil cephalus L.) subjected to intense handling stress

    NASA Astrophysics Data System (ADS)

    Hong, Wanshu

    1992-03-01

    The plasma cortisol and glucose concentrations were determined in mature female striped mullet ( Mugil cephalus L.) subjected to short term intense handling stress. The results indicated that plasma cortisol levels reached a peak 20 min after stress and declined gradually afterwards. The highest concentration of plasma glucose was observed 30 min after stress. The present study showed that the rise of plasma glucose was associated with the plasma cortisol levels.

  8. Temporal plasma vitamin concentrations are altered by fat-soluble vitamin administration in suckling pigs.

    PubMed

    Jang, Y D; Ma, J Y; Monegue, J S; Monegue, H J; Stuart, R L; Lindemann, M D

    2015-11-01

    Piglets are born with purportedly low plasma vitamin D levels. The objective of this study was to investigate the effect of fat-soluble vitamin administration, primarily vitamin D, by different administration routes on plasma vitamin concentrations in suckling pigs. A total of 45 pigs from 5 litters were allotted at birth to 3 treatments within each litter. Pigs were administered 400 IU of α-tocopherol, 40,000 IU of retinyl palmitate, and 40,000 IU of vitamin D at d 1 of age either orally or by i.m. injection and compared with control pigs with no supplemental vitamin administration. Blood samples were collected at d 0 (initial), 1, 2, 3, 4, 6, 9, 14, and 20 after administration. Plasma 25-hydroxycholecalciferol (25OHD), α-tocopherol, retinyl palmitate, and retinol concentrations were analyzed. Except for retinol, the effects of treatment, day, and day × treatment interaction ( < 0.01) were observed on plasma vitamin concentrations. Plasma concentrations of 25OHD and α-tocopherol increased immediately regardless of administration routes to peak at d 2 and 1 after administration, respectively. Plasma retinyl palmitate concentrations increased only with the injection treatment, with the peak at d 1 after administration. Plasma concentrations of 25OHD in both administration treatments and α-tocopherol in the injection treatment were maintained at greater levels than those in the control treatment until d 20 after administration. With regard to the pharmacokinetic parameters for plasma 25OHD concentrations, the injection treatment had greater elimination half-life ( < 0.01), maximum plasma concentrations ( < 0.05), and all area under the curve parameters ( < 0.01) but a lower elimination rate constant ( < 0.01) than the oral treatment. Relative bioavailability of oral administration compared with injection administration was 55.26%. These results indicate that plasma status of 25OHD,α-tocopherol, and retinyl palmitate are differentially changed between types of

  9. Temporal plasma vitamin concentrations are altered by fat-soluble vitamin administration in suckling pigs.

    PubMed

    Jang, Y D; Ma, J Y; Monegue, J S; Monegue, H J; Stuart, R L; Lindemann, M D

    2015-11-01

    Piglets are born with purportedly low plasma vitamin D levels. The objective of this study was to investigate the effect of fat-soluble vitamin administration, primarily vitamin D, by different administration routes on plasma vitamin concentrations in suckling pigs. A total of 45 pigs from 5 litters were allotted at birth to 3 treatments within each litter. Pigs were administered 400 IU of α-tocopherol, 40,000 IU of retinyl palmitate, and 40,000 IU of vitamin D at d 1 of age either orally or by i.m. injection and compared with control pigs with no supplemental vitamin administration. Blood samples were collected at d 0 (initial), 1, 2, 3, 4, 6, 9, 14, and 20 after administration. Plasma 25-hydroxycholecalciferol (25OHD), α-tocopherol, retinyl palmitate, and retinol concentrations were analyzed. Except for retinol, the effects of treatment, day, and day × treatment interaction ( < 0.01) were observed on plasma vitamin concentrations. Plasma concentrations of 25OHD and α-tocopherol increased immediately regardless of administration routes to peak at d 2 and 1 after administration, respectively. Plasma retinyl palmitate concentrations increased only with the injection treatment, with the peak at d 1 after administration. Plasma concentrations of 25OHD in both administration treatments and α-tocopherol in the injection treatment were maintained at greater levels than those in the control treatment until d 20 after administration. With regard to the pharmacokinetic parameters for plasma 25OHD concentrations, the injection treatment had greater elimination half-life ( < 0.01), maximum plasma concentrations ( < 0.05), and all area under the curve parameters ( < 0.01) but a lower elimination rate constant ( < 0.01) than the oral treatment. Relative bioavailability of oral administration compared with injection administration was 55.26%. These results indicate that plasma status of 25OHD,α-tocopherol, and retinyl palmitate are differentially changed between types of

  10. Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

    SciTech Connect

    Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa

    2014-10-15

    Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC{sub 50} was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress.

  11. Effects of prolonged nutrient restriction on baseline and periprandial plasma ghrelin concentrations of postpubertal Holstein heifers.

    PubMed

    Field, M E; Deaver, S E; Rhoads, R P; Collier, R J; Rhoads, M L

    2013-10-01

    Objectives of this study were to measure both daily and periprandial plasma ghrelin concentrations of postpubertal Holstein heifers during prolonged undernutrition. Following an acclimation period, Holstein heifers [n=10; 339.5 ± 8.6 kg of body weight (BW)] were fed ad libitum [well fed (WF); n=5] or restricted to 50% of ad libitum intake [underfed (UF); n=5) for 8 wk. Body condition scores (BCS) were recorded at the beginning and end of the treatment period, and weekly measurements of BW, plasma ghrelin, progesterone, and nonesterified fatty acids (NEFA) concentrations were obtained. Ovarian follicular and luteal structures were measured twice weekly via transrectal ultrasonography. Plasma ghrelin concentrations were also measured during a periprandial window bleed conducted at the end of the experiment. During the window bleed, samples were collected every 15 min between 0500 and 0900 h, with feed offered at 0700 h. Underfed heifers lost BW and BCS, whereas WF heifers gained weight and either increased or maintained BCS. Chronic underfeeding increased circulating ghrelin and NEFA concentrations. By wk 4 of the treatment period, circulating ghrelin concentrations of the UF heifers reached a plateau. Periprandial fluctuations in ghrelin concentrations were apparent as plasma ghrelin concentrations changed over time. Overall differences in periprandial plasma ghrelin concentrations were primarily due to prefeeding effects of plane of nutrition. Plasma ghrelin concentrations and change in BCS were negatively correlated such that heifers that lost the most BCS had the highest concentrations of circulating ghrelin. Two of the 5 UF heifers became anestrus by wk 3 of the treatment period. Despite being of similar age, the heifers that became anestrus had lower BW and plasma ghrelin concentrations than the UF heifers that continued to ovulate. In the current experiment, long-term undernutrition elicited ghrelin responses similar to those reported for shorter durations of

  12. Propafenone poisoning--a case report with plasma propafenone concentrations.

    PubMed

    Ovaska, Hanna; Ludman, Andrew; Spencer, Edgar P; Wood, David M; Jones, Alison L; Dargan, Paul I

    2010-03-01

    Propafenone is an anti-arrhythmic drug used in the management of supraventricular and ventricular arrhythmias. It is metabolised through cytochrome P450 2D6 pathways; the major metabolites possess anti-arrhythmic activity. The cytochrome P450 CYP2D6 is coded by more than 70 alleles resulting in great genetic polymorphism of CYP2D6 isoenzymes, and up to 7% of Caucasian population are poor metabolisers. This case report describes a patient with severe overdose of propafenone who presented with coma, seizures and cardiotoxicity. The patient was managed with intravenous glucagon, hypertonic sodium bicarbonate, hypertonic saline and inotropic support. The propafenone and its 5-hydroxypropafenone (5-OHP) metabolite were measured by high-performance liquid chromatography with ultraviolet detection (no assay was available at the time to measure N-despropyl propafenone concentrations). Toxicological screen showed propafenone concentrations at a maximum of 1.26 mg/L at 9-10 h post-presentation, falling to 0.25 mg/L at 27-28 h post-presentation. No propafenone metabolite 5-OHP was detected in any sample analysed. No antidepressant or analgesic drugs were detected in toxicological screen. Propafenone overdose has been reported to be associated with features of severe cardiovascular and CNS toxicity. Aggressive treatment, meticulous monitoring and supportive care was associated with a good outcome in this case. PMID:20373066

  13. Fruit and vegetable intakes in relation to plasma nutrient concentrations in women in Shanghai, China

    PubMed Central

    Frankenfeld, Cara L.; Lampe, Johanna W.; Shannon, Jackilen; Gao, Dao L.; Li, Wenjin; Ray, Roberta M.; Chen, Chu; King, Irena B.; Thomas, David B.

    2012-01-01

    Objective To evaluate the validity of fruit and vegetable intake, using three classification schemes, as it relates to plasma carotenoid and vitamin C concentrations among Chinese women. Design Intakes were calculated from an interviewer-administered food frequency questionnaire. Fruits and vegetables, botanical groups, and high-nutrient groups were evaluated. These three classification schemes were compared with plasma carotenoid and vitamin C concentrations from blood drawn within one week of questionnaire completion. Setting Shanghai, China Subjects Participants (n=2031) were drawn from women who participated in a case-control study of diet and breast diseases nested within a randomized trial of breast self-examination among textile workers (n=266,064) Results Fruit intake was significantly (p<0.05) and positively associated with plasma concentrations of α-tocopherol, β-cryptoxanthin, lycopene, α-carotene, β-carotene, retinyl palmitate, and vitamin C. Fruit intake was inversely associated with γ-tocopherol and lutein+zeaxanthin concentrations. Vegetable consumption was significantly and positively associated with γ-tocopherol, and β-cryptoxanthin concentrations. Each botanical and high-nutrient group was also significantly associated with particular plasma nutrient concentrations. Fruit and vegetable intake and most plasma nutrient concentrations were significantly associated with season of interview. Conclusions These results suggest that the manner in which fruits and vegetables are grouped provides different plasma nutrient exposure information, which may be an important consideration when testing and generating hypotheses regarding disease risk in relation to diet. Interview season should be considered when evaluating associations of reported intake and plasma nutrients with disease outcomes. PMID:21729475

  14. Plasma steroid concentrations and male phallus size in juvenile alligators from seven Florida lakes

    USGS Publications Warehouse

    Guillette, L.J.; Woodward, A.R.; Crain, D.A.; Pickford, D.B.; Rooney, A.A.; Percival, H.F.

    1999-01-01

    Neonatal and juvenile alligators from contaminated Lake Apopka in central Florida exhibit abnormal plasma sex steroid concentrations as well as morphological abnormalities of the gonad and phallus. This study addresses whether similar abnormalities occur in juvenile alligators inhabiting six other lakes in Florida. For analysis, animals were partitioned into two subsets, animals 40-79 cm total length (1-3 years old) and juveniles 80-130 cm total length (3-7 years old). Plasma testosterone (T) concentrations were lower in small males from lakes Apopka, Griffin, and Jessup than from Lake Woodruff National Wildlife Refuge (NWR). Similar differences were observed in the larger juveniles, with males from lakes Jessup, Apopka, and Okeechobee having lower plasma T concentrations than Lake Woodruff males. Plasma estradiol-17?? (E2) concentrations were significantly elevated in larger juvenile males from Lake Apopka compared to Lake Woodruff NWR. When compared to small juvenile females from Lake Woodruff NWR, females from lakes Griffin, Apopka, Orange, and Okeechobee had elevated plasma E2 concentrations. Phallus size was significantly smaller in males from lakes Griffin and Apopka when compared to males from Lake Woodruff NWR. An association existed between body size and phallus size on all lakes except Lake Apopka and between phallus size and plasma T concentration on all lakes except lakes Apopka and Orange. Multiple regression analysis, with body size and plasma T concentration as independent covariables, explained the majority of the variation in phallus size on all lakes. These data suggest that the differences in sex steroids and phallus size observed in alligators from Lake Apopka are not limited to that lake, nor to one with a history of a major pesticide spill. Further work examining the relationship of sex steroids and phallus size with specific biotic and abiotic factors, such as antiandrogenic or estrogenic contaminants, is needed.

  15. Plasma and erythrocyte concentrations of free amino acids in adult humans administered abuse doses of aspartame.

    PubMed

    Stegink, L D; Filer, L J; Baker, G L

    1981-02-01

    Plasma and erythrocyte concentrations of amino acids were measured in 18 fasting adult subjects (9 male, 9 female) administered abuse doses of aspartame (100, 150, and 200 mg/kg body weight) dissolved in 500 ml orange juice. Six subjects were studied at each dose. Plasma aspartate concentrations increased significantly (p less than or equal to 0.05) over baseline values after ingestion of each dose. However, the increase was small in each case, and maximal levels observed were below those noted postprandially in formula-fed infants. No significant changes (p greater than 0.05) were noted in erythrocyte glutamate, or erythrocyte aspartate concentrations after any dose. Plasma phenylalanine concentrations increased significantly over fasting concentrations (p less than 0.01) from 15 min to 6 h after each dose, and the increase was proportional to dose. Mean (+/- SD) peak plasma phenylalanine concentrations were 20.3 +/- 2.03, 35.1 +/- 11.3, and 48.7 +/- 15.5 mumol/dl, respectively, after aspartame doses of 100, 150, and 200 mg/kg. Erythrocyte phenylalanine concentrations showed similar changes. Although these phenylalanine concentrations are considerably above the normal postprandial range (12 +/- 3 mumol/dl), they are below values associated with toxic findings. These data indicate little risk to normal subjects from excessive aspartate or phenylalanine levels after ingestion of single abuse loads of aspartame.

  16. Nicotine and lung development.

    PubMed

    Maritz, Gert S

    2008-03-01

    Nicotine is found in tobacco smoke. It is a habit forming substance and is prescribed by health professionals to assist smokers to quit smoking. It is rapidly absorbed from the lungs of smokers. It crosses the placenta and accumulates in the developing fetus. Nicotine induces formation of oxygen radicals and at the same time also reduces the antioxidant capacity of the lungs. Nicotine and the oxidants cause point mutations in the DNA molecule, thereby changing the program that controls lung growth and maintenance of lung structure. The data available indicate that maternal nicotine exposure induces a persistent inhibition of glycolysis and a drastically increased cAMP level. These metabolic changes are thought to contribute to the faster aging of the lungs of the offspring of mothers that are exposed to nicotine via the placenta and mother's milk. The lungs of these animals are more susceptible to damage as shown by the gradual deterioration of the lung parenchyma. The rapid metabolic and structural aging of the lungs of the animals that were exposed to nicotine via the placenta and mother's milk, and thus during phases of lung development characterized by rapid cell division, is likely due to "programming" induced by nicotine. It is, therefore, not advisable to use nicotine during gestation and lactation. PMID:18383131

  17. Plasma corticosterone and thyroxine concentrations during chronic ingestion of crude oil in mallard ducks (Anas platyrhynchos)

    USGS Publications Warehouse

    Rattner, B.A.; Eastin, W.C., Jr.

    1981-01-01

    1. Blood samples were collected from mallard ducks after 6, 12, and 18 weeks of dietary exposure to mash containing 0.015%, 0.150%, and 1.500% crude oil. 2. Plasma corticosterone concentrations in ducks fed mash containing 0.150% or 1.500% Alaskan Prudhoe Bay crude oil were uniformly depressed when compared to values in untreated control birds. 3. Plasma thyroxine concentration was not altered in ducks chronically exposed to crude oil. 4. The observed alteration in corticosterone concentration could reduce tolerance to temperature and dietary fluctuations in the environment.

  18. Developmental cholinotoxicants: nicotine and chlorpyrifos.

    PubMed

    Slotkin, T A

    1999-02-01

    The stimulation of cholinergic receptors in target cells during a critical developmental period provides signals that influence cell replication and differentiation. Accordingly, environmental agents that promote cholinergic activity evoke neurodevelopmental damage because of the inappropriate timing or intensity of stimulation. Nicotine evokes mitotic arrest in brain cells possessing high concentrations of nicotinic cholinergic receptors. In addition, the cholinergic overstimulation programs the expression of genes that evoke apoptosis and delayed cell loss. Effects of cholinesterase inhibitors exhibit many similarities to those of nicotine. Chlorpyrifos administered to developing rats in doses that do not evoke signs of overt toxicity decreased DNA synthesis and caused shortfalls in cell numbers in brain regions enriched in cholinergic innervation. In embryo cultures, chlorpyrifos also evoked apoptosis during neurulation. However, chlorpyrifos also evokes noncholinergic disruption of cell development by interfering with cell signaling via adenylyl cyclase, leading to widespread disruption that is not limited to cholinergic systems. We have tested this hypothesis in vitro with PC12 cells, which lack the enzymes necessary to produce chlorpyrifos oxon, the metabolite that inhibits cholinesterase. Chlorpyrifos inhibited DNA synthesis in undifferentiated PC12 cells, which have relatively few cholinergic receptors. Furthermore, chlorpyrifos was more effective than nicotine and its effects were not blocked by cholinergic antagonists. When cells were allowed to differentiate in the presence of chlorpyrifos, cell replication was inhibited even more profoundly and cell acquisition was arrested. At higher concentrations, chlorpyrifos also inhibited neuritic outgrowth. Thus, chlorpyrifos elicits damage by both noncholinergic and cholinergic mechanisms extending from early stages of neural cell replication through late stages of axonogenesis and terminal differentiation

  19. Developmental cholinotoxicants: nicotine and chlorpyrifos.

    PubMed Central

    Slotkin, T A

    1999-01-01

    The stimulation of cholinergic receptors in target cells during a critical developmental period provides signals that influence cell replication and differentiation. Accordingly, environmental agents that promote cholinergic activity evoke neurodevelopmental damage because of the inappropriate timing or intensity of stimulation. Nicotine evokes mitotic arrest in brain cells possessing high concentrations of nicotinic cholinergic receptors. In addition, the cholinergic overstimulation programs the expression of genes that evoke apoptosis and delayed cell loss. Effects of cholinesterase inhibitors exhibit many similarities to those of nicotine. Chlorpyrifos administered to developing rats in doses that do not evoke signs of overt toxicity decreased DNA synthesis and caused shortfalls in cell numbers in brain regions enriched in cholinergic innervation. In embryo cultures, chlorpyrifos also evoked apoptosis during neurulation. However, chlorpyrifos also evokes noncholinergic disruption of cell development by interfering with cell signaling via adenylyl cyclase, leading to widespread disruption that is not limited to cholinergic systems. We have tested this hypothesis in vitro with PC12 cells, which lack the enzymes necessary to produce chlorpyrifos oxon, the metabolite that inhibits cholinesterase. Chlorpyrifos inhibited DNA synthesis in undifferentiated PC12 cells, which have relatively few cholinergic receptors. Furthermore, chlorpyrifos was more effective than nicotine and its effects were not blocked by cholinergic antagonists. When cells were allowed to differentiate in the presence of chlorpyrifos, cell replication was inhibited even more profoundly and cell acquisition was arrested. At higher concentrations, chlorpyrifos also inhibited neuritic outgrowth. Thus, chlorpyrifos elicits damage by both noncholinergic and cholinergic mechanisms extending from early stages of neural cell replication through late stages of axonogenesis and terminal differentiation

  20. The effect of feeding canola meal on concentrations of plasma amino acids.

    PubMed

    Martineau, R; Ouellet, D R; Lapierre, H

    2014-03-01

    An initial meta-analysis on isonitrogenous experiments where a protein source was replaced by canola meal (CM) showed that CM feeding increased yields of milk and milk protein and apparent N efficiency. The objective of the current study was to determine if these responses were related to increased changes in plasma AA concentrations. Although only half of the experiments of the initial meta-analysis reported concentrations of plasma AA and could be used in the current meta-analysis, lactational responses to CM feeding were similar to those reported previously. In the current meta-analysis, CM feeding increased plasma concentrations of total AA, total essential AA (EAA) and all individual EAA, but decreased concentrations of blood and milk urea-N. The current meta-analysis suggests that CM feeding increased the absorption of EAA, which would be responsible for the increased milk protein secretion and the increased apparent N efficiency.

  1. Seasonal variations in plasma testosterone concentrations in the male marsupial bandicoot Isoodon macrourus in captivity.

    PubMed

    Gemmell, R T; Johnston, G; Barnes, A

    1985-08-01

    Although bandicoots in Queensland mate throughout the year, the majority of births occur in late winter and spring. To ascertain whether this seasonality in mating is manifest in the male reproductive system; body weight, testes size, and plasma testosterone concentration were examined in eight bandicoots throughout the year. The size of the testes increased with age in all bandicoots and there was no evidence of seasonal variation. Plasma testosterone concentrations fluctuated from 0.1 to 70.0 ng/ml and a seasonal cycle was observed, with a nadir in concentrations in March and a peak in September. The peak in testosterone concentration coincided with the period of the year when the majority of births occurred. Subsequent statistical analysis suggested that the annual plasma testosterone profile correlated well with the rate of change of day length. PMID:4018558

  2. The effect of feeding canola meal on concentrations of plasma amino acids.

    PubMed

    Martineau, R; Ouellet, D R; Lapierre, H

    2014-03-01

    An initial meta-analysis on isonitrogenous experiments where a protein source was replaced by canola meal (CM) showed that CM feeding increased yields of milk and milk protein and apparent N efficiency. The objective of the current study was to determine if these responses were related to increased changes in plasma AA concentrations. Although only half of the experiments of the initial meta-analysis reported concentrations of plasma AA and could be used in the current meta-analysis, lactational responses to CM feeding were similar to those reported previously. In the current meta-analysis, CM feeding increased plasma concentrations of total AA, total essential AA (EAA) and all individual EAA, but decreased concentrations of blood and milk urea-N. The current meta-analysis suggests that CM feeding increased the absorption of EAA, which would be responsible for the increased milk protein secretion and the increased apparent N efficiency. PMID:24440260

  3. Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma

    NASA Technical Reports Server (NTRS)

    Conlay, L. A.; Maher, T. J.; Roberts, C. H.; Wurtman, R. J.

    1988-01-01

    Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord were examined. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial (H-3)tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of (H-3)tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

  4. Consumption of olive oil has opposite effects on plasma total cholesterol and sphingomyelin concentrations in rats.

    PubMed

    Geelen, M J; Beynen, A C

    2000-05-01

    The hypothesis that olive-oil consumption alters plasma sphingomyelin concentrations and hepatic sphingomyelin metabolism was tested. Rats were fed on purified, high-cholesterol diets with either coconut fat or olive-oil (180 g/kg). In accordance with previous work, olive-oil v. coconut-fat consumption significantly elevated hepatic and total plasma cholesterol concentrations. During the course of the experiment, the concentration of plasma sphingomyelin rose in the coconut-fat group and remained constant in the olive-oil group. When compared with the coconut-fat-fed group, the plasma sphingomyelin levels were significantly lower in the olive-oil-fed group after 14 and 21 d of treatment. Dietary olive oil raised the amounts of cholesterol and sphingomyelin in the VLDL density region, and this change was associated with a reduction in the cholesterol and sphingomyelin contents of the LDL and HDL density ranges. Olive-oil consumption reduced the activity of serine palmitoyltransferase, while the activities of phosphatidylcholine:ceramide cholinephosphotransferase and phosphatidylethanolamine:ceramide ethanolaminephosphotransferase were left unchanged. Dietary olive oil also enhanced the activity of acidic sphingomyelinase, but not that of neutral sphingomyelinase. The present data indicate that dietary olive oil v. coconut fat has opposite effects on total plasma cholesterol and sphingomyelin concentrations. The lower plasma sphingomyelin levels observed in olive-oil-fed, as compared with coconut-fat-fed rats, may be explained by a simultaneous elevation and reduction in sphingomyelin catabolism and synthesis respectively, as based on the measured enzyme activities.

  5. Evaluation of the serum fructosamine test to monitor plasma glucose concentration in the transition dairy cow.

    PubMed

    Sorondo, María L; Cirio, Alberto

    2009-05-01

    The usefulness of the serum fructosamine (Fser) to monitor the retrospective glucose concentrations in transitional dairy cows (n=17) was evaluated. In weekly blood samples (3 weeks before to 5 weeks after calving) concentrations of plasma glucose and serum fructosamine, beta-hydroxybutyrate (beta OHB) and total proteins were determined. The observed Fser concentrations (271+/-55 mean value, range 152-423 mumol/l) were within the range reported in the literature, and showed a progressive and significant decrease after calving. Mean plasma glucose concentration was 60.6+/-5.0 (range 39.9-82.2) mg/dl increasing from week 3 before calving to the week of calving and then decreasing during the next 5 weeks of lactation. This decrease was coincident with inverse relationships between plasma glucose and milk yield (P=0.03) and serum beta OHB (P<0.001). Linear regression analysis performed between serum fructosamine and (a) plasma glucose concentration of the same sampling and (b) plasma glucose concentration of 1, 2 and 3 weeks preceding the sampling, did not show significant and systematizing positive correlations. Persistent hypoproteinaemias that could affect the fructosamine concentrations were not found: mean value and range of serum proteins was 6.3+/-1.0 and 4.8-7.8 g/dl, respectively, and no correlation was found between serum proteins and Fser (P=0.26). Results did not support the possibility of retrospective monitoring of the plasma glucose concentration by serum fructosamine in dairy cows in the transition period.

  6. Motility of liquid stored ram spermatozoa is altered by dilution rate independent of seminal plasma concentration.

    PubMed

    Mata-Campuzano, M; Soleilhavoup, C; Tsikis, G; Martinez-Pastor, F; de Graaf, S P; Druart, X

    2015-11-01

    The fertility after use of liquid stored ram semen following cervical AI rapidly decreases if semen is stored beyond 12h. The dilution of seminal plasma is often cited as a key contributor to the diminished motility and fertility of ram spermatozoa subjected to liquid preservation. Two experiments were conducted to assess the effect of spermatozoa concentration (i.e. dilution rate) and percentage of seminal plasma on the motility and viability of liquid stored ram spermatozoa. In Experiment 1, semen was diluted to one of seven concentrations ranging from 0.2 to 1.4×10(9)spermatozoa/ml with milk and assessed for motility after 3 or 24h of storage at 15°C. In Experiment 2, semen was collected and washed to remove seminal plasma before re-dilution to 0.2-1.4×10(9)spermatozoa/ml with milk containing 0%, 20% or 40% (final v/v ratio) seminal plasma and assessed for viability and motility after 3 or 24h of storage at 15°C. Whereas motility was not affected by spermatozoa concentration after 3h of storage, the proportion of progressive spermatozoa decreased after 24h of storage when spermatozoa concentration was greater than 1.0×10(9)spermatozoa/ml. The duration of preservation and the spermatozoa concentration affected spermatozoa motility but had no impact on spermatozoa viability. This negative effect of greater spermatozoa concentrations on motility was independent of the presence and the concentration of seminal plasma. The seminal plasma at both concentrations (20% and 40%) had a protective effect on spermatozoa motility after 24h of storage. These findings have the potential to improve the efficiency of cervical AI with liquid stored ram semen.

  7. Plasma clusterin concentration is associated with longitudinal brain atrophy in mild cognitive impairment.

    PubMed

    Thambisetty, Madhav; An, Yang; Kinsey, Anna; Koka, Deepthi; Saleem, Muzamil; Güntert, Andreas; Kraut, Michael; Ferrucci, Luigi; Davatzikos, Christos; Lovestone, Simon; Resnick, Susan M

    2012-01-01

    Recent genetic and proteomic studies demonstrate that clusterin/apolipoprotein-J is associated with risk, pathology, and progression of Alzheimer's disease (AD). Our main aim was to examine associations between plasma clusterin concentration and longitudinal changes in brain volume in normal aging and mild cognitive impairment (MCI). A secondary objective was to examine associations between peripheral concentration of clusterin and its concentration in the brain within regions that undergo neuropathological changes in AD. Non-demented individuals (N=139; mean baseline age 70.5 years) received annual volumetric MRI (912 MRI scans in total) over a mean six-year interval. Sixteen participants (92 MRI scans in total) were diagnosed during the course of the study with amnestic MCI. Clusterin concentration was assayed by ELISA in plasma samples collected within a year of the baseline MRI. Mixed effects regression models investigated whether plasma clusterin concentration was associated with rates of brain atrophy for control and MCI groups and whether these associations differed between groups. In a separate autopsy sample of individuals with AD (N=17) and healthy controls (N=4), we examined the association between antemortem clusterin concentration in plasma and postmortem levels in the superior temporal gyrus, hippocampus and cerebellum. The associations of plasma clusterin concentration with rates of change in brain volume were significantly different between MCI and control groups in several volumes including whole brain, ventricular CSF, temporal gray matter as well as parahippocampal, superior temporal and cingulate gyri. Within the MCI but not control group, higher baseline concentration of plasma clusterin was associated with slower rates of brain atrophy in these regions. In the combined autopsy sample of AD and control cases, representing a range of severity in AD pathology, we observed a significant association between clusterin concentration in the plasma and

  8. Impact of Whole-Blood Processing Conditions on Plasma and Serum Concentrations of Cytokines.

    PubMed

    Lee, Jae-Eun; Kim, Jong-Wan; Han, Bok-Ghee; Shin, So-Youn

    2016-02-01

    Pre-analytical variations in plasma and serum samples can occur because of variability in whole-blood processing procedures. The aim of this study was to determine the impact of delayed separation of whole blood on the plasma and serum concentrations of cytokines. The concentrations of 16 cytokines were measured in plasma and serum samples when the centrifugation of whole blood at room temperature was delayed for 4, 6, 24, or 48 h, and the values were compared with those observed after separation within 2 h of whole-blood collection. Receiver operating characteristic (ROC) curve analysis was also performed for cytokines to determine whether cytokine levels in plasma and serum samples can be used to assess delayed separation of whole blood. Plasma concentrations of interleukin (IL)-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), and soluble CD40 ligand (sCD40L) and serum concentrations of IL-1β, IL-6, IL-8, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β increased significantly (>2-fold) when separation was delayed at room temperature for 24 h. The concentrations of 6 of these cytokines (all except serum IL-1β and IL-6) demonstrated high diagnostic performance (area under the ROC curve >0.8) for delayed separation of whole blood. Furthermore, these cytokine concentrations typically exhibited high sensitivity and specificity at each optimal cutoff point. Conversely, IL-17A was stable in both plasma and serum samples, even when whole-blood centrifugation was delayed at room temperature for 48 h. This study shows that certain cytokines (IL-1β, GM-CSF, sCD40L, IL-8, MIP-1α, and MIP-1β) could be used for assessing the quality of plasma or serum samples. PMID:26808439

  9. Cotinine antagonizes the behavioral effects of nicotine exposure in the planarian Girardia tigrina.

    PubMed

    Bach, Daniel J; Tenaglia, Matthew; Baker, Debra L; Deats, Sean; Montgomery, Erica; Pagán, Oné R

    2016-10-01

    Nicotine is one of the most addictive drugs abused by humans. Our laboratory and others have demonstrated that nicotine decreases motility and induces seizure-like behavior in planarians (pSLM, which are vigorous writhing and bending of the body) in a concentration-dependent manner. Nicotine also induces withdrawal-like behaviors in these worms. Cotinine is the major nicotine metabolite in humans, although it is not the final product of nicotine metabolism. Cotinine is mostly inactive in vertebrate nervous systems and is currently being explored as a molecule which possess most of nicotine's beneficial effects and few of its undesirable ones. It is not known whether cotinine is a product of nicotine metabolism in planarians. We found that cotinine by itself does not seem to elicit any behavioral effects in planarians up to a concentration of 1mM. We also show that cotinine antagonizes the aforementioned nicotine-induced motility decrease and also decreases the expression of nicotine-induced pSLMs in a concentration-dependent manner. Also cotinine prevents the manifestation of some of the withdrawal-like behaviors induced by nicotine in our experimental organism. Thus, we obtained evidence supporting that cotinine antagonizes nicotine in this planarian species. Possible explanations include competitive binding of both compounds at overlapping binding sites, at different nicotinic receptor subtypes, or maybe allosteric interactions. PMID:27616704

  10. Cotinine antagonizes the behavioral effects of nicotine exposure in the planarian Girardia tigrina.

    PubMed

    Bach, Daniel J; Tenaglia, Matthew; Baker, Debra L; Deats, Sean; Montgomery, Erica; Pagán, Oné R

    2016-10-01

    Nicotine is one of the most addictive drugs abused by humans. Our laboratory and others have demonstrated that nicotine decreases motility and induces seizure-like behavior in planarians (pSLM, which are vigorous writhing and bending of the body) in a concentration-dependent manner. Nicotine also induces withdrawal-like behaviors in these worms. Cotinine is the major nicotine metabolite in humans, although it is not the final product of nicotine metabolism. Cotinine is mostly inactive in vertebrate nervous systems and is currently being explored as a molecule which possess most of nicotine's beneficial effects and few of its undesirable ones. It is not known whether cotinine is a product of nicotine metabolism in planarians. We found that cotinine by itself does not seem to elicit any behavioral effects in planarians up to a concentration of 1mM. We also show that cotinine antagonizes the aforementioned nicotine-induced motility decrease and also decreases the expression of nicotine-induced pSLMs in a concentration-dependent manner. Also cotinine prevents the manifestation of some of the withdrawal-like behaviors induced by nicotine in our experimental organism. Thus, we obtained evidence supporting that cotinine antagonizes nicotine in this planarian species. Possible explanations include competitive binding of both compounds at overlapping binding sites, at different nicotinic receptor subtypes, or maybe allosteric interactions.

  11. Effects of nicotine-specific antibodies, Nic311 and Nic-IgG, on the transfer of nicotine across the human placenta.

    PubMed

    Nekhayeva, Ilona A; Nanovskaya, Tatiana N; Pentel, Paul R; Keyler, Dan E; Hankins, Gary D V; Ahmed, Mahmoud S

    2005-11-25

    The adverse effects of smoking during pregnancy on fetal development are, in part, due to nicotine. These effects may be due to the actions of nicotine in fetal circulation or on placental functions. In pregnant rats, vaccination with a nicotine immunogen reduces the transfer of nicotine from the maternal to fetal circulation. However, extrapolation of these results to pregnant women might not be valid due to the well-recognized differences between human and rat placentas. In the current investigation, the effects of nicotine-specific antibodies on the transfer of nicotine from the maternal to fetal circuit of the dually perfused human placental lobule were determined. Two types of nicotine-specific antibodies were investigated; nicotine-specific mouse monoclonal antibody (Nic311, K(d) for nicotine 60nM) and IgG from rabbits vaccinated with a nicotine immunogen (Nic-IgG, K(d) 1.6nM). Transfer of the antibodies from maternal to fetal circuits was negligible. Both rabbit Nic-IgG and, to a lesser extent, mouse monoclonal Nic311 significantly reduced nicotine transfer from the maternal to fetal circuit as well as the retention of the drug by placental tissue. These effects were mediated by a substantial increase in the protein binding of nicotine and a reduction in the unbound nicotine concentration. Therefore, the data cited in this report suggest that the use of nicotine-specific antibodies might reduce fetal exposure to the drug, and that antibody affinity for nicotine is a key determinant of the extent of nicotine transfer.

  12. Significance of nitric oxide concentration in plasma and uterine secretes with puerperal endometritis in dairy cows.

    PubMed

    Li, DeJun; Liu, YunFeng; Li, YanFei; Lv, Ying; Pei, XiaoYing; Guo, DingZong

    2010-04-01

    Endometritis is an inflammation of the endometrial lining of the uterus without systemic signs, which is associated with chronic postpartum infection of the uterus with pathogenic bacteria. Nitric oxide (NO) is an inflammatory mediator that among other effects causes smooth muscle relaxation and mediated cytoimmunity and inflammation toxicity. To see if the nitric oxide concentration in plasma and uterine secrets is related with postpartum endometritis, NO concentrations in plasma and uterine secrets were measured in dairy cows with puerperal endometritis (clinical endometritis (n = 60) and subclinical endometritis (n = 58)). Cows with clinical or subclinical endometritis showed higher concentrations of NO in both plasma and uterine secrets when compared with normal cows and the highest concentrations of NO in plasma and uterine secrets were found in dairy cows with clinical endometritis. Expression level of NOS2 mRNA in endometrial biopsies from cows with puerperal endometritis was also higher and the highest expression of NOS2 mRNA was found in cows with clinical endometritis. The results showed that concentrations of NO in plasma and uterine fluid are related with the degree of endometritis which may be useful to diagnose the endometritis in dairy cows. PMID:20414720

  13. Comparison of digoxin concentration in plastic serum tubes with clot activator and heparinized plasma tubes

    PubMed Central

    Dukić, Lora; Šimundić, Ana-Maria; Malogorski, Davorin

    2014-01-01

    Introduction: Sample type recommended by the manufacturer for the digoxin Abbott assay is either serum collected in glass tubes or plasma (sodium heparin, lithium heparin, citrate, EDTA or oxalate as anticoagulant) collected in plastic tubes. In our hospital samples are collected in plastic tubes. Our hypothesis was that the serum sample collected in plastic serum tube can be used interchangeably with plasma sample for measurement of digoxin concentration. Our aim was verification of plastic serum tubes for determination of digoxin concentration. Materials and methods: Concentration of digoxin was determined simultaneously in 26 venous blood plasma (plastic Vacuette, LH Lithium heparin) and serum (plastic Vacuette, Z Serum Clot activator; both Greiner Bio-One GmbH, Kremsmünster, Austria) samples, on Abbott AxSYM analyzer using the original Abbott Digoxin III assay (Abbott, Wiesbaden, Germany). Tube comparability was assessed using the Passing Bablok regression and Bland-Altman plot. Results: Serum and plasma digoxin concentrations are comparable. Passing Bablok intercept (0.08 [95% CI = −0.10 to 0.20]) and slope (0.99 [95% CI = 0.92 to 1.11]) showed there is no constant or proportional error. Conclusion: Blood samples drawn in plastic serum tubes and plastic plasma tubes can be interchangeably used for determination of digoxin concentration. PMID:24627723

  14. Optimized Preparation Method of Platelet-Concentrated Plasma and Noncoagulating Platelet-Derived Factor Concentrates: Maximization of Platelet Concentration and Removal of Fibrinogen

    PubMed Central

    Araki, Jun; Jona, Masahiro; Eto, Hitomi; Aoi, Noriyuki; Kato, Harunosuke; Suga, Hirotaka; Doi, Kentaro; Yatomi, Yutaka

    2012-01-01

    Abstract Platelet-rich plasma (PRP) has been clinically used as an easily prepared growth factor cocktail that can promote wound healing, angiogenesis, and tissue remodeling. However, the therapeutic effects of PRP are still controversial, due partly to the lack of optimized and standardized preparation protocols. We used whole blood (WB) samples to optimize the preparation protocols for PRP, white blood cell-containing (W-PRP), platelet-concentrated plasma (PCP), and noncoagulating platelet-derived factor concentrate (PFC). PRP and W-PRP were most efficiently collected by 10 min centrifugation in a 15-mL conical tube at 230–270 g and 70 g, respectively. To prepare PCP, platelets were precipitated by centrifugation of PRP at >2300 g, 90% of supernatant plasma was removed, and the platelets were resuspended. For preparation of noncoagulating PFC, the supernatant was replaced with one-tenth volume of saline, followed by platelet activation with thrombin. Platelet (before activation) and platelet-derived growth factor (PDGF)-BB (after activation) concentrations in PCP were approximately 20 times greater than those in WB, whereas PFC contained a 20-times greater concentration of platelets before platelet activation and a 50-times greater concentration of PDGF-BB without formation of a fibrin gel after platelet activation than WB. Surprisingly, total PDGF-BB content in the PFC was twice that of activated WB, which suggested that a substantial portion of the PDGF-BB became trapped in the fibrin glue, and replacement of plasma with saline is crucial for maximization of platelet-derived factors. As an anticoagulant, ethylene di-amine tetra-acetic acid disodium inhibited platelet aggregation more efficiently than acid citrate dextrose solution, resulting in higher nonaggregated platelet yield and final PDGF-BB content. These results increase our understanding of how to optimize and standardize preparation of platelet-derived factors at maximum concentrations. PMID

  15. Plasma aldosterone and sweat sodium concentrations after exercise and heat acclimation

    NASA Technical Reports Server (NTRS)

    Kirby, C. R.; Convertino, V. A.

    1986-01-01

    The relationship between plasma aldosterone levels and sweat sodium excretion after chronic exercise and heat acclimation was investigated, using subjects exercised, at 40 C and 45 percent humidity, for 2 h/day on ten consecutive days at 45 percent of their maximal oxygen uptake. The data indicate that, following heat acclimation, plasma aldosterone concentrations decrease, and that the eccrine gland responsiveness to aldosterone, as represented by sweat sodium reabsorption, may be augmented through exercise and heat acclimation.

  16. The impact of the concentration of drug binding plasma proteins on drug distribution according to Øie-Tozer's model.

    PubMed

    Svennebring, Andreas Mats

    2016-01-01

    1. New equations have been developed from an updated version of Øie-Tozer's model expressing how the free concentration and volume of distribution change in relation to changes in the concentration of drug binding plasma proteins. This updated model accommodates more than one drug binding plasma protein to contribute to the plasma protein binding. 2. Demonstrations of the model show that variability in the concentration of one plasma protein has considerably less impact on the free drug concentration and volume of distribution if other plasma proteins contribute to binding, than if they don't.

  17. Plasma free fatty acid metabolism during storage of platelet concentrates for transfusion.

    PubMed

    Cesar, J; DiMinno, G; Alam, I; Silver, M; Murphy, S

    1987-01-01

    New containers allow storage of platelet concentrates (PC) at 22 degrees C for up to 7 days, during which glycolytic and oxidative metabolism is vigorous. Recent evidence suggests that 85 percent of adenosine triphosphate regeneration is based on oxidative metabolism and that substrates other than glucose may be used. Because platelets can oxidize free fatty acids (FFA) as a possible source of energy during storage, the authors studied their availability, distribution, and turnover. Plasma FFA concentration was unchanged after 1 day of PC storage but significantly increased on Days 3, 5, and 7. Platelet-free plasma (PFP) stored under the same conditions as PC demonstrated a progressive increase in FFA, suggesting that some of the FFA accumulating in PC were derived from plasma rather than platelets. Indeed, during PC storage, plasma triglycerides decreased significantly, suggesting that they are a possible source of the increased levels of FFA found on Day 3 and thereafter. Thus, PC have a plasma FFA pool available continuously for oxidation during storage. Studies with radiolabeled palmitate suggested that FFA oxidation by platelets occurs during storage. The current findings show that plasma FFA could be a significant substrate for oxidative metabolism during storage of PC and that the oxidized FFA are replenished at least in part from plasma. These results may allow platelet storage to be improved, particularly in synthetic media. PMID:3629676

  18. Determining Concentrations and Temperatures in Semiconductor Manufacturing Plasmas via Submillimeter Absorption Spectroscopy

    NASA Astrophysics Data System (ADS)

    Helal, Yaser H.; Neese, Christopher F.; De Lucia, Frank C.; Ewing, Paul R.; Agarwal, Ankur; Craver, Barry; Stout, Phillip J.; Armacost, Michael D.

    2016-06-01

    Plasmas used in the manufacturing processes of semiconductors are similar in pressure and temperature to plasmas used in studying the spectroscopy of astrophysical species. Likewise, the developed technology in submillimeter absorption spectroscopy can be used for the study of industrial plasmas and for monitoring manufacturing processes. An advantage of submillimeter absorption spectroscopy is that it can be used to determine absolute concentrations and temperatures of plasma species without the need for intrusive probes. A continuous wave, 500 - 750 GHz absorption spectrometer was developed for the purpose of being used as a remote sensor of gas and plasma species. An important part of this work was the optical design to match the geometry of existing plasma reactors in the manufacturing industry. A software fitting routine was developed to simultaneously fit for the background and absorption signal, solving for concentration, rotational temperature, and translational temperature. Examples of measurements made on inductively coupled plasmas will be demonstrated. We would like to thank the Texas Analog Center of Excellence/Semiconductor Research Corporation (TxACE/SRC) and Applied Materials for their support of this work.

