Science.gov

Sample records for plasma nicotine concentration

  1. Cocaine, nicotine, caffeine, and metabolite plasma concentrations in neonates.

    PubMed

    Dempsey, D A; Partridge, J C; Jones, R T; Rowbotham, M C

    1998-01-01

    The objective of this study was to measure the umbilical cord plasma levels of cocaine, nicotine, caffeine, and their metabolites. Thirty-six neonates at risk for prenatal cocaine exposure were prospectively enrolled. Umbilical cord plasma was analyzed by gas chromatography-mass spectroscopy for cocaine, cocaethylene, benzoylecgonine (BZE), nicotine, cotinine, and caffeine. Eighteen neonates were plasma positive for BZE, and 50% of these were also positive for cocaine. Cocaethylene was not found. The maximum plasma cocaine concentration was 88 ng/mL (mean, 39 ng/mL). The maximum plasma BZE concentration was 3880 ng/mL (mean, 844 ng/mL). Among BZE-positive babies, the mean plasma drug levels were as follows: nicotine, 1.8 ng/mL; cotinine, 94 ng/mL; and caffeine, 1205 ng/mL. Among the BZE-negative babies, the mean plasma drug levels were as follows: nicotine, 5.2 ng/mL; cotinine, 97 ng/mL; and caffeine, 1440 ng/mL. These cocaine levels raise the possibility of pharmacological effects of cocaine in the early neonatal period.

  2. 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.

  3. Airborne Nicotine Concentrations in the Workplaces of Tobacco Farmers

    PubMed Central

    Yoo, Seok-Ju; Park, Sung-Jun; Kim, Byoung-Seok; Lim, Hyun-Sul; Kim, Jik-Su; Kim, In-Shik

    2014-01-01

    Objectives Nicotine is a natural alkaloid and insecticide in tobacco leaves. Green tobacco sickness (GTS) is known as a disease of acute nicotine intoxication among tobacco farmers. Until now, GTS has been recognized globally as a disease that results from nicotine absorption through the skin. However, we assumed that GTS might also result from nicotine inhalation as well as absorption. We aimed to measure the airborne nicotine concentrations in various work environments of Korean tobacco farmers. Methods We measured the nicotine concentrations in the tobacco fields, private curing barns, and joint curing barns of farmers from July to October 2010. All sampling and analyses of airborne nicotine were conducted according to the National Institute for Occupational Safety and Health manual of analytic methods. Results The airborne nicotine concentrations (geometric mean [geometric standard deviation]) in the tobacco field were 83.4 mg/m3 (1.2) in the upper region and 93.3 mg/m3 (1.2) in the lower region. In addition, the nicotine concentration by personal sampling was 150.1 mg/m3. Similarly, the nicotine concentrations in the private curing barn, workers in curing barns, the front yard of the curing barn, and in the joint curing barn were 323.7 mg/m3 (2.0), 121.0 mg/m3 (1.5), 73.7 mg/m3 (1.7), and 610.3 mg/m3 (1.0), respectively. Conclusions The nicotine concentration in the workplaces of tobacco farmers was very high. Future studies should measure the environmental concentration of nicotine that is inhaled by tobacco farmers. PMID:24921017

  4. 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.

  5. 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

  6. 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.

  7. Distribution analysis of airborne nicotine concentrations in hospitality facilities.

    PubMed

    Schorp, Matthias K; Leyden, Donald E

    2002-02-01

    A number of publications report statistical summaries for environmental tobacco smoke (ETS) concentrations. Despite compelling evidence for the data not being normally distributed, these publications typically report the arithmetic mean and standard deviation of the data, thereby losing important information related to the distribution of values contained in the original data. We were interested in the frequency distributions of reported nicotine concentrations in hospitality environments and subjected available data to distribution analyses. The distribution of experimental indoor airborne nicotine concentration data taken from hospitality facilities worldwide was fit to lognormal, Weibull, exponential, Pearson (Type V), logistic, and loglogistic distribution models. Comparison of goodness of fit (GOF) parameters and indications from the literature verified the selection of a lognormal distribution as the overall best model. When individual data were not reported in the literature, statistical summaries of results were used to model sets of lognormally distributed data that are intended to mimic the original data distribution. Grouping the data into various categories led to 31 frequency distributions that were further interpreted. The median values in nonsmoking environments are about half of the median values in smoking sections. When different continents are compared, Asian, European, and North American median values in restaurants are about a factor of three below levels encountered in other hospitality facilities. On a comparison of nicotine concentrations in North American smoking sections and nonsmoking sections, median values are about one-third of the European levels. The results obtained may be used to address issues related to exposure to ETS in the hospitality sector.

  8. 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.

  9. Nicotine in high concentration causes contraction of isolated strips of rabbit corpus cavernosum.

    PubMed

    Nguyen, Hoai Bac; Lee, Shin Young; Park, Soo Hyun; Han, Jun Hyun; Lee, Moo Yeol; Myung, Soon Chul

    2015-05-01

    It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations (10(-5)~10(-4) M) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with 10(-5) M hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with 10(-5) M indomethacin (nonspecific cyclooxygenase inhibitor) and with 10(-6) M NS-398 (selective cyclooxygenase inhibitor), but also with 10(-6) M Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane A2 synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane A2, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

  10. Nicotine at concentrations found in cigarette smokers activates and desensitizes nicotinic acetylcholine receptors in CA1 interneurons of rat hippocampus.

    PubMed

    Alkondon, M; Pereira, E F; Almeida, L E; Randall, W R; Albuquerque, E X

    2000-10-01

    Behavioral effects of cigarette smoking are attributed to the interactions of nicotine with brain nicotinic acetylcholine receptors (nAChRs). However, the mechanisms by which nAChR function in developing and mature brain is affected by a smoker's level of nicotine (50-500 nM) remain unclear. Thus, the objective of this study was to determine the concentration- and time-dependent effects of nicotine on alpha7 and alpha4beta2 nAChRs, the two major brain subtypes, natively expressed in CA1 interneurons of rat hippocampal slices. Only at concentrations > or =5 microM did nicotine (applied for 6-60 s) elicit action potentials or measurable whole-cell currents (EC(50)=158 microM) in stratum radiatum interneurons that express alpha7 nAChRs. Continuous exposure for 10-15 min of the neurons to nicotine (0.5-2.5 microM) inhibited alpha7 nAChR-mediated currents (IC(50)=640 nM) evoked by choline (10 mM). Nicotine (> or =0.125 microM) applied to the neurons for 1-5 min induced slowly desensitizing whole-cell currents (EC(50)=3.2 microM) in stratum lacunosum moleculare interneurons; this effect was mediated by alpha4beta2 nAChRs. Also via activation of alpha4beta2 nAChRs, nicotine (0.125-0.5 microM) increased the frequency and amplitude of GABAergic postsynaptic currents (PSCs) in stratum radiatum interneurons. However, exposure of the neurons for 10-15 min to nicotine (0.25-0.5 microM) resulted in desensitization of alpha4beta2 nAChRs. It is suggested that nanomolar concentrations of nicotine after acute intake suppress inhibitory inputs to pyramidal cells through a disinhibitory mechanism involving activation of alpha4beta2 nAChRs and desensitization of alpha7 nAChRs, and after chronic intake leads to up-regulation of both receptor subtypes via desensitization. These findings have direct implications to the actions of nicotine in cigarette smokers.

  11. Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.

    PubMed

    Bébarová, Markéta; Matejovič, Peter; Švecová, Olga; Kula, Roman; Šimurdová, Milena; Šimurda, Jiří

    2017-02-03

    Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach), a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

  12. 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.

  13. Influence of subunit composition on desensitization of neuronal acetylcholine receptors at low concentrations of nicotine.

    PubMed

    Fenster, C P; Rains, M F; Noerager, B; Quick, M W; Lester, R A

    1997-08-01

    The influence of alpha and beta subunits on the properties of nicotine-induced activation and desensitization of neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes was examined. Receptors containing alpha4 subunits were more sensitive to activation by nicotine than alpha3-containing receptors. At low concentrations of nicotine, nAChRs containing beta2 subunits reached near-maximal desensitization more rapidly than beta4-containing receptors. The concentration of nicotine producing half-maximal desensitization was influenced by the particular alpha subunit expressed; similar to results for activation, alpha4-containing receptors were more sensitive to desensitizing levels of nicotine than alpha3-containing receptors. The alpha subunit also influenced the rate of recovery from desensitization; this rate was approximately inversely proportional to the apparent nicotine affinity for the desensitized state. The homomeric alpha7 receptor showed the lowest sensitivity to nicotine for both activation and desensitization; alpha7 nAChRs also demonstrated the fastest desensitization kinetics. These subunit-dependent properties remained in the presence of external calcium, although subtle, receptor subtype-specific effects on both the apparent affinities for activation and desensitization and the desensitization kinetics were noted. These data imply that the subunit composition of various nAChRs determines the degree to which receptors are desensitized and/or activated by tobacco-related levels of nicotine. The subtype-specific balance between receptor activation and desensitization should be considered important when the cellular and behavioral actions of nicotine are interpreted.

  14. Intravenous and oral suicidal e-liquid poisonings with confirmed nicotine and cotinine concentrations.

    PubMed

    Sommerfeld, Karina; Łukasik-Głębocka, Magdalena; Kulza, Maksymilian; Drużdż, Artur; Panieński, Paweł; Florek, Ewa; Zielińska-Psuja, Barbara

    2016-05-01

    The increasing availability of e-cigarettes is a potential toxicological concern. E-cigarettes appeared on the Polish market in 2006, and since 2009 they have been widely available with a new source of nicotine, the so-called e-liquid. In this paper two cases of suicidal oral and intravenous poisonings with the e-liquid are described. The clinical courses of these poisonings are presented. Nicotine and cotinine concentrations in the patient's blood were determined using high performance liquid chromatography with diode array detection. In the course of intoxication patient No. 1, classic symptoms of acute nicotine poisoning without convulsions were observed. Nicotine and cotinine concentrations measured in serum were 0.096 and 4.4mg/L, respectively. The case of patient No. 2, admission with no typical symptoms of nicotine poisoning was identified, except unconsciousness and slow respiration. Nicotine and cotinine concentrations in the serum at the time of No. 2 admissions were determined to be 0.8 and 1.3mg/L, respectively. With the increasing number of e-liquid poisonings cases, it should be aware that these products can be a readily available source of poison.

  15. Determination of Nicotine Absorption from Multiple Tobacco Products and Nicotine Gum

    PubMed Central

    Digard, Helena; Proctor, Christopher; Kulasekaran, Anuradha; Malmqvist, Ulf

    2013-01-01

    Introduction: Snus is a smokeless tobacco product traditionally used in Scandinavia and available in pouched or loose forms. The objective of this study was to determine nicotine absorption for current pouched and loose snus products in comparison with a cigarette and an over-the-counter nicotine gum. Methods: We conducted an open-label, randomized, 6-way, crossover study involving 20 healthy snus and cigarette users. One of 6 products (2 pouched snus, 2 weights of loose snus, a cigarette, and a nicotine gum) was administered at each of 6 visits. Blood samples were taken at intervals over 120 min and sensory perception assessed by questionnaire. Results: For the 4 smokeless tobacco products and the nicotine gum, blood plasma levels of nicotine were ranked according to total nicotine content as follows: loose snus (27.1 mg nicotine) > pouched snus (14.7 mg nicotine) > loose snus (10.8 mg nicotine) = pouched snus (10.7 mg nicotine) > nicotine gum (4.2 mg nicotine). The area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax) of nicotine ranged from 26.9 to 13.1 ng.h/ml and 17.9 to 9.1 ng.h/ml, respectively across all the products. Nicotine was absorbed more rapidly from the cigarette but systemic exposure was within the range of the smokeless tobacco products (AUC = 14.8 ng.h/ml; Cmax = 12.8 ng.h/ml). Conclusions: This study has generated new information on comparative nicotine absorption from a cigarette, loose snus, and pouched snus typical of products sold in Scandinavia. The similar nicotine absorption for 1 g portions of loose and pouched snus with approximately 11 mg of nicotine indicate that absorption kinetics were dependent on quantity of tobacco by weight and total nicotine content rather than product form. PMID:22585541

  16. 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

  17. 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.

  18. Genetic and pharmacokinetic determinants of response to transdermal nicotine in white, black, and Asian nonsmokers.

    PubMed

    Dempsey, D A; St Helen, G; Jacob, P; Tyndale, R F; Benowitz, N L

    2013-12-01

    The aim of the study was to examine genetic, pharmacokinetic, and demographic factors that influence sensitivity to nicotine in never-smokers. Sixty never-smokers, balanced for gender and race (white, black, and Asian), wore 7-mg nicotine skin patches for up to 8 h. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, encoding the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in nine subjects and was strongly associated with rate of increase and peak concentrations of plasma nicotine. Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced-function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when they are used for treating medical conditions in nonsmokers, and possibly in vulnerability to developing nicotine dependence.

  19. Sub-toxic nicotine concentrations affect extracellular matrix and growth factor signaling gene expressions in human osteoblasts.

    PubMed

    Marinucci, Lorella; Bodo, Maria; Balloni, Stefania; Locci, Paola; Baroni, Tiziano

    2014-12-01

    Exposure to nicotine and other compounds contained in cigarette smoking affects human health. This study examined the effects of exposure to a single or multiple sub-toxic nicotine concentrations on human osteoblasts. Cell growth and expression of genes involved in bone differentiation, extracellular matrix (ECM) metabolism, and growth factor signaling pathways were investigated in nicotine-treated cells compared to untreated cells. Depending on osteoblast concentration and maturation stages, nicotine differently regulated cell growth. Real-time PCR showed regulated expressions of genes expressed by nicotine-treated osteoblasts compared to untreated cells. Among ECM genes, type I collagen was down-regulated and osteonectin was up-regulated in nicotine-treated osteoblasts; similarly, fibroblast growth factor-1 (FGF1) and fibroblast growth factor-2 (FGF2), two members of FGF signaling system, were discordantly modulated; genes involved in osteoblast maturation and differentiation such as alkaline phosphatase (ALP), runt-related transcription factor-2 (RUNX2), and bone sialoprotein (BSP) were over-expressed after drug treatment. Our results show a positive association between nicotine exposure and osteoblast phenotype and illustrate for the first time a mechanism whereby acute or chronic exposure to sub-toxic nicotine concentrations may affect bone formation through the impairment of growth factor signaling system and ECM metabolism.

  20. Nicotine, cotinine, and trans-3-hydroxycotinine levels in seminal plasma of smokers: effects on sperm parameters.

    PubMed

    Pacifici, R; Altieri, I; Gandini, L; Lenzi, A; Pichini, S; Rosa, M; Zuccaro, P; Dondero, F

    1993-10-01

    Sperm samples from 44 cigarette smokers and 50 nonsmokers attending an infertility clinic were examined by high-performance liquid chromatography (HPLC) assay and HPLC-mass spectrometry for the presence of nicotine (NIC), cotinine (COT), and trans-3'-hydroxycotinine (THOC) in seminal plasma. Smokers were found to have levels of COT and THOC in seminal plasma that were similar to those found in serum. The level of NIC was significantly increased in seminal plasma compared to serum. Total motility of spermatozoa was significantly and negatively correlated to COT and THOC levels in seminal plasma. Forward motility of spermatozoa was correlated only with cotinine semen levels. On the basis of these results, we suggest that the presence of tobacco smoke constituents in seminal plasma could provide a warning of the adverse effects of cigarette smoke on the physiology of reproduction.

  1. 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.

  2. Improved highly sensitive method for determination of nicotine and cotinine in human plasma by high-performance liquid chromatography.

    PubMed

    Nakajima, M; Yamamoto, T; Kuroiwa, Y; Yokoi, T

    2000-05-26

    A highly sensitive and reliable method for the determination of nicotine and its metabolite cotinine in human plasma by high-performance liquid chromatography was developed. Nicotine and cotinine were extracted from alkalinized plasma with dichloromethane and the volatility of nicotine was prevented by the addition of conc. HCl to the organic solvent during evaporation. The sensitivity of quantification at 260 nm absorption was improved by using a noise-base clean Uni-3 to 0.2 ng/ml nicotine and 1.0 ng/ml cotinine. The method was validated over linear ranges of 0.2-25.0 ng/ml for nicotine and 1.0-80.0 ng/ml for cotinine. The intra-day precision and accuracy were < or = 15.9% relative standard variation (RSD) and 89.9-103.5% for nicotine and < or = 8.0% RSD and 98.7-103.0% for cotinine. The inter-day precision and accuracy were < or = 17.0% RSD and 94.2-100.9% for nicotine and < or = 8.2% RSD and 98.0-105.1% for cotinine.

  3. Hair nicotine/cotinine concentrations as a method of monitoring exposure to tobacco smoke among infants and adults.

    PubMed

    Tzatzarakis, M N; Vardavas, C I; Terzi, I; Kavalakis, M; Kokkinakis, M; Liesivuori, J; Tsatsakis, A M

    2012-03-01

    In this pilot study, we examined the validity and usefulness of hair nicotine-cotinine evaluation as a biomarker of monitoring exposure to tobacco. Head hair samples were collected from 22 infants (<2 years of age) and 44 adults with different exposures to tobacco (through either active or passive smoking) and analyzed by liquid chromatography-mass spectrometry (LC-MS) for nicotine and cotinine. Hair samples were divided into three groups, infants, passive smoker adults and active smoker adults, and into eight subgroups according to the degree of exposure. The limit of quantification (LOQ) was 0.1 ng/mg for nicotine and 0.05 ng/mg for cotinine. Mean recovery was 69.15% for nicotine and 72.08% for cotinine. The within- and between-day precision for cotinine and nicotine was calculated at different concentrations. Moreover, hair nicotine and cotinine concentrations were highly correlated among adult active smokers (R (2) = 0.710, p < 0.001), among adult nonsmokers exposed to secondhand smoke (SHS; R (2) = 0.729, p < 0.001) and among infants (R (2) = 0.538, p = 0.01). Among the infants exposed to SHS from both parents the noted correlations were even stronger (R (2) = 0.835, p = 0.02). The above results identify the use of hair samples as an effective method for assessing exposure to tobacco, with a high association between nicotine and cotinine especially among infants heavily exposed to SHS.

  4. Combined active and passive immunization against nicotine: minimizing monoclonal antibody requirements using a target antibody concentration strategy.

    PubMed

    Cornish, Katherine E; Harris, Andrew C; LeSage, Mark G; Keyler, Dan E; Burroughs, Danielle; Earley, Cathy; Pentel, Paul R

    2011-11-01

    Nicotine vaccines have shown preliminary evidence of efficacy for enhancing smoking cessation rates, but the serum nicotine-specific antibody (NicAb) concentrations produced are highly variable and many subjects do not develop effective levels. As an alternative to vaccination, passive immunization with nicotine-specific monoclonal antibodies could produce more uniform serum NicAb concentrations, but its use is limited by their high cost and shorter elimination half-life. This study investigated supplementing vaccination with monoclonal antibodies in a targeted fashion to increase vaccine efficacy while minimizing the required monoclonal antibody dose. Rats were vaccinated and then given individualized supplemental doses of the nicotine-specific monoclonal antibody Nic311 to achieve a target total serum NicAb concentration known to be effective for blocking locomotor sensitization (LMS) to nicotine. Rats received vaccine, Nic311, both, or neither, followed by 0.3 mg/kg nicotine s.c. for 10 days to produce LMS. Combination immunotherapy completely blocked the development of LMS, while monotherapy with vaccine or Nic311 alone was only minimally effective. Lower brain nicotine levels were associated with reduced locomotor activity averaged over days 7-10. Despite its greater efficacy, combination immunotherapy did not reduce the variability in the resulting total serum NicAb concentrations. Variability in total serum NicAb concentrations was contributed to by both vaccine-generated antibody and by Nic311. These data show that combination immunotherapy, using a Nic311 dose that is by itself only minimally effective, can substantially enhance nicotine vaccine efficacy. However, variability in serum NicAb levels with combination immunotherapy may make translation of this approach challenging.

  5. High concentration plasma-reduced plateletapheresis concentrates.

    PubMed

    Perseghin, Paolo

    2011-06-01

    Single-donor hyperconcentrated plateletapheresis (dry-platelets) collection has been introduced in the 90's as a part of the newly developed multi-component collection strategy. This approach allowed to safely collect multiple components from a single apheresis donation, i.e. RBC, FFP and/or plateletpheresis units. Dry-platelets are usually resuspended in additive solution to maintain an adequate pH during the storage period until use. Some concern existed about possible higher degrees of platelet activation in dry-platelets units when compared to standard concentration (1.0-1.6 × 10(6)/μL platelets) units and its possible correlation with lower in vivo efficiency and/or survival of the former units. Several authors investigated this specific issue, and dry-platelets units proved to be equally effective than standard concentration plateletpheresis units in recipients. The use of dry-platelets units may reduce (i) the risk of passive infusion of naturally occurring ABO-related hemolytic antibodies when donor O platelets are given to group A, B, or AB recipient, (ii) the risk of TRALI when multiparous donors undergo plateletpheresis. Furthermore, dry-platelet collection may allow for an increased amount of FFP sent to industry. Finally, hyperconcentrated platelet units may be used for "niche" indications, such as intrauterine platelet transfusion or, in case of autologous dry-platelet collection, for further freezing for long term storage in selected patients within onco-hematological settings.

  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.

  7. Therapeutic concentrations of varenicline in the presence of nicotine increase action potential firing in human adrenal chromaffin cells.

    PubMed

    Hone, Arik J; Michael McIntosh, J; Rueda-Ruzafa, Lola; Passas, Juan; de Castro-Guerín, Cristina; Blázquez, Jesús; González-Enguita, Carmen; Albillos, Almudena

    2017-01-01

    Varenicline is a nicotinic acetylcholine receptor (nAChR) agonist used to treat nicotine addiction, but a live debate persists concerning its mechanism of action in reducing nicotine consumption. Although initially reported as α4β2 selective, varenicline was subsequently shown to activate other nAChR subtypes implicated in nicotine addiction including α3β4. However, it remains unclear whether activation of α3β4 nAChRs by therapeutically relevant concentrations of varenicline is sufficient to affect the behavior of cells that express this subtype. We used patch-clamp electrophysiology to assess the effects of varenicline on native α3β4* nAChRs (asterisk denotes the possible presence of other subunits) expressed in human adrenal chromaffin cells and compared its effects to those of nicotine. Varenicline and nicotine activated α3β4* nAChRs with EC50 values of 1.8 (1.2-2.7) μM and 19.4 (11.1-33.9) μM, respectively. Stimulation of adrenal chromaffin cells with 10 ms pulses of 300 μM acetylcholine (ACh) in current-clamp mode evoked sodium channel-dependent action potentials (APs). Under these conditions, perfusion of 50 or 100 nM varenicline showed very little effect on AP firing compared to control conditions (ACh stimulation alone), but at higher concentrations (250 nM) varenicline increased the number of APs fired up to 436 ± 150%. These results demonstrate that therapeutic concentrations of varenicline are unlikely to alter AP firing in chromaffin cells. In contrast, nicotine showed no effect on AP firing at any of the concentrations tested (50, 100, 250, and 500 nM). However, perfusion of 50 nM nicotine simultaneously with 100 nM varenicline increased AP firing by 290 ± 104% indicating that exposure to varenicline and nicotine concurrently may alter cellular behavior such as excitability and neurotransmitter release.

  8. Plasma lipid concentrations during episodic occupational stress.

    PubMed

    McCann, B S; Benjamin, G A; Wilkinson, C W; Retzlaff, B M; Russo, J; Knopp, R H

    1999-01-01

    The possibility that stress affects plasma lipid concentrations has been the subject of recent investigation, but the findings are equivocal in nonlaboratory settings. To determine whether psychological stress contributes to variability in plasma lipid concentrations and concomitant changes in health behaviors, the effect of increased work load on plasma lipids and apolipoproteins was examined in 173 lawyers. Plasma cholesterol, triglyceride, and apolipoprotein concentrations were studied during periods of high work load (corresponding to impending tax deadlines) and during periods of usual work load. Self-reports of stress, work load, and time pressure, and cortisol, blood pressure, and heart rate were measured to verify that impending deadlines were associated with increased stress levels. Health behaviors which may affect plasma lipoprotein concentrations, including dietary intake and exercise, were also examined. High work load was accompanied by increases in self-reported work load among lawyers most directly affected by the impending deadlines. Plasma apolipoprotein B and triglycerides increased during periods of high work load (M = 1.9 mg/dL, SD = 10.1 and M = 5.3, SD = 34.4, respectively). No changes in dietary intake and exercise were observed. Psychological stress (high work load) is associated with potentially atherogenic changes in plasma lipid concentrations. While the lipoprotein effect of this short-term work stress is small, the effects of longer-term stress on multiple rise factors including triglycerides and apolipoprotein B could have significance for the development of coronary artery disease.

  9. Solid-phase extraction and HPLC assay of nicotine and cotinine in plasma and brain.

    PubMed

    Dawson, Ralph; Messina, S M; Stokes, C; Salyani, S; Alcalay, N; De Fiebre, N C; De Fiebre, C M

    2002-01-01

    The aim of this study was to develop a simple and reliable assay for nicotine (NIC) and its major metabolite, cotinine (COT), in plasma and brain. A method was developed that uses an extraction method compatible with reverse-phase high-performance liquid chromatography (HPLC) separation and ultraviolet (UV) detection. Sequential solid-phase extraction on silica columns followed by extraction using octadecyl (C18) columns resulted in mean percent recovery (n = 5) of 51 +/- 5, 64 +/- 10, and 52 +/- 10% for NIC, COT, and phenylimidazole (PI), respectively, in spiked 1-mL serum samples. Recovery (mean +/- SEM) of the internal standard (PI) from spiked samples of nicotine-injected rats averaged 64.1 +/- 1.5% (n = 138) from plasma, and 20.7+/-0.8% (n = 128) from brain. The limits of detection of NIC in plasma samples were approximately 8 ng per mL, and of COT, 13.6 ng per mL. Further optimization of our extraction method, using slower flow rates and solid-phase extraction on silica columns, followed by C18 column extraction, yielded somewhat better recoveries (38 +/-3%) for 1-mL brain homogenates. Interassay precision (coefficient of variation) was determined on the basis of daily calibrations for 2 months and was found to be 7%, 9%, and 9% for NIC, COT, and PI, respectively, whereas intra-assay variability was 3.9% for both NIC and COT. Limited studies were performed on analytical columns for comparison of retention, resolution, asymmetry, and column capacity. We concluded that a simple two-step solid-phase extraction method, coupled with HPLC separation and UV detection, can be used routinely to measure NIC and COT in biological fluids and tissues.

  10. Plasma catecholamine concentrations associated with cerebral vasospasm.

    PubMed

    Loach, A B; Benedict, C R

    1980-03-01

    Plasma concentrations of adrenaline and noradrenaline were measured sequentially over the immediate post-operative period following clipping of an intracranial aneurysm in 11 patients. Those patients who developed local cerebral vasospasm showed a sustained rise in plasma catecholamines, particularly noradrenaline, whilst those patients who developed generalised cerebral vasospasm showed early peaks of very high concentrations of adrenaline and noradrenaline which preceded radiological evidence of generalized vasospam.

  11. 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

  12. 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

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

    PubMed Central

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

    2016-01-01

    Abstract 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

  14. Quantification of nicotine, cotinine, trans-3'-hydroxycotinine and varenicline in human plasma by a sensitive and specific UPLC-tandem mass-spectrometry procedure for a clinical study on smoking cessation.

    PubMed

    Dobrinas, Maria; Choong, Eva; Noetzli, Muriel; Cornuz, Jacques; Ansermot, Nicolas; Eap, Chin B

    2011-11-15

    A sensitive and specific ultra performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of nicotine, its metabolites cotinine and trans-3'-hydroxycotinine and varenicline in human plasma was developed and validated. Sample preparation was realized by solid phase extraction of the target compounds and of the internal standards (nicotine-d4, cotinine-d3, trans-3'-hydroxycotinine-d3 and CP-533,633, a structural analog of varenicline) from 0.5 mL of plasma, using a mixed-mode cation exchange support. Chromatographic separations were performed on a hydrophilic interaction liquid chromatography column (HILIC BEH 2.1×100 mm, 1.7 μm). A gradient program was used, with a 10 mM ammonium formate buffer pH 3/acetonitrile mobile phase at a flow of 0.4 mL/min. The compounds were detected on a triple quadrupole mass spectrometer, operated with an electrospray interface in positive ionization mode and quantification was performed using multiple reaction monitoring. Matrix effects were quantitatively evaluated with success, with coefficients of variation inferior to 8%. The procedure was fully validated according to Food and Drug Administration guidelines and to Société Française des Sciences et Techniques Pharmaceutiques. The concentration range was 2-500 ng/mL for nicotine, 1-1000 ng/mL for cotinine, 2-1000 ng/mL for trans-3'-hydroxycotinine and 1-500 ng/mL for varenicline, according to levels usually measured in plasma. Trueness (86.2-113.6%), repeatability (1.9-12.3%) and intermediate precision (4.4-15.9%) were found to be satisfactory, as well as stability in plasma. The procedure was successfully used to quantify nicotine, its metabolites and varenicline in more than 400 plasma samples from participants in a clinical study on smoking cessation.

  15. Doxepin concentrations in plasma and cerebrospinal fluid.

    PubMed

    Schomburg, Robert; Remane, Daniela; Fassbender, Klaus; Maurer, Hans H; Spiegel, Jörg

    2011-04-01

    Doxepin--like other antidepressant drugs (ADs)--shows a variable antidepressant effect in clinical practice. The cause for this variability is as yet unclear; however, pharmacokinetic factors such as the variable permeability of doxepin into the cerebrospinal fluid (CSF), may contribute to the difference in therapeutic efficacy. We measured and correlated the concentration of doxepin and its active metabolite nordoxepin in both the plasma and CSF. Plasma and CSF samples were taken simultaneously from 21 patients who were treated with doxepin due to different clinical indications. The plasma concentration of both doxepin and nordoxepin correlated significantly with the oral dosage of doxepin (doxepin: r = +0.66, p < 0.001; nordoxepin: r = +0.78, p < 0.0001; Spearman's correlation). Furthermore, we found significant correlations between the plasma and CSF concentrations of both doxepin (r = +0.71; p < 0.001; Pearson's correlation) and nordoxepin (r = +0.74; p < 0.001). These highly significant correlations between the plasma and CSF concentrations indicate a constant CSF permeability of doxepin and its active metabolite nordoxepin.

  16. 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

  17. Effects of nicotine administration on elemental concentrations in mouse granulosa cells, maturing oocytes and oviduct epithelium studied by X-ray microanalysis.

    PubMed

    Jin, Z; Jin, M; Nilsson, B O; Roomans, G M

    1998-10-01

    A normal maturation of the oocytes is dependent upon, among other things, normally functioning granulosa and corona radiata cells. Analyses performed during human in vitro fertilization programs have revealed that, in smokers, ovarian functions are affected and that smokers have a decreased fertilization rate. Further, animal studies have indicated that nicotine can reach the genital tractus, and that nicotine administration interferes with oocyte maturation, fertilization and early pregnancy. We applied X-ray microanalysis to monitor whether nicotine administration changed the ionic balance of cells in the reproductive tract (granulosa cells, oocytes and oviduct epithelial cells). The animals were given nicotine in the drinking water at a concentration of 108 mumol/l. After 15 days the animals were superovulated, ovaries and oviducts were frozen, and thick cryosections were prepared for energy-dispersive X-ray microanalysis. In the granulosa cells, the concentrations of Na and Cl increased after nicotine treatment, while the K concentrations decreased resulting in an increased Na/K ratio. The treated oocytes had a higher K concentration and a decreased Na/K ratio compared to the controls. In the epithelial cells of the oviduct, the concentrations of Na and K decreased after nicotine treatment without any changes in the Na/K ratio. Thus, heavy nicotine administration to mice causes significant changes in the ionic composition of the granulosa cells, the ovarian oocytes and the oviduct epithelium.

  18. Plasma aminotransferase concentrations in preterm infants.

    PubMed

    Victor, S; Dickinson, H; Turner, M A

    2011-03-01

    The aim of this study was to generate reference ranges for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in preterm infants by describing the observed plasma concentration of these enzymes in babies born between 22 and 36 weeks' gestation. A service evaluation was conducted in babies admitted to two large neonatal intensive care units in the UK. 7006 blood samples from 1860 infants admitted to the two units between 2004 and 2008 were included. Extremely premature infants had high plasma enzyme activities when compared to babies at a later corrected gestational age. This may be due to more severe illness immediately after birth.

  19. Chronic nicotine administration in the drinking water affects the striatal dopamine in mice.

    PubMed

    Pietilä, K; Ahtee, L

    2000-05-01

    Although tobacco contains a large variety of substances, its addictive properties are most probably due to the reinforcing actions of nicotine that motivates continued tobacco use. Animals and humans self-administer nicotine, a response that appears to involve the mesolimbic dopamine system and to be common to other abused drugs. The present article reviews animal models to administer nicotine chronically. We also describe a new animal model in which nicotine is given to mice in drinking water as their sole source of fluid. This treatment produced nicotine plasma concentrations comparable to or above those found in smokers. We found that mice withdrawn from nicotine were tolerant to the effects of nicotine challenge on striatal dopamine metabolism as well as on body temperature and locomotor activity. Furthermore, 3H-nicotine binding in the cortex and midbrain was significantly increased in mice withdrawn from nicotine. The last part of the article will focus on the effects of this chronic nicotine treatment on striatal dopamine. Dopamine and its metabolites and locomotor activity were increased in the forenoon in mice still drinking nicotine solutions. We also report recent data in which chronic nicotine administration in the drinking water enhanced the effect of dopamine receptor agonist, quinpirole, on striatal metabolism. The animal model described appears to be a relevant method for studying the mechanisms that are thought to be involved in nicotine dependence.

  20. 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.

  1. CSF and plasma vasopressin concentrations in dementia.

    PubMed Central

    Sørensen, P S; Hammer, M; Vorstrup, S; Gjerris, F

    1983-01-01

    In 16 patients with primary degenerative dementia mean CSF vasopressin concentration was lower (0.9 +/- 0.1 pg/ml (mean +/- SEM)) than in 28 control patients (1.3 +/- 0.1 (mean +/- SEM)) (p less than 0.01). In 18 patients with normal pressure hydrocephalus and potentially reversible dementia mean CSF vasopressin concentration (1.2 pg/ml +/- 0.1 (mean +/- SEM)) was not different from that found in controls. Several of the demented patients had inappropriate plasma vasopressin concentrations suggesting a defect in osmoregulation. These findings encourage further clinical trials of vasopressin in patients with primary degenerative dementia, but it is emphasised that the low CSF vasopressin concentration in these patients might be only a nonspecific phenomenon due to the diffuse loss of cells within the central nervous system. PMID:6644315

  2. Acute clozapine overdose: plasma concentration and outcome.

    PubMed

    Broich, K; Heinrich, S; Marneros, A

    1998-07-01

    Clozapine is a tricyclic dibenzodiazepine derivative that is classified as an "atypical neuroleptic" drug for treatment of psychotic diseases. A 19-year-old schizophrenic female, treated with 400 mg clozapine per day, was admitted to the emergency department after ingestion of 5000 mg (50 x 100 mg tablets) of clozapine. Clozapine plasma level 2.5 hours after ingestion was 3.8 microg/ml (normal range 0.2-0.7 microg/ml) and very high in gastric lavage. Contrary to reported cases with such high plasma concentrations the patient suffered only from somnolence with intermittent periods of agitation and a mild anticholinergic syndrome with sinus tachycardia and slight hypotension. After detoxication with gastric lavage and short-term administration of pyridostigmine she remained stable, and 24 hours after ingestion she was transferred to the psychiatric unit without further sequelae. To prevent late-onset complications she was carefully monitored for five days. The clozapine plasma level 24 hours after the first measurement was normal. This case and others reported in the literature confirm that signs and symptoms after clozapine intoxication are variable and that high plasma levels are not lethal in every case.

  3. A study of the bovine adrenal chromaffin nicotinic receptor using patch clamp and concentration-jump techniques.

    PubMed Central

    Maconochie, D J; Knight, D E

    1992-01-01

    1. Voltage clamp records have been obtained from bovine adrenal chromaffin cells in the outside-out and whole-cell configurations, in response to step changes of acetylcholine (ACh) concentration. The concentrations used ranged from 50 nM to 20 mM. 2. At high acetylcholine concentrations, the activation and desensitization kinetics of the nicotinic receptor, as observed in outside-out patches, may be described by a model incorporating a single, fast agonist binding step, and relatively slow isomerization to the open state. The affinity of the closed receptor for ACh is 310 microM, the channel opening rate constant is 460 s-1, and the closing rate constant is 29 s-1. 3. Single channel events, observed when nanomolar ACh concentrations are applied to whole cells, have two distinct channel lifetimes: 0.6 ms and 11-15 ms. The variation of the frequencies of the events with ACh concentration, suggests that the short lifetimes are openings of a singly liganded receptor and the longer lifetimes are openings of a doubly liganded receptor. 4. Only a single exponential associated with receptor desensitization is seen with outside-out patches, but two are seen with whole cells. It is postulated that there are two nicotinic receptor types present on adrenal chromaffin cells. 5. The rate of desensitization (9 s-1 and 26 s-1, whole cells; 24 s-1, patches), is fast enough to be significant in determining the open channel lifetime. 6. A sudden increase in current (rebound) is observed when a high concentration of ACh is abruptly removed from outside-out patches. This is evidence for a blocked state. The affinity of the blocking site for ACh is 1400 microM (outside-out patches). 7. The total number of activatable nicotinic channels per whole cell is estimated to be 2600. PMID:1282154

  4. 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.

  5. 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.

  6. Nicotine vapor inhalation escalates nicotine self-administration.

    PubMed

    Gilpin, Nicholas W; Whitaker, Annie M; Baynes, Brittni; Abdel, Abdelrahim Y; Weil, Madelyn T; George, Olivier

    2014-07-01

    Humans escalate their cigarette smoking over time, and a major obstacle in the field of pre-clinical nicotine addiction research has been the inability to produce escalated nicotine self-administration in rats. In experiment 1, male Wistar rats were trained to respond for nicotine in 2-hour operant sessions, then exposed to chronic intermittent (12 hours/day) nicotine vapor and repeatedly tested for nicotine self-administration at 8-12 hours of withdrawal. Rats were tested intermittently on days 1, 3 and 5 of the vapor exposure procedure, then tested with nicotine vapor exposure on 6-15 consecutive days. Rats exhibited transient increases in operant nicotine responding during intermittent testing, regardless of vapor condition, and this responding returned to baseline levels upon resumption of consecutive-days testing (i.e. nicotine deprivation effect). Nicotine vapor-exposed rats then escalated nicotine self-administration relative to both their own baseline (∼200% increase) and non-dependent controls (∼3× higher). In experiment 2, rats were exposed or not exposed to chronic intermittent nicotine vapor, then tested for spontaneous and precipitated somatic signs of nicotine withdrawal. Eight hours following removal from nicotine vapor, rats exhibited robust mecamylamine-precipitated somatic signs of withdrawal. There was a strong correlation between nicotine flow rate and air-nicotine concentration, and the air-nicotine concentrations used in experiments 1 and 2 resemble concentrations experienced by human smokers. Collectively, these results suggest that chronic intermittent nicotine vapor inhalation produces somatic and motivational signs of nicotine dependence, the latter of which is evidenced by escalation of nicotine self-administration.

  7. 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.

  8. Peripheral administration of CDP-choline, phosphocholine or choline increases plasma adrenaline and noradrenaline concentrations.

    PubMed

    Cansev, M; Ilcol, Y O; Yilmaz, M S; Hamurtekin, E; Ulus, I H

    2008-01-01

    1 Intraperitoneal (i.p.) injection of 200-600 mumol/kg of cytidine-5'-diphosphocholine (CDP-choline) increased plasma adrenaline and noradrenaline concentrations dose- and time-dependently. 2 CDP-choline treatment caused several-fold increases in plasma concentrations of CDP-choline and its metabolites phosphocholine, choline, cytidine monophosphate (CMP) and cytidine. 3 Equivalent doses (200-600 mumol/kg; i.p.) of phosphocholine or choline, but not CMP or cytidine, increased plasma adrenaline and noradrenaline dose-dependently. 4 CDP-choline, phosphocholine and choline (600 mumol/kg; i.p.) augmented the increases in plasma adrenaline and noradrenaline in response to graded haemorrhage. 5 The increases in plasma adrenaline and noradrenaline induced by i.p. 600 mumol/kg of CDP-choline, phosphocholine or choline were abolished by pre-treatment with hexamethonium (15 mg/kg; i.p.), but not atropine (2 mg/kg; i.p.). 6 At 320-32 000 mum concentrations, choline, but not CDP-choline or phosphocholine, evoked catecholamine secretion from perfused adrenal gland. Choline (3200 mum)-induced catecholamine secretion was attenuated by the presence of 1 mum of hexamethonium or mecamylamine, but not atropine, in the perfusion medium. 7 Intracerebroventricular (i.c.v.) injection of choline (0.5-1.5 mumol) also increased plasma adrenaline and noradrenaline dose- and time-dependently. Pre-treatment with mecamylamine (50 mug; i.c.v.) or hexamethonium (15 mg/kg; i.p.), but not atropine (10 mug; i.c.v.), prevented i.c.v. choline (1.5 mumol)-induced elevations in plasma adrenaline and noradrenaline. 8 It is concluded that i.p. administration of CDP-choline or its cholinergic metabolites phosphocholine and choline increases plasma adrenaline and noradrenaline concentrations by enhancing nicotinic cholinergic neurotransmission in the sympatho-adrenal system. Central choline also activates the sympatho-adrenal system by increasing central nicotinic cholinergic neurotransmission.

  9. 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.

  10. Involvement of inositol 1,4,5-trisphosphate in nicotinic calcium responses in dystrophic myotubes assessed by near-plasma membrane calcium measurement.

    PubMed

    Basset, Olivier; Boittin, François-Xavier; Dorchies, Olivier M; Chatton, Jean-Yves; van Breemen, Cornelis; Ruegg, Urs T

    2004-11-05

    In skeletal muscle cells, plasma membrane depolarization causes a rapid calcium release from the sarcoplasmic reticulum through ryanodine receptors triggering contraction. In Duchenne muscular dystrophy (DMD), a lethal disease that is caused by the lack of the cytoskeletal protein dystrophin, the cytosolic calcium concentration is known to be increased, and this increase may lead to cell necrosis. Here, we used myotubes derived from control and mdx mice, the murine model of DMD, to study the calcium responses induced by nicotinic acetylcholine receptor stimulation. The photoprotein aequorin was expressed in the cytosol or targeted to the plasma membrane as a fusion protein with the synaptosome-associated protein SNAP-25, thus allowing calcium measurements in a restricted area localized just below the plasma membrane. The carbachol-induced calcium responses were 4.5 times bigger in dystrophic myotubes than in control myotubes. Moreover, in dystrophic myotubes the carbachol-mediated calcium responses measured in the subsarcolemmal area were at least 10 times bigger than in the bulk cytosol. The initial calcium responses were due to calcium influx into the cells followed by a fast refilling/release phase from the sarcoplasmic reticulum. In addition and unexpectedly, the inositol 1,4,5-trisphosphate receptor pathway was involved in these calcium signals only in the dystrophic myotubes. This surprising involvement of this calcium release channel in the excitation-contraction coupling could open new ways for understanding exercise-induced calcium increases and downstream muscle degeneration in mdx mice and, therefore, in DMD.

  11. Nicotine Lozenges

    MedlinePlus

    ... other nicotine smoking cessation aid, such as the nicotine patch, gum, inhaler, or nasal spray.tell your doctor and pharmacist what other prescription and nonprescription medications, ... non-nicotine smoking cessation aids, such as bupropion (Wellbutrin) or ...

  12. Electronic Nicotine Delivery Systems.

    PubMed

    Walley, Susan C; Jenssen, Brian P

    2015-11-01

    Electronic nicotine delivery systems (ENDS) are rapidly growing in popularity among youth. ENDS are handheld devices that produce an aerosolized mixture from a solution typically containing concentrated nicotine, flavoring chemicals, and propylene glycol to be inhaled by the user. ENDS are marketed under a variety of names, most commonly electronic cigarettes and e-cigarettes. In 2014, more youth reported using ENDS than any other tobacco product. ENDS pose health risks to both users and nonusers. Nicotine, the major psychoactive ingredient in ENDS solutions, is both highly addictive and toxic. In addition to nicotine, other toxicants, carcinogens, and metal particles have been detected in solutions and aerosols of ENDS. Nonusers are involuntarily exposed to the emissions of these devices with secondhand and thirdhand aerosol. The concentrated and often flavored nicotine in ENDS solutions poses a poisoning risk for young children. Reports of acute nicotine toxicity from US poison control centers have been increasing, with at least 1 child death reported from unintentional exposure to a nicotine-containing ENDS solution. With flavors, design, and marketing that appeal to youth, ENDS threaten to renormalize and glamorize nicotine and tobacco product use. There is a critical need for ENDS regulation, legislative action, and counter promotion to protect youth. ENDS have the potential to addict a new generation of youth to nicotine and reverse more than 50 years of progress in tobacco control.

  13. Nicotine delivery, retention, and pharmacokinetics from various electronic cigarettes

    PubMed Central

    St. Helen, Gideon; Havel, Christopher; Dempsey, Delia; Jacob, Peyton; Benowitz, Neal L.

    2015-01-01

    Aims To measure the systemic retention of nicotine, propylene glycol (PG), and vegetable glycerin (VG) in electronic cigarette (e-cigarette) users, and assess the abuse liability of e-cigarettes by characterizing nicotine pharmacokinetics. Design E-cigarette users recruited over the Internet participated in a 1-day research ward study. Subjects took 15 puffs from their usual brand of e-cigarette. Exhaled breath was trapped in gas-washing bottles and blood was sampled before and several time after use. Setting San Francisco, California, USA. Participants Thirteen healthy, experienced adult e-cigarette users (6 females and 7 males). Measurements Plasma nicotine was analyzed by GC-MS/MS, and nicotine, VG, and PG in e-liquids and gas traps were analyzed by LC-MS/MS. Heart rate changes and subjective effects were assessed. Findings E-cigarettes delivered an average of 1.3 (0.9–1.8) mg (mean and 95% CI) of nicotine and 94% of the inhaled dose, 1.2 (0.8–1.7), was systemically retained. Average maximum plasma nicotine concentration (Cmax) was 8.4 (5.4–11.5) ng/mL and time of maximal concentration (Tmax) was 2 to 5 minutes; one participant had Tmax of 30 minutes. 89% and 92% of VG and PG, respectively, was systemically retained. Heart rate increased by an average of 8.0 bpm after 5 minutes. Withdrawal and urge to smoke decreased and the e-cigarettes were described as satisfying. Conclusions E-cigarettes can deliver levels of nicotine that are comparable to or higher than typical tobacco cigarettes, with similar systemic retention. Although the average maximum plasma nicotine concentration in experienced e-cigarettes users appears to be generally lower than what has been reported from tobacco cigarette use, the shape of the pharmacokinetic curve is similar, suggesting addictive potential. PMID:26430813

  14. 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...

