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Sample records for administration plasma concentrations

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Oxytocin plasma concentrations after single intranasal oxytocin administration - a study in healthy men.

    PubMed

    Gossen, A; Hahn, A; Westphal, L; Prinz, S; Schultz, R T; Gründer, G; Spreckelmeyer, K N

    2012-10-01

    The neuropeptide oxytocin has become a subject of great interest in studies investigating human social cognition. Single intranasal administration of the hormone has been reported to have positive behavioral effects, such as increasing trust or facilitating social approach, 45-80 min after administration. However, little is still known about the long-term pharmacokinetics of oxytocin nasal spray application in humans. This study addressed the question how long oxytocin plasma levels remain elevated following nasal spray administration. Another goal was to examine the influence of oxytocin administration on endogenous steroid hormones since such alterations might modulate social behavior via an indirect way. Eight healthy Caucasian men were challenged with a single intranasal application of 26 international units of oxytocin. Changes in oxytocin blood plasma levels, as well as steroid hormone levels of progesterone, testosterone and estradiol were assessed at 5 consecutive time points over a period of 3.5 h (-5, +30, +90, +150, +210 min relative to oxytocin administration). Results gave evidence for a substantial rise of oxytocin plasma levels 30 min after intranasal administration, observed in 7 of 8 participants. Group mean oxytocin plasma level was found to have returned to baseline already 90 min post administration, though in some individuals the plasma levels was still elevated relative to sampling at post 150 min. Steroid hormone analyses yielded a slight augmentation of endogenous testosterone levels 210 min after oxytocin administration. Our data confirms previous findings that oxytocin administered as a nasal spray enters the blood circulation, elevating oxytocin plasma levels for a limited time. Our findings suggest that this time window differs between individuals, but that, for the used dose, it does not extend beyond 150 min post administration. The data further provides preliminary evidence that intranasal oxytocin has an enhancing effect on

  6. [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.

  7. Influence of CYP2C19 and ABCB1 polymorphisms on plasma concentrations of lansoprazole enantiomers after enteral administration.

    PubMed

    Miura, Masatomo; Motoyama, Satoru; Hinai, Yudai; Niioka, Takenori; Endo, Masahiro; Hayakari, Makoto; Ogawa, Jun-ichi

    2010-09-01

    An intraoral annihilation enteric-coated preparation of lansoprazole is often administered via intestinal fistula. The purpose of this study was to determine the plasma concentrations of lansoprazole enantiomers after enteral administration in subjects with cytochrome P4502C19 (CYP2C19) and ABCB1 C3435T genotypes. Fifty-one patients who underwent a curative oesophagectomy for oesophageal cancer were enrolled in this study. After a single enteral dose of racemic lansoprazole (30 mg), plasma concentrations of lansoprazole enantiomers were measured 4 h post-dose (C(4h)). There were significant differences in the C(4h) of (R)- and (S)-lansoprazole and the R/S-enantiomer ratio for three CYP2C19 genotype groups (*1/*1, *1/*2 ± *1/*3, and *2/*2 ± *2/*3 ± *3/*3 (poor metabolizers (PMs)), but not the ABCB1 C3435T genotypes. In a stepwise forward selection multiple regression analysis, the C(4h) of (R)- and (S)-lansoprazole were associated with CYP2C19 PMs (p = 0.0005 and < 0.0001 respectively) and age (p = 0.0040 and 0.0121 respectively), while the R/S-enantiomer ratio was associated with CYP2C19*1/*1 (p = 0.0191) and CYP2C19 PMs (p = 0.0426). Direct administration to the jejunum is unaffected by residence time in the stomach and the gastric emptying rate. With enteral administration, CYP2C19 phenotyping of patients using the lansoprazole R/S enantiomer index at C(4h) could be possible.

  8. Effectiveness of increasing the frequency of posaconazole syrup administration to achieve optimal plasma concentrations in patients with haematological malignancy.

    PubMed

    Park, Wan Beom; Cho, Joo-Youn; Park, Sang-In; Kim, Eun Jung; Yoon, Seonghae; Yoon, Seo Hyun; Lee, Jeong-Ok; Koh, Youngil; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Yu, Kyung-Sang; Kim, Eu Suk; Bang, Su Mi; Kim, Nam Joong; Kim, Inho; Oh, Myoung-Don; Kim, Hong Bin; Song, Sang Hoon

    2016-07-01

    Few data are available on whether adjusting the dose of posaconazole syrup is effective in patients receiving anti-cancer chemotherapy. The aim of this prospective study was to analyse the impact of increasing the frequency of posaconazole administration on optimal plasma concentrations in adult patients with haematological malignancy. A total of 133 adult patients receiving chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome who received posaconazole syrup 200 mg three times daily for fungal prophylaxis were enrolled in this study. Drug trough levels were measured by liquid chromatography-tandem mass spectrometry. In 20.2% of patients (23/114) the steady-state concentration of posaconazole was suboptimal (<500 ng/mL) on Day 8. In these patients, the frequency of posaconazole administration was increased to 200 mg four times daily. On Day 15, the median posaconazole concentration was significantly increased from 368 ng/mL [interquartile range (IQR), 247-403 ng/mL] to 548 ng/mL (IQR, 424-887 ng/mL) (P = 0.0003). The median increase in posaconazole concentration was 251 ng/mL (IQR, 93-517 ng/mL). Among the patients with initially suboptimal levels, 79% achieved the optimal level unless the steady-state level was <200 ng/mL. This study shows that increasing the administration frequency of posaconazole syrup is effective for achieving optimal levels in patients with haematological malignancy undergoing chemotherapy.

  9. [Plasma hormone concentrations in induced abortion with local prostaglandin administration in the 1st trimester].

    PubMed

    Rath, W; König, A; Ulbrich, R; Hilgers, R; Kuske, R; Kuhn, W

    1983-01-01

    Abortion was performed by curettage on 71 women with pregnancies between the 7th and the 13th week of gestation seven to eight hours after intracervical application of a tylose gel containing 3mg prostaglandin F2 alpha. Prior to the application of the prostaglandin and immediately before the surgical intervention a sonographic examination for determining the vitality of the pregnancy was carried out.--Plasma progesteron, estradiol and HPL levels were determined radioimmunologically prior to the application of prostaglandin, at four-hour intervals on the day of intervention, and 24, 48 and 72 hours after the intervention. In 22 women a complete or an incomplete abortion occurred; in two cases a blighted ovum was observed; 47 pregnancies, according to sonographic examination, remained intact until curettage. After seven to eight hours duration of the effect of the prostaglandin gel, progesterone levels were found to be reduced to 60.5 per cent and 17-beta-estradiol to 31.4 per cent of the initial values, whereas the HPL values fell below the specificity of the testing procedure (12.5 ng/ml). Comparative investigations of the pregnancies which, according to sonographic findings, remained intact until curettage and those which were aborted after the application of prostaglandin did not, in spite of low plasma progesterone and estradiol levels in the abortive group, reveal any statistically significant differences. The abortive effect--even with local application--of the prostaglandins was confirmed. Conclusions regarding the effective mechanism of the prostaglandins upon the fetoplacental unit and the function of the corpus luteum remain subject to speculation.