  19. Pathogen inactivation and removal methods for plasma-derived clotting factor concentrates.

    PubMed

    Klamroth, Robert; Gröner, Albrecht; Simon, Toby L

    2014-05-01

    Pathogen safety is crucial for plasma-derived clotting factor concentrates used in the treatment of bleeding disorders. Plasma, the starting material for these products, is collected by plasmapheresis (source plasma) or derived from whole blood donations (recovered plasma). The primary measures regarding pathogen safety are selection of healthy donors donating in centers with appropriate epidemiologic data for the main blood-transmissible viruses, screening donations for the absence of relevant infectious blood-borne viruses, and release of plasma pools for further processing only if they are nonreactive for serologic markers and nucleic acids for these viruses. Despite this testing, pathogen inactivation and/or removal during the manufacturing process of plasma-derived clotting factor concentrates is required to ensure prevention of transmission of infectious agents. Historically, hepatitis viruses and human immunodeficiency virus have posed the greatest threat to patients receiving plasma-derived therapy for treatment of hemophilia or von Willebrand disease. Over the past 30 years, dedicated virus inactivation and removal steps have been integrated into factor concentrate production processes, essentially eliminating transmission of these viruses. Manufacturing steps used in the purification of factor concentrates have also proved to be successful in reducing potential prion infectivity. In this review, current techniques for inactivation and removal of pathogens from factor concentrates are discussed. Ideally, production processes should involve a combination of complementary steps for pathogen inactivation and/or removal to ensure product safety. Finally, potential batch-to-batch contamination is avoided by stringent cleaning and sanitization methods as part of the manufacturing process.

  20. Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence.

    PubMed

    Stegink, L D; Filer, L J; Bell, E F; Ziegler, E E

    1987-05-01

    Some clinical studies require administration of test compounds in capsules to assure that the compound cannot be distinguished from a placebo. This raises the question of whether the pharmacokinetic responses produced by capsule administration are similar to values obtained when test compounds are ingested in solution. To test this, plasma phenylalanine and aspartate concentrations were compared in ten normal subjects ingesting 3 g aspartame in solution and in capsules in a balanced Latin square design. Peak plasma phenylalanine levels were significantly higher (191 +/- 65.4 v 117 +/- 39.5 mumol/L, mean +/- SD) and were reached significantly earlier (32 +/- 15 v 123 +/- 74 minutes) when aspartame was administered in solution than when it was administered in capsules. The area under the four-hour plasma phenylalanine concentration-time curve was significantly higher (15,340 +/- 4,820 v 8,465 +/- 3,356 mumol/L X min) when aspartame was ingested in solution. Administration in solution also produced a significantly higher ratio of plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids (0.36 +/- 0.12 v 0.23 +/- 0.06). Similarly, peak plasma aspartate concentrations were significantly higher 26.2 +/- 16.3 v 10.4 +/- 5.0 mumol/L) and were reached significantly earlier (30 +/- 14 v 106 +/- 61.3 min) when aspartame was administered in solution. The data indicate different plasma phenylalanine and aspartate pharmacokinetics between solution and capsule administration of aspartame.

  1. Effects of differently composed feeds and physical stress on plasma gastrin concentration in horses.

    PubMed

    Sandin, A; Girma, K; Sjöholm, B; Lindholm, A; Nilsson, G

    1998-01-01

    Plasma gastrin concentrations were determined in 6 Standardbreds (4 geldings and 2 mares) after 3 different meals consisting of unlimited amounts of hay (8-9 kg per horse), a restricted amount of hay (0.6 kg/100 kg body-weight) and grain (0.2 kg/100 kg body-weight) in combination or of grain alone (0.2 kg/100 kg body-weight). In another series of experiments the possible role of gastrin as a stress hormone was investigated. Plasma gastrin and cortisol concentrations were determined during fasting and compared with concentrations during hay feeding. In addition, gastrin and cortisol concentrations were determined before, during and after 2 kinds of physical exercise on a treadmill. Meal stimulation significantly increased the plasma gastrin concentration, irrespective of the meal composition. An immediate and large increase in plasma gastrin concentration was found when voluminous meals were given, whereas a small meal evoked a later onset of gastrin release, suggesting that gastric distention plays an important role in inducing gastrin release during a meal. Meals consisting of grain seem to evoke a slower onset and then a more prolonged gastrin response than a hay meal, possibly due to different emptying rates of the stomach. Nervous excitation may play a minor role in the activation of gastrin release in horses. No experimental support was obtained for the idea that gastrin acts as a stress hormone in the horse.

  2. Power law relation between particle concentrations and their sizes in the blood plasma

    NASA Astrophysics Data System (ADS)

    Kirichenko, M. N.; Chaikov, L. L.; Zaritskii, A. R.

    2016-08-01

    This work is devoted to the investigation of sizes and concentrations of particles in blood plasma by dynamic light scattering (DLS). Blood plasma contains many different proteins and their aggregates, microparticles and vesicles. Their sizes, concentrations and shapes can give information about donor's health. Our DLS study of blood plasma reveals unexpected dependence: with increasing of the particle sizes r (from 1 nm up to 1 μm), their concentrations decrease as r-4 (almost by 12 orders). We found also that such dependence was repeated for model solution of fibrinogen and thrombin with power coefficient is -3,6. We believe that this relation is a fundamental law of nature that shows interaction of proteins (and other substances) in biological liquids.

  3. Plasma urea, creatinine and uric acid concentrations in relation to feeding in peregrine falcons (Falco peregrinus).

    PubMed

    Lumeij, J T; Remple, J D

    1991-03-01

    Significant post-prandial increases in plasma uric acid and plasma urea concentrations were observed in peregrine falcons. Post-prandial uric acid concentrations were similar to those in birds suffering from hyperuricaemia and gout and were well above the theoretical limit of solubility of sodium urate in plasma. It is not clear why under normal circumstances no urate deposits occur in peregrine falcons (and probably other raptorial birds), which show hyperuricaemia for at least 12 h after ingesting a natural meal. It is important to evaluate renal function in peregrine falcons (and perhaps other birds) after a 24-h fast to avoid misinterpretation due to physiological food-induced elevated concentrations of nonprotein nitrogen substances.

  4. Environmental fate and effects of nicotine released during cigarette production.

    PubMed

    Seckar, Joel A; Stavanja, Mari S; Harp, Paul R; Yi, Yongsheng; Garner, Charles D; Doi, Jon

    2008-07-01

    A variety of test methods were used to study the gradation, bioaccumulation, and toxicity of nicotine. Studies included determination of the octanol-water partition coefficient, conversion to CO2 in soil and activated sludge, and evaluation of the effects on microbiological and algal inhibition as well as plant germination and root elongation. The partitioning of nicotine between octanol and water indicated that nicotine will not bioaccumulate regardless of the pH of the medium. The aqueous and soil-based biodegradation studies indicated that nicotine is readily biodegradable in both types of media. The microbiological inhibition and aquatic and terrestrial toxicity tests indicated that nicotine has low toxicity. The U.S. Environmental Protection Agency Persistence, Bioaccumulation, and Toxicity Profiler model, based on the structure of nicotine and the predictive rates of hydroxyl radical and ozone reactions, estimated an atmospheric half-life of less than 5.0 h. Using this value in the Canadian Environmental Modeling Center level III model, the half-life of nicotine was estimated as 3.0 d in water and 0.5 d in soil. This model also estimated nicotine discharge into the environment; nicotine would be expected to be found predominantly in water (93%), followed by soil (4%), air (3%), and sediment (0.4%). Using the estimated nicotine concentrations in water, soil, and sediment and the proper median effective concentrations derived from the algal growth, biomass inhibition, and buttercrunch lettuce (Lactuca sativa) seed germination and root elongation studies, hazard quotients of between 10(-7) and 10(-8) were calculated, providing further support for the conclusion that the potential for nicotine toxicity to aquatic and terrestrial species in the environment is extremely low.

  5. Environmental fate and effects of nicotine released during cigarette production.

    PubMed

    Seckar, Joel A; Stavanja, Mari S; Harp, Paul R; Yi, Yongsheng; Garner, Charles D; Doi, Jon

    2008-07-01

    A variety of test methods were used to study the gradation, bioaccumulation, and toxicity of nicotine. Studies included determination of the octanol-water partition coefficient, conversion to CO2 in soil and activated sludge, and evaluation of the effects on microbiological and algal inhibition as well as plant germination and root elongation. The partitioning of nicotine between octanol and water indicated that nicotine will not bioaccumulate regardless of the pH of the medium. The aqueous and soil-based biodegradation studies indicated that nicotine is readily biodegradable in both types of media. The microbiological inhibition and aquatic and terrestrial toxicity tests indicated that nicotine has low toxicity. The U.S. Environmental Protection Agency Persistence, Bioaccumulation, and Toxicity Profiler model, based on the structure of nicotine and the predictive rates of hydroxyl radical and ozone reactions, estimated an atmospheric half-life of less than 5.0 h. Using this value in the Canadian Environmental Modeling Center level III model, the half-life of nicotine was estimated as 3.0 d in water and 0.5 d in soil. This model also estimated nicotine discharge into the environment; nicotine would be expected to be found predominantly in water (93%), followed by soil (4%), air (3%), and sediment (0.4%). Using the estimated nicotine concentrations in water, soil, and sediment and the proper median effective concentrations derived from the algal growth, biomass inhibition, and buttercrunch lettuce (Lactuca sativa) seed germination and root elongation studies, hazard quotients of between 10(-7) and 10(-8) were calculated, providing further support for the conclusion that the potential for nicotine toxicity to aquatic and terrestrial species in the environment is extremely low. PMID:18399728

  6. Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in brassica vegetables, and associated potential risk for hypothyroidism.

    PubMed

    Felker, Peter; Bunch, Ronald; Leung, Angela M

    2016-04-01

    Brassica vegetables are common components of the diet and have beneficial as well as potentially adverse health effects. Following enzymatic breakdown, some glucosinolates in brassica vegetables produce sulforaphane, phenethyl, and indolylic isothiocyanates that possess anticarcinogenic activity. In contrast, progoitrin and indolylic glucosinolates degrade to goitrin and thiocyanate, respectively, and may decrease thyroid hormone production. Radioiodine uptake to the thyroid is inhibited by 194 μmol of goitrin, but not by 77 μmol of goitrin. Collards, Brussels sprouts, and some Russian kale (Brassica napus) contain sufficient goitrin to potentially decrease iodine uptake by the thyroid. However, turnip tops, commercial broccoli, broccoli rabe, and kale belonging to Brassica oleracae contain less than 10 μmol of goitrin per 100-g serving and can be considered of minimal risk. Using sulforaphane plasma levels following glucoraphanin ingestion as a surrogate for thiocyanate plasma concentrations after indole glucosinolate ingestion, the maximum thiocyanate contribution from indole glucosinolate degradation is estimated to be 10 μM, which is significantly lower than background plasma thiocyanate concentrations (40-69 μM). Thiocyanate generated from consumption of indole glucosinolate can be assumed to have minimal adverse risks for thyroid health.

  7. Products of DNA, protein and lipid oxidative damage in relation to vitamin C plasma concentration.

    PubMed

    Krajcovicová-Kudlácková, M; Dusinská, M; Valachovicová, M; Blazícek, P; Pauková, V

    2006-01-01

    Oxidative stress plays an important role in the pathogenesis of numerous chronic age-related free radical-induced diseases. Improved antioxidant status minimizes oxidative damage to DNA, proteins, lipids and other biomolecules. Diet-derived antioxidants such as vitamin C, vitamin E, carotenoids and related plant pigments are important in antioxidative defense and maintaining health. The results of long-term epidemiological and clinical studies suggest that protective vitamin C plasma concentration for minimum risk of free radical disease is higher than 50 micromol/l. Products of oxidative damage to DNA (DNA strand breaks with oxidized purines and pyrimidines), proteins (carbonyls) and lipids (conjugated dienes of fatty acids, malondialdehyde) were estimated in a group of apparently healthy adult non-smoking population in dependence on different vitamin C plasma concentrations. Under conditions of protective plasma vitamin C concentrations (>50 micromol/l) significantly lower values of DNA, protein and lipid oxidative damage were found in comparison with the vitamin C-deficient group (<50 micromol/l). The inhibitory effect of higher fruit and vegetable consumption (leading to higher vitamin C intake and higher vitamin C plasma concentrations) on oxidation of DNA, proteins and lipids is also expressed by an inverse significant correlation between plasma vitamin C and products of oxidative damage. The results suggest an important role of higher and frequent consumption of protective food (fruit, vegetables, vegetable oils, nuts, seeds and cereal grains) in prevention of free radical disease.

  8. Plasma gonadotrophins, prolactin and corticosterone concentrations in male mice exposed to high altitude.

    PubMed

    Rattner, B A; Macmillan, B T; Michael, S D; Altland, P D

    1980-11-01

    Groups of sexually-naive male NFR/N mice were maintained at sea level or exposed to simulated altitudes of 18 000 ft (5486 m) or 22 000 ft (6705 m) for 1, 3, 7, 14 or 28 days. Plasma LH concentrations were slightly but not significantly depressed after 1 day of hypoxia. Plasma FSH values were reduced (P < 0.05) after 1, 7, 14 and 28 days of exposure to 22 000 ft when compared to the values in the other groups. Prolactin concentrations fluctuated considerably, but were not uniformly affected by high altitude exposure. Exposure to 18 000 ft resulted in an elevation of plasma corticosterone concentration (P < 0.05) for 3 days, which was followed by a decline to control group values, whereas at 22 000 ft corticosterone levels remained elevated. These findings indicate that plasma LH values are transiently reduced during the initial 24 h of exposure to high altitude and that plasma FSH concentrations are depressed in a sustained manner during severe hypoxia.

  9. Forced swimming and imipramine modify plasma and brain amino acid concentrations in mice.

    PubMed

    Murakami, Tatsuro; Yamane, Haruka; Tomonaga, Shozo; Furuse, Mitsuhiro

    2009-01-01

    The relationships between monoamine metabolism and forced swimming or antidepressants have been well studied, however information is lacking regarding amino acid metabolism under these conditions. Therefore, the aim of the present study was to investigate the effects of forced swimming and imipramine on amino acid concentrations in plasma, the cerebral cortex and the hypothalamus in mice. Forced swimming caused cerebral cortex concentrations of L-glutamine, L-alanine, and taurine to be increased, while imipramine treatment caused decreased concentrations of L-glutamate, L-alanine, L-tyrosine, L-methionine, and L-ornithine. In the hypothalamus, forced swimming decreased the concentration of L-serine while imipramine treatment caused increased concentration of beta-alanine. Forced swimming caused increased plasma concentration of taurine, while concentrations of L-serine, L-asparagine, L-glutamine and beta-alanine were decreased. Imipramine treatment caused increased plasma concentration of all amino acid, except for L-aspartate and taurine. In conclusion, forced swimming and imipramine treatment modify central and peripheral amino acid metabolism. These results may aid in the identification of amino acids that have antidepressant-like effects, or may help to refine the dosages of antidepressant drugs. PMID:19010319

  10. Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine.

    PubMed

    Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer; Stadler, Ashley; Levin, Edward D; Seidler, Frederic J

    2015-09-01

    Tobacco smoke contains thousands of compounds in addition to nicotine, a known neuroteratogen. We evaluated the developmental neurotoxicity of tobacco smoke extract (TSE) administered to pregnant rats starting preconception and continued through the second postnatal week. We simulated nicotine concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers, and compared TSE with an equivalent dose of nicotine alone, and to a 10-fold higher nicotine dose. We conducted longitudinal evaluations in multiple brain regions, starting in adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although both nicotine doses produced presynaptic cholinergic deficits, these were partially compensated by hyperinnervation and receptor upregulation, effects that were absent with TSE. TSE also produced deficits in serotonin receptors in females that were not seen with nicotine. Regression analysis showed a profound sex difference in the degree to which nicotine could account for overall TSE effects: whereas the 2 nicotine doses accounted for 36%-46% of TSE effects in males, it accounted for only 7%-13% in females. Our results show that the adverse effects of TSE on neurodevelopment exceed those that can be attributed to just the nicotine present in the mixture, and further, that the sensitivity extends down to levels commensurate with second-hand smoke exposure. Because nicotine itself evoked deficits at low exposures, "harm reduction" nicotine products do not eliminate the potential for neurodevelopmental damage.

  11. Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine.

    PubMed

    Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer; Stadler, Ashley; Levin, Edward D; Seidler, Frederic J

    2015-09-01

    Tobacco smoke contains thousands of compounds in addition to nicotine, a known neuroteratogen. We evaluated the developmental neurotoxicity of tobacco smoke extract (TSE) administered to pregnant rats starting preconception and continued through the second postnatal week. We simulated nicotine concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers, and compared TSE with an equivalent dose of nicotine alone, and to a 10-fold higher nicotine dose. We conducted longitudinal evaluations in multiple brain regions, starting in adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although both nicotine doses produced presynaptic cholinergic deficits, these were partially compensated by hyperinnervation and receptor upregulation, effects that were absent with TSE. TSE also produced deficits in serotonin receptors in females that were not seen with nicotine. Regression analysis showed a profound sex difference in the degree to which nicotine could account for overall TSE effects: whereas the 2 nicotine doses accounted for 36%-46% of TSE effects in males, it accounted for only 7%-13% in females. Our results show that the adverse effects of TSE on neurodevelopment exceed those that can be attributed to just the nicotine present in the mixture, and further, that the sensitivity extends down to levels commensurate with second-hand smoke exposure. Because nicotine itself evoked deficits at low exposures, "harm reduction" nicotine products do not eliminate the potential for neurodevelopmental damage. PMID:26085346

  12. Plasma concentrations of cortisol in cows with hypocalcaemia in relation to their responses to treatment with calcium.

    PubMed

    Waage, S; Sjaastad, O V; Blom, A K

    1984-03-01

    The mean plasma concentration of cortisol at the time of the first treatment for hypocalcaemia at calving was significantly higher in 17 cows which did not recover, than in 53 cows which recovered. Healthy periparturient cows had significantly lower cortisol levels than cows with hypocalcaemia. There was a negative correlation between plasma cortisol and plasma calcium at the time of the first treatment. After adjustment for differences in plasma calcium there was no significant difference between cortisol concentrations in healthy cows and paretic cows which recovered. Plasma cortisol was positively correlated with both packed cell volume (PCV) and serum creatine kinase (CK). At first treatment cows which did not recover had higher levels of PCV and serum CK than cows which recovered, and the difference between the mean plasma cortisol concentrations of these two groups was related to differences in plasma calcium, PCV and serum CK. Plasma cortisol concentrations remained high in cases of protracted paresis.

  13. Steady-state plasma concentration of donepezil enantiomers and its stereoselective metabolism and transport in vitro.

    PubMed

    Lili, Wan; Cheng, Guo; Zhiyong, Zhou; Qi, Yu; Yan, Li; Dan, Li; Xueli, Zheng; Yuan, Zhong

    2013-09-01

    The aim of the present study was to elucidate the differences in the plasma concentration of two enantiomers of donepezil in Chinese patients with Alzheimer's disease (AD) and investigate in vitro stereoselective metabolism and transport. Donepezil enantiomers were separated and determined by LC-MS/MS using D5-donepezil as an internal standard on a Sepax Chiralomix SB-5 column. In vitro stereoselective metabolism and transport of donepezil were investigated in human liver microsomes and MDCKII-MDR1 cell monolayer. Pre-dose (Css-min) plasma concentrations were determined in 52 patients. The mean plasma level of (R)-donepezil was 14.94 ng/ml and that of (S)-donepezil was 23.37 ng/ml. One patient's plasma concentration of (R)-donepezil was higher than (S)-donepezil and the ratio is 1.51. The mean plasma levels of (S)-donepezil were found to be higher than those of (R)-donepezil in 51 patients and the ratio of plasma (R)- to (S)-donepezil varies from 0.34 to 0.85. In the in vitro microsomal system, (R)-donepezil degraded faster than (S)-donepezil. V(max) of (R)-donepezil was significantly higher than (S)-donepezil. The P-gp inhibition experiment shown that the P(app) of the two enantiomers was higher than 200 and the efflux ratios were 1.11 and 0.99. The results of the P-gp inhibition identification experiment showed IC50 values of 35.5 and 20.4 μM, respectively, for the two enantiomers. The results indicate that donepezil exhibits stereoselective hepatic metabolism that may explain the differences in the steady-state plasma concentrations observed. Neither (R)- nor (S)-donepezil was a P-gp substance and the two enantiomers are highly permeable through the blood-brain barrier.

  14. Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran.

    PubMed

    Stangier, Joachim; Feuring, Martin

    2012-03-01

    The objective of the present study was to assess the suitability of an accurate, sensitive, standardized, chronometric blood coagulation test to determine the anticoagulation activity of dabigatran and to quantify concentrations of dabigatran in plasma. Dabigatran was spiked at increasing concentrations in pooled citrated normal human plasma to measure diluted thrombin time with the HEMOCLOT THROMBIN INHIBITOR assay. Calibration curve linearity, inter-assay and intra-assay precision, and assay accuracy were investigated. Dabigatran stability in plasma and the feasibility of lyophilized dabigatran standards for assay calibration were assessed. Data are presented as back-calculated plasma concentrations of dabigatran using regression analysis. Dabigatran's calibration curve for thrombin clotting time was linear over the concentration range 0-4000  nmol/l (0-1886  ng/ml). The R was 0.99. Total assay imprecision for dabigatran was 4.7-12.0% coefficient of variation, with 1.2-3.1% for intra-run imprecision, 4.0-10.0% for inter-run precision and 0.3-8.3% for between-day imprecision. Assay accuracy was determined at three dabigatran concentrations; deviation from sample target concentrations ranged from -20.7% (100  nmol/l; 47.15  ng/ml) to 5.6% (1500  nmol/l; 707.3  ng/ml). Assay robustness was determined by analysing identical dabigatran samples in two independent laboratories. The mean bias of dabigatran coagulation times between laboratories was 6.6%. The HEMOCLOT Thrombin Inhibitors assay is suitable for determining the anticoagulant activity and calculating plasma concentrations of dabigatran using simple and widely available chronometric coagulation devices. The use of this rapid, established, standardized and calibrated assay should provide accurate and consistent results when assessing the anticoagulant activity of dabigatran. PMID:22227958

  15. Relationship between plasma resistin concentrations, inflammatory chemokines, and components of the metabolic syndrome in adults.

    PubMed

    Aquilante, Christina L; Kosmiski, Lisa A; Knutsen, Shannon D; Zineh, Issam

    2008-04-01

    Recent data suggest that resistin, an adipocyte-derived cytokine, has a putative role in inflammatory processes and metabolic derangements. In vitro data suggest that resistin stimulates the production of inflammatory chemokines, yet the relationship in vivo is largely unknown. The purpose of this study was to determine if a relationship exists between plasma resistin concentrations, plasma inflammatory chemokine aged concentrations (ie, monocyte chemoattractant protein 1 [MCP-1] and epithelial neutrophil activator 78 [ENA-78]), and components of the metabolic syndrome in nondiabetic subjects without known cardiovascular disease (CVD). Plasma samples were obtained from nondiabetic subjects (N = 123) aged 18 to 55 years without known CVD or CVD risk equivalents. The presence of the metabolic syndrome was assessed using consensus guidelines. Fasting plasma resistin, MCP-1, ENA-78, and high-sensitivity C-reactive protein (hs-CRP) concentrations were analyzed. The study population consisted of 67.5% women and 68.3% Caucasians (mean age = 44 +/- 7 years and mean body mass index = 33.3 +/- 6 kg/m(2)). The metabolic syndrome was present in 46.3% of study participants. Resistin concentrations were significantly correlated with white blood cell count (r = 0.326, P < .001), hs-CRP concentrations (r = 0.293, P = .005), MCP-1 concentrations (r = 0.251, P = .005), body mass index (r = 0.193, P = .033), and high-density lipoprotein cholesterol (r = -0.182, P = .044). Resistin concentrations were 1.21 times higher in subjects with the metabolic syndrome compared with those without the metabolic syndrome (P = .003). In stepwise regression analysis, white blood cell count (P < .001) and MCP-1 concentrations (P = .002) were significantly associated with resistin concentrations, independent of hs-CRP, sex, body mass index, presence of the metabolic syndrome, and high-density lipoprotein cholesterol. Data from our cross-sectional study demonstrate that plasma resistin concentrations

  16. Plasma adiponectin concentrations are associated with dietary glycemic index in Malaysian patients with type 2 diabetes.

    PubMed

    Loh, Beng-In; Sathyasuryan, Daniel Robert; Mohamed, Hamid Jan Jan

    2013-01-01

    Adiponectin, an adipocyte-derived hormone has been implicated in the control of blood glucose and chronic inflammation in type 2 diabetes. However, limited studies have evaluated dietary factors on plasma adiponectin levels, especially among type 2 diabetic patients in Malaysia. The aim of this study was to investigate the influence of dietary glycemic index on plasma adiponectin concentrations in patients with type 2 diabetes. A cross-sectional study was conducted in 305 type 2 diabetic patients aged 19-75 years from the Penang General Hospital, Malaysia. Socio-demographic information was collected using a standard questionnaire while dietary details were determined by using a pre-validated semi-quantitative food frequency questionnaire. Anthropometry measurement included weight, height, BMI and waist circumference. Plasma adiponectin concentrations were measured using a commercial ELISA kit. Data were analyzed using multiple linear regression. After multivariate adjustment, dietary glycemic index was inversely associated with plasma adiponectin concentrations (β =-0.272, 95% CI -0.262, - 0.094; p<0.001). It was found that in individuals who consumed 1 unit of foods containing high dietary glycemic index that plasma adiponectin level reduced by 0.3 μg/mL. Thirty two percent (31.9%) of the variation in adiponectin concentrations was explained by age, sex, race, smoking status, BMI, waist circumference, HDL-C, triglycerides, magnesium, fiber and dietary glycemic index according to the multiple linear regression model (R2=0.319). These results support the hypothesis that dietary glycemic index influences plasma adiponectin concentrations in patients with type 2 diabetes. Controlled clinical trials are required to confirm our findings and to elucidate the underlying mechanism.

  17. Plasma ghrelin concentrations change with physiological state in a sciurid hibernator (Spermophilus lateralis).

    PubMed

    Healy, Jessica E; Ostrom, Cara E; Wilkerson, Gregory K; Florant, Gregory L

    2010-04-01

    Ghrelin is a recently discovered hormone which has profound effects on food intake and lipogenesis in mammals. In all mammals studied thus far, plasma ghrelin concentrations are increased before a meal and decrease immediately following a meal; ghrelin levels increase with fasting. The golden-mantled ground squirrel Spermophilus lateralis (also known as Callospermophilus lateralis (see Helgen et al., 2009) is a diurnal hibernator which has a robust annual cycle of body mass gain and loss that is primarily controlled by food intake. We hypothesized that in spring, summer, and autumn, the endogenous ghrelin concentrations of hibernators would be similar to those of non-hibernators, but that during the winter hibernation season, plasma ghrelin concentrations would be low or undetectable. We found that peripherally injected ghrelin significantly increased food intake in June. Plasma ghrelin concentrations were significantly increased through 5 days of fasting during a short-term fast in summer. Over a 24h period, ghrelin concentrations increased at night and decreased during the day with drops corresponding to times when squirrels were eating. In January, ghrelin concentrations are low but measurable even while animals are at low body temperature (Tb). This is the first report of ghrelin concentrations in a non-photoperiodic hibernator. We suggest that ghrelin may be important for the regulation of food intake and the body mass cycle in mammals that hibernate.

  18. Plasma ghrelin concentrations change with physiological state in a sciurid hibernator (Spermophilus lateralis).

    PubMed

    Healy, Jessica E; Ostrom, Cara E; Wilkerson, Gregory K; Florant, Gregory L

    2010-04-01

    Ghrelin is a recently discovered hormone which has profound effects on food intake and lipogenesis in mammals. In all mammals studied thus far, plasma ghrelin concentrations are increased before a meal and decrease immediately following a meal; ghrelin levels increase with fasting. The golden-mantled ground squirrel Spermophilus lateralis (also known as Callospermophilus lateralis (see Helgen et al., 2009) is a diurnal hibernator which has a robust annual cycle of body mass gain and loss that is primarily controlled by food intake. We hypothesized that in spring, summer, and autumn, the endogenous ghrelin concentrations of hibernators would be similar to those of non-hibernators, but that during the winter hibernation season, plasma ghrelin concentrations would be low or undetectable. We found that peripherally injected ghrelin significantly increased food intake in June. Plasma ghrelin concentrations were significantly increased through 5 days of fasting during a short-term fast in summer. Over a 24h period, ghrelin concentrations increased at night and decreased during the day with drops corresponding to times when squirrels were eating. In January, ghrelin concentrations are low but measurable even while animals are at low body temperature (Tb). This is the first report of ghrelin concentrations in a non-photoperiodic hibernator. We suggest that ghrelin may be important for the regulation of food intake and the body mass cycle in mammals that hibernate. PMID:20005230

  19. Honeybees and nectar nicotine: deterrence and reduced survival versus potential health benefits.

    PubMed

    Köhler, Angela; Pirk, Christian W W; Nicolson, Susan W

    2012-02-01

    Secondary metabolites produced by plants for herbivore defence are often found in floral nectar, but their effect on the foraging behaviour and physiological performance of pollinators is largely unknown. Nicotine is highly toxic to most herbivores, and nicotine-based insecticides may contribute to current pollinator declines. We examined the effects of nectar nicotine on honeybee foraging choices and worker longevity. Free-flying honeybee (Apis mellifera scutellata) workers from six colonies were given a choice between multiple nicotine concentrations (0-1000 μM) in artificial nectar (0.15-0.63 M sucrose). The dose-dependent deterrent effect of nicotine was stronger in lower sugar concentrations, but even the highest nicotine concentrations did not completely repel honeybees, i.e., bees did not stop feeding on these diets. Nicotine in nectar acts as a partial repellent, which may keep pollinators moving between plants and enhance cross-pollination. In the second part of the study, newly emerged workers from 12 colonies were caged and fed one of four nicotine concentrations (0-300 μM) in 0.63 M sucrose for 21 days. Moderate (≤30 μM) nicotine concentrations had no significant detrimental effect, but high nicotine concentrations reduced the survival of caged workers and their nectar storage in the honey comb. In contrast, worker groups that survived poorly on sugar-only diets demonstrated increased survival on all nicotine diets. In the absence of alternative nectar sources, honeybees tolerate naturally occurring nectar nicotine concentrations; and low concentrations can even be beneficial to honeybees. However, high nicotine concentrations may have a detrimental effect on colony fitness.

  20. Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in normal adults.

    PubMed

    Stegink, L D; Filer, L J; Baker, G L

    1988-03-01

    Aspartame (APM) is a dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester). It has been suggested that excessive use of the product might elevate plasma aspartate and phenylalanine concentrations. Eight normal adults (four male, four female) ingested three successive 12-oz servings of APM-sweetened beverage at two-hour intervals. The study was carried out in two parts in a randomized cross-over design. In one study the beverage was not sweetened. In the other, the beverage provided 10 mg APM/kg body weight per serving. Plasma amino acid concentrations were measured throughout the six-hour study period. The addition of APM to the beverage had no significant effect on plasma aspartate concentration. APM addition did increase plasma phenylalanine levels 1.64 to 2.05 mumol/dL above baseline values (5.09 +/- 0.82 mumol/dL) 30 to 45 minutes after each dose. However, plasma phenylalanine levels did not exceed normal postprandial values at any time. The data indicate ready metabolism of APM's amino acid content when administered at levels likely to be ingested by individuals who are heavy users of such beverages.

  1. Prenatal nicotine changes the response to postnatal chlorpyrifos: Interactions targeting serotonergic synaptic function and cognition.

    PubMed

    Slotkin, Theodore A; Skavicus, Samantha; Levin, Edward D; Seidler, Frederic J

    2015-02-01

    Nicotine and chlorpyrifos are developmental neurotoxicants that target serotonin systems. We examined whether prenatal nicotine exposure alters the subsequent response to chlorpyrifos given postnatally. Pregnant rats received nicotine throughout gestation at 3mg/kg/day, a regimen designed to achieve plasma levels seen in smokers; chlorpyrifos was given to pups on postnatal days (PN) 1-4 at 1mg/kg, just above the detection threshold for brain cholinesterase inhibition. We assessed long-term effects from adolescence (PN30) through full adulthood (PN150), measuring the expression of serotonin receptors and serotonin turnover (index of presynaptic impulse activity) in cerebrocortical brain regions encompassing the projections that are known targets for nicotine and chlorpyrifos. Nicotine or chlorpyrifos individually increased the expression of serotonin receptors, with greater effects on males than on females and with distinct temporal and regional patterns indicative of adaptive synaptic changes rather than simply an extension of initial injury. This interpretation was confirmed by our finding an increase in serotonin turnover, connoting presynaptic serotonergic hyperactivity. Animals receiving the combined treatment showed a reduction in these adaptive effects on receptor binding and turnover relative to the individual agents, or even an effect in the opposite direction; further, normal sex differences in serotonin receptor concentrations were dissipated or reversed, an effect that was confirmed by behavioral evaluations in the Novel Objection Recognition Test. In addition to the known liabilities associated with maternal smoking during pregnancy, our results point to additional costs in the form of heightened vulnerability to neurotoxic chemicals encountered later in life. PMID:25592617

  2. Rock climbing: observations on heart rate and plasma catecholamine concentrations and the influence of oxprenolol.

    PubMed Central

    Williams, E. S.; Taggart, P.; Carruthers, M.

    1978-01-01

    Observations are presented on the electrocardiogram and plasma catecholamine concentrations of 11 healthy men monitored during two rock climbing ascents. A placebo was administered prior to the first climb and an oral dose of the beta blocking agent oxprenolol ("Trasicor") prior to the second. Mean heart rates were 166 (+/- 20.4 SD) and 120 (+/- 10.2) respectively. Median plasma adrenaline concentrations were 0.05 microgram/1 and 0.33 microgram/1 before and after the climbs following the placebo. No significant difference was observed in the adrenaline concentrations before and after climbing following oxprenolol, or of noradrenaline concentrations on either occasion. These results are interpreted as suggesting that this popular sport represents more an anxiety-type of psychological stress than a physical stress and as such is likely to increase moral fibre rather than muscle fibre. PMID:719320

  3. Uptake of L-nicotine and of 6-hydroxy-L-nicotine by Arthrobacter nicotinovorans and by Escherichia coli is mediated by facilitated diffusion and not by passive diffusion or active transport.

    PubMed

    Ganas, Petra; Brandsch, Roderich

    2009-06-01

    The mechanism by which l-nicotine is taken up by bacteria that are able to grow on it is unknown. Nicotine degradation by Arthrobacter nicotinovorans, a Gram-positive soil bacterium, is linked to the presence of the catabolic megaplasmid pAO1. l-[(14)C]Nicotine uptake assays with A. nicotinovorans showed transport of nicotine across the cell membrane to be energy-independent and saturable with a K(m) of 6.2+/-0.1 microM and a V(max) of 0.70+/-0.08 micromol min(-1) (mg protein)(-1). This is in accord with a mechanism of facilitated diffusion, driven by the nicotine concentration gradient. Nicotine uptake was coupled to its intracellular degradation, and an A. nicotinovorans strain unable to degrade nicotine (pAO1(-)) showed no nicotine import. However, when the nicotine dehydrogenase genes were expressed in this strain, import of l-[(14)C]nicotine took place. A. nicotinovorans pAO1(-) and Escherichia coli were also unable to import 6-hydroxy-l-nicotine, but expression of the 6-hydroxy-l-nicotine oxidase gene allowed both bacteria to take up this compound. l-Nicotine uptake was inhibited by d-nicotine, 6-hydroxy-l-nicotine and 2-amino-l-nicotine, which may indicate transport of these nicotine derivatives by a common permease. Attempts to correlate nicotine uptake with pAO1 genes possessing similarity to amino acid transporters failed. In contrast to the situation at the blood-brain barrier, nicotine transport across the cell membrane by these bacteria was not by passive diffusion or active transport but by facilitated diffusion.

  4. Plasma concentrations of vitamin E in six species of bustard (Gruiformes: Otididae).

    PubMed

    Anderson, Susan J; Dawodu, Adekunle; Patel, Mahendra; Bailey, Thomas A; Silvanose, Christudas

    2002-04-01

    Vitamin E (measured as alpha-tocopherol) and cholesterol concentrations were determined in plasma samples collected from 86 clinically healthy captive adult bustards of six species and 23 captive juveniles (6-12 mo old) of two of these species. Adult houbara bustards (Chlamydotis undulata macqueenii) had higher plasma alpha-tocopherol concentrations than juveniles (adult: mean +/- SE, 11.07 +/- 0.41 micrograms/ml, n = 32; juvenile: 6.33 +/- 0.48, n = 12) and higher alpha-tocopherol: cholesterol ratios (adult: 6.09 +/- 0.44, n = 12; juvenile: 2.94 +/- 0.22, n = 11). No age difference was evident for kori bustard (Ardeotis kori) plasma alpha-tocopherol concentrations (adult: 4.43 +/- 0.42, n = 21; juvenile: 4.46 +/- 0.26, n = 11) or alpha-tocopherol: cholesterol ratios (adult: 3.67 +/- 0.44, n = 20; juvenile: 3.71 +/- 0.36, n = 11). Adult houbara bustards had significantly higher (P < 0.01) alpha-tocopherol concentrations compared with adult rufous-crested (Eupodotis ruficrista; 6.64 +/- 0.33, n = 19) and white-bellied (Eupodotis senegalensis; 7.75 +/- 0.81, n = 8) bustards, but similar alpha-tocopherol: cholesterol ratios (rufous-crested: 5.56 +/- 0.32, n = 18; white-bellied: 5.83 +/- 0.43, n = 8). Juvenile houbara bustards had higher plasma alpha-tocopherol concentrations than juvenile kori bustards but similar alpha-tocopherol:cholesterol ratios. Adult houbara bustard plasma alpha-tocopherol levels and alpha-tocopherol:cholesterol ratios did not differ significantly between sexes. The vitamin E status of adult bustards appeared to be influenced by environmental conditions that varied due to species-specific husbandry regimens, but no clear relationship was seen with dietary vitamin E levels. Juvenile bustards did not have higher vitamin E levels than adults, despite being maintained on four-fold dietary vitamin E concentrations and in similar environmental conditions. This paper presents the first published data for plasma vitamin E concentrations in bustards. The

  5. Plasma concentrations of vitamin E in six species of bustard (Gruiformes: Otididae).

    PubMed

    Anderson, Susan J; Dawodu, Adekunle; Patel, Mahendra; Bailey, Thomas A; Silvanose, Christudas

    2002-04-01

    Vitamin E (measured as alpha-tocopherol) and cholesterol concentrations were determined in plasma samples collected from 86 clinically healthy captive adult bustards of six species and 23 captive juveniles (6-12 mo old) of two of these species. Adult houbara bustards (Chlamydotis undulata macqueenii) had higher plasma alpha-tocopherol concentrations than juveniles (adult: mean +/- SE, 11.07 +/- 0.41 micrograms/ml, n = 32; juvenile: 6.33 +/- 0.48, n = 12) and higher alpha-tocopherol: cholesterol ratios (adult: 6.09 +/- 0.44, n = 12; juvenile: 2.94 +/- 0.22, n = 11). No age difference was evident for kori bustard (Ardeotis kori) plasma alpha-tocopherol concentrations (adult: 4.43 +/- 0.42, n = 21; juvenile: 4.46 +/- 0.26, n = 11) or alpha-tocopherol: cholesterol ratios (adult: 3.67 +/- 0.44, n = 20; juvenile: 3.71 +/- 0.36, n = 11). Adult houbara bustards had significantly higher (P < 0.01) alpha-tocopherol concentrations compared with adult rufous-crested (Eupodotis ruficrista; 6.64 +/- 0.33, n = 19) and white-bellied (Eupodotis senegalensis; 7.75 +/- 0.81, n = 8) bustards, but similar alpha-tocopherol: cholesterol ratios (rufous-crested: 5.56 +/- 0.32, n = 18; white-bellied: 5.83 +/- 0.43, n = 8). Juvenile houbara bustards had higher plasma alpha-tocopherol concentrations than juvenile kori bustards but similar alpha-tocopherol:cholesterol ratios. Adult houbara bustard plasma alpha-tocopherol levels and alpha-tocopherol:cholesterol ratios did not differ significantly between sexes. The vitamin E status of adult bustards appeared to be influenced by environmental conditions that varied due to species-specific husbandry regimens, but no clear relationship was seen with dietary vitamin E levels. Juvenile bustards did not have higher vitamin E levels than adults, despite being maintained on four-fold dietary vitamin E concentrations and in similar environmental conditions. This paper presents the first published data for plasma vitamin E concentrations in bustards. The

  6. Nicotine Nasal Spray

    MedlinePlus

    ... program, which may include support groups, counseling, or specific behavior change techniques. Nicotine nasal spray is in ... bottles at room temperature and away from excess heat and moisture (not in the bathroom). Discard used ...

  7. Nicotine and tobacco

    MedlinePlus

    ... ease your withdrawal symptoms. Health experts warn that e-cigarettes are not a replacement therapy for cigarette smoking. ... not known exactly how much nicotine is in e-cigarette cartridges, because information on labels is often wrong. ...

  8. Measurement and Comparison of Organic Compound Concentrations in Plasma, Whole Blood, and Dried Blood Spot Samples

    PubMed Central

    Batterman, Stuart A.; Chernyak, Sergey; Su, Feng-Chiao

    2016-01-01

    The preferred sampling medium for measuring human exposures of persistent organic compounds (POPs) is blood, and relevant sample types include whole blood, plasma, and dried blood spots (DBS). Because information regarding the performance and comparability of measurements across these sample types is limited, it is difficult to compare across studies. This study evaluates the performance of POP measurements in plasma, whole blood and DBS, and presents the distribution coefficients needed to convert concentrations among the three sample types. Blood samples were collected from adult volunteers, along with demographic and smoking information, and analyzed by GC/MS for organochlorine pesticides (OCPs), chlorinated hydrocarbons (CHCs), polychlorinated biphenyls (PCBs), and brominated diphenyl ethers (PBDEs). Regression models were used to evaluate the relationships between the sample types and possible effects of personal covariates. Distribution coefficients also were calculated using physically-based models. Across all compounds, concentrations in plasma were consistently the highest; concentrations in whole blood and DBS samples were comparable. Distribution coefficients for plasma to whole blood concentrations ranged from 1.74 to 2.26 for pesticides/CHCs, averaged 1.69 ± 0.06 for the PCBs, and averaged 1.65 ± 0.03 for the PBDEs. Regression models closely fit most chemicals (R2 > 0.80), and whole blood and DBS samples generally showed very good agreement. Distribution coefficients estimated using biologically-based models were near one and did not explain the observed distribution. Among the study population, median concentrations of several pesticides/CHCs and PBDEs exceeded levels reported in the 2007–2008 National Health and Nutrition Examination Survey, while levels of other OCPs and PBDEs were comparable or lower. Race and smoking status appeared to slightly affect plasma/blood concentration ratios for several POPs. The experimentally

  9. Species-dependent effective concentration of DTPA in plasma for chelation of 241Am

    PubMed Central

    Sueda, Katsuhiko; Sadgrove, Matthew P.; Jay, Michael; Di Pasqua, Anthony J.