  15. Adenosine strongly potentiates pressor responses to nicotine in rats.

    PubMed Central

    von Borstel, R W; Renshaw, A A; Wurtman, R J

    1984-01-01

    Intravenous infusion of subhypotensive doses of adenosine strongly potentiates the pressor response of anesthetized rats to nicotine. A dose of nicotine (40 micrograms/kg, i.v.), which, given alone, elicits a peak increase in diastolic pressure of approximately equal to 15 mm Hg, increases pressure by approximately equal to 70 mm Hg when arterial plasma adenosine levels have been increased to 2 microM from a basal concentration of approximately equal to 1 microM. The pressor response to cigarette smoke applied to the lungs is also strongly potentiated during infusion of adenosine. Slightly higher adenosine concentrations (approximately equal to 4 microM) attenuate pressor responses to electrical stimulation of preganglionic sympathetic nerves, or to injections of the alpha-adrenergic agonist phenylephrine, but continue to potentiate pressor responses to nicotine. Low doses (0.25-5 micrograms/kg) of the synthetic adenosine receptor agonists 5'-N-cyclopropylcarboxamidoadenosine, 2-chloroadenosine, and N6-L-phenylisopropyladenosine also potentiate pressor responses to nicotine. Caffeine and theophylline (10 mg/kg) block the potentiating effect of adenosine, and also decrease basal responses to nicotine, suggesting that endogenous adenosine might normally potentiate some nicotine responses. The synergism between nicotine and adenosine appears to take place within sympathetic ganglia. PMID:6591207

  16. Doxycycline plasma concentrations in macaws fed a medicate corn diet.

    PubMed

    Prus, S E; Clubb, S L; Flammer, K

    1992-01-01

    A trial was conducted to determine the doxycycline plasma concentrations attained by feeding a medicated corn diet to large psittacine birds. Doxycycline is the preferred drug for the treatment of chlamydiosis in psittacine birds. Healthy macaws were fed a 0.1% doxycycline-medicated corn diet for 45 days, and plasma doxycycline concentrations were determined by microbiological assay on treatment days 3, 15, 30, and 45. Plasma doxycycline concentrations exceeded 1 microgram/ml in 87% of the samples assayed. As blood concentrations of 1 microgram/ml are considered therapeutic, a doxycycline-medicated corn diet may be efficacious in the treatment of chlamydiosis in large psittacine birds.

  17. 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.

  18. Nanomolar concentrations of nicotine and cotinine alter the development of cultured hippocampal neurons via non-acetylcholine receptor-mediated mechanisms.

    PubMed

    Audesirk, T; Cabell, L

    1999-08-01

    We investigated the effects of nicotine and its metabolic byproduct cotinine on survival, differentiation and intracellular Ca2+ levels of cultured E18 rat hippocampal neurons. We used a range of concentrations from 1 nM to 10 microM, most of which are within the likely range of human fetal exposure from maternal smoking. Nicotine did not influence neuron survival or neurite production. However, at all concentrations tested, nicotine significantly increased branching of both axons and dendrites, an effect which was not reversed by co-culturing with alpha-bungarotoxin, which blocks the nicotinic acetylcholine receptors that predominate in hippocampal cultures (Alkondon and Albuquerque, 1993; Barrantes et al., 1995b). Cotinine at 100 nM and 1 microM significantly reduced neuron survival and neurite production of surviving neurons, but did not significantly alter axon or dendrite branching. These membrane-permeable compounds may work synergistically in the developing embryo to impair the survival and differentiation of hippocampal neurons via intracellular mechanisms.

  19. 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.

  20. Nicotine and tobacco

    MedlinePlus

    Withdrawal from nicotine; Smoking - nicotine addiction and withdrawal; Smokeless tobacco - nicotine addiction; Cigar smoking; Pipe smoking; Smokeless snuff; Tobacco use; Chewing tobacco; Nicotine addiction and tobacco

  1. 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.

  2. Prospective Determination of Plasma Imipenem Concentrations in Critically Ill Children

    PubMed Central

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

    2006-01-01

    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 4× at peak and >10× 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. PMID:16801447

  3. A study of the potential confounding effects of diet, caffeine, nicotine and lorazepam on the stability of plasma and urinary homovanillic acid levels in patients with schizophrenia.

    PubMed

    Donnelly, C L; McEvoy, J P; Wilson, W H; Narasimhachari, N

    1996-12-15

    Ten men inpatients who met DSM-III-R criteria for schizophrenia participated. On five occasions at least one week apart, each subject had an intravenous line placed at 0730 after an overnight fast. On each occasion blood samples were drawn at 0800 and hourly thereafter through 1200 noon for measurement of plasma homovanillic acid (HVA). Total four-hour urine collections were obtained for measurement of urinary HVA. Subjects received five experimental conditions, in randomized sequence: no intervention, smoking one cigarette per hour, drinking one caffeinated cola per hour, lorazepam 2 mg IV push, or a high monoamine meal. Baseline (0800) plasma HVA measures showed only minor intrinsic variability. The average standard deviation in baseline plasma HVA over five occasions of measurement was low relative to the changes in HVA produced during treatment with antipsychotic medications. The high monoamine meal significantly elevated plasma HVA, with a similar trend for urinary HVA. Neither caffeine, nicotine, nor lorazepam significantly affected plasma or urinary HVA.

  4. Plasma renin activities, angiotensin II concentrations, atrial natriuretic peptide concentrations and cardiopulmonary function values in dogs with severe heartworm disease.

    PubMed

    Kitagawa, H; Kitoh, K; Inoue, H; Ohba, Y; Suzuki, F; Sasaki, Y

    2000-04-01

    Relationships among plasma renin activities (PRA), plasma angiotensin II (ATII) concentrations, atrial natriuretic peptide (ANP) concentrations and cardiopulmonary function values were examined in dogs with ascitic pulmonary heartworm disease and acute- and chronic-vena caval syndrome (CS). PRA, plasma ATII concentration and plasma ANP concentration tended to be higher or were significantly higher in dogs with ascites, acute- and chronic-CS. PRA correlated significantly with plasma ATII concentration, WBC count, ALP activity, plasma concentrations of urea nitrogen, creatinine, sodium, potassium, and chloride, right ventricular endodiastolic pressure and right atrial pressure. Plasma ATII concentration correlated significantly with WBC count, plasma concentrations of urea nitrogen, sodium, and potassium, right ventricular endodiastolic pressure and right atrial pressure. Plasma ANP concentration did not correlate with PRA or ATII concentration, but correlated significantly only with pulmonary arterial pressure.

  5. Factors influencing post-exercise plasma protein carbonyl concentration.

    PubMed

    Wadley, Alex J; Turner, James E; Aldred, Sarah

    2016-01-01

    Exercise of sufficient intensity and duration can cause acute oxidative stress. Plasma protein carbonyl (PC) moieties are abundant, chemically stable, and easily detectable markers of oxidative stress that are widely used for the interpretation of exercise-induced changes in redox balance. Despite many studies reporting acute increases in plasma PC concentration in response to exercise, some studies, including those from our own laboratory have shown decreases. This review will discuss the differences between studies reporting increases, decreases, and no change in plasma PC concentration following exercise in humans; highlighting participant physiology (i.e. training status) and study design (i.e. intensity, duration, and novelty of the exercise bout) as the main factors driving the direction of the PC response to exercise. The role of the 20S proteasome system is proposed as a possible mechanism mediating the clearance of plasma PC following exercise. Resting and exercise-induced differences in plasma protein composition and balance between tissues are also discussed. We suggest that exercise may stimulate the clearance of plasma PC present at baseline, whereas simultaneously increasing reactive oxygen species production that facilitates the formation of new PC groups. The balance between these two processes likely explains why some studies have reported no change or even decreases in plasma PC level post-exercise when other biomarkers of oxidative stress (e.g. markers of lipid peroxidation) were elevated. Future studies should determine factors that influence the balance between PC clearance and formation following acute exercise.

  6. Platelet activation, adhesion, inflammation, and aggregation potential are altered in the presence of electronic cigarette extracts of variable nicotine concentrations.

    PubMed

    Hom, Sarah; Chen, Li; Wang, Tony; Ghebrehiwet, Berhane; Yin, Wei; Rubenstein, David A

    2016-11-01

    Tobacco smoke extracts prepared from both mainstream and sidestream smoking have been associated with heightened platelet activation, aggregation, adhesion, and inflammation. Conversely, it has been shown that pure nicotine inhibits similar platelet functions. In this work, we 1) evaluated the effects of e-cigarette extracts on platelet activities and 2) elucidated the differences between the nicotine-dependent and non-nicotine dependent (e.g. fine particulate matter or toxic compounds) effects of tobacco and e-cigarette products on platelet activities. To accomplish these goals, platelets from healthy volunteers (n = 50) were exposed to tobacco smoke extracts, e-cigarette vapor extracts, and pure nicotine and changes in platelet activation, adhesion, aggregation, and inflammation were evaluated, using optical aggregation, flow cytometry, and ELISA methods. Interestingly, the exposure of platelets to e-vapor extracts induced a significant up-regulation in the expression of the pro-inflammatory gC1qR and cC1qR and induced a marked increase in the deposition of C3b as compared with traditional tobacco smoke extracts. Similarly, platelet activation, as measured by a prothrombinase based assay, and platelet aggregation were also significantly enhanced after exposure to e-vapor extracts. Finally, platelet adhesion potential toward fibrinogen, von Willebrand factor, and other platelets was also enhanced after exposure to e-cigarette vapor extracts. In the presence of pure nicotine, platelet functions were observed to be inhibited, which further suggests that other constituents of tobacco smoke and electronic vapor can antagonize platelet functions, however, the presence of nicotine in extracts somewhat perpetuated the platelet functional changes in a dose-dependent manner.

  7. A validated method for the determination of nicotine, cotinine, trans-3'-hydroxycotinine, and norcotinine in human plasma using solid-phase extraction and liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry.

    PubMed

    Kim, Insook; Huestis, Marilyn A

    2006-06-01

    A liquid chromatographic-mass spectrometric method for the simultaneous determination of nicotine, cotinine, trans-3'-hydroxycotinine, and norcotinine in human plasma was developed and validated. Analytes and deuterated internal standards were extracted from human plasma using solid-phase extraction and analyzed by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometric detection with selected ion monitoring (SIM). Limits of detection and quantification were 1.0 and 2.5 ng/ml, respectively, for all analytes. Linearity ranged from 2.5 to 500 ng/ml of human plasma using a weighting factor of 1/x; correlation coefficients for the calibration curves were > 0.99. Intra- and inter-assay precision and accuracy were < 15.0%. Recoveries were 108.2-110.8% nicotine, 95.8-108.7% cotinine, 90.5-99.5% trans-3'-hydroxycotinine, and 99.5-109.5% norcotinine. The method was also partially validated in bovine serum, owing to the difficulty of obtaining nicotine-free human plasma for the preparation of calibrators and quality control (QC) samples. This method proved to be robust and accurate for the quantification of nicotine, cotinine, trans-3'-hydroxycotinine, and norcotinine in human plasma collected in clinical studies of acute nicotine effects on brain activity and on the development of neonates of maternal smokers.

  8. Effects of age and sex on olanzapine plasma concentrations.

    PubMed

    Weiss, Ulrike; Marksteiner, Josef; Kemmler, Georg; Saria, Alois; Aichhorn, Wolfgang

    2005-12-01

    Age and sex may influence both efficacy and side effects of second-generation antipsychotics. Women and elderly patients tend to have a higher prevalence for several side effects. Higher plasma levels in these groups of patients may be one reason. We studied the hypothesis that steady-state olanzapine plasma concentrations depend on age and sex. Sixty-seven inpatients on stable olanzapine dose were referred to routine therapeutic drug monitoring of olanzapine. Plasma levels were determined by high-performance liquid chromatography with electrochemical detection. Obtained data were then analyzed by analysis of covariance. Olanzapine plasma levels showed a marked sex difference with significantly higher mean concentrations in female patients (adjusted mean concentrations, 18.5 ng/mL for men and 31.7 ng/mL for women; P = 0.003). On average, the weight-corrected concentration/dose ratios shown by women were 33.5% higher than those shown by men, irrespective of age. Regarding the effect of age, weight-corrected concentration/dose ratios increased by an average of 9.4% per decade of life. All results were adjusted for smoking. Comedication did not significantly influence these results. In conclusion, age and sex are important variables to consider when prescribing olanzapine for women and in the elderly.

  9. Measuring tobacco smoke exposure: quantifying nicotine/cotinine concentration in biological samples by colorimetry, chromatography and immunoassay methods.

    PubMed

    Dhar, Preeti

    2004-04-01

    Procedures to assess tobacco smoke exposure are reviewed and biomarkers used for determining the smoking status of an individual are compared. Methods used to extract these biomarkers from saliva, urine, and blood and the advantages and disadvantages of the assays are discussed. Finally, the procedures used to measure the levels of cortisol, a stress hormone speculated to be linked to nicotine metabolism, are discussed.

  10. 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.

  11. Prazosin lowers plasma triglyceride concentration in rats: a preliminary report.

    PubMed

    Reaven, G M; Dall'Aglio, E

    1982-01-01

    Prazosin was administered by intraperitoneal injection (0.3 or 3.0 mg/kg) to normal chow-fed male rats for 14 days. Mean +/- SEM plasma triglyceride levels were lower (p less than 0.001) in the prazosin-treated rats (74 +/- 12 mg/dl and 72 +/- 9 mg/dl) than in saline-injected control rats (115 +/- 11 mg/dl). This effect was associated with commensurate reductions in very low density lipoprotein-triglyceride secretion in prazosin-treated rats. No changes were noted in either plasma total or high density lipoprotein cholesterol concentrations. In addition, prazosin was capable of reducing by approximately 50% the elevation in plasma triglyceride concentration produced by a high glucose diet in control rats. The mechanism of the observed effect of prazosin on very low density lipoprotein metabolism in the rat remains to be defined.

  12. Variations in plasma phytoestrogen concentrations in European adults.

    PubMed

    Peeters, Petra H M; Slimani, Nadia; van der Schouw, Yvonne T; Grace, Philip B; Navarro, Carmen; Tjonneland, Anne; Olsen, Anja; Clavel-Chapelon, Francoise; Touillaud, Marina; Boutron-Ruault, Marie-Christine; Jenab, Mazda; Kaaks, Rudolf; Linseisen, Jakob; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Dilis, Vardis; Boeing, Heiner; Weikert, Cornelia; Overvad, Kim; Pala, Valeria; Palli, Domenico; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Bueno-de-Mesquita, H Bas; van Gils, Carla H; Skeie, Guri; Jakszyn, Paula; Hallmans, Goran; Berglund, Goran; Key, Tim J; Travis, Ruth; Riboli, Elio; Bingham, Sheila A

    2007-05-01

    Dietary phytoestrogens may play a role in chronic disease occurrence. The aim of our study was to assess the variability of plasma concentrations in European populations. We included 15 geographical regions in 9 European countries (Denmark, France, Germany, Greece, Italy, Spain, Sweden, The Netherlands, and UK) and a 16th region, Oxford, UK, where participants were recruited from among vegans and vegetarians. All subjects were participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma concentrations of 3 isoflavones (daidzein, genistein, and glycitein), 2 metabolites of daidzein [O-desmethylangolensin (O-DMA) and equol] and 2 mammalian lignans (enterodiol and enterolactone) were measured in 1414 participants. We computed geometric means for each region and used multivariate regression analysis to assess the influence of region, adjusted for gender, age, BMI, alcohol intake, smoking status, and laboratory batch. Many subjects had concentrations below the detection limit [0.1 microg/L (0.4 nmol/L)] for glycitein (80%), O-DMA (73%) and equol (62%). Excluding subjects from Oxford, UK, the highest concentrations of isoflavones were in subjects from the Netherlands and Cambridge, UK [2-6 microg/L (7-24 nmol/L); P < 0.05], whereas concentrations for lignans were highest in Denmark [8 microg/L (27 nmol/L); P < 0.05]. Isoflavones varied 8- to 13-fold, whereas lignans varied 4-fold. In the vegetarian/vegan cohort of Oxford, concentrations of isoflavones were 5-50 times higher than in nonvegetarian regions. Region was the most important determinant of plasma concentrations for all 7 phytoestrogens. Despite the fact that plasma concentrations of phytoestrogens in Europe were low compared with Asian populations, they varied substantially among subjects from the 16 different regions.

  13. Plasma drug concentrations and physiological measures in 'dance party' participants.

    PubMed

    Irvine, Rodney J; Keane, Michael; Felgate, Peter; McCann, Una D; Callaghan, Paul D; White, Jason M

    2006-02-01

    The increasing use of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) in the setting of large dance parties ('raves') and clubs has been the source of some concern, because of potential acute adverse events, and because animal studies suggest that MDMA has the potential to damage brain serotonin (5-HT) neurons. However, it is not yet known whether MDMA, as used in the setting of dance parties, leads to plasma levels of MDMA that are associated with toxicity to 5-HT neurons in animals. The present study sought to address this question. Plasma MDMA concentrations, vital signs, and a variety of blood and urine measures were obtained prior to, and hours after, individuals attended a dance party. After the dance party, subjects were without clinical complaints, had measurable amounts of residual MDMA in plasma, and nearly half of the subjects also tested positive for methamphetamine, another amphetamine analog that has been shown to have 5-HT neurotoxic potential in animals. Plasma concentrations of MDMA did not correlate with self-reported use of 'ecstasy' and, in some subjects, overlapped with those that have been associated with 5-HT neurotoxicity in non-human primates. Additional subjects were likely to have had similar concentrations while at the dance party, when one considers the reported time of drug ingestion and the plasma half-life of MDMA in humans. Hematological and biochemical analyses were generally unremarkable. Moderate increases in blood pressure, heart rate and body temperature were observed in the subjects with the highest MDMA plasma concentrations. These findings are consistent with epidemiological findings that most people who use MDMA at dance parties do not develop serious clinical complications, and suggest that some of these individuals may be at risk for developing MDMA-induced toxicity to brain serotonin neurons.

  14. Nicotine potentiates proatherogenic effects of oxLDL by stimulating and upregulating macrophage CD36 signaling.

    PubMed

    Zhou, Ming-Sheng; Chadipiralla, Kiranmai; Mendez, Armando J; Jaimes, Edgar A; Silverstein, Roy L; Webster, Keith; Raij, Leopoldo

    2013-08-15

    Cigarette smoking is a major risk factor for atherosclerosis and cardiovascular disease. CD36 mediates oxidized LDL (oxLDL) uptake and contributes to macrophage foam cell formation. We investigated a role for the CD36 pathway in nicotine-induced activation of macrophages and foam cell formation in vitro and in vivo. Nicotine in the same plasma concentration range found in smokers increased the CD36(+)/CD14(+) cell population in human peripheral blood mononuclear cells, increased CD36 expression of human THP1 macrophages, and increased macrophage production of reactive oxygen species, PKCδ phosphorylation, and peroxisome proliferator-activated receptor-γ (PPARγ) expression. Nicotine-induced CD36 expression was suppressed by antioxidants and by specific PKCδ and PPARγ inhibitors, implicating mechanistic roles for these intermediates. Nicotine synergized with oxLDL to increase macrophage expression of CD36 and cytokines TNF-α, monocyte chemoattractant protein-1, IL-6, and CXCL9, all of which were prevented by CD36 small interfering (si)RNA. Incubation with oxLDL (50 μg/ml) for 72 h resulted in lipid deposition in macrophages and foam cell formation. Preincubation with nicotine further increased oxLDL-induced lipid accumulation and foam cell formation, which was also prevented by CD36 siRNA. Treatment of apoE-/- mice with nicotine markedly exacerbated inflammatory monocyte levels and atherosclerotic plaque accumulation, effects that were not seen in CD36-/- apoE-/- mice. Our results show that physiological levels of nicotine increase CD36 expression in macrophages, a pathway that may account at least in part for the known proinflammatory and proatherogenic properties of nicotine. These results identify such enhanced CD36 expression as a novel nicotine-mediated pathway that may constitute an independent risk factor for atherosclerosis in smokers. The results also suggest that exacerbated atherogenesis by this pathway may be an adverse side effect of extended use

  15. 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.

  16. Tocopherol isomers in intravenous lipid emulsions and resultant plasma concentrations.

    PubMed

    Gutcher, G R; Lax, A A; Farrell, P M

    1984-01-01

    Conflicting reports exist regarding the relative tocopherol isomer content of Intralipid ranging from 99% as alpha-tocopherol to as much as 90% as gamma-tocopherol. Our direct assay of Intralipid as well as plasma levels measured in premature infants receiving Intralipid confirm the existence of a low alpha, high gamma-tocopherol content and imply the need for alpha-tocopherol supplementation in patients receiving Intralipid, particularly the relatively tocopherol-deficient premature infant. Furthermore, the observation of abnormal erythrocyte hemolysis test values despite "normal" total tocopherol plasma concentrations may be explained by high plasma levels of non-alpha, biologically less active isomers. The quantitation of tocopherol isomers helps explain this discrepancy and suggests the need for future studies of vitamin E status to employ measurements of tocopherol isomers in reporting results.

  17. Electronic cigarettes and nicotine clinical pharmacology

    PubMed Central

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

  18. Social regulation of plasma estradiol concentration in a female anuran.

    PubMed

    Lynch, Kathleen S; Wilczynski, Walter

    2006-06-01

    The behavior of an individual within a social aggregation profoundly influences behavior and physiology of other animals within the aggregation in such a way that these social interactions can enhance reproductive success, survival and fitness. This phenomenon is particularly important during the breeding season when males and female must synchronize their reproductive efforts. We examined whether exposure to conspecific social cues can elevate sex steroid levels, specifically estradiol and androgens, in female túngara frogs (Physalaemus pustulosus). We compared plasma estradiol and androgen concentrations in wild-caught females before and after exposure to either natural mate choruses or random tones. After exposure to mate choruses for 10 consecutive nights, estradiol concentrations were significantly elevated whereas there was no significant elevation in estradiol concentrations in the group of females exposed to random tones for 10 nights. Plasma androgen concentrations were not significantly changed after exposure to either natural mate choruses or random tones for 10 consecutive nights. Social modulation of estradiol concentrations may be important in maintaining a female's reproductive state while males are chorusing. To our knowledge, this is the first study to demonstrate social regulation of estradiol concentration in female anurans.

  19. Epilepsy and the concentrations of plasma amino acids in humans.

    PubMed

    Huxtable, R J; Laird, H; Lippincott, S E; Walson, P

    1983-01-01

    We have examined the correlation between the presence of epilepsy in humans, and plasma amino acid levels. Subjects were divided into those having pure generalized tonic-clonic seizures (grand mal group), those having generalized tonic-clonic seizures plus other types of epilepsy (mixed group), and those suffering from epilepsies other than grand mal (no grand mal group). Compared to non-epileptic controls, the grand mal group had significantly higher fasting plasma levels of aspartate (100% increase) and glutamate (380% increase) but significant decreases were seen with phenylalanine (?23%), lysine (?27%), and tryptophan (?30%). The no grand mal group showed similar changes except for lysine. The mixed group showed elevations in glutamate, but decreases only in cysteine and methionine. In response to a high protein meal, plasma levels of alanine, cysteine and methionine rose significantly less for the no grand mal group compared to the control group. Increases in aspartate and glutamate concentrations strongly correlated with the prescription of phenytoin. However, the concentrations of these amino acids were not significantly correlated with the actual plasma levels of phenytoin.

  20. Plasma Polychlorinated Biphenyl Concentrations and Immune Function in Postmenopausal Women☆

    PubMed Central

    Spector, June T.; De Roos, Anneclaire J.; Ulrich, Cornelia M.; Sheppard, Lianne; Sjodin, Andreas; Wener, Mark H.; Wood, Brent; McTiernan, Anne

    2014-01-01

    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 per 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. PMID:24721136

  1. 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.

  2. Nicotine therapy for ulcerative colitis: a review of rationale, mechanisms, pharmacology, and clinical results.

    PubMed

    Sandborn, W J

    1999-05-01

    Smoking is protective against developing ulcerative colitis. Nicotine may be the cause of this protective effect. Controlled trials have demonstrated efficacy of transdermal nicotine for active ulcerative colitis. Side effects observed with transdermal nicotine include contact dermatitis, nausea, and lightheadedness. Topical administration of nicotine to the colon reduces nicotine blood concentrations and side effects, and may be of clinical benefit.

  3. Nicotine Gum

    MedlinePlus

    ... gum is used to help people stop smoking cigarettes. Nicotine chewing gum should be used together with ... by your doctor.If you smoke your first cigarette more than 30 minutes after waking up, use ...

  4. 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

  5. A convenient method to measure blood-plasma concentration ratio using routine plasma collection in in vivo pharmacokinetic studies.

    PubMed

    Berezhkovskiy, Leonid M; Zhang, Xiaolin; Cheong, Jonathan

    2011-12-01

    A practical time-saving method of determination of equilibrium blood-plasma concentration ratio is described. The method is based on the analysis of compound plasma concentrations in regular blood sample and the blood sample diluted with blank plasma. Since only plasma concentrations are analyzed, the method can be conveniently applied in routine pharmacokinetic studies with minimal additional work for obtaining blood-plasma ratio. The method can also be easily used in in vitro experiment. The results obtained by suggested method are in good agreement with that obtained by common in vitro measurements of blood-plasma ratio.

  6. 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.

  7. 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

  8. 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.

  9. Plasma carnitine concentrations in patients undergoing open heart surgery.

    PubMed

    Nemoto, Shintaro; Yasuhara, Kiyomitsu; Nakamura, Katsutoshi; Miyoshi, Yutaka; Sakai, Akira

    2004-02-01

    Carnitine is an essential cofactor for fatty acid (FA) metabolism, the predominant source of ATP in the normal aerobic heart. During myocardial ischemia, FA metabolism is impaired and tissue carnitine levels are depleted. Since the heart cannot synthesize carnitine, plasma carnitine could play an important role in maintaining myocardial carnitine levels during reperfusion. The purpose of this study was to determine the incidence of abnormal plasma carnitine concentrations in open heart surgery. Blood samples were obtained from eleven patients before, immediately after, and two hours after cardiopulmonary bypass (CPB). Total and free carnitine levels were significantly reduced immediately after CPB (p<0.01) and remained depressed until two hours after CPB (p<0.01 vs. pre CPB), while acyl carnitine levels were unchanged over the course of this study. These depressed free carnitine levels might affect cardiac metabolism in the heart after open heart surgery. Carnitine supplement might be a useful adjunct in the therapy after open heart surgery.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. In vitro human epidermal permeation of nicotine from electronic cigarette refill liquids and implications for dermal exposure assessment.

    PubMed

    Frasch, H Frederick; Barbero, Ana M

    2016-12-07

    Nicotine plus flavorings in a propylene glycol (PG) vehicle are the components of electronic cigarette liquids (e-liquids), which are vaporized and inhaled by the user. Dermal exposure to nicotine and e-liquids may occur among workers in mixing and filling of e-cigarettes in the manufacturing process. Inadvertent skin contact among consumers is also a concern. In vitro nicotine permeation studies using heat-separated human epidermis were performed with surrogate and two commercial e-liquids, neat and aqueous nicotine donor formulations. Steady-state fluxes (Jss), and lag times (tlag) were measured for each formulation. In addition, transient (4 h) exposure and finite dose (1-10 μl/cm(2)) experiments were undertaken using one commercial e-liquid. Average Jss (μg/cm(2)/h) from formulations were: nicotine in PG (24 mg/ml): 3.97; commercial e-liquid containing menthol (25 mg/ml nicotine): 10.2; commercial e-liquid containing limonene (25 mg/ml nicotine): 23.7; neat nicotine: 175. E-liquid lag times ranged from 5 to 10 h. Absorbed fraction of nicotine from finite doses was ≈0.3 at 48 h. The data were applied to transient exposure and finite dose dermal exposure assessment models and to a simple pharmacokinetic model. Three illustrative exposure scenarios demonstrate use of the data to predict systemic uptake and plasma concentrations from dermal exposure. The data demonstrate the potential for significant nicotine absorption through skin contact with e-cigarette refill solutions and the neat nicotine used to mix them.Journal of Exposure Science and Environmental Epidemiology advance online publication, 7 December 2016; doi:10.1038/jes.2016.68.

  15. The effect of three products of cigarette smoke (cyanide, thiocyanate and nicotine) on the concentration-response curves of 5-hydroxytryptamine, norepinephrine and epinephrine in the isolated human umbilical veins and arteries.

    PubMed

    Tunçel, N; Aydin, Y; Tikiz, H

    1994-02-01

    The effect of cyanide (10(-7) M), thiocyanate (10(-4) M) and nicotine (10(-7) M) on the concentration-response curves of 5-hydroxytryptamine, norepinephrine and epinephrine were investigated in human isolated umbilical arteries and veins. Cyanide significantly affected the responses of arterial strips to 5-hydroxytryptamine, norepinephrine and epinephrine: It caused significant leftward shifts of the 5-hydroxytryptamine concentration-response curves and significantly potentiated the contractile effects of norepinephrine and epinephrine in the case of norepinephrine, and epinephrine concentration reached 10(-6) and 10(-7) M respectively in the bath medium. Cyanide did not show any significant effect on the concentration-response curves of 5-hydroxytryptamine, norepinephrine and epinephrine in veins. Nicotine interacted with the response of adrenergic agonists both in arteries and veins; in arteries it potentiates the contractile response of epinephrine; in veins, it inhibited the dilatory responses of norepinephrine and potentiated the contractile effect of high concentration of epinephrine (10(-6) M). Thiocyanate did not cause any difference on any cumulative concentration-response curves either on the vessels. However, none of these individual effects of cyanide and nicotine were observed when the cyanide, thiocyanate and nicotine were added in combination in the isolated organ bath medium.

  16. 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.

  17. 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.

  18. Relationship between Plasma Albumin Concentration and Plasma Volume in 5 Inbred Rat Strains.

    PubMed

    Rose, Rajiv; Klemcke, Harold G

    2015-09-01

    Using the Evans Blue procedure, we previously found strain-related differences in plasma volumes in 5 inbred rat strains. Because albumin binds strongly with Evans blue, this protein is important in the Evans blue method of plasma volume determination. Therefore, we speculated that interstrain differences in plasma albumin concentration (PAC) could distort calculated plasma volumes. To address this concern, we used ELISA techniques to measure PAC in these inbred rat strains. In study A, the blood volume was measured by using Evans blue dye, and albumin was measured at the start of hemorrhage. In study B, blood volume was not measured, and albumin was measured twice, near the start and end of hemorrhage (approximately 14 min apart). Neither study revealed any interstrain differences in PAC, which decreased after hemorrhage in all 5 strains. No correlation was found between PAC and plasma volume, survival time, blood lactate, or blood base excess. Percentage changes in PAC during hemorrhage were greater in salt-sensitive compared with Lewis rats. Moreover, these percentage changes were associated with survival time in Fawn hooded hypertensive rats. Our data show that the plasma volumes we measured previously were not misrepresented due to variations in PAC.

  19. Approaches to modeling of plasmas containing impurity at arbitrary concentration

    NASA Astrophysics Data System (ADS)

    Tokar, Mikhail Z.

    2016-02-01

    A new approximate method to modeling of two-ion-species plasmas with arbitrary concentration of impurity is developed. It based on the usage of equations for the electron density and the ratio of the ion species densities as new dependent variables. In contrast to motion equations for the ion mass velocities used normally, those for the new variables have a singularity at the Debye sheath only, as in the case of a one species plasma. Computations for the most critical situations of weak and intermediate friction between species due to Coulomb collisions reproduce nearly perfectly the results got by solving the original equations, however within a calculation time reduced by a factor of 102-103. In the case of strong friction, where ions’ velocities are very close each other, the normal procedure does not converge at all, but the new one, being precise in this limit, operates very reliably. Calculations are done for conditions typical in the linear device PSI-2, with deuterium plasmas seeded by neon impurity. For fixed electron and ion temperatures a critical density of impurity atoms is found, at which the electron density grows without limits. Such a catastrophic behavior does not occur if the electron and ion heat balances are taken into account to calculate the temperature profiles self-consistently.

  20. Relationship between trough plasma and epithelial lining fluid concentrations of voriconazole in lung transplant recipients.

    PubMed

    Heng, Siow-Chin; Snell, Gregory I; Levvey, Bronwyn; Keating, Dominic; Westall, Glen P; Williams, Trevor J; Whitford, Helen; Nation, Roger L; Slavin, Monica A; Morrissey, Orla; Kong, David C M

    2013-09-01

    Trough (predose) voriconazole concentrations in plasma and pulmonary epithelial lining fluid (ELF) of lung transplant recipients receiving oral voriconazole preemptive treatment were determined. The mean (± standard deviation [SD]) ELF/plasma ratio was 12.5 ± 6.3. A strong positive linear relationship was noted between trough plasma and ELF voriconazole concentrations (r(2) = 0.87), suggesting the feasibility of using trough plasma voriconazole concentration as a surrogate to estimate the corresponding concentration in ELF of lung transplant recipients.

  1. 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

  2. Effect of Menthol on Nicotine Pharmacokinetics in Rats After Cigarette Smoke Inhalation

    PubMed Central

    2012-01-01

    Introduction: The effect of menthol on nicotine disposition is important in understanding smoking behaviors among different racial groups. The present study was to evaluate whether menthol affects the pharmacokinetics of nicotine after cigarette smoke inhalation. Methods: Rats were exposed to mainstream smoke from either a nonmentholated or mentholated cigarette (1 puff/min for 10 min) using a smoke inhalation apparatus. For the multiple-cigarette smoke inhalation, rats received the smoke from either nonmentholated or mentholated cigarette (10 puffs) every 12 hr for a total of 17 cigarettes. Serial blood samples were collected during the 10-min inhalation phase for the single-cigarette smoke or the 17th cigarette inhalation and for 30 hr thereafter. Nicotine and its major metabolite cotinine were assayed by radioimmunoassay methods. Results: Following single-cigarette smoke inhalation, mentholated cigarettes significantly decreased the mean peak concentrations of nicotine in plasma (Cmax) from 27.1 to 9.61 ng/ml and the total area under the plasma concentration–time curves (AUC) from 977 to 391 ng min/ml as compared with those after nonmentholated cigarette smoke inhalation. Cmax and AUC values for cotinine were also significantly reduced by menthol. Similarly after multiple smoke inhalation, Cmax, AUC, and the mean average steady-state plasma concentration of nicotine as well as cotinine were significantly lower in mentholated cigarette inhalation. Interestingly, there was a significant increase in the cotinine to nicotine AUC ratio from 13.8 for the nonmentholated to 21.1 for the mentholated cigarette. Conclusions: These results suggest that menthol in mentholated cigarettes can substantially decrease the absorption and/or increase the clearance of nicotine. PMID:22311961

  3. Plasma and salivary amoxicillin concentrations and effect against oral microorganisms.

    PubMed

    Baglie, S; Del Ruenis, A P Bortolo; Motta, R H Lopes; Baglie, R C Catelli; Franco, G C Nobre; Franco, L M; Rosalen, P L; Silva, P; Groppo, F C

    2007-10-01

    Plasma and salivary amoxicillin (AMO) concentrations were quantified following a single oral dose (875 mg) of two formulations of AMO (Amoxicillin-EMS Sigma Pharma and Amoxil BD 875 mg). In addition, the effect of amoxicillin against oral microorganisms was accessed. The open, randomized, two-period crossover study was carried out in 20 volunteers. Saliva and blood samples were collected at 0, 0.5, 1, 2, 4, 8 and 12 h after drug administration, and quantified using HPLC-ESI-MS and HPLC, respectively. Streptococci counts, anaerobe counts and total microorganism counts were obtained. No differences were observed between formulations (p > 0.05) in the plasma and salivary AMO concentrations and the pharmacokinetic parameters (C(max), t(max), AUC(0-8), and AUC(0-infinity)) also showed no statistically significant differences between formulations (p > 0.05). Microorganism counts for the two formulations at all sampling times did not differ (p > 0.05) but all microorganism counts at 60 min post-dose showed a significant decrease (p < 0.05). Amoxicillin was effective in reducing oral microorganism levels up to 12 h post-dose.

  4. Seasonal variation in plasma thyroid hormone concentrations in coastal versus inland populations of juvenile American alligators (Alligator mississippiensis): influence of plasma iodide concentrations.

    PubMed

    Boggs, Ashley S P; Hamlin, Heather J; Lowers, Russell H; Guillette, Louis J

    2011-12-01

    Thyroid hormones, essential for normal growth and health, are associated with changes in temperature, photoperiod, and reproduction. Iodide, a necessary element for thyroid hormone production, varies in diet, and is more abundant in estuarine environments, which could alter thyroid hormone variation. However, associations between thyroid hormone concentrations in animals from marine versus freshwater environments, which could become more pertinent with rising sea levels associated with global climate change, are not well studied. To determine the importance of dietary iodide in seasonal variation of plasma thyroid hormone concentrations, we analyzed seasonal variation of plasma thyroxine (T(4)) and triiodothyronine (T(3)) concentrations in juvenile alligators from an estuarine habitat (Merritt Island National Wildlife Refuge; MI) and a freshwater habitat (Lake Woodruff National Wildlife Refuge; LW) and compared these results to plasma inorganic iodide (PII) concentrations. Alligators from MI did not display seasonal variation in plasma T(4), but exhibited a seasonal pattern in plasma T(3) concentrations similar to alligators from LW. Plasma thyroid hormone concentrations were consistently higher at MI than at LW. PII concentrations were correlated with plasma T(4) and T(3) concentrations in juvenile alligators from LW but not MI. The data on plasma T(4) and T(3) concentrations suggest altered iodide metabolism in estuarine alligators. Differences in thyroid hormone concentrations between the populations could be due to differences in dietary iodide, which need to be further evaluated.

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

    PubMed

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

    2015-12-01

    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.

  6. 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

  7. Elevated Plasma Homocysteine Concentration in Opium-Addicted Individuals

    PubMed Central

    Masoomi, Mohammad; Azdaki, Nahid; Shahouzehi, Beydolah

    2015-01-01

    Background Although the triggering role of both opium use and elevated plasma homocysteine level for progressing atherosclerosis and, therefore, appearing coronary heart disease has been clearly determined, no study are available with respect to the relation between these to risk profiles. In the present study and for the first time, we hypothesized that the opium addiction can be potentially correlated with elevated homocysteine concentration. Methods 217 persons (103 opium-addicted and 114 non-addicted) were randomly selected from the Kerman Coronary Artery Disease Risk Study (KERCADRS), Iran, as a population-based, epidemiological prospective study. In all participants, an enzyme immunoassay kit was used to measure homocysteine in serum samples. Findings The serum level of homocysteine was significantly higher in the opium-addicted ones compared to non-addicted individuals (11.49 ± 7.45 vs. 8.02 ± 3.87 μmol/l) (P < 0.001). In this regard, 21.3% of the opium users and only 3.2% of the non-users had homocysteine concentration > 15 μmol/l (P < 0.001). On the other hand, individuals addicted to opiates exhibited significantly elevated odds of having homocysteine level higher than 15 [odds ratio (OR) = 8.244, 95% confidence interval (CI) = 3.117-21.806]. Multivariable linear regression model showed that the opium addiction could strongly predict elevated homocysteine level in the study individuals [beta = 3.524, standard error (SE) = 0.852] (P < 0.001). Conclusion Opium consumption can be strongly accompanied with the elevation of plasma homocysteine concentration, and thus opium addiction can exhibit elevated odds of having hyperhomocysteinemia. PMID:26885351

  8. Interactions of nucleoside analogs, caffeine, and nicotine with human concentrative nucleoside transporters 1 and 2 stably produced in a transport-defective human cell line.

    PubMed

    Lang, Thack T; Young, James D; Cass, Carol E

    2004-04-01

    Pharmacologically important drugs were examined as potential inhibitors or permeants of human concentrative nucleoside transporters 1 (hCNT1)- and 2 (hCNT2)-producing stable transfectants by assessing their abilities to inhibit uridine transport. hCNT1 exhibited high affinities for uridine analogs (5-fluorouridine, 2'-deoxyuridine, 5-fluoro-2'-deoxyuridine, and 5-fluoro-5'-deoxyuridine) with K(i) values of 22 to 33 microM, whereas hCNT2 exhibited moderate affinities for 5-fluoro-2'-deoxyuridine, high affinities for 2'-deoxyuridine and 5-fluorouridine, and low affinity for 5-fluoro-5'-deoxyuridine. The uridine analogs were transported at 2-fold higher rates (at 10 microM) by hCNT1 than by hCNT2. Enantiomeric configuration and the 3'-hydroxyl group of the ribose ring were important determinants for interaction with hCNTs, whereas the 2'-hydroxyl group was less important. Both transporters bound N(6)-(p-aminobenzyl)adenosine with affinities similar to those of adenosine (K(i) = 28-39 microM). Other adenosine receptor ligands, including caffeine, bound better to hCNT1 than to hCNT2 (K(i) = 46 versus 103 microM, respectively), whereas 2-chloroadenosine bound better to hCNT2 than to hCNT1 (K(i) = 37 and 101 microM, respectively). There was a greater than 3-fold difference in binding affinities between hCNT1 and hCNT2 for nicotine (K(i) = 63 versus 227 microM). However, direct measurements of nicotine and caffeine uptake rates (10 microM) failed to demonstrate mediated uptake by either transporter. Although hCNT1 bound several adenosine analogs relatively well, it did not transport 2-chloro-2'-deoxyadenosine (cladribine) or 2-fluoro-9-beta-d-arabinofuranosyladenine (fludarabine), whereas hCNT2 transported both, albeit with low activities. The results indicated that although hCNT1 and hCNT2 possess some overlap in transport of several uridine and adenosine analogs, they also exhibit distinct differences in capacity to interact with some adenosine receptor ligands

  9. 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

  10. [Concentration of elements in plasma of patients with essential hypertension].

    PubMed

    Goch, Aleksander

    2005-10-01

    Disturbances in macro- and microelements composition may play a significant role in the development of essential hypertension. The aim of the study was to estimate main and trace elements concentration in plasma of hypertensive patients. The study involved 150 subjects, aged 33-60 years, who were allotted into 2 groups: I--50 clinically healthy subjects (controls), II--100 patients with arterial hypertension. Age and sex ratio were similar in the examined groups. Those subjected to the study were not administered any drugs at least 3 months prior to the determination of macro- and microelements. Determinations of trace elements Ca, F, Na, K, Mg, Fe, Zn, Cu, Ni, Mo, Al, Cd, Fb, Mu, Se, Cr, Co, Li, V, B, Ba, were performed with atomic emission spectrometer with plasmic excitation (ICP MS Philips PU). In group II in comparison to group I (controls) higher values of Fe, Pb, Al, Cd, Co, B i Ba were observed, as well as higher Zn/Cu ratio; but lower values of Cu and lower Ca/Pb, Ca/Al, Zn/Fe, Se/Fe, Zn/Al, Zn/Cd, Se/Pb, Se/Al, Se/Cd ratio. Increase of prooxidative and decrease,of antioxidative elements in plasma may significantly contribute to the essential hypertension pathogenesis probably through oxidative stress development.

  11. The effect of concurrent aspirin upon plasma concentrations of tenoxicam.

    PubMed Central

    Day, R O; Paull, P D; Lam, S; Swanson, B R; Williams, K M; Wade, D N

    1988-01-01

    1. The effect of chronic, high-dose aspirin therapy upon the disposition of a single dose and multiple doses of tenoxicam was examined in normal volunteers. 2. Aspirin caused a 24% drop in the t1/2 (P less than 0.005), a 49% rise in the volume of distribution (P less than 0.0003) and a 98% increase in the clearance (P less than 0.0001) of tenoxicam after a single dose of the tenoxicam. 3. Steady-state concentrations of tenoxicam decreased significantly from 10.4 +/- 1.5 to 4.5 +/- 1.6 micrograms ml-1 in the presence of chronic, high-dose aspirin treatment. 4. Tenoxicam percentage free measured in plasma from a normal volunteer was 0.56 +/- 0.05% over the tenoxicam concentration range 1-20 micrograms ml-1 and rose to 1.24 +/- 0.07% in the presence of aspirin 150 micrograms ml-1. 5. The effect of aspirin upon the disposition of tenoxicam was consistent with a competitive protein binding interaction. PMID:3190995

  12. Seasonal variation in plasma thyroxine concentrations in juvenile alligators (Alligators mississippiensis) from three Florida Lakes.

    PubMed

    Bermudez, Dieldrich S; Milnes, Matthew R; Bryan, Teresa A; Gunderson, Mark P; Tubbs, Christopher; Woodward, Allan R; Guillette, Louis J

    2005-05-01

    Circulating concentrations of thyroxine (T(4)) vary seasonally in many vertebrates. This study examined the seasonal variation in plasma concentrations of T(4) in juvenile American alligators (Alligator mississippiensis) from three populations in central Florida, USA. One site, Lake Woodruff National Wildlife Refuge, is considered a reference site whereas the other two lakes, Lake Apopka and Orange Lake, are significantly impacted by human activity. Juvenile American alligators ranging from 75-150 cm in total length were hand-captured at night from November 2000-April 2002. Plasma thyroxine concentrations were analyzed using a radioimmunoassay (RIA) previously validated for alligator plasma. Juvenile American alligators display seasonal variation in circulating T(4) concentrations. Plasma T(4) concentrations decrease from August/September to November and then begin a slow rise until April, at which point they plateau. Sex of juveniles influenced plasma concentrations of T(4) in some months but did not appear to alter the pattern in seasonal variation. The pattern we observed in plasma T(4) concentrations is not directly related to an environmental factor such as ambient temperature but is similar to that seen in plasma sex steroid concentrations during the reproductive cycle of adult alligators. Although the pattern and plasma concentration of T(4) exhibits significant variation among the three lakes studied, the pattern in seasonal variation appears similar. Comparing the seasonal pattern in plasma T(4) with plasma concentrations of sex steroids (testosterone and estradiol-17beta) or corticosterone could provide important information on the peripubescent life stage of the American alligator.

  13. Nicotine exposure in adolescence alters the response of serotonin systems to nicotine administered subsequently in adulthood.

    PubMed

    Slotkin, Theodore A; Seidler, Frederic J

    2009-01-01

    Developmental nicotine exposure produces lasting changes in serotonin (5-HT) function. We gave nicotine to adolescent rats (postnatal days, PD, 30-47), simulating plasma levels in smokers, and then examined the subsequent effects of nicotine given again in young adulthood (PD 90-107), focusing on 5-HT(1A) and 5-HT(2) receptors and the 5-HT transporter during nicotine treatment (PD 105) and withdrawal (PD 110, 120, 130), and long-term changes (PD 180). Adolescent nicotine exposure by itself evoked long-term elevations in cerebrocortical binding parameters in males that emerged in young adulthood. Nicotine given in adulthood produced transient elevations in 5-HT receptor expression in both males and females during withdrawal, and persistent upregulation in the male cerebral cortex. In contrast, females showed decrements in cerebrocortical 5-HT receptors by PD 180. Adolescent nicotine exposure altered the responses to nicotine given in adulthood, sensitizing the initial effects and changing both the withdrawal response and long-term actions. Our results thus provide mechanistic evidence that nicotine exposure, during the period in which nearly all smokers begin to use tobacco, reprograms the future response of 5-HT systems to nicotine.

  14. Neuronal nicotinic acetylcholine receptors are modulated by zinc.

    PubMed

    Vázquez-Gómez, Elizabeth; García-Colunga, Jesús

    2009-01-01

    It is known that zinc modulates nicotinic acetylcholine receptors (nAChRs). Here, we studied the effects of zinc on neuronal alpha4beta4 nAChRs, expressed in Xenopus oocytes and activated by nicotine. Membrane ion currents elicited by nicotine (10 nM to 100 microM) were enhanced by zinc (100 microM). Maximal zinc potentiation of the nicotine-activated current (2530%) occurred at 50 nM nicotine, and potentiation gradually decreased as the nicotine concentration increased. The EC(50) and IC(50) for the nicotine-activated current were 639 nM and 14.7 microM nicotine, respectively. Both parameters decreased in the presence of zinc to 160 nM and 4.6 microM, respectively, probably due to an increase of sensitivity of nAChRs for nicotine. We used different concentrations and durations of exposure to nicotine, due to desensitization of nAChRs directly depends on both these factors. With 500 nM nicotine and 20 min washing periods between nicotine applications, zinc potentiation remained constant, 901% for 2 min and 813% for 20 min of nicotine exposure. With continuous application of nicotine, zinc potentiation decreased as the time of nicotine exposure increased, 721% for 2 min and 254% for 48 min of nicotine exposure. Our results indicate that zinc-potentiating effects on alpha4beta4 nAChRs strongly depend on both concentration and time of exposure to nicotine, suggesting that zinc potentiation depends on the degree of desensitization.

  15. Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: a validation study.