  10. Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.

    PubMed

    Dooley, Kelly; Flexner, Charles; Hackman, Judith; Peloquin, Charles A; Nuermberger, Eric; Chaisson, Richard E; Dorman, Susan E

    2008-11-01

    Moxifloxacin- and rifapentine-based regimens are under investigation for the treatment of tuberculosis. However, rifapentine may induce enzymes that metabolize moxifloxacin, resulting in decreased moxifloxacin concentrations. In this phase I, two-period, sequential-design study, 13 subjects received 400 mg moxifloxacin daily for 4 days followed by daily moxifloxacin coadministered with 900 mg rifapentine thrice weekly. Pharmacokinetic analyses were performed after the 4th and 19th doses of moxifloxacin and after the 1st and 7th doses of rifapentine. For moxifloxacin, the mean area under the concentration-time curve from 0 to 24 h (AUC(0-24)) decreased by 17.2% (P = 0.0006) when the drug was coadministered with rifapentine, and the mean half-life (t(1/2)) decreased from 11.1 to 8.9 h (P = 0.0033). For rifapentine, the mean AUC(0-48) after seven thrice-weekly doses decreased by 20.3% (P = 0.0035) compared to the AUC(0-48) after the first dose, and the mean t(1/2) decreased from 18.5 to 14.8 h (P = 0.0004). The AUC(0-48) for the 25-desacetyl-rifapentine metabolite diminished 21%. Two days after completing the study drugs, one subject developed a fever and hepatitis, and another developed a flu-like illness with a rash. In conclusion, rifapentine modestly reduced moxifloxacin concentrations. Changes consistent with rifapentine autoinduction of metabolism were seen. Adverse reactions in two subjects may have represented rifamycin hypersensitivity syndrome, although some features were atypical.

  11. Comparison of Capillary and Venous Plasma Drug Concentrations After Repeated Administration of Risperidone, Paliperidone, Quetiapine, Olanzapine, or Aripiprazole

    PubMed Central

    De Meulder, Marc; Ariyawansa, Jay; Savitz, Adam

    2016-01-01

    Abstract Quantification of blood levels of antipsychotic drugs may be useful for managing medication therapy. This open‐label, parallel‐group study was performed to compare finger‐stick‐based capillary with corresponding venous plasma concentrations for risperidone, paliperidone, quetiapine, olanzapine, and aripiprazole and their major metabolites after repeated dosing in patients with schizophrenia or related illnesses. Finger‐stick‐based capillary and venous blood samples were collected at various times within a dosing interval. All drug concentration measurements in the derived plasma samples were performed with validated liquid chromatography–tandem mass spectrometry methods. Finger‐stick‐based capillary and venous plasma drug concentrations after repeated dosing were generally similar. Olanzapine capillary plasma concentrations, however, were on average approximately 20% higher than venous concentrations, with a trend for a relatively greater difference occurring shortly after dosing. In addition, smaller capillary–venous differences were observed for extended‐release and long‐acting intramuscular formulations and for aripiprazole, a drug with a long half‐life, compared with drugs administered as an immediate‐release formulation (risperidone, olanzapine). After repeated dosing, plasma derived from finger‐stick‐based blood was observed to be predictive of the venous concentrations. Capillary sampling may be an appropriate alternative to venous sampling to readily evaluate systemic drug concentrations. PMID:27363344

  12. Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep

    PubMed Central

    Zullian, Chiara; Lema, Pablo; Lavoie, Melissa; Dodelet-Devillers, Aurore; Beaudry, Francis; Vachon, Pascal

    2016-01-01

    The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following blood collections at selected time points, plasma concentrations of buprenorphine was performed by tandem liquid chromatograph-mass spectrometry. Mean buprenorphine concentration was above 0.1 ng/mL at 48 h up to 192 h post-injection for group 1 and it was above 0.1 ng/mL at 48 h up to 72 h post-injection for group 2. In conclusion, a long lasting potential analgesic plasma level of buprenorphine is attained following a single subcutaneous injection of 0.1 mg/kg BW of SR buprenorphine in sheep. However the effective analgesic plasma threshold still needs to be determined in sheep. PMID:27408341

  13. Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep.

    PubMed

    Zullian, Chiara; Lema, Pablo; Lavoie, Melissa; Dodelet-Devillers, Aurore; Beaudry, Francis; Vachon, Pascal

    2016-07-01

    The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following blood collections at selected time points, plasma concentrations of buprenorphine was performed by tandem liquid chromatograph-mass spectrometry. Mean buprenorphine concentration was above 0.1 ng/mL at 48 h up to 192 h post-injection for group 1 and it was above 0.1 ng/mL at 48 h up to 72 h post-injection for group 2. In conclusion, a long lasting potential analgesic plasma level of buprenorphine is attained following a single subcutaneous injection of 0.1 mg/kg BW of SR buprenorphine in sheep. However the effective analgesic plasma threshold still needs to be determined in sheep.

  14. Effects of co-administration of fluoxetine or tianeptine with metyrapone on immobility time and plasma corticosterone concentration in rats subjected to the forced swim test.

    PubMed

    Rogóz, Zofia; Skuza, Grazyna; Leśkiewicz, Monika; Budziszewska, Bogusława

    2008-01-01

    Major depression is frequently associated with hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and glucocorticoid synthesis inhibitors have been shown to exert antidepressant action. The aim of the present study was to examine the effect of co-administration of fluoxetine or tianeptine with metyrapone on immobility time and plasma corticosterone concentration in male Wistar rats subjected to the forced swim test. Metyrapone alone (50 mg/kg, but not 25 mg/kg) reduced the immobility time of rats in the forced swim test; moreover, both doses tested (25 and 50 mg/kg), dose-dependently decreased the stress-induced plasma corticosterone concentration. Joint administration of fluoxetine or tianeptine (10 mg/kg) and metyrapone (25 mg/kg - a dose inactive per se) exhibited antidepressant-like activity in the forced swim test in rats. WAY 100636 (a 5-HT(1A) antagonist), but not prazosin (an alpha(1)-adrenergic antagonist), used in doses ineffective in the forced swim test, inhibited the antidepressant-like effect induced by co-administration of fluoxetine or tianeptine with metyrapone (25 mg/kg). Combined treatment of fluoxetine or tianeptine and metyrapone inhibited stress-induced corticosterone secretion to a similar extent as metyrapone alone. The obtained results indicate that metyrapone potentiates the antidepressant-like activity of fluoxetine or tianeptine and that, among other mechanisms, 5-HT(1A) receptors may play some role in this effect. Moreover, metyrapone exerts a beneficial effect on the stress-induced increase in plasma corticosterone concentration. These findings suggest that the co-administration of metyrapone and an antidepressant drug may be useful for the treatment of drug-resistant depression and/or depression associated with a high cortisol level.