    2013-01-01

    Diethylenetriaminepentaacetic acid (DTPA) is a chelating agent that is used to facilitate the elimination of radionuclides, such as americium, from contaminated individuals. Its primary site of action is in the blood, where it competes with various biological ligands, including transferrin and albumin, for the binding of radioactive metals. To evaluate the chelation potential of DTPA under these conditions, the competitive binding of 241Am between DTPA and plasma proteins was studied in rat, beagle and human plasma in vitro. Following incubation of DTPA and 241Am in plasma, the 241Am-bound ligands were fractionated by ultrafiltration and ion-exchange chromatography, and each fraction was assayed for 241Am content by gamma scintillation counting. Dose-response curves of DTPA for 241Am binding were established, and these models were used to calculate the 90% maximal effective concentration, or EC90, of DTPA in each plasma system. The EC90 were determined to be 31.4, 15.9 and 10.0 μM in rat, beagle and human plasma, respectively. These values correspond to plasma concentrations of DTPA that maximize 241Am chelation while minimizing excess DTPA. Based on the pharmacokinetic profile of DTPA in humans, after a standard 30 μmol kg−1 intravenous bolus injection, the plasma concentration of DTPA remains above EC90 for approximately 5.6 h. Likewise, the effective duration of DTPA in rat and beagle were determined to be 0.67 and 1.7 h, respectively. These results suggest that species differences must be considered when translating DTPA efficacy data from animals to humans and offer further insights into improving the current DTPA treatment regimen. PMID:23799506

  10. Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma123

    PubMed Central

    Fischer, Leslie M; da Costa, Kerry Ann; Galanko, Joseph; Sha, Wei; Stephenson, Brigitte; Vick, Julie; Zeisel, Steven H

    2010-01-01

    Background: Choline is essential for infant nutrition, and breast milk is a rich source of this nutrient. Common single nucleotide polymorphisms (SNPs) change dietary requirements for choline intake. Objective: The aim of this study was to determine whether total choline intake and/or SNPs influence concentrations of choline and its metabolites in human breast milk and plasma. Design: We gave a total of 103 pregnant women supplemental choline or a placebo from 18 wk gestation to 45 d postpartum and genotyped the women for 370 common SNPs. At 45 d postpartum, we measured choline metabolite concentrations in breast milk and plasma and assessed the dietary intake of choline by using a 3-d food record. Results: On average, lactating women in our study ate two-thirds of the recommended intake for choline (Adequate Intake = 550 mg choline/d). Dietary choline intake (no supplement) correlated with breast-milk phosphatidylcholine and plasma choline concentrations. A supplement further increased breast-milk choline, betaine, and phosphocholine concentrations and increased plasma choline and betaine concentrations. We identified 5 SNPs in MTHFR that altered the slope of the intake–metabolite concentration relations, and we identified 2 SNPs in PEMT that shifted these curves upward. Individuals who shared sets of common SNPs were outliers in plots of intake–metabolite concentration curves; we suggest that these SNPs should be further investigated to determine how they alter choline metabolism. Conclusion: Total intake of choline and genotype can influence the concentrations of choline and its metabolites in the breast milk and blood of lactating women and thereby affect the amount of choline available to the developing infant. This study was registered at clinicaltrials.gov as NCT00678925. PMID:20534746

  11. Analysis of apolipoprotein A5, C3 and plasma triglyceride concentrations in genetically engineered mice

    SciTech Connect

    Baroukh, Nadine; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Afzal, Veena; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

    2004-03-11

    To address the relationship between the apolipoprotein A5 and C3 genes, we generated independent lines of mice that either over-expressed or completely lacked both genes. We report both lines display normal triglyceride concentrations compared to over-expression or deletion of either gene alone. Together, these data support that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.

  12. Indicators of oxidative stress in weanling and pubertal rats following exposure to nicotine via milk.

    PubMed

    Halima, Ben Ahmed; Sarra, Khlifi; Kais, Rtibi; Salwa, Elfazaa; Najoua, Gharbi

    2010-06-01

    Nicotine, a major toxic component of tobacco, has been identified as an important risk factor for infant and children diseases. It is concentrated in breast milk and is absorbed by the infant. The purpose of the present study was to investigate the effects of maternal nicotine exposure during lactation on breast-fed rats and at the pubertal age by measuring biomarkers of oxidative stress. Particularly, a new parameter, the thiol concentration was evaluated. Two groups of lactating Wistar rats were used. For the first group, female rats were given an intraperitoenal injection of nicotine or saline (2 mg/kg per day) during lactation. For the second group, we reproduced the same process described above and then the female and male pups were separately kept after weaning without any treatment until the puberty (at 45 days of age). In the liver and lung of the offspring, we examined the malondialdehyde (MDA) level, the thiol concentration, and the activities of two antioxidant enzymes: superoxyde dismutase (SOD) and catalase (CAT). In the plasma, alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were measured. For rats aged 21 days, the treatment significantly reduced the thiol concentration, SOD, and CAT activities but increased MDA level, AST, and ALT activities. For rats aged 45 days, the males and females did not react the same way. In fact, the males were more affected. These results indicate that maternal nicotine exposure during the lactation period induces oxidative stress in the liver and lung of lactating offspring, which is maintained until the puberty, especially for the male rats. PMID:19900975

  13. Elevated plasma bile acid concentrations in two sisters with tyrosinaemia type I.

    PubMed

    Sass, J O; Skladal, D

    2000-02-01

    A 21-month-old girl suffering from tyrosinaemia type I and undergoing treatment with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione (NTBC) presented with pruritus which rapidly ceased with administration of high doses of ursodeoxycholic acid. Determination of plasma bile acids revealed clearly elevated levels both in samples taken before and after the onset of NTBC therapy, thus indicating, that the increase was not related to the administration of this drug. This result is corroborated by data from the first patient's newborn sister, diagnosed with the same disease, who showed elevated plasma bile acid concentrations in all samples examined, except for the cord plasma. This is the first report on altered bile acid concentrations in tyrosinaemia type I, and underlines the need for thorough investigation of bile acid metabolism in this disease.

  14. Blood pressure, plasma renin activity and aldosterone concentrations in vegans and omnivore controls.

    PubMed

    Sanders, T A; Key, T J

    1987-06-01

    Blood pressure, plasma renin activity and the concentrations of aldosterone and cholesterol in plasma and sodium and potassium in urine (48-h collections) and nutrient intakes were determined in 22 vegans (11 male and 11 female) and omnivore controls matched for age, sex and body build. The vegan diets contained less protein, sodium, calcium and sulphur but more carbohydrate, potassium and fibre than the diets of their controls. The mean urinary potassium sodium ratio was 1.13 in the vegans compared with 0.64 in the omnivores. Plasma renin and cholesterol concentrations were lower in the male but not female vegans compared with their respective controls. Blood pressures of the vegan subjects were inside the normal range but they tended to have higher mean diastolic blood pressures than their controls.

  15. Nutritional status influences plasma fibrinogen concentration: evidence from the THUSA survey.

    PubMed

    James, S; Vorster, H H; Venter, C S; Kruger, H S; Nell, T A; Veldman, F J; Ubbink, J B

    2000-06-01

    Nutritional status and risk factors for chronic diseases, including plasma fibrinogen and its determinants, of Africans in the Northwest Province of South Africa, have been studied in a cross-sectional survey. A representative sample of 1854 "apparently healthy" African men and women volunteers aged 15 years and older was recruited from 37 randomly selected sites throughout the Province and stratified for level of urbanisation. Information was collected using validated and culture-sensitive questionnaires. Fasting blood samples were drawn, and all measurements were done with standardised methodology using appropriate equipment, procedures, and controls. Fibrinogen concentration was measured in citrated plasma with the method of Clauss, using the ACL200 automated system and the international fibrinogen standard. The results revealed a population with a high mean plasma fibrinogen (3.17+/-1.10 g/L for HIV-negative men and 3. 64+/-1.12 g/L for HIV-negative women). Factors known to influence plasma fibrinogen, such as age, gender, smoking habit, and physical activity, were also observed in this population. Young rural men and women had the lowest fibrinogen level. Nasal snuff taking and HIV infection did not influence fibrinogen concentration. Multivariate analyses revealed that lower plasma fibrinogen was associated with low to normal body mass index in women, and with dietary intakes compatible with prudent dietary guidelines in men and women (low intakes of animal protein; trans fatty acids and higher intakes of plant protein; dietary fibre, vitamin E, and iron, and a high dietary P/S ratio). Subjects in the higher quartiles of plasma fibrinogen had significantly lower iron, vitamin E, and vitamin B6 (women) status. Increases in fibrinogen were associated with significant increases in serum lipids. Both under- and overnutrition seem to be associated with high plasma fibrinogen. It is concluded that overall nutritional status, possibly in addition to specific

  16. Unpredictability of nectar nicotine promotes outcrossing by hummingbirds in Nicotiana attenuata.

    PubMed

    Kessler, Danny; Bhattacharya, Samik; Diezel, Celia; Rothe, Eva; Gase, Klaus; Schöttner, Matthias; Baldwin, Ian T

    2012-08-01

    Many plants use sophisticated strategies to maximize their reproductive success via outcrossing. Nicotiana attenuata flowers produce nectar with nicotine at concentrations that are repellent to hummingbirds, increasing the number of flowers visited per plant. In choice tests using native hummingbirds, we show that these important pollinators learn to tolerate high-nicotine nectar but prefer low-nicotine nectar, and show no signs of nicotine addiction. Nectar nicotine concentrations, unlike those of other vegetative tissues, are unpredictably variable among flowers, not only among populations, but also within populations, and even among flowers within an inflorescence. To evaluate whether variations in nectar nicotine concentrations increase outcrossing, polymorphic microsatellite markers, optimized to evaluate paternity in native N. attenuata populations, were used to compare outcrossing in plants silenced for expression of a biosynthetic gene for nicotine production (Napmt1/2) and in control empty vector plants, which were antherectomized and transplanted into native populations. When only exposed to hummingbird pollinators, seeds produced by flowers with nicotine in their nectar had a greater number of genetically different sires, compared to seeds from nicotine-free flowers. As the variation in nectar nicotine levels among flowers in an inflorescence decreased in N. attenuata plants silenced in various combinations of three Dicer-like (DCL) proteins, small RNAs are probably involved in the unpredictable variation in nectar nicotine levels within a plant.

  17. Safflower oil consumption does not increase plasma conjugated linoleic acid concentrations in humans.

    PubMed

    Herbel, B K; McGuire, M K; McGuire, M A; Shultz, T D

    1998-02-01

    Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid (LA) with conjugated double bonds. CLA has anticarcinogenic properties and has been identified in human tissues, dairy products, meats, and certain vegetable oils. A variety of animal products are good sources of CLA, but plant oils contain much less. However, plant oils are a rich source of LA, which may be isomerized to CLA by intestinal microorganisms in humans. To investigate the effect of triacylglycerol-esterified LA consumption on plasma concentrations of esterified CLA in total lipids, a dietary intervention (6 wk) was conducted with six men and six women. During the intervention period a salad dressing containing 21 g safflower oil providing 16 g LA/d was added to the subjects' daily diets. Three-day diet records and fasting blood were obtained initially and during dietary and postdietary intervention periods. Although LA intake increased significantly during the dietary intervention, plasma CLA concentrations were not affected. Plasma total cholesterol and LDL-cholesterol concentrations were significantly lower after addition of safflower oil to the diet. In summary, consumption of triacylglycerol-esterified LA in safflower oil did not increase plasma concentrations of esterified CLA in total lipids.

  18. Plasma oxytocin concentrations during late pregnancy and parturition in the dog.

    PubMed

    Klarenbeek, M; Okkens, A C; Kooistra, H S; Mol, J A; M M Bevers; Taverne, M A M

    2007-11-01

    While oxytocin is widely used in the treatment of dystocia in dogs, there is little information about its secretion before and during normal unassisted whelping. We therefore measured plasma oxytocin concentrations during late pregnancy and the expulsive stage of parturition. Blood samples were collected from eight dogs at 3-min intervals during a 42-min period between the 2nd and 14th day before whelping and during parturition after the birth of 1-3 pups. The litters consisted of 5-15 pups and the progression of the expulsive stage was linear and nearly parallel in the eight bitches. The overall mean (+/-S.D.) plasma oxytocin concentration during late pregnancy was 3.6+/-2.1pg/ml. Mean values in individual dogs ranged from 1.2 to 7.4 pg/ml, but the intra-animal variation was rather small. During the expulsive stage the overall mean (+/-S.D.) plasma oxytocin concentration was 12.9+/-13.9 pg/ml, with mean values in individual dogs ranging from 3.5 to 46 pg/ml. The mean area under the oxytocin curve for parturient dogs was significantly higher (P<0.05) than for pregnant dogs. During the expulsive stage, the peak plasma oxytocin level in individual dogs ranged between 10 and 117 pg/ml. In six of the eight dogs a pup was born during blood collection and in five of these animals the plasma oxytocin concentration increased temporarily during periods of abdominal straining and expulsion. However, straining efforts and expulsion were not consistently associated with a rise in the circulating oxytocin level. It is concluded that in the dog plasma oxytocin levels are higher and more variable during the expulsive stage of parturition than during late pregnancy. Interrelationships between the secretion pattern of oxytocin, the level of uterine contractility, and the progress of fetal expulsion in dogs need further exploration.

  19. Overestimation of canine albumin concentration with the bromcresol green method in heparinized plasma samples.

    PubMed

    Stokol, Tracy; Tarrant, Jacqueline M.; Scarlett, Janet M.

    2001-01-01

    Albumin concentrations are routinely measured in dogs with bromcresol green (BCG)-binding assays on automated chemistry analyzers. Several variables affect this assay, including the length of reaction time, sample type, and lack of specificity of BCG for albumin. We observed that albumin concentrations measured with BCG appeared higher in heparinized plasma samples in sick dogs. The objective of this study was to determine the effect of anticoagulant and assay procedure on BCG albumin concentrations in clinically ill dogs. We hypothesized that albumin concentrations would be overestimated in heparinized plasma compared with serum because of the combination of heparin and fibrinogen. Furthermore, we hypothesized that the overestimation would be influenced by assay parameters. Blood was collected from 32 clinically ill dogs into tubes containing heparin, citrate, or no anticoagulant. Citrate was chosen to assess the effect of fibrinogen in the absence of heparin. Albumin concentration was measured in all 3 sample types from each dog using 2 different BCG procedures on an automated chemistry analyzer. The BCG procedures (standard and modified) differed in the wavelengths used for absorbance readings (standard, 600/700; modified, 570/505) and the time point at which absorbance was measured (standard, 100 seconds; modified, 40 seconds). In addition, the modified method incorporated a sample blank. Globulin fractions, fibrinogen concentration, and indices of lipemia, hemolysis, and icterus were evaluated for their contribution to the overestimation of albumin concentration in heparinized plasma compared with serum samples. Albumin concentrations were significantly higher (P plasma (mean +/- SE, 3.8 +/- 0.1 g/dL) than in serum (3.6 +/- 0.2 g/dL) or citrated plasma (3.2 +/- 0.1 g/dL). Overestimation was evident only with the standard BCG procedure. Multiple linear regression analysis indicated that fibrinogen was largely responsible for the higher

  20. Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians.

    PubMed

    Pagán, Oné R; Montgomery, Erica; Deats, Sean; Bach, Daniel; Baker, Debra

    2015-10-01

    Planarians are rapidly developing into very useful research subjects in pharmacology and neuroscience research. Here we report that curare, a cholinergic nicotinic receptor antagonist, alleviates the nicotine-induced planarian seizure-like movements (pSLM) by up to 50 % at equimolar concentrations of nicotine and curare (1 mM), while curare alone does not induce significant pSLMs. The simplest interpretation of our data is that there are nicotine induced behaviors insensitive to curare in our experimental organism. To the best of our knowledge, this is the first report on curare-insensitive, nicotine-induced effects in any organism.

  1. Polybrominated diphenyl ether (PBDE) concentrations in plasma of pregnant women from Western Australia.

    PubMed

    Stasinska, Ania; Heyworth, Jane; Reid, Alison; Callan, Anna; Odland, Jon Øyvind; Trong Duong, Phi; Van Ho, Quoc; Hinwood, Andrea

    2014-09-15

    PBDEs are a class of brominated flame retardants applied to consumer goods to reduce their flammability. These compounds are lipophilic, persistent and bioaccumulate through the food web. PBDEs have been detected in human blood, adipose tissue and breast milk. There are a small number of studies reporting concentrations of PBDEs in Australian populations. These indicate that concentrations are higher than in studies reporting concentrations from Europe but lower than those from Northern America. The aim of this paper was to determine the concentrations of PBDEs in the plasma of pregnant women participating in the Australian Maternal Exposure to Toxic Substances (AMETS) study in Western Australia. The samples comprised 164 pregnant women, aged 18 years and over, who were non-smokers and not occupationally exposed to persistent substances. Participants provided blood samples at 38 weeks gestation and these were analysed for five PBDE congeners. Maternal health and birth outcomes data were also obtained. The median for sum PBDE concentrations in plasma was 53.9 pg g(-1) (range 13.2 to 1390 pg g(-1)ww). Concentrations were adjusted for the estimated plasma lipid content. The concentrations of Σ5PBDE ranged from 2.44 to 258 ng g(-1) lipid with a median of 9.97 ng g(-1) lipid. BDE-47 was the dominant congener (median 21.4 pg g(-1), range <4.95 to 1030 pg g(-1)) followed by BDE-153 (median 12.2 pg g(-1), range <2.94 to 353 pg g(-1)). There were no significant associations between maternal, housing or dietary factors and concentrations of PBDEs in this study. Maternal PBDE concentrations were not associated with infant birth weight. This study builds upon previous Australian research and shows that concentrations in this sample of Western Australian women were higher than in parts of Europe. PMID:24973935

  2. Determining diabetes prevalence: a rational basis for the use of fasting plasma glucose concentrations?

    PubMed

    Finch, C F; Zimmet, P Z; Alberti, K G

    1990-08-01

    The World Health Organization and the National Diabetes Data Group each recommend a diagnostic cut-off point for diabetes of 7.8 mmol l-1 for fasting plasma glucose concentrations as part of the diagnostic criteria for epidemiological studies. However, this cut-off has been shown to be insensitive compared with a screening test based on 2-h plasma glucose levels. In thirteen Pacific populations, from four ethnic groups (Asian Indian, Melanesian, Micronesian, and Polynesian), we have examined whether a different cut-off point for fasting plasma glucose would be more accurate for obtaining an estimate of the prevalence of diabetes when compared with 2-h levels. A fasting plasma glucose diagnostic cut-off of 7.0 mmol l-1 gave an estimate of prevalence not significantly different from that based on the 2-h plasma glucose in 12 of the 13 populations (mean difference 0.27, range -1.51 to +2.44,%). On the other hand, when a cut-off of 7.8 mmol l-1 for fasting plasma glucose was used, the resulting prevalence over-estimated the 2-h glucose prevalence in all populations (mean difference 1.91, range 0.14-5.80,%). Thus for Pacific populations, a fasting plasma glucose cut-off of 7.0 mmol l-1 provides estimates of prevalence that are equivalent to those based on 2-h plasma glucose levels. In epidemiological studies designed to estimate diabetes prevalence, we recommend use of a fasting plasma glucose cut-off of 7.0 mmol l-1 in preference to a detection level of 7.8 mmol l-1, if glucose loading is not possible.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Plasma ghrelin concentrations change with physiological state in a sciurid hibernator (Spermophilus lateralis)

    PubMed Central

    Healy, Jessica E.; Ostrom, Cara E.; Wilkerson, Gregory K.; Florant, Gregory L.

    2009-01-01

    Ghrelin is a recently discovered hormone which has profound effects on food intake and lipogenesis in mammals. In all mammals studied thus far, plasma ghrelin concentrations are increased before a meal and decrease immediately following a meal; ghrelin levels increase with fasting. The golden-mantled ground squirrel Spermophilus lateralis (also known as Callospermophilus lateralis (see Helgen et al., 2009)) is a diurnal hibernator which has a robust annual cycle of body mass gain and loss that is primarily controlled by food intake. We hypothesized that in spring, summer, and autumn, the endogenous ghrelin concentrations of hibernators would be similar to those of non-hibernators, but that during the winter hibernation season, plasma ghrelin concentrations would be low or undetectable. We found that peripherally injected ghrelin significantly increased food intake in June. Plasma ghrelin concentrations were significantly increased through 5 days of fasting during a short-term fast in summer. Over a 24 hour period, ghrelin concentrations increased at night and decreased during the day with drops corresponding to times when squirrels were eating. In January, ghrelin concentrations are low but measurable even while animals are at low body temperature (Tb). The reason for the persistence of ghrelin in plasma at this time is unclear, but circulating ghrelin in hibernators may be involved with the control of sleep in these animals. This is the first report of ghrelin concentrations in a non-photoperiodic hibernator. We suggest that ghrelin may be important for the regulation of food intake and the body mass cycle in mammals that hibernate. PMID:20005230

  4. Real-time estimation of plasma insulin concentration from continuous glucose monitor measurements.

    PubMed

    de Pereda, Diego; Romero-Vivo, Sergio; Ricarte, Beatriz; Rossetti, Paolo; Ampudia-Blasco, Francisco Javier; Bondia, Jorge

    2016-01-01

    Continuous glucose monitors can measure interstitial glucose concentration in real time for closed-loop glucose control systems, known as artificial pancreas. These control systems use an insulin feedback to maintain plasma glucose concentration within a narrow and safe range, and thus to avoid health complications. As it is not possible to measure plasma insulin concentration in real time, insulin models have been used in literature to estimate them. Nevertheless, the significant inter- and intra-patient variability of insulin absorption jeopardizes the accuracy of these estimations. In order to reduce these limitations, our objective is to perform a real-time estimation of plasma insulin concentration from continuous glucose monitoring (CGM). Hovorka's glucose-insulin model has been incorporated in an extended Kalman filter in which different selected time-variant model parameters have been considered as extended states. The observability of the original Hovorka's model and of several extended models has been evaluated by their Lie derivatives. We have evaluated this methodology with an in-silico study with 100 patients with Type 1 diabetes during 25 h. Furthermore, it has been also validated using clinical data from 12 insulin pump patients with Type 1 diabetes who underwent four mixed meal studies. Real-time insulin estimations have been compared to plasma insulin measurements to assess performance showing the validity of the methodology here used in comparison with that formerly used for insulin models. Hence, real-time estimations for plasma insulin concentration based on subcutaneous glucose monitoring can be beneficial for increasing the efficiency of control algorithms for the artificial pancreas. PMID:26343364

  5. Ipecac-induced emesis and reduction of plasma concentrations of drugs following accidental overdose in children.

    PubMed

    Amitai, Y; Mitchell, A A; McGuigan, M A; Lovejoy, F H

    1987-09-01

    Syrup of ipecac is widely used following accidental drug overdosage in children. Proof of its efficacy, however, in reducing the risk of poisoning is limited. We prospectively studied the effect of early v late induction of emesis by ipecac in 50 children younger than 5 years of age with accidental acetaminophen poisoning. The mean estimated ingested dose was 165 mg/kg, and all patients vomited within 15 to 255 (mean 78) minutes postingestion. Although the predicted four-hour plasma acetaminophen concentration was 97 +/- 4 micrograms/mL (mean +/- SEM, calculated on the basis of the estimated ingested dose), the measured four-hour plasma acetaminophen concentration was 34 +/- 5 micrograms/mL (P less than .01). To assess the efficacy of early v late ipecac-induced emesis, we used the ratio of measured to predicted four-hour acetaminophen plasma concentration. The ratio of the measured to predicted four-hour level increased as the delay in time to vomiting increased (r = .60, P less than .001). Ipecac syrup was administered more promptly when available in the home than when obtained from a pharmacy or a medical facility (26 +/- 8 v 83 +/- 13 minutes postingestion, respectively; P less than .001) and vomiting occurred earlier (49 +/- 9 v 103 +/- 12 minutes postingestion; P less than .01). Although the mean estimated doses ingested were greater in patients who received ipecac syrup at home, their four-hour plasma acetaminophen concentrations were lower. These data suggest that prompt administration of ipecac syrup results in a greater reduction in plasma acetaminophen concentrations in potentially toxic overdosages in children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2888073

  6. Plasma concentrations of organohalogenated pollutants in predatory bird nestlings: associations to growth rate and dietary tracers.

    PubMed

    Bustnes, Jan O; Bårdsen, Bård J; Herzke, Dorte; Johnsen, Trond V; Eulaers, Igor; Ballesteros, Manuel; Hanssen, Sveinn A; Covaci, Adrian; Jaspers, Veerle L B; Eens, Marcel; Sonne, Christian; Halley, Duncan; Moum, Truls; Nøst, Therese Haugdal; Erikstad, Kjell E; Ims, Rolf Anker

    2013-11-01

    The extent to which persistent organic pollutants (POPs) with different physicochemical properties originated from the food (dietary input) was assessed in raptor nestlings. Lipophilic polychlorinated biphenyl (PCB) 153, 1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), and hexachlorobenzene (HCB), and protein-bound perfluorooctane sulfonate (PFOS), were measured repeatedly in blood plasma of individual goshawk (Accipiter gentilis) and white-tailed eagle (Haliaeetus albicilla) nestlings, 1 to 3 wk after hatching and near fledging. Maternally derived POPs dilute as nestlings grow (growth dilution), and increasing plasma concentrations would indicate dietary input. First, plasma concentrations given no dietary input were estimated, and concentrations of p,p'-DDE, HCB, and notably PFOS were significantly higher than predicted from a growth-dilution scenario (approximately 1.5-fold to 2.5-fold higher; p < 0.001). In contrast, PCB 153 declined in both species, although concentrations were still higher than predicted in white-tailed eagle nestlings (p < 0.05). Second, the relationships between plasma POP concentrations and trophic position (δ(15) N) and dietary carbon source (δ(13) C) were analyzed, controlling for growth rate. Both δ(15) N and δ(13) C (measured in body feathers) were significantly associated to the accumulation of most POPs, except PFOS. In conclusion, pollutant data acquired in plasma of nestling raptors should be interpreted and further investigated in the light of individual feeding ecology, and the use of raptor nestlings as sentinels for POP monitoring could be optimized by correcting for different factors such as body condition, brood size, and age.

  7. Plasma concentrations of organohalogenated pollutants in predatory bird nestlings: associations to growth rate and dietary tracers.

    PubMed

    Bustnes, Jan O; Bårdsen, Bård J; Herzke, Dorte; Johnsen, Trond V; Eulaers, Igor; Ballesteros, Manuel; Hanssen, Sveinn A; Covaci, Adrian; Jaspers, Veerle L B; Eens, Marcel; Sonne, Christian; Halley, Duncan; Moum, Truls; Nøst, Therese Haugdal; Erikstad, Kjell E; Ims, Rolf Anker

    2013-11-01

    The extent to which persistent organic pollutants (POPs) with different physicochemical properties originated from the food (dietary input) was assessed in raptor nestlings. Lipophilic polychlorinated biphenyl (PCB) 153, 1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), and hexachlorobenzene (HCB), and protein-bound perfluorooctane sulfonate (PFOS), were measured repeatedly in blood plasma of individual goshawk (Accipiter gentilis) and white-tailed eagle (Haliaeetus albicilla) nestlings, 1 to 3 wk after hatching and near fledging. Maternally derived POPs dilute as nestlings grow (growth dilution), and increasing plasma concentrations would indicate dietary input. First, plasma concentrations given no dietary input were estimated, and concentrations of p,p'-DDE, HCB, and notably PFOS were significantly higher than predicted from a growth-dilution scenario (approximately 1.5-fold to 2.5-fold higher; p < 0.001). In contrast, PCB 153 declined in both species, although concentrations were still higher than predicted in white-tailed eagle nestlings (p < 0.05). Second, the relationships between plasma POP concentrations and trophic position (δ(15) N) and dietary carbon source (δ(13) C) were analyzed, controlling for growth rate. Both δ(15) N and δ(13) C (measured in body feathers) were significantly associated to the accumulation of most POPs, except PFOS. In conclusion, pollutant data acquired in plasma of nestling raptors should be interpreted and further investigated in the light of individual feeding ecology, and the use of raptor nestlings as sentinels for POP monitoring could be optimized by correcting for different factors such as body condition, brood size, and age. PMID:23861300

  8. Relationships between circulating plasma concentrations and duodenal flows of essential amino acids in lactating dairy cows.

    PubMed

    Patton, R A; Hristov, A N; Parys, C; Lapierre, H

    2015-07-01

    The objective of this study was to better define essential AA (EAA) requirements in lactating dairy cows through examination of the relationship between plasma essential AA concentration (p[EAA]) and predicted duodenal flow of essential AA (EAAduo). Our hypothesis was that at a given level of milk protein output, p[EAA] would remain steady in response to increasing EAAduo until the EAA requirement was met, at which point p[EAA] would increase rapidly in response to greater duodenal flow of EAA until p[EAA] reached a plateau as other body processes degraded excess EAA to avoid toxicity. Thus, the requirement of each EAA would be fulfilled when p[EAA] increased rapidly. To investigate this hypothesis, we compiled a literature database that included 102 studies with 420 treatment means that reported p[EAA], dietary nutrient content, body weight, and milk production. A second database was produced to validate relationships developed in the first database and included 32 studies with 98 treatment means. All relationships were evaluated as regression equations with study as a random factor. Breed, days in milk, body weight, and milk protein production had no effect on the plasma concentration of any EAA. Other than metabolizable protein supply, nutritional content of the rations did not affect p[EAA]. Only p[Arg] was affected by parity, with primiparous cows having higher concentrations of Arg than older cows. No break points in the relationship between p[EAA] versus EAAduo were detected as either steep increases or plateaus. Plasma Arg, Ile, Lys, Thr, and Val concentrations were best associated with their respective EAAduo as quadratic equations, whereas His, Leu, Met, and Phe were associated only linearly. Adding a quadratic term improved the adjusted R(2) or decreased the root mean square error marginally (<2.0%). Thus, we conclude that the main effect of EAAduo on p[EAA] is linear. Abomasal or duodenal infusions of Met, Lys, His, Lys+Met, and casein revealed that Met

  9. Plasma BDNF Concentration, Val66Met Genetic Variant, and Depression-Related Personality Traits

    PubMed Central

    Terracciano, Antonio; Martin, Bronwen; Ansari, David; Tanaka, Toshiko; Ferrucci, Luigi; Maudsley, Stuart; Mattson, Mark P.; Costa, Paul T.

    2010-01-01

    Brain derived neurotrophic factor (BDNF) regulates synaptic plasticity and neurogenesis, and BDNF plasma and serum levels have been associated with depression, Alzheimer's disease, and other psychiatric and neurodegenerative disorders. In a relatively large community sample, drawn from the Baltimore Longitudinal Study of Aging (BLSA), we examine whether BDNF plasma concentration is associated with the Val66Met functional polymorphism of the BDNF gene (n = 335) and with depression-related personality traits assessed with the NEO-PI-R (n = 391). Plasma concentration of BDNF was not associated with the Val66Met variant in either men or women. However, in men, but not in women, BDNF plasma level was associated with personality traits linked to depression. Contrary to the notion that low BDNF is associated with negative outcomes, we found lower plasma levels in men who score lower on depression and vulnerability to stress (two facets of Neuroticism) and higher on Conscientiousness and Extraversion. These findings challenge the prevailing hypothesis that lower peripheral levels of BDNF are a marker of depression. PMID:20345896

  10. Free radical generation and concentration in a plasma polymer: the effect of aromaticity.

    PubMed

    Ershov, Sergey; Khelifa, Farid; Lemaur, Vincent; Cornil, Jérôme; Cossement, Damien; Habibi, Youssef; Dubois, Philippe; Snyders, Rony

    2014-08-13

    Plasma polymer films (PPF) have increasing applications in many fields due to the unique combination of properties of this class of materials. Among notable features arising from the specifics of plasma polymerization synthesis, a high surface reactivity can be advantageously used when exploited carefully. It is related to the presence of free radicals generated during the deposition process through manifold molecular bond scissions in the energetic plasma environment. In ambient atmosphere, these radicals undergo autoxidation reactions resulting in undesired polymer aging. However, when the reactivity of surface radicals is preserved and they are put in direct contact with a chemical group of interest, a specific surface functionalization or grafting of polymeric chains can be achieved. Therefore, the control of the surface free radical density of a plasma polymer is crucially important for a successful grafting. The present investigation focuses on the influence of the hydrocarbon precursor type, aromatic vs aliphatic, on the generation and concentration of free radicals on the surface of the PPF. Benzene and cyclohexane were chosen as model precursors. First, in situ FTIR analysis of the plasma phase supplemented by density functional theory calculations allowed the main fragmentation routes of precursor molecules in the discharge to be identified as a function of energy input. Using nitric oxide (NO) chemical labeling in combination with X-ray photoelectron spectroscopy analysis, a quantitative evaluation of concentration of surface free radicals as a function of input power has been assessed for both precursors. Different evolutions of the surface free radical density for the benzene- and cyclohexane-based PPF, namely, a continuous increase versus stabilization to a plateau, are attributed to different plasma polymerization mechanisms and resulting structures as illustrated by PPF characterization findings. The control of surface free radical density can be

  11. Cholinergic transmission during nicotine withdrawal is influenced by age and pre-exposure to nicotine: implications for teenage smoking.

    PubMed

    Carcoba, Luis M; Orfila, James E; Natividad, Luis A; Torres, Oscar V; Pipkin, Joseph A; Ferree, Patrick L; Castañeda, Eddie; Moss, Donald E; O'Dell, Laura E

    2014-01-01

    Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission during nicotine exposure and withdrawal in naïve adult rats compared to (1) adolescent rats and (2) adult rats that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAc) during nicotine exposure and precipitated withdrawal using microdialysis procedures. Adolescent (postnatal day, PND, 28-42) and adult rats (PND60-74) were prepared with osmotic pumps that delivered nicotine for 14 days (adolescents 4.7 mg/kg/day; adults 3.2 mg/kg/day; expressed as base). Another group of adults was exposed to nicotine during adolescence and then again in adulthood (pre-exposed adults) using similar methods. Control rats received a sham surgery. Following 13 days of nicotine exposure, the rats were implanted with microdialysis probes in the NAc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic receptor antagonist mecamylamine (1.5 and 3.0 mg/kg, i.p.) to precipitate withdrawal. A second study compared various metabolic differences in cholinergic transmission using the same treatment procedures as the first study. Following 14 days of nicotine exposure, the NAc was dissected and acetylcholinesterase (AChE) activity was compared across groups. In order to examine potential group differences in nicotine metabolism, blood plasma levels of cotinine (a nicotine metabolite) were also compared following 14 days of nicotine exposure. The results from the first study revealed that nicotine exposure increased baseline ACh levels to a greater extent in adolescent versus adult rats. During

  12. Cholinergic transmission during nicotine withdrawal is influenced by age and pre-exposure to nicotine: implications for teenage smoking.

    PubMed

    Carcoba, Luis M; Orfila, James E; Natividad, Luis A; Torres, Oscar V; Pipkin, Joseph A; Ferree, Patrick L; Castañeda, Eddie; Moss, Donald E; O'Dell, Laura E

    2014-01-01

    Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission during nicotine exposure and withdrawal in naïve adult rats compared to (1) adolescent rats and (2) adult rats that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAc) during nicotine exposure and precipitated withdrawal using microdialysis procedures. Adolescent (postnatal day, PND, 28-42) and adult rats (PND60-74) were prepared with osmotic pumps that delivered nicotine for 14 days (adolescents 4.7 mg/kg/day; adults 3.2 mg/kg/day; expressed as base). Another group of adults was exposed to nicotine during adolescence and then again in adulthood (pre-exposed adults) using similar methods. Control rats received a sham surgery. Following 13 days of nicotine exposure, the rats were implanted with microdialysis probes in the NAc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic receptor antagonist mecamylamine (1.5 and 3.0 mg/kg, i.p.) to precipitate withdrawal. A second study compared various metabolic differences in cholinergic transmission using the same treatment procedures as the first study. Following 14 days of nicotine exposure, the NAc was dissected and acetylcholinesterase (AChE) activity was compared across groups. In order to examine potential group differences in nicotine metabolism, blood plasma levels of cotinine (a nicotine metabolite) were also compared following 14 days of nicotine exposure. The results from the first study revealed that nicotine exposure increased baseline ACh levels to a greater extent in adolescent versus adult rats. During

  13. Consumption of canned citrus fruit meals increases human plasma β-cryptoxanthin concentration, whereas lycopene and β-carotene concentrations did not change in healthy adults.

    PubMed

    Zhu, Chenghao H; Gertz, Erik R; Cai, Yimeng; Burri, Betty J

    2016-07-01

    Several studies suggest that β-cryptoxanthin has a greater plasma response from its common food sources than other carotenoids such as β-carotene and lycopene. The hypothesis of this study is that changes in plasma β-cryptoxanthin concentrations will be greater than changes in plasma β-carotene or lycopene concentrations even if these carotenoids are fed in a similar food matrix, such as citrus fruit. We tested this hypothesis by measuring changes in plasma concentrations of β-cryptoxanthin, lycopene, and β-carotene after feeding measured amounts of canned tangerines and pink grapefruit to healthy nonsmoking adult humans. Volunteers served as their own controls and received both citrus fruit treatments randomly. In the first study, 8 subjects ate single meals of 234-304g of tangerines or 60-540g of pink grapefruit. The second study compared changes in plasma carotenoid concentration caused by feeding 234g of tangerines or 540g of pink grapefruit to 11 subjects. Blood was collected 5 times within 24hours after each citrus meal. Carotenoid concentrations were analyzed by reversed-phase high-performance liquid chromatography. Plasma β-cryptoxanthin concentrations increased within 5hours and then stabilized, remaining high throughout the 24hours measured. Plasma concentrations of lycopene and β-carotene did not change. These results show that β-cryptoxanthin concentrations increased after a citrus fruit meal, but lycopene and β-carotene concentrations did not change after a similar citrus fruit meal. These results support our hypothesis that changes in plasma β-cryptoxanthin are greater than changes in plasma lycopene or β-carotene, even when these carotenoids are fed in a similar food matrix. PMID:27333959

  14. Consumption of canned citrus fruit meals increases human plasma β-cryptoxanthin concentration, whereas lycopene and β-carotene concentrations did not change in healthy adults.

    PubMed

    Zhu, Chenghao H; Gertz, Erik R; Cai, Yimeng; Burri, Betty J

    2016-07-01

    Several studies suggest that β-cryptoxanthin has a greater plasma response from its common food sources than other carotenoids such as β-carotene and lycopene. The hypothesis of this study is that changes in plasma β-cryptoxanthin concentrations will be greater than changes in plasma β-carotene or lycopene concentrations even if these carotenoids are fed in a similar food matrix, such as citrus fruit. We tested this hypothesis by measuring changes in plasma concentrations of β-cryptoxanthin, lycopene, and β-carotene after feeding measured amounts of canned tangerines and pink grapefruit to healthy nonsmoking adult humans. Volunteers served as their own controls and received both citrus fruit treatments randomly. In the first study, 8 subjects ate single meals of 234-304g of tangerines or 60-540g of pink grapefruit. The second study compared changes in plasma carotenoid concentration caused by feeding 234g of tangerines or 540g of pink grapefruit to 11 subjects. Blood was collected 5 times within 24hours after each citrus meal. Carotenoid concentrations were analyzed by reversed-phase high-performance liquid chromatography. Plasma β-cryptoxanthin concentrations increased within 5hours and then stabilized, remaining high throughout the 24hours measured. Plasma concentrations of lycopene and β-carotene did not change. These results show that β-cryptoxanthin concentrations increased after a citrus fruit meal, but lycopene and β-carotene concentrations did not change after a similar citrus fruit meal. These results support our hypothesis that changes in plasma β-cryptoxanthin are greater than changes in plasma lycopene or β-carotene, even when these carotenoids are fed in a similar food matrix.

  15. [The concentration of free lidocaine in arterial, central venous and peripheral vein plasma following intravenous injection].

    PubMed

    Nolte, H; al Saydali, B; Weissenberg, W

    1990-03-01

    Ten intensive care patients and five healthy volunteers each received a bolus injection of lidocaine HCl (100 mg, 2%) over an injection period of 5 s. After 0.5, 1, 2, 4, 8, 15 and 25 min arterial, central venous and peripheral venous blood samples were collected. In four of the volunteers, arterial and central venous samples were also taken about 10 s after the end of injection. The fluorescence polarization method by means of the Abbott-TDx system was used, and plasma concentrations of lidocaine were determined. The measurements showed that lidocaine levels in central venous plasma 10 s after the end of administration were higher than those in arterial plasma. By 30 s after administration the opposite situation had developed, so that arterial concentrations were higher than those in central venous plasma. This relation did not change throughout the study, though the two levels became closer, as is shown by the ratios (Table 3, Fig. 2). Concentrations in peripheral venous plasma increased more slowly but remained far below those in arterial and central venous plasma, at least for the first 8 min. After 15 min lidocaine levels were almost the same in all three samples. During the entire study there were no ECG changes, and neither heart rate nor blood pressure showed any significant deviation from the values obtained at the beginning. The volunteers had minor toxic manifestations, such as dizziness, tinnitus and a metallic taste in the mouth; one person had a sensation of pressure in his chest, which improved following oxygen administration.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Nicotine nasal spray and vapor inhaler: abuse liability assessment.

    PubMed

    Schuh, K J; Schuh, L M; Henningfield, J E; Stitzer, M L

    1997-04-01

    Acute subjective and physiological effects were examined to provide information relevant to abuse liability of new nicotine delivery systems. Subjects (n = 12) were overnight-deprived smokers who received 0, 4, 8 and 16 active puffs from nicotine-containing cigarettes (0.1 mg per puff), 0, 1, 2 or 4 nasal sprays (0.5 mg nicotine per spray) and 0, 30, 60 and 120 vapor inhalations (estimated 0.013 mg nicotine per inhalation) in a within-subject single blinded design. While smokers clearly liked cigarette puffs, there was much less evidence of liking produced by either nasal spray or vapor inhaler; only modest elevations on a measure of good drug effects were observed. The novel delivery products engendered unpleasant effects of burning throat and nose, watery eyes, runny nose, coughing and sneezing that might be expected to limit abuse liability. Nicotine plasma level and heart rate increase was dose-related for cigarettes and nasal spray but not for vapor inhaler, indicating limited nicotine delivery with the latter device. Overall, results are consistent with the conclusion that the nicotine nasal spray and vapor inhaler are of substantially lower abuse liability than cigarettes in experienced cigarette smokers receiving initial exposure to these products. PMID:9160851

  17. Genetic Relationship between Schizophrenia and Nicotine Dependence

    PubMed Central

    Chen, Jingchun; Bacanu, Silviu-Alin; Yu, Hui; Zhao, Zhongming; Jia, Peilin; Kendler, Kenneth S.; Kranzler, Henry R.; Gelernter, Joel; Farrer, Lindsay; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Boomsma, Dorret I.; Penninx, Brenda W. J. H.; Tyndale, Rachel F.; Ware, Jennifer J.; Vink, Jacqueline M.; Kaprio, Jaakko; Munafò, Marcus; Chen, Xiangning; Ware, Jennifer J.; Chen, Xiangning; Vink, Jacqueline M.; Loukola, Anu; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Mangino, Massimo; Menni, Cristina; Chen, Jingchun; Peterson, Roseann; Auro, Kirsi; Lyytikäinen, Leo-Pekka; Wedenoja, Juho; Stiby, Alex I.; Hemani, Gibran; Willemsen, Gonneke; Hottenga, Jouke Jan; Korhonen, Tellervo; Heliövaara, Markku; Perola, Markus; Rose, Richard; Paternoster, Lavinia; Timpson, Nic; Wassenaar, Catherine A.; Zhu, Andy Z. X.; Smith, George Davey; Raitakari, Olli; Lehtimäki, Terho; Kähönen, Mika; Koskinen, Seppo; Spector, Timothy; Penninx, Brenda W. J. H.; Salomaa, Veikko; Boomsma, Dorret I.; Tyndale, Rachel F.; Kaprio, Jaakko; Munafò, Marcus; Ware, Jennifer J.; Chen, Xiangning; Vink, Jacqueline M.; Loukola, Anu; Minica, Camelia; Chen, Jingchun; Peterson, Roseann; Timpson, Nic; Taylor, Michelle; Boomsma, Dorret I.; Kaprio, Jaakko; Munafò, Marcus; Maes, Hermine; Riley, Brien; Kendler, Kenneth S.; Gelernter, Joel; Sherva, Richard; Farrer, Lindsay; Kranzler, Henry R.; Maher, Brion; Vanyukov, Michael

    2016-01-01

    It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10−3 and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10−3 and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity. PMID:27164557

  18. Genetic Relationship between Schizophrenia and Nicotine Dependence.

    PubMed

    Chen, Jingchun; Bacanu, Silviu-Alin; Yu, Hui; Zhao, Zhongming; Jia, Peilin; Kendler, Kenneth S; Kranzler, Henry R; Gelernter, Joel; Farrer, Lindsay; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Boomsma, Dorret I; Penninx, Brenda W J H; Tyndale, Rachel F; Ware, Jennifer J; Vink, Jacqueline M; Kaprio, Jaakko; Munafò, Marcus; Chen, Xiangning

    2016-01-01

    It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10(-3) and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10(-3) and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity. PMID:27164557

  19. Genetic Relationship between Schizophrenia and Nicotine Dependence.

    PubMed

    Chen, Jingchun; Bacanu, Silviu-Alin; Yu, Hui; Zhao, Zhongming; Jia, Peilin; Kendler, Kenneth S; Kranzler, Henry R; Gelernter, Joel; Farrer, Lindsay; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Boomsma, Dorret I; Penninx, Brenda W J H; Tyndale, Rachel F; Ware, Jennifer J; Vink, Jacqueline M; Kaprio, Jaakko; Munafò, Marcus; Chen, Xiangning

    2016-05-10

    It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10(-3) and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10(-3) and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity.