    PubMed

    Schnoll, Robert A; Patterson, Freda; Wileyto, E Paul; Tyndale, Rachel F; Benowitz, Neal; Lerman, Caryn

    2009-03-01

    Transdermal nicotine is widely used for smoking cessation, but only approximately 20% of smokers quit successfully with this medication. Interindividual variability in nicotine metabolism rate may influence treatment response. This study sought to validate, and extend in a larger sample, our previous finding that the ratio of plasma nicotine metabolites 3'-hydroxycotinine (3-HC)/cotinine, a measure of nicotine metabolism rate, predicts response to nicotine patch. A sample of 568 smokers was enrolled in a study that provided counseling and 8-weeks of 21 mg nicotine patch. Pretreatment 3-HC/cotinine ratio was examined as a predictor of 7-day point prevalence abstinence, verified with breath carbon monoxide (CO), 8 weeks after the quit date. Controlling for sex, race, age, and nicotine dependence, smokers in the upper 3 quartiles of 3-HC/cotinine ratio (faster metabolizers) were approximately 50% less likely to be abstinent vs. smokers in the first quartile (slow metabolizers; 28% vs. 42%; OR=.54 [95% CI:.36-.82], p=.003). Among abstainers, plasma nicotine levels (assessed 1 week after treatment began) decreased linearly across the 3-HC/cotinine ratio (beta=-3.38, t[355]=-3.09, p<.05). These data support the value of the 3-HC/cotinine ratio as a biomarker to predict success with transdermal nicotine for smoking cessation.

  16. Association of plasma concentration of 4β-hydroxycholesterol with CYP3A5 polymorphism and plasma concentration of indoxyl sulfate in stable kidney transplant recipients.

    PubMed

    Suzuki, Yosuke; Itoh, Hiroki; Fujioka, Takashi; Sato, Fuminori; Kawasaki, Kanako; Sato, Yukie; Sato, Yuhki; Ohno, Keiko; Mimata, Hiromitsu; Kishino, Satoshi

    2014-01-01

    Several studies have shown that renal failure decreases CYP3A activity and that uremic toxins may play a role via transcriptional or translational modifications of cytochrome P450 (P450) enzymes and direct inhibition of P450-mediated metabolism. In this study, we evaluated the relationship between CYP3A activity (using plasma concentration of 4β-hydroxycholesterol as a biomarker) and clinical characteristics including plasma concentrations of indoxyl sulfate (3-INDS) and indole-3-acetic acid (3-IAA) in stable kidney transplant recipients. Forty-five Japanese kidney transplant recipients who underwent transplantation more than 90 days prior to the study were included. Morning blood samples were collected and plasma concentrations of 4β-hydroxycholesterol, 3-INDS, and 3-IAA were measured. Plasma concentrations of 4β-hydroxycholesterol were 57.1 ± 11.2, 42.1 ± 11.8, and 34.5 ± 7.3 ng/ml in recipients with CYP3A5*1/*1 (n = 5), *1/*3 (n = 15), and *3/*3 (n = 25) genotypes, respectively, with significant differences between three genotypes. A significant correlation was observed between plasma concentrations of 4β-hydroxycholesterol and 3-INDS but not 3-IAA. Multiple regression analysis identified the number of CYP3A5*3 alleles in genotype, plasma concentration of 3-INDS, and body weight as independent variables associated with plasma concentration of 4β-hydroxycholesterol. In conclusion, these results suggest that CYP3A5 polymorphism and plasma concentration of 3-INDS may account for the interindividual variability of CYP3A activity, and that plasma concentration of 3-INDS may partially explain the gap in CYP3A activity that cannot be explained by genetic contribution in patients with renal failure.

  17. Doping concentration evaluation using plasma propagation models in plasma immersion ion implantation (PIII) system

    NASA Astrophysics Data System (ADS)

    Gupta, Dushyant; Prasad, B.; George, P. J.

    2004-01-01

    Plasma immersion ion implantation (PIII) is a high dose-rate implantation process technique in the area of semiconductor device fabrication used to fabricate various device structures like shallow junction, silicon on insulators and in the processing of flat panel display materials, trench doping, etc. The basic mechanism of ions source and their acceleration in PIII technique is different from that of the conventional ion-implantation. In this, the target is immersed in a plasma source and the implantation is done by accelerating the ions with a negative pulse bias voltage, applied to the target. The dynamics of ion transport and the implantation is different from line-of-sight implantation. In this paper, the doping of individual ions (Ar, He and N), in a collisionless PIII system is studied analytically when a negative pulse of 10 kV is applied to the target. The net ion doping concentration in one pulse duration has also been computed during the propagation of plasma sheaths.

  18. 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.

  19. 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.

  20. Pharmacokinetics and pharmacodynamics of oral mecamylamine - development of a nicotinic acetylcholine receptor antagonist cognitive challenge test using modelling and simulation.

    PubMed

    Alvarez-Jimenez, Ricardo; Baakman, Anne Catrien; Stevens, Jasper; Goulooze, Sebastiaan C; Hart, Ellen P; Rissmann, Robert; van Gerven, Joop Ma; Groeneveld, Geert Jan

    2017-02-01

    A pharmacologic challenge model with a nicotinic antagonist could be an important tool not only to understand the complex role of the nicotinic cholinergic system in cognition, but also to develop novel compounds acting on the nicotinic acetylcholine receptor. The objective was to develop a pharmacokinetic-pharmacodynamic (PKPD) model using nonlinear mixed effects (NLME) methods to quantitate the pharmacokinetics of three oral mecamylamine doses (10, 20 and 30 mg) and correlate the plasma concentrations to the pharmacodynamic effects on a cognitive and neurophysiologic battery of tests in healthy subjects. A one-compartment linear kinetic model best described the plasma concentrations of mecamylamine. Mecamylamine's estimated clearance was 0.28 ± 0.015 L min(-1). The peripheral volume of distribution (291 ± 5.15 L) was directly related to total body weight. Mecamylamine impaired the accuracy and increased the reaction time in tests evaluating short term working memory with a steep increase in the concentration-effect relationship at plasma concentrations below 100 μg L(-1). On the other hand, mecamylamine induced a decrease in performance of tests evaluating visual and fine motor coordination at higher plasma concentrations (EC50 97 μg L(-1)). Systolic and diastolic blood pressure decreased exponentially after a plasma mecamylamine concentration of 80 μg L(-1), a known effect previously poorly studied in healthy subjects. The developed mecamylamine PKPD model was used to quantify the effects of nicotinic blockade in a set of neurophysiological tests in humans with the goal to provide insight into the physiology and pharmacology of the nicotinic system in humans and the possibility to optimize future trials that use mecamylamine as a pharmacological challenge.

  1. Short-term treatment with transdermal nicotine affects the function of canine saphenous veins.

    PubMed

    Clouse, W D; Rud, K S; Hurt, R D; Miller, V M

    2000-01-01

    Experiments were designed to determine the effects of nicotine treatment on the functions of saphenous veins used for coronary artery bypass grafts in dogs. Dogs received either no treatment or transdermal nicotine for 5 weeks at doses of 11 mg, 22 mg or 44 mg/day. Saphenous veins were removed and suspended for the measurement of isometric force in organ chambers. Endothelium was removed mechanically from some rings. N(G)-mono-methyl-L-arginine (L-NMMA; 10(-4) M) was used to inhibit the production of nitric oxide. Contractions to alpha2-adrenergic stimulation were decreased in veins from dogs treated with a 22-mg/day dose of transdermal nicotine. In addition, endothelium-dependent relaxations to adenosine-diphosphate (10(-8)-10(-4) M) and the calcium ionophore A23,187 (10(-8)-10(-6) M) were decreased in veins from dogs with a 22-mg/day dose and increased in veins from dogs treated with a 44-mg/day dose. These relaxations were inhibited by L-NMMA. Plasma concentrations of oxidized products of nitric oxide were decreased only in dogs treated with 22 mg/day of nicotine. The relaxation of rings without endothelium (direct response on the smooth muscle) to nitric oxide were not altered by nicotine treatment. These results suggest that the short-term treatment of dogs with intermediate (22 mg/day) but not low (11 mg/day) or high (44 mg/day) doses of transdermal nicotine decreases the endothelial function of veins used for coronary artery bypass grafts. Therefore, changes in plasma products of nitric oxide and endothelium-dependent relaxations mediated by nitric oxide are related to the dose of nicotine treatment.

  2. 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.

  3. Atazanavir increases the plasma concentrations of 1200 mg raltegravir dose.

    PubMed

    Krishna, Rajesh; East, Lilly; Larson, Patrick; Valiathan, Chandni; Deschamps, Kathleen; Luk, Julie Ann; Bethel-Brown, Crystal; Manthos, Helen; Brejda, John; Gartner, Michael

    2016-12-01

    Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice-daily (b.i.d.). Raltegravir 1200 mg once-daily (q.d.) (investigational q.d. formulation of 2 × 600 mg tablets; q.d. RAL) was found to be generally well tolerated and non-inferior to the marketed 400 mg b.i.d. dose at 48 weeks in a phase 3 trial. Since raltegravir is eliminated mainly by metabolism via a uridine diphosphate glucuronosyltransferase (UGT) 1A1-mediated glucuronidation pathway, co-administration of UGT1A1 inhibitors may increase the plasma levels of q.d. RAL. To assess this potential, the drug interaction of 1200 mg raltegravir using atazanavir, a known UGT1A1 inhibitor, was studied. An open-label, randomized, 2-period, fixed-sequence phase 1 study was performed in adult healthy male and female (non-childbearing potential) subjects ≥ 19 and ≤ 55 years of age, with a body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m(2) . Subjects (n = 14) received a single oral dose of 1200 mg raltegravir in period 1. After a washout period of at least 7 days, the subjects received oral doses of 400 mg atazanavir q.d. for 9 consecutive days, with a single oral dose of 1200 mg raltegravir co-administered on day 7 of period 2. Serial blood samples were collected for 72 h following raltegravir dosing and analysed using a validated bioanalytical method to quantify raltegravir plasma concentrations. Co-administration with atazanavir yielded GMRs (90% CIs) for raltegravir AUC0-∞ , Cmax and C24 of 1.67 (1.34, 2.10), 1.16 (1.01, 1.33) and 1.26 (1.08, 1.46), respectively. There was no effect of raltegravir on serum total bilirubin. In contrast, atazanavir increased the mean bilirubin by up to 200%, an effect that was preserved in the atazanavir/raltegravir treatment group. Administration of single q.d. RAL alone and co-administered with multiple oral doses of atazanavir were generally well tolerated in healthy subjects. The results show that

  4. 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.

  5. A single-step extraction method for the determination of nicotine and cotinine in Jordanian smokers' blood and urine samples by RP-HPLC and GC-MS.

    PubMed

    Massadeh, Adnan M; Gharaibeh, Ahmad A; Omari, Khaled W

    2009-02-01

    A simple, rapid, reliable, and low cost one-step extraction method is developed and validated for the determination of nicotine and cotinine in human plasma and urine in smokers using reversed-phase high-performance liquid chromatography (RP-HPLC) and gas chromatography-mass spectrometry (GC-MS). The run times are 16 and 10 min for HPLC and GC-MS, respectively. The method is validated over a wide linear range of 1-5000 ng/mL with correlation coefficients being consistently greater than 0.9985. The criteria considered for validation are: limit of quantitation, linearity, accuracy, precision, recovery, specificity, and selectivity. This study is aimed to estimate the nicotine and cotinine in Jordanian smokers' blood and urine samples; to study the relationship between the concentration of nicotine in urine and plasma samples; and to investigate the effect of pH on the extraction of nicotine and cotinine in urine samples. In the presented study, one hundred blood and urine samples are collected from eighty smokers and twenty nonsmokers. Samples are taken from the same volunteer at the same time after each volunteer fills in a questionnaire. Results of nicotine concentrations in smokers' plasma are in the range of 181-3702 ng/mL with an average of 1263.1 ng/mL, whereas nicotine in urine samples is in the range of 1364-1972 ng/mL, with an average of 1618 ng/mL. Cotinine concentrations in smokers' plasma are in the range of 21-4420 ng/mL with an average of 379.4 ng/mL, whereas cotinine in urine is in the range of 6-3946 ng/mL with an average of 865 ng/mL. Statistical analysis indicates highly significant differences in nicotine and cotinine concentrations in smoker samples compared with nonsmoker samples (p<0.05).

  6. Differential effects of nicotine treatment and ethanol self-administration on CYP2A6, CYP2B6 and nicotine pharmacokinetics in African green monkeys.

    PubMed

    Ferguson, C S; Miksys, S; Palmour, R M; Tyndale, R F

    2012-12-01

    In primates, nicotine is metabolically inactivated in the liver by CYP2A6 and possibly CYP2B6. Changes in the levels of these two enzymes may affect nicotine pharmacokinetics and influence smoking behaviors. This study investigated the independent and combined effects of ethanol self-administration and nicotine treatment (0.5 mg/kg b.i.d. s.c.) on hepatic CYP2A6 and CYP2B6 levels (mRNA, protein, and enzymatic activity), in vitro nicotine metabolism, and in vivo nicotine pharmacokinetics in monkeys. CYP2A6 mRNA and protein levels and in vitro coumarin (selective CYP2A6 substrate) and nicotine metabolism were decreased by nicotine treatment but unaffected by ethanol. CYP2B6 protein levels and in vitro bupropion (selective CYP2B6 substrate) metabolism were increased by ethanol but unaffected by nicotine treatment; CYP2B6 mRNA levels were unaltered by either treatment. Combined ethanol and nicotine exposure decreased CYP2A6 mRNA and protein levels, as well as in vitro coumarin and nicotine metabolism, and increased CYP2B6 protein levels and in vitro bupropion metabolism, with no change in CYP2B6 mRNA levels. Chronic nicotine resulted in higher nicotine plasma levels achieved after nicotine administration, consistent with decreased CYP2A6. Ethanol alone, or combined with nicotine, resulted in lower nicotine plasma levels by a mechanism independent of the change in these enzymes. Thus, nicotine can decrease hepatic CYP2A6, reducing the metabolism of its substrates, including nicotine, whereas ethanol can increase hepatic CYP2B6, increasing the metabolism of CYP2B6 substrates. In vivo nicotine pharmacokinetics are differentially affected by ethanol and nicotine, but when both drugs are used in combination the effect more closely resembles ethanol alone.

  7. Decreased plasma brain-derived neurotrophic factor and vascular endothelial growth factor concentrations during military training.

    PubMed

    Suzuki, Go; Tokuno, Shinichi; Nibuya, Masashi; Ishida, Toru; Yamamoto, Tetsuo; Mukai, Yasuo; Mitani, Keiji; Tsumatori, Gentaro; Scott, Daniel; Shimizu, Kunio

    2014-01-01

    Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF) and serum BDNF have been proposed to be a state marker of depression and a biological indicator of loaded psychosocial stress. Stress evaluations of participants in military mission are critically important and appropriate objective biological parameters that evaluate stress are needed. In military circumstances, there are several problems to adopt plasma BDNF concentration as a stress biomarker. First, in addition to psychosocial stress, military missions inevitably involve physical exercise that increases plasma BDNF concentrations. Second, most participants in the mission do not have adequate quality or quantity of sleep, and sleep deprivation has also been reported to increase plasma BDNF concentration. We evaluated plasma BDNF concentrations in 52 participants on a 9-week military mission. The present study revealed that plasma BDNF concentration significantly decreased despite elevated serum enzymes that escaped from muscle and decreased quantity and quality of sleep, as detected by a wearable watch-type sensor. In addition, we observed a significant decrease in plasma vascular endothelial growth factor (VEGF) during the mission. VEGF is also neurotrophic and its expression in the brain has been reported to be up-regulated by antidepressive treatments and down-regulated by stress. This is the first report of decreased plasma VEGF concentrations by stress. We conclude that decreased plasma concentrations of neurotrophins can be candidates for mental stress indicators in actual stressful environments that include physical exercise and limited sleep.

  8. 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.

  9. Increase in plasma cortisol concentrations in ewes fed oestrogenic subterranean clover.

    PubMed

    Tang, B Y; Adams, N R; Sawyer, G J

    1979-11-01

    Pen-feeding oestrogenic clover to ewes increased their plasma cortisol concentration by the third day. This was not due to any change in the variation of cortisol concentration with time of day. Ovulation rate was not affected during the experiment as judged by the levels of plasma progesterone and laparoscopy. The plasma cortisol concentration of ewes also rose within three days of their being placed on oestrogenic clover pasture. During the next 21 days, their mean plasma cortisol was increased by 58 per cent. A previous history of clover disease did not affect this response.

  10. 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.

  11. Plasma nitrendipine concentrations in elderly hypertensive patients after single and multiple dosing.

    PubMed Central

    Crome, P; Baksi, A; MacMahon, D; Pandita-Gunawardena, N D; Edwards, J; Marley, J

    1988-01-01

    Twenty-three elderly hypertensive subjects received nitrendipine 10mg daily by mouth for 8 days. Plasma nitrendipine concentrations were measured after the first and last dose. There was no significant difference in plasma concentrations at any time point between the two days nor in derived pharmacokinetic measurements. Drug accumulation was not observed. PMID:3179170

  12. Nicotine potentiates proatherogenic effects of oxLDL by stimulating and upregulating macrophage CD36 signaling

    PubMed Central

    Chadipiralla, Kiranmai; Mendez, Armando J.; Jaimes, Edgar A.; Silverstein, Roy L.; Webster, Keith; Raij, Leopoldo

    2013-01-01

    Cigarette smoking is a major risk factor for atherosclerosis and cardiovascular disease. CD36 mediates oxidized LDL (oxLDL) uptake and contributes to macrophage foam cell formation. We investigated a role for the CD36 pathway in nicotine-induced activation of macrophages and foam cell formation in vitro and in vivo. Nicotine in the same plasma concentration range found in smokers increased the CD36+/CD14+ cell population in human peripheral blood mononuclear cells, increased CD36 expression of human THP1 macrophages, and increased macrophage production of reactive oxygen species, PKCδ phosphorylation, and peroxisome proliferator-activated receptor-γ (PPARγ) expression. Nicotine-induced CD36 expression was suppressed by antioxidants and by specific PKCδ and PPARγ inhibitors, implicating mechanistic roles for these intermediates. Nicotine synergized with oxLDL to increase macrophage expression of CD36 and cytokines TNF-α, monocyte chemoattractant protein-1, IL-6, and CXCL9, all of which were prevented by CD36 small interfering (si)RNA. Incubation with oxLDL (50 μg/ml) for 72 h resulted in lipid deposition in macrophages and foam cell formation. Preincubation with nicotine further increased oxLDL-induced lipid accumulation and foam cell formation, which was also prevented by CD36 siRNA. Treatment of apoE−/− mice with nicotine markedly exacerbated inflammatory monocyte levels and atherosclerotic plaque accumulation, effects that were not seen in CD36−/− apoE−/− mice. Our results show that physiological levels of nicotine increase CD36 expression in macrophages, a pathway that may account at least in part for the known proinflammatory and proatherogenic properties of nicotine. These results identify such enhanced CD36 expression as a novel nicotine-mediated pathway that may constitute an independent risk factor for atherosclerosis in smokers. The results also suggest that exacerbated atherogenesis by this pathway may be an adverse side effect of

  13. 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

  14. 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.

  15. [Transferrin concentration in seminal plasma in testicular varicocele with various sperm concentrations and various forms of azoospermia].

    PubMed

    Sigg, C; Brüngger, A; Rakosi, T

    1994-01-01

    Seminal plasma transferrin concentrations were measured in semen samples from 424 men attending a fertility unit. There was a clear positive correlation between seminal plasma transferrin concentration and sperm density: transferrin concentrations decrease with decreasing sperm density and are lowest in patients with azoospermia and those who have undergone vasectomy. The differences between the various groups in sperm density are highly significant, but individual data counts also vary widely. Furthermore, it was demonstrated that in polyzoospermia the seminal plasma transferrin concentration is increased, suggesting primary tubular hyperactivity. No correlations with other seminal parameters or hormonal values were found. Seminal plasma transferrin concentrations in normozoospermia and in varicocele testis or in cases with increased numbers of immature germ cells in the ejaculate were not significantly different. This may be interpreted as indicative of intact secretory activity of Sertoli cells in both varicocele and increased desquamation of immature germ cells. The absence of correlation with any of several important spermatological parameters and our inability to differentiate between azoospermia caused by obstruction and by tubular impairment indicate that seminal plasma transferrin is not a useful marker for Sertoli cell function or for seminiferous tubular dysfunction.

  16. Comparative changes in plasma protein concentration, hematocrit and plasma volume during exercise, bedrest and + Gz acceleration.

    NASA Technical Reports Server (NTRS)

    Van Beaumont, W.; Greenleaf, J. E.

    1972-01-01

    Discussion of experiments which indicate that under conditions of a constant red cell volume the proportional changes in hematocrit and plasma volume during exercise are never equal. On the basis of direct measurements and calculated changes of plasma volume it is concluded that during maximal exercise there is a small loss of protein from the plasma. It is clear that changes in content of blood constituents can only be evaluated correctly after determination of changes in plasma volume.

  17. [The influence of smoking on plasma non-enzymatic antioxidant concentrations in active smokers (preliminary report)].

    PubMed

    Szołtysek-Bołdys, Izabela; Sobczak, Andrzej; Król, Dorota

    2006-01-01

    Tobacco smoke contains many reactive oxygen species (ROS) that cause oxidative stress. Crucial role in defending the organism against ROS play vitamins E and A. The aim of the study was to investigate the influence of tobacco smoke on concentration of main ingredients of these vitamins alpha-tocopherol and gamma-tocopherol, as well as retinol. The study population consisted of 104 healthy males between the age of 34 and 45 years. Survey questionnaire and determination of plasma cotinine concentration were used to divide the group into smokers (62 males) and non-smokers (42 males). The arbitrary threshold value of plasma cotinine concentration was set to 15 ng/ml. High performance liquid chromatography (HPLC) was used to estimate the plasma concentration of alpha- and gamma-tocopherol, retinol and cotinine. Within the smoking part of the study population a significantly lower (by 12.5%) concentration of alpha-tocopherol, and non-significantly higher (by 15.7%) concentration of gamma-tocopherol was ascertained, when compared to the plasma concentration of those compounds in the non-smoking group. Practically no difference in concentration of retinol was found between the two studied groups. In order to determine the magnitude of interdependency between the extensiveness of exposure to tobacco smoke and the concentration of analyzed antioxidants, correlations between their plasma concentrations and plasma concentration of cotinine were investigated. A significant, moderate and negative correlation of alpha-tocopherol versus cotinin was determined, in the smoking group as well as in the entire study population (r = -0.291 and r = - 0,317, respectively). Other relationship: gamma-tocopherol versus cotinine and retinol versus cotinine did not show any correlation. The obtained results suggest that tobacco smoke weakens the organism's antioxidant barrier by decreasing the concentration of plasma alpha-tocopherol, while not influencing significantly the plasma

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

    PubMed Central

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

    2015-01-01

    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. PMID:26626731

  19. A simple, fast, and sensitive method for the measurement of serum nicotine, cotinine, and nornicotine by LC-MS/MS.

    PubMed

    Yuan, Chao; Kosewick, Justin; Wang, Sihe

    2013-08-01

    The measurement of nicotine and its metabolites has been used to monitor tobacco use. A high-sensitivity method (<1 ng/mL) is necessary for the measurement in serum or plasma to differentiate nonsmokers from passive smokers. Here, we report a novel LC-MS/MS method to quantify nicotine, cotinine, and nornicotine in serum with high sensitivity. Sample preparation involved only protein precipitation, followed by online turbulent flow extraction and analysis on a porous graphitic carbon column in alkaline conditions. The chromatography time was 4 min. No significant matrix effects or interference were observed. The lower limit of quantification was 0.36, 0.32, and 0.38 ng/mL for nicotine, cotinine, and nornicotine, respectively, while accuracy was 91.6-117.1%. No carryover was observed up to a concentration of 48 , 550, and 48 ng/mL for nicotine, cotinine, and nornicotine, respectively. Total CV was <6.5%. The measurement of nicotine and cotinine was compared with an independent LC-MS/MS method and concordant results were obtained. In conclusion, this new method was simple, fast, sensitive, and accurate. It was validated to measure nicotine, cotinine, and nornicotine in serum for monitoring tobacco use.

  20. Plasma prion protein concentration and progression of Alzheimer disease

    PubMed Central

    Schmidt, Christian; Becker, Harry; Peter, Christoph; Lange, Katharina; Friede, Tim; Zerr, Inga

    2014-01-01

    Background/Objective: Recently, PrPc has been linked to AD pathogenesis. Second, a relation of PrPc plasma levels with cognitive status and decline of healthy elderly subjects has been reported. Therefore, we hypothesized baseline plasma levels of PrPc to be associated with AD progression in cognitive and functional domains. Materials and Methods: AD patients (n = 84) were included into an observational study at time of diagnosis. Baseline plasma PrPc levels were determined. Decline was assessed annually (mean follow-up time 3 years) with the aid of different standardized tests (MMSE, iADL, bADL, GDS, UPDRSIII). Multiple regression analyses were used to uncover potential associations between decline and PrPc levels. Results: No association of PrPc and decline could be established. Presence of diabetes mellitus was linked to slower deterioration. Intake of neuroleptic drugs or memantine was associated with faster progression. Conclusion: Plasma PrPc at baseline could not be shown to be related to AD progression in this study. An interesting association of diabetes mellitus and decline warrants further investigation. PMID:24549099

  1. Plasma concentration of parasite DNA as a measure of disease severity in falciparum malaria.

    PubMed

    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

    2015-04-01

    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.

  2. 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

  3. Adolescent nicotine administration alters serotonin receptors and cell signaling mediated through adenylyl cyclase.

    PubMed

    Xu, Z; Seidler, F J; Cousins, M M; Slikker, W; Slotkin, T A

    2002-10-04

    Nicotine is a neuroteratogen that targets synaptic function during critical developmental stages and recent studies indicate that CNS vulnerability extends into adolescence, the age at which smoking typically commences. We administered nicotine to adolescent rats via continuous minipump infusions from PN30 to PN47.5, using 6 mg/kg/day, a dose rate that replicates the plasma nicotine levels found in smokers, and examined 5HT receptors and related cell signaling during nicotine administration (PN45) and in the post-treatment period (PN50, 60, 75). Adolescent nicotine decreased 5HT(2) receptor binding in brain regions containing 5HT projections (hippocampus and cerebral cortex), with selectivity for females in the cerebral cortex; regions containing 5HT cell bodies showed either an increase (midbrain in males) or no change (brainstem). In contrast, there were no significant changes in 5HT(1A) receptors; however, the ability of the receptors to signal through adenylyl cyclase (AC) showed a switch from stimulatory to inhibitory effects in females during the post-treatment period. There were also transient alterations in AC responses to beta-adrenergic receptor stimulation, as well as pronounced induction of the AC response to the non-receptor-mediated stimulant, forskolin. Our results indicate that adolescent nicotine exposure alters the concentrations and functions of postsynaptic 5HT receptors in a manner commensurate with impaired 5HT synaptic function. The direction of change, emergence of defects after the cessation of nicotine administration, and sex-preference for effects in females, all support a relationship of impaired 5HT function to the higher incidence of depression seen in adolescent smokers.

  4. Is plasma urotensin II concentration an indicator of myocardial damage in patients with acute coronary syndrome?

    PubMed Central

    Babińska, Magdalena; Holecki, Michał; Prochaczek, Fryderyk; Owczarek, Aleksander; Kokocińska, Danuta; Więcek, Andrzej

    2012-01-01

    Introduction Urotensin II (UII) is a vasoactive peptide secreted by endothelial cells. Increased plasma UII concentration was observed in patients with heart failure, liver cirrhosis, diabetic nephropathy and renal insufficiency. In patients with myocardial infarction both increased and decreased plasma UII concentrations were demonstrated. The aim of this study was to analyze whether plasma UII concentration reflects the severity of acute coronary syndrome (ACS). Material and methods One hundred and forty-nine consecutive patients with ACS, without age limit, were enrolled in the study. In all patients plasma concentration of creatinine, creatine kinase isoenzyme MB (CK-MB), troponin C, N-terminal prohormone of brain natriuretic peptide (NT-pro BNP), and UII were assessed, and echocardiography was performed in order to assess the degree of left ventricular hypertrophy, ejection fraction (EF) and mass (LVM). Results In patients with the highest risk (TIMI 5-7) plasma UII concentration was significantly lower than in those with low risk (TIMI 1-2): 2.61±1.47 ng/ml vs. 3.60±2.20 ng/ml. Significantly lower plasma UII concentration was found in patients with increased concentration of troponin C (2.60±1.52 ng/ml vs. 3.41±2.09 ng/ml). There was a significant negative correlation between plasma UII concentration and TIMI score or concentration of troponin C, but not CK-MB. Borderline correlation between plasma UII and ejection fraction (R = 0.157; p=0.063) or NT-proBNP (R = − 0.156; p=0.058) was found. Conclusions Decreased plasma urotensin II concentration in patients with ACS could be associated with more severe injury of myocardium. PMID:22851999

  5. Modulation of Intestinal Barrier and Bacterial Endotoxin Production Contributes to the Beneficial Effect of Nicotinic Acid on Alcohol-Induced Endotoxemia and Hepatic Inflammation in Rats

    PubMed Central

    Zhong, Wei; Li, Qiong; Zhang, Wenliang; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

    2015-01-01

    Alcohol consumption causes nicotinic acid deficiency. The present study was undertaken to determine whether dietary nicotinic acid supplementation provides beneficial effects on alcohol-induced endotoxin signaling and the possible mechanisms at the gut-liver axis. Male Sprague-Dawley rats were pair-fed the Lieber-DeCarli liquid diets containing ethanol or isocaloric maltose dextrin for eight weeks, with or without dietary supplementation with 750 mg/liter nicotinic acid. Chronic alcohol feeding elevated the plasma endotoxin level and activated hepatic endotoxin signaling cascade, which were attenuated by nicotinic acid supplementation. Alcohol consumption remarkably decreased the mRNA levels of claudin-1, claudin-5, and ZO-1 in the distal intestine, whereas nicotinic acid significantly up-regulated these genes. The concentrations of endotoxin, ethanol, and acetaldehyde in the intestinal contents were increased by alcohol exposure, and niacin supplementation reduced the intestinal endotoxin and acetaldehyde levels. Nicotinic acid supplementation upregulated the intestinal genes involved in aldehyde detoxification via transcriptional regulation. These results demonstrate that modulation of the intestinal barrier function and bacterial endotoxin production accounts for the inhibitory effects of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation. PMID:26501337

  6. Active-site concentrations of chemicals - are they a better predictor of effect than plasma/organ/tissue concentrations?

    PubMed

    Hammarlund-Udenaes, Margareta

    2010-03-01

    Active-site concentrations can be defined as the concentrations of unbound, pharmacologically active substances at the site of action. In contrast, the total concentrations of the drug in plasma/organ/tissue also include the protein- or tissue-bound molecules that are pharmacologically inactive. Plasma and whole tissue concentrations are used as predictors of effects and side effects because of their ease of sampling, while the concentrations of unbound drug in tissue are more difficult to measure. However, with the introduction of microdialysis and subsequently developed techniques, it has become possible to test the free drug hypothesis. The brain is an interesting organ in this regard because of the presence of the blood-brain barrier with its tight junctions and active efflux and influx transporters. We have proposed that research into brain drug delivery be divided into three main areas: the rate of delivery (PS, CL(in)), the extent of delivery (K(p,uu)) and the non-specific affinity of the drug to brain tissue, described by the volume of distribution of unbound drug in the brain (V(u,brain)). In this way, the concentration of unbound drug at the target site can be estimated from the total brain concentration and the plasma concentration after measuring the fraction of unbound drug. Results so far fully support the theory that active site concentrations are the best predictors when active transport is present. However, there is an urgent need to collect more relevant data for predicting active site concentrations in tissues with active transporters in their plasma membranes.

  7. Plasma soluble (pro)renin receptor is independent of plasma renin, prorenin, and aldosterone concentrations but is affected by ethnicity.

    PubMed

    Nguyen, Geneviève; Blanchard, Anne; Curis, Emmanuel; Bergerot, Damien; Chambon, Yann; Hirose, Takuo; Caumont-Prim, Aurore; Tabard, Sylvie Brailly; Baron, Stéphanie; Frank, Michael; Totsune, Kazuhito; Azizi, Michel

    2014-02-01

    A soluble (pro)renin receptor (sPRR) circulates in plasma and is able to bind renin and prorenin. It is not known whether plasma sPRR concentrations vary with the activity of the renin-angiotensin system. We measured plasma sPRR, renin, prorenin, and aldosterone concentrations in 121 white and 9 black healthy subjects, 40 patients with diabetes mellitus, 41 hypertensive patients with or without renin-angiotensin system blockers, 9 patients with primary aldosteronism, and 10 patients with Gitelman syndrome. Median physiological plasma sPRR concentration was 23.5 ng/mL (interquartile range, 20.9-26.5) under usual uncontrolled sodium diet. sPRR concentration in healthy subjects, unlike renin and prorenin, did not display circadian variation or dependence on age, sex, posture, or hormonal status. sPRR concentrations were ≈25% lower in black than in white subjects, whereas renin concentrations were ≈40% lower. Patients with diabetes mellitus (average renin-high prorenin levels) and with hypertension only (average renin-average prorenin levels) had sPRR concentrations similar to healthy subjects. Renin-angiotensin system blockade was associated with increase of sPRR concentration by ≈12%. sPRR in patients with primary aldosteronism (low renin-low prorenin) and Gitelman syndrome (high renin-high prorenin) were similar and ≈10% higher than in healthy subjects. There was no correlation between sPRR and renin or prorenin. In conclusion, our results show that plasma sPRR concentrations are dependent on ethnicity and independent of renin, prorenin, and aldosterone concentrations in healthy subjects and in patients with contrasted degrees of renin-angiotensin system activity.

  8. 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

  9. Decreased plasma isoleucine concentrations after upper gastrointestinal haemorrhage in humans.

    PubMed Central

    Dejong, C H; Meijerink, W J; van Berlo, C L; Deutz, N E; Soeters, P B

    1996-01-01

    BACKGROUND: A decrease in arterial isoleucine values after intragastric blood administration in pigs has been observed. This contrasted with increased values of most other amino acids, ammonia, and urea. After an isonitrogenous control meal in these pigs all amino acids including isoleucine increased, and urea increased to a lesser extent, suggesting a relation between the arterial isoleucine decrease and uraemia after gastrointestinal haemorrhage. METHODS: To extend these findings to humans, plasma amino acids were determined after gastrointestinal haemorrhage in patients with peptic ulcers (n = 9) or oesophageal varices induced by liver cirrhosis (n = 4) and compared with preoperative patients (n = 106). RESULTS: After gastrointestinal haemorrhage, isoleucine decreased in all patients by more than 60% and normalised within 48 hours. Most other amino acids increased and also normalised within 48 hours. Uraemia occurred in both groups, hyperammonaemia was seen in patients with liver cirrhosis. CONCLUSIONS: These results confirm previous findings in animals and healthy volunteers that plasma isoleucine decreases after simulated upper gastrointestinal haemorrhage. This supports the hypothesis that the absence of isoleucine in blood protein causes decreased plasma isoleucine values after gastrointestinal haemorrhage, and may be a contributory factor to uraemia and hyperammonaemia in patients with normal and impaired liver function, respectively. Intravenous isoleucine administration after gastrointestinal haemorrhage could be beneficial and will be the subject of further research. PMID:8881800

  10. 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.

  11. Clozapine and norclozapine concentrations in serum and plasma samples from schizophrenic patients.

    PubMed

    Hermida, Jesús; Paz, Eduardo; Tutor, J Carlos

    2008-02-01

    At present, the determination of steady-state trough serum/plasma concentrations of clozapine is considered a useful tool for the clinical management of schizophrenic patients treated with this drug. In a previously published study, it was indicated that only plasma should be used to avoid a significant underestimation of clozapine and norclozapine concentrations; however, a formal evaluation of this topic has still not been made, and a consensus on the use of plasma or serum for therapeutic clozapine monitoring may be desirable. Paired samples of serum and plasma (K3EDTA solution contained in Vacutainer tubes) were obtained from 40 schizophrenic patients, and clozapine and norclozapine concentrations were determined by high-performance liquid chromatography. For the parent drug and its metabolite, serum concentrations were higher than in plasma (approximately 7%), although the correction of plasma concentrations in function of hematocrit values reduced this difference to 3%. High correlation coefficients were found between the serum and uncorrected or corrected plasma clozapine concentrations (r = 0.996, P < 0.001), with clinically acceptable differences between the means and standard error of the estimate and consequently with transferability of the results. The clozapine and norclozapine concentrations in five lithium heparin-containing plasma samples (371.9 +/- 226.7 ng/mL and 217.9 +/- 113.1 ng/mL) were analogous to the corresponding hematocrit-corrected EDTA-containing plasma values (374.4 +/- 225.4 ng/mL and 223.5 +/- 115.2 ng/mL), with correlation coefficients of r > or = 0.998 (P < 0.001). Serum or plasma samples may be used for the therapeutic monitoring of clozapine, and no practical advantages have been found with regard to the stability of the drug or imprecision obtained by using either type of biological matrix.

  12. PLASMA ADIPONECTIN CONCENTRATIONS IN NON PREGNANT, NORMAL PREGNANCY AND OVERWEIGHT PREGNANT WOMEN

    PubMed Central

    Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Gomez, Ricardo; Edwin, Samuel; Mazor, Moshe; Espinoza, Jimmy; Yoon, Bo Hyun; Hassan, Sonia S.

    2008-01-01

    Aims Adiponectin is an adipokine that has anti-diabetic, anti-atherogenic, anti-inflammatory and angiogenic properties. This hormone has been implicated in both the physiological adaptation to normal pregnancy and obstetrical complications. The aims of this study were to determine normal maternal plasma concentrations of adiponectin throughout gestation and to explore the relationships between plasma adiponectin concentration, pregnancy, and maternal overweight. Study design A cross-sectional study was designed to include normal pregnant women (normal weight and overweight; 11–42 weeks of gestation), and non-pregnant women. Plasma adiponectin concentration was determined by immunoassay. Non-parametric statistics were used for analysis. Results (1) Adiponectin was detectable in the plasma of all patients; (2) there was no significant difference in the median adiponectin concentrations between pregnant and non-pregnant women; (3) plasma adiponectin concentrations were negatively correlated with gestational age only among normal weight pregnant women; and (4) overweight patients had significantly lower adiponectin concentrations than normal weight women. Conclusion Consistent with the increased insulin resistance and weight gain that occur in pregnancy, adiponectin concentrations were negatively correlated with gestational age. The results of this study and the nomogram herein presented can serve as the basis to explore the relationship between adiponectin and pregnancy complications and facilitate the clinical use of this important adipokine. Condensation Plasma adiponectin concentrations decrease with advancing gestational age only in nonobese women. PMID:17919116

  13. Nicotine replacement therapy

    MedlinePlus

    ... takes for the patch to work. The inhaler satisfies oral urges. Most of the nicotine vapor does ... spray provides a quick dose of nicotine to satisfy a craving you are unable to ignore. Levels ...

  14. A Phenomenological Model for Circadian and Sleep Allostatic Modulation of Plasma Cortisol Concentration

    DTIC Science & Technology

    2012-09-25

    RJ, Ortega-Soto H, Huerto-Delgadillo L, Camacho- Arroyo I, Roldán-Roldán G, Tamarkin L. The effect of total sleep deprivation on plasma melatonin and...A phenomenological model for circadian and sleep allostatic modulation of plasma cortisol concentration David Thorsley,1 Rachel Leproult,2,3 Karine...2012 Thorsley D, Leproult R, Spiegel K, Reifman J. A phenomenological model for circadian and sleep allostatic modulation of plasma cortisol

  15. Nicotine decreases the activity of glutamate transporter type 3.

    PubMed

    Yoon, Hea-Jo; Lim, Young-Jin; Zuo, Zhiyi; Hur, Wonseok; Do, Sang-Hwan

    2014-02-10

    Nicotine, the main ingredient of tobacco, elicits seizures in animal models and cigarette smoking is regarded as a behavioral risk factor associated with epilepsy or seizures. In the hippocampus, the origin of nicotine-induced seizures, most glutamate uptake could be performed primarily by excitatory amino acid transporter type 3 (EAAT3). An association between temporal lobe epilepsy and EAAT3 downregulation has been reported. Therefore, we hypothesized that nicotine may elicit seizures through the attenuation of EAAT3 activity. We investigated chronic nicotine exposure (72 h) cause reduction of the activity of EAAT3 in a Xenopus oocyte expression system using a two-electrode voltage clamp. The roles of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) were also determined. Nicotine (0.001-1 μM) resulted in a time- and dose-dependent decrease in EAAT3 activity with maximal inhibition at nicotine concentrations of 0.03 μM or higher and at an exposure time of 72 h. Vmax on the glutamate response was significantly reduced in the nicotine group (0.03 μM for 72 h), but the Km value of EAAT3 for glutamate was not altered. When nicotine-exposed oocytes (0.03 μM for 72 h) were pretreated with phorbol-12-myristate-13-acetate (PMA, a PKC activator), the nicotine-induced reduction in EAAT3 activity was abolished. PKC inhibitors (staurosporine, chelerythrine, and calphostin C) significantly reduced basal EAAT3 activity, but there were no significant differences among the PKC inhibitors, nicotine, and PKC inhibitors+nicotine groups. Similar response patterns were observed among PI3K inhibitors (wortmannin and LY294002), nicotine, and PI3K inhibitors+nicotine. In conclusion, this study suggests that nicotine decreases EAAT3 activity, and that this inhibition seems to be dependent on PKC and PI3K. Our results may provide an additional mechanism for nicotine-induced seizure.

  16. Effects of rice bran oil on plasma lipid concentrations, lipoprotein composition, and glucose dynamics in mares.

    PubMed

    Frank, N; Andrews, F M; Elliott, S B; Lew, J; Boston, R C

    2005-11-01

    Plasma lipid concentrations, lipoprotein composition, and glucose dynamics were measured and compared between mares fed diets containing added water, corn oil (CO), refined rice bran oil (RR), or crude rice bran oil (CR) to test the hypothesis that rice bran oil lowers plasma lipid concentrations, alters lipoprotein composition, and improves insulin sensitivity in mares. Eight healthy adult mares received a basal diet fed at 1.5 times the DE requirement for maintenance and each of the four treatments according to a repeated 4 x 4 Latin square design consisting of four 5-wk feeding periods. Blood samples were collected for lipid analysis after mares were deprived of feed overnight at 0 and 5 wk. Glucose dynamics were assessed at 0 and 4 wk in fed mares by combined intravenous glucose-insulin tolerance tests. Plasma glucose and insulin concentrations were measured, and estimated values of insulin sensitivity (SI), glucose effectiveness, and net insulin response were obtained using the minimal model. Mean BW increased (P = 0.014) by 29 kg (range = 10 to 50 kg) over 5 wk. Mean plasma concentrations of NEFA, triglyceride (TG), and very low-density lipoprotein (VLDL) decreased (P < 0.001) by 55, 30, and 39%, respectively, and plasma high-density lipoprotein and total cholesterol (TC) concentrations increased (P < 0.001) by 15 and 12%, respectively, over 5 wk. Changes in plasma NEFA (r = 0.58; P < 0.001) and TC (r = 0.44; P = 0.013) concentrations were positively correlated with weight gain over 5 wk. Lipid components of VLDL decreased (P < 0.001) in abundance over 5 wk, whereas the relative protein content of VLDL increased by 39% (P < 0.001). Addition of oil to the basal diet instead of water lowered plasma NEFA and TG concentrations further (P = 0.002 and 0.020, respectively) and increased plasma TC concentrations by a greater magnitude (P = 0.072). However, only plasma TG concentrations and VLDL free cholesterol content were affected (P = 0.024 and 0.009, respectively

  17. The QT interval: a predictor of the plasma and myocardial concentrations of amiodarone.

    PubMed Central

    Debbas, N M; du Cailar, C; Bexton, R S; Demaille, J G; Camm, A J; Puech, P

    1984-01-01

    A study was performed to assess whether plasma and myocardial concentrations of amiodarone correlated with changes on the surface electrocardiogram. Nine patients--seven with angina and two with paroxysmal ventricular tachycardia--were treated with oral amiodarone (200-400 mg daily) for at least nine months before undergoing cardiac surgery. QT intervals were measured from lead II of the surface electrocardiograms recorded before amiodarone treatment and immediately before surgery. Patients with prominent U waves after taking amiodarone were excluded from the study. Plasma and myocardial samples were collected at the beginning of the surgical procedure for estimating plasma and myocardial concentrations using the high performance liquid chromatographic technique. Amiodarone caused a significant lengthening of the QTc interval. There was a good correlation between plasma and myocardial concentrations, and both correlated well with the percentage increase in the QTc interval. Although there was a strong correlation between the dosage given (mg/kg/day) and both plasma and myocardial concentrations, the correlation with the percentage increase in the QTc interval was weaker but still highly significant. Despite previous reports to the contrary, the findings indicate that the plasma concentration of amiodarone does correlate well with the myocardial concentration. The degree of lengthening of the QTc interval may be used clinically to estimate the myocardial concentration of amiodarone. PMID:6696809

  18. High plasma uric acid concentration: causes and consequences

    PubMed Central

    2012-01-01

    High plasma uric acid (UA) is a precipitating factor for gout and renal calculi as well as a strong risk factor for Metabolic Syndrome and cardiovascular disease. The main causes for higher plasma UA are either lower excretion, higher synthesis or both. Higher waist circumference and the BMI are associated with higher insulin resistance and leptin production, and both reduce uric acid excretion. The synthesis of fatty acids (tryglicerides) in the liver is associated with the de novo synthesis of purine, accelerating UA production. The role played by diet on hyperuricemia has not yet been fully clarified, but high intake of fructose-rich industrialized food and high alcohol intake (particularly beer) seem to influence uricemia. It is not known whether UA would be a causal factor or an antioxidant protective response. Most authors do not consider the UA as a risk factor, but presenting antioxidant function. UA contributes to > 50% of the antioxidant capacity of the blood. There is still no consensus if UA is a protective or a risk factor, however, it seems that acute elevation is a protective factor, whereas chronic elevation a risk for disease. PMID:22475652

  19. Plasma IL-5 concentration and subclinical carotid atherosclerosis

    PubMed Central

    Silveira, Angela; McLeod, Olga; Strawbridge, Rona J.; Gertow, Karl; Sennblad, Bengt; Baldassarre, Damiano; Veglia, Fabrizio; Deleskog, Anna; Persson, Jonas; Leander, Karin; Gigante, Bruna; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Gustafsson, Sven; Söderberg, Stefan; Öhrvik, John; Humphries, Steve E.; Tremoli, Elena; de Faire, Ulf; Hamsten, Anders

    2015-01-01

    Objective Genetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis, as determined by measures of baseline severity and change over time of carotid intima-media thickness (cIMT). Methods We used biobank and databases of IMPROVE, a large European prospective cohort study of high-risk individuals (n = 3534) free of clinically overt cardiovascular disease at enrollment, in whom composite and segment-specific measures of cIMT were recorded at baseline and after 15 and 30 months. IL-5 was measured with an immunoassay in plasma samples taken at baseline. Results IL-5 levels were lower in women than in men, lower in the South than in North of Europe, and showed positive correlations with most established risk factors. IL-5 showed significant inverse relationships with cIMT change over time in the common carotid segment in women, but no significant relationships to baseline cIMT in either men or women. Conclusions Our results suggest that IL-5 may be part of protective mechanisms operating in early atherosclerosis, at least in women. However, the relationships are weak and whereas IL-5 has been proposed as a potential molecular target to treat allergies, it is difficult to envisage such a scenario in coronary artery disease. PMID:25587992

  20. Detoxification and elimination of nicotine by nectar-feeding birds.

    PubMed

    Lerch-Henning, S; Du Rand, E E; Nicolson, S W

    2017-02-01

    Many dilute nectars consumed by bird pollinators contain secondary metabolites, potentially toxic chemicals produced by plants as defences against herbivores. Consequently, nectar-feeding birds are challenged not only by frequent water excess, but also by the toxin content of their diet. High water turnover, however, could be advantageous to nectar consumers by enabling them to excrete secondary metabolites or their transformation products more easily. We investigated how the alkaloid nicotine, naturally present in nectar of Nicotiana species, influences osmoregulation in white-bellied sunbirds Cinnyris talatala and Cape white-eyes Zosterops virens. We also examined the metabolic fate of nicotine in these two species to shed more light on the post-ingestive mechanisms that allow nectar-feeding birds to tolerate nectar nicotine. A high concentration of nicotine (50 µM) decreased cloacal fluid output and increased its osmolality in both species, due to reduced food intake that led to dehydration. White-eyes excreted a higher proportion of the ingested nicotine-containing diet than sunbirds. However, sugar concentration did not affect nicotine detoxification and elimination. Both species metabolised nicotine, excreting very little unchanged nicotine. Cape white-eyes mainly metabolised nicotine through the cotinine metabolic pathway, with norcotinine being the most abundant metabolite in the excreta, while white-bellied sunbirds excreted mainly nornicotine. Both species also utilized phase II conjugation reactions to detoxify nicotine, with Cape white-eyes depending more on the mercapturic acid pathway to detoxify nicotine than white-bellied sunbirds. We found that sunbirds and white-eyes, despite having a similar nicotine tolerance, responded differently and used different nicotine-derived metabolites to excrete nicotine.