  15. Comparison of ELISA and LC-MS/MS for the measurement of flunixin plasma concentrations in beef cattle after intravenous and subcutaneous administration.

    PubMed

    Shelver, Weilin L; Tell, Lisa A; Wagner, Sarah; Wetzlich, Scott E; Baynes, Ronald E; Riviere, Jim E; Smith, David J

    2013-03-20

    Eight cattle (288 ± 22 kg) were treated with 2.2 mg/kg of body weight of flunixin free acid in a crossover design by subcutaneous (SC) and intravenous (IV) administration. After a minimum 1:10 dilution with 50 mM phosphate buffer, a commercial immunoassay was adapted to determine plasma concentrations of flunixin. The limit of detection was 0.42 ng/mL and the working range was 0.76-66.4 ng/mL when adjusted with the dilution factor. Plasma samples were extracted using mixed-mode cation exchange solid phase extraction prior to the LC-MS/MS analyses. The linear calibration curve for LC-MS/MS was 0.5-2000 ng/mL with a limit of detection of 0.1 ng/mL for flunixin and 0.3 ng/mL for 5-hydroxy flunixin. Flunixin concentrations determined using the ELISAs were compared to concentrations derived from the same samples using LC-MS/MS analyses. Pharmacokinetic parameters of time versus concentration data from each analysis were estimated and compared. Differences (P < 0.05) in estimates of area under the curve, volume of distribution, and clearance were apparent between ELISA and LC-MS/MS analyses after IV dosing; after SC dosing, however, there were no differences among the estimated parameters between the two methods. Quantitative immunoassay was a satisfactory method of flunixin analysis and that it would be difficult to differentiate routes of administration in healthy beef cattle based on the plasma elimination profile of flunixin after IV or SC administration.

  16. Oral Fluid with Three Modes of Collection and Plasma Methamphetamine and Amphetamine Enantiomer Concentrations After Controlled Intranasal l-Methamphetamine Administration

    PubMed Central

    Newmeyer, Matthew N.; Concheiro, Marta; da Costa, Jose Luiz; Flegel, Ronald; Gorelick, David A.; Huestis, Marilyn A.

    2015-01-01

    Methamphetamine is included in drug testing programs due to its high abuse potential. d-Methamphetamine is a scheduled potent central nervous system stimulant, while l-methamphetamine is the unscheduled active ingredient in the over-the-counter nasal decongestant Vicks® VapoInhaler™. No data are available in oral fluid (OF) and few in plasma after controlled Vicks VapoInhaler administration. We quantified methamphetamine and amphetamine enantiomers in OF collected with two different devices and plasma via a fully validated LC-MS/MS method. Additionally, OF were analyzed with an on-site screening device. Sixteen participants received 7 Vicks VapoInhaler doses according to manufacturer's recommendations. Specimens were collected before and up to 32h after the first dose. No d-methamphetamine or d-amphetamine was detected in any sample. All participants had measurable OF l-methamphetamine with median maximum concentrations 14.8 and 16.1μg/L in Quantisal™ and Oral-Eze® devices, respectively, after a median of 5 doses. One participant had measurable OF l-amphetamine with maximum concentrations 3.7 and 5.5μg/L after 6 doses with the Quantisal and Oral-Eze devices, respectively. There were no positive DrugTest® 5000 results. In the cutoff range 20-50μg/L methamphetamine with amphetamine ≥limit of detection, 3.1-10.1% of specimens were positive; first positive results were observed after 1-4 doses. Two participants had detectable plasma l-methamphetamine, with maximum observed concentrations 6.3 and 10.0μg/L after 2 and 5 doses, respectively. Positive OF and plasma methamphetamine results are possible after Vicks VapoInhaler administration. Chiral confirmatory analyses are necessary to rule out VapoInhaler intake. Implementing a selective d-methamphetamine screening assay can help eliminate false-positive OF results. PMID:25786659

  17. Plasma and intraprostatic concentrations of ertapenem following preoperative single dose administration: a single-centre prospective experience and clinical implications-the ERTAPRO study.

    PubMed

    Dariane, Charles; Amin, Alexandre; Lortholary, Olivier; Lalli, Alexandre; Michel, Constance; Le Guilchet, Thomas; Treluyer, Jean-Marc; Nguyen-Khoa, Thao; De Toma, Claudia; Urien, Saïk; Méjean, Arnaud; Bourget, Philippe; Timsit, Marc-Olivier

    2016-08-01

    The incidence of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing pathogens is increasing. These infections are associated with a long hospital stay in patients undergoing urological procedures. We aimed to demonstrate that significant intraprostatic diffusion of ertapenem is achieved after a single preoperative administration. A referred sample of 19 patients requiring surgery for benign prostatic hyperplasia was prospectively included. Patients received a 1 g intravenous (i.v.) dose of ertapenem 1 h (n = 10, group A) or 12 h (n = 9, group B) before blood and prostatic samples were collected. Plasma and intraprostatic concentrations of ertapenem were measured using LC-MS/MS. Intraprostatic concentrations were considered satisfactory when higher than the MIC90 value of urinary-targeted pathogens perioperatively and for 40% of the dosing interval. The Wilcoxon test and a pharmacokinetic predictive model were used. Median plasma concentrations of ertapenem were 144.3 mg/L (95% CI 126.5-157.9) in group A and 30.7 mg/L (95% CI 22.9-36.4) in group B (P < 0.001); median intraprostatic concentrations were 16.6 mg/L (95% CI 13.3-31.4 mg/L) and 4.2 mg/L (95% CI 3.1-4.9 mg/L), respectively (P < 0.001), which were above the MIC90 values of bacteria, including ESBL-producers, during surgery and for 40% of the dosing interval. The plasma-to-prostate concentration ratio was not significantly different between groups (P = 0.97). Single-dose i.v. ertapenem reached satisfactory intraprostatic concentrations, suggesting that it could be a relevant prophylactic strategy for carriers of ESBL-producing bacteria undergoing prostatic procedures, which needs to be confirmed by further prospective trials.

  18. Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs.