  20. Plasma concentrations of bupivacaine after combined spinal epidural anaesthesia in infants and neonates.

    PubMed

    Frawley, G; Ragg, P; Hack, H

    2000-01-01

    The unbound and bound plasma concentration of bupivacaine in 50 infants less than 55 weeks postconceptual age was determined following combined spinal and epidural anaesthesia (csea). Plasma concentrations were determined at 15-min intervals up to 60 min postspinal anaesthesia. Maximum plasma bupivacaine levels were recorded between 45 and 60 min post CseA. Total plasma concentrations above a toxic threshold level of 4 microg.ml(-1) were recorded in 4% of patients and above 2.5 microg.ml(-1) in 10% of patients. Unbound bupivacaine levels were greater than a presumed toxic level of 0.25 microg.ml(-1) in 16% of cases and above 0.3 microg. ml(-1) in 14% of cases. A wide range of protein binding was measured (varying from 53.8-98.2%) and could not be correlated with standard indicators of local anaesthetic binding. Two neonates had brief apnoeas in the immediate perioperative phase but no adverse cardiac or central nervous system events attributable to the performance of Csea were demonstrated.

  1. Plasma concentrations of carbohydrates and sugar alcohols in term newborns after milk feeding.

    PubMed

    Brown, Laura D; Cavalli, Claudio; Harwood, Jeri E F; Casadei, Annachiara; Teng, Cecilia C; Traggiai, Cristina; Serra, Giovanni; Bevilacqua, Giulio; Battaglia, Frederick C

    2008-08-01

    Nonglucose carbohydrates such as galactose, mannose, and inositol play a clinically important role in fetal and neonatal nutrition, though little is known about their metabolism in the neonate. The aim of this study was to determine whether postprandial changes in plasma carbohydrate and sugar alcohol concentrations are affected by clinical variables such as postnatal age (PNA), milk type, feeding volume, or feeding duration in term newborns. Neonates (n = 26) taking intermittent enteral feedings were enrolled. Blood samples were obtained at baseline (immediately before the start of a feeding) and at 2-3 subsequent time points up to 110 min. Postprandial rise was only observed for plasma glucose concentrations [Glu] and plasma galactose concentrations [Gal] and clinical variables did not predict this change. Despite equimolar delivery in milk, the median of [Glu] rise minus [Gal] rise from baseline to second postprandial plasma sample was 674 microM (-38, 3333 microM; p < 0.0001), reflecting efficient hepatic first-pass metabolism of galactose. A significant PNA effect on [Gal] was observed such that for each day PNA there was an 18% decrease in [Gal] (p = 0.03). [Gal] are a function of PNA, suggesting maintenance of a significant ductus venosus shunt in term infants.

  2. Diagnostics of PF-1000 Facility Operation and Plasma Concentration on the Basis of Spectral Measurements

    SciTech Connect

    Skladnik-Sadowska, E.; Malinowski, K.; Sadowski, M. J.; Scholz, M.; Tsarenko, A. V.

    2006-01-15

    The paper concerns the monitoring of high-current pulse discharges and the determination of the plasma concentration within the dense magnetized plasma by means of optical spectroscopy methods. In experiments with the large PF-1000 facility operated at IPPLM in Warsaw, Poland, attention was paid to the determination of the operational mode and electron concentration under different experimental conditions. To measure the visible radiation (VR) the use was made of the MECHELLE registered 900-spectrometer equipped with the CCD readout. The VR emission, observed at 65 deg. to the z-axis, originated from a part of the electrode surfaces, the collapsing current-sheath layer and the dense plasma pinch-region (40-50 mm from the electrode ends). Considerable differences were found in the optical spectra recorded for so-called 'good shots' and for cases of some failures. Estimates of the electron concentration, which were performed with different spectroscopic techniques, showed that it ranged from 5.56x1018 cm-3 to 4.8x1019 cm-3, depending on experimental conditions. The correlation of the fusion-neutron yield and the plasma density was proved.

  3. Correlation between heart disorders and concentrations of directly measured atrial natriuretic peptide in plasma.

    PubMed

    Fridrich, L; Szekeres, T; Hartter, E; Schweighofer, F; Gassner, A; Laczkovic, A

    1989-03-01

    We used new commercially available direct radioimmunoassay to measure human atrial natriuretic peptide (h-ANP) in plasma from 48 individuals who were being evaluated for left and right ventricular function. For 13 healthy individuals with normal ventricular function these concentrations ranged up to 54 ng/L. Measurements of h-ANP clearly differentiated between normal subjects, patients with coronary artery disease, and patients who had undergone orthotopic heart transplantation (ANOVA P less than 0.0001, significant differences between all groups)--all showing normal ventricular function at rest. There was a strong negative correlation (r = -0.64, P less than 0.001) between left ventricular ejection fraction and h-ANP concentrations in plasma of patients with proven coronary artery disease, patients with cardiomyopathy, and healthy individuals. Results by the present method and methods involving extraction of the sample correlated well. Evidently the direct assay of h-ANP in plasma yields information that could be used to help evaluate heart disorders and other pathophysiological conditions causing increased h-ANP concentrations in plasma.

  4. Subspecies differences in early fetal development and plasma pregnancy-associated glycoprotein concentrations in cattle.

    PubMed

    Mercadante, P M; Waters, K M; Mercadante, V R G; Lamb, G C; Elzo, M A; Johnson, S E; Rae, D O; Yelich, J V; Ealy, A D

    2013-08-01

    Inclusion of Bos indicus genetics improves production traits of cattle maintained in hot climates. Limited information exists detailing pregnancy-specific events as influenced by variable amounts of Bos indicus genetics. Three experiments were completed to examine the effect of Bos taurus and Bos indicus genotypes on fetal size and plasma pregnancy-associated glycoprotein (PAG) concentrations. In all experiments, cows were bred by AI after synchronization of ovulation. Fetal measurements were completed by transrectal ultrasonography and plasma PAG concentrations were quantified from plasma harvested the day of each fetal measurement. In Exp. 1, fetal size and plasma PAG concentrations were measured at d 53 of pregnancy in cows composed of various fractions of Angus and Brahman (n = 9 to 21 cows/group). Fetus size was greater in cows containing >80% Angus genetics compared with cows containing <80% Angus influence (3.40 ± 0.28 vs. 2.86 ± 0.28 cm crown-rump length; P < 0.01). Plasma PAG concentrations were reduced (P < 0.01) in cows containing >80% Angus genetics when compared with their contemporaries (6.0 ± 1.5 ng/mL vs. 9.4 ± 1.5 ng/mL). In Exp. 2, fetal measurements and plasma PAG concentrations were determined at d 35 and 62 of pregnancy in Angus and Brangus cows. Breed did not affect fetus size at d 35, but Angus cows contained larger fetuses than Brangus cows at d 62 [3.0 ± 0.03 vs. 2.8 ± 0.03 cm crown-nose length (CNL; P > 0.01)]. Plasma PAG concentrations were not different between breed at d 35 and 62 (P > 0.1). In Exp. 3, fetal measurements and plasma samples were collected at d 33/34, 40/41, 47/48, and 54/55 post-AI in Angus and Brangus cows. Fetus size was not different (P > 0.05) between genotypes on d 33/34, 40/41, and 47/48. Angus fetuses were larger than Brangus fetuses at d 54/55 (2.1 ± 0.03 vs. 1.9 ± 0.03 cm CNL; P = 0.001). Plasma PAG concentrations were less in Angus than Brangus cows at each time point (average 4.9 ± 0.9 vs. 8.2 ± 0

  5. Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

    PubMed Central

    Ruiz-Valderas, Rosa; Sánchez-Rivas, Elena; Lluch, Amparo; Gutierrez-Valencia, Alicia; Torres-Cornejo, Almudena; BenMarzouk-Hidalgo, Omar J.; Viciana, Pompeyo

    2013-01-01

    There is significant intra- and intersubject variability in lopinavir (LPV) plasma concentrations after standard dosing; thus, this prospective study was conducted to determine whether low plasma LPV concentrations could be associated with virological outcome throughout lopinavir-ritonavir maintenance monotherapy (mtLPVr) in the clinical practice setting. If this hypothesis would be confirmed, LPV drug monitoring could improve the efficacy of mtLPVr regimens. Patients with previous virological failure (VF) on protease inhibitor-based regimens were also included if the genotypic resistance tests showed no major resistance mutation associated with reduced susceptibility to lopinavir-ritonavir. VF was defined as 2 consecutive determinations of HIV RNA levels of >200 copies/ml. Efficacy was analyzed by per-protocol analysis. Plasma LPV trough concentrations were measured by high-performance liquid chromatography using a UV detector. A total of 127 patients were included (22% with previous failure on protease inhibitors). After 96 weeks, the efficacy rate was 82.3% (95% confidence interval [CI95], 75.3 to 89.3%). Virological efficacy was independent of LPV plasma concentrations even when LPVr was given once daily. An adherence of <90% (HR, 4.4 [CI95, 1.78 to 10.8; P = 0.001]) and the presence of blips in the preceding 12 months (HR, 3.06 [CI95, 1.17 to 8.01; P = 0.022]) were the only variables independently associated with time to VF. These findings suggest that the LPV concentrations achieved with the standard doses of LPVr are sufficient to maintain virological control during monotherapy and that measurement of LPV concentrations is not useful for predicting virological outcome. Tight control of viral replication in the previous months and strict adherence throughout the mtLPVr regimen could improve the virological efficacy of this maintenance regimen. PMID:23716055

  6. Plasma concentrations of posaconazole administered via nasogastric tube in patients in a surgical intensive care unit.

    PubMed

    Störzinger, Dominic; Borghorst, Stephan; Hofer, Stefan; Busch, Cornelius J; Lichtenstern, Christoph; Hempel, Georg; Weigand, Markus A; Hoppe-Tichy, Torsten

    2012-08-01

    Abdominal surgery may affect intestinal absorption and the resulting levels of posaconazole in the blood. We measured plasma posaconazole levels in surgical intensive care unit (SICU) patients and tried to develop a predictive population pharmacokinetics model. A total of 270 samples from 15 patients receiving posaconazole via nasogastric tube were measured by high-performance liquid chromatography (HPLC). SICU patients showed lower plasma drug concentrations, a higher apparent clearance, and a higher volume of distribution than those in hematology patients, possibly due to poor absorption.

  7. Toxicological evaluation of aerosols of a tobacco extract formulation and nicotine formulation in acute and short-term inhalation studies.

    PubMed

    Werley, Michael S; Jerome, Ann M; Oldham, Michael J

    2014-03-01

    A formulation of tobacco extract containing 4% nicotine (TE) and similar nicotine formulation containing vehicle and 4% nicotine (NF) were evaluated using animal inhalation assays. Two 4-h inhalation exposures at 1 and 2 mg/L aerosol exposure concentrations, respectively, of the tobacco extract with 4% nicotine formulation showed that the LC50 was greater than 2 mg/L, the maximum concentration tested. All inhalation exposures were conducted using the capillary aerosol generator (CAG). Increasing aerosol TPM concentrations (0, 10, 50, 200, 1000 mg/m(3) TE and 0, 50, 200, 500, 1000 mg/m(3) NF) were generated via the CAG and used to expose groups of male and female rats for 4-h per day for 14 days. In life monitors for potential effects included clinical observations, weekly body weights and food consumption. Post mortem evaluations included gross tissue findings, hematology, clinical chemistry, serum plasma and nicotine levels, absolute and normalized organ and tissue weights, and histopathology of target organs. Treatment-related changes were observed in body weights, hematology, clinical chemistry, organ weights and histopathological findings for TE at the 200 and 1000 mg/m(3) exposure levels, and in the 500 and 1000 mg/m(3) exposure groups for NF. Under the conditions of these studies, the no-observed-adverse-effect level in the rat was approximately 50 mg/m(3) for the TE aerosol-exposed groups, and approximately 200 mg/m(3) in the NF aerosol-exposed groups.

  8. Development of a microfluidic device for cell concentration and blood cell-plasma separation.

    PubMed

    Maria, M Sneha; Kumar, B S; Chandra, T S; Sen, A K

    2015-12-01

    This work presents design, fabrication and test of a microfluidic device which employs Fahraeus-Lindqvist and Zweifach-Fung effects for cell concentration and blood cell-plasma separation. The device design comprises a straight main channel with a series of branched channels placed symmetrically on both sides of the main channel. The design implements constrictions before each junction (branching point) in order to direct cells that would have migrated closer to the wall (naturally or after liquid extraction at a junction) towards the centre of the main channel. Theoretical and numerical analysis are performed for design of the microchannel network to ensure that a minimum flow rate ratio (of 2.5:1, main channel-to-side channels) is maintained at each junction and predict flow rate at the plasma outlet. The dimensions and location of the constrictions were determined using numerical simulations. The effect of presence of constrictions before the junctions was demonstrated by comparing the performances of the device with and without constrictions. To demonstrate the performance of the device, initial experiments were performed with polystyrene microbeads (10 and 15 μm size) and droplets. Finally, the device was used for concentration of HL60 cells and separation of plasma and cells in diluted blood samples. The cell concentration and blood-plasma purification efficiency was quantified using Haemocytometer and Fluorescence-Activated Cell Sorter (FACS). A seven-fold cell concentration was obtained with HL60 cells and a purification efficiency of 70 % and plasma recovery of 80 % was observed for diluted (1:20) blood sample. FACS was used to identify cell lysis and the cell viability was checked using Trypan Blue test which showed that more than 99 % cells are alive indicating the suitability of the device for practical use. The proposed device has potential to be used as a sample preparation module in lab on chip based diagnostic platforms.

  9. Perfluoroalkyl contaminants in plasma of five sea turtle species: comparisons in concentration and potential health risks.

    PubMed

    Keller, Jennifer M; Ngai, Lily; Braun McNeill, Joanne; Wood, Lawrence D; Stewart, Kelly R; O'Connell, Steven G; Kucklick, John R

    2012-06-01

    The authors compared blood plasma concentrations of 13 perfluoroalkyl contaminants (PFCs) in five sea turtle species with differing trophic levels. Wild sea turtles were blood sampled from the southeastern region of the United States, and plasma was analyzed using liquid chromatography tandem mass spectrometry. Mean concentrations of perfluorooctane sulfonate (PFOS), the predominant PFC, increased with trophic level from herbivorous greens (2.41 ng/g), jellyfish-eating leatherbacks (3.95 ng/g), omnivorous loggerheads (6.47 ng/g), to crab-eating Kemp's ridleys (15.7 ng/g). However, spongivorous hawksbills had surprisingly high concentrations of PFOS (11.9 ng/g) and other PFCs based on their trophic level. These baseline concentrations of biomagnifying PFCs demonstrate interesting species and geographical differences. The measured PFOS concentrations were compared with concentrations known to cause toxic effects in laboratory animals, and estimated margins of safety (EMOS) were calculated. Small EMOS (<100), suggestive of potential risk of adverse health effects, were observed for all five sea turtle species for immunosuppression. Estimated margins of safety less than 100 were also observed for liver, thyroid, and neurobehavorial effects for the more highly exposed species. These baseline concentrations and the preliminary EMOS exercise provide a better understanding of the potential health risks of PFCs for conservation managers to protect these threatened and endangered species.

  10. The influence of environmental variables on platelet concentration in horse platelet-rich plasma.

    PubMed

    Rinnovati, Riccardo; Romagnoli, Noemi; Gentilini, Fabio; Lambertini, Carlotta; Spadari, Alessandro

    2016-01-01

    Platelet-rich plasma (PRP) commonly refers to blood products which contain a higher platelet (PLT) concentration as compared to normal plasma. Autologous PRP has been shown to be safe and effective in promoting the natural processes of soft tissue healing or reconstruction in humans and horses. Variability in PLT concentration has been observed in practice between PRP preparations from different patients or from the same individual under different conditions. A change in PLT concentration could modify PRP efficacy in routine applications. The aim of this study was to test the influence of environmental, individual and agonistic variables on the PLT concentration of PRP in horses. Six healthy Standardbred mares were exposed to six different variables with a one-week washout period between variables, and PRP was subsequently obtained from each horse. The variables were time of withdrawal during the day (morning/evening), hydration status (overhydration/dehydration) treatment with anti-inflammatory drugs and training periods on a treadmill. The platelet concentration was significantly higher in horses treated with a non-steroidal anti-inflammatory drug (P = 0.03). The leukocyte concentration increased 2-9 fold with respect to whole blood in the PRP which was obtained after exposure to all the variable considered. Environmental variation in platelet concentration should be taken into consideration during PRP preparation. PMID:27377748

  11. The influence of environmental variables on platelet concentration in horse platelet-rich plasma.

    PubMed

    Rinnovati, Riccardo; Romagnoli, Noemi; Gentilini, Fabio; Lambertini, Carlotta; Spadari, Alessandro

    2016-07-04

    Platelet-rich plasma (PRP) commonly refers to blood products which contain a higher platelet (PLT) concentration as compared to normal plasma. Autologous PRP has been shown to be safe and effective in promoting the natural processes of soft tissue healing or reconstruction in humans and horses. Variability in PLT concentration has been observed in practice between PRP preparations from different patients or from the same individual under different conditions. A change in PLT concentration could modify PRP efficacy in routine applications. The aim of this study was to test the influence of environmental, individual and agonistic variables on the PLT concentration of PRP in horses. Six healthy Standardbred mares were exposed to six different variables with a one-week washout period between variables, and PRP was subsequently obtained from each horse. The variables were time of withdrawal during the day (morning/evening), hydration status (overhydration/dehydration) treatment with anti-inflammatory drugs and training periods on a treadmill. The platelet concentration was significantly higher in horses treated with a non-steroidal anti-inflammatory drug (P = 0.03). The leukocyte concentration increased 2-9 fold with respect to whole blood in the PRP which was obtained after exposure to all the variable considered. Environmental variation in platelet concentration should be taken into consideration during PRP preparation.

  12. Absorption of thiamine and nicotinic acid in the rat intestine during fasting and immobilization stress

    NASA Technical Reports Server (NTRS)

    Kirilyuk, O. G.; Khmelevskiy, Y. V.

    1980-01-01

    By perfusion of isolated sections of intestine with a solution containing thiamine at a concentration of 3.1 micromole, it was established that thiamine absorption in animals fasted for 72 hours decreased by 28 percent, whereas absorption increased by 12 percent in rats after 24 hour immobilization. After immobilization, absorption of label in the intestinal mucosa increased. Na K ATPase activity in the intestinal mucosa decreased by 10 percent during fasting, and it increased with immobilization of the animals. Activity of Na K ATPase in the intestinal mucosa cells determined the absorption rate of thiamine and nicotinic acid at the level of vitamin transport through the plasma membranes of the enterocytes.

  13. Relationship between gamma-hydroxybutyrate plasma concentrations and its electroencephalographic effects in the rat.

    PubMed

    Van Sassenbroeck, D K; De Paepe, P; Belpaire, F M; Rosseel, M T; Martens, P; Boon, P A; Buylaert, W A

    2001-12-01

    In view of the potential interest in an objective parameter for the depth of coma in intoxications with the recreational drug gamma-hydroxybutyrate (GHB), we have studied the relationship between the plasma concentrations and the electroencephalographic (EEG) changes induced by GHB in the rat. Fifteen rats randomly received either 150 (n = 3), 200 (n = 6) or 300 mg kg(-1) (n = 6) GHB over 5 min, followed by a supramaximal dose of 450 mg kg(-1) over 5 min at the end of the experiment. Plasma concentrations were determined with HPLC. The EEG was continuously recorded and the amplitude in the 15.5-30 Hz frequency band was quantified using aperiodic analysis. The plasma concentration-time profiles were fitted to a two-compartment model with Michaelis-Menten elimination. The pharmacokinetic parameters Vmax, Km and the apparent volume of distribution (Vd) proved to be independent of the dose and the mean pooled values were Vmax 2068 +/- 140 microg min(-1) kg(-1), Km 58 +/- 16 microg mL(-1) and Vd 476 +/- 12 mL kg(-1). The EEG amplitude in the 15.5-30 Hz frequency band displayed a monophasic inhibition and the effect-plasma concentration curve showed hysteresis. This hysteresis between EEG effect and plasma concentrations was minimized by simultaneous calculation of hypothetical effect-site concentrations and fitting the effect vs effect-site concentration curve to a sigmoid inhibitory Emax model. The descriptors of this Emax model (Emax, EC50, k(e,0), gamma and E0) were independent of the dose with an equilibration half-life t1/2k(e,0) of 5.6 +/- 0.3 min (mean value of the pooled results of the 5-min treatment groups). To investigate the origin of this hysteresis, a dose of 600 mg kg(-1) GHB was infused over either 45 or 60 min each in three animals. The hysteresis was much less pronounced with 45 min than with 5 min and was absent with 60-min infusions. This indicated that the hysteresis was due to a distribution delay between the central compartment and the effect site

  14. Effects of total gastrectomy on plasma silicon and amino acid concentrations in men.

    PubMed

    Tatara, Marcin R; Krupski, Witold; Szpetnar, Maria; Dąbrowski, Andrzej; Bury, Paweł; Szabelska, Anna; Charuta, Anna; Boguszewska-Czubara, Anna; Maciejewski, Ryszard; Wallner, Grzegorz

    2015-12-01

    The aim of the study was to determine one-year effects of total gastrectomy on plasma silicon and free amino acid concentrations in patients and evaluate changes of volumetric bone mineral density (vBMD) in lumbar spine. Eight patients were enrolled to the control (CTR) group. Six patients subjected to total gastrectomy (GX group) were included to the experimental group. vBMD in trabecular and cortical bone was measured in lumbar vertebrae at baseline (before surgery) and one year later using quantitative computed tomography. Plasma concentrations of silicon and free amino acids were determined at baseline and one year later using photometric method and ion-exchange chromatography. Body weights within CTR and GX groups were not different after one-year follow-up when compared to the baseline values (P > 0.05). An average annual decrease of vBMD in the trabecular bone in the gastrectomized patients reached 15.0% in lumbar spine and was significantly different in comparison to the percentage changes observed in CTR group (P = 0.02). One-year percentage change of vBMD in the cortical bone in L1 and L2 has shown significantly decreased values by 10.5 and 9.1% in the GX group when compared to the percentage change observed in the controls (P < 0.05). Plasma concentration of adipic acid was significantly higher by 101.6% one year after total gastrectomy procedure in the patients when compared to the baseline value (P = 0.01). Plasma concentration of silicon was significantly lowered by 26.7% one year after the total gastrectomy when compared to the baseline value (P = 0.009). Total gastrectomy in patients has induced severe osteoporotic changes in lumbar spine within one-year period. The observed osteoporotic changes were associated with decreased plasma concentration of silicon indicating importance of exocrine and endocrine functions of stomach for silicon homeostasis maintenance. Gastrectomy-induced bone loss was not related to decreased amino acid

  15. Effects of total gastrectomy on plasma silicon and amino acid concentrations in men

    PubMed Central

    Krupski, Witold; Szpetnar, Maria; Dąbrowski, Andrzej; Bury, Paweł; Szabelska, Anna; Charuta, Anna; Boguszewska-Czubara, Anna; Maciejewski, Ryszard; Wallner, Grzegorz

    2015-01-01

    The aim of the study was to determine one-year effects of total gastrectomy on plasma silicon and free amino acid concentrations in patients and evaluate changes of volumetric bone mineral density (vBMD) in lumbar spine. Eight patients were enrolled to the control (CTR) group. Six patients subjected to total gastrectomy (GX group) were included to the experimental group. vBMD in trabecular and cortical bone was measured in lumbar vertebrae at baseline (before surgery) and one year later using quantitative computed tomography. Plasma concentrations of silicon and free amino acids were determined at baseline and one year later using photometric method and ion-exchange chromatography. Body weights within CTR and GX groups were not different after one-year follow-up when compared to the baseline values (P > 0.05). An average annual decrease of vBMD in the trabecular bone in the gastrectomized patients reached 15.0% in lumbar spine and was significantly different in comparison to the percentage changes observed in CTR group (P = 0.02). One-year percentage change of vBMD in the cortical bone in L1 and L2 has shown significantly decreased values by 10.5 and 9.1% in the GX group when compared to the percentage change observed in the controls (P < 0.05). Plasma concentration of adipic acid was significantly higher by 101.6% one year after total gastrectomy procedure in the patients when compared to the baseline value (P = 0.01). Plasma concentration of silicon was significantly lowered by 26.7% one year after the total gastrectomy when compared to the baseline value (P = 0.009). Total gastrectomy in patients has induced severe osteoporotic changes in lumbar spine within one-year period. The observed osteoporotic changes were associated with decreased plasma concentration of silicon indicating importance of exocrine and endocrine functions of stomach for silicon homeostasis maintenance. Gastrectomy-induced bone loss was not related to decreased amino acid

  16. Relationship between Physical Activity and Plasma Fibrinogen Concentrations in Adults without Chronic Diseases

    PubMed Central

    Gomez-Marcos, Manuel A.; Recio-Rodríguez, José I.; Patino-Alonso, Maria C.; Martinez-Vizcaino, Vicente; Martin-Borras, Carme; de-la-Cal-dela-Fuente, Aventina; Sauras-Llera, Ines; Sanchez-Perez, Alvaro; Agudo-Conde, Cristina; García-Ortiz, Luis

    2014-01-01

    Objective To analyze the relationship between regular physical activity, as assessed by accelerometer and 7-day physical activity recall (PAR), and plasma fibrinogen concentrations. Methods A cross-sectional study in a previously established cohort of healthy subjects was performed. This study analyzed 1284 subjects who were included in the EVIDENT study (mean age 55.0±13.6 years; 60.90% women). Fibrinogen concentrations were measured in blood plasma. Physical activity was assessed with a 7-day PAR (metabolic equivalents (METs)/hour/week) and GT3X ActiGraph accelerometer (counts/minute) for 7 days. Results Physical exercise, which was evaluated with both an accelerometer (Median: 237.28 counts/minute) and 7-day PAR (Median: 8 METs/hour/week). Physical activity was negatively correlated with plasma fibrinogen concentrations, which was evaluated by counts/min (r = −0.100; p<0.001) and METs/hour/week (r = −0.162; p<0.001). In a multiple linear regression analysis, fibrinogen concentrations of the subjects who performed more physical activity (third tertile of count/minute and METs/hour/week) respect to subjects who performed less (first tertile), maintained statistical significance after adjustments for age and others confounders (β = −0.03; p = 0.046 and β = −0.06; p<0.001, respectively). Conclusions Physical activity, as assessed by accelerometer and 7-day PAR, was negatively associated with plasma fibrinogen concentrations. This relation is maintained in subjects who performed more exercise even after adjusting for age and other confounders. PMID:24498413

  17. Determination of neutral carbon concentration in electron cyclotron resonance generated plasma discharges

    SciTech Connect

    Ene, A. B.; Lindner, P.; Stirn, R.; Schumacher, U.

    2007-12-15

    Carbon containing plasmas play an important role not only in plasma technology but also in thermonuclear fusion research. In order to understand and control the processes taking place in the plasma, the knowledge of the carbon ground state density is of major importance. It can be determined by absorption and emission spectroscopy. Detailed measurements were performed in the past to determine the silicon ground state density by means of spectroscopy of the self-absorbed spectral lines of the silicon ground state multiplet at 251 nm. The same procedure was applied for the determination of the carbon concentration, for which the carbon multiplet at 165 nm was analyzed and compared to a simulated spectrum. The ground state density was determined by two independent methods.

  18. Plasma gamma-hexachlorocyclohexane concentrations in forestry workers exposed to lindane.

    PubMed Central

    Drummond, L; Gillanders, E M; Wilson, H K

    1988-01-01

    Plasma gamma-hexachlorocyclohexane (gamma-HCH) and three urinary trichlorophenols were measured in forestry workers who were engaged in planting seedlings treated with gamma-HCH. These two procedures were assessed as potential biological monitoring methods and the data were compared with reported clinical symptoms. The measurement of plasma gamma-HCH was considered to be a feasible and valid monitoring method for use in routine practice and is a useful indicator of gamma-HCH absorption. The data were used to illustrate the need to be vigilant about personal hygiene and the efficacy of protective clothing. Plasma gamma-HCH concentrations above 70 nmol/l were measured in two workers which coincided with persistent non-specific clinical symptoms. Trichlorophenols were identified in urine but the extensive and variable metabolism of gamma-HCH makes this approach less suitable for biological monitoring. PMID:2456092

  19. Reflex sympathetic dystrophy: the significance of differing plasma catecholamine concentrations in affected and unaffected limbs.

    PubMed

    Drummond, P D; Finch, P M; Smythe, G A

    1991-10-01

    In 26 patients with features of reflex sympathetic dystrophy, venous blood was collected from painful and unaffected limbs. Levels of plasma adrenaline, noradrenaline and its intracellular metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG), were measured by combined gas chromatography/mass spectrometry. Plasma DHPG was lower on the painful side. Concentration of plasma noradrenaline was also lower on the painful side in patients with widespread allodynia, and in those with hyperhidrosis in the affected hand or foot. These findings do not support the widely held view that autonomic disturbances in reflex sympathetic dystrophy are due to sympathetic overactivity. Rather, they suggest that sweating and changes in peripheral blood flow result from supersensitivity to sympathetic neurotransmitters. After injury, supersensitivity to noradrenaline may also contribute to spontaneous pain and allodynia by disrupting efferent sympathetic modulation of sensation. This would explain why pain and allodynia are relieved by sympathetic blockade, and why noradrenaline rekindles pain in sympathectomized skin. PMID:1933231

  20. Effects of major depression, aging and gender upon calculated diurnal free plasma cortisol concentrations: a re-evaluation study.

    PubMed

    Deuschle, M; Weber, B; Colla, M; Depner, M; Heuser, I

    1998-12-01

    Depression, aging and female gender are associated with increased diurnal concentrations of total plasma cortisol. For the physical effects of hypercortisolemia, however, it is generally assumed that free rather than total plasma cortisol concentrations are of importance. Herein, we report a mathematical approach to determine free plasma cortisol concentrations on the basis of total cortisol, corticosteroid binding-globulin (CBG) and albumin plasma concentrations. This approach was used to re-evaluate two sets of data in order to estimate the effect of depression as well as the effect of aging and gender upon free plasma cortisol concentrations. Comparing male depressed patients with healthy controls, we found 24-hour free cortisol minima (MIN: 4.1 +/- 1.8 vs. 1.6 +/- 1.1 nmol/l, p < 0.0001), mean (MEAN: 25.5 +/- 6.7 vs. 10.4 +/- 2.7 nmol/l, p < 0.0001) and maximal (MAX: 85.3 +/- 23.3 vs. 45.2 +/- 15. 8 nmol/l, p < 0.0001) concentrations to be significantly increased in depressed patients. In general, the impact of depression upon total plasma cortisol were not only maintained, but stronger regarding free plasma cortisol. Also, age was associated with free plasma cortisol MIN (F1,30= 10.8, p < 0.003) and free plasma cortisol MEAN (F1,30 = 8.9, p < 0.006). All effects of age upon total plasma cortisol were generally also found in free plasma cortisol, though with less impact. No effect of gender upon any of the given free plasma cortisol outcome variables was found. Taken together, our re-evaluation clearly shows not only depression but also aging to be associated with increases in free plasma cortisol concentrations. This finding is in line with the observation that in both conditions medical problems triggered and/or maintained by glucocorticoids (e.g. osteoporosis) are frequently seen.

  1. Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children.

    PubMed

    Carson, D S; Berquist, S W; Trujillo, T H; Garner, J P; Hannah, S L; Hyde, S A; Sumiyoshi, R D; Jackson, L P; Moss, J K; Strehlow, M C; Cheshier, S H; Partap, S; Hardan, A Y; Parker, K J

    2015-09-01

    The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=-0.92, P=0.0262, N=10) and CSF (r=-0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.

  2. Electronic Cigarettes Are a Source of Thirdhand Exposure to Nicotine

    PubMed Central

    Lee, Lily

    2015-01-01

    Introduction: Substances remaining on the surfaces in areas where people have smoked contribute to thirdhand exposure. Nicotine from tobacco smoke has been shown to react with oxidizing chemicals in the air to form secondary pollutants, such as carcinogenic nitrosamines. While prev ious studies have demonstrated thirdhand exposure to nicotine from tobacco smoke, none have investigated whether nicotine from electronic cigarettes (e-cigarettes) can also be deposited on various surfaces. Methods: Three brands of e-cigarettes were refilled with varying nicotine concentrations. We released 100 puffs from each product directly into an exposure chamber. Surface wipe samples were taken from 5 indoor 100cm2 surfaces (window, walls, floor, wood, and metal) pre- and post-release of vapors. Nicotine was extracted from the wipes and was analyzed using gas chromatography. Results: Three of the 4 experiments showed significant increases in the amount of nicotine on all five surfaces. The floor and glass windows had the greatest increases in nicotine, on average by a factor of 47 and 6, respectively (p < .05). The average amount of nicotine deposited on a floor during each experiment was 205 μg/m2 and varied from limit of quantitation to 550 μg/m2. Conclusions: This study indicates that there is a risk for thirdhand exposure to nicotine from e-cigarettes. Thirdhand exposure levels differ depending on the surface and the e-cigarette brand. Future research should explore the potential risks of thirdhand exposure to carcinogens formed from the nicotine that is released from e-cigarettes. PMID:25173774

  3. Toxicity of aerosols of nicotine and pyruvic acid (separate and combined) in Sprague-Dawley rats in a 28-day OECD 412 inhalation study and assessment of systems toxicology.

    PubMed

    Phillips, Blaine; Esposito, Marco; Verbeeck, Jan; Boué, Stéphanie; Iskandar, Anita; Vuillaume, Gregory; Leroy, Patrice; Krishnan, Subash; Kogel, Ulrike; Utan, Aneli; Schlage, Walter K; Bera, Monali; Veljkovic, Emilija; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2015-01-01

    Toxicity of nebulized nicotine (Nic) and nicotine/pyruvic acid mixtures (Nic/Pyr) was characterized in a 28-day Organization for Economic Co-operation and Development 412 inhalation study with additional transcriptomic and lipidomic analyses. Sprague-Dawley rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, saline, nicotine (50 µg/l), sodium pyruvate (NaPyr, 33.9 µg/l) or equimolar Nic/Pyr mixtures (18, 25 and 50 µg nicotine/l). Saline and NaPyr caused no health effects, but rats exposed to nicotine-containing aerosols had decreased body weight gains and concentration-dependent increases in liver weight. Blood neutrophil counts were increased and lymphocyte counts decreased in rats exposed to nicotine; activities of alkaline phosphatase and alanine aminotransferase were increased, and levels of cholesterol and glucose decreased. The only histopathologic finding in non-respiratory tract organs was increased liver vacuolation and glycogen content. Respiratory tract findings upon nicotine exposure (but also some phosphate-buffered saline aerosol effects) were observed only in the larynx and were limited to adaptive changes. Gene expression changes in the lung and liver were very weak. Nic and Nic/Pyr caused few significant changes (including Cyp1a1 gene upregulation). Changes were predominantly related to energy metabolism and fatty acid metabolism but did not indicate an obvious toxicity-related response. Nicotine exposure lowered plasma lipids, including cholesteryl ester (CE) and free cholesterol and, in the liver, phospholipids and sphingolipids. Nic, NaPyr and Nic/Pyr decreased hepatic triacylglycerol and CE. In the lung, Nic and Nic/Pyr increased CE levels. These data suggest that only minor biologic effects related to inhalation of Nic or Nic/Pyr aerosols were observed in this 28-day study.

  4. Resistin in Dairy Cows: Plasma Concentrations during Early Lactation, Expression and Potential Role in Adipose Tissue

    PubMed Central

    Reverchon, Maxime; Ramé, Christelle; Cognié, Juliette; Briant, Eric; Elis, Sébastien; Guillaume, Daniel; Dupont, Joëlle

    2014-01-01

    Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA) levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6) in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase) in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro. PMID:24675707

  5. Resistin in dairy cows: plasma concentrations during early lactation, expression and potential role in adipose tissue.

    PubMed

    Reverchon, Maxime; Ramé, Christelle; Cognié, Juliette; Briant, Eric; Elis, Sébastien; Guillaume, Daniel; Dupont, Joëlle

    2014-01-01

    Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA) levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6) in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase) in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro. PMID:24675707

  6. An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma

    PubMed Central

    Xu, Huixin; Jiang, Haojun; Xie, Weiwei; Chen, Fang; Zeng, Peng; Li, Xuchao; Xie, Yifan; Liu, Hongtai; Huang, Guodong; Chen, Dayang; Liu, Ping; Jiang, Hui; Zhang, Xiuqing

    2016-01-01

    Background With the speedy development of sequencing technologies, noninvasive prenatal testing (NIPT) has been widely applied in clinical practice for testing for fetal aneuploidy. The cell-free fetal DNA (cffDNA) concentration in maternal plasma is the most critical parameter for this technology because it affects the accuracy of NIPT-based sequencing for fetal trisomies 21, 18 and 13. Several approaches have been developed to calculate the cffDNA fraction of the total cell-free DNA in the maternal plasma. However, most approaches depend on specific single nucleotide polymorphism (SNP) allele information or are restricted to male fetuses. Methods In this study, we present an innovative method to accurately deduce the concentration of the cffDNA fraction using only maternal plasma DNA. SNPs were classified into four maternal-fetal genotype combinations and three boundaries were added to capture effective SNP loci in which the mother was homozygous and the fetus was heterozygous. The median value of the concentration of the fetal DNA fraction was estimated using the effective SNPs. A depth-bias correction was performed using simulated data and corresponding regression equations for adjustments when the depth of the sequencing data was below 100-fold or the cffDNA fraction is less than 10%. Results Using our approach, the median of the relative bias was 0.4% in 18 maternal plasma samples with a median sequencing depth of 125-fold. There was a significant association (r = 0.935) between our estimations and the estimations inferred from the Y chromosome. Furthermore, this approach could precisely estimate a cffDNA fraction as low as 3%, using only maternal plasma DNA at the targeted region with a sequencing depth of 65-fold. We also used PCR instead of parallel sequencing to calculate the cffDNA fraction. There was a significant association (r = 98.2%) between our estimations and those inferred from the Y chromosome. PMID:27662469

  7. Technical note: Effect of determining baseline plasma urea nitrogen concentrations on subsequent posttreatment plasma urea nitrogen concentrations in 20- to 50-kilogram pigs.

    PubMed

    Waguespack, A M; Powell, S; Roux, M L; Frugé, E D; Bidner, T D; Payne, R L; Southern, L L

    2011-12-01

    Plasma urea N (PUN) has been used as an indicator of AA requirements and efficiency of AA utilization in swine. However, PUN concentrations vary among a population of pigs, even a population with a close range of BW and fed the same diet. Thus, pretreatment or baseline PUN concentrations are used as a covariate to reduce variation of posttreatment PUN. However, this procedure increases experimental costs and stress to the pigs. Data from 14 experiments (26 to 28 d in duration) conducted using PUN as a response variable were compiled into 1 data set. Each experiment had 4 to 6 treatments. The purpose of this technical report was to summarize the effect of determining pretreatment baseline PUN concentrations on subsequent posttreatment PUN concentrations in 20- to 50-kg pigs. In all experiments, pigs were fed corn- and soybean meal-based diets and low-CP diets with various AA additions; pigs were assigned to dietary treatments in a randomized complete block design with a minimum of 4 replicates of 3 to 5 pigs each. Before the start of each experiment, all pigs were fed a common diet for a minimum of 3 d. Blood samples were collected from each pig before allotment to dietary treatments (d 0) and at the end of each experiment. The baseline (d 0) PUN was analyzed as a covariate for posttreatment PUN. Data from each experiment were analyzed without and with baseline PUN in the statistical model. In all experiments combined, there were 768 possible treatment comparisons. The covariate baseline PUN was statistically significant (P < 0.10) in 9 of 14 experiments. However, only 8 treatment differences changed statistical significance as a result of analyzing the data with baseline PUN as a covariate. These 8 treatment differences were in 3 experiments. These results indicate that it is not always necessary to determine baseline PUN concentrations when feeding diets with large differences in AA content.

  8. A simple pharmacokinetic model linking plasma progesterone concentrations with the hormone released from bovine intravaginal inserts.

    PubMed

    Mariano, R N; Turino, L N; Cabrera, M I; Scándolo, D E; Maciel, M G; Grau, R J A

    2010-10-01

    On the basis of pharmacokinetic modeling, this study provides some insights into predicting in vivo plasma progesterone concentrations when using bovine intravaginal inserts for systemic progesterone delivery. More significantly, this contribution is the first attempt to build a simple pharmacokinetic model that links plasma progesterone concentrations with the hormone released from bovine intravaginal inserts. After evaluating three rival pharmacokinetic models and considering some phenomena involved in the intravaginal administration of progesterone, a primary pharmacokinetic model having a good data fitting capability with only two adjustable parameters is proposed to the above mentioned task. Kinetic parameters are given for lactating Holstein dairy cows with two levels of daily milk yields; and non-pregnant, non-lactating Holstein-Friesian cattle. Model predictions indicate the occurrence of a preferential distribution of the intravaginally administered progesterone dose through a first uterine pass effect.

  9. Plasma osmotic and electrolyte concentrations of largemouth bass from some acidic Florida lakes

    SciTech Connect

    Canfield, D.E. Jr.; Maceina, M.J.; Nordlie, F.G.; Shireman, J.V.

    1985-05-01

    Five acidic clear (pH 3.7-4.9), three acidic colored (pH 4.1-4.6), and three neutral (pH 6.9-7.3) north-central Florida lakes were surveyed in 1983 to determine plasma osmotic and electrolyte concentrations, growth, and coefficients of condition for largemouth bass Micropterus salmoides floridanus. Plasma osmotic concentrations averaged greater than 273 milliosmoles/kg in fish from acidic colored and circumneutral lakes, but averaged less than 269 milliosmoles/kg in four of the acidic clear lakes. Growth and coefficients of condition of largemouth bass > 305 mm total length in the acidic lakes were significantly lower than in the neutral lakes. Reductions in fish growth and condition, however, could be related to either acidic conditions or lake trophic status. 29 references, 3 tables.

  10. Plasma and urine diketopiperazine concentrations in normal adults ingesting large quantities of aspartame.

    PubMed

    Cho, E S; Coon, J D; Stegink, L D

    1987-07-01

    In aqueous solution, aspartame can cyclicize to form its corresponding diketopiperazine (3-carboxymethyl-6-benzyl-2,5-diketopiperazine; DKP) and methanol. We measured plasma and urinary concentrations of DKP in samples obtained from six normal adult subjects ingesting 2.2 mg DKP/kg body weight. The DKP was administered as part of a dose of 200 mg aspartame/kg body weight. DKP concentrations in plasma were below the detection limit (less than 1 microgram/ml) of the high-pressure liquid chromatographic method at each time interval after ingestion at which they were measured. Mean (+/- SD) total urinary DKP excreted during the first 24-hr period after dosing was 6.68 +/- 1.30 mg (4.83 +/- 0.23% of the ingested DKP dose). Approximately 44% of the total DKP excreted was excreted in the first 4 hr after dosing.

  11. Nicotine elicits methamphetamine-seeking in rats previously administered nicotine.

    PubMed

    Neugebauer, N M; Harrod, S B; Bardo, M T

    2010-01-01

    Research has indicated a high correlation between psychostimulant use and tobacco cigarette smoking in human substance abusers. The objective of the current study was to examine the effects of acute and repeated nicotine administration on responding for intravenous methamphetamine (0.03 mg/kg/infusion) in a rodent model of self-administration, as well as the potential of nicotine to induce reinstatement of previously extinguished drug-taking behavior in male Sprague-Dawley rats. In addition, it was assessed whether nicotine-induced reinstatement of methamphetamine-seeking behavior and nicotine-induced locomotor sensitization require that nicotine be temporally paired with the methamphetamine self-administration session or the locomotor activity chamber. Nicotine acutely decreased methamphetamine self-administration, but did not persistently alter responding during the maintenance of methamphetamine self-administration. However, following extinction of methamphetamine self-administration, nicotine administration reinstated methamphetamine-seeking behavior only in rats that had previously been administered nicotine. Nicotine-induced reinstatement and expression of locomotor sensitization were not dependent on a temporal pairing of nicotine with either the methamphetamine self-administration session or the locomotor activity chamber, respectively. These results indicate that nicotine may be acting, at least in part, through a non-associative mechanism to reinstate methamphetamine-seeking behavior.