  1. Seasonal changes in concentrations of plasma hormones in the male ring dove (Streptopelia risoria).

    PubMed

    Lea, R W; Sharp, P J; Klandorf, H; Harvey, S; Dunn, I C; Vowles, D M

    1986-03-01

    Seasonal changes in concentrations of plasma LH, prolactin, thyroxine (T4), GH and corticosterone were measured in captive male ring doves exposed to natural lighting at latitude 56 degrees N. Plasma LH levels decreased steeply in autumn when the daylength fell below about 12.5 h but increased in November as the birds became short-day refractory. In comparison with plasma LH concentrations in a group of short-day refractory birds exposed to 6 h light/day from the winter solstice, plasma LH levels in birds exposed to natural lighting increased further in spring after the natural daylength reached about 12.5 h. There were no seasonal changes in plasma prolactin concentrations and plasma T4 concentrations were at their highest during December, January and February, the coldest months of the year. The seasonal fall in plasma LH levels in September was associated with a transitory increase in plasma T4, a transitory decrease in plasma corticosterone and a sustained increase in plasma GH. It is suggested that in the ring dove, short-day refractoriness develops rapidly in November to allow the bird to breed when the opportunity arises, during the winter and early spring. The annual breeding cycle is synchronized by a short-day induced regression of the reproductive system in the autumn, the primary function of which may be to enable the birds to meet the energy requirements for the annual moult. The changes in plasma T4, corticosterone and especially of GH at this time of year are probably concerned with the control of moult or the associated changes in energy requirements.

  2. 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.

  3. 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

  4. Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs.

    PubMed

    Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

    2014-01-01

    In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, p<0.001), TGF-β1 (r=0.85, p<0.001), VEGF (r=0.46, p<0.01) and PDGF-bb (r=0.9, p<0.001). Our results demonstrate that selected growth factors are present in the platelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors.

  5. Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs

    PubMed Central

    Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

    2014-01-01

    In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, p<0.001), TGF-β1 (r=0.85, p<0.001), VEGF (r=0.46, p<0.01) and PDGF-bb (r=0.9, p<0.001). Our results demonstrate that selected growth factors are present in the platelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors. PMID:26504722

  6. 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

  7. Coronary Artery Vitamin D Receptor Expression and Plasma Concentrations of Vitamin D: Their Association with Atherosclerosis

    PubMed Central

    Schnatz, Peter F.; Nudy, Matthew; O’Sullivan, David M.; Jiang, Xuezhi; Cline, J. Mark; Kaplan, Jay R.; Clarkson, Thomas B.; Appt, Susan E.

    2012-01-01

    Objective To analyze coronary artery vitamin D receptor (VDR) expression, plasma concentration of vitamin D3 [25OHD3], and their relationship with coronary artery atherosclerosis. Methods Premenopausal cynomolgus monkeys were fed atherogenic diets containing the equivalent of 1,000 IU/day of 25OHD3. Protein was derived from casein-lactalbumin (C/L, n=10), soy protein isolate (soy, n=10), or a combination (n=19). After 32 months consuming the diets, each monkey underwent surgical menopause. After 32 post-menopausal months, coronary atherosclerosis was measured in the left circumflex artery (LCX) and left anterior descending artery (LAD). VDR expression was determined for the LAD and 25OHD3 concentrations were assessed. Results Both the cross-sectional area of atherosclerotic plaques (mm2) and plaque thickness (mm) in the LCX as well as the LAD were analyzed in these monkeys. Those with higher plasma 25OHD3 concentrations and higher VDR were compared to those with higher plasma 25OHD3 concentrations and lower VDR. Significantly smaller plaque sizes were noted with higher plasma 25OHD3 concentrations and higher VDR. For the LCX, there was also a significantly lower plaque size (both plaque thickness and cross sectional area) in those with higher VDR and lower 25OHD3 concentrations versus those with lower quantities of VDR and higher plasma concentrations of 25OHD3, p=0.040 and p=0.009, respectively. Conclusions Cynomolgus monkeys with higher quantities of VDR have significantly less atherosclerosis than those with lower quantities of VDR and higher plasma 25OHD3 concentrations. If these findings translate to human beings, it might explain why some individuals with higher plasma concentrations of 25OHD3 have more coronary artery atherosclerosis. PMID:22617336

  8. Partitioning of Homologous Nicotinic Acid Ester Prodrugs (Nicotinates) into Dipalmitoylphosphatidylcholine (DPPC) Membrane Bilayers

    PubMed Central

    Ojogun, Vivian; Vyas, Sandhya M.; Lehmler, Hans-Joachim; Knutson, Barbara L

    2010-01-01

    The partitioning behavior of a series of perhydrocarbon nicotinic acid esters (nicotinates) between aqueous solution and dipalmitoylphosphatidylcholine (DPPC) membrane bilayers is investigated as a function of increasing alkyl chain length. The hydrocarbon nicotinates represent putative prodrugs, derivatives of the polar drug nicotinic acid, whose functionalization provides the hydrophobic character necessary for pulmonary delivery in a hydrophobic, fluorocarbon solvent, such as perfluorooctyl bromide. Independent techniques of differential scanning calorimetry and 1,6-diphenyl-1,3,5 hexatriene (DPH) fluorescence anisotropy measurements are used to analyze the thermotropic phase behavior and lipid bilayer fluidity as a function of nicotinate concentration. At increasing concentrations of nicotinates over the DPPC mole fraction range examined (XDPPC = 0.6 – 1.0), all the nicotinates (ethyl (C2H5); butyl (C4H9); hexyl (C6H13); and octyl (C8H17)) partition into the lipid bilayer at sufficient levels to eliminate the pretransition, and decrease and broaden the gel to fluid phase transition temperature. The concentration at which these effects occur is chain length-dependent; the shortest chain nicotinate, C2H5, elicits the least dramatic response. Similarly, the DPH anisotropy results demonstrate an alteration of the bilayer organization in the liposomes as a consequence of the chain length-dependent partitioning of the nicotinates into DPPC bilayers. The membrane partition coefficients (logarithm values), determined from the depressed bilayer phase transition temperatures, increase from 2.18 for C2H5 to 5.25 for C8H17. The DPPC membrane/water partitioning of the perhydrocarbon nicotinate series correlates with trends in the octanol/water partitioning of these solutes, suggesting that their incorporation into the bilayer is driven by increasing hydrophobicity. PMID:20227859

  9. 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

  10. Circadian Rhythm of Plasma Aldosterone Concentration in Patients with Primary Aldosteronism

    PubMed Central

    Kem, David C.; Weinberger, Myron H.; Gomez-Sanchez, Celso; Kramer, Norman J.; Lerman, Robert; Furuyama, Shunsuke; Nugent, Charles A.

    1973-01-01

    Plasma aldosterone, cortisol, and renin activity were measured in nine recumbent patients with hyperaldosteronism, including seven with adenomas, one with idiopathic hyperplasia, and one with glucocorticoid suppressible hyperplasia. All had peak values of plasma aldosterone concentration from 3 a.m. to noon and lowest values at 6 p.m. or midnight. This rhythm was similar to the circadian pattern of plasma cortisol in the same patients. When these data were normalized to eliminate the wide variation in ranges of plasma aldosterone and cortisol between individuals, there was an excellent correlation (r = + 0.87, P < 0.005) between the two hormones. In contrast, plasma aldosterone concentrations did not correlate with plasma renin activity before or after normalization of data. Short term suppression of ACTH by administration of dexamethasone eliminated the circadian variation of plasma aldosterone in both patients with hyperplasia and in four of five patients with adenomas, while it markedly altered the rhythm in the fifth. Similar doses of dexamethasone were administered to four normal subjects and did not flatten the circadian rhythm of plasma aldosterone. These data suggest that patients with primary aldosteronism have a circadian rhythm of plasma aldosterone mediated by changes in ACTH. PMID:4353776

  11. Thermodynamic analysis of the plasma production of ferroniobium from a loparite concentrate

    NASA Astrophysics Data System (ADS)

    Nikolaev, A. A.; Kirpichev, D. E.; Nikolaev, A. V.; Tsvetkov, Yu. V.

    2013-11-01

    The possibility of pyrometallurgical processing of a loparite concentrate at a temperature of 2000-4000 K and a pressure of 0.1 MPa is thermodynamically studied using the TERRA software package. It is found that the niobium concentration in the concentrate almost doubles during plasma heating as a result of thermal decomposition and the precipitation of rare-earth metals into a gas phase. Crude niobium can be extracted from the thermally decomposed concentrate by carbothermic or aluminothermic reduction. After plasma-arc vacuum refining, crude niobium can be used for making commercial ferroniobium. The calculated energy consumed for the plasma production of ferroniobium from the loparite concentrate by carbothermic or aluminothermic reduction under adiabatic conditions is 46.6 or 79.0 GJ/(t ferroniobium), respectively. The energy consumption can even be increased severalfold, and the implementation of the process remains economically efficient at the existing market price of ferroniobium.

  12. 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.

  13. Plasma pyrimethamine concentrations during long-term treatment for cerebral toxoplasmosis in patients with AIDS.

    PubMed Central

    Klinker, H; Langmann, P; Richter, E

    1996-01-01

    Steady-state plasma pyrimethamine levels were measured by gas chromatography. The specimens were taken from 74 adults with advanced human immunodeficiency virus infection receiving pyrimethamine-containing drugs for prophylaxis or curative therapy of reactivated cerebral toxoplasmosis. During an overall treatment period of 1,049 months, 1,012 plasma samples were investigated. Pyrimethamine concentrations could be evaluated in 904 plasma samples. The weekly dosage of pyrimethamine ranged from 25 to 1,400 mg; one patient with severe diarrhea received 2,100 mg/week. Steady-state plasma pyrimethamine concentrations were achieved after 12 to 20 days. Pyrimethamine concentrations evidently increased with the weekly dosage given. Mean concentrations were 253 +/- 151 ng/ml with 50 mg of pyrimethamine per week, 471 +/- 214 ng/ml with 100 mg of pyrimethamine per week, 1,893 +/- 1,182 ng/ml with 350 mg of pyrimethamine per week and 3,369 +/- 1,726 ng/ml with 1,050 mg of pyrimethamine per week. A widespread interpatient range was found for every dosage. With the simultaneous use of enzyme-inducing comedication, the plasma pyrimethamine levels decreased in several patients. Mild chronic liver disease did not influence plasma pyrimethamine concentrations. To avoid ineffective therapy or severe side effects, monitoring of pyrimethamine could be useful in patients receiving enzyme-inducing comedications and in patients with severe diarrhea or poor compliance. PMID:8807051

  14. Natriuretic peptides in cetaceans: identification, molecular characterization and changes in plasma concentration after landing.

    PubMed

    Naka, Tadaomi; Katsumata, Etsuko; Sasaki, Kazuki; Minamino, Naoto; Yoshioka, Motoi; Takei, Yoshio

    2007-06-01

    Dolphins are aquatic animals free from gravity, and this may have imposed significant changes in their cardiovascular status and its hormonal regulation compared with terrestrial animals. This study molecularly characterized two major cardiovascular hormones, atrial and B-type natriuretic peptides (ANP and BNP) and measured their changes in dolphin plasma concentrations in relation to the cardiovascular status of the animal. We initially identified ANP and BNP in three species of dolphins (Lagenorhynchus obliquidens, Phocoenoides dalli and Tursiops truncatus). ANP precursors are highly conserved in most mammals, but dolphin BNP precursors were more variable. In molecular phylogenetic analyses, dolphin ANP and BNP precursors grouped with those of artiodactyls, particularly to the camel peptides. The chromatographic characterization of tissue and plasma molecular forms using specific radioimmunoassays showed that the predominant ANP and BNP in the atrium are prohormone and mature peptide, respectively, whereas mature ANP and BNP are circulating in the dolphin blood. A mass spectrometric analysis showed that atrial BNP consists of 26 amino acids, rather than the 32-amino-acid form detected in other mammals. Finally, changes in plasma ANP and BNP concentrations were examined in captive bottlenose dolphins (Tursiops truncatus) after their pool was drained. Plasma ANP and BNP concentrations did not change after landing, unlike terrestrial mammals. Plasma angiotensin II and cortisol concentrations did not change either, showing minor stress after landing. Since landed dolphins show a different cardiovascular status on land than terrestrial mammals, plasma ANP and BNP concentrations seem to reflect the cardiovascular status characteristic of dolphins.

  15. Plasma concentrations of testosterone and nandrolone in racing and nonracing intact male horses.

    PubMed

    Soma, L R; Uboh, C E; You, Y; Guan, F; McDonnell, S

    2012-04-01

    Pennsylvania (PA) State Racing Commissions regulate the endogenous androgenic steroid, testosterone (TES), in racing intact males (RIM) by quantification of TES in post-race samples. Post-race plasma samples (2209) collected between March 2008 and November 2010 were analyzed for TES, nandrolone (NAN), and other anabolic steroids (ABS). Of the 2209 plasma samples, 2098 had quantifiable TES ≥ 25 pg/mL. Plasma (mean ± SD) concentrations of TES and NAN in RIM were 329.2 ± 266.4 and 96.0 ± 67.8 pg/mL, respectively. Only 64.6% of RIM had quantifiable concentration of NAN, and there was no relationship between TES and NAN. Plasma TES concentrations were significantly (P < 0.0001) higher during the months of April, May, June, July, and August. A significantly higher (P < 0.006) plasma TES was observed in Thoroughbred (TB) (347.6 ± 288.5 pg/mL) vs. that in Standardbred (STB) (315.4 ± 247.7 pg/mL). Plasma concentrations of TES from breeding stallions (BS) were 601.6 ± 356.5 pg/mL. Statistically significant (P < 0.0001) lower plasma concentrations of the two steroids were observed in RIM horses. Based on quantile distribution of TES in the RIM and BS populations, 99.5% were at or below 1546.1 and 1778.0 pg/mL, respectively. Based on this population of RIM, the suggested upper threshold plasma concentration of endogenous TES in horses competing in PA should remain at 2000 pg/mL.

  16. 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

  17. 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.

  18. 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.

  19. Hormones, Nicotine and Cocaine: Clinical Studies

    PubMed Central

    Mello, Nancy K.

    2009-01-01

    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 (two 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 implications for treatment of these addictive disorders is discussed. PMID:19835877

  20. Effects of feed on plasma leptin and ghrelin concentrations in crib-biting horses.

    PubMed

    Hemmann, Karin E; Koho, Ninna M; Vainio, Outi M; Raekallio, Marja R

    2013-10-01

    The reason why some horses begin an oral stereotypy such as crib-biting is not known. The aim of this study was to measure ghrelin and leptin concentrations in plasma concentrations to determine whether there is a link to crib-biting in horses. Plasma samples (n=3) were collected for plasma leptin and ghrelin assay before and during the morning first feeding in the usual environments of 15 horses with stereotypic crib-biting and 15 matched controls. The crib-biting intensity was scored in three 5-min phases, and a subgroup of verified crib-biters (n=8) was defined as horses that were seen to crib-bite during this study. Plasma leptin concentration (mean and 95% confidence interval [CI]) was lower in horses observed to crib-bite before and after feeding of concentrates (1.2, CI 0.8-1.7 ng/mL and 1.0, CI 0.6-1.7) than in non-crib-biters (2.3, CI 1.6-3.4 and 2.3, CI 1.6-3.4 ng/mL, respectively) and correlated negatively with crib-biting intensity. Crib-biting intensity was significantly higher shortly after feeding than before or 30 min later. Plasma ghrelin concentration was significantly higher before feeding concentrate than before hay feeding or after the concentrate, but did not differ between groups. There was a significant negative correlation between body composition score and plasma ghrelin concentration. These findings suggest that leptin concentrations may be associated with crib-biting behaviour in horses.

  1. 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.

  2. 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

  3. Insulin resistance is not related to plasma homocysteine concentration in healthy premenapausal women.

    PubMed

    Tanrikulu-Kiliç, F; Bekpinar, S; Unlüçerçi, Y; Orhan, Y

    2006-01-01

    This study was performed to test whether plasma homocysteine concentrations are related to insulin resistance in healthy premenopausal women. For this purpose, the relationship between insulin resistance (as assessed by HOMA index) and fasting plasma homocysteine level was determined in 83 healthy volunteers. The results indicated that homocysteine concentrations did not vary as a function of HOMA index (r = -0.147). Plasma homocysteine concentrations also did not vary as a function of other parameters of insulin resistance such as HDL-cholesterol and triglycerides, which they correlated inversely with body mass index (BMI). Furthermore, when individuals were classified according to quartiles of insulin resistance (HOMA index), plasma homocysteine concentrations from the lowest to the highest quartiles were not significantly different. On the other hand, the HOMA index correlated significantly with triglyceride concentrations (r = 0.377, p< 0.001), HDL-cholesterol (r = -0.310, p< 0.01) and BMI (r = 0.468, p< 0.001). These results suggest that plasma homocysteine concentrations are not related to insulin resistance and/or metabolic abnormalities associated with it in premenopausal women.

  4. Amino acid concentrations in plasma and erythrocytes in aregeneratory and haemolytic anaemias.

    PubMed

    Seip, M; Lindemann, R; Gjesdahl, P; Gjessing, L R

    1975-10-01

    The concentrations of unbound amino acids in erythrocytes and in plasma from 7 normal individuals, 11 patients with various types of aregeneratory anaemia, and 4 patients with hereditary haemolytic anaemias were determined on a Technicon Amino Acid Analyzer (Perry et al 1970). Most amino acids were normally found in higher concentrations in plasma than intracellularly. Cystine, methionine and trypotophan were almost exclusively present in plasma. Aspartic acid, however, was mainly found in erythrocytes, and glutathione only in erythrocytes. Glutamic acid and ornithine were more concentrated in the cells, while glycine and asparagine showed approximately the same concentrations in erythrocytes as in plasma. In the patients, plasma amino acids showed little deviations from normal, but in the erythrocytes there were striking changes. Erythrocyte glutamic acid concentrations were moderately to markedly elevated in all patients studied, and glycine concentrations in 13 out of 15 patients. In addition, the following amino acids were increased intracellularly in more than one patient: glutamine (8 patients), serine (7), asparagine (5), threonine (4), taurine (3), alanine (2), valine (2), ornithine (2), lysine (2), citrulline (2). Aspartic acid was decreased in erythrocytes from 4 patients with aregeneratory and 1 with haemolytic anaemia.

  5. 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.

  6. High-Performance Liquid-Chromatographic Analysis of Plasma Iohexol Concentrations.

    PubMed

    Schwertner, Harvey A; Weld, Kyle J

    2015-10-01

    In this study, a high-performance liquid-chromatographic (HPLC) method using photodiode array detection and isocratic conditions was developed for the analysis of plasma iohexol concentrations. Plasma proteins were precipitated with 1:1 volume of plasma and acetonitrile-ethanol-water (60:38.4:1.6, v/v/v). Iohexol concentrations in the supernatant phase were analyzed on a Waters Symmetry C-18 reversed-phase column under isocratic conditions at 245 nm. The extraction recoveries of iohexol from plasma were >95% and the plasma iohexol calibration curves were linear (R(2) ≥ 0.9998) from 10 to 1500 µg/mL. The within-day coefficients of variation (CVs) at plasma iohexol concentrations of 100, 375, 750 and 1500 µg/mL were 5.1, 3.5, 1.3 and 2.5%, respectively; the between-day CVs at 100, 375, 750 and 1500 µg/mL were 8.6, 4.2, 4.0 and 3.7%, respectively. The day-to-day accuracies of the method at plasma iohexol concentrations of 50, 100, 375, 750 and 1500 µg/mL were 89.0, 99.4, 108.4, 103.6 and 101.2%, respectively (n = 5). The lower limit of plasma iohexol quantitation was 10 µg/mL and no interferences >9 µg/mL were found in over 75 pre-dose porcine plasma samples. The applicability of the method was demonstrated by determining the glomerular filtration rates of iohexol in the porcine (Sus scrofa) model.

  7. Zinc and magnesium concentrations in plasma and red blood cells in patients on digitalis medication

    SciTech Connect

    Zumkley, H.; Bertram, H.P.; Vetter, H.; Zidek, W.; Wessels, F.

    1981-06-01

    Determinations of zinc, sodium, potassium and magnesium in plasma and red blood cells (RBC) were performed in 31 controls and 63 patients treated with digitalis. In digitalized patients Na and Zn concentrations in RBC were significantly increased, whereas the intraerythrocyte Mg concentration was only slightly elevated. Plasma concentrations of all investigated electrolytes as well as of Zn remained within the normal range. There was a close relationship between the increase of Na and Zn content in RBC indicating alterations in transmembrane transport mechanisms induced by digitalis therapy.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Influence of androgens on plasma concentrations of growth hormone in growing castrated and intact chickens.

    PubMed

    Fennell, M J; Johnson, A L; Scanes, C G

    1990-03-01

    Castrated chicks implanted with testosterone or 5 alpha-dihydrotestosterone (5 alpha-DHT) had circulating concentrations of the respective androgen similar to or less than in sham-operated chicks. In castrated chicks, 5 alpha-DHT or 19-nortestosterone (19-NorT) inhibited growth as indicated by body weight, while testosterone and 5 beta-dihydrotestosterone (5 beta-DHT) were without effect. In intact male or female chicks, growth was inhibited by either testosterone or 5 alpha-DHT but was unaffected by 5 beta-DHT or estradiol-17 beta. Plasma concentrations of luteinizing hormone (LH) were reduced in castrated chicks receiving implants of either testosterone or 19-NorT. Only the highest dose of 5 alpha-DHT depressed the circulating concentration of LH; lower doses of 5 alpha-DHT being without effect. During the first 6 weeks of growth, plasma concentrations of GH were unaffected by most steroid treatments (5 alpha-DHT, 5 beta-DHT, low doses of testosterone, estradiol-17 beta) in castrated or in intact male or in female chicks. Similarly, 19-NorT did not affect plasma concentrations of GH in castrated chicks. The high dose of testosterone, however, depressed plasma concentrations of GH in castrated chicks between 2 and 6 weeks of age. Between 8 and 12 weeks of age, all steroids tested, except 5 alpha-DHT, were without effect on plasma concentrations of GH. Plasma concentrations of GH were increased in 5 alpha-DHT-treated chickens. This effect was observed irrespective of dose of 5 alpha-DHT or whether the androgen was administered to castrated or to intact male or to female chicks.

  13. Transport mechanisms of nicotine across the human intestinal epithelial cell line Caco-2.

    PubMed

    Fukada, Atsuko; Saito, Hideyuki; Inui, Ken-Ichi

    2002-08-01

    Ulcerative colitis is a disease more commonly seen in nonsmokers. Because nicotine was postulated to be a beneficial component of tobacco smoke for ulcerative colitis, various formulations of nicotine have been developed to improve the local bioavailability within the gastrointestinal tissue. In the present study, to characterize the disposition of nicotine in the intestines, we investigated intestinal nicotine transport using Caco-2 cells. Nicotine was predominantly transported across Caco-2 cell monolayers in a unidirectional mode, corresponding to intestinal secretion, by pH-dependent specific transport systems. The specific uptake systems appear to be distinct from organic cation transporters and the transport system for tertiary amines, in terms of its substrate specificity and the pattern of the interaction. These transport systems could play a role in the intestinal accumulation of nicotine from plasma and could also be responsible for the topical delivery of nicotine for ulcerative colitis therapy. These findings could provide useful information for the design of effective nicotine delivery.

  14. Carbohydrate supplementation and alterations in neutrophils, and plasma cortisol and myoglobin concentration after intense exercise.

    PubMed

    Peake, Jonathan; Wilson, Gary; Mackinnon, Laurel; Coombes, Jeff S

    2005-03-01

    The present study examined the effect of carbohydrate supplementation on changes in neutrophil counts, and the plasma concentrations of cortisol and myoglobin after intense exercise. Eight well-trained male runners ran on a treadmill for 1 h at 85% maximal oxygen uptake on two separate occasions. In a double-blind cross-over design, subjects consumed either 750 ml of a 10% carbohydrate (CHO) drink or a placebo drink on each occasion. The order of the trials was counter-balanced. Blood was drawn immediately before and after exercise, and 1 h after exercise. Immediately after exercise, neutrophil counts (CHO, 49%; placebo, 65%; P<0.05), plasma concentrations of glucose (CHO, 43%; P<0.05), lactate (CHO, 130%; placebo, 130%; P<0.01), cortisol (CHO, 100%; placebo, 161%; P<0.01), myoglobin (CHO, 194%; placebo, 342%; P<0.01) all increased significantly. One hour post-exercise, plasma myoglobin concentration (CHO, 331%; placebo, 482%; P<0.01) and neutrophil count (CHO, 151%; placebo, 230% P<0.01) both increased further above baseline. CHO significantly attenuated plasma myoglobin concentration and the neutrophil count after exercise (P<0.01), but did not affect plasma cortisol concentration. The effects of CHO on plasma myoglobin concentration may be due to alterations in cytokine synthesis, insulin responses or myoglobin clearance rates from the bloodstream during exercise. Plasma cortisol responses to CHO during exercise may depend on the intensity of exercise, or the amount of CHO consumed. Lastly, cortisol appears to play a minor role in the mobilisation of neutrophils after intense exercise.

  15. Effects of a smoking ban on clozapine plasma concentrations in a nonsecure psychiatric unit

    PubMed Central

    Gee, Siobhan H.; Taylor, David M.; Shergill, Sukhwinder S.; Flanagan, Robert; MacCabe, James H.

    2016-01-01

    Background: Tobacco smoke is known to affect plasma levels of some drugs, including the antipsychotic clozapine. The effects of suddenly stopping smoking on patients who take clozapine can be severe, as plasma concentrations are expected to rapidly rise, potentially leading to toxicity. A ban on smoking at South London and the Maudsley NHS Foundation Trust (SLaM) was implemented in 2014, and this was expected to affect the plasma concentrations of clozapine for inpatients at the time. This study aimed to determine whether plasma concentrations of clozapine were affected, and additionally, in line with observations from other authors, whether levels of reported violence would also be affected. Methods: The smoking habits of all patients at SLaM who smoked and were prescribed clozapine were recorded both before and after the ban. The Glasgow Antipsychotic Side Effect Scale for Clozapine (GASS-C) scale was used to evaluate side-effect burden. Clozapine doses and plasma concentrations were also collected. Results: In total, 31 patients were included in this study. The mean clozapine dose before the ban was 502 mg/day, and this did not change significantly after the ban. Similarly, there were no significant changes in clozapine or norclozapine plasma concentrations, or in GASS-C scores. There was no change in the amount of tobacco patients reported smoking before or after the ban. A modest but statistically significant reduction in violent incidences was observed. Conclusions: Our data suggest that a ban on smoking for patients taking clozapine on open wards at inpatient hospital sites had little impact on clozapine plasma concentrations, because patients continued to smoke tobacco if allowed to leave. Smoking bans may result in a reduction in violent incidences. PMID:28255437

  16. 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.

  17. Changes in plasma leptin concentration during different types of exercises performed by horses.

    PubMed

    Kędzierski, W

    2014-09-01

    Leptin is a tissue-derivative adipokine that regulates appetite, food intake and energy expenditure. It is still not clear how exercise affects plasma leptin concentration in horses. The aim of this study was to evaluate the influence of exercise intensity and duration on plasma leptin levels in working horses. A total of 38 horses were prospectively included in the study and grouped according to the type of exercise they performed: dressage (six stallions, group D), jumping (12 stallions, group J), race (12 Thoroughbred horses, six stallions and six mares, group R) and harness (10 light draft stallions, group H). Blood samples were taken both before and after routine exercise (immediately after the exercise, 30 min and 24 h after). Blood lactic acid (LA) and plasma concentration of leptin, cortisol, uric acid, triacylglycerols, glycerol and free fatty acids were determined. Immediately after exercise, group R had the highest level of LA, whereas groups D and J had the lowest levels. A significant increase in plasma leptin concentration was stated only in group H in samples taken immediately after the end of the exercise period and 30 min after the exercise period, as compared with the values obtained at rest. A significant increase in plasma cortisol concentration was found immediately after the end of the exercise period in groups R and H. Leptin exercise-to-rest ratio was significantly correlated with cortisol exercise-to-rest ratio (r=0.64; P<0.001). The increase in plasma leptin concentration in exercised horses was related to the increased plasma cortisol concentration and took place only during long-lasting exercise, which was not intensive.

  18. A vaccine for nicotine dependence: targeting the drug rather than the brain.

    PubMed

    Pentel, Paul; Malin, David

    2002-01-01

    Nicotine is the principal addictive component of tobacco. Vaccination of rats against nicotine elicits the production of nicotine-specific antibodies which can bind and sequester nicotine in serum and extracellular fluid, reduce nicotine distribution to brain, and reduce many of nicotine's physiologic and behavioral effects. Vaccination reduces the distribution to brain of both a single nicotine dose and chronic nicotine infusion at rates approximating cigarette smoking. The passive transfer of nicotine-specific antibodies (from vaccinated rabbits) into rats attenuates numerous actions of nicotine: increases in blood pressure and locomotor activity, the induction of nicotine dependence, the relief of nicotine withdrawal by subsequent nicotine and the stimulus properties that allow rats to discriminate a nicotine from a saline injection. Vaccination of rats against nicotine also reduces nicotine-induced dopamine release in the reward pathway of the brain and the reinstatement of nicotine responding, a model for relapse. Because nicotine vaccines target the drug rather than the brain, and the antibodies themselves do not cross the blood-brain barrier, immunization should circumvent the central nervous system side effects that limit the usable dosage of other medications for tobacco dependence. Nicotine vaccines have not yet been tested in humans. The effects of these vaccines in rats are highly dependent upon the concentration of antibody in serum, and are more often partial than complete. If effective for treating tobacco dependence in humans, vaccination will likely benefit from concurrent use of counseling (as is the case with other medications for smoking cessation) and perhaps from its combination with other medications that act via different mechanisms.

  19. Effect of carnitine supplement to the dam on plasma carnitine concentration in the sucking foal.

    PubMed

    Benamou, A E; Harris, R C

    1993-01-01

    The changes in carnitine in plasma and milk during the first 3 months of lactation were studied in 14 broodmares and their foals. Six of the mares (Group S) were given a supplement of 10 g carnitine split between the morning and evening feeds, starting 2 weeks before birth. At birth the plasma carnitine concentration in Group S mares was about twice that in Group NS mares (no supplement). In both groups the concentration initially declined in the days after birth. Whilst this trend was reversed in Group S mares, the concentration in Group NS mares remained at a reduced level for the remainder of the study. Milk concentrations declined continuously over the monitoring period in both groups. There was no apparent relationship between milk and plasma concentrations. Despite this the milk concentration tended to be higher in Group S than in Group NS mares although differences were not significant. There was an immediate drop in the plasma concentration in foals after birth which was reversed in foals of Group S mares but not in those of Group NS mares. There were no apparent side effects of carnitine supplementation.

  20. Effect of thyroid hormone on concentrations of plasma calcitonin in broiler chicks.

    PubMed

    Klandorf, H; Boyce, C S; Holt, S B; Iqbal, M; Killefer, J; Peterson, R A; Deaver, D R

    1999-01-01

    The purpose of these studies was to determine the effect of thyroidectomy (Tx), and thyroid hormone (T3/T4) treatment on concentrations of plasma CT in chicks. In addition, the turnover of CT in Tx- and T3/T4-treated chicks was estimated using a novel nonradioactive salmon CT preparation. One-week-old broiler chicks (Gallus domesticus) (n = 75) were divided into three groups. Group I was sham-injected daily (i.m. saline), Group II was injected with 50 micrograms/day of T3/T4 while Group III was injected with the goitrogen, methimazole, (150 mg/kg BW per day) for 8 weeks. Chicks (8-9 weeks old) were implanted with catheters in the brachial wing vein and administered ruthenium-labeled salmon CT. Blood samples were collected at 30 s, 1, 2, 4, 8, 20 min, and 3 h after injection. Results showed that concentrations of plasma CT were decreased in T3/T4-injected birds. There was no significant effect of methimazole on circulating concentrations of plasma CT. The half-life of CT was significantly increased (P < 0.05) in both T3/T4-injected (n = 6; 1.34 +/- 0.16 min) and goitrogen-treated birds (n = 2; 5.81 +/- 2.83 min) compared to controls (n = 7; 54 +/- 3 s) The results demonstrate that changes in concentrations of plasma thyroid hormones can significantly affect concentrations of plasma CT.

  1. Nicotine activates the chemosensory cation channel TRPA1.

    PubMed

    Talavera, Karel; Gees, Maarten; Karashima, Yuji; Meseguer, Víctor M; Vanoirbeek, Jeroen A J; Damann, Nils; Everaerts, Wouter; Benoit, Melissa; Janssens, Annelies; Vennekens, Rudi; Viana, Félix; Nemery, Benoit; Nilius, Bernd; Voets, Thomas

    2009-10-01

    Topical application of nicotine, as used in nicotine replacement therapies, causes irritation of the mucosa and skin. This reaction has been attributed to activation of nicotinic acetylcholine receptors (nAChRs) in chemosensory neurons. In contrast with this view, we found that the chemosensory cation channel transient receptor potential A1 (TRPA1) is crucially involved in nicotine-induced irritation. We found that micromolar concentrations of nicotine activated heterologously expressed mouse and human TRPA1. Nicotine acted in a membrane-delimited manner, stabilizing the open state(s) and destabilizing the closed state(s) of the channel. In the presence of the general nAChR blocker hexamethonium, nociceptive neurons showed nicotine-induced responses that were strongly reduced in TRPA1-deficient mice. Finally, TRPA1 mediated the mouse airway constriction reflex to nasal instillation of nicotine. The identification of TRPA1 as a nicotine target suggests that existing models of nicotine-induced irritation should be revised and may facilitate the development of smoking cessation therapies with less adverse effects.

  2. Nicotine depresses the functions of multiple cardiac potassium channels.

    PubMed

    Wang, H; Shi, H; Wang, Z

    1999-01-01

    Nicotine is the main constituent of tobacco smoke responsible for the elevated risk of the cardiovascular disease and sudden coronary death associated with smoking, presumably by provoking cardiac arrhythmias. The cellular mechanisms may be related to the ability of nicotine to prolong action potentials and to depolarize membrane potential. However, the underlying ionic mechanisms remained unknown. We showed here that nicotine blocked multiple types of K+ currents, including the native currents in canine ventricular myocytes and the cloned channels expressed in Xenopus oocytes: A-type K+ currents (I(to)/Kv4.3), delayed rectifier K+ currents (I(Kr)/HERG) and inward rectifier K+ currents (I(K1)/Kir2.1). Most noticeably, nicotine at a concentration as low as of 10 nM significantly suppressed I(to) and Kv4.3 by approximately 20%. The effects of nicotine were independent of nicotinic receptor simulation or catecholamine release. Our results indicate that nicotine is a non-specific blocker of K+ channels and the inhibitory effects are the consequence of direct interactions between nicotine molecules and the channel proteins. Our study provided for the first time the evidence for the direct inhibition of cardiac K+ channels by nicotine and established a novel aspect of nicotine pharmacology.

  3. 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.

  4. 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.

  5. Optimized preparation method of platelet-concentrated plasma and noncoagulating platelet-derived factor concentrates: maximization of platelet concentration and removal of fibrinogen.

    PubMed

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

    2012-03-01

    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.

  6. 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.

  7. 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.

  8. 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.

  9. Effect of dietary fat source on lipoprotein composition and plasma lipid concentrations in pigs.

    PubMed

    Faidley, T D; Luhman, C M; Galloway, S T; Foley, M K; Beitz, D C

    1990-10-01

    Most studies of the effects of dietary fat sources on plasma lipid components have used diets with extreme fat compositions; the current study was designed to more nearly mimic human dietary fat intake. Young growing pigs were fed diets containing either 20 or 40% of energy as soy oil, beef tallow or a 50/50 blend of soy oil and tallow. Different dietary fats did not affect concentrations of cholesterol, triacylglycerol or protein in plasma or major lipoprotein fractions. The concentration of phospholipid was less in plasma and in very low density lipoproteins with soy oil feeding than with tallow feeding. The weight percentage of cholesteryl ester in the low density lipoprotein fraction tended to be greater with 40% than with 20% tallow and tended to be less with 40% than with 20% soy oil. Phospholipid as a weight percentage of low density lipoprotein was least in pigs fed soy oil. Tallow feeding increased the percentage of myristic, palmitic, palmitoleic and oleic acids in plasma, relative to both other groups. Soy oil feeding increased the percentage of linoleic and linolenic acids. These moderate diets were not hypercholesterolemic, but they did alter plasma fatty acid composition and phospholipid concentrations in plasma and very low density lipoprotein.

  10. Plasma Oxytocin Concentration during Pregnancy is associated with Development of Postpartum Depression

    PubMed Central

    Skrundz, Marta; Bolten, Margarete; Nast, Irina; Hellhammer, Dirk H; Meinlschmidt, Gunther

    2011-01-01

    Postpartum depression (PPD) affects up to 19% of all women after parturition. The non-apeptide oxytocin (OXT) is involved in adjustment to pregnancy, maternal behavior, and bonding. Our aim was to examine the possible association between plasma OXT during pregnancy and the development of PPD symptoms. A total of 74 healthy, pregnant women were included in this prospective study. During the third trimester of pregnancy and within 2 weeks after parturition, PPD symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Blood samples for plasma OXT assessment were collected in the third trimester. Following the literature, participants with postpartum EPDS scores of 10 or more were regarded as being at risk for PPD development (rPPD group). In a logistic regression analysis, plasma OXT was included as a potential predictor for being at risk for PPD. Results were controlled for prepartal EPDS score, sociodemographic and birth-outcome variables. Plasma OXT concentration in mid-pregnancy significantly predicted PPD symptoms at 2 weeks postpartum. Compared with the no-risk-for-PPD group, the rPPD group was characterized by lower plasma OXT concentrations. To our knowledge, this is the first study to show an association between prepartal plasma OXT concentration and postpartal symptoms of PPD in humans. Assuming a causal relationship, enhancing OXT release during pregnancy could serve as a potential target in prepartum PPD prevention, and help to minimize adverse effects of PPD on the mother–child relationship. PMID:21562482

  11. 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.

  12. Dietary predictors and plasma concentrations of perfluorinated alkyl acids in a Singapore population.

    PubMed

    Liu, Yu; Su, Jin; van Dam, Rob M; Prem, Kiesha; Hoong, Joey Y S; Zou, Li; Lu, Yonghai; Ong, Choon Nam

    2017-03-01

    Perfluorinated alkyl acids (PFAAs), a family of man-made organofluorinated compounds, have drawn much attention due to their ubiquitous existence in the environment and their bioaccumulation potential. Here, we examined the plasma concentrations of thirteen PFAAs in a healthy population (N = 270) in Singapore, and investigated the association between major food groups and plasma PFAA concentrations. We detected eight types of PFAAs in more than 75% of all samples (N = 270), and their median concentrations ranged from 0.05 to 8.34 ng mL(-1). Age- and gender-related differences were observed for the three dominant PFAAs, i.e., perfluorooctanesulfonic acid (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorooctanoate acid (PFOA), with concentrations being higher in men and older adults. Multiple linear regression analyses showed that fish, shellfish, red meat and poultry were associated with increased PFAAs concentrations in plasma, whereas grains and soy products showed inverse associations with PFAAs. Further, significant correlations were observed between various long-chain PFAAs and plasma concentrations of omega-3 fatty acids, suggesting seafood was a significant source of these PFAAs, within this population. Future studies on diet exposure to PFAAs are encouraged to focus more on the effects on diet pattern.

  13. 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.

  14. 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.

  15. Variations in plasma motilin, somatostatin, and pancreatic polypeptide concentrations and the interdigestive myoelectric complex in dog.

    PubMed

    Poitras, P; Lemoyne, M; Tasse, D; Trudel, L; Yamada, T; Taylor, I L

    1985-12-01

    We have looked at the plasma concentrations of motilin, pancreatic polypeptide (PP), and somatostatin (STS) during the various phases of the interdigestive motor complex (IDMC) in dogs. As expected, motilin cyclical increase was always associated with the phase III of the IDMC. Statistical analysis of PP variations revealed a significant rise 10 min before duodenal phase III; however, in individual animals, this relationship was inconsistent. Although a dose-related increase in PP blood levels was induced by administration of synthetic canine motilin (0-200 ng kg-1 iv), fasting plasma levels of PP were not correlated with the concentrations of circulating endogenous motilin. After truncal vagotomy, while motilin release and the intestinal motility pattern remained unaltered, the phase III associated cyclical increases of PP disappeared. Infusion of physiological amounts of PP (1 microgram kg-1 h-1 for 3 h) mimicking the postprandial release failed to reproduce a fed pattern type of intestinal motility and of motilin secretion. No statistical correlation could be established between STS plasma levels and the motor activity of the intestine. STS plasma levels were not correlated with circulating concentrations of motilin and the exogenous administration of physiological doses of synthetic canine motilin failed to modify STS plasma levels. Morphine (200 micrograms kg-1 iv) stimulated only the release of motilin. These data suggest that the role played by circulating concentrations of PP and STS in the control of the IDMC in dog is at most minimal.

  16. Endocannabinoids concentrations in plasma associated with feed efficiency and carcass composition of beef steers.

    PubMed

    Artegoitia, V M; Foote, A P; Lewis, R M; King, D A; Shackelford, S D; Wheeler, T L; Freetly, H C

    2016-12-01

    Endocannabinoids, including anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are a class of endogenous lipid mediators that activate cannabinoids receptors and may be involved in the control of feed intake and energy metabolism. The objective of this study was to quantify AEA and 2-AG in plasma and identify possible associations with production traits and carcass composition in finishing beef steers. Individual DMI and BW gain were measured on 140 Angus-sired steers for 105 d on a finishing ration. Blood samples were collected on d 84 of the experiment, which was 40 d before slaughter. Variables were analyzed using Pearson CORR procedure of SAS. Mean endocannabinoid concentrations in plasma were 4.48 ± 1.82 ng/mL and 0.44 ± 0.24 ng/mL for AEA and 2-AG, respectively. The AEA concentration was positively correlated with G:F ratio ( = 0.20; = 0.02), indicating that more efficient animals had greater AEA plasma concentrations. In addition, AEA concentration tended to be negatively correlated with the 12th rib fat thickness ( = -0.17; = 0.07); but no correlation was found with USDA-calculated yield grade ( = -0.14; = 0.11), or marbling score ( = 0.05; = 0.54). The concentration of 2-AG was positively correlated with AEA ( = 0.21; = 0.01); however, 2-AG concentration was not correlated with parameters of feed efficiency or carcass composition. To our knowledge, this study is the first to report plasma concentration of endocannabinoids in steers. These results provide evidence that plasma concentration of a key endocannabinoid, AEA, was favorably correlated with feed efficiency and fat thickness in finishing steers.

  17. Plasma concentrations of adrenomedullin and atrial and brain natriuretic peptides in patients with adrenal pheochromocytoma.

    PubMed

    Hu, Wei; Shi, Lei; Zhou, Pang-Hu; Zhang, Xiao-Bin

    2015-11-01

    The present study aimed to evaluate any changes in the plasma concentrations of adrenomedullin (ADM), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with adrenal pheochromocytoma (PC). The plasma concentrations of the three peptides were measured in 45 healthy control individuals and 90 untreated patients with PC, who consisted of 20 normotensive patients, 30 borderline hypertensive patients and 40 hypertensive patients. After 4 weeks of effective antihypertensive therapy for hypertensive PC patients, the concentrations of ADM, ANP and BNP were measured again, and laparoscopic adrenalectomy was then performed for all PC patients with values that were measured 2 weeks later. The plasma concentrations of the three peptides were significantly increased in the borderline hypertensive and hypertensive patients compared with the concentrations in control individuals and normotensive patients. In addition, there were significant differences between the levels of ADM, ANP and BNP in the borderline and hypertensive groups. The plasma ADM concentration was not associated with the blood urea nitrogen levels, serum creatinine levels or glomerular filtration rate, but was correlated with the serum epinephrine, serum norepinephrine and urine vanillylmandelic acid levels. In addition, the ADM concentration was associated with the systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular mass index and plasma concentrations of ANP and BNP in the hypertensive patients with PC. After 4 weeks of antihypertensive treatment, the values of the three peptides in the hypertensive patients with PC were not significantly changed. As expected, the values in borderline and hypertensive groups were significantly decreased 2 weeks subsequent to surgery, whereas there were no significant changes in the normotensive group. ADM may participate, along with ANP and BNP, in the mechanisms that counteract further elevation

  18. 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.

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

    PubMed Central

    Bunch, Ronald; Leung, Angela M.

    2016-01-01

    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. PMID:26946249

  20. The establish of the HPLC method to examine the plasma concentration of lamotrigine and oxcarbazepine.

    PubMed

    Zhu, Xue-Ping; Zhao, Yao-Dong; Cheng, Zhi; Zhao, Ning Min; Li, Hao

    2015-05-01

    To establish the HPLC method to examine plasma concentration of lamotrigine and oxcarbazepine. This study set chlorzoxazone as the internal standard, chromatographic column was Column C18 (200×4.6mm, 5um) of DIKMA company, the mobile phase was methanol, water and trifluoroacetic acid, with rate of 40: 60: 0.0005, at a flow rate of 1 mllmin(-1), the detected wavelength was 240 nm. The plasma concentrations of lamotrigine was 0.5-50ug•mL(-1), the standard curve was excellent for Y=0.5511C-0.5669, r=0.9940, average recovery was 91.40%; The plasma concentrations of oxcarbazepine was 0.5-50ugmL-1, the standard curve was good for Y=0.4026C-0.5895, r=0.9925, and the average recovery was 89.59%; The three plasma concentrations of lamotrigine were respectively 25μg•mL(-1), 10 μg•mL(-1) and 2μg•mL(-1) and its five parallel sample for injection RSD were respectively 4.01%, 6.15% and 4.64%; The three plasma concentration of oxcarbazepine were 25μg•mL(-1)-1(-1), 10μg•mL(-1)-1(-1) and 2μg•mL(-1)-1(-1), and its five parallel sample for injection RSD were respectively 3.05%, 4.27% and 9.01%. This method was easy to operate, high recovery and high precision, and was applicable to the clinical detection for plasma concentration of lamotrigine and oxcarbazepine.

  1. Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment

    PubMed Central

    Saunders, Erika FH; Reider, Aubrey; Singh, Gagan; Gelenberg, Alan J; Rapoport, Stanley I

    2015-01-01

    Objectives Omega (n)-3 and n-6 polyunsaturated fatty acids (PUFA) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n-3 PUFA would be lower and of n-6 PUFA higher in subjects with bipolar disorder (BD) compared to healthy controls (HC), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids. Methods This observational, parallel group study compared biomarkers between HC (n = 31), and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow-up). Plasma concentrations of five PUFA [linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], of two saturated fatty acids (palmitic acid and stearic acid) and of two monounsaturated fatty acids (palmitoleic acid, oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFA, ratios of n-3 PUFA (DHA:ALA, EPA:ALA, EPA:DHA), and the ratio of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t-tests, between the BD group at baseline and follow-up using paired t-tests. Comparison of categorical variables was performed using Chi-square tests. Pearson’s r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis. Results UE EPA was lower in BD than HC, with a large effect size (Cohen’s d = 0.86, p < 0.002), however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between BD and HC after Bonferroni correction for 40

  2. Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India.