    PubMed

    Bimazubute, M; Cambier, C; Baert, K; Vanbelle, S; Chiap, P; Gustin, P

    2011-04-01

    The penetration of oxytetracycline (OTC) in plasma and nasal secretions of healthy pigs was evaluated during the first study, in response to oral dose of 20 mg of OTC per kg of body weight (bwt) per day as a 400 mg/kg feed medication (n = 5) and to intramuscular (i.m.)-administered formulations at 10 mg/kg bwt (n = 5), 20 mg/kg bwt (n = 5), 40 mg/kg bwt (n = 5). Concentrations of OTC in plasma and nasal secretions were determined by a validated ultra-high performance liquid chromatography associated to tandem mass spectrometry method (UPLC/MS/MS). The objectives were to select the efficacy treatment and to evaluate the possibility to predict nasal secretions concentrations from those determined in plasma. The animals were housed together in each experiment. In each group, the treatment was administered once daily during 6 consecutive days, and nasal secretions and plasma were collected after 4 and 24 h at day 2 and day 6. For oral administration, only one medicated feed was prepared and distributed to all the animals together and was consumed in approximately 1 h. To meet recommendations of efficacy for OTC in nasal secretions, only the i.m. of 40 mg/kg bwt associated to an inter-dosing interval of 24 h provides and maintains concentrations in nasal secretions ≥1 μg/mL, appropriate to the MIC 50 and 90 of Pasteurella multocida and Bordetella bronchiseptica, respectively, the main pathological strains in nasal secretions. It has been demonstrated that, using a generalized linear mixed model (GLMM), OTC in the nasal secretions (μg/mL) can be predicted taking into account the OTC concentrations in plasma (μg/mL), according to the following equation: OTC(nasal secretions)  = 0.28 OTC(plasma) -1.49. In a second study, the pharmacokinetic behaviour of OTC in plasma and nasal secretions of healthy pigs was investigated, after single-dose i.m. of 40 mg/kg bwt of the drug. Blood samples and nasal secretions were collected at

  19. Oral fluid with three modes of collection and plasma methamphetamine and amphetamine enantiomer concentrations after controlled intranasal l-methamphetamine administration.

    PubMed

    Newmeyer, Matthew N; Concheiro, Marta; da Costa, Jose Luiz; Flegel, Ronald; Gorelick, David A; Huestis, Marilyn A

    2015-10-01

    Methamphetamine is included in drug testing programmes due to its high abuse potential. d-Methamphetamine is a scheduled potent central nervous system stimulant, while l-methamphetamine is the unscheduled active ingredient in the over-the-counter nasal decongestant Vicks® VapoInhaler™. No data are available in oral fluid (OF) and few in plasma after controlled Vicks® VapoInhaler™ administration. We quantified methamphetamine and amphetamine enantiomers in OF collected with two different devices and plasma via a fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Additionally, OF were analyzed with an on-site screening device. Sixteen participants received 7 Vicks® VapoInhaler™ doses according to manufacturer's recommendations. Specimens were collected before and up to 32 h after the first dose. No d-methamphetamine or d-amphetamine was detected in any sample. All participants had measurable OF l-methamphetamine with median maximum concentrations 14.8 and 16.1 μg/L in Quantisal™ and Oral-Eze® devices, respectively, after a median of 5 doses. One participant had measurable OF l-amphetamine with maximum concentrations 3.7 and 5.5 μg/L after 6 doses with the Quantisal™ and Oral-Eze® devices, respectively. There were no positive DrugTest® 5000 results. In the cutoff range 20-50 μg/L methamphetamine with amphetamine ≥limit of detection, 3.1-10.1% of specimens were positive; first positive results were observed after 1-4 doses. Two participants had detectable plasma l-methamphetamine, with maximum observed concentrations 6.3 and 10.0 μg/L after 2 and 5 doses, respectively. Positive OF and plasma methamphetamine results are possible after Vicks® VapoInhaler™ administration. Chiral confirmatory analyses are necessary to rule out VapoInhaler™ intake. Implementing a selective d-methamphetamine screening assay can help eliminate false-positive OF results.

  20. The truth about the lower plasma concentration of the (-)-isomer after racemic doxazosin administration in rats: Stereoselective inhibition of the (-)-isomer by the (+)-isomer at CYP3A.

    PubMed

    Kong, Dezhi; Li, Qing; Zhang, Panpan; Zhang, Wei; Zhen, Yaqin; Ren, Leiming

    2015-09-18

    Doxazosin (DOX), a long-lasting α1-adrenoceptor antagonist, is used clinically as a racemate that consists of two optical isomers. In humans and rats, following oral administration of racemic DOX [(±)-DOX], the plasma concentration of the (-)-isomer is lower than that of the (+)-isomer, but the mechanism for this interaction is not known. In this study, a chiral HPLC with fluorescence detection was used to measure the drug concentrations for analysis of the stereoselective metabolism of DOX in in vivo and in vitro experiments. We found that the plasma levels of the (-)-isomer were significantly lower than those of the (+)-enantiomer following i.v. administration of (±)-DOX to the rats and that the depletion rate constant (kdep) of (-)-DOX (0.0107±0.0007L/min) was significantly larger than that of (+)-DOX (kdep 0.0088±0.0005L/min) (p<0.05) when (±)-DOX was incubated with rat liver microsomes (RLMs). However, (-)-DOX was not depleted faster than (+)-DOX following their separate incubation with RLMs. The metabolism of (-)- or (+)-isomer in RLMs was catalysed by CYP3A because the depletion of the compounds was inhibited by ketoconazole (a potent CYP3A-selective inhibitor) similarly. More importantly, the kdep of (+)-DOX in the 1.0/2.0 and 0.5/2.5 (+)-DOX/(-)-DOX mixtures was significantly lower than that of (-)-DOX in the 1.0/2.0 and 0.5/2.5 (-)-DOX/(+)-DOX mixtures (p<0.05). In conclusion, although (-)-DOX is not depleted faster than (+)-DOX when only a single isomer of DOX is incubated with rat liver microsomes, it is depleted much faster than (+)-DOX when a mixture of the two isomers was used, suggesting a prominent and stereoselective inhibition of the (-)-isomer over the (+)-isomer at the CYP3A enzyme.

  1. Gastric pH influences the appearance of double peaks in the plasma concentration-time profiles of cimetidine after oral administration in dogs.

    PubMed

    Mummaneni, V; Amidon, G L; Dressman, J B

    1995-05-01

    The plasma concentration-time profiles of cimetidine often exhibit two peaks following oral administration of a single dose in the fasted state, while the concurrent administration of some antacids results in a lower extent as well as rate of absorption. In the present work, absorption of cimetidine after a single dose in the fasted state was studied as a function of gastric pH in male beagle dogs to determine whether gastric pH plays a role in the double peak phenomenon and/or can account for the decrease in bioavailability when antacids are coadministered. The extent of absorption of cimetidine was not influenced significantly by gastric pH, indicating that elevation of gastric pH is not the cause of decreases in the bioavailability of cimetidine when it is administered with antacids. Distinct double peaks or plateaux were noted in 8 of 10 plasma profiles when the gastric pH was 3 or below. Irregular absorption behavior was observed in 2 of 6 profiles in the pH range of 3 to 5, while single peaks were observed in all 10 profiles when the gastric pH was maintained at pH > or = 5. It was concluded that gastric pH is a major factor in the generation of cimetidine double peaks. Changes in gastric pH also resulted in changes in the apparent kinetics of absorption. Below pH 5, absorption mostly followed zero-order kinetics (9 of 16 profiles) or a more complex kinetic process involving at least two components to the absorption phase (5 of 16 profiles). At gastric pH > or = 5, however, absorption followed first order kinetics in 7 of 10 profiles. These differences in kinetics of absorption are postulated to arise from variations in gastric emptying as a function of pH and/or carryover effects of gastric pH into the upper intestine.