  12. Association between dietary factors and plasma fetuin-A concentrations in the general population.

    PubMed

    Nimptsch, Katharina; Janke, Jürgen; Pischon, Tobias; Linseisen, Jakob

    2015-10-28

    Circulating fetuin-A, a novel marker for hepatic fat accumulation, has been related to a higher risk of type 2 diabetes and cardiovascular diseases in a growing number of prospective studies. However, little is known about dietary determinants of fetuin-A concentrations in the general population. Therefore, we aimed to investigate the association between dietary intake of energy, energy-providing nutrients, alcohol and major food groups and plasma fetuin-A concentrations in the Bavarian Food Consumption Survey II. Dietary intake was assessed by three 24-h dietary recalls, and plasma concentrations of fetuin-A were measured in 558 adults (18-81 years). After multivariable adjustment for lifestyle factors and body fatness, higher energy intake was nonsignificantly associated with higher fetuin-A concentrations (per 2092 kJ/d (500 kcal/d) 3·7 µg/ml, 95 % CI -0·5, 7·8 µg/ml). There was no clear association between energy-providing nutrients and fetuin-A concentrations. Higher alcohol intake was associated with lower fetuin-A concentrations (P trend 0·003): mean fetuin-A concentrations were 324 (95 % CI 313, 335) µg/ml in non-drinkers, and with 293 (95 % CI 281, 306) µg/ml significantly lower in participants who drank ≥30 g alcohol per d. Mean fetuin-A concentrations decreased across quintiles of milk and dairy product intake (lowest quintile 319 (95 % CI 309, 330) µg/ml; highest quintile 304 (95 % CI 293, 314) µg/ml; P trend 0·03), and each 150-g increment in milk/dairy products per d was associated with 5·6 (95 % CI -9·6, -1·5) µg/ml lower fetuin-A. Dietary intakes of vegetables, meat or fish were not associated with fetuin-A concentrations. Because of the preventive potential of our findings, further exploration is warranted. PMID:26316198

  13. Plasma Drug Concentrations of Orally Administered Rosuvastatin in Hispaniolan Amazon Parrots (Amazona ventralis).

    PubMed

    Beaufrère, Hugues; Papich, Mark G; Brandão, João; Nevarez, Javier; Tully, Thomas N

    2015-03-01

    Atherosclerotic diseases are common in pet psittacine birds, in particular Amazon parrots. While hypercholesterolemia and dyslipidemia have not definitely been associated with increased susceptibility to atherosclerosis in parrots, these are important and well-known risk factors in humans. Therefore statin drugs such as rosuvastatin constitute the mainstay of human treatment of dyslipidemia and the prevention of atherosclerosis. No pharmacologic studies have been performed in psittacine birds despite the high prevalence of atherosclerosis in captivity. Thirteen Hispaniolan Amazon parrots were used to test a single oral dose of 10 mg/kg of rosuvastatin with blood sampling performed according to a balanced incomplete block design over 36 hours. Because low plasma concentrations were produced in the first study, a subsequent pilot study using a dose of 25 mg/kg in 2 Amazon parrots was performed. Most plasma samples for the 10 mg/kg dose and all samples for the 25 mg/kg dose had rosuvastatin concentration below the limits of quantitation. For the 10 mg/kg study, the median peak plasma concentration and time to peak plasma concentration were 0.032 μg/mL and 2 hours, respectively. Our results indicate that rosuvastatin does not appear suitable in Amazon parrots as compounded and used at the dose in this study. Pharmacodynamic studies investigating lipid-lowering effects of statins rather than pharmacokinetic studies may be more practical and cost effective in future studies to screen for a statin with more ideal properties for potential use in psittacine dyslipidemia and atherosclerotic diseases.

  14. Modifications of plasma 5-HT concentrations during the allergic bronchoconstriction in guinea pigs.

    PubMed

    Arreola-Ramírez, José Luis; Vargas, Mario H; Manjarrez-Gutiérrez, Gabriel; Alquicira, Jesús; Gutiérrez, Julio; Córdoba, Guadalupe; Campos-Bedolla, Patricia; Segura-Medina, Patricia

    2013-09-01

    Several contractile mediators involved in the antigen-induced airway obstruction have been identified, but the role of 5-HT (5-hydroxytryptamine or serotonin) has been scantily investigated. In this work, the potential role of 5-HT in the allergic bronchoconstriction was evaluated through a pharmacological approach and plasma 5-HT measurement in blood samples from the right and left ventricles of anesthetized guinea-pigs. Intravenous 5-HT caused a dose-dependent increase of the lung resistance in anesthetized, nonsensitized guinea pigs. Likewise, in sensitized animals the antigenic challenge with ovalbumin also caused a transient bronchoconstriction (356 ± 60% the basal value), which was largely inhibited by the blockade of serotonergic receptors with methiothepin plus tropisetron (134 ± 10%, P = .007). Sensitized animals tended to have plasma 5-HT concentrations higher than nonsensitized controls, and shortly after the peak of the allergic bronchoconstriction the 5-HT levels in the left ventricle (blood flowing out from lungs) tended to be higher than in the right ventricle (blood entering the lungs), although data dispersion precluded the obtaining of statistical significance. Interestingly, the degree of bronchoconstriction highly correlated with the concentrations of 5-HT found in the left ventricle and measured either in platelet-rich plasma (r = 0.97 P = .007) or platelet-poor plasma (r = 0.97, P = .006). After the obstructive response subsided these correlations were lost, but now the degree of bronchoconstriction turned to be correlated with 5-HT concentration in platelet concentrate (r = 0.76, P = .03). In conclusion, our results suggested that 5-HT is actively released from lungs during the antigenic challenge and that this autacoid is involved in the generation of the airway obstruction.

  15. Effects of Hypergravity Exposure on Plasma Oxytocin (OT) Concentrations in Pregnant and Lactating Rat Dams

    NASA Technical Reports Server (NTRS)

    Baer, Lisa A.; Wade, Charles E.; Plaut, Karen; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    From pregnancy to weaning there is a progressive elevation of plasma oxytocin (OT) levels associated with nursing activity, irrespective of litter size. In the present study, we analyzed the effects of continuous 1.5G, 1.75G and 2.0G hypergravity exposure on OT plasma concentration in prepartum (Gestation Day 20) (G20) and lactating (Postnatal day) (P10) rat dams. For this study, litter size was controlled with a yoking procedure established in our lab where individual control litters were yoked-matched to individual hypergravity litters. We reviewed all data at hypergravity irrespective of gravitational level and compared the values with the controls in both G20 (HG, n=15;SC, n=9) and P10 (HG, n=21;SC, n=16). Results showed that over time, we did observe the expected OT increase in both groups. In G20 dams, measurement of OT concentrations showed no significance. However, at P10, measurements of OT concentrations suggest a reduction of about 20% compared to established controls in our laboratory, 0.9+/-0.09 ng/ml for the controls and 0.7+/-0.06 ng/ml for centrifuged animals (p<0.02). These data suggest that exposure to centrifugation may reduce OT levels during lactation. When these plasma samples were obtained, the dams were removed from the litters, and values were not adjusted for the size of the litters. The reduction in OT with centrifugation may reflect a decrease in nursing activity or a decreased responsiveness of the mammary hypothalamic axis. In addition, we have analyzed data on plasma prolactin concentrations and mammary gland development, which may give additional insight to the results of our OT measurements.

  16. Adherence to a Mediterranean diet and plasma concentrations of lipid peroxidation in premenopausal women123

    PubMed Central

    Gaskins, Audrey J; Rovner, Alisha J; Mumford, Sunni L; Yeung, Edwina; Browne, Richard W; Trevisan, Maurizio; Perkins, Neil J; Wactawski-Wende, Jean; Schisterman, Enrique F

    2010-01-01

    Background: A Mediterranean diet has been associated with a reduced risk of cardiovascular disease and mortality. A possible mechanism is through a decrease in lipid peroxidation (LPO); however, evidence linking the Mediterranean diet with lower LPO in premenopausal women is sparse. Objective: We investigated whether adherence to a Mediterranean diet was associated with lower LPO concentrations in premenopausal women. Design: Two hundred fifty-nine healthy women aged 18–44 y were followed for ≤2 menstrual cycles. Plasma concentrations of F2-isoprostane (8-iso-PGF2α), 9-hydroxyoctadecadieneoic acid (9-HODE), and thiobarbituric acid reactive substances (TBARS) were measured ≤8 times per cycle at visits scheduled by using fertility monitors. Diet was assessed ≤4 times per cycle by using 24-h dietary recalls. The alternate Mediterranean Diet Score (aMED) (range: 0–9) was calculated on the basis of intake of vegetables, legumes, fruit, nuts, whole grains, red and processed meat, fish, and alcohol and the ratio of monounsaturated to saturated fat. Results: A 1-unit increase in aMED was associated with a 4.50% decrease in 8-iso-PGF2α concentrations (95% CI: −6.32%, −2.65%) and a 14.01% decrease in 9-HODE concentrations (95% CI: −17.88%, −9.96%) after adjustment for energy intake, age, race, body mass index, plasma ascorbic acid, and serum cholesterol. No significant association was observed between aMED and TBARS. A 1-unit increase in aMED was associated with a 1.39% increase (95% CI: 0.07%, 2.72%) in plasma ascorbic acid concentrations. Conclusions: Adherence to a Mediterranean diet is associated with lower LPO and higher ascorbic acid concentrations. These results confirm that decreased LPO is a plausible mechanism linking a Mediterranean diet to reduced cardiovascular disease risk. PMID:20943796

  17. Evidence that plasma concentration rather than dose per kilogram body weight predicts ribavirin-induced anaemia.

    PubMed

    Lindahl, K; Schvarcz, R; Bruchfeld, A; Ståhle, L

    2004-01-01

    Ribavirin in combination with interferon alpha-2 or pegylated interferon is the standard treatment for chronic hepatitis C. The current dosage recommendations for ribavirin are based on body weight (bw). Ribavirin is mainly eliminated by the kidneys and we have recently shown that ribavirin plasma concentrations are determined primarily by renal function. It is therefore reasonable to hypothesize that side-effects of ribavirin, i.e. anaemia, should be more closely related to plasma concentrations of ribavirin than to the dose per kg bw. A total of 108 consecutive patients eligible for treatment of chronic hepatitis C were studied. Ribavirin concentrations in plasma were measured by high-performance liquid chromatography (HPLC)-UV after solid-phase extraction in trough samples taken 4, 8 and 12 weeks after the treatment commenced. A total of 213 samples were obtained and the change in the haemoglobin level and the creatinine concentration was measured in addition to ribavirin. The dose of ribavirin per kg bw did not correlate with the drop in haemoglobin level induced by ribavirin. The concentration of ribavirin was non-linearly related to the drop in the haemoglobin level as revealed by fitting a standard Hill equation type dose-response curve. The half maximal drop in haemoglobin was obtained at 4.4 microm. The results from this study suggest that the anaemia induced by ribavirin depends primarily on the concentration of ribavirin, and not on the dose per kg bw. This lends further support to the idea that ribavirin should be dosed according to renal function.

  18. Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats

    PubMed Central

    Vigna, Steven R.

    2016-01-01

    Nicotine is protective in ulcerative colitis but not Crohn's disease of the small intestine, but little is known about the effects of nicotine on Clostridium difficile toxin A-induced enteritis. Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B4 (LTB4), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB4. PMID:26881175

  19. Effect of extracorporeal shockwave lithotripsy on plasma and urine endothelin concentrations.

    PubMed

    Esen, A A; Gezer, S; Gemalmaz, A; Kirkali, G; Kirkali, Z

    1996-08-01

    Since the first reports of extracorporeal shockwave lithotripsy (SWL), there have been increasing numbers of articles in the literature documenting renal blood flow impairment and blood pressure elevation as complications. However, little is known about the pathophysiology and prevention of these complications. In this prospective study, the influence of high-energy shockwaves on plasma and urine endothelin concentrations was investigated in 20 patients with renal stones. The patients were randomly assigned to receive a calcium channel blocker, 10 mg of nitrendipine (Bypress; Bayer) (N = 10) 2 hours before SWL or no medication (control group; N = 10). Blood samples were taken just before and 1 minute after application of 3000 shocks. Urine samples were collected by ureteral catheters. The plasma endothelin-1 concentrations were significantly elevated after SWL in the control group (P = 0.003). On the other hand, nitrendipine significantly reduced plasma endothelin concentrations after SWL (P = 0.003). No significant change was observed in urine samples and blood pressure measurements. These results suggest that endothelin release after SWL may be a cause for lithotripsy-induced hemodynamic changes. Medical prevention with calcium channel blockers warrants further investigation.

  20. Plasma membrane calcium ATPase is concentrated in the head of sea urchin spermatozoa.

    PubMed

    Gunaratne, Herath Jayantha; Neill, Anna T; Vacquier, Victor D

    2006-05-01

    Plasma membrane Ca2+ATPases (PMCAs) export Ca2+ from cells in a highly regulated manner, providing fine-tuning to the maintenance of intracellular Ca2+ concentrations. There are few studies of PMCAs in spermatozoa, which is surprising considering the importance of this enzyme in all cell types. Here we describe the primary structure and localization of the PMCA of sea urchin spermatozoa (suPMCA). The suPMCA is 1,154 amino acids and has 56% identity and 76% similarity to all 4 human PMCA isoforms. The suPMCA shares the features of a typical PMCA, including domains for calmodulin binding, ATP binding, ATPase phosphorylation, and 10 putative transmembrane segments with two large cytoplasmic loops. Southern blots show that suPMCA is a single copy gene. Treatment of live sea urchin sperm with the PMCA inhibitor, 5-(-6)-carboxyeosin, results in elevations of intracellular Ca2+ and loss of flagellar motility. Immunoblotting and immunoflorescence show that suPMCA is concentrated in the sperm head plasma membrane. In previous work, we showed that a plasma membrane K+ dependent Na+/Ca2+ exchanger (suNCKX), which also keeps Ca2+ low in these cells, is concentrated in the sperm flagellum. Thus, the sperm head and flagellum localize different gene products, both functioning to keep intracellular Ca2+ low, while the sperm swims in seawater containing 10 mM Ca2+. PMID:16358326

  1. Aging effect on plasma metabolites and hormones concentrations in riding horses

    PubMed Central

    Kawasumi, K.; Yamamoto, M.; Koide, M.; Okada, Y.; Mori, N.; Yamamoto, I.; Arai, T.

    2015-01-01

    Age effects on plasma metabolites, hormone concentrations, and enzyme activities related to energy metabolism were investigated in 20 riding horses. Animals were divided into two groups: Young (3-8 years) and aged (11-18 years). They were clinically healthy, and not obese. Plasma adiponectin (ADN) concentrations in aged horses were significantly lower than those in young horses (mean±SE, 6.5±1.3 µg mL-1 vs, 10.9±1.7 µg mL-1, Mann-Whitney U test, respectively; P=0.0233). Plasma non-esterified fatty acid levels and Insulin and malondialdehyde concentrations in aged group tended to increase compared to those in young group although there were not significant differences statistically. In aged group, malate dehydrogenase/lactate dehydrogenase (M/L) ratio, which is considered an energy metabolic indicator, did not change significantly compared to that in young group. Present data suggest that aging may negatively affect nutrition metabolism, but not induce remarkable changes in M/L ratio in riding horses. PMID:26623382

  2. Organophosphorus insecticide induced decrease in plasma luteinizing hormone concentration in white-footed mice

    USGS Publications Warehouse

    Rattner, B.A.; Michael, S.D.

    1985-01-01

    Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days substantially inhibited brain AChE activity, but did not affect plasma LH concentration. These preliminary findings suggest that acute exposure to organophosphorus insecticides may affect LH secretion and possibly reproductive function.

  3. Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

    SciTech Connect

    Biegon, A.; Biegon, A.; Kim, S.-W.; Logan, J.; Hooker, J.M.; Muench, L.; Fowler, J.S.

    2010-01-12

    Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor [{sup 11}C]vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Nicotine administration produced significant, dose-dependent reductions in [{sup 11}C]vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.

  4. Plasma volumes, blood volumes, and plasma protein concentrations after moderate haemodilution with fluosol-DA or normal saline in the rat.

    PubMed

    Shrewsbury, R P

    1991-05-01

    Plasma volumes, blood volumes, and plasma total protein, albumin, and bilirubin concentrations have been determined in rats for 72 h following 20 or 40 mL kg-1 haemodilution with Fluosol-DA or 0.9% NaCl. Haemodilution with 20 mL kg-1 of either haemodiluent had no influence on the measured values. Plasma and blood volumes did not change after Fluosol-DA haemodilution at 40 mL kg-1, but albumin and bilirubin concentrations were decreased for 72 h. Only bilirubin concentrations were decreased for 72 h following haemodilution with 40 mL kg-1 of 0.9% NaCl. It was concluded that changes in a drug's plasma protein binding, and not the plasma or blood volume, are responsible for the reported alterations in a drug's apparent volume of distribution after haemodilution.

  5. Factors affecting the plasma insulin concentration shortly after accidental injury in man.

    PubMed Central

    Frayn, K N; Maycock, P F; Little, R A; Yates, D W; Stoner, H B

    1987-01-01

    There are conflicting reports on plasma insulin concentrations in the acutely injured. Plasma insulin and glucose concentrations have been measured in 504 patients within 8 h of injury, and related to the severity of injury as assessed by the injury severity score (ISS). As in previous surveys of injured patients, an extremely wide range of insulin concentrations was found (2-141 mU/l). Most of the variability occurred at lower severities of injury. In very severely injured patients (ISS greater than or equal to 30), insulin concentrations were uniformly suppressed (less than 20 mU/l), especially in relation to the hyperglycaemia in these patients. Two small subgroups, patients dying within 3 h of injury and known psychiatric patients on psycho-active drugs, differed from the general pattern in displaying elevated insulin concentrations despite very severe injuries. The results bear out the idea that insulin secretion is usually acutely suppressed by adrenaline after severe injury; after less severe injuries, however, the response is much less uniform. PMID:3304325

  6. Molybdenum-Containing Nicotine Hydroxylase Genes in a Nicotine Degradation Pathway That Is a Variant of the Pyridine and Pyrrolidine Pathways

    PubMed Central

    Yu, Hao; Li, Yangyang

    2015-01-01

    Ochrobactrum sp. strain SJY1 utilizes nicotine as a sole source of carbon, nitrogen, and energy via a variant of the pyridine and pyrrolidine pathways (the VPP pathway). Several strains and genes involved in the VPP pathway have recently been reported; however, the first catalyzing step for enzymatic turnover of nicotine is still unclear. In this study, a nicotine hydroxylase for the initial hydroxylation step of nicotine degradation was identified and characterized. The nicotine hydroxylase (VppA), which converts nicotine to 6-hydroxynicotine in the strain SJY1, is encoded by two open reading frames (vppAS and vppAL [subunits S and L, respectively]). The vppA genes were heterologously expressed in the non-nicotine-degrading strains Escherichia coli DH5α and Pseudomonas putida KT2440; only the Pseudomonas strain acquired the ability to degrade nicotine. The small subunit of VppA contained a [2Fe-2S] cluster-binding domain, and the large subunit of VppA contained a molybdenum cofactor-binding domain; however, an FAD-binding domain was not found in VppA. Resting cells cultivated in a molybdenum-deficient medium had low nicotine transformation activity, and excess molybdenum was detected in the purified VppA by inductively coupled plasma-mass spectrometry analysis. Thus, it is demonstrated that VppA is a two-component molybdenum-containing hydroxylase. PMID:26407884

  7. Molybdenum-containing nicotine hydroxylase genes in a nicotine degradation pathway that is a variant of the pyridine and pyrrolidine pathways.

    PubMed

    Yu, Hao; Tang, Hongzhi; Li, Yangyang; Xu, Ping

    2015-12-01

    Ochrobactrum sp. strain SJY1 utilizes nicotine as a sole source of carbon, nitrogen, and energy via a variant of the pyridine and pyrrolidine pathways (the VPP pathway). Several strains and genes involved in the VPP pathway have recently been reported; however, the first catalyzing step for enzymatic turnover of nicotine is still unclear. In this study, a nicotine hydroxylase for the initial hydroxylation step of nicotine degradation was identified and characterized. The nicotine hydroxylase (VppA), which converts nicotine to 6-hydroxynicotine in the strain SJY1, is encoded by two open reading frames (vppAS and vppAL [subunits S and L, respectively]). The vppA genes were heterologously expressed in the non-nicotine-degrading strains Escherichia coli DH5α and Pseudomonas putida KT2440; only the Pseudomonas strain acquired the ability to degrade nicotine. The small subunit of VppA contained a [2Fe-2S] cluster-binding domain, and the large subunit of VppA contained a molybdenum cofactor-binding domain; however, an FAD-binding domain was not found in VppA. Resting cells cultivated in a molybdenum-deficient medium had low nicotine transformation activity, and excess molybdenum was detected in the purified VppA by inductively coupled plasma-mass spectrometry analysis. Thus, it is demonstrated that VppA is a two-component molybdenum-containing hydroxylase.

  8. Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate.

    PubMed

    Ekstrand, C; Bondesson, U; Gabrielsson, J; Hedeland, M; Kallings, P; Olsén, L; Ingvast-Larsson, C

    2015-06-01

    Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03 mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC-MS/MS. Dexamethasone was quantifiable in plasma for 8.3 ± 2.9 days (LLOQ: 0.025 μg/L) and in urine for 9.8 ± 3.1 days (LLOQ: 0.15 μg/L). Maximum observed dexamethasone concentration in plasma was 0.61 ± 0.12 μg/L and in urine 4.2 ± 0.9 μg/L. Terminal plasma half-life was 38.7 ± 19 h. Hydrocortisone was significantly suppressed for 140 h. The plasma half-life of hydrocortisone was 2.7 ± 1.3 h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 ± 0.04 μg/L, 0.95 ± 0.04 and 6.2 ± 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone.

  9. Neonatal screening for congenital hypothyroidism by measurement of plasma thyroxine and thyroid stimulating hormone concentrations.

    PubMed Central

    Griffiths, K D; Virdi, N K; Rayner, P H; Green, A

    1985-01-01

    Neonatal screening for congenital hypothyroidism was introduced in the City of Birmingham in 1980 by measuring concentrations of both thyroid stimulating hormone and thyroxine in plasma. Over two years 30 108 babies were tested. Thirty one babies were recalled because of thyroid stimulating hormone concentrations greater than 40 mU/l, of whom 12 were treated with replacement thyroxine. Six babies were found to have low thyroxine concentrations because of reduced thyroxine binding globulin and five raised thyroxine values because of increased thyroxine binding globulin. As a result of this study screening was continued with measurement of thyroid stimulating hormone only as the primary test for congenital hypothyroidism, the thyroxine value being measured only when the concentration of thyroid stimulating hormone exceeded 20 mU/l. PMID:3926078

  10. Estimation of electron concentration in plasma and plasma frequency in the vicinity of a hypersonic aircraft that moves in atmosphere and analysis of propagation frequencies of electromagnetic waves in such plasma

    NASA Astrophysics Data System (ADS)

    Fedorov, V. A.

    2016-05-01

    Electron concentration in plasma and plasma frequency are estimated for the plasma that is formed in the vicinity of a hypersonic aircraft that moves in atmosphere. The frequencies of electromagnetic waves that may propagate in plasma emerging in the vicinity of the aircraft are determined. Formulas that make it possible to analytically (rather than graphically) calculate electron concentration in plasma at altitudes of 30, 60, and 90 km are derived for two speeds. Several specific features of variations in the electron concentration in plasma depending on the above altitudes and speeds are presented. Quasi-periodic variations in the plasma concentration can be obtained using an increase and decrease in the speed of aircraft.

  11. Positive correlations of age and parity with plasma concentration of macrophage migration inhibitory factor in Japanese black cows

    PubMed Central

    KOIZUMI, Motoya; NAHAR, Asrafun; YAMABE, Ryusei; KADOKAWA, Hiroya

    2016-01-01

    Plasma Macrophage migration inhibitory factor (MIF) concentration correlates positively with age, and negatively with self-rated health in women, and optimal MIF concentration may promote proper reproductive function. This study was conducted to evaluate the hypotheses that plasma MIF concentration changes with parturition or postpartum first ovulation, and that age in months and parity correlate with plasma MIF concentration in Japanese black cows. Western blotting utilizing an anti-MIF mouse monoclonal antibody of various tissues and plasma from females indicated that MIF expression was stronger in the anterior pituitary than in other tissues. We developed a competitive EIA utilizing the same anti-MIF mouse monoclonal antibody with sufficient sensitivity and reliable performance for measuring bovine plasma samples. We then measured MIF concentrations in bovine plasma collected from 4 weeks before parturition to 4 weeks after postpartum first ovulation. There was no significant difference in plasma MIF concentration pre- and post-parturition, or before and after the postpartum first ovulation. Plasma MIF concentrations were positively correlated (P < 0.01) with parity (r = 0.703), age in months on the day of parturition (r = 0.647), and age in months on the day of the postpartum first ovulation (r = 0.553) when we used almost all data, except for that from a third-parity cow with an abnormally high plasma MIF concentration. We therefore concluded that plasma MIF concentrations may increase with age in months and parity, but do not change either before and after parturition or before and after postpartum first ovulation in Japanese black cows. PMID:26853787

  12. Nicotine Replacement Therapy: An Overview

    PubMed Central

    Wadgave, Umesh; Nagesh, L

    2016-01-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder. PMID:27610066

  13. Nicotine Replacement Therapy: An Overview.

    PubMed

    Wadgave, Umesh; Nagesh, L

    2016-07-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder.

  14. Nicotine Replacement Therapy: An Overview.

    PubMed

    Wadgave, Umesh; Nagesh, L

    2016-07-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder. PMID:27610066

  15. Nicotine Replacement Therapy: An Overview

    PubMed Central

    Wadgave, Umesh; Nagesh, L

    2016-01-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder.

  16. Arginines Plasma Concentration and Oxidative Stress in Mild to Moderate COPD

    PubMed Central

    Zinellu, Angelo; Fois, Alessandro Giuseppe; Sotgia, Salvatore; Sotgiu, Elisabetta; Zinellu, Elisabetta; Bifulco, Fabiana; Mangoni, Arduino A; Pirina, Pietro; Carru, Ciriaco

    2016-01-01

    Background Elevated plasma concentrations of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) have been observed in respiratory conditions such as asthma and cystic fibrosis. Since oxidative stress has been shown to increase the activity of arginine methylating enzymes, hence increased ADMA synthesis, and to reduce ADMA degrading enzymes, hence increased ADMA concentrations, we assessed methylated arginines concentrations in chronic obstructive pulmonary disease (COPD), a disease characterized by increased oxidative stress. Methods Plasma arginine, ADMA and symmetric dimethylarginine (SDMA), oxidative stress markers (thiobarbituric acid reactive substances, TBARS, and plasma proteins SH, PSH) and antioxidants (taurine and paraoxonase 1, PON1, activity) were measured in 43 COPD patients with mild (n = 29) or moderate (n = 14) disease and 43 age- and sex-matched controls. Results TBARS significantly increased with COPD presence and severity (median 2.93 vs 3.18 vs 3.64 μmol/L, respectively in controls, mild and moderate group, p<0.0001 by ANOVA) whereas PSH decreased (6.69±1.15 vs 6.04±0.85 vs 5.33±0.96 μmol/gr prot, p<0.0001 by ANOVA). Increased ADMA/arginine ratio, primarily due to reduced arginine concentrations, was also observed with COPD presence and severity (median 0.0067 vs 0.0075 vs 0.0100, p<0.0001 by ANOVA). In multiple logistic regression analysis, only TBARS (OR 0.44, 95% CI 0.25–0.77; p = 0.0045) and ADMA/Arginine ratio (OR 1.72, 95% CI 2.27–13.05; p = 0.02) were independently associated with COPD severity. Conclusion COPD presence and severity are associated with increased oxidative stress and alterations in arginine metabolism. The reduced arginine concentrations in COPD may offer a new target for therapeutic interventions increasing arginine availability. PMID:27479314

  17. Plasma concentrations resulting from florfenicol preparations given to pigs in their drinking water.

    PubMed

    Gutiérrez, L; Vargas, D; Ocampo, L; Sumano, H; Martinez, R; Tapia, G

    2011-09-01

    Florfenicol administered through the drinking water has been recommended as a metaphylactic antibacterial drug to control outbreaks of respiratory diseases in pigs caused by strains of Actinobacillus pleuropneumoniae and Pasteurella multocida, yet it is difficult to pinpoint in practice when the drug is given metaphylactically or therapeutically. Further, pigs are likely to reject florfenicol-medicated water, and plasma concentrations of the drug are likely to be marginal for diseases caused by Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. The reported minimal inhibitory concentration (MIC) values for these organisms show a breakpoint of 2 to 3 μg/mL. An experiment was conducted during September and October 2009. One hundred twenty healthy crossbred pigs (Landrace-Yorkshire), weighing 23 ± 6.2 kg, were used in this trial. They were randomly assigned to 5 groups, with 3 replicates of 8 animals/group. Two commercial preparations of florfenicol were administered through the drinking water at 2 concentrations (0.01 and 0.015%). Water intake was measured before and after medication, and plasma concentrations of florfenicol were determined by HPLC. Considerable rejection of florfenicol-medicated water was observed. However, plasma florfenicol concentrations were of a range sufficient for a methaphylaxis approach to preventing disease by bacteria, with MIC breakpoints of ≤ 0.25 μg/mL. Decreased efficacy as a metaphylactic medication should be expected for bacteria with MIC >0.25 μg/mL, considering the reported existence of bacteria resistant to florfenicol and the natural resistance of Streptococcus suis or E. coli to this drug.

  18. Determinants of plasma concentrations of perfluoroalkyl substances in pregnant Norwegian women

    PubMed Central

    Whitworth, KW; Ydersbond, TA; Haug, LS; Haugen, M; Knutsen, HK; Thomsen, C; Meltzer, HM; Becher, G; Sabaredzovic, A; Hoppin, JA; Eggesbø, M; Longnecker, MP

    2013-01-01

    Background Perfluoroalkyl substances (PFASs) are widespread pollutants that have been associated with adverse health effects although not on a consistent basis. Diet has been considered the main source of exposure. The aim of the present study was to identify determinants of four plasma PFASs in pregnant Norwegian women. Methods This study is based in the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Our sample included 487 women who enrolled in MoBa from 2003–2004. A questionnaire regarding sociodemographic, medical, and reproductive history was completed at 17 weeks gestation and a dietary questionnaire was completed at 22 weeks gestation. Maternal plasma samples were obtained around 17 weeks of gestation. Plasma concentrations of four PFASs (perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA)) were examined in relation to demographic, lifestyle, dietary, and pregnancy-related covariates. Predictors were identified by optimizing multiple linear regression models using Akaike’s information criterion (AIC). Results Parity was the determinant with the largest influence on plasma PFAS concentrations, with r2 between 0.09 and 0.32 in simple regression models. In optimal multivariate models, when compared to nulliparous women, parous women had 46%, 70%, 19%, and 62% lower concentrations of PFOS, PFOA, PFHxS, and PFNA respectively (p<0.001 except for PFHxS, p<0.01). In all these models, duration of breastfeeding was associated with reduced PFAS levels. PFOA showed the largest reduction from breastfeeding, with a 2–3% reduction per month of breastfeeding in typical cases. Levels of PFOS, PFOA, and PFNA increased with time since most recent pregnancy. While pregnancy-related factors were the most important predictors, diet was a significant factor explaining up to 4% of the variance. One quartile increase in estimated dietary PFAS intake

  19. Plasma catecholamine concentrations in rainbow trout (Salmo gairdneri) at rest and after anesthesia and surgery

    USGS Publications Warehouse

    Gingerich, W.H.; Drottar, K.R.

    1989-01-01

    The effects of surgery and anesthesia on concentrations of plasma epinephrine (E), norepinephrine (NE), and dopamine (DA) were investigated in rainbow trout fitted with dorsal aorta cannulae. Baseline catecholamines (CA) concentrations, established in resting rainbow trout, were 1.55 ± 0.90 ϱmol/ml (X ± SD) for E, 2.07 ± 1.26 for NE, and 1.33 ± 0.87 for DA. These values were based on the pooled analyses of five individual fish taken over seven different sampling periods. The E:NE ratio in resting fish was always less than 1.0. In a second experiment, fish were subjected to dorsal aorta cannulation and sequential blood samples were taken immediately after surgery, and 6, 24, and 48 hr later. Plasma E concentrations were 36 times greater than baseline values in the first sample; NE was 15 times greater and DA was 41 times greater. After surgery, plasma concentrations of all CAs fell rapidly but values were still higher than baseline 6 hr after surgery, then were near baseline at 24 and 48 hr after surgery. The E:NE ratio was about 3.0 immediately after surgery, dropped to 1.8 at 6 hr, and was about 1.0 at 24 and 48 hr. In a third experiment, plasma CAs were determined in a group of five animals anesthetized with tricaine methanesulfonate (100 mg/ml) to advanced anesthesia, and then allowed to recover in flowing well water over a 12-hr observation period. Plasma E and NE concentrations in the fish during early anes-thesia (1.14 ± 0.14 min) were not significantly different from preanesthesia values. During advanced anesthesia (2.31 ± 0.21 min), values for E and NE were significantly greater and continued to be elevated during the 12-hr recovery period. The E:NE ratio exceeded 1.0 during advanced anesthesia and for the rest of the experiment.

  20. Effects of using electronic cigarettes on nicotine delivery and cardiovascular function in comparison with regular cigarettes.

    PubMed

    Yan, X Sherwin; D'Ruiz, Carl

    2015-02-01

    The development of electronic cigarettes (e-cigs) has the potential to offer a less harmful alternative for tobacco users. This clinical study was designed to characterize e-cig users' exposure to nicotine, and to investigate the acute effects of e-cigs on the hemodynamic measurements (blood pressure and heart rate) in comparison with the effects of regular smoking. Five e-cigs and one Marlboro® cigarette were randomized for twenty-three participants under two exposure scenarios from Day 1 to Day 11: half-hour controlled administration and one hour ad lib use. The nicotine plasma concentrations after 1.5h of product use (C90) were significantly lower in the users of e-cigs than of Marlboro® cigarettes. The combination of glycerin and propylene glycol as the vehicle facilitated delivery of more nicotine than glycerin alone. The heart rate, systolic and diastolic blood pressure were significantly elevated after use of Marlboro® cigarettes, but the elevation was less after use of most of the e-cigs. Use of e-cigs had no impact on the exhaled CO levels, whereas the Marlboro® cigarette significantly increased the exhaled CO more than 8 times above the baseline. In conclusion, e-cigs could be a less harmful alternative for tobacco users. PMID:25460033

  1. The effects of exercise training programs on plasma concentrations of proenkephalin Peptide F and catecholamines.

    PubMed

    Kraemer, William J; Gordon, Scott E; Fragala, Maren S; Bush, Jill A; Szivak, Tunde K; Flanagan, Shawn D; Hooper, David R; Looney, David P; Triplett, N Travis; DuPont, William H; Dziados, Joseph E; Marchitelli, Louis J; Patton, John F

    2015-02-01

    To determine if exercise training alters the pattern and magnitude of plasma concentrations of proenkephalin Peptide F and epinephrine, plasma proenkephalin [107-140] Peptide F(ir) and catecholamines were examined pre-training (T-1), and after 4- (T-2), 8- (T-3), and 12-weeks (T-4) of training. 26 healthy men were matched and randomly assigned to one of three groups: heavy resistance strength training (Strength, n=9), high intensity endurance training (Endurance, n=8), or both training modalities combined (Combined, n=9). Blood was collected using a syringe with a cannula inserted into a superficial arm vein with samples collected at rest, after each 7 min stage and 5 and 15 min into recovery. With training, all groups observed shifted plasma Peptide F responses to graded exercise, where significant increases were observed at lower exercise intensities. Increases in plasma epinephrine with exercise were observed in all groups. The Combined group saw increases at 25% at T-3 and for 50% at T-2, T-3, and T-4 which was higher than T-1. The Endurance group demonstrated increases for 50% at T-1, T-2, T-3 but not at T-4. The plasma epinephrine response to graded exercise was reduced in the Strength group. Increases in plasma norepinephrine above rest were observed starting at 50% . The Strength group demonstrated a significant reduction in norepinephrine observed at 100% at T-3 and T-4. Peptide F and catecholamines responses to graded exercise can be altered by different types of physical exercise training. Simultaneous high intensity training may produce adrenal medulla exhaustion when compared to single mode training.

  2. Increased Nutrient Sensitivity and Plasma Concentrations of Enteral Hormones during Duodenal Nutrient Infusion in Functional Dyspepsia

    PubMed Central

    Bharucha, Adil E.; Camilleri, Michael; Burton, Duane D.; Thieke, Shannon L.; Feuerhak, Kelly J.; Basu, Ananda; Zinsmeister, Alan R.

    2015-01-01

    Objectives Functional dyspepsia is predominantly attributed to gastric sensorimotor dysfunctions. The contribution of intestinal chemosensitivity to symptoms is not understood. We evaluated symptoms and plasma hormones during enteral nutrient infusion and the association with impaired glucose tolerance and quality-of-life (QOL) scores in functional dyspepsia vs health. Design Enteral hormonal responses and symptoms were measured during isocaloric and isovolumic dextrose and lipid infusions into the duodenum in 30 patients with functional dyspepsia (n=27) or nausea and vomiting (n=3) and 35 healthy controls. Infusions were administered in randomized order over 120 minutes each, with a 120-minute washout. Cholecystokinin, glucose-dependent insulinotropic peptide, glucagonlike peptide 1 (GLP1), and peptide YY were measured during infusions. Results Moderate or more severe symptoms during lipid (4 controls vs 14 patients) and dextrose (1 control vs 12 patients) infusions were more prevalent in patients than controls (P≤.01), associated with higher dyspepsia symptom score (P=.01), worse QOL (P=.01), and greater plasma hormone concentrations (eg, GLP1 during lipid infusion). Moderate or more severe symptoms during enteral infusion explained 18%, and depression score explained 21%, of interpatient variation in QOL. Eight patients had impaired glucose tolerance, associated with greater plasma GLP1 and peptide YY concentrations during dextrose and lipid infusions, respectively. Conclusions Increased sensitivity to enteral dextrose and lipid infusions was associated with greater plasma enteral hormone concentrations, more severe daily symptoms, and worse QOL in functional dyspepsia. These observations are consistent with the hypothesis that enteral hormones mediate increased intestinal sensitivity to nutrients in functional dyspepsia. PMID:25403365

  3. BEHAVIORAL MECHANISMS UNDERLYING NICOTINE REINFORCEMENT

    PubMed Central

    Rupprecht, Laura E.; Smith, Tracy T.; Schassburger, Rachel L.; Buffalari, Deanne M.; Sved, Alan F.; Donny, Eric C.

    2015-01-01

    Cigarette smoking is the leading cause of preventable deaths worldwide and nicotine, the primary psychoactive constituent in tobacco, drives sustained use. The behavioral actions of nicotine are complex and extend well beyond the actions of the drug as a primary reinforcer. Stimuli that are consistently paired with nicotine can, through associative learning, take on reinforcing properties as conditioned stimuli. These conditioned stimuli can then impact the rate and probability of behavior and even function as conditioning reinforcers that maintain behavior in the absence of nicotine. Nicotine can also act as a conditioned stimulus, predicting the delivery of other reinforcers, which may allow nicotine to acquire value as a conditioned reinforcer. These associative effects, establishing non-nicotine stimuli as conditioned stimuli with discriminative stimulus and conditioned reinforcing properties as well as establishing nicotine as a conditioned stimulus, are predicted by basic conditioning principles. However, nicotine can also act non-associatively. Nicotine directly enhances the reinforcing efficacy of other reinforcing stimuli in the environment, an effect that does not require a temporal or predictive relationship between nicotine and either the stimulus or the behavior. Hence, the reinforcing actions of nicotine stem both from the primary reinforcing actions of the drug (and the subsequent associative learning effects) as well as the reinforcement enhancement action of nicotine which is non-associative in nature. Gaining a better understanding of how nicotine impacts behavior will allow for maximally effective tobacco control efforts aimed at reducing the harm associated with tobacco use by reducing and/or treating its addictiveness. PMID:25638333

  4. Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking.

    PubMed

    Gamaleddin, Islam; Wertheim, Carrie; Zhu, Andy Z X; Coen, Kathleen M; Vemuri, Kiran; Makryannis, Alex; Goldberg, Steven R; Le Foll, Bernard

    2012-01-01

    The cannabinoid system appears to play a critical facilitative role in mediating the reinforcing effects of nicotine and relapse to nicotine-seeking behaviour in abstinent subjects based on the actions of cannabinoid (CB) receptor antagonists. However, the effects of CB receptor stimulation on nicotine self-administration and reinstatement have not been systematically studied. Here, we studied the effects of WIN 55,212-2, a CB1/2 agonist, on intravenous nicotine self-administration under fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement in rats. The effects of WIN 55,212-2 on responding for food under similar schedules were also studied. In addition, the effects of WIN 55,212-2 on nicotine- and cue-induced reinstatement of nicotine seeking were also studied, as well as the effects of WIN 55,212-2 on nicotine discrimination. WIN 55,212-2 decreased nicotine self-administration under the FR schedule. However, co-administration of WIN 55,212-2 with nicotine decreased responding for food, which suggests that this effect was non-selective. In contrast, WIN 55,212-2 increased both nicotine self-administration and responding for food under the PR schedule, produced dose-dependent reinstatement of nicotine seeking, and enhanced the reinstatement effects of nicotine-associated cues. Some of these effects were reversed by the CB1 antagonist rimonabant, but not by the CB2 antagonist AM630. In the drug discrimination tests between saline and 0.4 mg/kg nicotine, WIN 55,212-2 produced no nicotine-like discriminative effects but significantly potentiated discriminative stimulus effects of nicotine at the low dose through a CB1-receptor-dependent mechanism. These findings indicate that cannabinoid CB1-receptor stimulation increases the reinforcing effects of nicotine and precipitates relapse to nicotine-seeking behaviour in abstinent subjects. Thus, modulating CB1-receptor signalling might have therapeutic value for treating nicotine dependence. PMID:21521420

  5. Variability and determinants of total homocysteine concentrations in plasma in an elderly population.

    PubMed

    Clarke, R; Woodhouse, P; Ulvik, A; Frost, C; Sherliker, P; Refsum, H; Ueland, P M; Khaw, K T

    1998-01-01

    The variability of plasma total homocysteine (tHcy) was examined in 96 individuals over a 1-yr period. Blood tHcy concentrations varied from 7.1 micromol/L in the bottom quintile to 14.5 micromol/L in the top quintile. The mean tHcy was 10.4 micromol/L, the between-person SD was 2.5 micromol/L, and the within-person SD was 0.93 micromol/L. There was little seasonal variation, and the reliability coefficient was 0.88. Mean tHcy concentrations were inversely related to mean plasma folate (r = -0.36) and vitamin B12 (r = -0.35) concentrations. Median tHcy concentrations were approximately 1 micromol/L higher in men than in women and in older (70 to 74 years) than in younger (65 to 69 years) individuals and higher in those with the TT and CT genotypes for the methylenetetrahydrofolate reductase polymorphism than in those with the CC genotype (10.7 and 10.6 vs 9.6 micromol/L). Epidemiological studies based on single tHcy measurements may underestimate the magnitude of any risk associations with disease by 10-15%. PMID:9550566

  6. Variability and determinants of total homocysteine concentrations in plasma in an elderly population.

    PubMed

    Clarke, R; Woodhouse, P; Ulvik, A; Frost, C; Sherliker, P; Refsum, H; Ueland, P M; Khaw, K T

    1998-01-01

    The variability of plasma total homocysteine (tHcy) was examined in 96 individuals over a 1-yr period. Blood tHcy concentrations varied from 7.1 micromol/L in the bottom quintile to 14.5 micromol/L in the top quintile. The mean tHcy was 10.4 micromol/L, the between-person SD was 2.5 micromol/L, and the within-person SD was 0.93 micromol/L. There was little seasonal variation, and the reliability coefficient was 0.88. Mean tHcy concentrations were inversely related to mean plasma folate (r = -0.36) and vitamin B12 (r = -0.35) concentrations. Median tHcy concentrations were approximately 1 micromol/L higher in men than in women and in older (70 to 74 years) than in younger (65 to 69 years) individuals and higher in those with the TT and CT genotypes for the methylenetetrahydrofolate reductase polymorphism than in those with the CC genotype (10.7 and 10.6 vs 9.6 micromol/L). Epidemiological studies based on single tHcy measurements may underestimate the magnitude of any risk associations with disease by 10-15%.