    PubMed

    Yajnik, Chittaranjan S; Lubree, Himangi G; Thuse, Nileema V; Ramdas, Lalita V; Deshpande, Swapna S; Deshpande, Vaishali U; Deshpande, Jyoti A; Uradey, Bhagyashree S; Ganpule, Anjali A; Naik, Sadanand S; Joshi, Niranjan P; Farrant, Hannah; Refsum, Helga

    2007-01-01

    People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations. In a proof of principle trial, we studied the effect of oral vitamin B12 (500 microg) and/or 100 g cooked green leafy vegetables (GLV) every alternate day in a 2x2 factorial design over a 6-week period. Forty-two non-pregnant vegetarian women (age 20-50 years) were randomly allocated to four study groups. Clinical measurements were made at the beginning and at the end of the study, and blood samples were collected before, and 2 and 6 weeks after commencement of intervention. Forty women completed the trial. Twenty-six women had low vitamin B12 status (<150 pmol/L) and 24 had hyperhomocysteinemia (>15 micromol/L). GLV supplementation did not alter plasma folate or tHcy. Vitamin B12 supplementation increased plasma vitamin B12 concentration (125 to 215 pmol/L, p <0.05) and reduced tHcy concentration (18.0 to 13.0 micromol/L, p <0.05) within first 2 weeks, both of which remained stable for the next 4 weeks. Plasma vitamin B12 and tHcy concentrations did not change in those who did not receive vitamin B12, and there was no change in plasma folate concentration in any of the groups. Blood haemoglobin concentration increased marginally within first two weeks in those women who received vitamin B12 (by 3 g/L, p <0.05) and the number of women with macrocytosis decreased from 2 to zero. There was no change in vibration sensory threshold during the period of the study. High-dose per oral vitamin B12 supplementation significantly reduced plasma tHcy within 2 weeks but did not achieve normal plasma tHcy concentration even after 6 weeks. People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations.

  3. Plasma concentrations of the enantiomers of halofantrine and its main metabolite in malaria patients.

    PubMed

    Gimenez, F; Gillotin, C; Basco, L K; Bouchaud, O; Aubry, A F; Wainer, I W; Le Bras, J; Farinotti, R

    1994-01-01

    The plasma concentrations of the enantiomers of halofantrine and its N-desbutyl metabolite in six patients with malaria were measured after oral administration of 3 x 750 mg doses of micronised, racemic halofantrine hydrochloride given at 6-hour intervals. Significant differences were observed between the plasma concentrations of the enantiomers both of halofantrine and its N-monodesbutyl metabolite. AUC(0)84h values were higher for (+)halofantrine (9917 micrograms.ml-1.h) than for (-)-halofantrine (6127 micrograms.ml-1.h). The clinical significance of these observations is not known. The isomers have equipotent activity in vitro but their relative toxicity has not yet been assessed.

  4. Relationship between reproductive success and male plasma vitellogenin concentrations in cunner, Tautogolabrus adspersus.

    PubMed Central

    Mills, Lesley J; Gutjahr-Gobell, Ruth E; Horowitz, Doranne Borsay; Denslow, Nancy D; Chow, Marjorie C; Zaroogian, Gerald E

    2003-01-01

    The gene for vitellogenin, an egg yolk protein precursor, is usually silent in male fish but can be induced by estrogen exposure. For this reason, vitellogenin production in male fish has become a widely used indicator of exposure to exogenous estrogens or estrogen mimics in the aquatic environment. The utility of this indicator to predict impacts on fish reproductive success is unclear because information on the relationship between male plasma vitellogenin and reproductive end points in male and female fish is limited. In the research reported in this article, we investigated whether the presence of male plasma vitellogenin is a reliable indicator of decreased reproductive success in mature fish. Adult and sexually mature male and female cunner (Tautogolabrus adspersus) were exposed to 17ss-estradiol, ethynylestradiol, or estrone, three steroidal estrogens that elicit the vitellogenic response. Data were gathered and pooled on egg production, egg viability, egg fertility, sperm motility, and male plasma vitellogenin concentrations. All males, including two with plasma vitellogenin levels exceeding 300 mg/mL, produced motile sperm. Neither percent fertile eggs nor percent viable eggs produced by reproductively active fish demonstrated a significant correlation with male plasma vitellogenin concentrations. Male gonadosomatic index and average daily egg production by females showed significant, but weak, negative correlation with male plasma vitellogenin concentrations. Results suggest that male plasma vitellogenin expression is not a reliable indicator of male reproductive dysfunction in adult cunner exposed to estrogens for 2-8 weeks during their reproductive season, at least in relation to capacity to produce motile sperm or fertilize eggs. Male plasma vitellogenin expression may serve as an indicator of reduced female reproductive function caused by estrogen exposure. PMID:12515685

  5. Nicotine is highly effective at producing desensitization of rat α4β2 neuronal nicotinic receptors

    PubMed Central

    Paradiso, K G; Steinbach, Joe Henry

    2003-01-01

    We examined desensitization by acetylcholine (ACh) and nicotine at the rat α4β2 neuronal nicotinic receptor stably expressed in HEK cells. For both agonists, the decay in response due to desensitization (‘onset’) was best fitted by the sum of two exponentials with the fast component dominant at concentrations > 1 μm. The time constants for onset were similar for both agonists, and showed little concentration dependence over the range of 0.1–100 μm. Recovery from desensitization also showed two exponential components. In contrast to the similarity in onset, nicotine produced longer lasting desensitization, resulting from an increase in the proportion of receptors in the slowly recovering population and from an increase in the time constant for the slow recovery process. The proportion of receptors in the slowly recovering population increased as the duration of the desensitizing pulse increased. Desensitization was also induced by low concentrations of agonist, with no apparent macroscopic response. A 100 s application of 10 nm nicotine desensitized 70 % of the peak response, while 100 s of 10 nm ACh desensitized only 15 %. At higher concentrations of agonist, which result in a macroscopic response, desensitization in the absence of activation also can occur. Nicotine is a very potent and efficacious desensitizing agent at this neuronal nicotinic receptor. PMID:14555718

  6. 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.

  7. Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects.

    PubMed

    Zhang, Wei; Wang, Xiaobing; Liu, Yi; Tian, Haimei; Flickinger, Brent; Empie, Mark W; Sun, Sam Z

    2008-06-01

    Lignans, derived from flaxseed, are phyto-oestrogens being increasingly studied for their health benefits. An 8-week, randomised, double-blind, placebo-controlled study was conducted in fifty-five hypercholesterolaemic subjects, using treatments of 0 (placebo), 300 or 600 mg/d of dietary secoisolariciresinol diglucoside (SDG) from flaxseed extract to determine the effect on plasma lipids and fasting glucose levels. Significant treatment effects were achieved (P < 0.05 to < 0.001) for the decrease of total cholesterol (TC), LDL-cholesterol (LDL-C) and glucose concentrations, as well as their percentage decrease from baseline. At weeks 6 and 8 in the 600 mg SDG group, the decreases of TC and LDL-C concentrations were in the range from 22.0 to 24.38 % respectively (all P < 0.005 compared with placebo). For the 300 mg SDG group, only significant differences from baseline were observed for decreases of TC and LDL-C. A substantial effect on lowering concentrations of fasting plasma glucose was also noted in the 600 mg SDG group at weeks 6 and 8, especially in the subjects with baseline glucose concentrations > or = 5.83 mmol/l (lowered 25.56 and 24.96 %; P = 0.015 and P = 0.012 compared with placebo, respectively). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED) and enterolactone were all significantly raised in the groups supplemented with flaxseed lignan. The observed cholesterol-lowering values were correlated with the concentrations of plasma SECO and ED (r 0.128-0.302; P < 0.05 to < 0.001). In conclusion, dietary flaxseed lignan extract decreased plasma cholesterol and glucose concentrations in a dose-dependent manner.

  8. Plasma cortisol concentrations and perceived anxiety in response to on-sight rock climbing.

    PubMed

    Draper, N; Dickson, T; Fryer, S; Blackwell, G; Winter, D; Scarrott, C; Ellis, G

    2012-01-01

    Previous research suggested plasma cortisol concentrations in response to rock climbing have a cubic relationship with state anxiety and self-confidence. This research, however, was conducted in a situation where the climbers had previously climbed the route. The purpose of our study was to examine this relationship in response to on-sight climbing. Nineteen (13 male, 6 female) intermediate climbers volunteered to attend anthropometric and baseline testing sessions, prior to an on-sight ascent (lead climb or top-rope) of the test climb (grade 19 Ewbank/6a sport/5.10b YDS). Data recorded included state anxiety, self-confidence and cortisol concentrations prior to completing the climb. Results indicated that there were no significant differences in state anxiety, self-confidence and plasma cortisol concentration regardless of the style of ascent (lead climb or top-rope) in an on-sight sport climbing context. Regression analysis indicated there was a significant linear relationship between plasma cortisol concentrations and self-confidence (r= - 0.52, R2=0.267, p=0.024), cognitive (r=0.5, R2=0.253, p=0.028), and somatic anxieties (r=0.46, R2=0.210, p=0.049). In an on-sight condition the relationships between plasma cortisol concentrations with anxiety (cognitive and somatic) and self-confidence were linear.

  9. Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects.

    PubMed

    Misaka, S; Yatabe, J; Müller, F; Takano, K; Kawabe, K; Glaeser, H; Yatabe, M S; Onoue, S; Werba, J P; Watanabe, H; Yamada, S; Fromm, M F; Kimura, J

    2014-04-01

    This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the β-blocker nadolol. Ten healthy volunteers received a single oral dose of 30 mg nadolol with green tea or water after repeated consumption of green tea (700 ml/day) or water for 14 days. Catechin concentrations in green tea and plasma were determined. Green tea markedly decreased the maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-48)) of nadolol by 85.3% and 85.0%, respectively (P < 0.01), without altering renal clearance of nadolol. The effects of nadolol on systolic blood pressure were significantly reduced by green tea. [(3)H]-Nadolol uptake assays in human embryonic kidney 293 cells stably expressing the organic anion-transporting polypeptides OATP1A2 and OATP2B1 revealed that nadolol is a substrate of OATP1A2 (Michaelis constant (K(m)) = 84.3 μmol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated nadolol uptake (half-maximal inhibitory concentration, IC(50) = 1.36%). These results suggest that green tea reduces plasma concentrations of nadolol possibly in part by inhibition of OATP1A2-mediated uptake of nadolol in the intestine.

  10. Perioperative plasma concentrations of stable nitric oxide products are predictive of cognitive dysfunction after laparoscopic cholecystectomy.

    PubMed

    Iohom, G; Szarvas, S; Larney, V; O'Brien, J; Buckley, E; Butler, M; Shorten, G

    2004-10-01

    In this study our objectives were to determine the incidence of postoperative cognitive dysfunction (POCD) after laparoscopic cholecystectomy under sevoflurane anesthesia in patients aged >40 and <85 yr and to examine the associations between plasma concentrations of i) S-100beta protein and ii) stable nitric oxide (NO) products and POCD in this clinical setting. Neuropsychological tests were performed on 42 ASA physical status I-II patients the day before, and 4 days and 6 wk after surgery. Patient spouses (n = 13) were studied as controls. Cognitive dysfunction was defined as deficit in one or more cognitive domain(s). Serial measurements of serum concentrations of S-100beta protein and plasma concentrations of stable NO products (nitrate/nitrite, NOx) were performed perioperatively. Four days after surgery, new cognitive deficit was present in 16 (40%) patients and in 1 (7%) control subject (P = 0.01). Six weeks postoperatively, new cognitive deficit was present in 21 (53%) patients and 3 (23%) control subjects (P = 0.03). Compared with the "no deficit" group, patients who demonstrated a new cognitive deficit 4 days postoperatively had larger plasma NOx at each perioperative time point (P < 0.05 for each time point). Serum S-100beta protein concentrations were similar in the 2 groups. In conclusion, preoperative (and postoperative) plasma concentrations of stable NO products (but not S-100beta) are associated with early POCD. The former represents a potential biochemical predictor of POCD.

  11. The dynamic observation of plasma concentration of antimicrobial agents during balanced ultrafiltration in vitro.

    PubMed

    Fang, Yinghui; Guan, Yulong; Wan, Caihong; Fu, Zhida; Jiang, Juanjuan; Wu, Chunfu; Zhao, Ju; Sun, Peng; Long, Cun

    2014-01-01

    Routine perioperative intravenous antimicrobial agents are administered as surgical prophylaxis. However, whether balanced ultrafiltration during extracorporeal circulation has substantial effect on the concentration of antimicrobial agents remains unclear. The concentrations of antimicrobial agents in plasma and ultrafiltrate samples were measured in this pseudo-extracorporeal circulation model. Extracorporeal circulation consisted of cardiotomy reservoir, membrane oxygenator, and pediatric arterial line filter. A hemoconcentrator was placed between the arterial purge line and oxygenator venous reservoir. Fresh donor human whole blood was added into the circuit and mixed with Ringer's solution to obtain a final hematocrit of 24-28%. Two kinds of antimicrobial agents, cefotiam (320 mg) and cefmetazole (160 mg), were bolus added into the circuit. After 30 min of extracorporeal circulation, zero-balanced ultrafiltration was initiated and arterial line pressure was maintained at approximately 100 mm Hg with a Hoffman clamp. The rate of ultrafiltration (12 mL/min) was controlled by ultrafiltrate outlet pressure. An identical volume of Plasmalyte A was dripped into the circuit to maintain stable hematocrit during 45 min of experiment. Plasma and ultrafiltrate samples were drawn every 5 min, and concentrations of antimicrobial agents (including cefotiam and cefmetazole) were measured with high performance liquid chromatography. Both antimicrobial agents were detected in ultrafiltrate, demonstrating hemoconcentration may remove antimicrobial agents. The concentrations of plasma antimicrobial agents decreased linearly with the increase of ultrafiltrate volume. At end of balanced ultrafiltration, the concentration of plasma cefotiam was 104.96 ± 44.36 mg/L, which is about 44.38% ± 7.42% of the initial concentration (238.95 ± 101.12 mg/L) (P < 0.001); the concentration of plasma cefmetazole decreased linearly to 25.76 ± 14.78

  12. 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.

  13. Treatment of nicotine dependence.

    PubMed

    Haxby, D G

    1995-02-01

    Drug and nondrug interventions used in treating nicotine dependence are reviewed. Tobacco use is the leading preventable cause of death in the United States. Risks of smoking-related disease and death decline sharply when smokers quit, but 26% of Americans continue to smoke. Most smokers find it extremely difficult to quit smoking because of their nicotine addiction. Nonpharmacologic interventions used to promote smoking cessation include behavioral therapy, setting a specific date for quitting, receiving advice to quit from a health care professional, follow-up visits to review progress, self-help approaches, group counseling, filtration devices, hypnosis, and acupuncture. The efficacy of these approaches ranges from substantial to almost nil. The only pharmacologic agent with FDA-approved labeling for use in smoking-cessation therapy is nicotine. When used in conjunction with appropriate nonpharmacologic interventions, nicotine-replacement therapy roughly doubles the rate of quitting obtained with placebo. Nicotine-replacement therapies consist of nicotine transdermal (patch) systems and nicotine chewing gum. The nicotine patch is the first-line replacement therapy because it is effective when accompanied by only minimal (as opposed to more intensive) nonpharmacologic interventions and because it is easier to use and comply with than gum. Clonidine, antidepressants, and buspirone require further study to determine what role, if any, they should play in the treatment of nicotine dependence. The stages of smoking cessation are precontemplation, contemplation, action, and maintenance; interventions are selected on the basis of the stage the smoker is in. Nicotine dependence is difficult to treat, but there are aids that boost a smoker's chances of quitting. Nicotine patches and chewing gum offer the most effective pharmacologic options, especially when combined with behavioral interventions and counseling.

  14. Intrathyroidal iodide binding rates and plasma methimazole concentrations in hyperthyroid patients on small doses of carbimazole.

    PubMed Central

    Low, L C; McCruden, D C; Alexander, W D; Hilditch, T E; Skellern, G G; Knight, B I

    1981-01-01

    1 The effect of small doses of carbimazole on the binding rate constant of intrathyroidal iodide, plasma methimazole concentrations and circulating thyroid hormone concentrations in five hyperthyroid patients is presented. 2 In all patients there was a marked reduction in iodide binding with carbimazole doses as low as 5 to 10 mg daily. 3 In three patients little further reduction in the observed binding rate occurred with daily doses in excess of 10 mg despite progressive increases in plasma methimazole concentrations. 4 At the end of 4 weeks' treatment with 10 mg carbimazole daily, the reduction in thyroid hormone concentrations and clinical improvement were such as to suggest that this dose may be an effective starting dose in many patients. PMID:7295461

  15. Effect of exchange transfusions with citrated blood on plasma concentrations of vitamin D metabolites in neonates.

    PubMed

    Markestad, T; Aksnes, L; Finne, P H; Aarskog, D

    1984-05-01

    The plasma concentrations of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D), and 24,25-dihydroxyvitamin D (24,25-(OH)2D) were determined pre- and postexchange , and in donors' blood in 10 blood exchange transfusions with citrated blood for neonatal hyperbilirubinemia. The postexchange concentrations of 25-OHD and 24,25-(OH)2D were intermediate between the levels before exchange and in donors' blood. Before therapy, the 1,25-(OH)2D concentrations were higher in the infants' than in donors' blood, and the pre-exchange levels were re-established during the procedure. The results suggest that postexchange concentrations of 25-OHD and 24,25-(OH)2D could be explained on the basis of redistribution of the metabolites between plasma and extravascular pools, whereas de novo synthesis was the most likely cause for the restoration of 1,25-(OH)2D levels.

  16. Plasma prostaglandin E2 concentrations after single dose administration of ketorolac tromethamine (Toradol) in dogs.

    PubMed Central

    Pasloske, K; Burger, J; Conlon, P

    1998-01-01

    Ketorolac tromethamine (Toradol) is a relatively new, potent, non-narcotic analgesic with cyclooxygenase (COX) inhibitory activity and has been associated with gastric and renal toxicity in people and dogs. The objectives of this study were to establish whether endogenous PGE2 exists in the plasma of healthy dogs and to determine if, and to what magnitude, ketorolac alters PGE2 plasma concentrations after administration. Enzyme immunoassay measurement of a stable PGE2 derivative, bicyclo PGE2, showed that after i.v. administration of 0.5 mg/kg ketorolac tromethamine, 1 and 24 h plasma samples contained significantly (P < or = 0.01) less PGE2 than did plasma samples collected from dogs before the drug treatment. After p.o. administration, 1 h plasma samples contained significantly (P < or = 0.01) less PGE2 than did pretreatment samples, and the 24 h post-drug administration samples contained significantly (P < or = 0.01) less plasma PGE2 than the 96 h plasma samples. The results of this study suggest that a clinically effective single i.v. or p.o. dose of ketorolac tromethamine to healthy dogs causes a significant but reversible decrease in endogenous PGE2 production which may partially explain the drug's low therapeutic index. PMID:9684056

  17. 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

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

    PubMed

    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 (R (2) > 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

  19. 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

  20. Changes of concentration of cyclic AMP in rat brain and plasma in the clinical death model.

    PubMed

    Kapuściński, A

    1991-01-01

    In the experimental model of clinical death in rats (Korpachev et al. 1982) cyclic AMP concentrations were evaluated in the brain and plasma at the end of 5-min clinical death, and 5, 15, 30, 60 and 120 min after resuscitation. The cAMP 125I assay system has been used. At the end of clinical death the cAMP level decreased in the brain with normalization 15 min after resuscitation; the second decrease of the cAMP level was observed 30 min post resuscitation with normalization in later periods. In the plasma cAMP concentration did not change at the end of clinical death, followed by a significant increase 5 min after resuscitation. Later the level of plasma cAMP decreased being still above the control value after 2 hours. The possible role of endogenous catecholamines stimulation on adenylate cyclase activity is discussed.

  1. Plasma concentration of calcium, magnesium and phosphorus in chinchilla with and without tooth overgrowth.

    PubMed

    Muszczyński, Zbigniew; Sulik, Małgorzata; Ogoński, Tadeusz; Antoszek, Jolanta

    2010-01-01

    The aim of the study was to identify the causes underlying overgrowth of incisors in chinchillas through an analysis of selected plasma electrolyte concentrations, with particular consideration of minerals involved in the formation of osseous tissue, i.e., Ca, Mg, and P. The analysis involved 40 female standard chinchillas managed in a commercial farm system, aged 2 to 4 years, divided into two groups of 20 individuals each: D--chinchillas with incisor overgrowth and C--controls with normal dentition. Concentrations of Ca, Mg, and P were measured in blood plasma. The analysis was carried out using ICP OES (inductively coupled plasma optical emission spectrometry) by means of the Optima 2000 DV instrument (Perkin Elmer). The resulting data were analysed statistically using one-way ANOVA with Duncan's range test. The results show that abnormal metabolism of dental tissue minerals, especially Ca and P, cannot be excluded as the cause of tooth overgrowth in chinchilla.

  2. Plasma albumin concentrations and intestinal permeability in Bangladeshi children infected with Ascaris lumbricoides.

    PubMed

    Northrop, C A; Lunn, P G; Wainwright, M; Evans, J

    1987-01-01

    Plasma albumin concentration and intestinal permeability have been investigated in Bangladeshi children before and 9-14 d after successful treatment for ascariasis. Children infected with A. lumbricoides had lower plasma albumin concentrations than counterparts not harbouring this worm and values increased with successful treatment. Intestinal permeability tests indicated that the children had impaired gastrointestinal function and some loss of mucosal integrity; these factors had not improved 9-14 d after A. lumbricoides expulsion. The lowered nitrogen nutritional status implied by the reduced plasma albumin values in infected children, and the improvement following treatment, are in keeping with previous reports that A. lumbricoides impairs protein digestion or absorption. This may be the basis of the better growth rates of dewormed children in this area.

  3. Effects of Different Heavy-Resistance Exercise Protocols on Plasma Beta-Endorphin Concentrations

    DTIC Science & Technology

    1993-01-01

    exercise increases in muscular hypertrophy (27). Thus each exer- protocols used previously. Each subject gave informed cise series provides for...ANTE. P. D., AND M. E. HOUSTON. Effects of concentric and DUDLEY. C. M. MARESH, L. MARCHIrELLI, C. CRUTHIRDS, T. eccentric exercise on protein catabolism...DTIC Effects of different heavy-resistance exercise ELECTE protocols on plasma #-endorphin concentrations MAR 3 0 1993 C WILLIAM J. KRAEMER, JOSEPH E

  4. The effect of assembly and transit stressors on plasma fibrinogen concentration of beef calves.

    PubMed Central

    Phillips, W A

    1984-01-01

    Plasma fibrinogen concentration was measured in beef calves at various points within the system presently used to assemble, market and transport calves from one production point to another in order to determine the effect of the stresses encountered. A short haul of 160 km immediately after weaning did not significantly elevate fibrinogen concentration above the pretransit values. Yearling steers transported 400 km and confined in unfamiliar surroundings for 15 h did have an elevated (P less than 0.01) concentration of fibrinogen, but this increase was not significantly different from that of steers which were confined but not transported, thus confinement may be a significant portion of the stress associated with transit. The change in plasma fibrinogen concentration during assembly and transit was dependent upon the farm from which the calves originated. The magnitude of the change in fibrinogen concentration as a result of assembly and transit varied between the years studied. In one year pretransit assembly for ten days resulted in a higher fibrinogen concentration before and after transit than assembly for four days, but no difference was noted between the two groups in the second year. Bovine plasma fibrinogen concentration does increase in response to the stresses associated with assembly and transit. The stress of fasting and housing in unfamiliar surroundings also increase bovine plasma fibrinogen concentration and are present in the assembly and transit system. These two stresses may account for a majority of the stress associated with marketing and transit. The response of beef calves to the marketing and transit system varied between years. PMID:6713254

  5. 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.

  6. 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

  7. Effect of nicotine on in vitro maturation of bovine oocytes.

    PubMed

    Liu, Ying; Li, Guang-Peng; Rickords, Lee F; White, Kenneth L; Sessions, Benjamin R; Aston, Kenneth I; Bunch, Thomas D

    2008-01-15

    The putative effect of nicotine on maturation and the chromosomal complement of bovine oocytes were investigated in the present study. Cumulus-enclosed oocytes were incubated in maturation medium with 0, 0.5, 1.0, 2.5, 5.0, and 10.0 mmol concentrations of nicotine. The results indicated that: (1) nicotine affected cumulus cell expansion in a dose-dependent manner and the perivitelline space failed to form when concentrations were equal to or greater than 5.0 mmol; (2) oocytes treated with 0.5 and 1.0 mmol nicotine concentrations resulted in maturation rates (83.3% and 85.9%, respectively) which was similar to the control (86.2%), whereas treatment with 2.5 and 5.0 mmol concentrations significantly decreased maturation rates to 70.2% and 26.7%, respectively; (3) nicotine at or over 2.5 mmol caused extremely irregular meiotic spindles and interrupted microfilament organization; (4) chromosomal analyses of oocytes with PB1 showed that oocytes derived from 0.5 and 1.0 mmol nicotine groups had haploid complements similar to the control (87-90%), but when the concentrations were increased to 2.5 and 5.0 mmol the haploid state was significantly reduced to around 70%; (5) oocytes at GVBD (germinal vesicle breakdown) and metaphase I stages were less affected by nicotine at 5.0 and 10.0 mmol concentrations than GV-stage oocytes; (6) maturation rates of the short-term nicotine-treated oocytes could be improved when subsequently incubated in normal maturation medium. Prolonged culture of nicotine-pretreated oocytes resulted in self-activation and some oocytes formed 1 or 2 pronuclei. In conclusion, nicotine affects bovine oocyte cumulus cell expansion, maturation rate, and chromosomal complement in a dose-dependent and an oocyte-stage-dependent manner.

  8. The Effect of Central Injection of Ghrelin and Bombesin on Mean Plasma Thyroid Hormones Concentration

    PubMed Central

    Mahmoudi, Fariba; Mohsennezhad, Fatemeh; Khazali, Homayoun; Ehtesham, Haleh

    2011-01-01

    Ghrelin increases food intakes and body weight. Bombesin decreases food intakes and inhibits the stimulatory effect of Ghrelin on food intakes. Thyroid hormones have a crucial role in the regulation of body weight and yet the effect of bombesin on thyroid axis activity is not fully clear. Therefore, the goal of this study was to determine the effect of different doses of Ghrelin or bombesin on mean plasma thyroid-stimulating hormone (TSH), Triiodothyronine (T3) and Thyroxin (T4) concentration and also, the effect of interaction between Ghrelin and bombesin on thyroid axis activity. Forty-nine rats in seven groups received saline or different doses of Ghrelin (4, 10 or 15 nmol) and bombesin ( 2.5, 5 or 10 nmol) and forty-two rats in six groups received simultaneous injection of Ghrelin (10 or 15 nmol) and different doses of bombesin (2.5, 5 or 10 nmol) via lateral cerebral ventricle. Blood samples were collected via decapitation 20 min after the injection and plasma was assayed for plasma TSH, T3 and T4 concentration by Radioimmunoassay (RIA). Ghrelin significantly decreased the concentration of mean plasma thyroid hormones compared to saline. Bombesin did not significantly increase thyroid hormones concentration compared to saline but bombesin blocked the inhibitory effect of Ghrelin on thyroid axis activity. Bombesin may be the antagonist of Ghrelin action. PMID:24250396

  9. Phenylbutyrate reduces plasma leucine concentrations without affecting the flux of leucine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phenylbutyrate (PB) has been used as an alternative pathway to excrete nitrogen in urea cycle disorder patients for the last 20 years. PB, after oxidation to phenylacetate, is conjugated with glutamine and excreted in the urine. A reduction in the plasma concentration of branched amino acids (BCAA) ...

  10. Changes in plasma amino acid concentrations with increasing age in patients with propionic acidemia.

    PubMed

    Scholl-Bürgi, Sabine; Sass, Jörn Oliver; Heinz-Erian, Peter; Amann, Edda; Haberlandt, Edda; Albrecht, Ursula; Ertl, Claudia; Sigl, Sara Baumgartner; Lagler, Florian; Rostasy, Kevin; Karall, Daniela

    2010-05-01

    The objective of the study is to analyze plasma amino acid concentrations in propionic acidemia (PA) for the purpose of elucidating possible correlations between propionyl-CoA carboxylase deficiency and distinct amino acid behavior. Plasma concentrations of 19 amino acids were measured in 240 random samples from 11 patients (6 families) with enzymatically and/or genetically proven propionic acidemia (sampling period, January 2001-December 2007). They were compared with reference values from the literature and correlated with age using the Pearson correlation coefficient test. Decreased plasma concentrations were observed for glutamine, histidine, threonine, valine, isoleucine, leucine, phenylalanine and arginine. Levels of glycine, alanine and aspartate were elevated, while values of serine, asparagine, ornithine and glutamate were normal. For lysine, proline and methionine a clear association was not possible. Significant correlations with age were observed for 13 amino acids (positive correlation: asparagine, glutamine, proline, alanine, histidine, threonine, methionine, arginine; negative correlation: leucine, phenylalanine, ornithine, glutamate and aspartate). This study gives new insight over long-term changes in plasma amino acid concentrations and may provide options for future therapies (e.g., substitution of anaplerotic substances) in PA patients.

  11. Paracetamol interaction with oral contraceptive steroids: increased plasma concentrations of ethinyloestradiol.

    PubMed Central

    Rogers, S M; Back, D J; Stevenson, P J; Grimmer, S F; Orme, M L

    1987-01-01

    The effect of a single dose of paracetamol (1 g) on plasma concentrations of the oral contraceptive steroids ethinyloestradiol (EE2) and levonorgestrel (LNG) has been studied in six healthy female volunteers. The area under the plasma concentration-time curve (AUC0-24) of EE2 was significantly increased following paracetamol administration by 22% (control 2221 +/- 291; following paracetamol, 2702 +/- 452 pg ml-1 h; mean +/- s.d.; P less than or equal to 0.05). The greatest effect was evident in the time period 0-3 h. There was a significant decrease in the AUC of EE2-sulphate after paracetamol (7736 +/- 3791 pg ml-1 h) compared with control (13161 +/- 4535 pg ml-1 h; P less than or equal to 0.05). Plasma concentrations of LNG were unaltered by concurrent paracetamol administration. We conclude that the administration of a single 1 g dose of paracetamol causes an increase in plasma concentrations of EE2 as a result of a reduction in the sulphation of the steroid. This interaction may be of clinical significance in women on oral contraceptive steroids who regularly take paracetamol. PMID:3111513

  12. Diurnal variations in the plasma concentrations of mevalonic acid in patients with abetalipoproteinaemia.

    PubMed

    Pappu, A S; Illingworth, D R

    1994-10-01

    Previous studies have demonstrated that changes in the rates of cholesterol biosynthesis can be evaluated by the determination of plasma concentrations of sterol intermediates, including mevalonic acid and lathosterol and that, in normal human subjects, a diurnal rhythm exists in which the highest concentrations of sterol intermediates are observed at night. The factors responsible for this diurnal rhythm in cholesterol synthesis are, however, unknown. To test the hypothesis that the nocturnal increase in cholesterol biosynthesis is attributable to a reduced rate of hepatic uptake of chylomicron remnants at night as compared to higher rates of uptake during the daytime in response to alimentary lipaemia, we have examined the diurnal rhythm of mevalonic acid in six normal volunteers and three patients with phenotypic abetalipoproteinaemia. The latter patients do not absorb appreciable amounts of dietary cholesterol and are unable to synthesize chylomicron particles. Plasma concentrations of mevalonic acid exhibited a diurnal rhythm in the normal subjects, and the highest plasma concentrations were observed between 24.00 hours/04.00 hours. A similar rhythm was observed in the plasma of patients with abetalipoproteinaemia. These results suggest that the nocturnal increase in cholesterol biosynthesis which occurs in humans is not attributable to reduced hepatic uptake of chylomicron remnants at night; further studies are needed to better define those factors which influence the periodicity of cholesterol biosynthesis in humans.

  13. Ethanol vapor above skin: determination by a gas sensor instrument and relationship with plasma concentration.

    PubMed

    Giles, H G; Meggiorini, S; Renaud, G E; Thiessen, J J; Vidins, E I; Compton, K V; Saldivia, V; Orrego, H; Israel, Y

    1987-06-01

    Studies with a new instrument show that blood ethanol concentrations in rats and humans can be estimated by measurement of ethanol vapor above the skin. After intravenous bolus administration of ethanol (1 g/kg) to rats a novel device based on the Figaro sensor was placed above the animal's abdomen. Plasma and skin vapor ethanol concentrations, analyzed by gas chromatography and sensor, respectively, declined in parallel (r = 0.96). In healthy human subjects, plasma and skin vapor concentrations, measured on the palm, also declined in parallel after intravenous ethanol infusion (1 hr, 0.5 g/kg), r = 0.99. In 10 alcoholic liver disease outpatients attending clinic in whom plasma ethanol concentrations ranged from 32-304 mg/dl, the correlation of plasma ethanol determined directly by gas chromatography and indirectly by skin vapor analysis was slope = 0.93, intercept = 1.8, r = 0.94. In controlled studies, skin vapor measurements are comparable with breathalyzer determinations; they may be performed in situations where breathalyzer measurements are inconvenient or where continuous monitoring is desirable.

  14. [Determination of cyclohexanone concentration in the plasma separator by gas chromatography].

    PubMed

    Huang, Min-Ju; Yan, Lin; He, Yan-Ying; Lin, Wei-Cong

    2009-09-01

    This essay is to determine the cyclohexanone concentration of the plasma separator. The compound was introduced into the GC analytical system by the carrier gas. The determination was performed by the measurement of their peak area and by the external standard method.

  15. Coal pyrolysis to acetylene using dc hydrogen plasma torch: effects of system variables on acetylene concentration

    NASA Astrophysics Data System (ADS)

    Chen, Longwei; Meng, Yuedong; Shen, Jie; Shu, Xingsheng; Fang, Shidong; Xiong, Xinyang

    2009-03-01

    In order to unveil the inner mechanisms that determine acetylene concentration, experimental studies on the effect of several parameters such as plasma torch power, hydrogen flux and coal flux were carried out from coal pyrolysis in a dc plasma torch. Xinjiang long flame coals including volatile constituents at a level of about 42% were used in the experiment. Under the following experimental conditions, namely plasma torch power, hydrogen flow rate and pulverized coal feed speed of 2.12 MW, 32 kg h-1 and 900 kg h-1, respectively, acetylene volume concentration of about 9.4% was achieved. The experimental results indicate that parameters such as plasma torch power and coal flux play important roles in the formation of acetylene. Acetylene concentration increases inconspicuously with hydrogen flux. A chemical thermodynamic equilibrium model using the free energy method is introduced in this paper to numerically simulate each experimental condition. The numerical results are qualitatively consistent with the experimental results. Two parameters, i.e. the gas temperature and the ratio of hydrogen/carbon, are considered to be the dominant and independent factors that determine acetylene concentration.

  16. 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.

  17. Zinc and iron concentration and SOD activity in human semen and seminal plasma.

    PubMed

    Marzec-Wróblewska, Urszula; Kamiński, Piotr; Lakota, Paweł; Szymański, Marek; Wasilow, Karolina; Ludwikowski, Grzegorz; Kuligowska-Prusińska, Magdalena; Odrowąż-Sypniewska, Grażyna; Stuczyński, Tomasz; Michałkiewicz, Jacek

    2011-10-01

    The aim of the present study was to measure zinc (Zn) and iron (Fe) concentration in human semen and superoxide dismutase (SOD) activity in seminal plasma and correlate the results with sperm quality. Semen samples were obtained from men (N = 168) undergoing routine infertility evaluation. The study design included two groups based on the ejaculate parameters. Group I (n = 39) consisted of males with normal ejaculate (normozoospermia), and group II (n = 129) consisted of males with pathological spermiogram. Seminal Zn and Fe were measured in 162 samples (group I, n = 38; group II, n = 124) and SOD activity in 149 samples (group I, n = 37; group II, n = 112). Correlations were found between SOD activity and Fe and Zn concentration, and between Fe and Zn concentration. SOD activity was negatively associated with volume of semen and positively associated with rapid progressive motility, nonprogressive motility, and concentration. Negative correlation was stated between Fe concentration and normal morphology. Mean SOD activity in seminal plasma of semen from men of group I was higher than in seminal plasma of semen from men of group II. Fe concentration was higher in teratozoospermic males than in males with normal morphology of spermatozoa in group II. Our results suggest that Fe may influence spermatozoa morphology.

  18. 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

    2016-10-06

    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.

  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. Nicotine administration in adolescence reprograms the subsequent response to nicotine treatment and withdrawal in adulthood: sex-selective effects on cerebrocortical serotonergic function.

    PubMed

    Slotkin, Theodore A; Card, Jennifer; Seidler, Frederic J

    2014-03-01

    Nicotine exposure in adolescence produces lasting changes in subsequent behavioral responses to addictive agents. We gave nicotine to adolescent rats (postnatal days PN30-47), simulating plasma levels in smokers, and then examined the subsequent effects of nicotine given again in adulthood (PN90-107), focusing on cerebrocortical serotonin levels and utilization (turnover) as an index of presynaptic activity of circuits involved in emotional state. Our evaluations encompassed responses during the period of adult nicotine treatment (PN105) and withdrawal (PN110, PN120, PN130), as well as long-term changes (PN180). In males, prior exposure to nicotine in adolescence greatly augmented the increase in serotonin turnover evoked by nicotine given in adulthood, an interaction that was further exacerbated during withdrawal. The effect was sufficiently large that it led to significant depletion of serotonin stores, an effect that was not seen with nicotine given alone in either adolescence or adulthood. In females, adolescent nicotine exposure blunted or delayed the spike in serotonin turnover evoked by withdrawal from adult nicotine treatment, a totally different effect from the interaction seen in males. Combined with earlier work showing persistent dysregulation of serotonin receptor expression and receptor coupling, the present results indicate that adolescent nicotine exposure reprograms future responses of 5HT systems to nicotine, changes that may contribute to life-long vulnerability to relapse and re-addiction.

  1. Low plasma selenium concentration is associated with elevated risk to neoplastic polyps of the colon

    SciTech Connect

    Clark, L.C.; Hixson, L.G.; Sampliner, R.E. ); Combs, G.F. Jr. )

    1991-03-11

    A cross-sectional study was conducted to examine the relationship of selenium (Se) status and polyps incidence in a sequential series of 100 patients undergoing outpatient colonoscopies at the Tucson VA Hospital. Se was measured in plasma samples by electrothermal atomic absorption spectrophotometry with Zeeman background correction using a reduced palladium matrix modified. The activities of the Se-dependent enzyme glutathione peroxidase (SeGSHpx) were measured using H{sub 2}O{sub 2} as substrate in all plasma samples and in colonic mucosal biopsies obtained from some patients. The mean plasma Se concentration of patients without polyps was 134 ng/ml. Mean plasma Se levels of patients with only diminutive or large polyps were 127 ng/ml and 125 ng/ml; while patients with polyps of both sizes had a mean plasma Se level of 121 ng/ml. Patients with no reported history of cancer, neoplastic polyps or prior colonoscopy, showed an inverse association of plasma Se level and risk of benign colonic neoplasms. The age-adjusted odds ratio for neoplastic polyps was 3.8 for patients with plasma Se levels below vs. above the median value. This association was stronger for patients under 68 yrs of age than for older patients. Activities of SeGSHpx in plasma or colonic mucosa were not related to plasma Se level; however, smokers showed greater SeGSHpx activities than non-smokers. This study is the first to detect an association of Se status and risk to neoplastic polyps of the colon.

  2. 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.

  3. Validation of a GC-FID method for rapid quantification of nicotine in fermented extracts prepared from Nicotiana tabacum fresh leaves and studies of nicotine metabolites.

    PubMed

    Millet, Agnès; Stintzing, Florian; Merfort, Irmgard

    2009-07-12

    A new GC-FID method, which allows rapid and reliable quantitation of nicotine in tobacco leaf extracts, was developed and validated. To avoid nicotine adsorption on the column, an amine-deactivated capillary column was used. The method developed was applied to study the degradation of nicotine in a fermented aqueous extract, and a loss of nearly 20% of nicotine over 12 months was observed. Careful inspection of GC-MS runs from concentrated samples of the same extract revealed the presence of nicotine metabolites such as nornicotine, anatabine, myosmine, 2,3'-bipyridyl, and 2-pyrrolidinone.

  4. Nicotine exposure and decontamination on tobacco harvesters' hands.

    PubMed

    Curwin, Brian D; Hein, Misty J; Sanderson, Wayne T; Nishioka, Marcia G; Buhler, Wayne

    2005-07-01

    Green tobacco sickness is an illness associated with nicotine exposures among tobacco harvesters. Agricultural workers manually harvest tobacco and thus have the potential for skin exposure to nicotine, particularly on the hands. Often gloves are not worn as it hinders the harvesters' ability to harvest the tobacco leaves. The purposes of this study were to measure the concentration of nicotine residue on the hands of tobacco harvesters and the effectiveness of hand washing at removing the residue. Wipe samples from the hands of 12 tobacco harvesters were collected at the end of morning and afternoon work periods over two consecutive days. Each harvester had one hand wiped before washing his hands, and the other hand wiped after washing his hands with soap and water. Eight samples per worker were collected over the two days for a total of 96 samples collected. In addition to the hand-wipe samples, leaf-wipe samples were collected from 15 tobacco plants to estimate the amount of nicotine residue on the plants. The average nicotine level in leaf-wipe samples was 1.0 microg cm(-2). The geometric mean pre-wash and post-wash nicotine levels on the hands were 10 and 0.38 microg cm(-2), respectively. Nicotine leaf-wipe level, right or left hand and time of sampling did not significantly influence exposure. Job position-working on the bottom versus the top of the tobacco harvesting machine-was associated with nicotine levels. Pre-wash nicotine levels were higher for workers on the bottom of the harvester but not significantly higher (P = 0.17). Post-wash nicotine levels were significantly higher for workers on the bottom of the harvester (P = 0.012). A substantial amount of nicotine was transferred to the hands, but washing with soap and water in the field significantly reduced nicotine levels by an average of 96% (P < 0.0001).

  5. Cellular basis for the olfactory response to nicotine.

    PubMed

    Bryant, Bruce; Xu, Jiang; Audige, Valery; Lischka, Fritz W; Rawson, Nancy E

    2010-03-17

    Smokers regulate their smoking behavior on the basis of sensory stimuli independently of the pharmacological effects of nicotine (Rose J. E., et al. (1993) Pharmacol., Biochem. Behav.44 (4), 891-900). A better understanding of sensory mechanisms underlying smoking behavior may help to develop more effective smoking alternatives. Olfactory stimulation by nicotine makes up a considerable part of the flavor of tobacco smoke, yet our understanding of the cellular mechanisms responsible for olfactory detection of nicotine remains incomplete. We used biophysical methods to characterize the nicotine sensitivity and response mechanisms of neurons from olfactory epithelium. In view of substantial differences in the olfactory receptor repertoire between rodent and human (Mombaerts P. (1999) Annu. Rev. Neurosci.22, 487-509), we studied biopsied human olfactory sensory neurons (OSNs), cultured human olfactory cells (Gomez G., et al. (2000) J. Neurosci. Res.62 (5), 737-749), and rat olfactory neurons. Rat and human OSNs responded to S(-)-nicotine with a concentration dependent influx of calcium and activation of adenylate cyclase. Some rat OSNs displayed some stereoselectivity, with neurons responding to either enantiomer alone or to both. Freshly biopsied and primary cultured human olfactory neurons were less stereoselective. Nicotinic cholinergic antagonists had no effect on the responses of rat or human OSNs to nicotine. Patch clamp recording of rat OSNs revealed a nicotine-activated, calcium-sensitive nonspecific cation channel. These results indicate that nicotine activates a canonical olfactory receptor pathway rather than nicotinic cholinergic receptors on OSNs. Further, because the nicotine-sensitive mechanisms of rodents appear generally similar to those of humans, this animal model is an appropriate one for studies of nicotine sensation.

  6. Cholesterol concentration in seminal plasma as a predictive tool for quality semen evaluation.

    PubMed

    Beer-Ljubić, B; Aladrović, J; Marenjak, T S; Laskaj, R; Majić-Balić, I; Milinković-Tur, S

    2009-11-01

    The aim of this study was to investigate the relationship between lipid composition of bovine serum and seminal plasma, seasonality, and semen quality. The experiment was carried out in two groups of Simmental breeding bulls: Group I (ages 2 to 4 yr) and Group II (ages 5 to 10 yr). Blood samples were collected from jugular vein, and bovine semen was sampled with an artificial vagina once per season. Serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triacylglycerols, nonesterified fatty acids (NEFAs), and lipoprotein electrophoretic patterns were determined. Seminal plasma concentrations of total cholesterol, HDL-C, and LDL-C were assayed. Serum concentration of triacylglycerols in young bulls was significantly higher in winter compared with that in autumn, whereas serum NEFA concentration was significantly higher in autumn compared with that in other seasons. Serum concentration of total cholesterol, LDL-C, and LDL lipoproteins in older bulls was significantly higher in winter than in spring. Seminal plasma concentration of total cholesterol in young bulls was significantly higher in spring compared with that in summer, whereas in older bulls it was significantly higher in winter compared with that in autumn samples. Sperm volume of both groups was significantly higher in summer compared with that in autumn and winter. Sperm motility in young bulls was lowest in summer and differed significantly from the values recorded in other seasons. The changes observed in seminal plasma cholesterol concentration were associated with extracellular lipid use and appeared to be applicable as a biochemical marker of sperm quality.

  7. The effect of carbohydrate ingestion on plasma interleukin-6, hepcidin and iron concentrations following prolonged exercise.

    PubMed

    Robson-Ansley, Paula; Walshe, Ian; Ward, Douglas

    2011-02-01

    The aim of our study was twofold, firstly to examine the relationship between plasma concentrations of IL-6, hepcidin and iron following prolonged exercise and secondly, to assess the effect of carbohydrate ingestion on circulating hepcidin concentration post-exercise. The study was a randomised double-blind cross-over design, with participants consuming either a carbohydrate (CHO) or an isovolumetric placebo drink throughout the trial. Nine healthy, trained males completed a treadmill run at 60% vVO(2max) for 120 min followed by a 5 km time trial. Plasma concentrations of both IL-6 and hepcidin significantly increased post-exercise following both trials (p<.05) and returned to baseline by 24 h post (p>.05). A positive correlation between hepcidin and IL-6 was demonstrated immediately following exercise during PLA while there was a trend for a moderate correlation during CHO (PLA trial rho=0.81, p<0.001; CHO trial rho=0.36, p=0.07). Plasma iron was unaffected immediately post-exercise but significantly reduced by 24 h post-exercise compared to baseline. CHO ingestion significantly reduced post-exercise IL-6 (p<.05) but this had no effect on plasma hepcidin or iron concentration. Our data demonstrate CHO supplementation does not alter the rapid hepcidin response associated with exercise and does not prevent a subsequent fall in plasma iron concentration. This finding adds further support to the theory that an exercise-induced, up-regulation of hepcidin activity is a mechanism causing iron deficiency in endurance athletes.

  8. High Variability of Plasma Drug Concentrations in Dual Protease Inhibitor Regimens

    PubMed Central

    Guiard-Schmid, Jean-Baptiste; Poirier, Jean-Marie; Meynard, Jean-Luc; Bonnard, Philippe; Gbadoe, Ayi Hola; Amiel, Corinne; Calligaris, Frédérique; Abraham, Bruno; Pialoux, Gilles; Girard, Pierre-Marie; Jaillon, Patrice; Rozenbaum, Willy

    2003-01-01

    Ritonavir (RTV) strongly increases the concentrations of protease inhibitors (PIs) in plasma in patients given a combination of RTV and another PI. This pharmacological interaction is complex and poorly characterized and shows marked inter- and intraindividual variations. In addition, RTV interacts differently with saquinavir (SQV), indinavir (IDV), amprenavir (APV), and lopinavir (LPV). In this retrospective study on 542 human immunodeficiency virus-infected patients, we compared inter- and intraindividual variability of plasma PI concentrations and correlations between the Cmin (minimum concentration of drug in plasma) values for RTV and the coadministered PI Cmin values. Mean RTV Cmins are significantly lower in patients receiving combinations containing APV or LPV than in combinations with SQV or IDV. With the most common PI dose regimens (600 mg of IDV twice a day [BID], 800 mg of SQV BID, and 400 mg of LPV BID), the interindividual Cmin variability of patients treated with a PI and RTV seemed to be lower with APV and LPV than with IDV and SQV. As regards intraindividual variability, APV also differed from the other PIs, exhibiting lower Cmin variability than with the other combinations. Significant positive correlations between RTV Cmin and boosted PI Cmin were observed with IDV, SQV, and LPV, but not with APV. Individual dose adjustments must take into account the specificity the pharmacological interaction of each RTV/PI combination and the large inter- and intraindividual variability of plasma PI levels to avoid suboptimal plasma drug concentrations which may lead to treatment failure and too high concentrations which may induce toxicity and therefore reduce patient compliance. PMID:12604531

  9. 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.