  2. Comparison of ELISA and LC-MS/MS for the measurement of flunixin plasma concentrations in beef cattle after intravenous and subcutaneous administration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The feasibility of using an enzyme linked immunosorbant assay (ELISA) with only simple preparation steps to determine flunixin plasma concentrations in healthy beef cattle was explored. Eight cattle (288 ± 22 kg) were treated with 2.2 mg/kg bw flunixin free acid in a cross-over design by subcutaneo...

  3. Effect of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration and anxiety behaviors in adult rat offspring.

    PubMed

    Nakhjiri, Elnaz; Saboory, Ehsan; Roshan-Milani, Shiva; Rasmi, Yousef; Khalafkhani, Davod

    2017-03-28

    Stressful events and exposure to opiates during gestation have important effects on the later mental health of the offspring. Anxiety is among the most common mental disorders. The present study aimed to identify effects of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration (PVC) and anxiety behaviors in rats. Pregnant rats were divided into four groups (n = 6, each): saline, morphine, stress + saline and stress + morphine treatment. The stress procedure consisted of restraint twice per day, two hours per session, for three consecutive days starting on day 15 of pregnancy. Rats in the saline and morphine groups received either 0.9% saline or morphine intraperitoneally on the same days. In the morphine/saline + stress groups, rats were exposed to restraint stress and received either morphine or saline intraperitoneally. All offspring were tested in an elevated plus maze (EPM) on postnatal day 90 (n = 6, each sex), and anxiety behaviors of each rat were recorded. Finally, blood samples were collected to determine PVC. Prenatal morphine exposure reduced anxiety-like behaviors. Co-administration of prenatal stress and morphine increased locomotor activity (LA) and PVC. PVC was significantly lower in female offspring of the morphine and morphine + stress groups compared with males in the same group, but the opposite was seen in the saline + stress group. These data emphasize the impact of prenatal stress and morphine on fetal neuroendocrine development, with long-term changes in anxiety-like behaviors and vasopressin secretion. These changes are sex specific, indicating differential impact of prenatal stress and morphine on fetal neuroendocrine system development. Lay Summary Pregnant women are sometimes exposed to stressful and painful conditions which may lead to poor outcomes for offspring. Opiates may provide pain and stress relief to these mothers. In this study, we used an experimental model of

  4. Hydrogen concentration in expired air analyzed with a new hydrogen sensor, plasma glucose rise, and symptoms of lactose intolerance after oral administration of 100 gram lactose.

    PubMed

    Berg, A; Eriksson, M; Bárány, F; Einarsson, K; Sundgren, H; Nylander, C; Lundström, I; Blomstrand, R

    1985-09-01

    A rapid breath hydrogen analyzer to detect lactose malabsorption is described. After ingestion of a lactose solution the patient expires into a mouthpiece attached to a hydrogen sensor at 30-min intervals for 3 1/2 h. The hydrogen of the expired air causes a voltage change that can be transformed into ppm from a calibration curve. A tolerance test with a load of 100 g lactose was performed in 43 consecutive patients with various gastrointestinal disturbances, referred to the laboratory for the commonly used lactose tolerance test based on plasma glucose measurements. Eleven patients developed symptoms of lactose intolerance during the test. Biopsy specimens from the distal duodenum or proximal jejunum showed partial villous atrophy in one, in whom celiac disease with lactose intolerance was diagnosed; the other 10 had normal specimens. In nine of them lactose intolerance was diagnosed and confirmed by observation for months on a lactose-poor diet. The 10th patient (H.P.L.) did not improve on such a diet. He also showed pronounced symptoms of intolerance during a test with monosaccharides (glucose + galactose). His intestinal disease remained undiagnosed. The 11 patients with symptoms of intolerance and 3 patients without symptoms during the lactose load showed a flat plasma glucose curve after drinking the lactose solution--that is, a maximum rise of the glucose concentration of 1.5 mmol/l. One of the symptom-free patients dropped out and could not be observed, another did not improve on a lactose-poor diet, and the third noticed a favorable effect of the diet on stool consistency but not on other abdominal symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. L-carnitine administration and withdrawal affect plasma and hepatic carnitine concentrations, plasma lipid and lipoprotein composition, and in vitro hepatic lipogenesis from labeled mevalonate and oleate in normal rabbits.

    PubMed

    Bell, F P; Vidmar, T J; Raymond, T L

    1992-04-01

    Carnitine was administered to normal rabbits to investigate the possible effects of pharmacologic doses on various aspects of normal lipid and lipoprotein metabolism. Carnitine concentrations were measured in the plasma and liver of normal rabbits that received L-carnitine orally [40 mg/(kg.d)] for 21 d and after withdrawal from the carnitine supplement for 21 d. Plasma lipids, plasma lipoprotein composition and in vitro hepatic lipid biosynthesis from [2-14C]mevalonate and [1-14C]oleate were also measured. Threefold elevations in plasma carnitine with carnitine treatment were essentially reversed after 48 h of carnitine withdrawal, but elevated hepatic carnitine accumulation (twofold) persisted for 21 d, suggesting that the accumulated carnitine constituted a pool that is only slowly miscible with plasma. The rabbits withdrawn from L-carnitine for 21 d experienced a 35% decrease in plasma cholesterol, a 50% decrease in VLDL cholesterol, and an increase in the protein content of HDL and of intermediate density lipoprotein + LDL. Additionally, the proportion of [14C]oleate incorporated into hepatic phospholipids increased 35% at the expense of triglyceride and the ratio of hepatic [14C]cholesterol to [14C]squalene derived from [14C]mevalonate increased over twofold following carnitine withdrawal. These studies provide evidence that normal lipid homeostasis can be altered by supplemental carnitine and that the perturbations are reflected by changes in plasma lipids and lipoproteins and in the proportions of the hepatic lipids synthesized.

  6. 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.

  7. 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.

  8. Comparison of ELISA and LC-MS/MS for the measurement of flunixin plasma concentrations in beef cattle after intravenous and subcutaneous administration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eight cattle (288 +/- 22 kg) were treated with 2.2 mg/kg of flunixin in a cross-over design using subcutaneous (SC) and intravenous (IV) administration. The limit of detection (LOD) was 0.42 ng/mL and the working range was 0.76 - 66.4 ng/mL for ELISA when adjusted for dilution. The linear calibrat...

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  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. 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.

  17. 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.