  7. Plasma lactate concentration increases as a parabola with delay during ramp exercise.

    PubMed

    Péronnet, F; Morton, R H

    1994-01-01

    This study presents an elementary model of a system which relates plasma lactate concentration ([La-]) during ramp exercise to its rate of accumulation (Rc) within its extramuscular distribution space (S). Under the parsimonious assumptions that Rc increases linearly with time (t) with a kinetic delay (delta), and that the volume of S is constant, it is shown that plasma [La-] increases as a parabola with the kinetic delay delta when t increases. This elementary system model describes changes in plasma [La-] observed in five healthy young subjects during ramp exercise on the cycle ergometer (1 W every 2 s) with great accuracy (r > 0.99) with very small residuals (average value less than 0.01 mmol.l-1), randomly distributed around the fitting curves. The delay between the beginning of exercise and the onset of increase in Rc could be due to the fact that at the corresponding work rates: (1) rate of lactate appearance (Ra), which is equal to the rate of lactate disappearance (Rd), is not modified from rest, since the exercising muscles work in fully aerobic conditions (hypothesis of the anaerobic threshold); or (2) the increase in Ra is associated with a similar increase in Rd. An alternate or complementary hypothesis is that, during ramp exercise, plasma [La-] could reflect metabolic events within the muscles, with a significant delay.

  8. A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

    PubMed Central

    Chouraki, V; De Bruijn, RFAG; Chapuis, J; Bis, JC; Reitz, C; Schraen, S; Ibrahim-Verbaas, CA; Grenier-Boley, B; Delay, C; Rogers, R; Demiautte, F; Mounier, A; Fitzpatrick, AL; Berr, C; Dartigues, J-F; Uitterlinden, AG; Hofman, A; Breteler, M; Becker, JT; Lathrop, M; Schupf, N; Alpérovitch, A; Mayeux, R; van Duijn, CM; Buée, L; Amouyel, P; Lopez, OL; Ikram, MA; Tzourio, C; Lambert, J-C

    2014-01-01

    Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides’ functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1–40 and Aβ1–42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10−5). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1–42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1–42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites. PMID:24535457

  9. Impurity identifications, concentrations and particle fluxes from spectral measurements of the EXTRAP T2R plasma

    NASA Astrophysics Data System (ADS)

    Menmuir, S.; Kuldkepp, M.; Rachlew, E.

    2006-10-01

    An absolute intensity calibrated 0.5 m spectrometer with optical multi-channel analyser detector was used to observe the visible-UV radiation from the plasma in the EXTRAP T2R reversed field pinch experiment. Spectral lines were identified indicating the presence of oxygen, chromium, iron and molybdenum impurities in the hydrogen plasma. Certain regions of interest were examined in more detail and at different times in the plasma discharge. Impurity concentration calculations were made using the absolute intensities of lines of OIV and OV measured at 1-2 ms into the discharge generating estimates of the order of 0.2% of ne in the central region rising to 0.7% of ne at greater radii for OIV and 0.3% rising to 0.6% for OV. Edge electron temperatures of 0.5-5 eV at electron densities of 5-10×1011 cm-3 were calculated from the measured relative intensities of hydrogen Balmer lines. The absolute intensities of hydrogen lines and of multiplets of neutral chromium and molybdenum were used to determine particle fluxes (at 4-5 ms into the plasma) of the order 1×1016, 7×1013 and 3×1013 particles cm-2 s-1, respectively.

  10. A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly.

    PubMed

    Chouraki, V; De Bruijn, R F A G; Chapuis, J; Bis, J C; Reitz, C; Schraen, S; Ibrahim-Verbaas, C A; Grenier-Boley, B; Delay, C; Rogers, R; Demiautte, F; Mounier, A; Fitzpatrick, A L; Berr, C; Dartigues, J-F; Uitterlinden, A G; Hofman, A; Breteler, M; Becker, J T; Lathrop, M; Schupf, N; Alpérovitch, A; Mayeux, R; van Duijn, C M; Buée, L; Amouyel, P; Lopez, O L; Ikram, M A; Tzourio, C; Lambert, J-C

    2014-12-01

    Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1-40 and Aβ1-42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10(-)(5)). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1-42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1-42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.

  11. Plasma cytokine concentration changes induced by the antitumor agents dipterinyl calcium pentahydrate (DCP) and related calcium pterins.

    PubMed

    Moheno, Phillip; Pfleiderer, Wolfgang; Fuchs, Dietmar

    2009-01-01

    Analysis of plasma cytokine concentration changes determined that oral dosing with the antitumor agent (1:4 mol:mol) calcium pterin (CaPterin) increased plasma IL-10, decreased plasma IL-6, and decreased plasma IFN-gamma concentrations in nude mice with MDA-MB-231 xenograph tumors [Moheno, P., Pfleiderer, W., Dipasquale, A.G., Rheingold, A.L., Fuchs, D., 2008. Cytokine and IDO metabolite changes effected by calcium pterin during inhibition of MDA-MB-231 xenograph tumors in nude mice. Int. J. Pharm. 355, 238-248]. A further analysis, reported here, of plasma cytokine concentration changes in nude mice with the same tumor xenographs treated with dipterinyl calcium pentahydrate (DCP), (1:2 mol:mol) calcium pterin, and CaCl(2).2H(2)O has been carried out. The measured cytokines included: IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-gamma, and TNF-alpha. The major preliminary findings from the analyses of these data are that (1) the overall relative tumor volumes for the treatments correlated significantly with a full study antitumor plasma cytokine pattern (fsAPCP), a composite measure consisting of decreased plasma IL-6 and increased IL-4 concentrations, and (2) DCP induces a significant threshold antitumor response strongly correlated to a derived DCP antitumor plasma cytokine pattern (DCP/APCP) consisting of plasma IL-12, IL-6, and IL-4 concentration changes. This DCP/APCP composite measure identifies plasma IL-12 concentration increases, plasma IL-6 concentration decreases, and plasma IL-4 concentration increases correlated to relative tumor volume decreases caused by DCP dosing. The finding that the novel calcium pterins and CaCl(2).2H(2)O treatments decrease plasma IL-6 concentrations corroborates the previous finding that CaPterin dosing decreases plasma IL-6 concentrations in this mouse/tumor system [Moheno, P., Pfleiderer, W., Dipasquale, A.G., Rheingold, A.L., Fuchs, D., 2008. Cytokine and IDO metabolite changes effected by calcium pterin during inhibition

  12. Nicotinic Receptors in Neurodegeneration

    PubMed Central

    Posadas, Inmaculada; López-Hernández, Beatriz; Ceña, Valentín

    2013-01-01

    Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (α2-α10) and 3 beta (β2-β4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and propensity to desensitize. In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have been found to be involved in a complex range of CNS disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, Tourette´s syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD and age-associated memory and mild cognitive impairment. PMID:24179465

  13. Effect of training on blood volume and plasma hormone concentrations in the elderly

    NASA Technical Reports Server (NTRS)

    Carroll, J. F.; Convertino, V. A.; Wood, C. E.; Graves, J. E.; Lowenthal, D. T.; Pollock, M. L.

    1995-01-01

    The purpose of this investigation was to determine the effects of 6 months of endurance training on resting plasma (PV) and blood volume (BV), and resting hormone and electrolyte concentrations in the elderly. Thirty-eight elderly men and women (ages 60-82 yr) were assigned to endurance exercise training (N = 29) or to control (N = 9) groups. Resting plasma levels of adrenocorticotropic hormone, vasopressin, aldosterone, norepinephrine, epinephrine, sodium, potassium, and protein were measured at the start (T1) and end (T2) of 26 wk of training. PV measurement was performed using the Evan's blue dye technique. Endurance training consisted of uphill treadmill walking or stairclimbing exercise 3 times.wk-1, 30-45 min.d-1, at 75-84% of maximal heart rate reserve. The exercise group increased VO2max by 11.2% (P < or = 0.05) and increased resting PV and BV by 11.2% and 12.7% (P < or = 0.05), respectively. Hormone and electrolyte levels in the exercise group remained unchanged; all variables were unchanged in the control group. These results are similar to findings in younger individuals. Because plasma hormone concentrations were maintained despite a chronically elevated BV, endurance training in healthy, elderly subjects may be associated with a resetting of volume receptors.

  14. Measurement of plasma and tissue triiodothyronine concentration in the rat by radioimmunoassay.

    PubMed

    Nejad, I; Bollinger, J; Mitnick, M A; Sullivan, P; Reichlin, S

    1975-03-01

    This paper reports a radioimmunoassay method for triiodothyronine (T3) and the application of this assay to the study of plasma and tissue T3 concentration in the rat. Several antisera formed to a T3-bovine fibrogen complex in guinea pigs and T3-thyroglobulin complex in rabbits are shown to have low or no cross reactivity with T4, monoiodotyrosine, diiodotyrosine, tetraiodothyroacetic acid (TETRAC) and reverse T3. Cross reactivity with T3 derivatives, triiodothyroacetic acid (TRIAC), and triiodothyropropionic (TRIPROP) was variable, some antisera differentiating moderately well and others not at all. An extraction method is described which removes approximately 85% of added 125I-T3 or unlabelled T3 from tissues and in the final step represents 57% of total tissue T3. Mean plasma T3 in 5 normal male rats was 58 plus or minus 6.0 ng/100 ml (SEM), in liver 769 plus or minus 56 ng/100 g, and kidney 627 plus or minus 39 ng/100 g. Tissue to plasma concentration gradients for liver and kidney were 13.3 and 10.8, respectively.

  15. Effect of intravenous lipid emulsion on bupivacaine plasma concentration in humans.

    PubMed

    Litonius, E; Tarkkila, P; Neuvonen, P J; Rosenberg, P H

    2012-06-01

    Intravenous lipid emulsion is the recommended treatment for severe local anaesthetic intoxication. Lipid emulsion may entrap lipid soluble drugs by functioning as a 'lipid sink', but its effect on bupivacaine pharmacokinetics remains unknown. In this randomised, double-blind, crossover study, eight healthy male volunteers were infused bupivacaine 0.5mg.kg(-1) intravenously over 20 min, followed by an infusion of either intravenous lipid emulsion or Hartmann's solution for 30 min. At 20 and 30 min after the start of the infusion, the total plasma bupivacaine concentration was lower while receiving lipid emulsion than Hartmann's solution (mean difference 111 (95% CI 55-167) μg.l(-1) and 75 (95% CI 26-124 μg.l(-1) at 20 and 30 min, respectively; p<0.02). However, there were no differences in un-entrapped (non-lipid bound) or free (non-protein bound) bupivacaine plasma concentrations during the infusion. Intravenous lipid emulsion infusion reduced the context-sensitive half-life of total plasma bupivacaine from 45 (95% CI 32-76)min to 25 (95% CI 20-33)min; p=0.01. We observed no significant adverse effects of lipid emulsion. In conclusion, lipid emulsion may slightly increase the rate of bupivacaine tissue distribution. No 'lipid sink' effect was observed with the non-toxic dose of bupivacaine used.

  16. Removal of low-concentration BTX in air using a combined plasma catalysis system.

    PubMed

    Fan, X; Zhu, T L; Wang, M Y; Li, X M

    2009-06-01

    The behavior of non-thermal plasma (NTP) and combined plasma catalysis (CPC) was investigated for removal of low-concentration benzene, toluene and p-xylene (BTX mixture) in air using a link tooth wheel-cylinder plasma reactor. Combining NTP with MnO(x)/Al(2)O(3) catalyst after the discharge zone (CPC) significantly promoted BTX conversion and improved the energy efficiency. For a specific input energy (SIE) of 10 JL(-1), the conversion of benzene, toluene and p-xylene reached 94%, 97% and 95%, respectively. The introduction of MnO(x)/Al(2)O(3) catalyst also moved the BTX conversion towards total oxidation and reduced the emission of O(3) and NO(2) as compared to NTP alone. For an SIE of 10 JL(-1), the O(3) outlet concentration decreased from 46.7 for NTP alone to 1.9 ppm for CPC, while the NO(2) emission correspondingly decreased from 1380 to 40 ppb.

  17. Higher Plasma S100B Concentrations in Schizophrenia Patients, and Dependently Associated with Inflammatory Markers

    PubMed Central

    Hong, Wu; Zhao, Min; Li, Haozhe; Peng, Fanglan; Wang, Fan; Li, Ningning; Xiang, Hui; Su, Yousong; Huang, Yueqi; Zhang, Shengyu; Zhao, Guoqin; Zhou, Rubai; Mao, Ling; Lin, Zhiguang; Fang, Yiru; Zhang, Qinting; Xie, Bin

    2016-01-01

    Glial damage and immune dysfunction are involved in pathogenesis of schizophrenia. However, interaction between glial damage and immune dysfunction in schizophrenia is undefined. This study aims to compare plasma S100 calcium binding protein (S100B) levels between schizophrenia patients and healthy participants, and to determine if immune markers are independently related with concentration of S100B in schizophrenia patients. Forty-one schizophrenia patients and thirty-three healthy volunteers were enrolled. Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of plasma S100B and inflammatory markers. We found that concentrations of S100B were elevated in schizophrenia patients than healthy participants (p < 0.05), and were negatively related with the severity of symptoms (p = 0.046). Receiver operating characteristic (ROC) curve analysis showed that different S100B levels between schizophrenia and healthy participants can be used as a clinical diagnostic factor (predictive value: 0.666, p = 0.015). Multiple linear regression analysis found that length of illness (Beta = −0.161), plasma levels of inflammatory regulation factors (including TGF-β1, logIL-23 and logIL-10) (Beta = 0.119, 0.475, 0.514) were independently associated with concentrations of S100B (Adjusted R2 = 0.897, p < 0.001). Therefore, our results suggest the possible function of S100B in pathogenesis of schizophrenia, and implicate the important role of autoimmune response and balance to glial dysfunction in patients with schizophrenia. PMID:27279465

  18. Nicotinic acetylcholine receptors in glucose homeostasis: the acute hyperglycemic and chronic insulin-sensitive effects of nicotine suggest dual opposing roles of the receptors in male mice.

    PubMed

    Vu, Christine U; Siddiqui, Jawed A; Wadensweiler, Paul; Gayen, Jiaur R; Avolio, Ennio; Bandyopadhyay, Gautam K; Biswas, Nilima; Chi, Nai-Wen; O'Connor, Daniel T; Mahata, Sushil K

    2014-10-01

    Cigarette smoking causes insulin resistance. However, nicotine induces anti-inflammation and improves glucose tolerance in insulin-resistant animal models. Here, we determined the effects of nicotine on glucose metabolism in insulin-sensitive C57BL/J6 mice. Acute nicotine administration (30 min) caused fasting hyperglycemia and lowered insulin sensitivity acutely, which depended on the activation of nicotinic-acetylcholine receptors (nAChRs) and correlated with increased catecholamine secretion, nitric oxide (NO) production, and glycogenolysis. Chlorisondamine, an inhibitor of nAChRs, reduced acute nicotine-induced hyperglycemia. qRT-PCR analysis revealed that the liver and muscle express predominantly β4 > α10 > α3 > α7 and β4 > α10 > β1 > α1 mRNA for nAChR subunits respectively, whereas the adrenal gland expresses β4 > α3 > α7 > α10 mRNA. Chronic nicotine treatment significantly suppressed expression of α3-nAChR (predominant peripheral α-subunit) in liver. Whereas acute nicotine treatment raised plasma norepinephrine (NE) and epinephrine (Epi) levels, chronic nicotine exposure raised only Epi. Acute nicotine treatment raised both basal and glucose-stimulated insulin secretion (GSIS). After chronic nicotine treatment, basal insulin level was elevated, but GSIS after acute saline or nicotine treatment was blunted. Chronic nicotine exposure caused an increased buildup of NO in plasma and liver, leading to decreased glycogen storage, along with a concomitant suppression of Pepck and G6Pase mRNA, thus preventing hyperglycemia. The insulin-sensitizing effect of chronic nicotine was independent of weight loss. Chronic nicotine treatment enhanced PI-3-kinase activities and increased Akt and glycogen synthase kinase (GSK)-3β phosphorylation in an nAChR-dependent manner coupled with decreased cAMP response element-binding protein (CREB) phosphorylation. The latter effects caused suppression of Pepck and G6Pase gene expression. Thus, nicotine causes both

  19. Nicotine analysis in neonates' hair for measuring gestational exposure to tobacco.

    PubMed

    Kintz, P; Kieffer, I; Messer, J; Mangin, P

    1993-01-01

    Hair samples were collected at time of delivery from 40 neonates whose mothers were known to be smokers during the prenatal period. Hair was decontaminated in dichloromethane, homogenized in NaOH, and nicotine was extracted in diethyl ether. After separation on a BP-5 capillary column, nicotine was identified and quantified by GC/MS using selected ion monitoring. In all cases, nicotine was found in the neonatal hair and in the hair of the corresponding mother. The ranges of nicotine levels were 0.15 to 11.80 ng/mg, and 0.37 to 63.50 ng/mg, for the neonates, and their mothers, respectively. It was possible to establish a significant correlation between both concentrations, and the correlation coefficient was 0.83. These findings suggest the possibility of monitoring the transfer of maternal nicotine through the placenta by measuring nicotine concentration in neonatal hair.

  20. Oral administration and younger age decrease plasma concentrations of voriconazole in pediatric patients.

    PubMed

    Kato, Karin; Nagao, Miki; Yamamoto, Masaki; Matsumura, Yasufumi; Takakura, Shunji; Fukuda, Kazuhiko; Ichiyama, Satoshi

    2016-01-01

    Voriconazole is used for treating or preventing invasive aspergillosis and other invasive fungal infections. To minimize adverse reactions and to maximize treatment effects, therapeutic drug monitoring should be performed. However, it is challenging to optimize daily voriconazole dosing because limited data have been published so far on pediatric patients. We retrospectively analyzed voriconazole concentrations in patients aged 0-18 years. In addition, a literature review was conducted. In our study cohort, younger age and oral administration were significantly associated with lower plasma voriconazole concentrations (P < 0.01). An unfavorable outcome was associated with low concentrations of voriconazole (P = 0.01). Reports of voriconazole administration in pediatric patients show that higher doses are required in younger children and in patients receiving oral administration. Hence, the current data suggest that we should escalate both initial and maintenance doses of voriconazole in pediatric patients, particularly in patients of younger age receiving an oral administration of voriconazole. PMID:26538245

  1. Plasma catecholamine concentration during sedation in ventilated patients requiring intensive therapy.

    PubMed

    Kong, K L; Willatts, S M; Prys-Roberts, C; Harvey, J T; Gorman, S

    1990-01-01

    The effects of isoflurane and midazolam sedation on the catecholamine responses of ventilated patients were studied over a 24-h period. Sixty ventilated patients admitted to our intensive therapy unit were allocated randomly to receive either isoflurane or midazolam sedation. Arterial blood samples for plasma catecholamine concentrations were taken at baseline, 6 h after starting sedation and at the end of the study period. Patients sedated with isoflurane showed a progressive reduction in both adrenaline and noradrenaline concentrations during the period of sedation which reached statistical significance for adrenaline at 6 h (p less than 0.02) and at the end of the study (p less than 0.001). Patients sedated with midazolam showed no significant changes of adrenaline or noradrenaline concentrations. Overall, a more satisfactory degree of sedation was achieved with isoflurane.

  2. Concentrations of Methadone in Breast Milk and Plasma in the Immediate Perinatal Period

    PubMed Central

    Jansson, Lauren M.; Choo, Robin E.; Harrow, Cheryl; Velez, Martha; Schroeder, Jennifer R.; Lowe, Ross; Huestis, Marilyn A.

    2009-01-01

    This study evaluates concentrations of methadone in breast milk and plasma among a sample of methadone-maintained women in the immediate perinatal period. Twelve methadone-maintained, lactating women provided blood and breast milk specimens 1, 2, 3, and 4 days after delivery. Specimens were collected at the time of trough (just before methadone dose) and peak (3 hours after dosing) maternal methadone levels. Paired specimens of foremilk (prefeed) and hindmilk (postfeed) were obtained at each sampling time. Although there was a significant increase in methadone concentration in breast milk over time for the peak postfeed sampling time, t(22) = 2.40, P = .0255, methadone concentrations in breast milk were small, ranging from 21 to 314 ng/mL, and were unrelated to maternal methadone dose. Results obtained from this study contribute to the recommendation of breastfeeding for methadone-maintained women regardless of methadone dose. PMID:17478871

  3. Vaccines against nicotine.

    PubMed

    Cerny, Erich H; Cerny, Thomas

    2009-04-01

    Medications against any dependence-inducing drug face a dilemma: if they are efficient, they will induce withdrawal symptoms and the patient is likely to stop taking his medication. Anti drug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting rather with the drug in the blood than with a receptor in the brain, the vaccines are, in addition, free of side effects due to central interaction. For drugs like nicotine interacting with different types of receptors in many organs, this is a further advantage. There are three reasons that anti drug vaccines have first been developed against nicotine. Firstly, in most parts of the world 20 to 50% of the adult population smoke and any smoking cessation treatment will have an important impact on public health and be commercially a very attractive product. The second reason are the smokers themselves, who would like to quit in significant numbers and who have shown good compliance for any form of treatment. Thirdly, the quantities of cocaine or heroine taken by dependant persons are higher than the quantity of nicotine per cigarette, which makes an anti nicotine vaccine the easier vaccine project. Three anti nicotine vaccines are today in an advanced stage of clinical evaluation. We report here how those vaccines work, on the progress of the trials and future developments to expect. Results show that the efficiency of the vaccines is directly related to the antibody levels of the probates, a fact which will help to optimize further the vaccine effect. We expect the vaccines to appear on the market during a time window between 2009 and 2011. PMID:19276649

  4. Nicotinic receptors and attention.

    PubMed

    Hahn, Britta

    2015-01-01

    Facilitation of different attentional functions by nicotinic acetylcholine receptor (nAChR) agonists may be of therapeutic potential in disease conditions such as Alzheimer's disease or schizophrenia. For this reason, the neuronal mechanisms underlying these effects have been the focus of research in humans and in preclinical models. Attention-enhancing effects of the nonselective nAChR agonist nicotine can be observed in human nonsmokers and in laboratory animals, suggesting that benefits go beyond a reversal of withdrawal deficits in smokers. The ultimate aim is to develop compounds acting with greater selectivity than nicotine at a subset of nAChRs, with an effects profile narrowly matching the targeted cognitive deficits and minimizing unwanted effects. To date, compounds tested clinically target the nAChR subtypes most abundant in the brain. To help pinpoint more selectively expressed subtypes critical for attention, studies have aimed at identifying the secondary neurotransmitter systems whose stimulation mediates the attention-enhancing properties of nicotine. Evidence indicates that noradrenaline and glutamate, but not dopamine release, are critical mediators. Thus, attention-enhancing nAChR agents could spare the system central to nicotine dependence. Neuroimaging studies suggest that nAChR agonists act on a variety of brain systems by enhancing activation, reducing activation, and enhancing deactivation by attention tasks. This supports the notion that effects on different attentional functions may be mediated by distinct central mechanisms, consistent with the fact that nAChRs interact with a multitude of brain sites and neurotransmitter systems. The challenge will be to achieve the optimal tone at the right subset of nAChR subtypes to modulate specific attentional functions, employing not just direct agonist properties, but also positive allosteric modulation and low-dose antagonism.

  5. The Effect of Topiramate Plasma Concentration on Linguistic Behavior, Verbal Recall and Working Memory

    PubMed Central

    Marino, S.E.; Pakhomov, S.V.S.; Han, S.; Anderson, K.L.; Ding, M.; Eberly, L.E.; Loring, D.W.; Hawkins-Taylor, C.; Rarick, J.O.; Leppik, I.E.; Cibula, J.E.; Birnbaum, A.K.

    2012-01-01

    This is the first study of the effect of topiramate on linguistic behavior and verbal recall using a computational linguistics system for automated language and speech analysis to detect and quantify drug-induced changes in speech recorded during discourse level tasks. Healthy volunteers were administered a single, 100 mg oral dose of topiramate in two double-blind, randomized, placebo-controlled, crossover studies. Subjects’ topiramate plasma levels ranged from 0.23–2.81ug/mL. We found a significant association between topiramate levels and impairment on measures of verbal fluency elicited during a picture description task, correct number of words recalled on a paragraph recall test, and reaction time recorded during a working memory task. Using the tools of clinical pharmacology and computational linguistics, we elucidated the relationship between the determinants of a drug’s disposition as reflected in plasma concentrations and their impact on cognitive functioning as reflected in spoken language discourse. PMID:22658432

  6. Histological changes, rhinoscopical findings and nickel concentration in plasma and urine in retired nickel workers.

    PubMed

    Boysen, M; Solberg, L A; Torjussen, W; Poppe, S; Høgetveit, A C

    1984-01-01

    Histological examination of nasal biopsy specimens, rhinoscopical evaluation and nickel analysis in plasma and urine were performed on 59 retired nickel workers. The histological characteristics were graded according to a numerical classification table. Workers with short employment and short retirement time had a significantly lower mean histological scores than those with long employment and long retirement. Thirteen persons (22%) showed epithelial dysplasia, possibly representing precancerous lesions. Also included in the material were four cases of nasal carcinoma. Presence of hyperplastic/polypoid nasal mucosa was inversely related to the duration of retirement, possibly reflecting gradual regression of the mucosal swelling after termination of the irritation. The nickel concentration in plasma and urine was significantly higher among former roasting/smelting workers than in former electrolysis and non-process workers. This is probably a consequence of the slow release of heavy soluble nickel compounds that have accumulated in the organism at the former place of work. PMID:6689819

  7. Histological changes, rhinoscopical findings and nickel concentration in plasma and urine in retired nickel workers.

    PubMed

    Boysen, M; Solberg, L A; Torjussen, W; Poppe, S; Høgetveit, A C

    1984-01-01

    Histological examination of nasal biopsy specimens, rhinoscopical evaluation and nickel analysis in plasma and urine were performed on 59 retired nickel workers. The histological characteristics were graded according to a numerical classification table. Workers with short employment and short retirement time had a significantly lower mean histological scores than those with long employment and long retirement. Thirteen persons (22%) showed epithelial dysplasia, possibly representing precancerous lesions. Also included in the material were four cases of nasal carcinoma. Presence of hyperplastic/polypoid nasal mucosa was inversely related to the duration of retirement, possibly reflecting gradual regression of the mucosal swelling after termination of the irritation. The nickel concentration in plasma and urine was significantly higher among former roasting/smelting workers than in former electrolysis and non-process workers. This is probably a consequence of the slow release of heavy soluble nickel compounds that have accumulated in the organism at the former place of work.

  8. Concentrations of atomoxetine and its metabolites in plasma and oral fluid from paediatric patients with attention deficit/hyperactivity disorder.

    PubMed

    Papaseit, Esther; Marchei, Emilia; Farré, Magí; Garcia-Algar, Oscar; Pacifici, Roberta; Pichini, Simona

    2013-06-01

    Atomoxetine (ATX) is a non-stimulant drug approved for the treatment of children and adolescents with attention deficit/hyperactivity disorder (ADHD). We aimed to study the excretion profile of ATX and its principal metabolites 4-hydroxyatomoxetine (4-OH-ATX) and N-desmethylatomoxetine (desmethyl-ATX) in oral fluid and plasma of ADHD paediatric subjects, after administration of different dosage regimens. Oral fluid and plasma samples were obtained from one child and five adolescents treated with different ATX doses (18-60 mg/day). ATX and its metabolites were measured in oral fluid and plasma by liquid chromatography-mass spectrometry (LC-MS). Apparent pharmacokinetic parameters of ATX in oral fluid and plasma were estimated for each subject. All analytes under investigation were detected in plasma samples with concentrations from 0.6 to 1065.7 ng/ml for ATX, 0.7 to 17.1 ng/ml for 4-OH-ATX and 0.7 to 126.2 ng/ml for desmethyl-ATX. Only ATX and 4-OH-ATX were detected in oral fluid samples with concentrations from 0.5 to 36.0 ng/ml and 0.5 to 4.7 ng/ml, respectively. ATX concentrations in oral fluid were between one and two orders of magnitude lower than those in plasma. 4-OH-ATX was found in oral fluid at a peak concentration approximately one-fourth those in plasma with a mean tmax of 2.3 in plasma and 3.0 h in oral fluid. The correlations between ATX and 4-OH-ATX concentrations in the two biological fluids indicate that oral fluid concentrations of this drug and its principal metabolite may be a predictor of plasma concentrations, even if values are too low and variable to be considered an alternative to plasma.

  9. Plasma thyrotropin-releasing hormone concentrations in the rat. Effect of thyroid excess and deficiency and cold exposure.

    PubMed Central

    Emerson, C H; Utiger, R D

    1975-01-01

    To investigate the physiology of thyrotropin-releasing hormone (TRH) secretion from hypothalamus and brain, a method for measurement of peripheral plasma TRH concentrations in rats was developed. Blood was collected in heparin and dimercaptopropanol containing [3H]TRH to determine recovery. The plasma was extracted with methanol and the redissolved dried methanol extracts applied to anti-TRH Sepharose columns. These columns bound greater than 80% of 125I-TRH applied and had a capacity in excess of 20 ng TRH. TRH was eluted from the anti-TRH Sepharose with acetic acid and quantitated by radioimmunoassay of the lyophilized acetic acid eluate. Mean recovery of unlabeled TRH was 44.7+/-6.1% (SD) and mean recovery of [3H]TRH was 44.0+/-4.0%. Mean plasma TRH concentrations, corrected for recovery, in plasma pools from eight groups of normal male rats (four to seven pools/experiment, five to seven rats/pool) ranged from 7 to 30 pg/ml (mean, 16). In experiments in which rats were given 5, 10, 15, 0r 50 mug thyroxine daily for 1 wk or in thyroidectomized rats, mean plasma TRH concentrations did not differ significantly from those of control animals sacrificed at the same time. In each experiment, four to seven plasma pools, each from five to seven rats, were processed from both control and experimental groups. No changes in plasma TRH concentrations were found in rats exposed to cold (4degreeC) for 30, 60, and 90-180 min. Signigicant increases in plasma thyrotropin (TSH) concentrations were found in all cold-exposed animals. These results provide no evidence that thyroid hormone excess of deficiency affects TRH secretion. If TRH secretion is responsible for cold-induced increases in plasma TSH concentrations, the increase in TRH secretion is of insufficient magnitude to alter periperal plasma TRH concentrations. PMID:811690

  10. Behavioral, Biochemical, and Molecular Indices of Stress are Enhanced in Female Versus Male Rats Experiencing Nicotine Withdrawal

    PubMed Central

    Torres, Oscar V.; Gentil, Luciana G.; Natividad, Luis A.; Carcoba, Luis M.; O’Dell, Laura E.

    2013-01-01

    Stress is a major factor that promotes tobacco use and relapse during withdrawal. Although women are more vulnerable to tobacco use than men, the manner in which stress contributes to tobacco use in women versus men is unclear. Thus, the goal of this study was to compare behavioral and biological indices of stress in male and female rats during nicotine withdrawal. Since the effects of nicotine withdrawal are age-dependent, this study also included adolescent rats. An initial study was conducted to provide comparable nicotine doses across age and sex during nicotine exposure and withdrawal. Rats received sham surgery or an osmotic pump that delivered nicotine. After 14 days of nicotine, the pumps were removed and controls received a sham surgery. Twenty-four hours later, anxiety-like behavior and plasma corticosterone were assessed. The nucleus accumbens (NAcc), amygdala, and hypothalamus were examined for changes in corticotropin-releasing factor (CRF) gene expression. In order to differentiate the effects of nicotine withdrawal from exposure to nicotine, a cohort of rats did not have their pumps removed. The major finding is that during nicotine withdrawal, adult females display higher levels of anxiety-like behavior, plasma corticosterone, and CRF mRNA expression in the NAcc relative to adult males. However, during nicotine exposure, adult males exhibited higher levels of corticosterone and CRF mRNA in the amygdala relative to females. Adolescents displayed less nicotine withdrawal than adults. Moreover, adolescent males displayed an increase in anxiety-like behavior and an up-regulation of CRF mRNA in the amygdala during nicotine exposure and withdrawal. These findings are likely related to stress produced by the high doses of nicotine that were administered to adolescents to produce equivalent levels of cotinine as adults. In conclusion, these findings suggest that intense stress produced by nicotine withdrawal may contribute to tobacco use in women. PMID

  11. Plasma Amino Acid Concentrations Predict Mortality in Patients with End-Stage Liver Disease

    PubMed Central

    Kinny-Köster, Benedict; Bartels, Michael; Becker, Susen; Scholz, Markus; Thiery, Joachim

    2016-01-01

    Background The liver plays a key role in amino acid metabolism. In former studies, a ratio between branched-chain and aromatic amino acids (Fischer’s ratio) revealed associations with hepatic encephalopathy. Furthermore, low concentrations of branched-chain amino acids were linked to sarcopenia in literature. Encephalopathy and sarcopenia are known to dramatically worsen the prognosis. Aim of this study was to investigate a complex panel of plasma amino acids in the context of mortality in patients with end-stage liver disease. Methods 166 patients evaluated for orthotopic liver transplantation were included. 19 amino acids were measured from citrated plasma samples using mass spectrometry. We performed survival analysis for plasma amino acid constellations and examined the relationship to established mortality predictors. Results 33/166 (19.9%) patients died during follow-up. Lower values of valine (p<0.001), Fischer’s ratio (p<0.001) and valine to phenylalanine ratio (p<0.001) and higher values of phenylalanine (p<0.05) and tyrosine (p<0.05) were significantly associated with mortality. When divided in three groups, the tertiles discriminated cumulative survival for valine (p = 0.016), phenylalanine (p = 0.024) and in particular for valine to phenylalanine ratio (p = 0.003) and Fischer’s ratio (p = 0.005). Parameters were also significantly correlated with MELD and MELD-Na score. Conclusions Amino acids in plasma are valuable biomarkers to determine increased risk of mortality in patients with end-stage liver disease. In particular, valine concentrations and constellations composed of branched-chain and aromatic amino acids were strongly associated with prognosis. Due to their pathophysiological importance, the identified amino acids could be used to examine individual dietary recommendations to serve as potential therapeutic targets. PMID:27410482

  12. Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response.

    PubMed

    Mauri, Massimo C; Volonteri, Lucia S; Colasanti, Alessandro; Fiorentini, Alessio; De Gaspari, Ilaria F; Bareggi, Silvio R

    2007-01-01

    In the past, the information about the dose-clinical effectiveness of typical antipsychotics was not complete and this led to the risk of extrapyramidal adverse effects. This, together with the intention of improving patients' quality of life and therapeutic compliance, resulted in the development of atypical or second-generation antipsychotics (SGAs). This review will concentrate on the pharmacokinetics and metabolism of clozapine, risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole and sertindole, and will discuss the main aspects of their pharmacodynamics. In psychopharmacology, therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding adverse effects by keeping long-term exposure to the minimal effective blood concentration. The rationale for using therapeutic drug monitoring in relation to SGAs is still a matter of debate, but there is growing evidence that it can improve efficacy, especially when patients do not respond to therapeutic doses or when they develop adverse effects. Here, we review the literature concerning the relationships between plasma concentrations of SGAs and clinical responses by dividing the studies on the basis of the length of their observation periods. Studies with clozapine evidenced a positive relationship between plasma concentrations and clinical response, with a threshold of 350-420 ng/mL associated with good clinical response. The usefulness of therapeutic drug monitoring is well established because high plasma concentrations of clozapine can increase the risk of epileptic seizures. Plasma clozapine concentrations seem to be influenced by many factors such as altered cytochrome P450 1A4 activity, age, sex and smoking. The pharmacological effects of risperidone depend on the sum of the plasma concentrations of risperidone and its 9-hydroxyrisperidone metabolite, so monitoring the plasma concentrations of the parent compound alone can lead to erroneous

  13. Nicotine-Induced Modulation of the Cholinergic Twitch Response in the Ileum of Guinea Pig.

    PubMed

    Donnerer, Josef; Liebmann, Ingrid

    2015-01-01

    In the present study, the direct drug effects of nicotine and its effects on the cholinergic twitch responses of the electrically stimulated longitudinal muscle-myenteric plexus strip from the ileum of guinea pig were investigated. Nicotine dose-dependently (0.3-10 µmol/l) evoked the well-known contractile responses on its own. Whereas the interposed twitch responses remained present without a change in height at 1 µmol/l nicotine, a nicotine concentration of 3 µmol/l slightly and a concentration of 10 µmol/l markedly diminished the twitch during their presence. After the washout of 1-10 µmol/l nicotine, the height of the twitch response was also temporarily and significantly reduced by 30-77%. The P2X purinoceptor agonist αβ-methylene ATP (1-10 µmol/l) dose-dependently induced contractions on its own and reduced the twitch response during its presence in the organ bath; however, it did not diminish the twitch responses after washout of the drug as nicotine did. The P2X antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid, the NMDA channel blocker MK-801 and the inhibitor of small conductance Ca(2+)-activated K(+) (SK) channels apamin reduced the contractile effect of 1 µmol/l nicotine. Apamin also significantly prevented the 'post-nicotine inhibition of the twitch' following the washout of 1-3 µmol/l nicotine. As a conclusion, we provide evidence for a functional interaction between nicotinic receptors and the P2X receptors in the ileum of the guinea pig. The 'post-nicotine inhibition of the twitch' is not due to nicotinic acetylcholine receptor desensitization or transmitter depletion, but most probably the secondary effects of nicotine on SK channels determine the reduced cholinergic motor neuron excitability. PMID:26088942

  14. Purification of L-( sup 3 H) Nicotine eliminates low affinity binding

    SciTech Connect

    Romm, E.; Marks, M.J.; Collins, A.C. ); Lippiello, P.M. )

    1990-01-01

    Some studies of L-({sup 3}H) nicotine binding to rodent and human brain tissue have detected two binding sites as evidenced by nonlinear Scatchard plots. Evidence presented here indicated that the low affinity binding site is not stereospecific, is not inhibited by low concentrations of cholinergic agonists and is probably due to breakdown products of nicotine since purification of the L-({sup 3}H)nicotine eliminates the low affinity site.

  15. Concentration of Selected Metals in Whole Blood, Plasma, and Urine in Short Stature and Healthy Children.

    PubMed

    Klatka, Maria; Błażewicz, Anna; Partyka, Małgorzata; Kołłątaj, Witold; Zienkiewicz, Ewa; Kocjan, Ryszard

    2015-08-01

    The short stature in children is defined as height below the third percentile from the mean for age and gender. This problem affects about 3% of young people. More than 20,000 children in Poland have problems with short stature. There is not much information available in the literature on the study of metals in blood, plasma, and urine in children with short stature. The study was conducted on a group of 56 short stature Polish children and 35 healthy children. The content of metals was determined using high-performance ion chromatography and inductively coupled plasma mass spectrometry methods. The study revealed significant differences between the content of selected metals in body fluids between a short stature group and healthy children. There were significant differences in the Fe, Cu, and Ni concentrations between the groups with respect to the hormonal therapy. There were no significant differences between the groups with respect to the area where the children lived. The results showed no statistically significant differences between metal concentration and age, body weight, and height. The study demonstrated statistically significant differences between the content of metals in body fluids in short stature children compared with the healthy children. It seems that the difference in the concentration of certain elements may also be the result of growth hormone therapy and the interaction between various metals. Both the alterations in the content of metals and their mutual interactions may play an important role in the pathogenesis of short stature children.

  16. Experience of stress in childhood negatively correlates with plasma oxytocin concentration in adult men.

    PubMed

    Opacka-Juffry, Jolanta; Mohiyeddini, Changiz

    2012-01-01

    Early life experience is known to affect responses to stress in adulthood. Adverse experience in childhood and/or adolescence sensitises to life events that precipitate depression in later life. Published evidence suggests a relationship between depression and oxytocin (OT), but the extent to which early life experience influences OT disposition in adulthood deserves further exploration. This study hypothesised that early life stress (ELS) has a long-term negative effect on OT system activity. The study was performed on 90 male volunteers (18-56 years; mean ± standard deviation = 27.7 ± 7.09 years). Several questionnaires were used to assess: health, early life stressful experiences in childhood (ELS-C, up to 12 years) and early life stressful adolescence (13-18 years), recent stressful life events, depressive symptoms, state-trait anxiety and social desirability. Plasma OT concentration was estimated by means of a competitive enzyme immunoassay. Lower OT concentrations were significantly associated with higher levels of ELS-C (p < 0.01), and with depressive symptoms and trait anxiety (both p < 0.05). The interaction between ELS-C and trait anxiety was significant (p < 0.05), indicating that the link between ELS-C and plasma OT concentration is moderated by trait anxiety. These results contribute to the evidence that early life adverse experience is negatively associated with OT system activity in adulthood, and offer further insight into mediator and moderator effects on this link.

  17. Whey protein supplementation increases methionine intake but not homocysteine plasma concentration in rats.

    PubMed

    Deminice, Rafael; Comparotto, Hugo; Jordao, Alceu Afonso

    2015-01-01

    The purpose of this study was to examine the effects of whey protein supplementation on homocysteine (Hcy) metabolism and liver oxidative stress in rats. Twenty-four rats were divided into 3 groups (n = 8) to receive one of the following diets for 4 weeks: control diet (C), whey protein-composed diet (WP), and whey protein-supplemented diet (WPS). The C and WP diets consisted of AIN-93 with 20% casein and 20% whey protein as protein source, respectively. WPS was AIN-93 (20% casein) supplemented by the addition of 20% (w/w) whey protein. Four weeks of ingesting a WPS diet resulted in a significantly higher (P < 0.05) total protein and methionine intakes. Although a significant increase (P < 0.05) in the hepatic S-adenosylmethionine and S-adenosylhomocysteine levels occurred in WPS group compared with C and WP, no significant change was observed in plasma Hcy concentration between groups. Furthermore, the levels of lipid hydroperoxides and advanced oxidation protein products, known liver oxidative stress markers, were increased in the WPS group compared with the C group. In addition, no change in glutathione liver concentration was observed in any of the groups studied. In conclusion, whey protein supplementation increases methionine intake substantially; however, it does not change plasma Hcy concentrations. On the other hand, increased hepatic oxidative stress markers were observed in whey protein supplemented rats were probably due to high protein intake.

  18. Seminal plasma HIV-1 RNA concentration is strongly associated with altered levels of seminal plasma interferon-γ, interleukin-17, and interleukin-5.

    PubMed

    Hoffman, Jennifer C; Anton, Peter A; Baldwin, Gayle Cocita; Elliott, Julie; Anisman-Posner, Deborah; Tanner, Karen; Grogan, Tristan; Elashoff, David; Sugar, Catherine; Yang, Otto O; Hoffman, Risa M

    2014-11-01

    Seminal plasma HIV-1 RNA level is an important determinant of the risk of HIV-1 sexual transmission. We investigated potential associations between seminal plasma cytokine levels and viral concentration in the seminal plasma of HIV-1-infected men. This was a prospective, observational study of paired blood and semen samples from 18 HIV-1 chronically infected men off antiretroviral therapy. HIV-1 RNA levels and cytokine levels in seminal plasma and blood plasma were measured and analyzed using simple linear regressions to screen for associations between cytokines and seminal plasma HIV-1 levels. Forward stepwise regression was performed to construct the final multivariate model. The median HIV-1 RNA concentrations were 4.42 log10 copies/ml (IQR 2.98, 4.70) and 2.96 log10 copies/ml (IQR 2, 4.18) in blood and seminal plasma, respectively. In stepwise multivariate linear regression analysis, blood HIV-1 RNA level (p<0.0001) was most strongly associated with seminal plasma HIV-1 RNA level. After controlling for blood HIV-1 RNA level, seminal plasma HIV-1 RNA level was positively associated with interferon (IFN)-γ (p=0.03) and interleukin (IL)-17 (p=0.03) and negatively associated with IL-5 (p=0.0007) in seminal plasma. In addition to blood HIV-1 RNA level, cytokine profiles in the male genital tract are associated with HIV-1 RNA levels in semen. The Th1 and Th17 cytokines IFN-γ and IL-17 are associated with increased seminal plasma HIV-1 RNA, while the Th2 cytokine IL-5 is associated with decreased seminal plasma HIV-1 RNA. These results support the importance of genital tract immunomodulation in HIV-1 transmission.

  19. Plasma prolactin, growth hormone and progesterone concentrations in pseudopregnant, hysterectomized and pregnant goats.