  10. Concentrations of triiodothyronine, growth hormone, and luteinizing hormone in the plasma of thyroidectomised fowl (Gallus domesticus).

    PubMed

    Harvey, S; Sterling, R J; Klandorf, H

    1983-05-01

    Surgical thyroidectomy increased (P less than 0.05) the basal concentrations of growth hormone (GH) and luteinizing hormone (LH) in the plasma of 10- to 12-week-old domestic fowl. The administration of thyrotrophin releasing hormone (TRH) (100 micrograms, sc) increased (P less than 0.01) the GH concentration in both intact and thyroidectomised birds. The magnitude of the TRH-induced increase in GH level was greater (P less than 0.01) in thyroidectomised birds than in intact controls. Although TRH had no effect on LH secretion in the controls, it induced a small (P less than 0.05) rise in the plasma LH level in thyroidectomised birds. In both the intact and thyroidectomised birds the LH concentration was enhanced (P less than 0.05) following the administration of LH-releasing hormone (LH-RH) (20 micrograms, sc). The increase in the LH level by LH-RH in the thyroidectomised birds was greater (P less than 0.001) than that in the intact controls. Plasma GH concentrations were unaffected by LH-RH treatment. These results suggest that thyroid hormones inhibit the secretion of LH and GH in birds. In thyroidectomised birds low levels of immunoreactive triiodothyronine (T3)-like material were measurable in the circulation, despite the absence of regenerated thyroid tissue. The administration of TRH (100 micrograms, sc) did not enhance the plasma level of this material in thyroidectomised birds, whereas plasma T3 concentrations were enhanced in intact birds following TRH treatment. These results suggest that the T3 immunoreactive substance in thyroidectomised birds is extrathyroidal in origin.

  11. Effect of nicotine on cariogenic virulence of Streptococcus mutans.

    PubMed

    Li, Mingyun; Huang, Ruijie; Zhou, Xuedong; Qiu, Wei; Xu, Xin; Gregory, Richard L

    2016-11-01

    Nicotine has well-documented effects on the growth and colonization of Streptococcus mutans. This study attempts to investigate the effects of nicotine on pathogenic factors of S. mutans, such as the effect on biofilm formation and viability, expression of pathogenic genes, and metabolites of S. mutans. The results demonstrated that addition of nicotine did not significantly influence the viability of S. mutans cells. The biofilms became increasingly compact as the concentrations of nicotine increased. The expression of virulence genes, such as ldh and phosphotransferase system (PTS)-associated genes, was upregulated, and nlmC was upregulated significantly, while ftf was downregulated. The lactate concentration of S. mutans grown in 1 mg/mL of nicotine was increased up to twofold over either biofilm or planktonic cells grown without nicotine. Changes in the metabolites involved in central carbon metabolism from sucrose indicated that most selected metabolites were detectable and influenced by increased concentrations of nicotine. This study demonstrated that nicotine can influence the pathogenicity of S. mutans and may lead to increased dental caries through the production of more lactate and the upregulation of virulence genes.

  12. Dimethylsulfoxide-soluble smoking particles and nicotine affect vascular contractibility.

    PubMed

    Zhang, Jin-Yan; Cao, Lei; Zheng, Xiao-Hui; Xu, Cang-Bao; Cao, Yong-Xiao

    2009-10-01

    The aim is to study the effect of dimethylsulfoxide-soluble smoking particles (DSP) and nicotine on the contractility of rat mesenteric artery. The superior mesenteric artery segments were cultured with DSP or nicotine for 24 h. The vascular contractibility was recorded with myograph system. DSP 0.4 mL/L and nicotine 0.48 and 0.96 mg/L shifted the concentration-contractile curves induced by sarafotoxin 6c, a selective agonist for ET(B) receptor toward the left with increased E(max). DSP 0.4 mL/L and nicotine 0.96 mg/L shifted ET(A) receptor-mediated the concentration-contractile curves toward the left with increased E(max). However, nicotine 0.06 mg/L which is the equivalent concentration of nicotine in DSP 0.4 mL/L did not affect the curves and the E(max) mediated with ET(A) receptor and ET(B) receptor. DSP 0.2 and 0.4 mL/L shifted the concentration-contractile curves induced by noradrenaline toward the right with decreased E(max). Neither did nicotine 0.06 and 0.96 mg/L. Both DSP and nicotine shifted the concentration-contractile curves induced by 5-hydroxytryptamine (5-HT) toward the right parallely. DSP changed the phenotypes towards an increased efficacy of ET(A) receptor and ET(B) receptor, and a reduced efficacy of 5-HT receptor and alpha-adrenocceptor. The effects of DSP on ET(B) receptor, ET(A) receptor and alpha-adrenocceptor were independent of nicotine. The effect on 5-HT receptor was responsible to nicotine.

  13. Prenatal nicotine exposure alters the responses to subsequent nicotine administration and withdrawal in adolescence: Serotonin receptors and cell signaling.

    PubMed

    Slotkin, Theodore A; Tate, Charlotte A; Cousins, Mandy M; Seidler, Frederic J

    2006-11-01

    Offspring of women who smoke during pregnancy are themselves more likely to take up smoking in adolescence, effects that are associated with a high rate of depression and increased sensitivity to withdrawal symptoms. To evaluate the biological basis for this relationship, we assessed effects on serotonin (5-hydroxytryptamine, 5HT) receptors and 5HT-mediated cellular responses in rats exposed to nicotine throughout prenatal development and then given nicotine in adolescence (postnatal days PN30-47.5), using regimens that reproduce plasma nicotine levels found in smokers. Evaluations were then made during the period of adolescent nicotine treatment and for up to one month after the end of treatment. Prenatal nicotine exposure, which elicits damage to 5HT projections in the cerebral cortex and striatum, produced sex-selective changes in the expression of 5HT(1A) and 5HT2 receptors, along with induction of adenylyl cyclase (AC), leading to sensitization of heterologous inputs operating through this signaling pathway. Superimposed on these effects, the AC response to 5HT was shifted toward inhibition. By itself, adolescent nicotine administration, which damages the same pathways, produced similar effects on receptors and the 5HT-mediated response, but a smaller overall induction of AC. Animals exposed to prenatal nicotine showed a reduced response to nicotine administered in adolescence, results in keeping with earlier findings of persistent desensitization. Our results indicate that prenatal nicotine exposure alters parameters of 5HT synaptic communication lasting into adolescence and changes the response to nicotine administration and withdrawal in adolescence, actions which may contribute to a subpopulation especially vulnerable to nicotine dependence.

  14. Plasma BDNF concentration, Val66Met genetic variant and depression-related personality traits.

    PubMed

    Terracciano, A; Martin, B; Ansari, D; Tanaka, T; Ferrucci, L; Maudsley, S; Mattson, M P; Costa, P T

    2010-07-01

    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.

  15. [The ultrafiltration at pre-analytical stage under detection of concentration of lactic acid in blood plasma].

    PubMed

    Alekseevskaia, E S; Zhloba, A A; Subbotina, T F

    2013-11-01

    The detection of concentration of lactic acid in blood plasma and other objects is especially applied to discover the mitochondria dysfunctions. The study was organized to analyze samplings of blood plasma and plasma ultra-filtrates taken from 80 healthy persons and 73 patients with activation of intravascular coagulation and fibrinolysis using lactate-oxidase test. The comparative analysis of results of detection of concentrations of lactic acid in blood plasma and its ultra-filtrate established that in 72% of cases the higher values of concentration of detecting lactic acid took place after procedure of ultra-filtration enabling separation of overwhelming quantity of protein. In accordance with accumulated experience in the field of clinical diagnostic practice the enzyme tests are to be applied to detect the concentration of lactic acid in blood plasma and other objects. The present study demonstrated the expediency of application of plasma ultra-filtrate to detect the concentration of lactic acid.

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

    PubMed

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

    2014-10-01

    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 EC50 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.

  17. Seasonal variation in plasma sex steroid concentrations in juvenile American alligators.

    PubMed

    Rooney, Andrew A; Crain, D Andrew; Woodward, Allan R; Guillette, Louis J

    2004-01-01

    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 a limited comparison of these seasonal patterns on two different lakes in Florida. Male juvenile alligators from a reference lake, Lake Woodruff, displayed temporal patterns in plasma testosterone (T) concentrations that appear to be seasonal. A similar pattern in plasma estradiol-17beta (E(2)) was observed in juvenile females from Lake Woodruff. Males had significantly elevated T concentrations during the spring and late summer, whereas females had elevated E(2) in the spring and late summer and significantly depressed E(2) concentrations during the winter. A limited 4-month survey of animals from contaminated Lake Apopka found a lack of such seasonality. These results suggest that: (1) healthy wild populations of juvenile alligators have a prolonged peripubescent period that is marked by seasonal hormonal cycles, (2) juvenile alligators exposed to environmental contaminants can lack such seasonal cyclicity, and (3) future studies of juvenile alligators should incorporate such seasonality into the experimental design.

  18. 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

  19. Targeting glutamate homeostasis for potential treatment of nicotine dependence

    PubMed Central

    Alasmari, Fawaz; Al-Rejaie, Salim S.; AlSharari, Shakir D.; Sari, Youssef

    2015-01-01

    Several studies demonstrated that impairment in glutamatergic neurotransmission is linked to drug dependence and drug-seeking behavior. Increased extracellular glutamate concentration in mesocorticolimbic regions has been observed in animals developing nicotine dependence. Changes in glutamate release might be associated with stimulatory effect of nicotinic acetylcholine receptors (nAChRs) via nicotine exposure. We and others have shown increased extracellular glutamate concentration, which was associated with downregulation of the major glutamate transporter, glutamate transporter 1 (GLT-1), in brain reward regions of animals exposed to drug abuse, including nicotine and ethanol. Importantly, studies from our laboratory and others showed that upregulation of GLT-1 expression in the mesocorticolimbic brain regions may have potential therapeutic effects in drug dependence. In this review article, we discussed the effect of antagonizing presynaptic nAChRs in glutamate release, the upregulatory effect in GLT-1 expression and the role of glutamate receptors antagonists in the treatment of nicotine dependence. PMID:26589642

  20. Anti-tumor Effects of Plasma Activated Media and Correlation with Hydrogen Peroxide Concentration

    NASA Astrophysics Data System (ADS)

    Laroussi, Mounir; Mohades, Soheila; Barekzi, Nazir; Maruthamuthu, Venkat; Razavi, Hamid

    2016-09-01

    Plasma activated media (PAM) can induce death in cancer cells. In our research, PAM is produced by exposing liquid culture medium to a helium plasma pencil. Reactive oxygen and nitrogen species in the aqueous state are known factors in anti-tumor effects of PAM. The duration of plasma exposure determines the concentrations of reactive species produced in PAM. Stability of the plasma generated reactive species and their lifetime depend on parameters such as the chemical composition of the medium. Here, a complete cell culture medium was employed to make PAM. Later, PAM was used to treat SCaBER cancer cells either as an immediate PAM (right after exposure) or as an aged-PAM (after storage). SCaBER (ATCC®HTB-3™) is an epithelial cell line from a human bladder with the squamous carcinoma disease. A normal epithelial cell line from a kidney tissue of a dog - MDCK (ATCC®CCL-34™) - was used to analyze the selective effect of PAM. Correspondingly, we measured the concentration of hydrogen peroxide- as a stable species with biological impact on cell viability- in both immediate PAM and aged-PAM. In addition, we report on the effect of serum supplemented in PAM on the H2O2 concentration measured by Amplex red assay kit. Finally, we evaluate the effects of PAM on growth and morphological changes in MDCK cells using fluorescence microscopy.

  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. 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

  3. 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.

  4. Effects of methoxsalen, a CYP2A5/6 inhibitor, on nicotine dependence behaviors in mice

    PubMed Central

    Bagdas, Deniz; Muldoon, Pretal P.; Zhu, Andy Z.X.; Tyndale, Rachel F.; Damaj, M. Imad

    2014-01-01

    Metabolism of nicotine to inactive cotinine by hepatic enzyme CYP2A6 is the principal pathway by which active nicotine is removed from circulation. We therefore hypothesized that inhibition of mouse CYP2A5, the orthologue of human CYP2A6, by methoxsalen (8-methoxypsoralen) should block nicotine metabolism and decrease its subsequent systemic clearance. Consequently, methoxsalen will alter dependence-related behaviors of nicotine in the mouse. In the first part of the study, a conditioned place preference (CPP) test was used in animals to explore the appetitive reward-like properties of nicotine. In the second part of the study, mice chronically exposed to nicotine were challenged with mecamylamine, a nicotinic antagonist, and tested for physical (somatic and hyperalgesia) and affective (anxiety-related behaviors) precipitated withdrawal signs. The nicotine plasma levels were also measured with or without methoxsalen pretreatment. Methoxsalen (15 and 30 mg/kg, intraperitoneally) pretreatment 15 min before nicotine (0.1 mg/kg, subcutaneously) induced a significant enhancement of nicotine-induced preference in mice (p<0.05). This potentiation was significantly accompanied by an increase in nicotine plasma levels (p<0.05). However, there was a lack of enhancement of nicotine in the CPP test after the highest dose of the CYP-2A5 inhibitor. Similarly to the CPP results, repeated administration of methoxsalen with nicotine increased the intensity of mecamylamine-precipitated withdrawal signs on test day. The potentiation of withdrawal intensity by methoxsalen was accompanied by significant increase in nicotine plasma levels in these mice (p<0.05). Finally, methoxsalen enhanced the ability of nicotine to reverse withdrawal signs in mice undergoing spontaneous withdrawal after chronic nicotine infusion. Spontaneous withdrawal from chronic nicotine administration (36 mg/kg/day in minipumps for 7 days) significantly increased the number of somatic signs and induced

  5. Upregulation of surface alpha4beta2 nicotinic receptors is initiated by receptor desensitization after chronic exposure to nicotine.

    PubMed

    Fenster, C P; Whitworth, T L; Sheffield, E B; Quick, M W; Lester, R A

    1999-06-15

    It is hypothesized that desensitization of neuronal nicotinic acetylcholine receptors (nAChRs) induced by chronic exposure to nicotine initiates upregulation of nAChR number. To test this hypothesis directly, oocytes expressing alpha4beta2 receptors were chronically incubated (24-48 hr) in nicotine, and the resulting changes in specific [3H]nicotine binding to surface receptors on intact oocytes were compared with functional receptor desensitization. Four lines of evidence strongly support the hypothesis. (1) The half-maximal nicotine concentration necessary to produce desensitization (9.7 nM) was the same as that needed to induce upregulation (9.9 nM). (2) The concentration of [3H]nicotine for half-maximal binding to surface nAChRs on intact oocytes was also similar (11.1 nM), as predicted from cyclical desensitization models. (3) Functional desensitization of alpha3beta4 receptors required 10-fold higher nicotine concentrations, and this was mirrored by a 10-fold shift in concentrations necessary for upregulation. (4) Mutant alpha4beta2 receptors that do not recover fully from desensitization, but not wild-type channels, were upregulated after acute (1 hr) applications of nicotine. Interestingly, the nicotine concentration required for half-maximal binding of alpha4beta2 receptors in total cell membrane homogenates was 20-fold lower than that measured for surface nAChRs in intact oocytes. These data suggest that cell homogenate binding assays may not accurately reflect the in vivo desensitization affinity of surface nAChRs and may account for some of the previously reported differences in the efficacy of nicotine for inducing nAChR desensitization and upregulation.

  6. 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.

  7. EXTENDED STORAGE OF BUFFY-COAT PLATELET CONCENTRATES IN PLASMA OR A PLATELET ADDITIVE SOLUTION

    PubMed Central

    Slichter, Sherrill J.; Bolgiano, Doug; Corson, Jill; Jones, Mary Kay; Christoffel, Todd; Bailey, S. Lawrence; Pellham, Esther

    2014-01-01

    Background Platelet concentrates prepared from whole blood in the U.S. are made using the platelet-rich-plasma (PRP) method. The platelet concentrates must be made within 8 hours of blood collection and stored for only 5 days. In Europe and Canada, platelet concentrates are made using the buffy-coat (BC) method from whole blood held overnight at 22°C and storage times may be up to 7 days. Our studies were designed to determine how long BC platelets can be stored in plasma or Plasmalyte while meeting the FDA’s post-storage viability criteria. Study Design, Materials, And Methods Normal subjects donated whole blood that was stored at 22°C for 22 ± 2 hours prior to preparation of BC platelets. Platelets were stored for 5 to 8 days in either plasma or Plasmalyte concentrations of 65% or 80%. Radiolabeled autologous stored versus fresh platelet recoveries and survivals were assessed as well as post-storage in vitro assays. Results BC platelets stored in either plasma or 65% Plasmalyte met FDA post-storage platelet recovery criteria for 7 days but survivals for only 6 days, while storage in 80% Plasmalyte gave very poor results. Both stored platelet recoveries and survivals correlated with the same donor’s fresh results, but the correlation was much stronger between recoveries than survivals. In vitro measures of extent of shape change, morphology score, and pH best predicted post-storage platelet recoveries, while annexin V binding best predicted platelet survivals. Conclusion BC platelets stored in either plasma or 65% Plasmalyte meet FDA’s post-storage viability criteria for 6 days. PMID:24673482

  8. Variation in Nicotine Consumption in Inbred Mice Is Not Linked to Orosensory Ability

    PubMed Central

    Glatt, A. Rebecca; Denton, Kelley

    2009-01-01

    Genetic studies of nicotine addiction in mice have utilized the oral self-administration model. However, it is unclear if strain differences in nicotine consumption are influenced by variation in bitter taste sensitivity. We measured both nicotine consumption and nicotine brief-access licking behavior in several commonly used inbred strains of mice that were previously shown to differ in nicotine consumption. A/J (A), C57BL/6J (B6), and DBA/2J (D2) mice were given a 2-bottle choice test with a single concentration of nicotine (75 μg/ml; nicotine vs. water). Mice of these strains were also tested with a range of nicotine concentrations (5–400 μg/ml) using a brief-access test, which measures orosensory response and minimizes postingestive effects. Although B6 mice consumed more 75-μg/ml nicotine than A or D2 mice in the 2-bottle test, these strains did not differ in level of aversion to nicotine when tested with the brief-access procedure. Strain differences in orosensory response to nicotine were not found; yet, differences emerged during the 2-bottle tests. This study provides evidence that variation in intake level of nicotine is likely not due to differences in taste or trigeminal sensitivity but likely due to postingestive factors. PMID:18775876

  9. 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.

  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

    2016-07-04

    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.

  11. AAV-directed persistent expression of a gene encoding anti-nicotine antibody for smoking cessation.

    PubMed

    Hicks, Martin J; Rosenberg, Jonathan B; De, Bishnu P; Pagovich, Odelya E; Young, Colin N; Qiu, Jian-ping; Kaminsky, Stephen M; Hackett, Neil R; Worgall, Stefan; Janda, Kim D; Davisson, Robin L; Crystal, Ronald G

    2012-06-27

    Current strategies to help tobacco smokers quit have limited success as a result of the addictive properties of the nicotine in cigarette smoke. We hypothesized that a single administration of an adeno-associated virus (AAV) gene transfer vector expressing high levels of an anti-nicotine antibody would persistently prevent nicotine from reaching its receptors in the brain. To test this hypothesis, we constructed an AAVrh.10 vector that expressed a full-length, high-affinity, anti-nicotine antibody derived from the Fab fragment of the anti-nicotine monoclonal antibody NIC9D9 (AAVantiNic). In mice treated with this vector, blood concentrations of the anti-nicotine antibody were dose-dependent, and the antibody showed high specificity and affinity for nicotine. The antibody shielded the brain from systemically administered nicotine, reducing brain nicotine concentrations to 15% of those in naïve mice. The amount of nicotine sequestered in the serum of vector-treated mice was more than seven times greater than that in untreated mice, with 83% of serum nicotine bound to immunoglobulin G. Treatment with the AAVantiNic vector blocked nicotine-mediated alterations in arterial blood pressure, heart rate, and locomotor activity. In summary, a single administration of a gene transfer vector expressing a high-affinity anti-nicotine monoclonal antibody elicited persistent (18 weeks), high titers of an anti-nicotine antibody that obviated the physiologic effects of nicotine. If this degree of efficacy translates to humans, AAVantiNic could be an effective preventative therapy for nicotine addiction.

  12. 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

  13. 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

  14. Plasma concentrations of progesterone and testosterone in captive woolly opossums (Caluromys philander).

    PubMed

    Perret, M; Atramentowicz, M

    1989-01-01

    Plasma testosterone and progesterone concentrations were measured in captive woolly opossums, a didelphid marsupial originating from neotropical forests in French Guyana. Although not exposed to cyclic environmental conditions as in the field, both sexes exhibited spontaneous circannual changes in sexual hormones. Males showed synchronous variations in plasma testosterone characterized by significant elevated concentrations during April and September (8.6 +/- 1 ng/ml, N = 5) and lower levels from May to July (3.6 +/- 0.4 ng/ml). In females, synchronous periods of 2-3 successive oestrous cycles occurred. Between these periods, females remained acyclic. The oestrous cycle, determined by urogenital smears, lasted 28-45 days (n = 14) and included a 20-day spontaneous luteal phase in which progesterone concentrations reached 30-40 ng/ml plasma. Even though testosterone concentrations in paired males increased significantly in response to oestrous periods of the paired females, spontaneous circannual rhythms of sexual activity were not well synchronized between the sexes in captivity. When compared to field data, sexual activity of captive animals followed a pattern similar to that in wild animals, without any changes in males but with a delay of 3 months in females.

  15. Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris.

    PubMed

    Pine, M; Favrot, L; Smith, S; McDonald, K; Chidsey, C A

    1975-11-01

    The therapeutic response to propranolol was evaluated in patients with documented coronary artery disease at doses varying from 40 to 320 mg/day. Therapeutic response was quantified by evaluating exercise performance on a treadmill and then related to plasma propranolol concentration. Plasma propranolol was defined in terms of beta-adrenergic blockade by comparison with dose (concentration) response curves in normal subjects. Individual therapeutic benefit occurred at doses which averaged 144 +/- 21 mg/day and at concentrations which averaged 30 +/- 7 ng/ml. There was a wide variation between both dose and concentration among the patients at maximum therapeutic response, but when the plasma propranolol was related to pharmacologic activity, the maximum therapeutic response was observed between 64 to 98% of total blockade. Despite the increased exercise performance in these patients, the double product of heart rate and systolic blood pressure was always less, suggesting either an alteration of the relation between myocardial oxygen consumption and the double product during propranolol or a reduction on oxygen delivery to the myocardium as the result of beta-adrenergic blockade of the coronary vasculature.

  16. Forearm mineral content in normal men: relationship to weight, height and plasma testosterone concentrations

    SciTech Connect

    McElduff, A.; Wilkinson, M.; Ward, P.; Posen, S.

    1988-01-01

    We measured forearm bone mineral content by single photon absorptiometry together with height, weight and the plasma concentrations of testosterone, free testosterone and sex steroid binding globulin in 66 normal Caucasian males aged 29-46 years. Multiple regression analysis suggests that bone mineral content in either the dominant or the nondominant arm is correlated with weight and sex steroid binding globulin (p less than 0.05 for both parameters). The partial negative correlation of bone mineral content (corrected for weight and sex steroid binding globulin) with plasma testosterone failed to reach statistical significance (p = 0.07). The parsimonious regression equation which best explained the bone mineral content measurements in the nondominant forearm in these men was bone mineral content = 29.1-0.374 (plasma testosterone) + 0.383 (weight) + 0.220 (sex steroid binding globulin) with an R2 value of 29.7%. A similar equation was generated for the dominant arm.

  17. Relationship between postabsorptive respiratory exchange ratio and plasma free fatty acid concentrations

    PubMed Central

    Jensen, Michael D.; Bajnárek, Jiří; Lee, Sang Yeoup; Nielsen, Soren; Koutsari, Christina

    2009-01-01

    The relationship between overnight postabsorptive (fasting) respiratory exchange ratio (RER) and plasma FFA concentrations was addressed using data from three separate protocols, each of which involved careful control of the antecedent diet. Protocol 1 examined the relationship between fasting RER and the previous daytime RER. In Protocol 2 fasting, RER and plasma palmitate concentrations were measured in 29 women and 31 men (body mass index <30 kg·m−2). Protocol 3 analyzed data from Nielsen et al. (Nielsen, S., Z. K. Guo, J. B. Albu, S. Klein, P. C. O'Brien, M. D. Jensen. 2003. Energy expenditure, sex and endogenous fuel availability in humans. J. Clin. Invest. 111: 981-988.) to understand how fasting RER and palmitate concentrations relate within individuals during four consecutive measurements. The results were as follows: 1) Fasting RER was correlated (r = 0.74, P < 0.001) with the previous day's average RER, and less so with RER variability. 2) Fasting RER was correlated (r = −0.39, P = 0.007) with fasting plasma palmitate concentrations. 3) The pattern of the RER/palmitate relationship was similar within individuals and between individuals; a negative slope was observed significantly more often than a positive slope (χ2 test; P < 0.001). Our findings suggest that, despite a fixed food quotient, the slight departures from energy equilibrium in a controlled General Clinical Research Center environment can effect plasma FFA concentrations. We suggest that including indirect calorimetry as part of FFA metabolism studies may aid in data interpretation. PMID:19383980

  18. Pharmacokinetics of methimazole in children and adolescents with Graves' disease. Studies on plasma and intrathyroidal concentrations.

    PubMed

    Okuno, A; Yano, K; Inyaku, F; Suzuki, Y; Sanae, N; Kumai, M; Naitoh, Y

    1987-05-01

    Methimazole concentrations in plasma and in the thyroid glands were measured by means of high-performance liquid chromatography. Pharmacokinetics of methimazole were studied after a single oral dose (175 mumol/m2) in nine children and adolescent who were in the thyrotoxic state. Plasma levels of methimazole showed peak concentrations of 4.4 to 12.6 (median 9.2) mumol/l at 0.5 to 4 h after drug administration. Plasma half-life, area under the curve, and distribution volume ranged from 2.73 to 6.04 h, 32.8 to 77.9 mumol X l-1 X h-1, and 0.516 to 0.913 l/kg, respectively. These pharmacokinetic parameters showed a wide variation among the patients, but were quite reproducible in the same subject. Intrathyroidal concentrations of methimazole were measured in another nine subjects including four adolescents and five adults who underwent thyroidectomy. The drug concentrations in the thyroid glands ranged between 3.5 and 23.8 mumol/kg tissue and were far higher than those in the plasma obtained at the time of surgery. In this series of experiments, the dose of the drug varied from 76 to 319 mumol/m2, time after the last dose to surgery from 5 to 24 h, and the mode of drug administration from a single to three divided doses. Among these variable factors, only the daily dose of methimazole corrected by body surface area showed significant correlation with the intrathyroidal concentration, whereas the time after the last dose of the drug and the mode of drug administration did not.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. 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

  20. 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.

  1. Programmable transdermal delivery of nicotine in hairless guinea pigs using carbon nanotube membrane pumps.

    PubMed

    Paudel, Kalpana S; Wu, Ji; Hinds, Bruce J; Stinchcomb, Audra L

    2012-10-01

    A compact switchable transdermal nicotine patch device was demonstrated to be effective in vivo in a hairless guinea pig animal model. This required the development and validation of a quantitative method for the simultaneous determination of cotinine and nicotine in hairless guinea pig plasma by liquid chromatography-mass spectrometry. Nicotine metabolism in hairless guinea pigs is rapid and cotinine was found to be the viable nicotine marker. The portable carbon nanotube membrane device, powered by a 1.5 V watch battery, was demonstrated to be a power efficient method to pump nicotine at levels six to eight times that of passive diffusion. Cotinine blood plasma levels in hairless guinea pigs were seen to increase from 6 to 12 ng/mL when the patch was turned from passive diffusion to an active pumping state. These nicotine patch devices are highly promising for potential clinical applications, with programmed delivery based on remote counseling, in order to improve smoking cessation treatments.

  2. 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.

  3. 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.

  4. Pyrilamine inhibits nicotine-induced catecholamine secretion.

    PubMed

    Kim, Dong-Chan; Yun, So Jeong; Park, Yong-Soo; Jun, Dong-Jae; Kim, Dongjin; Jiten Singh, N; Kim, Sanguk; Kim, Kyong-Tai

    2014-07-01

    Function of nicotine, which induces activation of all parts of the body including our brain, has been receiving much attention for a long period of time and also been actively studied by researchers for its pharmacological actions in the central nervous system. The modulation of nicotine concentration and the inhibition of nicotine binding on target receptors in the brain are the key factors for smoking addiction therapy. In previous studies showed that influx of nicotine at the blood-brain barrier was through the pyrilamine-sensitive organic cation transporters. But the direct interacting mechanism of pyrilamine on the nicotine binding target receptors has not yet been clarified. The aim of the present study is to investigate the direct binding mechanisms of a pyrilamine on the nicotinic acetylcholine receptors (nAChRs). We found that pyrilamine shares the same ligand binding pocket of nicotine (NCT) on nAChRs but interacts with more amino acid residues than NCT does. The extended part of pyrilamine interacts with additional residues in the ligand binding pocket of nAChRs which are located nearby the entrance of the binding pocket. The catecholamine (CA) secretion induced by nAChR agonist (NCT') was significantly inhibited by the pyrilamine pretreatment. Real time carbon-fiber amperometry confirmed the inhibition of the NCT'-induced exocytosis by pyrilamine in a single cell level. We also found that pyrilamine inhibited the NCT'-induced [Ca(2+)]i. In contrast, pyrilamine did not affect the increase in calcium induced by high K(+). Overall, these data suggest that pyrilamine directly docks into the ligand binding site of nAChRs and specifically inhibits the nAChR-mediated effects thereby causing inhibition of CA secretion. Therefore, pyrilamine may play an important role to explore new treatments to aid smoking cessation.

  5. Unchanged peripheral sympathetic activity following withdrawal of chronic metoprolol treatment. A study of noradrenaline concentrations and kinetics in plasma.

    PubMed Central

    Olsson, G; Daleskog, M; Hjemdahl, P; Rehnqvist, N

    1984-01-01

    Noradrenaline plasma kinetics were assessed in 17 male patients, who had been treated with metoprolol 100-200 mg daily (n = 8) or placebo for 3 years after an acute myocardial infarction, before and 1 week after gradual withdrawal (during 1 week) of the study treatment. Endogenous noradrenaline concentrations in plasma were measured by high performance liquid chromatography. Noradrenaline spillover rate, plasma clearance and the t1/2 for the rapid removal from plasma were determined by radio-tracer methodology. During treatment the plasma noradrenaline concentrations and noradrenaline plasma kinetic variables were similar in the two groups. Venous plasma noradrenaline concentrations were more closely correlated to the spillover rates of noradrenaline to plasma than to the clearance of noradrenaline from plasma, but the spillover rates were correlated to the clearance rates. Following the withdrawal of metoprolol noradrenaline clearance from plasma increased slightly (by 18 +/- 5%, P less than 0.05), but the plasma concentrations and spillover rates of noradrenaline were unchanged. In the placebo group withdrawal did not result in any significant changes. Our results indicate that a generalised increase in sympathetic nerve activity is not the cause of so-called rebound phenomena following withdrawal of chronic beta-adrenoceptor blockade. PMID:6487497

  6. 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.

  7. Vitamin C plasma concentrations and leg weakness in the forelegs of growing pigs.

    PubMed

    Armocida, A; Beskow, P; Amcoff, P; Kallner, A; Ekman, S

    2001-04-01

    Four litters (41 pigs) of cross-bred pigs were studied from 6 to 26 weeks of age. Blood samples were collected at 6, 13, 21 and 26 weeks of age and analysed for contents of vitamin C, calcium (Ca), inorganic phosphorus (P) and alkaline phosphatase (ALP). The pigs were examined clinically for foreleg weakness at the ages of 21 and 26 weeks. At the age of 26 weeks the pigs were slaughtered and the right forelegs were examined macroscopically and selected samples were collected for radiological, histological and ultrastructural examination. The prevalence of foreleg lesions was high, with lesions of dyschondroplasia of the distal growth plate of the ulna in 30 pigs, synovitis of the elbow joint in 24 pigs and osteochondritis dissecans of the elbow joint in 25 pigs. At the ages of 21 and 26 weeks, five pigs had evidently crooked forelegs and 14 pigs (age 21 weeks) and 25 pigs (age 26 weeks) had mildly deformed forelegs. The serum levels of Ca, P and ALP were within normal values for growing-finishing pigs. The range of vitamin C concentrations in plasma showed a wide difference (7.1-49.8 mumol/l) but was not associated with deformed forelegs. The serum concentrations of Ca, P and ALP and the plasma concentration of vitamin C differed significantly (P = 0.05) between age groups and there was a significant (P = 0.001) positive correlation between the levels of vitamin C in plasma and the serum levels of ALP at 6 weeks of age. The aim of the present study was to determine if there was any association between the plasma levels of vitamin C and the extent of crooked or deviated forelegs in growing-finishing pigs. We could not find a vitamin C deficiency during the study and no association between low levels of vitamin C in plasma and the presence of deformed forelegs of these 40 pigs.

  8. 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

  9. ADAMTS13 content in plasma-derived factor VIII/von Willebrand factor concentrates.

    PubMed

    Peyvandi, Flora; Mannucci, Pier M; Valsecchi, Carla; Pontiggia, Silvia; Farina, Claudio; Retzios, Anastassios D

    2013-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy syndrome caused by a congenital or acquired deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor (VWF) and thus prevents the formation of platelet-rich thrombi in the microcirculation. TTP can be fatal if not appropriately and timely treated with the infusion of fresh frozen plasma (FFP) or exchange plasmapheresis, that reverse the process of microangiopathy by removing anti-ADAMTS13 autoantibodies and replacing functional ADAMTS13. The treatment of TTP with FFP is not free from risks and must be administered in hospitals or clinics, owing to the substantial amount of plasma volume infused or exchanged and the frequent need of catheter application. Moreover, most FFPs are not subjected to treatments to remove or inactivate blood-borne infectious agents. A number of recent reports indicate that certain plasma-derived VWF-factor VIII (FVIII) concentrates are clinically effective in the treatment of congenital TTP. In this study, we measured ADAMTS13 levels in various plasma-derived VWF-FVIII concentrates, showing that Koate(®) -DVI (Grifols), contained relatively high amounts of ADAMTS13 and that Alphanate(®) (Grifols) was the closest other product in terms of protease content. Koate(®) -DVI contains, on average (five lots tested), 0.091 ± 0.007 Units of ADAMTS13 activity per IU of FVIII. On the basis of this analysis and other reports of VWF-FVIII concentrate utilization in congenital TTP, potential dosing, and future clinical developments are discussed.

  10. Post cardiac surgery vasoplegia is associated with high preoperative copeptin plasma concentration

    PubMed Central

    2011-01-01

    Introduction Post cardiac surgery vasodilatation (PCSV) is possibly related to a vasopressin deficiency that could relate to chronic stimulation of adeno-hypophysis. To assess vasopressin system activation, a perioperative course of copeptin and vasopressin plasma concentrations were studied in consecutive patients operated on for cardiac surgery. Methods Sixty-four consecutive patients scheduled for elective cardiac surgery with cardiopulmonary bypass were studied. Hemodynamic, laboratory and clinical data were recorded before and during cardiopulmonary bypass, and at the eighth postoperative hour (H8). At the same time, blood was withdrawn to determine plasma concentrations of arginine vasopressin (AVP, radioimmunoassay) and copeptin (immunoluminometric assay). PCSV was defined as mean arterial blood pressure < 60 mmHg with cardiac index ≥ 2.2 l/min/m2, and was treated with norepinephrine to restore mean blood pressure > 60 mmHg. Patients with PCSV were compared with the other patients (controls). Student's t test, Fisher's exact test, or nonparametric tests (Mann-Whitney, Wilcoxon) were used when appropriate. Correlation between AVP and copeptin was evaluated and receiver-operator characteristic analysis assessed the utility of preoperative copeptin to distinguish between controls and PCSV patients. Results Patients who experienced PCSV had significantly higher copeptin plasma concentration before cardiopulmonary bypass (P < 0.001) but lower AVP concentrations at H8 (P < 0.01) than controls. PCSV patients had preoperative hyponatremia and decreased left ventricle ejection fraction, and experienced more complex surgery (redo). The area under the receiver-operator characteristic curve of preoperative copeptin concentration was 0.86 ± 0.04 (95% confidence interval = 0.78 to 0.94; P < 0.001). The best predictive value for preoperative copeptin plasma concentration was 9.43 pmol/l with a sensitivity of 90% and a specificity of 77%. Conclusions High preoperative

  11. Continuous intragastric delivery of fenoldopam: relationship between plasma concentration and effects on renal function.

    PubMed Central

    Ziemniak, J A; Boppana, V K; Cyronak, M J; Beck, T R; Familiar, R G; Dubb, J W; Allison, N L; Stote, R M

    1988-01-01

    1. The pharmacodynamics of the dopamine DA1 agonist fenoldopam were examined in six healthy male volunteers after constant intragastric infusions of fenoldopam at dosages of 0, 10, 25, 50 and 75 mg h-1 for 6 h. 2. Hourly p-aminohippurate (PAH) clearance was used to assess fenoldopam induced renal plasma flow changes. Marked dose-related increases in renal plasma flow were noted with a maximal increase of 65% over baseline values of 711 ml min-1 being seen at the 75 mg h-1 rate. No changes in sodium excretion and glomerular filtration rate were observed. 3. Mean steady-state fenoldopam plasma concentrations were related to mean PAH clearance based on an Emax model (r = 0.996) with an Emax of 1350 ml min-1 and an EC50 of 6.2 ng ml-1. 4. Mean steady-state plasma concentrations of fenoldopam-7-sulphate and fenoldopam-8-sulphate failed to increase with dose but were linearly correlated to mean PAH changes (r = 0.998, r = 0.981 respectively). 5. These results support the concept of extending fenoldopam's duration of action through the development of an oral sustained delivery system. PMID:2896014

  12. Low Plasma Klotho Concentrations and Decline of Knee Strength in Older Adults

    PubMed Central

    Ferrucci, Luigi; Sun, Kai; Simonsick, Eleanor; Turner, Randi; Miljkovic, Iva; Harris, Tamara; Schwartz, Ann V.; Asao, Keiko; Kritchevsky, Stephen; Newman, Anne B.

    2016-01-01

    Background. Although the “anti-aging hormone” klotho is associated with sarcopenia in mice, the relationship between klotho and muscle strength in older adults is not well known. Methods. Plasma klotho concentrations were measured in 2,734 older adults, aged 71–80 years, who participated in the Health, Aging and Body Composition Study, a prospective observational cohort study conducted in Memphis, TN and Pittsburgh, PA. Knee extension strength was measured using isokinetic dynamometry at baseline and follow-up 2 and 4 years later. Knee extension strength was normalized for weight. Results. At baseline, participants in the highest tertile of plasma klotho had higher knee extension strength (β = .72, standard error [SE] = .018, p < .0001) compared with those in the lowest tertile in a multivariable linear regression model adjusting for age, sex, race, smoking, study site, C-reactive protein, interleukin-6, and diabetes. Participants in the highest tertile of plasma klotho at baseline had less of a decline in knee strength over 4 years of follow-up (β = −.025, SE = .011, p = .02) compared with those in the lowest tertile in a multivariable linear regression model adjusting for the same covariates above. Conclusions. Plasma klotho concentrations were an independent predictor of changes in knee strength over time in older adults. Further studies are needed to identify the biological mechanisms by which circulating klotho could modify skeletal muscle strength. PMID:26359247

  13. Plasma concentrations of endogenous benzodiazepine-receptor ligands in patients with hepatic encephalopathy: a comparative study.

    PubMed Central

    Hernández-Avila, C A; Shoemaker, W J; Ortega-Soto, H A

    1998-01-01

    OBJECTIVE: Hepatic encephalopathy (HE) is a complex neuropsychiatric disorder secondary to acute or chronic liver failure. Although the exact causes of HE have not been clarified, enhanced central nervous system inhibition at the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex, mediated by increased levels of endogenous benzodiazepine-receptor ligands (BZRL), has been proposed. Research exploring this hypothesis has yielded contradictory findings. This study evaluated the presence and levels of BZRL in plasma from patients with HE and 3 comparison groups. DESIGN: Cross-sectional study. PATIENTS: Twenty-four patients with HE, 10 patients with liver cirrhosis without encephalopathy (LC), 4 patients with uremic encephalopathy (UE), and 9 healthy subjects. INTERVENTIONS: Radio-receptor assay of plasma samples from patients and controls. MAIN OUTCOME MEASURES: Plasma levels of BZRL. RESULTS: The patients in the HE group had significantly higher plasma BZRL levels than the patients with UE and the healthy subjects, but not than those with LC, in whom these compounds were also detected in significant concentrations. When patients were classified according to the severity of HE, plasma of BZRL showed a modest correlation with stage of severity (r = 0.37). Interestingly, approximately one-third of the patients with HE did not have detectable levels of BZRL. CONCLUSION: Endogenous BZRL may play a role in the pathogenesis of HE, although neuropsychiatric symptoms in HE are difficult to explain in terms of these compounds alone. Images Fig. 1 PMID:9785700

  14. The influence of age, smoking and hyperthyroidism on plasma propranolol steady state concentration.

    PubMed Central

    Feely, J; Crooks, J; Stevenson, I H

    1981-01-01

    1 Plasma propranolol steady state concentration (Css) was determined during chronic dosage (160 mg/day) in 22 hyperthyroid patients (aged 16-75 years, 11 smokers, 11 non-smokers) and again following treatment when euthyroid. 2 There was a positive correlation between plasma propranolol Css and age in patients both when hyperthyroid (r = 0.74, P less than 0.01) and when euthyroid (r = 0.58, P less than 0.05). 3 Plasma propranolol Css in hyperthyroid patients were lower (P less than 0.05) in smokers than in non-smokers. 4 Following correction of hyperthyroidism there was a significant increase (P less than 0.01) in both the plasma propranolol Css and degree of plasma protein binding of propranolol. 5 Hyperthyroidism and smoking are known to increase the rate of drug metabolism and it is suggested that these variables may give rise to or accentuate an age related reduction in propranolol clearance. PMID:6264937

  15. 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.

  16. Evolution of the protein corona of lipid gene vectors as a function of plasma concentration.

    PubMed

    Caracciolo, Giulio; Pozzi, Daniela; Capriotti, Anna Laura; Cavaliere, Chiara; Foglia, Patrizia; Amenitsch, Heinz; Laganà, Aldo

    2011-12-20

    The concept that the effective unit of interest in the cell-nanomaterial interaction is the particle and its corona of associated proteins is emerging. Here we investigate the compositional evolution of the protein corona of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) cationic liposomes (CLs) and DOTAP/DNA lipoplexes over a wide range of plasma concentrations (2.5-80%). The composition of the hard corona of lipoplexes is quite stable, but that of CLs does evolve considerably. We show that the protein corona of CLs is made of both low-affinity and competitive-binding proteins whose relative abundance changes with the plasma concentration. This result may have deep biological implications for the application of lipid-based gene vectors both in vitro and in vivo.

  17. 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.

  18. Effects of shallow scoop and deep scoop dehorning on plasma cortisol concentrations in calves.

    PubMed

    McMeekan, C M; Mellor, D J; Stafford, K J; Bruce, R A; Ward, R N; Gregory, N G

    1997-04-01

    Scoop dehorning is one method of horn amputation. Plasma cortisol concentrations were used to investigate the effects of wound depth caused by shallow scoop and deep scoop dehorning on the acute pain-induced distress experienced by 15 week-old calves during the first 9 hours following horn amputation. Shallow scoop and deep scoop dehorning caused a prolonged cortisol elevation which returned to control values within 8 hours and 6 hours, respectively. There were no significant differences between shallow and deep dehorning with regard to mean plasma cortisol concentrations and integrated cortisol responses during the 9 hours after dehorning. Linear regression analysis revealed no significant correlation between wound depth and integrated cortisol response. Hence, at the investigated scoop wound depths, there was no detectable benefit in implementing a shallow scoop strategy in order to reduce acute pain-induced distress caused by scoop dehorning in 15 week-old calves.

  19. 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.

  20. Nicotine inhibits memory CTL programming.

    PubMed

    Sun, Zhifeng; Smyth, Kendra; Garcia, Karla; Mattson, Elliot; Li, Lei; Xiao, Zhengguo

    2013-01-01

    Nicotine is the main tobacco component responsible for tobacco addiction and is used extensively in smoking and smoking cessation therapies. However, little is known about its effects on the immune system. We confirmed that multiple nicotinic receptors are expressed on mouse and human cytotoxic T lymphocytes (CTLs) and demonstrated that nicotinic receptors on mouse CTLs are regulated during activation. Acute nicotine presence during activation increases primary CTL expansion in vitro, but impairs in vivo expansion after transfer and subsequent memory CTL differentiation, which reduces protection against subsequent pathogen challenges. Furthermore, nicotine abolishes the regulatory effect of rapamycin on memory CTL programming, which can be attributed to the fact that rapamycin enhances expression of nicotinic receptors. Interestingly, naïve CTLs from chronic nicotine-treated mice have normal memory programming, which is impaired by nicotine during activation in vitro. In conclusion, simultaneous exposure to nicotine and antigen during CTL activation negatively affects memory development.

  1. 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.

  2. Associations between intestinal mucosal function and changes in plasma zinc concentration following zinc supplementation1

    PubMed Central

    Wessells, K. Ryan; Hess, Sonja Y.; Rouamba, Noel; Ouédraogo, Zinewendé P.; Kellogg, Mark; Goto, Rie; Duggan, Christopher; Ouédraogo, Jean-Bosco; Brown, Kenneth H.

    2015-01-01

    Objectives Subclinical environmental enteropathy is associated with malabsorption of fats, carbohydrates, and vitamins A, B12 and folate; however, little information is available on mineral absorption. We therefore investigated the relationship between intestinal mucosal function (measured by the lactulose:mannitol permeability test and plasma citrulline concentration), and zinc absorption, as estimated by the change in plasma zinc concentration (PZC) following short-term zinc or placebo supplementation. Methods We conducted a randomized, partially-masked, placebo-controlled trial among 282 apparently healthy children 6–23 mo of age in Burkina Faso. After completing baseline intestinal function tests, participants received either 5 mg zinc, as zinc sulfate, or placebo, daily for 21 d. Results At baseline, mean ± SD PZC was 62.9 ± 11.9 µg/dL; median (IQR) urinary lactulose:mannitol (L:M) recovery ratio and plasma citrulline concentration were 0.04 (0.03 – 0.07) and 11.4 (9.0 – 15.6) µmol/L, respectively. Change in PZC was significantly greater in the zinc supplemented versus placebo group (15.6 ± 13.3 µg/dL vs. 0.02 ± 10.9 µg/dL; P < 0.0001), and was negatively associated with initial urinary L:M recovery ratio (−1.1 µg/dL per 50% increase in urinary L:M recovery ratio; P = 0.014); this latter relationship did not differ between supplementation groups (P = 0.26). Baseline plasma citrulline concentration was not associated with change in PZC. Conclusions Although altered intestinal permeability may reduce dietary zinc absorption, it likely does not undermine the efficacy of zinc supplementation, given the large increases in PZC following short-term zinc supplementation observed in this study, even among those with increased urinary L:M recovery ratios. PMID:23689263

  3. 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.