  18. 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

  19. Effects of Oral Administration of Chitin Nanofiber on Plasma Metabolites and Gut Microorganisms

    PubMed Central

    Azuma, Kazuo; Izumi, Ryotaro; Kawata, Mari; Nagae, Tomone; Osaki, Tomohiro; Murahata, Yusuke; Tsuka, Takeshi; Imagawa, Tomohiro; Ito, Norihiko; Okamoto, Yoshiharu; Morimoto, Minoru; Izawa, Hironori; Saimoto, Hiroyuki; Ifuku, Shinsuke

    2015-01-01

    The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs) and surface-deacetylated (SDA) CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations of CNFs and SDACNFs. Healthy female mice (six-week-old) were fed a normal diet and administered tap water with 0.1% (v/v) CNFs or SDACNFs for 28 days. Oral administration of CNFs increased plasma levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and serotonin (5-hydroxytryptamine, 5-HT). Oral administration of SDACNFs affected the metabolisms of acyl-carnitines and fatty acids. The fecal organic level analysis indicated that oral administration of CNFs stimulated and activated the functions of microbiota. These results indicate that oral administration of CNFs increases plasma levels of ATP and 5-HT via activation of gut microbiota. PMID:26378523

  20. Effects of Oral Administration of Chitin Nanofiber on Plasma Metabolites and Gut Microorganisms.

    PubMed

    Azuma, Kazuo; Izumi, Ryotaro; Kawata, Mari; Nagae, Tomone; Osaki, Tomohiro; Murahata, Yusuke; Tsuka, Takeshi; Imagawa, Tomohiro; Ito, Norihiko; Okamoto, Yoshiharu; Morimoto, Minoru; Izawa, Hironori; Saimoto, Hiroyuki; Ifuku, Shinsuke

    2015-09-10

    The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs) and surface-deacetylated (SDA) CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations of CNFs and SDACNFs. Healthy female mice (six-week-old) were fed a normal diet and administered tap water with 0.1% (v/v) CNFs or SDACNFs for 28 days. Oral administration of CNFs increased plasma levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and serotonin (5-hydroxytryptamine, 5-HT). Oral administration of SDACNFs affected the metabolisms of acyl-carnitines and fatty acids. The fecal organic level analysis indicated that oral administration of CNFs stimulated and activated the functions of microbiota. These results indicate that oral administration of CNFs increases plasma levels of ATP and 5-HT via activation of gut microbiota.

  1. Plasma prolactin concentrations in lead exposed workers.

    PubMed

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

    1987-01-01

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

  2. Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

    PubMed Central

    Osaki, Tomohiro; Kurozumi, Seiji; Sato, Kimihiko; Terashi, Taro; Azuma, Kazuo; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2015-01-01

    N-acetyl-d-glucosamine (GlcNAc) is a monosaccharide that polymerizes linearly through (1,4)-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001). To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism. PMID:26262626

  3. Increases in Serum Growth Hormone Concentrations Associated with GHB Administration.

    PubMed

    Brailsford, Alan D; Bartlett, Christiaan; Kicman, Andrew T; Cowan, David A

    2017-01-01

    The administration of gamma-hydroxybutyrate (GHB) has been reported to augment the increase in growth hormone (GH) secretion associated with the onset of sleep. The ability of GHB to stimulate GH production in the absence of sleep in both male and female volunteers was investigated as part of a GHB administration study. Twelve healthy volunteers (six men and six women) were given a small oral dose (25 mg/kg) of GHB (as Xyrem(®)) at 10:00 h. Basal blood samples (as serum) were taken 10 min prior to GHB administration, with additional samples taken at 10, 15, 20, 25, 30, 45, 60, 90, 120, 150, 180, 240, 360 and 480 min post-administration. The serum concentrations of GHB were measured by GC-MS and GH by immunometric assay. Following GHB administration, volunteers exhibited effects consistent with mild sedation, i.e., relaxed with normal responses to verbal stimuli. Despite none being asleep, an increase in serum GH concentration occurred in 11 out of the 12 volunteers (5 women and 6 men). In these volunteers, peak GH concentrations occurred 45-60 min post-administration compared with a mean serum tmax for GHB of 23 min (SD = 5.4 min). The absolute increase in GH was similar for men and women, averaging 3.4 and 3.7 ng/mL, respectively. The mean intra-individual increase in GH was much greater in males (29 times) compared with females (2 times), as males had (as expected) smaller basal GH concentrations (mean = 0.26 ng/mL) compared with females (mean = 5.4 ng/mL). After maximizing, the GH concentration decreased rapidly (in agreement with GHB concentrations), returning to basal concentrations at ~90-120 min post-administration. GHB administration at a small therapeutic dose results in increases in serum GH concentrations in healthy male and female volunteers in the absence of sleep onset.

  4. Plasma and dermal pharmacokinetics of terpinen-4-ol in rats following intravenous administration.

    PubMed

    Chooluck, K; Singh, R P; Sathirakul, K; Derendorf, H

    2013-02-01

    Terpinen-4-ol, a naturally occurring monoterpene, has been shown to possess antibacterial, antioxidant and anti-inflammatory activities. Furthermore, recent reports have demonstrated that terpinen-4-ol could be developed as new therapies against melanoma either in systemic administration or targeted drug delivery. The purpose of this study was to investigate the pharmacokinetics of terpinen-4-ol in rat plasma and dermal tissue following intravenous (i.v.) bolus injection of terpinen-4-ol at a dose of 2 mg/kg. Unbound concentrations of terpinen-4-ol in dermis were continuously determined by dermal microdialysis. Simultaneously, a conventional blood sampling was performed. The concentrations of terpinen-4-ol in plasma and microdialysates were determined by validated gas chromatography-mass spectrometry. Following i.v. bolus administration, terpinen-4-ol rapidly distributed into the dermis and reached relatively low levels with an average maximum concentration (Cmax) of 0.10 +/- 0.06 microg/ml in comparison with a plasma Cmax of 6.30 +/- 1.90 microg/ml. The free terpinen-4-ol concentrations in dermal tissue were lower than the corresponding total and free plasma concentrations for the entire length of study, indicating that plasma levels do not provide information of actual terpinen-4-ol concentrations in the skin. This study demonstrates that dermal microdialysis is an effective and minimally invasive tool to evaluate the dermal pharmacokinetics of terpinen-4-ol following systemic administration.

  5. 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.

  6. 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.

  7. 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...