    PubMed

    Kornalijnslijper, J E; Kemp, B; Bevers, M M; van Oord, H A; Taverne, M A

    1997-12-01

    Jugular plasma prolactin (PRL), growth hormone (GH) and progesterone (P4) levels were estimated in goats under three different conditions with prolonged luteal function (P4 > or = 1 ng/ml): pseudopregnant animals (n = 4), goats hysterectomized during early pregnancy (n = 4) and does with normal pregnancy (n = 4). Mean duration (+/- S.E.M.) of luteal phases were 189 +/- 20, 171 +/- 10, and 147 +/- 2 days in the three groups, respectively. Until day 120, mean PRL levels were below 150 ng/ml in each group. After day 120 of the luteal phase, PRL concentrations were significantly higher than before, but continued to increase up to 800 ng/ml only in pregnant animals around parturition. Mean GH levels varied between 2 and 3 ng/ml in animals of each group during the luteal phase. Only after parturition, a significant elevation occurred. P4 levels in pseudopregnant animals were significantly lower than in the other two groups between days 10 and 55, and showed a gradual but continuous decline towards the end of the luteal phase. After hysterectomy of early pregnant animals, P4 concentrations decreased to levels measured in pseudopregnant animals but were significantly higher again as compared to pseudopregnant animals between days 121 and 150. It is concluded that a pseudopregnant condition, characterized by intrauterine fluid accumulation, is not related to increased plasma PRL and GH concentrations. The low and gradually decreasing plasma progesterone levels in the pseudopregnant animals probably reflect the absence of a luteotrophic stimulus by the conceptus. The progesterone profile in the animals that were hysterectomized during early pregnancy suggests that the corpora lutea of these does have been permanently changed by the presence of the conceptus during the first weeks of the luteal phase. PMID:9505110

  20. St John's wort greatly decreases the plasma concentrations of oral S-ketamine.

    PubMed

    Peltoniemi, Marko A; Saari, Teijo I; Hagelberg, Nora M; Laine, Kari; Neuvonen, Pertti J; Olkkola, Klaus T

    2012-12-01

    Ketamine is an intravenous anaesthetic and analgesic agent but it can also be used orally as an adjuvant in the treatment of chronic pain. This study investigated the effect of the herbal antidepressant St John's wort, an inducer of cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of oral S-ketamine. In a randomized cross-over study with two phases, 12 healthy subjects were pretreated with oral St John's wort or placebo for 14 days. On day 14, they were given an oral dose of 0.3 mg/kg of S-ketamine. Plasma concentrations of ketamine and norketamine were measured for 24 h and pharmacodynamic variables for 12 h. St John's wort decreased the mean area under the plasma concentration-time curve (AUC(0-∞)) of ketamine by 58% (P < 0.001) and decreased the peak plasma concentration (C(max)) of ketamine by 66% (P < 0.001) when compared with placebo. Mean C(max) of norketamine (the major metabolite of ketamine) was decreased by 23% (P = 0.002) and mean AUC(0-∞) of norketamine by 18% (P < 0.001) by St John's wort. There was a statistically significant linear correlation between the self-reported drug effect and C(max) of ketamine (r = 0.55; P < 0.01). St John's wort greatly decreased the exposure to oral S-ketamine in healthy volunteers. Although this decrease was not associated with significant changes in the analgesic or behavioural effects of ketamine in the present study, usual doses of S-ketamine may become ineffective if used concomitantly with St John's wort.

  1. Nicotine exposure and metabolizer phenotypes from analysis of urinary nicotine and its 15 metabolites by LC–MS

    PubMed Central

    Rangiah, Kannan; Hwang, Wei-Ting; Mesaros, Clementina; Vachani, Anil; Blair, Ian A

    2011-01-01

    Smokers who inhale less deeply are exposed to lower amounts of the toxic substances present in tobacco smoke. In order to more rigorously assess tobacco smoke exposure, it is necessary to have an accurate method for quantifying nicotine and all of its known metabolites. Methods A stable-isotope dilution LC–MRM/MS assay has been developed for quantification of urinary nicotine and the 15 possible metabolites that could arise from known metabolic pathways. Nicotine, cotinine, trans-3′-hydroxy-cotinine, nicotine-N-oxide, cotinine-N-oxide, nornicotine, norcotinine and 4-hydroxy-4-(3-pyridyl)butanoic acid were quantified by direct analysis. The corresponding glucuronide metabolites were quantified after urine hydrolysis with β-glucuronidase. Results Nicotine and all 15 nicotine metabolites were quantified by LC MRM/MS in most urine samples from 61 tobacco smokers. Urinary nicotine and metabolite concentrations ranged from 7.9 to 337.8 μM (mean 75.5 ± 67.8 μM). Three nicotine metabolizer phenotypes were established as reduced metabolizers (ratio < 8), normal metabolizers (ratio 8–30), and extensive metabolizers (ratio > 30). 4-hydroxy-4-(3-pyridyl)butanoic acid, which has not been quantified previously, was an abundant metabolite in all three phenotypes. Conclusion Using this assay it will now be possible to determine whether there are relationships between nicotine exposure and/or metabolizer phenotype with exposure to toxic substances that are present in tobacco smoke and/or to biological response biomarkers to tobacco smoking. This will help in identifying individuals at high risk for developing smoking-related diseases as well as those amenable to smoking cessation programs. PMID:21452992

  2. Pharmacokinetics and effects on plasma retinol concentrations of 13-cis-retinoic acid in melanoma patients.

    PubMed Central

    Formelli, F.; Cavadini, E.; Mascheroni, L.; Belli, F.; Cascinelli, N.

    1997-01-01

    The pharmacokinetics of 13-cis-retinoic acid (13cisRA) and its effects on retinol plasma levels were investigated after the first and the last doses in melanoma patients, who participated in a study run to assess tolerance over a long period of a treatment schedule of 13cisRA associated with recombinant interferon alpha2a (rIFN-alpha2a). Melanoma patients with regional node metastases after radical surgery were randomized to be treated for 3 months with rIFN-alpha2a, 3 x 10(6) IU s.c. every other day, associated with oral 13cisRA at doses of 20 mg day(-1) (five patients) or 40 mg every other day (seven patients). Maximum 13cisRA blood concentrations usually occurred 4 h after drug administration, with average values of 406 and 633 ng ml(-1) (i.e. 1.3 and 2.1 microM) after the 20 and 40 mg dose respectively. The average half-life (t(1/2)) was approximately 30 h. The maximum concentration, the t(1/2) and the area under the concentration-time curves from 0 to 48 h (AUC(0-48)) of 13cisRA did not change after multiple dosing, whereas the AUC(0-48) of its major blood metabolite, 4-oxo-13-cis-retinoic acid, increased. Immediately after 13cisRA treatment, retinol plasma levels started to decline and they reached the lowest values (approximately 20% reduction) shortly after the time of maximum 13cisRA concentrations (i.e. 4-12 h after drug intake). Afterwards, values returned to baseline. The amount of retinol reduction in time was correlated with 13cisRA maximum concentrations. PMID:9413958

  3. Manifestation of cryptic fibroblast tissue factor occurs at detergent concentrations which dissolve the plasma membrane.

    PubMed

    Carson, S D

    1996-04-01

    Cultured fibroblasts treated with increasing concentrations of detergents expressed only encrypted levels of tissue factor activity (measured by fX activation in the presence of fVIIa), characteristic of undamaged cells, until each detergent reached a critical concentration at which the cryptic tissue factor activity was manifested. Beyond the narrow ranges of concentrations over which the detergents stimulated tissue factor activity, the detergents were inhibitory. Studies with Triton X-100 and octyl glucoside revealed that manifestation of tissue factor activity coincided with breakdown of the plasma membrane. The magnitude of the increased tissue factor activity differed among detergents, with octyl glucoside giving the largest response. The tissue factor that was active after Triton X-100 treatment remained mostly associated with the insoluble cell residue, whereas the concentration of octyl glucoside which stimulated activity released tissue factor activity into the supernatant. Radiolabeled antibody against human tissue factor was used to show that a small percentage of the total accessible tissue factor remained in the insoluble fraction after treatment with either non-ionic detergent. Chromatographic analysis of lipids extracted from cells treated with detergents and dansyl chloride showed dansyl-reactivity of phosphatidylserine on intact cells, and solubilization of membrane lipids at sublytic concentrations of detergents. These findings reveal that there is a critical level of detergent-induced membrane damage at which tissue factor activity is maximally expressed, in essentially an all-or-none manner. The results are consistent with a major role for phospholipid asymmetry in regulation of tissue factor specific activity, but require either maintenance of asymmetry during sublytic detergent perturbation of the plasma membrane or additional control mechanisms.

  4. Comprehensive Profiling of Plasma Fatty Acid Concentrations in Young Healthy Canadian Adults

    PubMed Central

    Abdelmagid, Salma A.; Clarke, Shannon E.; Nielsen, Daiva E.; Badawi, Alaa; El-Sohemy, Ahmed; Mutch, David M.; Ma, David W. L.

    2015-01-01

    Circulating fatty acids (FA) are associated with a multitude of chronic diseases. However, a major gap in establishing such relationships is the lack of accepted fatty acid reference ranges representing healthy individuals. Data on validated FA reference ranges would provide a better understanding of study baseline measures and aid in the evaluation and interpretation of pharmaceutical or dietary interventions. Reference ranges for plasma FA levels have been reported in a few small studies and on a limited number of FA. Therefore, we determined the average and percentiles of a broad set of 61 FA (C14 - C24:1) from plasma total lipids from an ethnically diverse population of healthy young Canadian males and females (Total n = 826). Plasma concentrations of some of the major FA ranged from 0.3 to 4.1 mmol/L for palmitic acid, 0.1 to 1.0 mmol/L for stearic acid, 0.03 to 3.2 mmol/L for oleic acid, 0.2 to 5.0 mmol/L for linoleic acid (LA), 12.0 to 186.9 μmol/L for α-linolenic acid, and 7.2 to 237.5 μmol/L for docosahexaenoic acid (DHA). Males had significantly higher plasma concentrations of γ-linolenic acid (GLA) and n-3 docosapentaenoic acid and lower concentrations of palmitoleic acid, LA and DHA than females. Comparison of FA concentrations between Caucasians, East Asians and South Asians revealed that South Asians had significantly lower levels of palmitoleic acid (p < 0.01) and oleic acid (p = 0.01) while East Asians had lower levels of GLA (p = 0.02) and dihomo-γ-linolenic acid (p = 0.03). Overall, these data provide a comprehensive set of quantitative values that profiles a small cohort of Canadians which highlights the utility of establishing validated FA reference ranges that may be used to understand how deficient, suboptimal, or excess amounts of a given FA may be associated with chronic disease. PMID:25675440

  5. [Isolation, extractive concentration, and determination of caffeine in the studies of blood plasma].

    PubMed

    Korenman, Ia I; Shormanov, V K; Mokshina, N Ia; Krivosheeva, O A; Golubitskiĭ, G B

    2012-01-01

    The optimal conditions for the isolation of caffeine from human blood by means of acetone extraction are described with special reference to the peculiarities of extraction from aqueous solutions. The possibility of concentration and purification of caffeine from blood plasma using acetone and aceton-chlorophorm mixture (2:8) as the solvents is illustrated. In addition, purification by silica-gel thin layer chromatography is discussed. Thin layer chromatography, UV-spectrophotometry, and high performance liquid chromatography are considered as potential methods for the identification and quantitative determination of caffeine.

  6. Nicotine exposure and the progression of chronic kidney disease: role of the α7-nicotinic acetylcholine receptor.

    PubMed

    Rezonzew, Gabriel; Chumley, Phillip; Feng, Wenguang; Hua, Ping; Siegal, Gene P; Jaimes, Edgar A

    2012-07-15

    Clinical studies have established the role of cigarette smoking as a risk factor in the progression of chronic kidney disease (CKD). We have shown that nicotine promotes mesangial cell proliferation and hypertrophy via nonneuronal nicotinic acetylcholine receptors (nAChRs). The α7-nAChR is one of the most important subunits of the nAChRs. These studies were designed to test the hypothesis that nicotine worsens renal injury in rats with 5/6 nephrectomy (5/6Nx) and that the α7-nAChR subunit is required for these effects. We studied five different groups: Sham, 5/6Nx, 5/6Nx + nicotine (Nic; 100 μg/ml dry wt), 5/6Nx + Nic + α7-nAChR blocker methyllicaconitine (MLA; 3 mg·kg(-1)·day(-1) sq), and Sham + Nic. Blood pressure was measured by the tail-cuff method, and urine was collected for proteinuria. After 12 wk, the rats were euthanized and kidneys were collected. We observed expression of the α7-nAChR in the proximal and distal tubules. The administration of nicotine induced a small increase in blood pressure and resulted in cotinine levels similar to those found in the plasma of smokers. In 5/6Nx rats, the administration of nicotine significantly increased urinary protein excretion (onefold), worsened the glomerular injury score and increased fibronectin (∼ 50%), NADPH oxidase 4 (NOX4; ∼100%), and transforming growth factor-β expression (∼200%). The administration of nicotine to sham rats increased total proteinuria but not albuminuria, suggesting direct effects on tubular protein reabsorption. These effects were prevented by MLA, demonstrating a critical role for the α7-nAChR as a mediator of the effects of nicotine in the progression of CKD.

  7. Regional Metabolite Levels and Turnover in the Awake Rat Brain under the Influence of Nicotine

    PubMed Central

    Wang, Jie; Jiang, Lihong; Jiang, Yifeng; Ma, Xiaoxian; Graeme, F. Mason

    2010-01-01

    As one of the most widespread drugs of abuse, nicotine has long been known to impact the brain, particularly with respect to addiction. However, the regional effects of nicotine on the concentrations and kinetics of amino acid neurotransmitters and some energetically related neurochemicals have been little studied. In this investigation, acute effects of nicotine were measured by 1H-observed/13C-edited nuclear magnetic resonance spectroscopy method in extracts obtained from nicotine-naïve, freely moving rats given 0.7 mg/kg nicotine or saline, with [1-13C] glucose to track metabolism. Nicotine was observed to exert significant effects on the concentrations of N-acetylaspartate (NAA), and γ-aminobutyric acid (GABA), particularly in the striatum. Nicotine decreased brain glucose oxidation, glutamate-glutamine neurotransmitter cycling, and GABA synthesis regionally, including in the parietal and occipital cortices and the striatum. The olfactory bulb showed kinetics that differed markedly from those observed in the rest of the brain. Independently of nicotine, the concentration of glutamate was found to be correlated significantly with levels of NAA and GABA, suggesting a potential interplay of energetics and excitatory and inhibitory neurotransmission. In summary, the study revealed that the neurochemicals were most affected in the cortex and striatum of the rat brain after acute nicotine treatment. PMID:20345764

  8. Functional expression of nicotine influx transporter in A549 human alveolar epithelial cells.

    PubMed

    Tega, Yuma; Yuzurihara, Chihiro; Kubo, Yoshiyuki; Akanuma, Shin-ichi; Ehrhardt, Carsten; Hosoya, Ken-ichi

    2016-02-01

    Nicotine is a potent addictive alkaloid, and is rapidly absorbed through the alveoli of the lung. However, the transport mechanism of nicotine at the human alveolar epithelial barrier has not been investigated in great detail. In the present study, the transport mechanism of nicotine across alveolar epithelium was investigated in vitro using A549 cells, a human adenocarcinoma-derived cell line with an alveolar epithelial cell like phenotype. Nicotine uptake by A549 cells exhibited time-, temperature-, and concentration-dependence with a Km of 50.4 μM. These results suggest that a carrier-mediated transport process is involved in nicotine transport in human alveolar epithelial cells. Nicotine uptake by A549 cells was insensitive to change in extracellular pH. Moreover, nicotine uptake by A549 cells could be inhibited by organic cations such as verapamil and pyrilamine, but not typical substrates of organic cation transporters and β2-agonist. These results suggest that a novel, not yet molecularly identified, organic cation transporter plays a role in nicotine transport which is unlikely to interact with β2-agonist transport. This nicotine influx transporter in human alveolar epithelium might have implications for the rapid absorption of nicotine into the systemic circulation. PMID:26830082

  9. Free-Base and Protonated Nicotine in Electronic Cigarette Liquids and Aerosols.

    PubMed

    El-Hellani, Ahmad; El-Hage, Rachel; Baalbaki, Rima; Salman, Rola; Talih, Soha; Shihadeh, Alan; Saliba, Najat A

    2015-08-17

    As with other tobacco aerosols, nicotine delivery from e-cigarettes (ECIG) depends on the total nicotine and its partitioning between free-base (Nic) and protonated (NicH(+)) forms. Previous studies of ECIG nicotine emissions have generally reported "nicotine yield" without attention to whether the methods employed resulted in quantification of the total nicotine or only one of its forms, making reported results difficult to compare across studies or to evaluate against reported blood exposure. This study reports a convenient solvent extraction method for determining total nicotine and its partitioning in ECIG liquids and aerosols by gas chromatography. Commercial ECIG liquids and aerosols were analyzed, and it was found that most of the nicotine was in the Nic form, with aerosols exhibiting higher Nic fraction than the parent liquids. Apparent pH was found to correlate with nicotine partitioning and can provide a useful indirect measure when chromatography is unavailable. Finally, labeled ECIG liquid nicotine concentration in commercial products was often inconsistent with measured nicotine.

  10. Human colon adenocarcinoma HT-29 cell: electrochemistry and nicotine stimulation.

    PubMed

    Oliveira, S C B; Santarino, I B; Enache, T A; Nunes, C; Laranjinha, J; Barbosa, R M; Oliveira-Brett, A M

    2013-12-01

    Recently, it was demonstrated that colorectal cancer HT-29 cells can secrete epinephrine (adrenaline) in an autocrine manner to auto-stimulate cellular growth by adrenoreceptors activation, and that this secretion is enhanced by nicotine, showing an indirect relation between colorectal cancer and tobacco. The electrochemical behaviour of human colon adenocarcinoma HT-29 cells from a colorectal adenocarcinoma cell line, the hormone and neurotransmitter epinephrine, and nicotine, were investigated by cyclic voltammetry, using indium tin oxide (ITO), glassy carbon (GC) and screen printed carbon (SPC) electrodes. The oxidation of the HT-29 cells, previously grown onto ITO or SPC surfaces, followed an irreversible oxidation process that involved the formation of a main oxidation product that undergoes irreversible reduction, as in the epinephrine oxidation mechanism. The effect of nicotine stimulation of the HT-29 cells was also investigated. Nicotine, at different concentration levels 1, 2 and 15 mM, was introduced in the culture medium and an increase with incubation time, 0 to 3h and 30 min, of the HT-29 cells oxidation and reduction peaks was observed. The interaction of nicotine with the HT-29 cells stimulated the epinephrine secretion causing an increase in epinephrine release concentration, and enabling the conclusion that epinephrine and nicotine play an important role in the colorectal tumour growth.

  11. Concentrations of oestradiol-17 beta in plasma and milk and progesterone in plasma during the oestrus cycle and in early pregnancy in goats.

    PubMed

    Abeyawardene, S A; Pope, G S

    1990-01-01

    Pre-ovulatory peaks in oestradiol-17 beta concentrations were observed on days 1 or 2 and post-ovulatory peaks between days 4 and 7, both in jugular venous plasma and defatted milk, day 1 being the day of the onset of oestrus in the goats. Mean values of the magnitudes of these concentration peaks and of their timing (relative to oestrus) during the oestrus cycle did not differ significantly (P greater than 0.05) from those when the goats were mated and became pregnant. Pre-ovulatory oestradiol-17 beta peaks were invariably greater than the corresponding post-ovulatory peaks, as were peak concentrations in plasma relative to those in defatted milk collected on the same day. Mean intervals between the pre- and post-ovulatory peaks in oestradiol-17 beta concentrations were respectively 4.2 days for plasma and 4.0 days for defatted milk. Concentrations of oestradiol-17 beta in jugular venous plasma and defatted milk were strongly correlated: rank correlation coefficients for the three goats studied were 0.871, 0.668 and 0.739. It is suggested that in goats, as in cattle, ovarian follicular oestradiol-17 beta secretion approaching pre-ovulatory level is restored by 4 days after oestrus and its rapid decline after this time may be due to the inhibitory influence of the rapidly rising plasma progesterone concentration. PMID:2331587

  12. Spectroscopic measurements of temperature and plasma impurity concentration during magnetic reconnection at the Swarthmore Spheromak Experiment

    SciTech Connect

    Chaplin, V. H.; Brown, M. R.; Cohen, D. H.; Gray, T.; Cothran, C. D.

    2009-04-15

    Electron temperature measurements during counterhelicity spheromak merging studies at the Swarthmore Spheromak Experiment (SSX) [M. R. Brown, Phys. Plasmas 6, 1717 (1999)] are presented. VUV monochromator measurements of impurity emission lines are compared with model spectra produced by the non-LTE excitation kinematics code PRISMSPECT[J. J. MacFarlane et al., in Proceedings of the Third Conference on Inertial Fusion Science and Applications (2004)] to yield the electron temperature in the plasma with 1 {mu}s time resolution. Average T{sub e} is seen to increase from 12 to 19 eV during spheromak merging. Average C III ion temperature, measured with a new ion Doppler spectrometer (IDS) [C. D. Cothran et al., Rev. Sci. Instrum. 77, 063504 (2006)], likewise rises during spheromak merging, peaking at {approx}22 eV, but a similar increase in T{sub i} is seen during single spheromak discharges with no merging. The VUV emission line measurements are also used to constrain the concentrations of various impurities in the SSX plasma, which are dominated by carbon, but include some oxygen and nitrogen. A burst of soft x-ray emission is seen during reconnection with a new four-channel detector (SXR). There is evidence for spectral changes in the soft x-ray emission as reconnection progresses, although our single-temperature equilibrium spectral models are not able to provide adequate fits to all the SXR data.

  13. Spectroscopic measurements of temperature and plasma impurity concentration during magnetic reconnection at the Swarthmore Spheromak Experiment

    NASA Astrophysics Data System (ADS)

    Chaplin, V. H.; Brown, M. R.; Cohen, D. H.; Gray, T.; Cothran, C. D.

    2009-04-01

    Electron temperature measurements during counterhelicity spheromak merging studies at the Swarthmore Spheromak Experiment (SSX) [M. R. Brown, Phys. Plasmas 6, 1717 (1999)] are presented. VUV monochromator measurements of impurity emission lines are compared with model spectra produced by the non-LTE excitation kinematics code PRISMSPECT [J. J. MacFarlane et al., in Proceedings of the Third Conference on Inertial Fusion Science and Applications (2004)] to yield the electron temperature in the plasma with 1 μs time resolution. Average Te is seen to increase from 12 to 19 eV during spheromak merging. Average C III ion temperature, measured with a new ion Doppler spectrometer (IDS) [C. D. Cothran et al., Rev. Sci. Instrum. 77, 063504 (2006)], likewise rises during spheromak merging, peaking at ˜22 eV, but a similar increase in Ti is seen during single spheromak discharges with no merging. The VUV emission line measurements are also used to constrain the concentrations of various impurities in the SSX plasma, which are dominated by carbon, but include some oxygen and nitrogen. A burst of soft x-ray emission is seen during reconnection with a new four-channel detector (SXR). There is evidence for spectral changes in the soft x-ray emission as reconnection progresses, although our single-temperature equilibrium spectral models are not able to provide adequate fits to all the SXR data.

  14. Plasma mitomycin C concentrations determined by HPLC coupled to solid-phase extraction.

    PubMed

    Paroni, R; Arcelloni, C; De Vecchi, E; Fermo, I; Mauri, D; Colombo, R

    1997-04-01

    The aim of this study was to set up a method for quantification of plasma mitomycin C (MMC) concentrations during intravesical chemotherapy delivered in the presence of local bladder hyperthermia (HT). In comparison with existing methods, this assay, characterized by relative simplicity and efficiency, resulted in the facilitation of performance with nondedicated instrumentation or nonspecialized staff. Purification from plasma matrix was carried out by solid-phase extraction under vaccuum. The purified drug was then collected directly into the vials of the HPLC autosampler. Chromatographic analysis was performed on a reversed-phase C18 column with water:acetonitrile (85:15 by vol) as the mobile phase and the UV detector set at 365 nm. The use of porfiromycin as internal standard provided a method with good within-day precision (CV 6.0% at 5 micrograms/L, n = 6), linearity (0.5-50 micrograms/L), and specificity. The lower limit of detection (< or = 0.5 microgram/L) proved to be suitable for plasma pharmacokinetics monitoring in two tested patients treated with MMC + HT for superficial bladder cancer. PMID:9105262

  15. Dietary fat type and energy restriction interactively influence plasma leptin concentration in rats.

    PubMed

    Cha, M C; Jones, P J

    1998-08-01

    To investigate whether dietary fat source and energy restriction interactively influence plasma leptin levels and its association of leptin with insulin action, rats were fed diets containing either fish, safflower oil, or beef tallow (20% wt/wt) for 10 weeks. Groups of rats consumed each diet ad libitum or at 85% or 70% of ad libitum energy intake in a design that held fat intake constant. Graded levels of energy restriction caused body weight to decrease (P < 0.001) differently according to the dietary fat provided. Plasma leptin concentrations were 60% higher (P < 0.05) in the groups fed fish oil and safflower oil ad libitum compared with those in the beef tallow group, despite smaller perirenal fat mass and fat cell size in the fish oil-fed animals. Energy restriction resulted in a 62% decrease (P < 0.05) in leptin levels in fish oil- and safflower oil-fed rats, whereas no changes were observed in beef tallow-fed animals. Plasma insulin levels were lower (P < 0.05) in the fish oil group fed ad libitum compared with those in the two other diet groups. These data demonstrate a hyperleptinemic effect in animals consuming diets rich in polyunsaturated fatty acid, which can be normalized to the level of saturated fat consumption by mild energy restriction. Thus, dietary fatty acid composition, independent of adipose tissue mass, is an important determinant of circulating leptin level in diet-induced obesity.

  16. Effect of application sites and multiple doses on nicotine pharmacokinetics in healthy male Japanese smokers following application of the transdermal nicotine patch.

    PubMed

    Sobue, Satoshi; Sekiguchi, Kaneo; Kikkawa, Hironori; Irie, Shin

    2005-12-01

    The transdermal nicotine patch, which contains 25 mg nicotine per 30 cm(2), is designed to deliver approximately 15 mg nicotine to the blood circulation in 16 hours of application for the treatment of smoking cessation. It was applied to 3 different skin sites (upper arm, abdomen, and back) to examine regional variations in percutaneous nicotine absorption in a single-dose, 3-period, crossover study involving 9 healthy male Japanese smokers. Nicotine pharmacokinetics during once-daily application of the transdermal nicotine patch for 5 days was also investigated in 10 healthy smokers. There were statistically significant effects of application sites on percutaneous nicotine absorption. The ratios (90% confidence intervals) of AUC and C(max) for comparison to the upper arm were 102% (88, 117%) and 106% (95, 119%) for the back and 75% (65, 87%) and 75% (66, 84%) for the abdomen, respectively. These suggest that systemic exposure after application to the upper arm was greater compared with the abdomen but equivalent to the back. Following multiple doses, linear pharmacokinetics and no significant accumulation of nicotine concentrations were observed, and steady state was reached by day 2. Only mild itching and erythema were observed at the application sites. The transdermal nicotine patch was well tolerated in both studies.

  17. A prospective study of plasma 25-hydroxyvitamin D concentration and prostate cancer risk.

    PubMed

    Deschasaux, Mélanie; Souberbielle, Jean-Claude; Latino-Martel, Paule; Sutton, Angela; Charnaux, Nathalie; Druesne-Pecollo, Nathalie; Galan, Pilar; Hercberg, Serge; Le Clerc, Sigrid; Kesse-Guyot, Emmanuelle; Ezzedine, Khaled; Touvier, Mathilde

    2016-01-28

    Mechanistic hypotheses suggest that vitamin D and the closely related parathyroid hormone (PTH) may be involved in prostate carcinogenesis. However, epidemiological evidence is lacking for PTH and inconsistent for vitamin D. Our objectives were to prospectively investigate the association between vitamin D status, vitamin D-related gene polymorphisms, PTH and prostate cancer risk. A total of 129 cases diagnosed within the Supplémentation en Vitamines et Minéraux Antioxydants cohort were included in a nested case-control study and matched to 167 controls (13 years of follow-up). 25-Hydroxyvitamin D (25(OH)D) and PTH concentrations were assessed from baseline plasma samples. Conditional logistic regression models were computed. Higher 25(OH)D concentration was associated with decreased risk of prostate cancer (ORQ4 v. Q1 0·30; 95 % CI 0·12, 0·77; P trend=0·007). PTH concentration was not associated with prostate cancer risk (P trend=0·4) neither did the studied vitamin D-related gene polymorphisms. In this prospective study, prostate cancer risk was inversely associated with 25(OH)D concentration but not with PTH concentration. These results bring a new contribution to the understanding of the relationship between vitamin D and prostate cancer, which deserves further investigation. PMID:26568368

  18. Plasma 24,25-dihydroxyvitamin D concentration of Dahl salt-sensitive rats decreases during high salt intake

    NASA Technical Reports Server (NTRS)

    Thierry-Palmer, Myrtle; Tewolde, Teclemicael K.; Forte, Camille; Wang, Min; Bayorh, Mohamed A.; Emmett, Nerimiah L.; White, Jolanda; Griffin, Keri

    2002-01-01

    Dahl salt-sensitive rats, but not salt-resistant rats, develop hypertension in response to high salt intake. We have previously shown an inverse relationship between plasma 25-hydroxyvitamin D (25-OHD) concentration and blood pressure of Dahl salt-sensitive rats during high salt intake. In this study, we report on the relationship between high salt intake and plasma 24,25-dihydroxyvitamin D (24,25-(OH)(2)D) concentration of Dahl salt-sensitive and salt-resistant rats. Rats were fed a high salt diet (8%) and sacrificed at day 2, 7, 14, 21, and 28. Plasma 24,25-(OH)(2)D concentrations of salt-sensitive rats were reduced to 50% of that at baseline at day 2-when blood pressure and plasma 25-OHD concentration were unchanged, but 25-OHD content in the kidney was 81% of that at baseline. Plasma 24,25-(OH)(2)D concentration was reduced further to 10% of that at baseline from day 7 to 14 of high salt intake, a reduction that was prevented in rats switched to a low salt (0.3%) diet at day 7. Exogenous 24,25-dihydroxycholecalciferol (24,25-(OH)(2)D(3)), administered at a level that increased plasma 24,25-(OH)(2)D concentration to five times normal, did not attenuate the salt-induced hypertension of salt-sensitive rats. Plasma 24,25-(OH)(2)D concentration of salt-resistant rats was gradually reduced to 50% of that at baseline at day 14 and returned to baseline value at day 28 of high salt intake. We conclude that the decrease in plasma 24,25-(OH)(2)D concentration in salt-sensitive rats during high salt intake is caused by decreased 25-OHD content in the kidney and also by another unidentified mechanism.

  19. Midlife plasma vitamin D concentrations and performance in different cognitive domains assessed 13 years later.

    PubMed

    Assmann, Karen E; Touvier, Mathilde; Andreeva, Valentina A; Deschasaux, Mélanie; Constans, Thierry; Hercberg, Serge; Galan, Pilar; Kesse-Guyot, Emmanuelle

    2015-05-28

    25-Hydroxyvitamin D (25(OH)D) insufficiency is very common in many countries. Yet, the extent to which 25(OH)D status affects cognitive performance remains unclear. The objective of the present study was to evaluate the cross-time association between midlife plasma 25(OH)D concentrations and subsequent cognitive performance, using a subsample from the French 'SUpplémentation en Vitamines et Minéraux AntioXydants' randomised trial (SU.VI.MAX, 1994-2002) and the SU.VI.MAX 2 observational follow-up study (2007-9). 25(OH)D concentrations were measured in plasma samples drawn in 1994-5, using an electrochemoluminescent immunoassay. Cognitive performance was evaluated in 2007-9 with a neuropsychological battery including phonemic and semantic fluency tasks, the RI-48 (rappel indicé-48 items) cued recall test, the Trail Making Test and the forward and backward digit span. Cognitive factors were extracted via principal component analysis (PCA). Data from 1009 individuals, aged 45-60 years at baseline, with available 25(OH)D and cognitive measurements were analysed by multivariable linear regression models and ANCOVA, stratified by educational level. PCA yielded two factors, designated as 'verbal memory' (strongly correlated with the RI-48 and phonemic/semantic fluency tasks) and 'short-term/working memory' (strongly correlated with the digit span tasks). In the fully adjusted regression model, among individuals with low education, there was a positive association between 25(OH)D concentrations and the 'short-term/working memory' factor (P=0.02), mainly driven by the backward digit span (P=0.004). No association with either cognitive factor was found among better educated participants. In conclusion, higher midlife 25(OH)D concentrations were linked to better outcomes concerning short-term and working memory. However, these results were specific to subjects with low education, suggesting a modifying effect of cognitive reserve. PMID:25864611

  20. Risk Factors for a Low Linezolid Trough Plasma Concentration in Acute Infections

    PubMed Central

    Morata, Laura; Cuesta, Marta; Rojas, Jhon F.; Rodriguez, Sebastian; Brunet, Merce; Casals, Gregori; Cobos, Nazareth; Hernandez, Cristina; Martínez, José A.; Mensa, Josep

    2013-01-01

    Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (Cmin) and to determine factors associated with a Cmin < 2 mg/liter and other clinically relevant thresholds. Characteristics of 78 patients receiving 600 mg/12 h of linezolid with a Cmin determination at the steady state and within the first 10 days of treatment were retrospectively reviewed. Concentrations were measured using high-pressure liquid chromatography. Univariate and multivariate analysis were performed to identify risk factors of low Cmin. A total of 29.5% of patients had a Cmin < 2 mg/liter. The percentage was significantly higher in patients with an estimated glomerular filtration (eGF) > 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of Cmin < 2 mg/liter were an eGF > 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P = 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P = 0.006). A linezolid Cmin of <2 mg/liter was found in 29.5% of cases, and the risk was significantly higher among those with an eGF > 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy. PMID:23403416

  1. Nasal midazolam in children, plasma concentrations and the effect on respiration.

    PubMed

    Fösel, T; Hack, C; Knoll, R; Kraus, G B; Larsen, R

    1995-01-01

    Twenty ASA 1 children, one to six years old, weighing 10-20 kg, scheduled for a combination of general and caudal anaesthesia received at random midazolam 0.2, 0.4, or 0.6 mg.kg-1 or NaCl 0.9% (control group) intranasally. Drug or NaCl 0.9% were administered in one nostril, after inhalation induction of anaesthesia, intubation without relaxant and caudal anaesthesia. Spontaneous respiration was via a circle system and fresh gas flow of 6 l.min-1 (N2O/O2 = 2:1), PEEP 5 cm H2O, endtidal halothane 0.4%. Immediately before and 2, 5, 8, 12, 16, 20, 30, 60 and 120 min after application of the drug 2.5 ml blood was sampled for plasma levels of midazolam. Endtidal CO2, respiratory rate, and oxygen saturation were recorded as long as the children were intubated. Endtidal CO2 and respiratory rate showed no statistical difference between the groups at any time, however, in the group receiving 0.6 mg.kg-1, endtidal CO2 increased significantly from 5.3 kPa (41 mm Hg) at the start to 5.9 kPa (45.5 mm Hg) after 30 min. Plasma levels of midazolam were detected 2 min after application in 10 of 15 patients. Median peak levels were found between 12 and 16 min. Medians of peak plasma levels showed no statistical difference between the three groups (0.2 mg.kg-1:111 ng.ml-1, 0.4 mg.kg-1:136 ng.ml-1, 0.6 mg.kg-1:277 ng.ml-1). After 30, 60 and 120 min medians of midazolam plasma concentration were significantly higher in the group 0.6 mg.kg-1.

  2. Plasma concentrations and pharmacokinetics of phenylalanine in rats and mice administered aspartame.

    PubMed

    Hjelle, J J; Dudley, R E; Marietta, M P; Sanders, P G; Dickie, B C; Brisson, J; Kotsonis, F N

    1992-01-01

    Aspartame (L-aspartyl-L-phenylalanine methyl ester) is an esterified, dipeptide sweetener that is rapidly and completely metabolized in the gastrointestinal tract to phenylalanine, aspartic acid and methanol. The pharmacokinetics of phenylalanine (PHE) and tyrosine (TYR) were examined following the administration of oral doses of aspartame (APM) to fasted male Sprague-Dawley rats (0, 50, 100, 200, 500 and 1,000 mg/kg) and CD-1 mice (0, 100, 200, 500, 1,000 and 2,000 mg/kg). Peak plasma PHE/large neutral amino acid (LNAA) ratios were calculated. Maximal plasma PHE and TYR concentrations were observed within 1 h after dosing and returned to baseline within 4-8 h in both species regardless of the dose of APM. Mean PHE Cmaxs ranged from 73.6 to 1,161 nmol/ml in the rat, and from 78.6 to 1,967 nmol/ml in the mouse. TYR Cmaxs ranged from 91.6 to 502 nmol/ml and from 89.2 to 792 nmol/ml in the rat and mouse, respectively. AUCs and Cmaxs were linear with dose in both species. Peak plasma PHE/LNAA ratios ranged from 0.112 to 1.117 in rats and from 0.121 to 1.769 in mice. Comparison of these ratios with those observed previously in humans indicates that rodents require a 2-6 times higher dose of APM than humans to produce similar increases in plasma PHE/LNAA ratios.

  3. Nicotinic receptors and schizophrenia.

    PubMed

    Ripoll, Nadège; Bronnec, Marie; Bourin, Michel

    2004-07-01

    The incidence of smoking is very high in non-schizophrenic subjects presenting various psychiatric disorders (35 to 54%). However, the incidence of smoking is extremely high in schizophrenic patients: 80% to 90%, versus 25% to 30% of the general population. Various studies have demonstrated that the use of tobacco transiently restores the schizophrenic patient's cognitive and sensory deficits. Smoking cessation also appears to exacerbate the symptoms of the disease. Post-mortem binding studies have revealed a disturbance of nicotinic receptor expression, affecting the alpha(7) and alpha(4)beta(2) subunits, in various cerebral areas. Genetic linkage studies have also shown that the alpha(7) subunit is involved in schizophrenia. This review assesses the involvement of the nicotinic system in schizophrenia and suggests ways in which this system may participate in the pathophysiology of this disease.

  4. Nicotine and periodontal tissues

    PubMed Central

    Malhotra, Ranjan; Kapoor, Anoop; Grover, Vishakha; Kaushal, Sumit

    2010-01-01

    Tobacco use has been recognized to be a significant risk factor for the development and progression of periodontal disease. Its use is associated with increased pocket depths, loss of periodontal attachment, alveolar bone and a higher rate of tooth loss. Nicotine, a major component and most pharmacologically active agent in tobacco is likely to be a significant contributing factor for the exacerbation of periodontal diseases. Available literature suggests that nicotine affects gingival blood flow, cytokine production, neutrophil and other immune cell function; connective tissue turnover, which can be the possible mechanisms responsible for overall effects of tobacco on periodontal tissues. Inclusion of tobacco cessation as a part of periodontal therapy encourages dental professionals to become more active in tobacco cessation counseling. This will have far reaching positive effects on our patients’ oral and general health. PMID:20922084

  5. The future of nicotine replacement.

    PubMed

    Russell, M A

    1991-05-01

    Following in the wake of progress forged by nicotine chewing gum, a new generation of nicotine replacement products will soon be available as aids to giving up smoking. These range from nicotine skin patches, which take 6-8 hrs to give very flat steady-state peak blood levels, to nicotine vapour inhalers which mimic the transient high-nicotine boli that follow within a few seconds of each inhaled puff of cigarette smoke. Other products undergoing clinical trials include a nasal nicotine spray and nicotine lozenges. It is argued here that it is not so much the efficacy of new nicotine delivery systems as temporary aids to cessation, but their potential as long-term alternatives to tobacco that makes the virtual elimination of tobacco a realistic future target. Their relative safety compared with tobacco is discussed. A case is advanced for selected nicotine replacement products to be made as palatable and acceptable as possible and actively promoted on the open market to enable them to compete with tobacco products. They will also need health authority endorsement, tax advantages and support from the anti-smoking movement if tobacco use is to be gradually phased out altogether.

  6. Beneficial effects of Hippophae rhamnoides L. on nicotine induced oxidative stress in rat blood compared with vitamin E.

    PubMed

    Suleyman, Halis; Gumustekin, Kenan; Taysi, Seyithan; Keles, Sait; Oztasan, Nuray; Aktas, Omer; Altinkaynak, Konca; Timur, Handan; Akcay, Fatih; Akar, Sedat; Dane, Senol; Gul, Mustafa

    2002-09-01

    The aim of this study was to determine the effects of Hippophae rhamnoides L. extract (HRe-1) and also vitamin E as a positive control on nicotine-induced oxidative stress in rat blood, specifically alterations in erythrocyte malondialdehyde (MDA) level, activities of some erythrocyte antioxidant enzymes, and plasma vitamin E and A levels. The groups were: nicotine (0.5 mg/kg/d, intraperitoneal, i.p.); nicotine+vitamin E (75 mg/kg/d, intragastric, i.g.); nicotine+HRe-1 (1 ml/kg/d, i.g.); and control group (receiving only vehicles). There were 8 rats per group and the supplementation period was 3 weeks. Nicotine-induced increase in erythrocyte MDA level was prevented by both HRe-1 and vitamin E. Nicotine-induced decrease in erythrocyte superoxide dismutase (SOD) activity was prevented by HRe-1, but not vitamin E. HRe-1 increased the erythrocyte glutathione peroxidase (GSH-Px) activity compared with nicotine and the vitamin E groups. Catalase activity was not affected. Vitamin E supplementation increased plasma vitamin E level. Plasma vitamin A level was higher in both vitamin E and HRe-1 supplemented groups compared with nicotine and control groups. The results suggest that HRe-1 extract can be used as a dietary supplement, especially by people who smoke, in order to prevent nicotine-induced oxidative stress. PMID:12230103

  7. Fasting plasma carotenoids concentrations in Crohn's and pancreatic cancer patients compared to control subjects.

    PubMed

    Drai, J; Borel, P; Faure, H; Galabert, C; Le Moël, G; Laromiguière, M; Fayol, V

    2009-03-01

    Carotenoids are colored molecules that are widespread in the plant kingdom, but animals cannot synthesize them. Carotenes are long, apolar molecules which require fully functioning digestive processes to be absorbed properly. Hence they could be interesting markers of intestinal absorption and digestion. Indeed, only few tests are available to assess these processes and only the D-xylose tolerance test is routinely used. However D-xylose is a sugar that tests only the absorption of water-soluble compounds and it only tests duodenal absorption. In this study, we have evaluated carotenoids as markers of digestion and absorption. We compared fasting plasma carotenoids concentrations in 21 control subjects, 20 patients with Crohn's disease, and 18 patients with pancreatic cancer. Crohn's disease alters intestinal absorption while pancreatic cancer decreases pancreatic enzyme secretion thus impairing digestion. Results show that all carotenoids are significantly lower in Crohn's and cancer patients as compared to control subjects and the multifactorial analysis shows that this decrease is mostly independent of dietary intake. Interestingly, maldigestion as seen in pancreatic cancer more strongly influences plasma lutein and lycopene concentrations while malabsorption in Crohn's disease acts on other carotenoids. Thus carotenoids could be interesting alternatives for testing and following patients that are suspected of having malabsorption or maldigestion syndromes. PMID:20108210

  8. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

    PubMed

    Chambers, John C; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Van der Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E; Coin, Lachlan J; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L; Hottenga, Jouke-Jan; Kühnel, Brigitte; Kumar, Vinod; Lagou, Vasiliki; Liang, Liming; Luan, Jian'an; Vidal, Pedro Marques; Mateo Leach, Irene; O'Reilly, Paul F; Peden, John F; Rahmioglu, Nilufer; Soininen, Pasi; Speliotes, Elizabeth K; Yuan, Xin; Thorleifsson, Gudmar; Alizadeh, Behrooz Z; Atwood, Larry D; Borecki, Ingrid B; Brown, Morris J; Charoen, Pimphen; Cucca, Francesco; Das, Debashish; de Geus, Eco J C; Dixon, Anna L; Döring, Angela; Ehret, Georg; Eyjolfsson, Gudmundur I; Farrall, Martin; Forouhi, Nita G; Friedrich, Nele; Goessling, Wolfram; Gudbjartsson, Daniel F; Harris, Tamara B; Hartikainen, Anna-Liisa; Heath, Simon; Hirschfield, Gideon M; Hofman, Albert; Homuth, Georg; Hyppönen, Elina; Janssen, Harry L A; Johnson, Toby; Kangas, Antti J; Kema, Ido P; Kühn, Jens P; Lai, Sandra; Lathrop, Mark; Lerch, Markus M; Li, Yun; Liang, T Jake; Lin, Jing-Ping; Loos, Ruth J F; Martin, Nicholas G; Moffatt, Miriam F; Montgomery, Grant W; Munroe, Patricia B; Musunuru, Kiran; Nakamura, Yusuke; O'Donnell, Christopher J; Olafsson, Isleifur; Penninx, Brenda W; Pouta, Anneli; Prins, Bram P; Prokopenko, Inga; Puls, Ralf; Ruokonen, Aimo; Savolainen, Markku J; Schlessinger, David; Schouten, Jeoffrey N L; Seedorf, Udo; Sen-Chowdhry, Srijita; Siminovitch, Katherine A; Smit, Johannes H; Spector, Timothy D; Tan, Wenting; Teslovich, Tanya M; Tukiainen, Taru; Uitterlinden, Andre G; Van der Klauw, Melanie M; Vasan, Ramachandran S; Wallace, Chris; Wallaschofski, Henri; Wichmann, H-Erich; Willemsen, Gonneke; Würtz, Peter; Xu, Chun; Yerges-Armstrong, Laura M; Abecasis, Goncalo R; Ahmadi, Kourosh R; Boomsma, Dorret I; Caulfield, Mark; Cookson, William O; van Duijn, Cornelia M; Froguel, Philippe; Matsuda, Koichi; McCarthy, Mark I; Meisinger, Christa; Mooser, Vincent; Pietiläinen, Kirsi H; Schumann, Gunter; Snieder, Harold; Sternberg, Michael J E; Stolk, Ronald P; Thomas, Howard C; Thorsteinsdottir, Unnur; Uda, Manuela; Waeber, Gérard; Wareham, Nicholas J; Waterworth, Dawn M; Watkins, Hugh; Whitfield, John B; Witteman, Jacqueline C M; Wolffenbuttel, Bruce H R; Fox, Caroline S; Ala-Korpela, Mika; Stefansson, Kari; Vollenweider, Peter; Völzke, Henry; Schadt, Eric E; Scott, James; Järvelin, Marjo-Riitta; Elliott, Paul; Kooner, Jaspal S

    2011-10-16

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.