  4. Dietary Intake of Choline and Plasma Choline Concentrations in Pregnant Women in Jamaica

    PubMed Central

    Gossell-Williams, M; Fletcher, H; McFarlane-Anderson, N; Jacob, A; Patel, J; Zeisel, S

    2008-01-01

    Choline is an essential nutrient for humans and its availability during pregnancy is important for optimal fetal development. The Food and Nutrition Board of the Institute of Medicine in the United States of America has set the adequate choline intake during pregnancy at 450 mg/day. There is limited data available on normal plasma choline concentrations in pregnancy. Moreover, there are neither documented studies of choline intake among pregnant women in the Jamaican population nor of free plasma choline concentrations during pregnancy. Sixteen women presenting to the antenatal clinic of the University Hospital of the West Indies (UHWI) at 10−15 weeks of gestation were selected for this pilot study. A food frequency questionnaire was administered to estimate frequency of consumption of foods rich in choline. Fasting blood samples were collected by venepuncture and plasma assayed for choline using liquid chromatography electrospray ionization isotopic dilution mass spectrometry. Most of the women reported consumption of diets that delivered less than the recommended choline intake (mean ± SEM, 278.5 ± 28.9 mg). Mean plasma choline concentration was 8.4 ± 0.4 μmol/L. This falls below the normal concentration (10 μmol/L) reported for individuals that are not pregnant and pregnant (14.5 μmol/L). The results of this study may be an indication that the choline included in the diet of pregnant women in Jamaica may not be adequate to meet both the needs of the mother and fetus and that further studies are warranted to determine clinical implications. PMID:16642650

  5. 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.

  6. Behavioral mechanisms underlying nicotine reinforcement.

    PubMed

    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 (CS), 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 CS, 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.

  7. 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

  8. Mechanism-based medication development for the treatment of nicotine dependence.

    PubMed

    Xi, Zheng-xiong; Spiller, Krista; Gardner, Eliot L

    2009-06-01

    Tobacco use is a global problem with serious health consequences. Though some treatment options exist, there remains a great need for new effective pharmacotherapies to aid smokers in maintaining long-term abstinence. In the present article, we first discuss the neural mechanisms underlying nicotine reward, and then review various mechanism-based pharmacological agents for the treatment of nicotine dependence. An oversimplified hypothesis of addiction to tobacco is that nicotine is the major addictive component of tobacco. Nicotine binds to alpha4beta2 and alpha7 nicotinic acetylcholine receptors (nAChRs) located on dopaminergic, glutamatergic and GABAergic neurons in the mesolimbic dopamine (DA) system, which causes an increase in extracellular DA in the nucleus accumbens (NAc). That increase in DA reinforces tobacco use, particularly during the acquisition phase. Enhanced glutamate transmission to DA neurons in the ventral tegmental area appears to play an important role in this process. In addition, chronic nicotine treatment increases endocannabinoid levels in the mesolimbic DA system, which indirectly modulates NAc DA release and nicotine reward. Accordingly, pharmacological agents that target brain acetylcholine, DA, glutamate, GABA, or endocannabonoid signaling systems have been proposed to interrupt nicotine action. Furthermore, pharmacokinetic strategies that alter plasma nicotine availability, metabolism and clearance also significantly alter nicotine's action in the brain. Progress using these pharmacodynamic and pharmacokinetic agents is reviewed. For drugs in each category, we discuss the mechanistic rationale for their potential anti-nicotine efficacy, major findings in preclinical and clinical studies, and future research directions.

  9. Nicotine and health.

    PubMed

    2014-07-01

    Nicotine, an alkaloid derived from the leaves of tobacco plants (Nicotiana tabacum and Nicotiana rustica) is the primary addictive agent in tobacco products.(1,2) There are different ways of administering the various products including smoking cigarettes, chewing tobacco, holding moist snuff in the mouth, inhaling dry snuff through the nose, inhaling smoke from a waterpipe and inhaling vapour from an electronic cigarette.(3-6) It can be difficult differentiating the effects of nicotine from the many other toxic substances these products also contain. Here we review the pharmacological effects of nicotine but we will not review the well-known harmful effects of cigarettes, where it is primarily the toxins and carcinogens in tobacco smoke rather than the nicotine that cause illness and death.(7) A future article will consider the use of electronic cigarettes.

  10. Voluntary co-consumption of alcohol and nicotine: Effects of abstinence, intermittency, and withdrawal in mice.

    PubMed

    O'Rourke, Kyu Y; Touchette, Jillienne C; Hartell, Elizabeth C; Bade, Elizabeth J; Lee, Anna M

    2016-10-01

    Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction.

  11. [Plasma concentration of C-reactive protein in patients with high estrogen levels].

    PubMed

    Ricoux, R; Pontet, M; Tresca, J P; Engler, R

    1994-01-01

    The monitoring of inflammatory activity in patients with a high level of estrogen is controversial because the significance of a raised estradiol level on C-reactive protein (CRP) concentrations is a debated question. This prompted us to assay CRP by a sensitive Elisa in a sample of 30 patients with ovarian stimulation for in vitro fertilization, thus with high levels of estradiol. For 15 of these women, six to nine plasma samples were analyzed allowing a kinetic study of plasma levels of CRP, estradiol and sex steroid-binding plasma protein (SBP). No significant correlation was found between the concentrations of estradiol and CRP for the 30 patients. In the kinetic study, as mean estradiol levels rose exponentially from 50 to 1400 ng/l between day 5 and 14, the CRP level tended to vary markedly from one patient to another and sometimes from day to day, but there was never any relation with estradiol level. Furthermore, CRP did not significantly modify the slope of the regression line between estradiol concentration and the day of the menstrual cycle. In contrast, the effect of estradiol on SBP was clear, which supports the absence of estradiol effect on CRP level.

  12. 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

  13. Posaconazole plasma concentrations in pediatric patients receiving antifungal prophylaxis during neutropenia.

    PubMed

    Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Klinker, Hartwig; Eikemeier, Melinda; Feucht, Judith; Blaeschke, Franziska; Schwarze, Carl-Philipp; Ebinger, Martin; Feuchtinger, Tobias; Handgretinger, Rupert; Heinz, Werner J

    2016-10-04

    Invasive fungal infections are one of the major complications in pediatric patients during prolonged neutropenia after chemotherapy. Evaluation of the efficacy and safety of the triazole posaconazole in these patients is missing. This multicenter survey analyzed trough concentrations of 33 pediatric patients with a median age of 8 years during 108 neutropenic episodes who received prophylactic posaconazole oral suspension. A total of 172 posaconazole trough levels were determined to median 438 ng/ml (range 111-2011 ng/ml; mean 468 ± 244 ng/ml). Age and gender had no influence on posaconazole plasma levels. Posaconazole was not discontinued due to adverse events in any of the patients. Only hepatic parameters significantly increased beyond the upper normal limit to median values of ALT of 87 U/l (P < .0001), and AST of 67 U/l (P < .0001). One patient with a median posaconazole trough concentration of 306 ng/ml experienced an invasive fungal infection. In conclusion, posaconazole was effective, safe and feasible in 33 pediatric patients with neutropenia ≥5 days after chemotherapy. Median posaconazole plasma concentrations were approximately 1.6-fold lower than the recommended plasma level of 700 ng/ml. Larger patient cohorts are needed to evaluate these findings.

  14. Decreased dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrations in plasma of Alzheimer's disease (AD) patients.

    PubMed

    Aldred, Sarah; Mecocci, Patrizia

    2010-01-01

    DHEA is secreted by the adrenal cortex and is also a neurosteroid. Its sulfate (DHEAS) is the most abundant steroid in circulation. The levels of both are seen to decline in concentration with age. Evidence is available for altered levels of DHEA and DHEAS in AD but is limited to relatively few studies assessing small cohorts. This study assessed plasma DHEA and DHEAS levels in AD sufferers (n=72) and compared them to age-matched controls (n=72). Plasma DHEA concentrations were significantly lower in AD patients compared to control (4.24+/-0.4 ng/ml for AD; 3.38+/-0.3 ng/ml for control, p=0.027, Mann-Whitney 1-tailed) and DHEA levels were significantly correlated to DHEAS levels in both control and AD conditions (Spearman's rho correlation coefficient=0.635 in controls and 0.467 in AD, pconcentrations in plasma from a large cohort of patients suffering from AD when compared to age-matched controls.

  15. Plasma neurofilament pNF-H concentration is not increased in acute equine grass sickness.

    PubMed

    Stratford, C H; Pemberton, A; Cameron, L; McGorum, B C

    2013-03-01

    Although a presumptive diagnosis of acute grass sickness (AGS) can be made on the basis of clinical signs, a definitive ante mortem diagnosis currently requires histological examination of enteric ganglia. Development of an accurate noninvasive ante mortem diagnostic test is therefore warranted. The objective of this study was to determine whether quantification of the plasma concentrations of the heavily phosphorylated form of major neurofilament subunit NF-H (pNF-H), which mirror the degree of axonal degeneration in some human and animal neurodegenerative disorders, could distinguish AGS-affected and control horses. The pNF-H was quantified in plasma from 20 AGS cases and 20 control horses using a commercial enzyme-linked immunosorbent assay kit. Five AGS and 4 control samples had detectable pNF-H concentrations (>0.0759 ng/ml). There was no significant intergroup difference in pNF-H concentrations. It was concluded that plasma pNF-H is not a useful biomarker for the diagnosis of AGS.

  16. Effects of body mass on nicotine-induced thermogenesis and catecholamine release in male smokers.

    PubMed

    Walker, J F; Kane, C J

    2002-10-25

    The aims of this study were to examine the effects of nicotine on resting energy expenditure (REE) and plasma catecholamine release following ad libitum smoking in fasted, middle-aged males; and, to determine if the acute responses in REE and catecholamine release to smoking differ between normal weight (< or = 25 kg/m(2)) and overweight (> 25 kg/m(2)) smoker groups. REE was measured by indirect calorimetry in 32 fasted male smokers prior to, and 30 minutes after, consuming either two 0.16 mg nicotine (low yield) or two 1.74 mg nicotine (high yield) cigarettes. Plasma nicotine and norepinephrine levels were simultaneously measured. There was no thermic effect of nicotine or catecholamine response after smoking low yield cigarettes in both groups, nor after smoking high yield cigarettes in the overweight group. In contrast, REE increased 7.2%, which was accompanied by an increase in plasma norepinephrine release, after smoking high yield cigarettes in the normal weight group. Controlling plasma nicotine level ablated these increases. In conclusion, body mass interacts with the thermic effect of nicotine and neuroendocrine function in male smokers. Smoking-induced increase in the plasma nicotine level accounts for the observed responses, which are blunted in overweight smokers. This finding may have implications for potential weight gain following smoking cessation by normal weight individuals, related to lost smoking-induced thermogenesis.

  17. 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.

  18. Correlation of a clot-weight and radial immunodiffusion method for estimation of plasma fibrinogen concentration.

    PubMed

    Reid, H L; Onwuameze, I C

    1984-03-01

    A clot-weight and radial immunodiffusion method for estimating fibrinogen concentration were compared using plasma from 58 pregnant women and diabetic patients. The two methods gave a correlation coefficient, r = 0.53 (p less than 0.005). There was no significant variation between the mean fibrinogen concentrations as determined by both methods. The coefficient of variation for the clot-weight and immunodiffusion methods were 1.54% and 2.9%, respectively. It is concluded that the clot-weight method is more readily applicable than the radial immunodiffusion method to fibrinogen measurements, especially in patients when rapid results are required.

  19. 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.

  20. Development of a novel prolonged-release nicotine transdermal patch.

    PubMed

    Davaran, Soodabeh; Rashidi, Mohammad R; Khandaghi, Reza; Hashemi, Mahdi

    2005-03-01

    A transdermal patch for delivering nicotine for periods of 12-48h was designed. An inclusion complex formed between the nicotine and beta-cyclodextrine (beta-CD) was used in drug depot. The usefulness of a specially cross-linked polyvinyl alcohol (cross-PVA) membrane was investigated as a rate controlling membrane. The influence of carbopol polymers, type C-934P and C-940 and propylene glycol on transdermal permeation of nicotine through the rat skin was investigated. The results indicated a maximum flux of 42 microgcm(-2)h(-1) after 48 h from the patches made from C-934P when the propylene glycol concentration was 15% and the nicotine-beta-CD mole ratio in the inclusion complex was 3:1. These nicotine transdermal patches can be fabricated to obtain a controlled release, zero order systems.

  1. Effect of exogenous selenium on nicotine induced hyperlipidemia in rats.

    PubMed

    Sreekala, S; Indira, M

    2008-01-01

    The effect of two different doses (1 microg Se/Kg and 50 microg Se/Kg Body wt) of selenium on nicotine induced hyperlipidemia was investigated in rats. Results revealed that nicotine intake caused an increase in concentration of cholesterol, triglycerides, free fatty acids, phospholipids and low density lipoprotein compared to control group. Coadministration of selenium along with nicotine reduced the levels of lipids compared to nicotine group. This reduction was due to reduction in the biosynthesis of lipids as evidenced by the reduced activity of HMGCoA reductase and lipogenic enzymes. Nicotine intake also reduced the absorption of selenium in the intestine. Histopathological studies revealed that selenium at a dose of 1 microg was more effective in reducing lipid levels and higher dose of selenium was toxic.

  2. Negative allosteric modulation of nicotinic acetylcholine receptors blocks nicotine self-administration in rats.

    PubMed

    Yoshimura, Ryan F; Hogenkamp, Derk J; Li, Wen Y; Tran, Minhtam B; Belluzzi, James D; Whittemore, Edward R; Leslie, Frances M; Gee, Kelvin W

    2007-12-01

    Drugs that antagonize nicotinic acetylcholine receptors (nAChRs) can be used to inhibit nicotine-induced behavior in both humans and animals. The aim of our experiments is to establish a proof-of-principle that antagonism of nAChRs by negative allosteric modulation can alter behavior in a relevant animal model of addiction, nicotine self-administration. We have identified a novel, negative allosteric modulator of nAChRs, UCI-30002 [N-(1,2,3,4-tetrahydro-1-naphthyl)-4-nitroaniline], with selectivity for the major neuronal nAChR subtypes over muscle-type nAChRs. After systemic administration, UCI-30002 significantly reduces nicotine self-administration in rats on both fixed ratio and progressive ratio schedules of reinforcement. The minimum effective dose that significantly alters nicotine self-administration corresponds to brain concentrations of UCI-30002 that produce at least 30% inhibition of the major neuronal nAChR subtypes measured in vitro. UCI-30002 has no effect on responding for food reinforcement in rats on either type of schedule, indicating that there is no effect on general responding or natural reward. UCI-30002 represents validation of the concept that negative allosteric modulators may have significant benefits as a strategy for treating nicotine addiction and encourages the development of subtype-selective modulators.

  3. 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

  4. Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats

    PubMed Central

    O’Dell, Laura E.; Torres, Oscar V.; Natividad, Luis A.; Tejeda, Hugo A.

    2012-01-01

    Vulnerability to nicotine addiction is significantly increased in individuals who begin smoking during adolescence; however, the underlying mechanisms of this phenomenon remain unclear. This study examined the motivational effects of nicotine withdrawal in adolescent (PND 27–42) and adult (PND 60–75) rats using the conditioned place aversion paradigm. Male Wistar rats were tested for their initial preference for either of two distinct compartments of our conditioning apparatus. Rats were then implanted with subcutaneous (sc) pumps that produce equivalent blood plasma levels of nicotine for 14 days. Conditioning was conducted over the last 8 days of nicotine exposure. Rats received the nicotinic antagonist mecamylamine (1.5 or 3.0 mg/kg, sc) to precipitate withdrawal in their initially preferred compartment, and on alternate days they received saline in their non-preferred compartment. Following conditioning, rats were re-tested for their preference for each compartment. A subsequent study was conducted to examine potential developmental differences in learning place aversion produced by another aversive stimulus, lithium chloride (LiCl). Rats received LiCl (0, 10, 30, or 100 mg/kg, sc) in their initially preferred side using similar conditioning procedures. Adults displayed robust place aversion produced by nicotine withdrawal. This effect was lower in adolescent rats even in a group of young rats that received 7 additional days of nicotine exposure prior to conditioning. This developmental difference was specific to nicotine withdrawal since there were no differences between adolescents and adults in learning place aversion with LiCl. Our findings demonstrating reduced effects of nicotine withdrawal constitute a powerful basis for the increased vulnerability to nicotine dependence during adolescence. PMID:17184972

  5. High plasma efavirenz concentration and CYP2B6 polymorphisms in Thai HIV-1 infections.

    PubMed

    Sukasem, Chonlaphat; Chamnanphon, Montri; Koomdee, Napatrupron; Puangpetch, Apichaya; Santon, Siwalee; Jantararoungtong, Thawinee; Prommas, Santirat; Chantratita, Wasun; Manosuthi, Weerawat

    2013-01-01

      Efavirenz is mainly metabolized by cytochrome P450 2B6 (CYP2B6). This study aimed to examine the frequencies of CYP2B6 and the association between CYP2B6 polymorphisms and plasma efavirenz concentrations in an HIV-1 infected Thai population. Mid-dose plasma efavirenz concentration was determined at 12 weeks following the initiation of an antiretroviral therapy (tenofovir, lamivudine and efavirenz) in 100 Thai adults with HIV-1 infection using high-performance liquid chromatography. Candidate CYP2B6 polymorphisms (c.64C>T, c.499C>G, c.516G>T, c.785A>G, c.1375A>G, c.1459C>T) were conducted by real-time PCR-based allelic discrimination. The most frequent polymorphisms among this cohort were the CYP2B6 c.785A>G and c.516G>T, which had a frequency of 0.36 and 0.32, respectively. From the cases observed, two single nucleotide polymorphisms (SNPs) (c.516G>T and c.785A>G) were significantly associated with high efavirenz plasma levels (p < 0.05). The most frequent haplotypic combinations were *1/*6, *1/*1, *1/*2 and *6/*6 at a frequency of 42.0%, 32.0%, 8.0% and 7.0%, respectively. Increased plasma concentrations of efavirenz were present in individuals with CYP2B6 *6/*6 [7.210 mg/L; interquartile range (IQR), 5.020-9.260] when compared to those with CYP2B6*1/*1 (1.570 mg/L; IQR, 1.295-2.670), p < 0.001. In our study, the impact of SNPs which are correlated with a high level of efavirenz plasma concentrations was found. The genetic configuration of SNPs which are associated with high plasma efavirenz levels may be useful in optimizing the efavirenz dose that is used in HIV-1 infected patients.

  6. 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

  7. Comparison of plasma ferritin concentration versus the ratio of plasma transferrin receptor to ferritin in estimating body iron stores: results of 4 intervention trials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: To develop global programs for the control of iron deficiency, simple, low-cost, accurate indicators of iron status are needed. Objectives: To compare estimates of body iron stores, as calculated from either plasma ferritin concentration alone (BI-ferritin) or the ratio of plasma transf...

  8. The relationship between the response of clinical symptoms and plasma olanzapine concentration, based on pharmacogenetics: Juntendo University Schizophrenia Projects (JUSP).

    PubMed

    Nozawa, Motohiro; Ohnuma, Tohru; Matsubara, Yoichiro; Sakai, Yoshie; Hatano, Tokiko; Hanzawa, Ryo; Shibata, Nobuto; Arai, Heii

    2008-02-01

    The monitoring of plasma olanzapine concentrations has been found to be an important and useful tool for optimizing psychiatric treatment. The present study investigated the effect that clinical factors, such as smoking and age, and functional polymorphisms of UGT1A4, CYP1A2, and CYP2D6 genes have on plasma olanzapine concentration, as well as the effects of plasma olanzapine concentrations on Japanese schizophrenic patients' clinical symptoms. The subjects included 51 chronic schizophrenic patients whose symptoms were not controlled with chronic conventional antipsychotics and therefore were switched to olanzapine. Male smokers had a significantly lower olanzapine concentration-dose ratio and olanzapine/4'-N-desmethyl olanzapine ratio (which reflects CYP1A2 activity) than male nonsmokers and female nonsmokers. The results of a 2-way analysis of covariance showed that smoking had the main effect, rather than gender or age. The functional gene polymorphisms that were studied had no effect on the plasma olanzapine and metabolite concentrations. An improved total Brief Psychiatric Rating Scale (BPRS) score was not correlated with the plasma olanzapine concentration, but individual BPRS scores related to improvement of suspiciousness, hallucinations, and blunted affect were significantly correlated with plasma olanzapine concentration. Clinical factors, especially smoking, were more important modulators of olanzapine metabolism than the functional genotypes. Long-term olanzapine treatment with adequate plasma olanzapine concentrations could be more effective in improving some symptoms than treatment with conventional antipsychotics.

  9. Influence of pesticide physicochemical properties on the association between plasma and hair concentration.

    PubMed

    Chata, Caroline; M Hardy, Emilie; Grova, Nathalie; Appenzeller, Brice M R

    2016-05-01

    Although the relationship between chemical intake and resulting concentration in hair remains incompletely elucidated, the transfer from blood to hair bulb living cells is generally considered the main route of incorporation. The present work investigated the correlation between blood and hair concentration of 23 pesticides/metabolites from different chemical classes in rats submitted to chronic controlled exposure. Long-Evans rats were administered pesticides by gavage three times per week over a 90-day period. After hair sample decontamination, pulverization, and extraction, compounds were analyzed by gas chromatography tandem mass spectrometry (GC-MS/MS). Blood was collected at sacrifice, immediately turned into plasma, and analyzed after extraction for the same compounds by GC-MS/MS. The data obtained for all the investigated compounds demonstrated significant association between plasma and hair concentrations (P value of 2.97E-45 and R(Pearson) of 0.875), with the exception of three outliers. For all the target compounds, water solubility, lipophilicity, molecular weight, and charge were therefore investigated in order to understand the role of these parameters in outliers' specific behavior. Although a possible change in the charge through the transfer from blood to hair might be suspected for two outliers, on the whole the physicochemical parameters investigated here did not seem to influence incorporation of chemicals into hair. Our results support that the concentration of chemicals in hair mainly depends on the respective concentration in plasma and suggest that for most compounds, the transfer from blood to hair would not represent a limiting step in the incorporation.

  10. 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.

  11. 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.

  12. Identification and quantification of nicotine biomarkers in human oral fluid from individuals receiving low-dose transdermal nicotine: a preliminary study.

    PubMed

    Miller, Eleanor I; Norris, Hye-Ryun K; Rollins, Douglas E; Tiffany, Stephen T; Moore, Christine M; Vincent, Michael J; Agrawal, Alpana; Wilkins, Diana G

    2010-09-01

    The objective of this preliminary study was to identify and quantify potential nicotine (NIC) biomarkers in post-exposure oral fluid samples collected from 10 NIC-abstinent human participants administered 7 mg transdermal NIC using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Oral fluid samples were collected prior to NIC patch application and at 0.5 and 0.75 h after patch removal using the Quantisal() oral fluid collection device. The validated LC-MS-MS analyte panel included nicotine-Nbeta-D-glucuronide, cotinine-N-oxide, trans-3-hydroxycotinine, norcotinine, trans-nicotine-1'-N-oxide, cotinine (COT), nornicotine, NIC, anatabine, anabasine, and cotinine-N-beta-D-glucuronide. Analytes and corresponding deuterated internal standards were extracted by solid-phase extraction. NIC and COT concentrations were quantifiable in oral fluid samples collected from 6 of the 10 participants 0.5 h after patch removal and in oral fluid samples collected from 7 of the 10 participants 0.75 h after patch removal. Based on the mean NIC and COT concentrations in oral fluid and plasma for the participants with both quantifiable NIC and COT at the 0.5 and 0.75 h collection times, the oral fluid-plasma ratio was 6.4 for NIC and 3.3 for COT. An ELISA procedure was also validated and successfully applied as a screening tool for these oral fluid samples in conjunction with LC-MS-MS confirmation. An ELISA cut-off concentration of 5.0 ng/mL provided excellent sensitivity for discrimination of COT-positive post-exposure oral fluid samples collected after low-level transdermal NIC exposure and oral fluid samples collected prior to patch application.

  13. Elevated GM3 plasma concentration in idiopathic Parkinson’s disease: A lipidomic analysis

    PubMed Central

    Chan, Robin B.; Perotte, Adler J.; Zhou, Bowen; Liong, Christopher; Shorr, Evan J.; Marder, Karen S.; Kang, Un J.; Waters, Cheryl H.; Levy, Oren A.; Xu, Yimeng; Shim, Hong Bin; Pe’er, Itsik; Di Paolo, Gilbert

    2017-01-01

    Parkinson’s disease (PD) is a common neurodegenerative disease whose pathological hallmark is the accumulation of intracellular α-synuclein aggregates in Lewy bodies. Lipid metabolism dysregulation may play a significant role in PD pathogenesis; however, large plasma lipidomic studies in PD are lacking. In the current study, we analyzed the lipidomic profile of plasma obtained from 150 idiopathic PD patients and 100 controls, taken from the ‘Spot’ study at Columbia University Medical Center in New York. Our mass spectrometry based analytical panel consisted of 520 lipid species from 39 lipid subclasses including all major classes of glycerophospholipids, sphingolipids, glycerolipids and sterols. Each lipid species was analyzed using a logistic regression model. The plasma concentrations of two lipid subclasses, triglycerides and monosialodihexosylganglioside (GM3), were different between PD and control participants. GM3 ganglioside concentration had the most significant difference between PD and controls (1.531±0.037 pmol/μl versus 1.337±0.040 pmol/μl respectively; p-value = 5.96E-04; q-value = 0.048; when normalized to total lipid: p-value = 2.890E-05; q-value = 2.933E-03). Next, we used a collection of 20 GM3 and glucosylceramide (GlcCer) species concentrations normalized to total lipid to perform a ROC curve analysis, and found that these lipids compare favorably with biomarkers reported in previous studies (AUC = 0.742 for males, AUC = 0.644 for females). Our results suggest that higher plasma GM3 levels are associated with PD. GM3 lies in the same glycosphingolipid metabolic pathway as GlcCer, a substrate of the enzyme glucocerebrosidase, which has been associated with PD. These findings are consistent with previous reports implicating lower glucocerebrosidase activity with PD risk. PMID:28212433

  14. Elevated GM3 plasma concentration in idiopathic Parkinson's disease: A lipidomic analysis.

    PubMed

    Chan, Robin B; Perotte, Adler J; Zhou, Bowen; Liong, Christopher; Shorr, Evan J; Marder, Karen S; Kang, Un J; Waters, Cheryl H; Levy, Oren A; Xu, Yimeng; Shim, Hong Bin; Pe'er, Itsik; Di Paolo, Gilbert; Alcalay, Roy N

    2017-01-01

    Parkinson's disease (PD) is a common neurodegenerative disease whose pathological hallmark is the accumulation of intracellular α-synuclein aggregates in Lewy bodies. Lipid metabolism dysregulation may play a significant role in PD pathogenesis; however, large plasma lipidomic studies in PD are lacking. In the current study, we analyzed the lipidomic profile of plasma obtained from 150 idiopathic PD patients and 100 controls, taken from the 'Spot' study at Columbia University Medical Center in New York. Our mass spectrometry based analytical panel consisted of 520 lipid species from 39 lipid subclasses including all major classes of glycerophospholipids, sphingolipids, glycerolipids and sterols. Each lipid species was analyzed using a logistic regression model. The plasma concentrations of two lipid subclasses, triglycerides and monosialodihexosylganglioside (GM3), were different between PD and control participants. GM3 ganglioside concentration had the most significant difference between PD and controls (1.531±0.037 pmol/μl versus 1.337±0.040 pmol/μl respectively; p-value = 5.96E-04; q-value = 0.048; when normalized to total lipid: p-value = 2.890E-05; q-value = 2.933E-03). Next, we used a collection of 20 GM3 and glucosylceramide (GlcCer) species concentrations normalized to total lipid to perform a ROC curve analysis, and found that these lipids compare favorably with biomarkers reported in previous studies (AUC = 0.742 for males, AUC = 0.644 for females). Our results suggest that higher plasma GM3 levels are associated with PD. GM3 lies in the same glycosphingolipid metabolic pathway as GlcCer, a substrate of the enzyme glucocerebrosidase, which has been associated with PD. These findings are consistent with previous reports implicating lower glucocerebrosidase activity with PD risk.

  15. Inactivation gating determines nicotine blockade of human HERG channels.

    PubMed

    Wang, H Z; Shi, H; Liao, S J; Wang, Z

    1999-09-01

    We have previously found that nicotine blocked multiple K+ currents, including the rapid component of delayed rectifier K+ currents (IKr), by interacting directly with the channels. To shed some light on the mechanisms of interaction between nicotine and channels, we performed detailed analysis on the human ether-à-go-go-related gene (HERG) channels, which are believed to be equivalent to the native I(Kr) when expressed in Xenopus oocytes. Nicotine suppressed the HERG channels in a concentration-dependent manner with greater potency with voltage protocols, which favor channel inactivation. Nicotine caused dramatic shifts of the voltage-dependent inactivation curve to more negative potentials and accelerated the inactivation process. Conversely, maneuvers that weakened the channel inactivation gating considerably relieved the blockade. Elevating the extracellular K+ concentration from 5 to 20 mM increased the nicotine concentration (by approximately 100-fold) needed to achieve the same degree of inhibition. Moreover, nicotine lost its ability to block the HERG channels when a single mutation was introduced to a residue located after transmembrane domain 6 (S631A) to remove the rapid channel inactivation. Our data suggest that the inactivation gating determines nicotine blockade of the HERG channels.

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

    PubMed Central

    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 as compared to 1) adolescents and 2) adults that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAcc) during nicotine exposure and precipitated withdrawal using microdialysis procedures. Adolescent (PND 28–42) and adult rats (PND 60–74) were prepared with osmotic pumps that delivered nicotine for 14 days (4.7 mg/kg/day adolescents; 3.2 mg/kg/day adults). 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, rats were implanted with microdialysis probes in the NAcc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic-receptor antagonist mecamylamine (1.5 mg/kg and 3.0 mg/kg, IP) 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 NAcc 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 nicotine withdrawal, ACh levels in

  17. 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

  18. 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

  19. Changes in plasma cortisol concentrations in bitches in response to different combinations of halothane and butorphanol, with or without ovariohysterectomy.

    PubMed

    Fox, S M; Mellor, D J; Lawoko, C R; Hodge, H; Firth, E C

    1998-01-01

    Changes in plasma cortisol concentrations were assessed in bitches in response to nine treatments: control, anaesthesia, analgesia, analgesia followed by anaesthesia, anaesthesia followed by analgesia at intubation, anaesthesia followed by analgesia at extubation, anaesthesia plus surgery, analgesia followed by anaesthesia plus surgery, and anaesthesia plus surgery followed by analgesia. The anaesthetic was halothane, the analgesic was butorphanol (0.4 mg kg(-1)) and the surgery was ovariohysterectomy. Blood samples, for plasma cortisol assays, were taken regularly from before treatment for five hours and then again after 24 hours. A small transient rise in plasma cortisol concentration in the control group was attributed to mild distress associated with novel experiences. A more pronounced and protracted rise in cortisol concentration in the analgesia group was ascribed to a dysphoric state of bitches under the influence of the agonist-antagonist butorphanol. Halothane anaesthesia alone resulted in no change in plasma cortisol concentration. When butorphanol was given after anaesthesia was induced or while the animal was still under the influence of anaesthesia (immediately after tracheal extubation), there was no immediate rise in plasma cortisol concentration and low concentrations were maintained for up to 60 minutes after halothane withdrawal. A marked rise in plasma cortisol concentration, which was sustained above pretreatment values for at least five hours, occurred in all surgery groups. Giving intravenous butorphanol 30 minutes prior to surgery had no effect on the surgically-induced rise in plasma cortisol concentration and no effect on the postsurgical plasma cortisol concentration. In contrast, butorphanol given at extubation did reduce plasma cortisol concentrations during the postsurgical period. These observations did not support the hypothesis that preoperative use of butorphanol would reduce the cortisol response after surgery under halothane

  20. Effects of variable dietary sitostanol concentrations on plasma lipid profile and phytosterol metabolism in hamsters.

    PubMed

    Ntanios, F Y; Jones, P J

    1998-02-23

    To examine how variable sitostanol (SI) levels in phytosterol-supplemented diets influence plasma and hepatic lipid concentrations, fifty hamsters were divided into five groups and fed semipurified diets containing 0.25% (w/w) cholesterol for 45 days ad libitum. Four groups were fed this diet with 1% (w/w) phytosterol mixtures which contained 0.01% (w/w) SI derived from soybean, 0.2% (w/w) SI derived from tall oil, 0.2% (w/w) synthetic SI mixture (SIM) and 1% (w/w) pure SI, respectively. A control group did not receive phytosterols. Dietary SI supplementation at 1% (w/w) decreased total and non-apolipoprotein-A cholesterol levels in plasma by 34% (P=0.001) and 55% (P=0.04), respectively, whereas mean plasma total cholesterol level in the 0.2% (w/w) SI group was 23% (P=0.001) lower than that of the control group. Conversely, plasma lipid profile in hamsters fed 1 or 0.2% (w/w) SI did not differ from the 0.01% (w/w) SI group. Liver weights were 15 and 20% (P=0.012) higher in the control group compared with those fed 0.01% and 1% (w/w) SI, respectively, while the hepatic cholesterol content in the control group was greater (P<0.0001) than that of all other groups. Plasma campesterol levels were higher (P=0.04) in the 0.01% and 0.2% (w/w) SI fed groups than in the control, 0.2% (w/w) SIM and 1% (w/w) SI groups. Hepatic sitosterol content was elevated (P=0.002) in the SIM fed group compared to other groups. We conclude that dietary SI effect is proportional to its concentration in phytosterol mixtures and in the diet. Dietary SI lowered plasma cholesterol levels at concentrations higher than 0.2% (w/w) in hamsters. (c) 1998 Elsevier Science B.V.

  1. Treatment with clozapine and its effect on plasma homovanillic acid and norepinephrine concentrations in schizophrenia.

    PubMed

    Davidson, M; Kahn, R S; Stern, R G; Hirschowitz, J; Apter, S; Knott, P; Davis, K L

    1993-02-01

    Measurement of plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA), is an indirect tool to assess changes in dopamine turnover. Levels of pHVA have been reported to decrease during treatment with conventional antidopaminergic, neuroleptics, with the decrement correlating with symptomatic improvement in schizophrenic symptoms. Clozapine, an atypical neuroleptic, is the only drug proved to be effective in treatment-refractory patients. However, the mechanism mediating this unique efficacy has not been fully elucidated. This study examined the effect of clozapine on pHVA concentrations in schizophrenic patients. Since clozapine potently binds to alpha 2-adrenergic receptors, plasma norepinephrine (pNE) concentrations were also measured. Twenty-eight treatment-refractory schizophrenic patients (24 men, 4 women) were treated with clozapine (up to 600 mg/day) for 5 weeks, after a minimum 1-week drug-free period. Symptomatology and pHVA and pNE concentrations were measured at the last drug-free day and weekly for 5 weeks. Fourteen patients responded to clozapine treatment, while an equal number did not. Mean pHVA concentrations did not significantly change during treatment with clozapine. Although clozapine tended to lower pHVA concentrations in treatment responders, the effect was small and not significant. Clozapine treatment significantly raised pNE concentrations, but this did not differentiate responders from nonresponders to clozapine. These findings suggest that clozapine's effect on DA turnover is small and that clozapine may be effective in treatment-refractory schizophrenia by mechanisms other than, or in addition to, dopamine receptor blockade. However, since about one-third of NE is metabolized into HVA, the clozapine-induced increase in pNE may have overshadowed a possible lowering effect of clozapine on pHVA.

  2. 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.

  3. 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.

  4. Relationship between plasma oxipurinol concentrations and xanthine oxidase activity in volunteers dosed with allopurinol.

    PubMed Central

    Day, R O; Miners, J; Birkett, D J; Graham, G G; Whitehead, A

    1988-01-01

    1. 1-methyl xanthine (1-MX) is metabolized exclusively to 1-methyl uric acid (1-MU) by the enzyme xanthine oxidase. 2. The ratio of 1-MU to 1-MX in the urine, following a dose of 50 mg of 1-MX infused intravenously over 20 min, was used to measure the inhibition of xanthine oxidase induced by different doses of allopurinol. 3. Normal volunteers (n = 8) were given allopurinol 50, 100, 300 and 600 mg daily for 1 week each, in random order and 1 week separated each treatment. Inhibition of xanthine oxidase was assessed twice, on the last 2 days of each treatment week. 4. Steady-state oxipurinol concentrations increased linearly with increasing dose of allopurinol. 5. There was a hyperbolic relationship between the 1-MU/1-MX ratio and plasma oxipurinol concentrations, with an initial steep decline in the ratio which plateaued when plasma oxipurinol was around 4-6 mg l-1. This reduction in the ratio was quickly reversible upon cessation of allopurinol. 6. The 50% and 90% effective inhibitory oxipurinol concentrations, in relation to the 1-MU-/1-MX ratio were 1.4 +/- 0.46 and 4.08 +/- 2.03 mg l-1 respectively. 7. The concentration of oxipurinol required for almost complete inhibition of the enzyme was substantially less than those often observed in clinical practice. PMID:3190993

  5. Acceptable Raltegravir and Etravirine Concentrations in Plasma when Administered via Gastrostomy Tube

    PubMed Central

    Sandkovsky, Uriel; Swindells, Susan; Moore, Ryan; Acosta, Edward P.; Fletcher, Courtney V.

    2011-01-01

    Background Circumstances arise in clinical practice when alternative antiretroviral formulations are urgently needed for those unable to take available tablet or capsule formulations orally. Currently, only a few agents can be administered with commercially available liquid, powder or parenteral formulations. Methods A patient infected with multidrug-resistant human immunodeficiency virus (HIV) and hepatitis B required antiretroviral therapy via a gastrostomy because of esophageal perforations. Tablets of the patient’s current regimen of raltegravir, etravirine, tenofovir and emtricitabine (Truvada®) were crushed or dispersed and mixed with water and administered via the gastrostomy tube. Plasma samples 2-hour and 12-hour post dose were obtained and drug concentrations quantitated using validated assays. Results were compared to those in published pharmacokinetic studies from HIV-Infected persons and healthy volunteers. Results The 2 and 12-hour post dose measured raltegravir concentrations were 1,220 ng/mL and 446 ng/mL, respectively. The 2 and 12-hour post dose etravirine concentrations were 212 ng/mL and 274 ng/mL; emtricitabine was 1148 and 164 ng/mL and tenofovir was 320 and 94 ng/mL respectively. Conclusions Plasma concentrations of raltegravir, etravirine, emtricitabine and tenofovir when administered via gastrostomy tube compared favorably with published values. PMID:22392423

  6. Physiological Concentrations of Choline Activate Native α7-Containing Nicotinic Acetylcholine Receptors in the Presence of PNU-120596 [1-(5-Chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)-urea

    PubMed Central

    Gusev, Alexander G.

    2010-01-01

    The use of PNU-120596 [1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)-urea], a positive allosteric modulator of α7 nicotinic acetylcholine receptor (nAChR), may be beneficial for enhancing cholinergic therapies. However, the effects of PNU-120596 on activation of native α7-containing nAChRs by physiological concentrations of choline are not known and were investigated in this study using patch-clamp electrophysiology and histaminergic tuberomammillary neurons in hypothalamic slices. In the presence of PNU-120596, subthreshold (i.e., inactive) physiological concentrations of choline (∼10 μM) elicited repetitive step-like whole-cell responses reminiscent of single ion channel openings that were reversibly blocked by 20 nM methyllycaconitine, a selective α7 nAChR antagonist. The effects of choline and PNU-120596 were synergistic as administration of 10 to 40 μM choline or 1 to 4 μM PNU-120596 alone did not elicit responses. In voltage clamp at −60 mV, the persistent activation of α7-containing nAChRs by 10 μM choline plus 1 μM PNU-120596 was estimated to produce a sustained influx of Ca2+ ions at a rate of 8.4 pC/min (∼0.14 pA). In the presence of PNU-120596 in current clamp, transient step-like depolarizations (∼5 mV) enhanced neuronal excitability and triggered voltage-gated conductances; a single opening of an α7-containing nAChR channel appeared to transiently depolarize the entire neuron and facilitate spontaneous firing. Therefore, this study tested and confirmed the hypothesis that PNU-120596 enhances the effects of subthreshold concentrations of choline on native α7-containing nAChRs, allowing physiological levels of choline to activate these receptors and produce whole-cell responses in the absence of exogenous nicotinic agents. In certain neurological disorders, this activation may be therapeutically beneficial, more efficacious, and safer than treatments with nAChR agonists. PMID:19923442

  7. The concentrations of adipokines in goat milk: relation to plasma levels, inflammatory status, milk quality and composition

    PubMed Central

    GUZEL, Saime; YIBAR, Artun; BELENLI, Deniz; CETIN, Ismail; TANRIVERDI, Meltem

    2017-01-01

    The main objectives of our study were to measure the major adipokines adiponectin, leptin and resistin in goat milk, to assess their interrelationships and to assess their relationships with the plasma and serum concentrations of total protein, cholesterol, total lipids, plasma C-reactive protein (CRP), milk somatic cell count (SCC), milk total aerobic colony and lactobacillus count, and milk components in lactating Saanen goats. The study was performed on eighteen lactating Saanen goats. Milk and blood samples were collected on days 20, 35, 50, 65 and 80 of lactation postpartum. The milk and plasma adiponectin levels on days 50, 65 and 80 postpartum were significantly higher than those on day 20. The milk and plasma leptin levels were lower on day 20 than on days 35, 50, 65 and 80. The milk concentrations of these major adipokines were positively intercorrelated. The milk and plasma concentrations of these three adipokines were also positively correlated. The plasma CRP concentrations correlated positively with milk leptin and resistin concentrations and inversely with milk adiponectin concentration. Milk adiponectin concentration was inversely related with its SCC. These data confirm that adiponectin, leptin and resistin are present in goat milk. The milk concentrations of these three adipokines were interrelated and interacted with the general inflammatory marker, CRP. The inverse relationship between milk adiponectin concentrations and its SCC suggests that variations in milk adiponectin might be involved in the udder health of lactating goats, but clinical trials are needed to support this hypothesis. PMID:28111374

  8. 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.

  9. Effect of sesaminol on plasma and tissue alpha-tocopherol and alpha-tocotrienol concentrations in rats fed a vitamin E concentrate rich in tocotrienols.

    PubMed

    Yamashita, Kanae; Ikeda, Saiko; Iizuka, Yoshie; Ikeda, Ikuo

    2002-04-01

    We have shown that sesame lignans added to rat diet resulted in significantly greater plasma and tissue concentrations of alpha- and gamma-tocopherol concentrations in supplemented rats than in rats without supplementation. In the present studies we examined whether sesaminol, a sesame lignan, enhances tocotrienol concentrations in plasma and tissues of rats fed diets containing a tocotrienol-rich fraction of palm oil (T-mix). In Experiment 1, effects of sesaminol on tocotrienol concentrations in plasma, liver, and kidney were evaluated in rats fed diets containing 20 mg/kg of T-mix (20T) and 50 mg/kg of T-mix (50T) with or without 0.1% sesaminol. Although the T-mix contained 23% alpha-tocopherol, 22% alpha-tocotrienol, and 34% gamma-tocotrienol, alpha-tocopherol constituted most or all of the vitamin E in plasma and tissue (from 97% in kidney to 100% in plasma), with no or very little alpha-tocotrienol and no gamma-tocotrienol at all. Addition of sesaminol to the T-mix resulted in significantly higher plasma, liver, and kidney alpha-tocopherol concentrations compared to values for T-mix alone. Further, T-mix with sesaminol resulted in significantly higher alpha-tocotrienol concentrations in kidney, although the concentration was very low. In Experiment 2, we examined whether sesaminol caused enhanced absorption of alpha-tocopherol and alpha-tocotrienol in a dosage regimen supplying T-mix and sesaminol on alternating days and observed significantly higher levels of alpha-tocopherol and alpha-tocotrienol in rats fed sesaminol, even without simultaneous intake, compared to those in rats without sesaminol. In Experiment 3, alpha-tocopherol was supplied to the stomach with and without sesaminol, and alpha-tocopherol concentrations in the lymph fluid were measured. a-Tocopherol concentrations were not different between groups. These results indicated that sesaminol produced markedly higher alpha-tocopherol concentrations in plasma and tissue and significantly greater

  10. Adjustment of urinary concentration to urinary volume in relation to erythrocyte and plasma concentrations: an evaluation of urinary heavy metals and organic substances

    SciTech Connect

    Araki, S.; Aono, H.; Murata, K.

    1986-05-01

    The effects of urinary volume on adjusted and nonadjusted urinary excretion of 11 heavy metals and organic substances were examined in relation to plasma and erythrocyte concentrations in 19 metal workers under conditions of water restriction and loading. Blood lead concentrations in these workers ranged from 25 to 59 micrograms/dl. The results indicated that: urinary volume significantly affects not only nonadjusted urinary concentration for all substances, but also affects timed excretion and concentrations adjusted to urinary specific gravity and to urinary creatinine for most substances; the concentration adjusted to urinary volume is, on the other hand, independent of urinary volume; and urinary excretion of lead and mercury is related more closely to erythrocyte concentration than to plasma concentration. This last finding reflects complex renal excretory mechanisms for these heavy metals.

  11. Clinical effectiveness of fresh frozen plasma compared with fibrinogen concentrate: a systematic review

    PubMed Central

    2011-01-01

    Introduction Haemostatic therapy in surgical and/or massive trauma patients typically involves transfusion of fresh frozen plasma (FFP). Purified human fibrinogen concentrate may offer an alternative to FFP in some instances. In this systematic review, we investigated the current evidence for the use of FFP and fibrinogen concentrate in the perioperative or massive trauma setting. Methods Studies reporting the outcome (blood loss, transfusion requirement, length of stay, survival and plasma fibrinogen level) of FFP or fibrinogen concentrate administration to patients in a perioperative or massive trauma setting were identified in electronic databases (1995 to 2010). Studies were included regardless of type, patient age, sample size or duration of patient follow-up. Studies of patients with congenital clotting factor deficiencies or other haematological disorders were excluded. Studies were assessed for eligibility, and data were extracted and tabulated. Results Ninety-one eligible studies (70 FFP and 21 fibrinogen concentrate) reported outcomes of interest. Few were high-quality prospective studies. Evidence for the efficacy of FFP was inconsistent across all assessed outcomes. Overall, FFP showed a positive effect for 28% of outcomes and a negative effect for 22% of outcomes. There was limited evidence that FFP reduced mortality: 50% of outcomes associated FFP with reduced mortality (typically trauma and/or massive bleeding), and 20% were associated with increased mortality (typically surgical and/or nonmassive bleeding). Five studies reported the outcome of fibrinogen concentrate versus a comparator. The evidence was consistently positive (70% of all outcomes), with no negative effects reported (0% of all outcomes). Fibrinogen concentrate was compared directly with FFP in three high-quality studies and was found to be superior for > 50% of outcomes in terms of reducing blood loss, allogeneic transfusion requirements, length of intensive care unit and hospital

  12. Plasma Adiponectin Concentration and Its Association with Metabolic Syndrome in Patients with Heart Failure

    PubMed Central

    Won, Hoyoun; Shin, Min-Jeong; Oh, Jaewon; Hong, Namki; Park, Sungha; Lee, Sang-Hak; Jang, Yangsoo; Chung, Namsik

    2012-01-01

    Purpose Plasma adiponectin concentrations are inversely related with metabolic syndrome (MetS), and MetS is associated with increased risk for heart failure (HF). However, the relationship between adiponectin and MetS in HF remains undetermined. Therefore, we tested whether MetS was associated with the degree of plasma adiponectin concentrations in HF patients. Materials and Methods One hundred twenty eight ambulatory HF patients with left ventricular ejection fraction of <50% (80 males, 61.8±11.9 years old) were enrolled for this cross-sectional study. Echocardiographic measurements were performed, and plasma concentrations of adiponectin, lipoproteins, apolipoproteins (apoB, apoA1) and high sensitive C-reactive protein (hsCRP) were measured. Results Adiponectin concentrations in HF patients with MetS (n=43) were significantly lower than those without MetS (n=85) (9.7±7.0 vs. 15.8±10.9 µg/mL, p=0.001). Higher concentrations of apoB (p=0.017), apoB/A1 ratio (p<0.001), blood urea nitrogen (p=0.034), creatinine (p=0.003), and fasting insulin (p=0.004) were observed in HF patients with MetS compared with those without MetS. In HF patients with MetS, adiponectin concentrations were negatively correlated with hsCRP (r=-0.388, p=0.015) and positively correlated with the ratio of early mitral inflow velocity to early diastolic mitral annular velocity, E/E' (r=0.399, p=0.015). There was a significant trend towards decreased adiponectin concentrations with an increasing number of components of MetS (p for trend=0.012). Conclusion Our study demonstrated that adiponectin concentrations decreased in HF patients with MetS, and that relationship between adiponectin, inflammation and abnormal diastolic function, possibly leading to the progression of HF. PMID:22187237

  13. Dietary protein and plasma total homocysteine, cysteine concentrations in coronary angiographic subjects

    PubMed Central

    2013-01-01

    Background Dietary patterns are associated with plasma total homocysteine (tHcy) concentrations in healthy populations, but the associations between dietary protein and tHcy, total cysteine (tCys) in high risk populations are unclear. We therefore examined the association between dietary protein and tHcy and tCys concentrations in coronary angiographic subjects. Methods We conducted a cross-sectional study of 1015 Chinese patients who underwent coronary angiography (40–85 y old). With the use of food-frequency questionnaires, we divided the total protein intakes into high animal-protein and high plant-protein diets. Circulating concentrations of tHcy and tCys were simultaneously measured by high-performance liquid chromatography with fluorescence detection. Results We found that high animal-protein diet was positively associated with hyperhomocysteinemia after adjustment for potential confounders, with the subjects in the highest quartile of intake having the greatest increase in risk (OR: 4.14, 95% CI: 2.67-6.43), whereas high plant-protein diet was inversely related to hyperhomocysteinemia, with a higher intake being protective. Compared with the first quartile of intake, the adjusted OR was 0.59 (95% CI: 0.38-0.91) for the fourth quartile. The total protein intake was positively associated with the risk of hypercysteinemia and the participants in highest quartile had significant OR of 1.69 (95% CI: 1.02-2.87) compared with those in lowest quartile. In multivariate linear regression analyses, high animal-protein and total-protein intakes were positively associated with plasma tHcy and tCys concentrations. The plant-protein intake was a negative determinant of plasma tHcy concentrations. Conclusions High animal-protein diet was positively associated with high tHcy concentrations, whereas high plant-protein diet was inversely associated with tHcy concentrations. Furthermore the total protein intake was strongly related to tCys concentrations. PMID:24195518

  14. Acute fasting in heifers as a model for assessing the relationship between plasma and follicular fluid NEFA concentrations.