  8. Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration

    PubMed Central

    Bach-Huynh, Thien-Giang; Nayak, Bindu; Loh, Jennifer; Soldin, Steven; Jonklaas, Jacqueline

    2009-01-01

    Context: Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption. The serum thyrotropin concentration is the therapeutic index of levothyroxine action. Objective: The study objective was to determine the effect of the timing of levothyroxine administration in relationship to food on serum thyrotropin levels. Design: Participants were randomized to one of six sequences, each consisting of three 8-wk regimens in a three-period crossover design. These regimens were in a fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T4, and total T3 during each of the three timing regimens were documented. The primary outcome was the difference between serum TSH concentrations under fasting conditions compared with concentrations during the other 8-wk regimens. Setting: The study was conducted in an academic medical center. Participants: Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer. Results: Sixty-five patients completed the study. The mean thyrotropin concentration was 1.06 ± 1.23 mIU/liter when levothyroxine was administered in the fasting state. When levothyroxine was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 ± 3.29 mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration was also significantly higher (2.19 ± 2.66 mIU/liter). Conclusion: Nonfasting regimens of levothyroxine administration are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH concentrations remain within the narrowest target range. PMID:19584184

  9. Plasma disposition and tissue residue of Moxifloxacin in Japanese quails (Coturnix japonica) following different routes of administration.

    PubMed

    Goudah, A; Hasabelnaby, S

    2014-01-01

    The disposition kinetics and the plasma availability of moxifloxacin were investigated in Japanese quails (Coturnix japonica) following different routes of administration at 5 mg/kg body weight. Tissue residue profiles (liver, kidney, lung and muscle) and plasma were also studied after multiple intramuscular and oral administrations of 5 mg/kg body weight, once daily for 5 consecutive days. Following intravenous injection, plasma concentration-time curves were best described by a two-compartment open model. After intramuscular and oral administration of moxifloxacin, the peak plasma concentrations (Cmax) were 2.14 and 1.94 μg/ml and were obtained at 1.40 and 1.87 h (Tmax), post administration, respectively. The systemic bioavailabilities following intramuscular and oral administration, respectively, of moxifloxacin were 92.48 and 87.94%. 6. Tissue concentrations following i.m. and p.o. administration were highest in liver and kidney, respectively, and decreased in the following order: plasma, lung and muscle. No moxifloxacin residues were detected in tissues and plasma after 120 h after i.m. or oral administration.

  10. Plasma prolactin changes during the administration of human menopausal gonadotropins in nonovulatory women.

    PubMed

    Kemmann, E; GEMZELL, C A; Beinert, W C; Beling, C B; Jones, J R

    1977-09-15

    Plasma prolactin concentrations were determined in 16 nonovulatory women during treatment with human meonpausal gonadotropins (hMG). In eight patients with initially normal prolactin levels of less than 20 ng. per milliliter, a significant rise was noted at the end of hMG administration, this is thought to be a response to increased endogenous estrogen concentrations. A similar rise in plasma prolactin levels was seen in some but not all of the eight patients with initially elevated "basal" prolactin concentrations. Three of these hyperprolactinemic patients had radiographic evidence of a pituitary lesion--either a pituitary adenoma or a "microadenoma"--but the variance in prolactin response could not be explained on this basis. The two groups of normo- and hyper-prolactinemic patients showed no significant difference in the required dosage and duration or hMG treatment, plasma estradiol-17 beta response, and ovulatory and pregnancy outcome.

  11. Oral Fluid and Plasma Cannabinoid Ratios after Around-the-Clock Controlled Oral Δ9-Tetrahydrocannabinol Administration

    PubMed Central

    Milman, Garry; Schwope, David M.; Schwilke, Eugene W.; Darwin, William D.; Kelly, Deanna L.; Goodwin, Robert S.; Gorelick, David A.; Huestis, Marilyn A.

    2013-01-01

    BACKGROUND Oral fluid (OF) testing is increasingly important for drug treatment, workplace, and drugged-driving programs. There is interest in predicting plasma or whole-blood concentrations from OF concentrations; however, the relationship between these matrices is incompletely characterized because of few controlled drug-administration studies. METHODS Ten male daily cannabis smokers received around-the-clock escalating 20-mg oral Δ9-tetrahydrocannabinol (THC, dronabinol) doses (40–120 mg/day) for 8 days. Plasma and OF samples were simultaneously collected before, during, and after dosing. OF THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC (THCCOOH) were quantified by GC-MS at 0.5-μg/L, 0.5-μg/L, and 7.5-ng/L limits of quantification (LOQs), respectively. In plasma, the LOQs were 0.25 μg/L for THC and THCCOOH, and 0.5 μg/L for 11-hydroxy-THC. RESULTS Despite multiple oral THC administrations each day and increasing plasma THC concentrations, OF THC concentrations generally decreased over time, reflecting primarily previously self-administered smoked cannabis. The logarithms of the THC concentrations in oral fluid and plasma were not significantly correlated (r = −0.10; P = 0.065). The OF and plasma THCCOOH concentrations, albeit with 1000-fold higher concentrations in plasma, increased throughout dosing. The logarithms of OF and plasma THCCOOH concentrations were significantly correlated (r = 0.63; P < 0.001), although there was high interindividual variation. A high OF/plasma THC ratio and a high OF THC/THCCOOH ratio indicated recent cannabis smoking. CONCLUSIONS OF monitoring does not reliably detect oral dronabinol intake. The time courses of THC and THCCOOH concentrations in plasma and OF were different after repeated oral THC doses, and high inter-individual variation was observed. For these reasons, OF cannabinoid concentrations cannot predict concurrent plasma concentrations. PMID:21875944

  12. 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.

  13. 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.

  14. 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

  15. Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice.

    PubMed

    Neumann, Inga D; Maloumby, Rodrigue; Beiderbeck, Daniela I; Lukas, Michael; Landgraf, Rainer

    2013-10-01

    The possibility to improve socio-emotional behaviors in humans by intranasal administration of synthetic oxytocin (OXT) attracts increasing attention, but its uptake into the brain has never been demonstrated so far. Here we used simultaneous microdialysis in both the dorsal hippocampus and amygdala of rats and mice in combination with concomitant blood sampling from the jugular vein to study the dynamics of the neuropeptide in brain extracellular fluid and plasma after its nasal administration. OXT was found to be increased in microdialysates from both the hippocampus and amygdala with peak levels occurring 30-60min after nasal administration. Despite a similar temporal profile of OXT concentrations in plasma, peripheral OXT is unlikely to contribute to dialysate OXT as calculated from in vitro recovery data, indicating a central route of transport. Moreover, intraperitoneal administration of synthetic OXT in identical amounts caused rapid peak levels in brain dialysates and plasma during the first 30min after treatment and a subsequent return toward baseline. While the precise route(s) of central transport remain to be elucidated, our data provide the first evidence that nasally applied OXT indeed reaches behaviorally relevant brain areas, and this uptake is paralleled by changes in plasma OXT.

  16. Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys.

    PubMed

    Gokbulut, Cengiz; Akar, Ferda; McKellar, Quintin A

    2006-07-01

    Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is

  17. 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.