  9. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

    PubMed

    Chambers, John C; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Van der Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E; Coin, Lachlan J; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L; Hottenga, Jouke-Jan; Kühnel, Brigitte; Kumar, Vinod; Lagou, Vasiliki; Liang, Liming; Luan, Jian'an; Vidal, Pedro Marques; Mateo Leach, Irene; O'Reilly, Paul F; Peden, John F; Rahmioglu, Nilufer; Soininen, Pasi; Speliotes, Elizabeth K; Yuan, Xin; Thorleifsson, Gudmar; Alizadeh, Behrooz Z; Atwood, Larry D; Borecki, Ingrid B; Brown, Morris J; Charoen, Pimphen; Cucca, Francesco; Das, Debashish; de Geus, Eco J C; Dixon, Anna L; Döring, Angela; Ehret, Georg; Eyjolfsson, Gudmundur I; Farrall, Martin; Forouhi, Nita G; Friedrich, Nele; Goessling, Wolfram; Gudbjartsson, Daniel F; Harris, Tamara B; Hartikainen, Anna-Liisa; Heath, Simon; Hirschfield, Gideon M; Hofman, Albert; Homuth, Georg; Hyppönen, Elina; Janssen, Harry L A; Johnson, Toby; Kangas, Antti J; Kema, Ido P; Kühn, Jens P; Lai, Sandra; Lathrop, Mark; Lerch, Markus M; Li, Yun; Liang, T Jake; Lin, Jing-Ping; Loos, Ruth J F; Martin, Nicholas G; Moffatt, Miriam F; Montgomery, Grant W; Munroe, Patricia B; Musunuru, Kiran; Nakamura, Yusuke; O'Donnell, Christopher J; Olafsson, Isleifur; Penninx, Brenda W; Pouta, Anneli; Prins, Bram P; Prokopenko, Inga; Puls, Ralf; Ruokonen, Aimo; Savolainen, Markku J; Schlessinger, David; Schouten, Jeoffrey N L; Seedorf, Udo; Sen-Chowdhry, Srijita; Siminovitch, Katherine A; Smit, Johannes H; Spector, Timothy D; Tan, Wenting; Teslovich, Tanya M; Tukiainen, Taru; Uitterlinden, Andre G; Van der Klauw, Melanie M; Vasan, Ramachandran S; Wallace, Chris; Wallaschofski, Henri; Wichmann, H-Erich; Willemsen, Gonneke; Würtz, Peter; Xu, Chun; Yerges-Armstrong, Laura M; Abecasis, Goncalo R; Ahmadi, Kourosh R; Boomsma, Dorret I; Caulfield, Mark; Cookson, William O; van Duijn, Cornelia M; Froguel, Philippe; Matsuda, Koichi; McCarthy, Mark I; Meisinger, Christa; Mooser, Vincent; Pietiläinen, Kirsi H; Schumann, Gunter; Snieder, Harold; Sternberg, Michael J E; Stolk, Ronald P; Thomas, Howard C; Thorsteinsdottir, Unnur; Uda, Manuela; Waeber, Gérard; Wareham, Nicholas J; Waterworth, Dawn M; Watkins, Hugh; Whitfield, John B; Witteman, Jacqueline C M; Wolffenbuttel, Bruce H R; Fox, Caroline S; Ala-Korpela, Mika; Stefansson, Kari; Vollenweider, Peter; Völzke, Henry; Schadt, Eric E; Scott, James; Järvelin, Marjo-Riitta; Elliott, Paul; Kooner, Jaspal S

    2011-11-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function. PMID:22001757

  10. Determining the Volume of Additive Solution and Residual Plasma in Whole Blood Filtered and Buffy Coat Processed Red Cell Concentrates

    PubMed Central

    Jordan, Andrew; Acker, Jason P.

    2016-01-01

    Summary Background Residual plasma in transfused red cell concentrates (RCCs) has been associated with adverse transfusion outcomes. Despite this, there is no consensus on the standard procedure for measuring residual plasma volume. Methods The volumes of residual plasma and additive solution were measured in RCCs processed using two separation methods: whole blood filtration (WBF) and buffy coat (BC)/RCC filtration. The concentration of mannitol and albumin in RCC components was measured using colorimetric assays. Mannitol concentration was used to calculate additive solution volume. Residual plasma volume was calculated using two methods. Results Calculated RCC supernatant volumes were much lower in BC-processed components compared to WBF-processed components (BC = 97 ± 6 ml, WBF = 109 ± 4 ml; p < 0.05). Calculated additive solution volumes were greater in WBF- than in BC-processed components (BC = 81 ± 4 ml, WBF = 105 ± 2 ml; p < 0.05). Absolute residual plasma volume varied significantly based on the calculation method used. Conclusion Disparity between plasma volume calculation methods was observed. Efforts should be made to standardize residual plasma volume measurement methods in order to accurately assess the impact of residual plasma on transfusion outcomes. PMID:27330533

  11. Comparison of Oseltamivir and Oseltamivir Carboxylate Concentrations in Venous Plasma, Venous Blood, and Capillary Blood in Healthy Volunteers

    PubMed Central

    Instiaty, Insti; Lindegardh, Niklas; Jittmala, Podjanee; Hanpithakpong, Warunee; Blessborn, Daniel; Pukrittayakamee, Sasithon; White, Nicholas J.

    2013-01-01

    Oseltamivir and oseltamivir carboxylate concentrations were measured in venous plasma, venous blood, and capillary blood taken simultaneously from 24 healthy volunteers. Median (range) venous-blood-to-plasma ratios were 1.42 (0.920 to 1.97) for oseltamivir and 0.673 (0.564 to 0.814) for oseltamivir carboxylate. Capillary blood/venous plasma ratios were 1.32 (0.737 to 3.16) for oseltamivir and 0.685 (0.502 to 1.34) for oseltamivir carboxylate. Oseltamivir concentrations in venous and capillary blood were similar. Oseltamivir carboxylate showed a time-dependent distribution between venous and capillary blood. PMID:23507284

  12. Serum and plasma concentration of oxidant and antioxidants in patients of Helicobacter pylori gastritis and its correlation with gastric cancer.

    PubMed

    Khanzode, Shruti S; Khanzode, Suchet D; Dakhale, Ganesh N

    2003-05-30

    Serum superoxide dismutase, plasma ascorbic acid and lipid peroxidation in H. pylori gastritis and gastric cancer patients were compared with values for age matched healthy subjects. Serum superoxide dismutase and serum malondialdehyde were analyzed spectrophotometrically whereas plasma ascorbic acid was determined by colorimetric method. Significant increase in serum superoxide dismutase and serum malondialdehyde and significant decrease in plasma ascorbic acid were observed in H. pylori gastritis and gastric cancer patients compared to control subjects. The concentration of serum superoxide dismutase and serum malondialdehyde was significantly higher and plasma ascorbic acid was significantly lower in gastric cancer as compared to H. pylori gastritis patients. Our results demonstrate that a correlation existed between the concentration of serum superoxide dismutase, plasma ascorbic acid and lipid peroxidation in H. pylori gastritis and gastric cancer patients.

  13. Plasma and urine concentrations of marbofloxacin following single subcutaneous administration to cats.

    PubMed

    Kietzmann, Manfred; Niedorf, Frank; Kramer, Sabine; Hoffmann, Marina; Schneider, Marc; Vallé, Marc; Pankow, Rüdiger

    2011-01-01

    The pharmacokinetic properties of marbofoxacin, a third generation fluoroquinolone, were investigated in 12 healthy adult cats after single subcutaneous (SC) administration of 2 mg/kg BW (Part I, n=8 cats) and 4 mg/kg BW (Part II, n=4 cats). In each part of the study blood and urine samples were collected before treatment and thereafter for 5 days. The plasma and urine concentrations of marbofloxacin were determined by HPLC with UV detection. Pharmacokinetic calculations were performed for each treated animal using an open one-compartment-model with first-order elimination after SC dosing. Marbofloxacin in plasma (means): Maximum concentrations (Cmax) of about 1.2 and 3.0 microg/ml were measured 2.3 and 4 hours (tmax) after dosing of 2 and 4 mg/kg BW, respectively. Elimination from the body was low with a total clearance (Cl/F) of approximately 0.1 l/h/kg for both dosages. The half-life (t 1/2) for this process was calculated with 8-10 hours. AUC increased almost proportional when doubling the dose, i.e., 19.77 +/- 6.25 microg * h/ml (2 mg/kg BW) and 51.26 +/- 11.83 microg * h/ml (4 mg/kg BW). Plasma kinetics measured were in accordance with data from literature. Marbofloxacin in urine (means): Maximum drug concentrations were detected 4 and 8 hours after dosing with 70 microg/ml (2 mg/kg BW) and 160 microg/ml (4 mg/kg BW), respectively. Inhibitory effects of the urinary matrix on the antimicrobial activity of the drug were taken into account when performing PK/PD calculations. However, a concentration-dependent bactericidal activity (Cmax/MIC > 8-10) which is claimed for fluoroquinolones was sufficiently met with focus on Escherichia (E.) coli (MIC90 0.5 microg/ml). In the same matrix a threshold value of 1.0 microg/ml was undercut 82 and 116 hours after SC dosing, respectively. Hence, a time-dependent bacteria killing kinetic (T > MIC) which may be of relevance for some Gram-positive germs like Staphylococcus spp. (MIC90 1.0 microg/ml) should be covered, too.

  14. Genetics of nicotinic acetylcholine receptors: relevance to nicotine addiction

    PubMed Central

    Mineur, Yann S.; Picciotto, Marina R.

    2008-01-01

    Human twin studies have suggested that there is a substantial genetic component underlying nicotine dependence, ongoing smoking and ability to quit. Similarly, animal studies have identified a number of genes and gene products that are critical for behaviors related to nicotine addiction. Classical genetic approaches, gene association studies and genetic engineering techniques have been used to identify the gene products involved in nicotine dependence. One class of genes involved in nicotine-related behavior is the family of nicotinic acetylcholine receptors (nAChRs). These receptors are the primary targets for nicotine in the brain. Genetic engineering studies in mice have identified a number of subunits that are critical for the ability of nicotine to activate the reward system in the brain, consisting of the dopaminergic cell bodies in the ventral tegmental area and their terminals in the nucleus accumbens and other portions of the mesolimbic system. In this review we will discuss the various lines of evidence suggesting that nAChRs may be involved in smoking behavior, and will review the human and animal studies that have been performed to date examining the genetic basis for nicotine dependence and smoking. PMID:17632086

  15. Effect of vacuum conditions and plasma concentration on the chemical composition and adhesion of vacuum-plasma coatings

    NASA Astrophysics Data System (ADS)

    Borisov, D. P.; Kuznetsov, V. M.; Slabodchikov, V. A.

    2015-11-01

    The paper reports on the chemical composition of titanium nitride (TiN) and silicon (Si) coatings deposited with a new technological vacuum plasma setup which comprises magnetron sputtering systems, arc evaporators, and an efficient plasma generator. It is shown that due to highly clean vacuum conditions and highly clean surface treatment in the gas discharge plasma, both the coating-substrate interface and the coatings as such are almost free from oxygen and carbon. It is found that the coating-substrate interface represents a layer of thickness ≥ 60 nm formed through vacuum plasma mixing of the coating and substrate materials. The TiN coatings obtained on the new equipment display a higher adhesion compared to brass coatings deposited by industrial technologies via intermediate titanium oxide layers. It is concluded that the designed vacuum plasma equipment allows efficient surface modification of materials and articles by vacuum plasma immersion processes.

  16. Cardiovascular responses to microinjections of nicotine into the caudal ventrolateral medulla of the rat.

    PubMed

    Aberger, K; Chitravanshi, V C; Sapru, H N

    2001-02-16

    This study focuses on the role of nicotinic receptors located in the caudal ventrolateral medullary depressor area (CVLM) in regulating/modulating cardiovascular function. Blood pressure and heart rate were monitored by standard techniques in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Multi-barreled glass-micropipettes (tip size 20-40 microm) were used to make microinjections (100 nl) into the CVLM. Concentrations of nicotine ranging from 250 micromto 10 mM were microinjected unilaterally into the CVLM. The maximum depressor and bradycardic responses were elicited by a 1 mM concentration of nicotine. Sequential microinjections of mecamylamine (1 mM), an antagonist for nicotinic receptors containing alpha3beta4 subunits, then alpha-bungarotoxin (1 microm), an antagonist for nicotinic receptors containing alpha-7 subunits, were made into the CVLM. Microinjecting a combination of a nicotinic receptor blocker and toxin resulted in the complete blockade of the cardiovascular responses induced by nicotine (1 mM, 100 nl). These results indicate that: (1) nicotinic receptors are present in the CVLM; (2) activation of these receptors results in depressor and bradycardic responses; (3) for a complete blockade of nicotine-induced cardiovascular responses, it is necessary to use a combination of mecamylamine and alpha-bungarotoxin; (4) since mecamylamine and alpha-bungarotoxin are known to block nicotinic receptors containing alpha3beta4 and alpha-7 subunits, respectively, two different subtypes of nicotinic receptors (one which contains a combination of alpha3beta4 subunits, and one which contains alpha-7 subunits) must be present in the CVLM; and (5) it is not clear whether these two subtypes of nicotinic receptor are located on the same or different populations of CVLM-neurons.

  17. Prognostic and diagnostic value of plasma soluble ST2 concentrations in Acute Respiratory Distress Syndrome

    PubMed Central

    Bajwa, Ednan K.; Volk, Jessica A.; Christiani, David C.; Harris, R. Scott; Matthay, Michael A.; Thompson, B. Taylor; Januzzi, James L.

    2013-01-01

    Objective Soluble ST2 (sST2) is a biomarker of myocardial strain and inflammation. The characteristics of acute respiratory distress syndrome (ARDS) include inflammation and cardiovascular dysfunction. We sought to determine whether plasma sST2 concentration is associated with outcome and response to conservative fluid management, and whether sST2 concentration discriminates ARDS from decompensated heart failure (HF). Design, Setting, and Patients We assayed plasma sST2 concentrations in 826 patients in the Fluid and Catheter Treatment Trial (FACTT), a multi-center randomized controlled trial of conservative fluid management in ARDS, as well as a cohort of patients with decompensated HF. We tested whether sST2 was associated with outcome, response to therapy, and diagnostic utility for ARDS vs. HF. Measurements and Main Results Non-survivors had higher day 0 (P<.0001) and day 3 (P<.0001) sST2 concentrations. After adjustment for severity of illness, higher sST2 concentration was associated with mortality, with odds ratio (ORadj) 1.47 (95% confidence interval [CI] 0.99 – 2.20, P=.06) at day 0, 2.94 (95% CI 2.00 – 4.33, P<.0001) at day 3, and 3.63 (95% CI 2.38 – 5.53, P<.0001) if sST2 increased between days. Cumulative fluid balance was more positive among patients with higher day 0 (median 5212 mL, interquartile range [IQR] 200 – 12284 vs. 2020 mL, −2034 – 7091; P<0.0001), and day 3 sST2 (median 7678 mL, IQR 2217 – 14278 vs. 1492 mL, −2384 – 6239; P<0.0001). sST2 showed excellent discriminative ability between the FACTT and HF populations (Area under ROC curve=0.98, P<0.0001). Conclusions Higher sST2 concentrations are associated with worse outcome in ARDS and may have value for discriminating ARDS from heart failure. PMID:23939353

  18. Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock

    PubMed Central

    Strandberg, G; Larsson, A; Lipcsey, M; Michalek, J; Eriksson, M

    2015-01-01

    Background We aimed to investigate whether comparable antibiotic concentrations could be reached with intraosseous and intravenous administration during septic shock. Methods In this randomized, prospective experimental study conducted at an animal research laboratory at the University Hospital of Uppsala, eight anesthetized pigs, weighing 21.2 to 29.1 kg (mean: 25.2 ± 2.3 kg), received endotoxin infusion at 4 μg/kg/h for 6 h. At the onset of clinical shock, alternatively after 3 h of endotoxemia, they received 75 mg/kg of cefotaxime and 7 mg/kg of gentamicin either in a proximal tibial intraosseous catheter or in a peripheral intravenous catheter. Mixed venous samples were taken after 5, 15, 30, 60, 120 and 180 min and analyzed for antibiotic concentrations. Results For both antibiotics, plasma concentrations after intraosseous and intravenous administration followed similar curves throughout the observation period, and peak concentrations were comparable. Mean concentration area under the curve (AUC mg × h/l) for cefotaxime was 108.1 ± 19.5 after intraosseous and 116.5 ± 11.1 after intravenous administration; ratio 0.93, (95% CI 0.71–1.19). Mean AUC for gentamicin was 28.1 ± 6.8 for intraosseous and 32.2 ± 3.5 for intravenous administration; ratio 0.87 (95% CI 0.62–1.19). Conclusions In this porcine septic shock model, intraosseous and intravenous administration of gentamicin and cefotaxime yielded comparable concentrations. In an emergency, intraosseous administration of these antibiotics may be considered in severe infections when venous access is difficult. PMID:25557933

  19. Choice of anesthetic technique on plasma concentrations of interleukins and cell adhesion molecules

    PubMed Central

    2013-01-01

    Background Whether inflammatory responses to surgery are comparably activated during total intravenous anesthesia (TIVA) and during volatile anesthesia remains unclear. We thus compared the perioperative effects of TIVA and isoflurane anesthesia on plasma concentrations of proinflammatory and anti-inflammatory interleukins and cell adhesion molecules. Methods Patients having laparoscopic cholecystectomies were randomly allocated to two groups: 44 were assigned to TIVA and 44 to isoflurane anesthesia. IL-1β, IL-6, IL-8, IL-10, IL-13, and the cellular adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were determined preoperatively, before incision, and at 2 and 24 hours postoperatively. Our primary outcomes were area-under-the-curve cytokine and adhesion molecule concentrations over 24 postoperative hours. Results The only statistically significant difference in area-under-the-curve concentrations was for IL-6, which was greater in patients given isoflurane:78 (95% confidence interval (CI): 52 to 109) pg/ml versus 33 (22 to 50) pg/ml, P= 0.006. Two hours after surgery, IL-6 was significantly greater than baseline in patients assigned to isoflurane: 47 (95% CI: 4 to 216, P<0.001) pg/ml versus 18 (95%CI: 4 to 374, P<0.001) pg/ml in the TIVA group. In contrast, IL-10 was significantly greater in patients assigned to TIVA: 20 (95% CI: 2 to 140, P<0.001) pg/ml versus 12 (95% CI: 3 to 126, P<0.001) pg/ml. By 24 hours after surgery, concentrations were generally similar between study groups and similar to baseline values. Conclusion The only biomarker whose postoperative area-under-the-curve concentrations differed significantly as a function of anesthetic management was IL-6. Two hours after surgery, IL-6 concentrations were significantly greater in patients given isoflurane than TIVA. However, the differences were modest and seem unlikely to prove clinically important. Further studies are needed. PMID:24472144

  20. Nicotine Delivery to Rats via Lung Alveolar Region-Targeted Aerosol Technology Produces Blood Pharmacokinetics Resembling Human Smoking

    PubMed Central

    2013-01-01

    Introduction: Nicotine is a heavily used addictive drug acquired through smoking tobacco. Nicotine in cigarette smoke is deposited and absorbed in the lungs, which results in a rapidly peaked slowly declining arterial concentration. This pattern plays an important role in initiation of nicotine addiction. Methods: A method and device were developed for delivering nicotine to rodents with lung alveolar region-targeted aerosol technology. The dose of delivery can be controlled by the nicotine aerosol concentration and duration of exposure. Results: Our data showed that, in the breathing zone of the nose-only exposure chamber, the aerosol droplet size distribution was within the respirable diameter range. Rats were exposed to nicotine aerosol for 2min. The arterial blood nicotine concentration reached 43.2±15.7ng/ml (mean ± SD) within 1–4min and declined over the next 20min, closely resembling the magnitude and early pharmacokinetics of a human smoking a cigarette. The acute inhalation toxicity of nicotine: LC50 = 2.3mg/L was determined; it was affected by pH, suggesting that acidification decreases nicotine absorption and/or bioavailability. Conclusions: A noninvasive method and toolkit were developed for delivering nicotine to rodents that enable rapid delivery of a controllable amount of nicotine into the systemic circulation and brain-inducing dose-dependent pharmacological effects, even a lethal dose. Aerosol inhalation can produce nicotine kinetics in both arterial and venous blood resembling human smoking. This method can be applied to studies of the effects of chronic intermittent nicotine exposure, nicotine addiction, toxicology, tobacco-related diseases, teratogenicity, and for discovery of pharmacological therapeutics. PMID:23239844

  1. Effects of storage time on total protein and globulin concentrations in bovine fresh frozen plasma obtained for transfusion.

    PubMed

    Proverbio, D; Spada, E; Baggiani, L; Bagnagatti De Giorgi, G; Roggero, N; Belloli, A; Pravettoni, D; Perego, R

    2015-01-01

    To evaluate the effects of storage conditions on total protein (TP) and globulin fractions in fresh frozen bovine plasma units prepared and stored for transfusion, TP and globulin fractions were evaluated in fresh plasma and at 1 month and 6 and 12 months after blood collection in plasma stored at -20°C. Significant differences in concentrations were found in the median concentration of total protein (P=0.0336), between 0 months and 1 month (P=0.0108), 0 and 6 months (P=0.0023), and 0 and 12 months (P=0.0027), in mean concentration (g/dL) of albumin (P=0.0394), between 0 months and 1 month (P=0.0131), 0 and 6 months (P=0.0035), and 0 and 12 months (P=0.0038), and beta-2 fraction (P=0.0401), between 0 and 6 months (P=0.0401) and 0 and 12 months (P=0.0230). This study suggests that total gamma globulin concentration in bovine frozen plasma is stable for 12 months at -20°C. Total protein, ALB, and beta-2 fraction have significantly different concentrations (g/dL) when compared to prestorage. This study has shown IgG protein fraction stability in bovine fresh frozen plasma collected for transfusion; therefore, bovine fresh frozen plasma seems to be suitable for the treatment of hypogammaglobulinemia (failure of passive transfer) in calves when stored for 12 months at -20°C.

  2. Randomised trial investigating effect of a novel nicotine delivery device (Eclipse) and a nicotine oral inhaler on smoking behaviour, nicotine and carbon monoxide exposure, and motivation to quit

    PubMed Central

    Fagerstrom, K.; Hughes, J.; Rasmussen, T.; Callas, P.

    2000-01-01

    OBJECTIVE—To monitor the effect of a novel nicotine delivery device that may produce fewer carcinogens (Eclipse) on cigarette smoking, carbon monoxide and nicotine concentrations, and motivation to give up smoking. The smoker's own brand of cigarette and a nicotine replacement product (Nicotrol inhaler) were used as comparisons.
DESIGN—After baseline data were recorded, smokers were randomised to either Eclipse or inhaler for two weeks and then switched to the other product for another two weeks. Thereafter a second baseline was obtained.
SETTING AND PARTICIPANTS— Fifty smokers were included and data are reported for the 40 with complete data sets. The smokers were not trying to quit but were interested in trying a new product to reduce their risk. They visited a smoking clinic 10 times during the six week period of the trial.
INTERVENTION—No counselling to aid reduction by Eclipse or inhaler was given.
MAIN OUTCOME MEASURES—At each visit smoking status and carbon monoxide concentrations were recorded. In half of the visits withdrawal symptoms, attitudes towards smoking, heart rate, and blood nicotine concentrations were also recorded.
RESULTS—Eclipse use decreased the number of cigarettes smoked per day (cpd) from 19.1 cpd at baseline to 2.1 cpd (p < 0.001), but increased carbon monoxide concentrations in parts per million (ppm) from 21.0 ppm to 33.0 ppm (p < 0.001). A similar decrease in cigarettes smoked per day was seen with the Nicotrol inhaler, from 19.1 cpd to 4.8 cpd (p < 0.001), but carbon monoxide decreased from 21.0 ppm to 12.7 ppm (p < 0.001). The blood nicotine concentration remained fairly stable with Eclipse, increasing slightly from 16.8 ng/ml to 18.0 ng/ml, while for the inhaler a significant drop was noted, from 16.8 ng/ml to 12.2 ng/ml (p < 0.002). Craving and withdrawal did not increase with Eclipse. Few significant adverse events occurred with Eclipse.
CONCLUSIONS—Eclipse can dramatically

  3. Plasma progesterone and prolactin concentrations in overtly pseudopregnant bitches: a clinical study.

    PubMed

    Tsutsui, T; Kirihara, N; Hori, T; Concannon, P W

    2007-03-15

    Plasma concentrations of progesterone (P(4)) and prolactin (PRL) were measured in 35 bitches presented at veterinary clinics for symptoms of overt pseudopregnancy (PSP) between 50 and 95 days after the onset of proestrus. Results were compared to those from samples collected from 35 control bitches at comparable stages of the ovarian cycle (expressed as days after the onset of observed signs of proestrus). In the PSP bitches at 71.4+/-1.6 (mean+/-S.E.M.) days of the cycle, P(4) (1.5+/-0.2ng/mL) was lower (P<0.01) and PRL (16.0+/-1.9ng/mL) was higher (P<0.01), compared to P(4) (2.7+/-0.4ng/mL) and PRL (2.9+/-0.6ng/mL) in control bitches at 70.6+/-1.5 days of the cycle. Low P(4) was not a prerequisite for elevated PRL. Although elevated (> or =10ng/mL) PRL (20.9+/-2.0ng/mL) occurred more often with low (<2ng/mL) P(4) (20 of 24 cases) it also occurred with P(4) above 3ng/mL in two affected bitches and in two control bitches. Whether the occurrence of relatively low PRL concentrations (<4ng/mL) in samples obtained from 4 of the 35 pseudopregnant bitches reflected variable and often elevated PRL secretion or increased sensitivity to PRL in the absence of elevated prolactin in those animals was not determined. We inferred that elevated plasma PRL was often involved in the etiology of overt PSP; furthermore, a premature decline in circulating P(4) concentrations may be a factor in some instances.

  4. Concentrations, metabolic clearance rates, production rates and plasma binding of cortisol in Antarctic phocid seals.

    PubMed

    Liggins, G C; France, J T; Schneider, R C; Knox, B S; Zapol, W M

    1993-10-01

    We have reported previously that plasma of the Weddell seal, a member of the phocid family, contains a very high concentration of cortisol. The present study was undertaken to determine whether high cortisol levels were common to seals in the Antarctic environment, or to other phocidae, and to determine the mechanism of the hypercortisolaemia. High levels of cortisol (0.82-2.38 mumol/l) were found in 4 phocidae (Weddell, crabeater, leopard and Southern elephant seals), whereas levels in a member of the otariid family (Antarctic fur seal) were similar to human values. Metabolic clearance rates (MCR) and production rates (PR) of cortisol were determined in the field in Weddell (N = 1), crabeater (N = 3) and leopard (N = 3) seals following bolus injections of [3H] cortisol. The MCR and PR did not differ between the three phocids, but whereas the MCR of 410-590 1/day was twice that of human values, the PR of 460-1180 mumol.m-2 x d-1 was up to 40-fold greater. The binding capacity of corticosteroid-binding globulin (CBG) was equal to or greater than the plasma concentrations of cortisol, resulting in relatively low concentrations of free cortisol. We conclude that hypercortisolaemia is maintained in phocid seals mainly by a high production rate--the highest (corrected for surface area) reported in any species. The relatively low cortisol levels in otariid seals studied in the same environment suggest that the high PR in phocidae is unrelated to the harsh climatic conditions, but may be part of their adaptation for diving to extreme depths.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Hydrogen peroxide and antioxidizing enzymes involved in modulation of transient facilitatory effects of nicotine on neurogenic contractile responses in rat gastric fundus.

    PubMed

    Ozger Ilhan, Sevil; Sarioglu, Yusuf; Vural, Ismail Mert; Dileköz, Ergin; Oztürk, Gökçe Sevim; Ercan, Zeynep Sevim

    2008-06-10

    Nicotine acts as an agonist of nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors play a role in the modulation of neurotransmitter release in both the central and the peripheral nervous system. Moderate reactive oxygen species levels modulate the regulation of physiological functions e.g. neurotransmitter release. Previously in rabbit gastric fundus we demonstrated that nicotine transiently increased neurogenic contraction induced by electrical field stimulation (EFS). In this study we aimed to investigate the effects of hydrogen peroxide (H2O2), antioxidizing enzymes catalase and superoxide dismutase (SOD) on nicotine induced increases at cholinergic neurotransmission in rabbit gastric fundus. Although H2O2 did not alter nicotine induced transient neurogenic contractions at concentrations of 10(-6) and 10(-5) M, at high concentration (10(-4) M) H2O2 inhibited nicotine induced increases. Catalase (500 units/ml), enhanced the effect of nicotine but did not alter nicotine induced transient neurogenic contractions at the concentrations of 100 and 250 units/ml. SOD (75,150 and 225 units/ml) did not alter nicotine induced transient neurogenic contractions. In conclusion, at high concentration H2O2 (10(-4) M) inhibited nicotine's transient ability to augment neurogenic contractions and catalase (500 units/ml) enhanced the effect of nicotine. PMID:18455720

  6. Genotoxic and antiapoptotic effect of nicotine on human gingival fibroblasts.

    PubMed

    Argentin, Gabriella; Cicchetti, Rosadele

    2004-05-01

    Growing evidence suggests that nicotine, the addictive component of cigarettes, can have a direct role in tumor development by enhancing cell proliferation and impairing apoptotic process in certain types of human cancer cell lines. Since the correlation between apoptosis and DNA damage is already well documented, we investigated the response of human gingival fibroblasts (HGFs) to nicotine exposure by examining its effect on DNA damage induction and apoptotic process in parallel. To assess the genotoxicity of this drug, the cytokinesis-block micronucleus (CBMN) test was performed. Treatment of HGFs with nicotine, at a concentration of 1 microM, caused a statistically significant increase of micronucleus (MN) frequency at the tested time intervals, while no change was detected in cell growth under the same conditions. Furthermore, we found that preincubation of HGFs with 1 microM nicotine strongly attenuated staurosporine (STP)-induced apoptosis. Finally, we found that cultures exposed to nicotine showed an increase of reactive oxygen species, as determined by increased levels of 2,7-dichlorofluorescein (DCF). When cells were prelabeled with N-acetyl-cysteine (NAC), a substrate for glutathione synthesis, and catalase (CAT), the oxygen free radical scavenger, a significant reduction in cytogenetic damage was observed. Thus, for the first time, we report a concomitant genotoxic and antiapoptotic effect of nicotine in HGFs. PMID:14718647

  7. Characterization of Surface-Enhanced Raman Scattering of Nicotine Utilizing Plasmonic Nanometals for the Applications of Medical and Chemical Sensing

    NASA Astrophysics Data System (ADS)

    Jackson, Ashley; Rigo, Maria; Seo, Jaetae; HU Team

    2011-05-01

    Raman spectroscopy has received a great deal of interest for its applications in biological sensing and cell imaging due to the ease with which it can be used to extract significant data from tissue and cells. This study has focused on the application of SERS for nicotine detection. Liquid nicotine was diluted and combined with Au nanoparticles (NPs). The nicotine-gold solution was analyzed by acquiring Raman spectra data using a Delta Nu Spectrometer. Absorption data shows the characteristic peak of Au NPs at ~528 nm while showing successful aggregation of the nicotine particles. Data taken from Raman spectra shows characteristic Raman shifts of nicotine at ~1030 cm-1 and ~1590 cm-1. Currently work is being done to optimize the SERS signal for nicotine in the 1590-1600 region using higher concentrations of nicotine and various sizes of Au NPs. This work at Hampton University was supported by the National Science Foundation (HRD-0734635 and HRD-063037).

  8. Comparison of blood lead and blood and plasma δ-aminolevulinic acid concentrations as biomarkers for lead poisoning in cattle.

    PubMed

    Kang, Hwan Goo; Bischoff, Karyn; Ebel, Joseph G; Cha, Sang Ho; McCardle, James; Choi, Cheong Up

    2010-11-01

    Lead (Pb) concentrations in whole blood and δ-aminolevulinic acid (ALA) concentrations in plasma and whole blood from 37 cattle with suspected Pb exposure were determined in order to investigate the usefulness of ALA as a biological indicator for Pb poisoning in cattle. Cows were divided into 4 groups based on blood Pb, as follows: <30 ppb (group 1), 30-100 ppb (group 2), 100-300 ppb (group 3), and >300 ppb (group 4). The derivatization reaction for ALA was improved by a greater than 2-fold measure in whole blood and by a 10-fold measure in plasma by adding 75 and 50 µl of 0.1 N HCl, respectively. Blood Pb concentrations ranged from <25 ppb to 1,006 ppb (185.5 ± 254.9 ppb), with 17 samples containing >50 ppb Pb. Delta-aminolevulinic acid concentrations in whole blood and plasma ranged from <62.7 ppb to 96.9 ppb (77.4 ± 8.4 ppb) and from <5.0 ppb to 24.0 ppb (4.6 ± 3.8 ppb), respectively. Whole blood ALA did not correlate with blood lead concentrations in any group. Increase in plasma ALA concentration was dependent on blood Pb concentration. There was no correlation between blood Pb concentration and plasma ALA concentration in group 2 (n  =  4), but correlation coefficients were 0.736 in group 3 and 0.807 in group 4, respectively. The correlation coefficient was increased to 0.851 when groups 3 and 4 were combined. Based on these observations, in cattle, plasma ALA is a more reliable biological biomarker for Pb exposure than is blood ALA.

  9. Nicotine cue: lack of effect of the alpha 7 nicotinic receptor antagonist methyllycaconitine.

    PubMed

    Brioni, J D; Kim, D J; O'Neill, A B

    1996-04-22

    To assess the role of the alpha 7 neuronal nicotinic acetylcholine receptor in the discriminative stimulus properties of (-)-nicotine, this study investigated the ability of the alpha 7 receptor antagonist methyllycaconitine to modulate the nicotine cue. In rats trained to discriminate (-)-nicotine from saline, intraperitoneal injections of methyllycaconitine neither induced nor blocked the nicotine cue. Intracerebroventricular administration of methyllycaconitine, neither potentiated nor blocked the effect of (-)-nicotine. On the other hand, intracerebroventricular injections of mecamylamine blocked the nicotine cue. The available evidence indicate that the nicotinic acetylcholine receptors in the brain blocked by methyllycaconitine, those presumably containing alpha 7 subunits, do not participate in the expression of the discriminative stimulus properties of (-)-nicotine.

  10. New method of tracing blood hemoglobin concentration to hematocrit ratio for monitoring plasma dilution and osmotic origin shifts in blood.

    PubMed

    Andrijauskas, Audrius; Ivaskevicius, Juozas

    2006-01-01

    Blood hemoglobin concentration and hematocrit are probably the most widely used parameters for outpatient and inpatient examination. In addition to their inherent significance for evaluation of blood viscosity and oxygen carrying capacity, these parameters are traditionally used as tracers of plasma dilution. Blood test derived results are conventionally recorded on multiple pages in patient's medical records making dynamical investigations tedious and time-consuming. In addition, research results describing plasma dilution by means of hemoglobin or hematocrit are presented in a clinically unpractical way. A new method, referred to as HBS Graphics (patent pending--USA serial # 60/712809) is introduced for the first time in this article. This method of evaluation of dynamical hemoglobin concentration, hematocrit and mean corpuscular hemoglobin concentration value deploys interfering parameter shifts for the evaluation of plasma dilution in relation to osmotic dynamics. The HBS Graphics complements two coordinate systems--hemoglobin concentration and hematocrit--with incorporated mean corpuscular hemoglobin concentration value specific trends referred to as radiating lines. Isosmotic plasma dilution and erythrocyte volume shifts follow radiating lines, while osmotic shifts induce intertrend shifts. This article also reviews other methods of tracing plasma dilution by means of blood hemoglobin concentration and hematocrit dynamics.

  11. The Concentrations of Circulating Plasma Oxytocin and the Pattern of Oxytocin Release in Mare during Oestrus and after Ovulation

    NASA Astrophysics Data System (ADS)

    Bae, Sung Eun

    Mares susceptible to persistent mating-induced endometritis (PMIE) accumulate intrauterine fluid after mating. One of the factors causing delayed uterine clearance is thought to be impaired uterine contractility. Oxytocin is central in controlling myometrial contractility. The objective of the present study was to describe peripheral oxytocin release during estrus and in the early postovulatory period in reproductively-normal mares and to compare the baseline circulating oxytocin concentrations in reproductively-normal mares and mares with PMIE. Blood samples were collected from reproductively-normal mares (n=5) from day -5 of estrus to day 2 postovulation and every 5 min for 30 min from reproductively-normal mares (n=5) and mares with PMIE (n=5) on day 3 of estrus. Pulsatile secretion of oxytocin was observed in all mares. Mean plasma oxytocin concentrations were significantly higher (P<0.05) in estrus (day -5 to day -2) than on the day of ovulation (day 0). After ovulation, plasma oxytocin concentrations tended to increase. On day 3 of estrus, plasma oxytocin concentrations were significantly higher (P<0.01) in reproductively-normal mares than in mares with PMIE. The results showed there is a significant difference in plasma oxytocin concentrations between mares to PMIE. The low plasma oxytocin concentrations in mares with PMIE may contribute to predisposing factors in their poor uterine clearance in these mares.

  12. Variability of plasma HDL subclass concentrations in men and women over time.

    PubMed

    Williams, P T; Dreon, D M; Blanche, P J; Krauss, R M

    1997-04-01

    Plasma HDL subclasses were examined by gradient gel electrophoresis in repeated samples to assess variability over time. Absorbance of the protein stain was used as an index of mass concentrations at 0.01-nm intervals within five HDL subclasses: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 nm). Three separate longitudinal studies of men showed that repeated samples of HDL over time were correlated most strongly within HDL2b, somewhat less within HDL2a, and more weakly within HDL3a, HDL3b, and HDL3c. As in men, repeated samples in women from two studies were significantly correlated within the HDL2b, HDL2a, and HDL3b intervals. Plasma HDL2b levels were significantly more stable in men than in women. Although the variability of HDL subclass measurements includes both methodological and physiological sources, differences in laboratory measurement error do not appear to explain the differences in correlations among subclasses. Specifically, analysis of 288 replications from frozen aliquots suggested that laboratory error had the least effect on correlations involving HDL3 subclasses and only slightly greater effect on correlations involving HDL2 subclasses. Our results suggest that for plasma sampled over time, the stability of HDL subclass levels increases with particle size. Prior reports of subclass-specific correlations between HDL and other variables (eg, diet, exercise, and other lipids) are unlikely to be artifacts of laboratory precision but could arise from subclass differences in variability that are physiological.

  13. Physiologically relevant plasma d,l-homocysteine concentrations mobilize Cd from human serum albumin.

    PubMed

    Sagmeister, Peter; Gibson, Matthew A; McDade, Kyle H; Gailer, Jürgen

    2016-08-01

    Although low-level chronic exposure of humans to cadmium (Cd(2+)) can result in a variety of adverse health effects, little is known about the role that its interactions with plasma proteins and small molecular weight (SMW) ligands in the bloodstream may play in delivering this metal to its target organs. To gain insight, a Cd-human serum albumin (HSA) 1:1 (molar ratio) complex was analyzed by size exclusion chromatography (SEC) coupled on-line to a flame atomic absorption spectrometer (FAAS). Using a phosphate buffered saline (PBS)-buffer mobile phase, the stability of the Cd-HSA complex was investigated in the presence of 2.0mM of SMW ligands, including taurine, acetaminophen, l-methionine, l-cysteine (Cys), d,l-homocysteine (hCys) or l-cysteine methyl-ester (Cys-Me). While taurine, acetaminophen and l-methionine did not affect its integrity, Cys, hCys and Cys-Me completely abstracted Cd from HSA. Subsequent investigations into the effect of 1.5, 1.0 and 0.5mM Cys and hCys on the integrity of the Cd-HSA complex revealed clear differences with regard to the nature of the eluting SMW-Cd species between these structurally related endogenous thiols. Interestingly, the Cd-specific chromatograms that were obtained for 0.5mM hCys revealed the elution of an apparent mixture of the parent Cd-HSA complex with a significant contribution of a structurally uncharacterized CdxhCysy species. Since this hCys concentration is encountered in blood plasma of hyperhomocysteinemia patients and since previous studies by others have revealed that a SH-containing carrier mediates the uptake of Cd into hepatocytes, our results suggest that plasma hCys may play a role in the toxicologically relevant translocation of Cd from the bloodstream to mammalian target organs. PMID:27294530

  14. Physiologically relevant plasma d,l-homocysteine concentrations mobilize Cd from human serum albumin.

    PubMed

    Sagmeister, Peter; Gibson, Matthew A; McDade, Kyle H; Gailer, Jürgen

    2016-08-01

    Although low-level chronic exposure of humans to cadmium (Cd(2+)) can result in a variety of adverse health effects, little is known about the role that its interactions with plasma proteins and small molecular weight (SMW) ligands in the bloodstream may play in delivering this metal to its target organs. To gain insight, a Cd-human serum albumin (HSA) 1:1 (molar ratio) complex was analyzed by size exclusion chromatography (SEC) coupled on-line to a flame atomic absorption spectrometer (FAAS). Using a phosphate buffered saline (PBS)-buffer mobile phase, the stability of the Cd-HSA complex was investigated in the presence of 2.0mM of SMW ligands, including taurine, acetaminophen, l-methionine, l-cysteine (Cys), d,l-homocysteine (hCys) or l-cysteine methyl-ester (Cys-Me). While taurine, acetaminophen and l-methionine did not affect its integrity, Cys, hCys and Cys-Me completely abstracted Cd from HSA. Subsequent investigations into the effect of 1.5, 1.0 and 0.5mM Cys and hCys on the integrity of the Cd-HSA complex revealed clear differences with regard to the nature of the eluting SMW-Cd species between these structurally related endogenous thiols. Interestingly, the Cd-specific chromatograms that were obtained for 0.5mM hCys revealed the elution of an apparent mixture of the parent Cd-HSA complex with a significant contribution of a structurally uncharacterized CdxhCysy species. Since this hCys concentration is encountered in blood plasma of hyperhomocysteinemia patients and since previ