    PubMed

    Jorritsma, R; de Groot, M W; Vos, P L A M; Kruip, T A M; Wensing, Th; Noordhuizen, J P T M

    2003-06-01

    It is known from epidemiological studies that negative energy balance in early lactating dairy cows is related to a depression in reproductive performance. Elevated plasma concentrations of non-esterified fatty acids (NEFA) are a typical metabolic characteristic of these animals and are proposed as the possible link. The suggestion is that NEFA might have a direct effect on the ovary, by affecting development of the oocyte or the granulosa cells. However, no data is available concerning the relationship between the concentration of NEFA in follicular fluid and plasma. Therefore, a cross-over study with 10 heifers around 15 months of age was conducted to analyze this relationship and examine the suggested effects of the negative energy balance on follicular growth. Investigation of these effects was performed on fasted heifers. The experimental treatment consisted of feeding hay with a subsequent period of fasting, to induce elevated plasma NEFA concentrations. Sampling of follicular fluid was performed using transvaginal aspiration of follicles, which were standardized using a synchronization protocol. In addition, concentrations of glucose, insulin, NEFA, and estradiol were measured in plasma. Follicular estradiol and progesterone concentrations were also measured to assess the quality of the dominant follicle. Fasting resulted in significantly lower plasma glucose (P=0.0006) and plasma insulin (P<0.0001) concentrations, higher plasma estradiol (P=0.008) and higher NEFA (P<0.001) concentrations, and smaller follicles (P=0.04) with lower estradiol:progesterone (E/P) ratios (P=0.05). Concentrations of NEFA in follicular fluid and plasma were closely related. Given this close relationship, we concluded that the presence of high plasma NEFA concentrations might link energy metabolism in early lactation with fertility.

  15. Rifampicin and isoniazid plasma concentrations in relation to adverse reactions in tuberculosis patients: a retrospective analysis

    PubMed Central

    Aït Moussa, L.; El Bouazzi, O.; Serragui, S.; Soussi Tanani, D.; Soulaymani, A.; Soulaymani, R.

    2016-01-01

    Objective: High concentrations of antituberculosis (anti-TB) drugs can be associated with many adverse drug reactions (ADRs). The objective of this study was to examine the plasma concentrations of rifampicin (RMP) and isoniazid (INH) in patients with and without ADRs. Methods: Concentration monitoring data of patients treated with anti-TB drugs were retrospectively analyzed from 2009 to 2011. RMP and INH plasma concentrations were measured 2 and 3 h after drug administration respectively using high-performance liquid chromatography. Results: A total of 54 out of 120 patients have experienced ADRs to anti-TB drugs. The median concentrations [interquartile range (IQR)] obtained in patients with and without ADRs were 6.7 mg/l (3.7–9.9) and 5.6 mg/l (2.9–8.6) (p = 0.56) for RMP and 4.3 mg/l (2.3–5.3) and 3.1 mg/l (1.7–4.8) (p = 0.04) for INH, respectively. Related median doses (IQR) were 8.7 mg/kg (8.0–10.0) and 8.6 mg/kg (6.5–9.9) (p = 0.42) for RMP and 4.8 mg/kg (4.3–5.0) and 4.0 mg/kg (2.8–5) (p < 0.01) for INH, respectively. Concentrations above the expected range in patients with and without ADRs were not reached for RMP, but were 76% and 65% for INH, respectively. Correlation between concentrations and doses has not been established for RMP or INH. In addition, high INH concentrations showed no association with sex, age, liver injury or renal or diabetes. Conclusions: High INH concentrations were common in patients with and without ADRs whereas RMP concentrations were low or within the normal range in most patients. Further studies are required to assess the association between high INH concentrations and the occurrence of ADRs. PMID:27904742

  16. A rapid, quantitative GLC method for the simultaneous determination of nicotine and cotinine.

    PubMed

    Verebey, K G; DePace, A; Mulé, S J; Kanzler, M; Jaffe, J H

    1982-01-01

    Published gas-liquid chromatographic (GLC) methods for the determination of nicotine and cotinine have proved impractical for the analysis of a large number of clinical samples. Significant improvements over other methods have been achieved, being low sample volume (0.5 mL plasma), rapid two-step extraction from plasma, no evaporation step, and good separation. The lower limits of sensitivity for nicotine and cotinine were 1 and 5 ng/mL, respectively. The method was validated by the analysis of plasma samples from cigarette-smoking volunteers. The method described permits the quick, routine determination of nicotine and cotinine in a large number of samples.

  17. Increased fasting plasma acylation-stimulating protein concentrations in nephrotic syndrome.

    PubMed

    Ozata, Metin; Oktenli, Cagatay; Gulec, Mustafa; Ozgurtas, Taner; Bulucu, Fatih; Caglar, Kayser; Bingol, Necati; Vural, Abdulgaffar; Ozdemir, I Caglayan

    2002-02-01

    Acylation-stimulating protein (ASP) is an adipocyte-derived protein that has recently been suggested to play an important role in the regulation of lipoprotein metabolism and triglyceride (TG) storage. ASP also appears to have a role in the regulation of energy balance. In addition to its role as a hormonal regulator of body weight and energy expenditure, leptin is now implicated as a regulatory molecule in lipid metabolism. However, little is known about the alterations in fasting plasma ASP and leptin concentrations in the nephrotic syndrome. As hyperlipidemia is one of the most striking manifestations of the nephrotic syndrome, we have investigated fasting plasma ASP and leptin levels and their relation to lipid levels in this syndrome. Twenty-five patients with untreated nephrotic syndrome and 25 age-, sex-, and body mass index-matched healthy controls were included in the study. Fasting plasma lipoproteins, TG, total cholesterol, lipoprotein(a), apolipoprotein AI (apoAI), apoB, urinary protein, plasma albumin, third component of complement (C3), ASP, and leptin levels were measured in both groups. Total cholesterol, TG, low and very low density lipoproteins, lipoprotein(a), apoB, and urinary protein levels were increased in the patient group, whereas plasma albumin, high density lipoprotein cholesterol, and apoAI levels were decreased compared with those in the control group (P < 0.001). Plasma ASP levels were significantly higher in the patient group compared with the control subjects (133.72 +/- 65.14 vs. 29.93 +/- 12.68 nmol/liter; P < 0.001), whereas leptin (2.69 +/- 2.06 vs. 3.99 +/- 2.99 ng/ml; P = 0.118) and C3 (1.01 +/- 0.25 vs. 1.06 +/- 0.23 g/liter; P = 0.662) levels were not significantly different between the two groups. Plasma leptin levels were correlated with body mass index in both nephrotic patients (r(s) = 0.86; P < 0.001) and controls (r(s) = 0.98; P < 0.001), but were not correlated with the other parameters. Fasting ASP concentrations

  18. Nicotine therapy for ulcerative colitis.

    PubMed

    Kennedy, L D

    1996-09-01

    Smoking has been associated with a decreased frequency of UC. Currently, the role of nicotine for the treatment of UC is not established. Several studies have evaluated nicotine gum and transdermal patches as supplemental therapy for stable UC, but nicotine has not been compared with other treatment modalities. Nicotine dosages in the studies have varied from 5 to 30 mg/d without apparent dose-related therapeutic effects, and many patients have found relief from placebo treatment. Patients often do not tolerate nicotine therapy's adverse effects, which can include nausea, light-headedness, and headache. Due to the cyclic disease course of UC and the potential addictiveness of nicotine, further large studies are warranted to assess the benefits of nicotine therapy for UC. These studies should be conducted using a randomized, double-blind design with an extensive follow-up period. Until further trials are conducted, nicotine should generally not be recommended for UC treatment.

  19. 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.

  20. 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

  1. Dynamics of statistically confident particle sizes and concentrations in blood plasma obtained by the dynamic light scattering method

    NASA Astrophysics Data System (ADS)

    Chaikov, Leonid L.; Kirichenko, Marina N.; Krivokhizha, Svetlana V.; Zaritskiy, Alexander R.

    2015-05-01

    The work is devoted to the study of sizes and concentrations of proteins, and their aggregates in blood plasma samples, using static and dynamic light scattering methods. A new approach is proposed based on multiple repetition of measurements of intensity size distribution and on counting the number of registrations of different sizes, which made it possible to obtain statistically confident particle sizes and concentrations in the blood plasma. It was revealed that statistically confident particle sizes in the blood plasma were stable during 30 h of observations, whereas the concentrations of particles of different sizes varied as a result of redistribution of material between them owing to the protein degradation processes.

  2. Dynamics of statistically confident particle sizes and concentrations in blood plasma obtained by the dynamic light scattering method.

    PubMed

    Chaikov, Leonid L; Kirichenko, Marina N; Krivokhizha, Svetlana V; Zaritskiy, Alexander R

    2015-05-01

    The work is devoted to the study of sizes and concentrations of proteins, and their aggregates in blood plasma samples, using static and dynamic light scattering methods. A new approach is proposed based on multiple repetition of measurements of intensity size distribution and on counting the number of registrations of different sizes, which made it possible to obtain statistically confident particle sizes and concentrations in the blood plasma. It was revealed that statistically confident particle sizes in the blood plasma were stable during 30 h of observations, whereas the concentrations of particles of different sizes varied as a result of redistribution of material between them owing to the protein degradation processes.

  3. Changes in plasma pyridoxal 5'-phosphate concentration during pregnancy stages in Japanese women.

    PubMed

    Shibata, Katsumi; Tachiki, Akiko; Mukaeda, Kana; Fukuwatari, Tsutomu; Sasaki, Satoshi; Jinno, Yoshiki

    2013-01-01

    Most Japanese women do not consume the estimated average requirement of vitamin B6 (1.7 mg/d) during pregnancy. Nevertheless, these deficiencies are not reported. We investigated a nutritional biomarker of vitamin B6 in pregnant Japanese women as well as their vitamin B6 intakes. Vitamin B6 intakes in the first, second, and third trimesters of pregnancy, and 1 mo after delivery were 0.79±0.61 (n=56), 0.81±0.29 (n=71), 0.90±0.35 (n=92), and 1.00±0.31 (n=44) mg/d, respectively. Plasma pyridoxal 5'-phosphate (PLP) concentrations in the first, second, and third trimesters of pregnancy, and 1 mo after delivery were 57.1±27.6 (n=56), 23.3±16.7 (n=71), 18.3±12.5 (n=92), and 43.9±33.4 (n=44) nmol/L, respectively. The plasma concentrations significantly decreased in the second and third trimesters of pregnancy compared to values from the first trimester (p<0.05), and these concentrations returned to the values of the first trimester of pregnancy 1 mo after birth.

  4. 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.

  5. Plasma-derived versus recombinant factor concentrates in PUPs: a never ending debate?

    PubMed

    Berntorp, Erik

    2017-01-31

    Inhibitor development in haemophilia is a serious complication to treatment with factor concentrates. Since the advent of more pure products, especially developed using recombinant DNA technology, some studies have shown an increased incidence of inhibitors in previously untreated patients (PUPs) receiving recombinant products whereas plasma-derived concentrates sometimes have been claimed to have a protective role, probably due to the content of von Willebrand factor (VWF). In fact, experiments indicate that the VWF may block uptake of factor VIII into macrophages for further processing to the immune system. Also, a competition between VWF and inhibitor binding to the C2 domain of factor VIII has been suggested. Recently, large cohort and surveillance studies have created a vigorous debate about the role of product class for inhibitor development as results have been conflicting. The only randomised prospective study, the SIPPET study, was published in 2016, and substantiated previous reports claiming that plasma derived concentrates give less inhibitors in patients with severe haemophilia A, previously not exposed to factor VIII. The debate will continue.

  6. The ratios of aldosterone / plasma renin activity (ARR) versus aldosterone / direct renin concentration (ADRR).

    PubMed

    Glinicki, Piotr; Jeske, Wojciech; Bednarek-Papierska, Lucyna; Kruszyńska, Aleksandra; Gietka-Czernel, Małgorzata; Rosłonowska, Elżbieta; Słowińska-Srzednicka, Jadwiga; Kasperlik-Załuska, Anna; Zgliczyński, Wojciech

    2015-12-01

    Primary aldosteronism (PA) is estimated to occur in 5-12% of patients with hypertension. Assessment of aldosterone / plasma renin activity (PRA) ratio (ARR) has been used as a screening test in patients suspected of PA. Direct determination of renin (DRC) and calculation of aldosterone / direct renin concentration ratio (ADRR) could be similarly useful for screening patients suspected of PA. The study included 62 patients with indication for evaluation of the renin-angiotensin-aldosterone system and 35 healthy volunteers. In all participants we measured concentrations of serum aldosterone, plasma direct renin, and PRA after a night's rest and again after walking for two hours. The concentrations of aldosterone, direct renin, and PRA were measured by isotopic methods (radioimmunoassay (RIA) / immunoradiometric assay (IRMA)). Correlations of ARR with ADRR in the supine position were r = 0.9162, r(2) = 0.8165 (p < 0.01); and in the up-right position were r = 0.7765, r(2) = 0.9153 (p < 0.01). The cut-off values of ARR and ADRR ≥ 100 presented highest specificity (99%) for the diagnosis of PA; however, quite acceptable specificity and sensitivity (> 80% and 100%, respectively) appeared for the ratios ≥ 30. We suggest that for practical and economic reasons ARR can be replaced by ADRR.

  7. 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.

  8. 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.

  9. 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.

  10. Evaluation of the influence of physical activity on the plasma concentrations of several trace metals.

    PubMed

    Rodríguez Tuya, I; Pinilla Gil, E; Maynar Mariño, M; García-Moncó Carra, R M; Sánchez Misiego, A

    1996-01-01

    Our study was carried out with the aim of evaluating the influence that the degree of physical activity may have on plasma concentrations of essential and toxic elements. Copper and zinc, elements of known importance in basic cellular processes, have been analysed as essential, and cadmium and lead as toxic for the body in abnormal doses. The study was performed on a total population of 50 healthy individuals, 34 of them professional sportsmen and the rest who undertook moderate physical activity (control group), all of them living in a polluted environment (Madrid, Spain). Sampling was conducted at the beginning of the season (October). Electro-analytical techniques of proved reliability and accuracy were used for the determination of the metals. The results were related to data obtained using graphite furnace atomic absorption spectrophotometry and by use of biological reference materials. We found significantly higher zinc plasma concentrations in the sportsmen involved in anaerobic-type training (judo, fencing) compared to those undertaking aerobic activities (endurance, cycling) (P < 0.05). The values in both cases were higher than those found in the control group. Our study showed an increase of plasma copper concentrations in professional sportsmen, especially in those performing anaerobic activities, compared to those subjects undertaking moderate activity (control group) (P < 0.05). In summary, our results showed that there were no deficiencies of copper and zinc in the athletes studied at the beginning of the season. The levels were higher than those of the control population. As for the toxic metals, cadmium and lead, we observed lower levels in the athletes than in the control group (cadmium P < 0.005, lead P < 0.05). These results may indicate the existence of possible elimination systems for these metals in athletes, when they are training in a polluted environment.

  11. Plasma concentrations and effects of salbutamol administered orally to patients with cystic fibrosis.

    PubMed Central

    Demnati, R; Michoud, M C; Jeanneret-Grosjean, A; Ong, H; Du Souich, P

    1995-01-01

    1. To test whether cystic fibrosis (CF) altered the kinetics and dynamics of oral salbutamol, 11 patients with CF (19-33 years old; five females; FEV1: 37 +/- 12% of predicted value) and 10 healthy volunteers (20-41 years old; five females; FEV1: 99 +/- 14% of predicted value) received orally 4 mg salbutamol. 2. The estimated pharmacokinetic parameters of salbutamol in patients with CF were identical to those in healthy subjects. For instance, peak plasma concentrations of salbutamol were 10.5 +/- 2.6 (mean +/- s.d.) and 10.2 +/- 2.9 ng ml-1 (NS), and the area under salbutamol plasma concentrations as a function of time (AUC (0, 7 h)) was 43.0 +/- 9.3 ng ml-1 h and 43.3 +/- 12.7 ng ml-1 h (NS) in CF patients and in healthy subjects, respectively. Since on a mg kg-1 dose basis, CF patients received a dose 28% greater than healthy subjects, this lack of differences implies a decrease in the amount of salbutamol absorbed, or alternatively, an increase in both clearance and volume of distribution of salbutamol. 3. Salbutamol did not elicit bronchodilation in CF patients, but increased heart rate from 77 +/- 2 to 103 +/- 3 beats min-1 (P < 0.05). 4. Salbutamol decreased plasma potassium concentrations from 4.5 +/- 0.1 to 3.8 +/- 0.1 mmol l-1 in the CF group (P < 0.05) and from 4.1 +/- 0.2 to 3.4 +/- 0.1 mmol l-1 in the controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8554933

  12. Interactions of Morphine and Peptide 234 on Mean Plasma Testosterone Concentration

    PubMed Central

    Mahmoudi, Fariba; Khazali, Homayoun; Janahmadi, Mahyar

    2014-01-01

    Background: Kisspeptin-GPR54 system stimulates the hypothalamus-pituitary-gonadal (HPG) axis; dysfunction of the gene encoding the GPR54 receptor causes hypogonadism and infertility. Opioid peptides inhibit the reproductive axis. Peptide 234 is a GPR54 receptor antagonist and blocks the stimulatory effects of kisspeptin on HPG axis. Objectives: Interactions of morphine, kisspeptin and peptide 234 on mean plasma testosterone concentration was investigated in rats. . Materials and Methods: In the present experimental study, seventy male Wistar rats in 14 groups (n = 5 in each group) received saline, different doses of kisspeptin (100 pmol, 1 or 3 nmol, Intracerebroventricular (ICV)), P234 (1 or 2.5 nmol) or Co- administration of kisspeptin, P234, morphine and naloxone at 09:00 - 09:30 am. In the co-administrated groups, kisspeptin was injected at 15 min following P234, morphine or naloxone injections. Blood samples were collected 60 min following injections. Plasma testosterone concentration was measured using the rat testosterone ELISA kit. Results: Injections of kisspeptin (1 or 3 nmol) significantly increased the mean testosterone concentration compared to saline. Injection of different doses of P234 (1 or 2.5nmol) did not significantly decrease mean testosterone compared to saline. Co-administration of kisspeptin and different doses of P234 significantly decreased mean testosterone concentration compared to the kisspeptin group. Co-administration of P234/morphine or P234/naloxone significantly decreased mean testosterone concentration compared to kisspeptin/saline, kisspeptin/morphine or kisspeptin/ naloxone groups. Conclusions: Morphine and kisspeptin/GPR54 signaling pathway may interact with each other to control the hypothalamic-pituitary-gonadal axis. PMID:24696695

  13. Adenosine plasma level correlates with homocysteine and uric acid concentrations in patients with coronary artery disease.

    PubMed

    Fromonot, J; Deharo, P; Bruzzese, L; Cuisset, T; Quilici, J; Bonatti, S; Fenouillet, E; Mottola, G; Ruf, J; Guieu, R

    2016-03-01

    The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration (APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7). Seventy-eight patients (mean age ± SD: 66.3 ± 11.3; mean SYNTAX score: 19.9 ± 12.3) and 30 healthy subjects (mean age: 61 ± 13) were included. We incubated HuH7 cells with increasing concentrations of adenosine and addressed the effect on HCys level in cell culture supernatant. Patients vs. controls had higher APC (0.82 ± 0.5 μmol/L vs 0.53 ± 0.14 μmol/L; p < 0.01), HCys (15 ± 7.6 μmol/L vs 6.8 ± 3 μmol/L, p < 0.0001), and uric acid (242.6 ± 97 vs 202 ± 59, p < 0.05) levels. APC was correlated with HCys and uric acid concentrations in patients (Pearson's R = 0.65 and 0.52; p < 0.0001, respectively). The SYNTAX score was correlated with HCys concentration. Adenosine induced a time- and dose-dependent increase in HCys in cell culture. Our data suggest that high APC is associated with HCys and uric acid concentrations in CAD patients. Whether the increased APC participates in atherosclerosis or, conversely, is part of a protective regulation process needs further investigations.

  14. Dietary phosphorus regulates intestinal transport and plasma concentrations of phosphate in rainbow trout.

    PubMed

    Avila, E M; Tu, H; Basantes, S; Ferraris, R P

    2000-05-01

    Intestinal inorganic phosphate transport and its regulation have not been studied in fish. In this study, we initially characterized the mechanisms of intestinal inorganic phosphate transport in rainbow trout (Oncorhynchus mykiss) then determined the effects of dietary phosphorus concentrations on intestinal inorganic phosphate uptake, plasma inorganic phosphate, and intestinal luminal inorganic phosphate concentrations. In 11-g trout, the saturable mechanism of brushborder inorganic phosphate uptake had a Kt= 1.2 mmol l(-1) and a Vmax = 0.22 nmol mg(-1) min(-1), while the diffusive component had a Kd = 0.012 min(-1). Similar kinetic constants were obtained from 51-g trout, suggesting that development or size had little effect on transport. Tracer inorganic phosphate (1.18 mmol l(-1)) uptake was almost completely inhibited (>95%) by 20 mmol l(-1) unlabeled inorganic phosphate. Inorganic phosphate uptake (0.2 mmol l(-1)) was strongly inhibited (approximately 75% inhibition) by phosphonoformic acid, a competitive inhibitor of mammalian inorganic phosphate transport, as well as by the absence of Na+ (approximately 90% inhibition). Northern blot and reverse transcription-polymerase chain reaction indicated that the intestinal inorganic phosphate transporter in trout is not related to the cloned Na+ inorganic phosphate-II transporter of winter flounder. Intestinal luminal and plasma inorganic phosphate concentrations each increased with dietary P concentrations. Intestinal inorganic phosphate, but not proline, absorption rates decreased with dietary phosphorus concentrations. As in mammals and birds, a Na-dependent inorganic phosphate carrier that is tightly regulated by diet is present in trout small intestine.

  15. Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals

    PubMed Central

    Ortega, Emilio; Koska, Juraj; Pannacciulli, Nicola; Bunt, Joy C; Krakoff, Jonathan

    2008-01-01

    Background Thyroid hormones (TH) may influence glucose metabolism. Hyperthyroid subjects have higher insulin secretion rates when compared with euthyroid individuals. Objective To evaluate the association between TH concentrations and insulin secretion in euthyroid, healthy Pima Indian adults (n=55, 29±7 years, females/males 36/19) with normal glucose tolerance (NGT) admitted to a Clinical Research Unit. Methods TSH, free thyroxine (FT4), 3,5,3′-L-tri-iodothyronine (FT3), and fasting plasma insulin (FPI) concentrations were measured in fasting plasma samples, percentage of body fat (%BF) by dual energy x-ray absorptiometry (DXA), acute insulin response (AIR), and incremental area under the curve (AUC) of insulin in response to a 25 g intravenous glucose tolerance test (IVGTT) and 75 g oral glucose tolerance test (OGTT) respectively and insulin action (M) during an euglycemic clamp. Results FT3 concentrations were associated with FPI, AIR, and insulin AUC both before (r=0.33, P=0.01; r=0.29, P=0.03; and r=0.35, P=0.008 respectively) and after adjustment for age, sex, %BF, glucose (fasting concentrations or glucose AUC), and M (β=0.09, P=0.01; β=0.16, P=0.03; and β=0.24, P=0.0007 respectively). No associations were found for TSH or FT4. Conclusion FT3 was associated with several measurements of insulin secretion in euthyroid individuals with NGT. T3 concentrations may play a role in the regulation of insulin secretion. PMID:18230829

  16. Posaconazole Plasma Concentrations on Days Three to Five Predict Steady-State Levels

    PubMed Central

    Prattes, Jürgen; Duettmann, Wiebke

    2016-01-01

    Low posaconazole plasma concentrations (PPCs) have been associated with breakthrough invasive fungal infections. We assessed the correlation between pre-steady-state PPCs (obtained between days 3 and 5) and PPCs obtained during steady state in 48 patients with underlying hematological malignancies receiving posaconazole oral-solution prophylaxis. Pre-steady-state PPCs correlated significantly with PPCs obtained at steady state (Spearman r = 0.754; P < 0.001). Receiver operating characteristic (ROC) curve analysis of pre-steady-state PPCs revealed an area under the curve (AUC) of 0.884 (95% confidence interval [CI], 0.790 to 0.977) for predicting satisfactory PPCs at steady state. PMID:27324763

  17. Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

    PubMed Central

    2012-01-01

    Background Ketoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO) and intra muscular (IM) routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers between those routes of administration in growing pigs. Methods Eleven pigs received racemic ketoprofen at dose rates of 4 mg/kg PO and 3 mg/kg IM in a randomized, crossover design with a 6-day washout period. Enantiomers were separated on a chiral column and their concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated and relative bioavailability (Frel) was determined for S and R –ketoprofen. Results S-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The mean (± SD) maximum S-ketoprofen concentration in plasma (7.42 mg/L ± 2.35 in PO and 7.32 mg/L ± 0.75 in IM) was more than twice as high as that of R-ketoprofen (2.55 mg/L ± 0.99 in PO and 3.23 mg/L ± 0.70 in IM), and the terminal half-life was three times longer for S-ketoprofen (3.40 h ± 0.91 in PO and 2.89 h ± 0.85 in IM) than R-ketoprofen (1.1 h ± 0.90 in PO and 0.75 h ± 0.48 in IM). The mean (± SD) relative bioavailability (PO compared to IM) was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively. Conclusions Although some minor differences were detected in the ketoprofen enantiomer concentrations in plasma after PO and IM administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen should be comparable after intramuscular and oral routes of administration in growing pigs

  18. [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.

  19. Relationship between plasma concentrations of the l-enantiomer of methadone and response to methadone maintenance treatment.

    PubMed

    Meini, Milo; Moncini, Marco; Daini, Laura; Giarratana, Tania; Scaramelli, Daniela; Chericoni, Silvio; Stefanelli, Fabio; Rucci, Paola

    2015-08-05

    This study evaluated the relationship between the plasma concentration of l-methadone and response to methadone in real-world patients, in order to identify a minimum plasma concentration above which methadone treatment is effective. Ninety-four patients with opioid dependence under maintenance methadone treatment were consecutively recruited. Response was defined as negative urine analyses in the three weeks prior to the blood sampling. The percentage of participants with a plasma l-methadone concentration between 100 and 250 ng/ml was 54.2% among those with a methadone dosage ≥60 mg/day. Plasma l-methadone concentrations were significantly higher in patients with negative urine analyses compared with those with positive urine analyses (median 93 vs. 77 ng/ml, Mann-Whitney test, P<0.05). Above plasma l-methadone concentrations of 200 ng/ml no heroin use was reported and urine analyses were negative. Moreover, above concentrations of 250 ng/ml craving was absent. Examination of demographic correlates of treatment outcome indicated that older age, a stable job and being married were protective against the use of heroin. Mean plasma l-methadone concentration was significantly lower in patients who used cannabis compared with those who did not use cannabis, after adjusting for methadone dosage. In conclusion our results identify specific cut-offs for plasma l-methadone concentrations about which therapeutic response is observed and provide new evidence that therapeutic response is associated with patient׳s demographic characteristics. This underscores the need to monitor plasma methadone concentrations as part of Drug Addiction Services routine practice, in order to provide an objective framework for changing the methadone dosage.

  20. Novel insights on the effect of nicotine in a murine colitis model.

    PubMed

    AlSharari, Shakir D; Akbarali, Hamid I; Abdullah, Rehab A; Shahab, Omer; Auttachoat, Wimolnut; Ferreira, Gabriela A; White, Kimber L; Lichtman, Aron H; Cabral, Guy A; Damaj, M Imad

    2013-01-01

    Studies showed that nicotine has a positive influence on symptoms of ulcerative colitis. In the present study, we explored the effect of nicotine treatment using different routes of administration in the dextran sodium sulfate (DSS) colitis mouse model. We also investigated the effects of cotinine, a major metabolite of nicotine, in the model. C57BL6 adult male mice were given DSS solution freely in the drinking water for seven consecutive days, and tap water was given thereafter. Disease severity, length of the colon, colon tissue histology, and inflammatory markers, including colonic myeloperoxidase activity and colonic tumor necrosis factor-α levels, were evaluated. The effect of nicotine and cotinine treatments via various different routes of administration were examined the DSS model. In addition, we measured the plasma levels of nicotine and cotinine in our treatment protocols. Administration of low, but not high, doses of oral nicotine in DSS-treated mice resulted in a significant decrease in disease severity, histologic damage scores, as well as colonic level of tumor necrosis factor-α. However, the anti-inflammatory effect of nicotine was not seen after chronic s.c. or minipump infusion of the drug. Differences in plasma levels of nicotine and cotinine do not seem to account for this lack of effect. Finally, oral cotinine alone failed to show a significant effect in the DSS model of colitis. These results highlight that dose and route of administration play a critical role in the protective effect of nicotine in the DSS mouse colitis model.

  1. Surveillance of moist snuff: total nicotine, moisture, pH, un-ionized nicotine, and tobacco-specific nitrosamines.

    PubMed

    Richter, Patricia; Hodge, Knachelle; Stanfill, Stephen; Zhang, Liqin; Watson, Clifford

    2008-11-01

    In 2005, approximately 2.3% of U.S. adults used smokeless tobacco. Moist snuff leads all types of smokeless tobacco in revenues and marketing expenditures. The U.S. Surgeon General has concluded that smokeless tobacco use can lead to nicotine addiction. The National Toxicology Program of the National Institutes of Health has classified smokeless tobacco as a human carcinogen. Tobacco-specific nitrosamines (TSNAs) are potent carcinogens in smokeless tobacco products, and the pH of the product influences the content of un-ionized nicotine which is the form of nicotine most rapidly absorbed in the mouth. The Centers for Disease Control and Prevention analyzed 40 top-selling brands of moist snuff to measure nicotine, moisture, pH, un-ionized nicotine, and TSNAs, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The study findings indicate that moist snuff brands varied widely in content of rapidly absorbed, addictive un-ionized nicotine (500-fold range) and of carcinogenic TSNAs (18-fold range). Product characteristics such as packaging and moisture content appeared to be correlated with concentrations of un-ionized nicotine, and flavor characteristics of low-priced brands may correlate with TSNA concentrations. These findings warrant further study in light of (a) the marketing of smokeless tobacco for use in places where smoking is prohibited, (b) the promotion of smokeless tobacco as a harm-reduction product, and (c) the ever-expanding number of highly flavored smokeless varieties brought to the market.

  2. 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.

  3. 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

  4. Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats.

    PubMed

    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.

  5. 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.

  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. [Study on THz spectra of nicotinic acid, nicotinamide and nicotine].

    PubMed

    Yu, Bin; Huang, Zhen; Wang, Xiao-yan; Zhao, Guo-zhong

    2009-09-01

    The terahertz (THz) spectra of nicotinic acid, nicotinamide and nicotine were studied at room temperature. The time-domain THz spectra were measured. The frequency-domain spectra were obtained by fast Fourier transform (FFT). The spectral response and the dispersive relationship of refractive index in THz spectral range were obtained. The results show that the samples have obvious spectral response in THz spectral range except nicotine. The corresponding stimulated spectra were given by using density functional theory (DFT) method for both nicotinamide and nicotinic acid. The origin of the absorption peaks of nicotinic acid and nicotinamide was explored. It is thought that the absorption peak of nicotinic acid is caused by the torsion and wagging of the molecule, but the absorption peaks of nicotinamide (except 1.93 THz) are caused by intermolecular or phonon mode. It was shown that the molecule structure and vibrational modes of nicotinic acid and nicotinamide can be analyzed by the combination of simulation and experimental results.

  8. Lipid concentrations of fillets, liver, plasma and lipoproteins of African catfish, Clarias gariepinus (Burchell 1822), fed diets with varying protein concentrations.

    PubMed

    Matter, F; Peganova, S; Eder, K

    2004-08-01

    This study investigated the effect of the dietary protein concentration on lipid concentrations in fillet and liver and concentrations of lipids in plasma and lipoproteins in African catfish. Two experiments were carried out, in which African catfish were fed diets with various protein concentrations. In experiment 1, semisynthetic diets with various concentrations of casein (350, 450 or 550 g protein/kg) were used. In experiment 2, diets were based on a commercial trout diet supplemented with various amounts of casein or carbohydrates, resulting in protein concentrations between 282 and 545 g/kg diet. In both experiments, the dietary protein concentration had a significant effect on growth, feed conversion ratio and carcass composition. Maximum of body weight gains and feed efficiency ratios were reached in both experiments at the highest dietary protein concentrations. Increasing the dietary protein concentration continuously increased masses of fillets and reduced masses of the liver and adipose tissue in the abdominal cavity. Fish fed the diets with the highest protein concentrations had the lowest concentration of total lipids, triglycerides and cholesterol in the fillets, the highest percentage of polyunsaturated fatty acids (PUFA) in total lipids of fillets and the lowest concentrations of saturated fatty acids (SFA). Fish fed the diets with the highest protein concentration also had the lowest concentrations of triglycerides in the liver, the highest percentages of PUFA in liver total lipids and the lowest percentages of SFA. Moreover, fish fed diets with high protein concentrations (501 and 545 g/kg) had significantly lower concentrations of triglycerides, cholesterol and phospholipids in plasma than fish fed diets with lower protein concentrations. In conclusion, this study shows that the dietary protein concentration does not only influence growth, feed efficiency and carcass composition in African catfish, but also influences their lipid metabolism and

  9. Ion mobility spectrometry as a simple and rapid method to measure the plasma propofol concentrations for intravenous anaesthesia monitoring

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Zhou, Qinghua; Jiang, Dandan; Gong, Yulei; Li, Enyou; Li, Haiyang

    2016-11-01

    The plasma propofol concentration is important information for anaesthetists to monitor and adjust the anaesthesia depth for patients during a surgery operation. In this paper, a stand-alone ion mobility spectrometer (IMS) was constructed for the rapid measurement of the plasma propofol concentrations. Without any sample pre-treatment, the plasma samples were dropped on a piece of glass microfiber paper and then introduced into the IMS cell by the thermal desorption directly. Each individual measurement could be accomplished within 1 min. For the plasma propofol concentrations from 1 to 12 μg mL‑1, the IMS response was linear with a correlation coefficient R2 of 0.998, while the limit of detection was evaluated to be 0.1 μg mL‑1. These measurement results did meet the clinical application requirements. Furthermore, other clinically-often-used drugs, including remifentanil, flurbiprofen and atracurium, were found no significant interference with the qualitative and quantitative analysis of the plasma propofol. The plasma propofol concentrations measured by IMS were correlated well with those measured by the high performance liquid chromatography (HPLC). The results confirmed an excellent agreement between these two methods. Finally, this method was applied to monitor the plasma propofol concentrations for a patient undergoing surgery, demonstrating its capability of anaesthesia monitoring in real clinical environments.

  10. Ion mobility spectrometry as a simple and rapid method to measure the plasma propofol concentrations for intravenous anaesthesia monitoring

    PubMed Central

    Wang, Xin; Zhou, Qinghua; Jiang, Dandan; Gong, Yulei; Li, Enyou; Li, Haiyang

    2016-01-01

    The plasma propofol concentration is important information for anaesthetists to monitor and adjust the anaesthesia depth for patients during a surgery operation. In this paper, a stand-alone ion mobility spectrometer (IMS) was constructed for the rapid measurement of the plasma propofol concentrations. Without any sample pre-treatment, the plasma samples were dropped on a piece of glass microfiber paper and then introduced into the IMS cell by the thermal desorption directly. Each individual measurement could be accomplished within 1 min. For the plasma propofol concentrations from 1 to 12 μg mL−1, the IMS response was linear with a correlation coefficient R2 of 0.998, while the limit of detection was evaluated to be 0.1 μg mL−1. These measurement results did meet the clinical application requirements. Furthermore, other clinically-often-used drugs, including remifentanil, flurbiprofen and atracurium, were found no significant interference with the qualitative and quantitative analysis of the plasma propofol. The plasma propofol concentrations measured by IMS were correlated well with those measured by the high performance liquid chromatography (HPLC). The results confirmed an excellent agreement between these two methods. Finally, this method was applied to monitor the plasma propofol concentrations for a patient undergoing surgery, demonstrating its capability of anaesthesia monitoring in real clinical environments. PMID:27869199

  11. 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.

  12. Comparison of five methods for determination of total plasma protein concentration.

    PubMed

    Okutucu, Burcu; Dinçer, Ayşşe; Habib, Omer; Zihnioglu, Figen

    2007-08-01

    Quantitation of exact total protein content is often a key step and is common to many applications in general biochemistry research and routine clinical laboratory practice. Before embarking on any type of protein analysis, particularly comparative techniques, it is important to accurately quantitate the amount of protein in the sample. In order to assess the quality of total protein estimation results, five methods were tested and were applied to the same pooled plasma sample. For this aim, Bradford (Coomassie Brilliant Blue), Lowry (Folin-Ciocalteau), Biüret, Pesce and Strande (Ponceau-S/TCA), and modified method of Schaffner-Weismann (Amido Black 10B) were used. The last two methods employ simultaneous precipitation of proteins with the acid containing dye solutions followed by dissolution of precipitate in a NaOH solution. It is shown that each assay has advantages and disadvantages relative to sensitivity, ease of performance, acceptance in literature, accuracy and reproducibility/coefficient of variation. All of the methods tested show a CV %<6. Besides pooled plasma, a known concentration of human serum albumin was also analyzed and discussed by means of standardization of plasma total protein content.

  13. [Plasma concentrations and renal excretion of vincamine after oral administration in man (author's transl)].

    PubMed

    Siegers, C P; Iven, H; Strubelt, O

    1977-01-01

    Plasma concentrations and renal excretion of 14,15-dihydro-14beta-hydroxy-(3alpha,16alpha)-eburnamenine-14-carbonic acid methylester (vincamine, Vincapront) were studied in 5 healthy volunteers following the oral intake of 30 or 60 mg vincamine, respectively. After the higher dose (60 mg vincamine), the treatment was continued by the daily intake of 3 X 20 mg vincamine for 5 days. Plasma vincamine levels were determined in the morning prior to the ingestion of the first 20-mg dose and in the evening 2 h after the intake of the third 20-mg dose. Our results prove that vincamine is rapidly liberated and absorbed from the tablet formulation used, the maximum plasma levels being reached 90 min after ingestion and amounting to a mean value of 139 ng/ml after 30 mg and to a mean of 252 ng/ml after 60 mg of vincamine. There was a biphasic elimination of vincamine after both doses indicating a process of distribution influencing also the elimination phase. In the 24-h urine, unchanged vincamine amounted to 5.8% of the applied dose after 30 mg and to 7.3% after 60 mg vincamine. Vincamine did not accumulate during the daily intake of 60 mg for 6 days. Side-effects were not observed in any volunteer during the period of observation.

  14. 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.

  15. Algal sterols are as effective as β-sitosterol in reducing plasma cholesterol concentration.

    PubMed

    Chen, Jingnan; Jiao, Rui; Jiang, Yue; Bi, Yanlan; Chen, Zhen-Yu

    2014-01-22

    The present study examined the cholesterol-lowering activity of sterol extract (SE) derived from alga Schizochytrium sp. and its interaction with gene expression of transporters, receptors, and enzymes involved in cholesterol absorption and metabolism. GC-MS analyses found that SE was a mixture of various sterols including lathosterol, ergosterol, stigmasterol, 24-ethylcholesta-5,7,22-trienol, stigmasta-7,24(24(1))-dien-3β-ol, and cholesterol. Results showed that SE at doses of 0.06 and 0.30 g/kg diet were able to decrease plasma cholesterol concentration by 19.5 and 34%, respectively, compared with the control, in hamsters maintained on a 0.1% high-cholesterol diet. SE at a dose of 0.30 g/kg diet was as effective as β-sitosterol in reducing plasma total cholesterol (TC). SE-induced reduction in plasma TC was accompanied by down-regulation of intestinal acyl-CoA:cholesterol acyltransferase 2 (ACAT2) and hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and up-regulation of hepatic low-density lipoprotein (LDL) receptor. Addition of SE to the diet increased the excretion of total fecal sterols. It was concluded that SE possessed the same cholesterol-lowering activity as β-sitosterol and the underlying mechanisms were mediated by increasing sterol excretion and decreasing cholesterol absorption and synthesis.

  16. Platelet concentration in platelet-rich plasma affects tenocyte behavior in vitro.

    PubMed

    Giusti, Ilaria; D'Ascenzo, Sandra; Mancò, Annalisa; Di Stefano, Gabriella; Di Francesco, Marianna; Rughetti, Anna; Dal Mas, Antonella; Properzi, Gianfranco; Calvisi, Vittorio; Dolo, Vincenza

    2014-01-01

    Since tendon injuries and tendinopathy are a growing problem, sometimes requiring surgery, new strategies that improve conservative therapies are needed. Platelet-rich plasma (PRP) seems to be a good candidate by virtue of its high content of growth factors, most of which are involved in tendon healing. This study aimed to evaluate if different concentrations of platelets in PRP have different effects on the biological features of normal human tenocytes that are usually required during tendon healing. The different platelet concentrations tested (up to 5 × 10(6) plt/µL) stimulated differently tenocytes behavior; intermediate concentrations (0.5 × 10(6), 1 × 10(6) plt/µL) strongly induced all tested processes (proliferation, migration, collagen, and MMPs production) if compared to untreated cells; on the contrary, the highest concentration had inhibitory effects on proliferation and strongly reduced migration abilities and overall collagen production but, at the same time, induced increasing MMP production, which could be counterproductive because excessive proteolysis could impair tendon mechanical stability. Thus, these in vitro data strongly suggest the need for a compromise between extremely high and low platelet concentrations to obtain an optimal global effect when inducing in vivo tendon healing.

  17. Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte Behavior In Vitro

    PubMed Central

    Rughetti, Anna; Dal Mas, Antonella; Properzi, Gianfranco; Calvisi, Vittorio

    2014-01-01

    Since tendon injuries and tendinopathy are a growing problem, sometimes requiring surgery, new strategies that improve conservative therapies are needed. Platelet-rich plasma (PRP) seems to be a good candidate by virtue of its high content of growth factors, most of which are involved in tendon healing. This study aimed to evaluate if different concentrations of platelets in PRP have different effects on the biological features of normal human tenocytes that are usually required during tendon healing. The different platelet concentrations tested (up to 5 × 106 plt/µL) stimulated differently tenocytes behavior; intermediate concentrations (0.5 × 106, 1 × 106 plt/µL) strongly induced all tested processes (proliferation, migration, collagen, and MMPs production) if compared to untreated cells; on the contrary, the highest concentration had inhibitory effects on proliferation and strongly reduced migration abilities and overall collagen production but, at the same time, induced increasing MMP production, which could be counterproductive because excessive proteolysis could impair tendon mechanical stability. Thus, these in vitro data strongly suggest the need for a compromise between extremely high and low platelet concentrations to obtain an optimal global effect when inducing in vivo tendon healing. PMID:25147809

  18. Embryo-maternal distribution of basic compounds in the CD-1 mouse: doxylamine and nicotine.

    PubMed

    Roberts, L G; Luck, W; Holder, C L; Scott, W J; Nau, H; Slikker, W

    1989-01-01

    The intracellular pH of the early postimplantation rodent embryo (pHi) is alkaline with respect to the corresponding plasma of the pregnant dam. This transplacental pH gradient is of considerable importance in the accumulation of teratogenic weak acids by the embryo. The importance of pH in the partitioning of basic drugs across the early mammalian placenta has not been investigated. Theoretically, the maternal plasma should retain a higher concentration of basic drugs than the embryo due to a greater degree of drug ionization in the more acidic plasma. To explore the significance of pH partitioning upon the transplacental distribution of basic compounds, two bases, doxylamine and nicotine, were administered to pregnant CD-1 mice during early organogenesis. The maternal plasma and embryonic concentrations of the bases were measured and the resulting embryo/maternal plasma (E/P) ratio was calculated and compared to the ratio predicted by the Henderson-Hasselbalch equation. Following ip injection of nicotine on Day 9 of gestation, the E/P ratio was significantly greater than the predicted ratio 10 min after injection and continued to rise for 3 hr. For doxylamine succinate administered by oral gavage on Day 9 or 10, the E/P ratio was also significantly greater than the ratio predicted from the pH gradient. Our results indicate that the partitioning of these basic compounds between the maternal plasma and the early postimplantation rodent embryo is not a consequence of the pH gradient between the two compartments alone.

  19. Estimating time of last oral ingestion of cannabis from plasma THC and THCCOOH concentrations.

    PubMed

    Huestis, Marilyn A; Elsohly, Mahmoud; Nebro, Wesenyalsh; Barnes, Allan; Gustafson, Richard A; Smith, Michael L

    2006-08-01

    Estimating the time of last cannabis use is important in assessing possible impairment of drivers involved in accidents, in verifying accuracy of court testimony and in the future, helpful in therapeutic monitoring of cannabis agonists. In 1992, Huestis et al developed model 1, based on plasma Delta-tetrahydrocannabinol (THC) concentrations, and model 2, on plasma 11-nor-9-carboxy-Delta(9)-tetrahydrocannbinol/THC ratios, that predicted 95% confidence intervals for time of last cannabis use. These models seemed to be valuable when applied to the small amount of data from published studies of oral ingestion, a route of administration more popular with the advent of cannabis therapies. A study was designed to further validate the models after oral ingestion of THC, and to determine whether they could predict last usage after multiple oral doses. Eighteen subjects in IRB-approved studies participated after providing informed consent. Each of 12 subjects in one group received a single 10 mg oral dose of dronabinol (synthetic THC). In another protocol, 6 subjects received 4 different oral daily doses, divided into thirds and administered with meals for 5 consecutive days. There was a 10-day washout period between each dosing regimen. Daily doses were 0.39, 0.47, and 14.8 mg THC in hemp oil and 7.5 mg dronabinol. Blood specimens were collected throughout the study and analyzed for plasma THC and 11-nor-9-carboxy-Delta(9)-tetrahydrocannbinol by gas chromatography/mass spectrometry with limits of quantification (LOQs) of 0.5 and 1.0 ng/mL, respectively. Actual times between ingestion of THC and blood collection spanned 0.5 to 16 hours. All plasma specimens with analyte concentrations >LOQ (n=90) were evaluated. Models 1 and 2 correctly predicted time of last THC ingestion for 74.4% and 90.0% of plasma specimens, respectively. 96.7% of predicted times were correct with one overestimate and 2 underestimates using the ti