  18. The Effects of Fat-soluble Vitamin Administration on Plasma Vitamin Status of Nursing Pigs Differ When Provided by Oral Administration or Injection

    PubMed Central

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

    2014-01-01

    Four experiments were conducted to investigate the effect of fat-soluble vitamin administration to sows or newborn pigs on plasma vitamin status. In Exp. 1 and 2, a total of 24 and 43 newborn pigs were allotted to control and vitamin treatments (vitamin D3 with variable addition of vitamins A and E) orally or by i.m. injection. In Exp. 3, pigs from Exp. 2 were allotted to 2 treatments (±vitamins D3 and E in drinking water) for 14 d postweaning. In Exp. 4, twenty-four gestating sows were used for 2 treatments (±injection of a vitamin D3/A/E product 2 wk prepartum). In Exp. 1 and 2, when vitamin D3 was administrated orally or by i.m. injection on d 1 of age, pigs had increased plasma 25-hydroxycholecalciferol (25-OH D3) concentration 10 d after administration compared with control pigs (p<0.05). The injectable administration with vitamin D3 and E was able to achieve higher plasma 25-OH D3 (p<0.05) and α-tocopherol (p<0.05) concentrations than oral administration. At weaning, the pigs in the injection group had higher plasma 25-OH D3 concentration than those in the other groups in both studies (p<0.05). In Exp. 3, water supplementation of vitamin D3 and E postweaning increased plasma 25-OH D3 and α-tocopherol concentrations at d 14 postweaning (p<0.01). In Exp. 4, when sows were injected with the vitamin D3 product prepartum, serum 25-OH D3 concentrations of sows at farrowing (p<0.01), and in their progeny at birth (p<0.01) and weaning (p<0.05) were increased. These results demonstrated that fat-soluble vitamin administration to newborn pigs increased plasma 25-OH D3 concentration regardless of administration routes and α-tocopherol concentration by the injectable route, and that water supplementation of vitamin D3 and E to nursery pigs increased plasma 25-OH D3 and α-tocopherol concentrations. Additionally, injecting sows with vitamin D3 prepartum increased 25-OH D3 in sows and their offspring. If continued research demonstrates that the serum levels of 25-OH D

  19. 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.

  20. 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

  1. Effect of fatty acid administration on plasma thyroid hormones in the domestic fowl.

    PubMed

    Klandorf, H; Chua Teco, G N; Chopra, I J

    1988-06-01

    In birds a severe stress is associated with a reduction in concentrations of plasma thyroxine. Studies in man and the rat have demonstrated that severe illness is associated with an increase in serum concentrations of free fatty acids, notably oleic acid, and that they are associated with a reduction in concentrations of serum thyroxine (T4) and/or triiodothyronine (T3). Since stress is associated with increased fatty acids in birds, we have, in the present study, examined the role of oleic acid and another polyunsaturated fatty acid, arachidonic acid, on thyroid function tests (plasma thyroxine, triiodothyronine, and T3 resin uptake (RT3U) index) and on the thyroidal response to exogenous thyroid-stimulating hormone (TSH) in the domestic fowl. In the first study we observed that the iv administration of arachidonic (10 mg/kg) or oleic acid (15 mg/kg) to groups of 10-week-old cockerels (six per group) was associated with a significant reduction in concentrations of plasma T4, whereas there was little change in saline-injected controls. However, administration of fatty acids to chickens was not associated with a significant change in RT3U index or in the levels of plasma T3. In the second study, groups of animals (n = 6) were injected with bovine TSH (0.5 IU/kg, im) or saline 2.5 hr after the fatty acid injection and blood samples were obtained at -2.5 to 24 hr after the TSH injection. A similar progressive increase in serum T4 was observed for the three groups studied whereas there was little change in the concentrations of plasma T3.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Plasma disposition of enrofloxacin following intravenous and intramuscular administration in donkeys.

    PubMed

    Sekkin, S; Gokbulut, C; Kum, C; Karademir, U

    2012-11-03

    This study was designed to investigate the plasma disposition and systemic availability of enrofloxacin (ENR) following intramuscular and intravenous administrations. Six donkeys (Equus asinus) were used in this study. The animals were allocated into two groups (intramuscular and intravenous groups). After a 2-week washout period, the experiment was repeated with the groups reversed according to a two-phase crossover design. In phase I, group I received intravenously the commercially available injectable solution of ENR at the dose of 5 mg/kg and group II received intramuscularly the same ENR formulation at the same dose rate. Blood samples were collected 1 hour prior to drug administration and various times between 5 minutes and 48 hours post-treatments. The samples were analysed by high performance liquid chromatography with fluorescence detector. The half-life and mean residence time of ENR (12.08 hours and 17.85 hours) after intramuscular route were significantly longer compared with intravenous administration (9.54 hours and 7.46 hours, respectively) and these were associated with a flip-flop phenomenon. A marked proportion of ENR (20-21 per cent) was metabolised to ciprofloxacin (CPR) following both administration routes and the half-life of CPR paralleled that of the parent drug after intramuscular administration. Mean absorption time was relatively long (10.39 hours), and the bioavailability of ENR was 76.56 per cent after intramuscular route in the donkeys. The plasma concentration is lower after intramuscular administration at a dose rate of 5 mg/kg, and may need a higher dose to provide sufficient plasma concentration in donkeys compared with horses.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  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. Evaluation of plasma antioxidant activity in rats given excess EGCg with reference to endogenous antioxidants concentrations and assay methods.

    PubMed

    Yokotani, Kaori; Umegaki, Keizo

    2017-02-01

    The contribution of (-)-epigallocatechin gallate (EGCg) intake to in vivo antioxidant activity is unclear, even with respect to plasma. In this study, we examined how administration of EGCg contributes to plasma antioxidant activity, relative to its concentration, endogenous antioxidants, and assay methods, namely oxygen radical absorbance capacity (ORAC) and ferric reducing/antioxidant power (FRAP). Administration of EGCg (500 mg/kg) to rats increased plasma EGCg (4μmol/L as free form) and ascorbic acid (1.7-fold), as well as ORAC (1.2-fold) and FRAP (3-fold) values. The increase in plasma ascorbic acid following EGCg administration was accompanied by its relocation from the adrenal glands and lymphocytes into plasma, and was related to the increase in FRAP. Plasma deproteinization and assays in plasma model solutions revealed that protein levels significantly contributed to ORAC values, where <3 μmol/L EGCg in the presence of protein exhibited minimal antioxidant activity, as measured by both FRAP and ORAC. As the concentration of plasma ascorbic acid was not influenced by deproteinization, differences in FRAP values with and without deproteinization were estimated to determine the contribution of enhanced ascorbic acid attributable to EGCg administration. These results will help to understand the points that should be considered when evaluating EGCg antioxidant activity in plasma.

  12. Comparison of Capillary and Venous Drug Concentrations After Administration of a Single Dose of Risperidone, Paliperidone, Quetiapine, Olanzapine, or Aripiprazole

    PubMed Central

    De Meulder, Marc; Weiner, Sveta; Savitz, Adam

    2016-01-01

    Abstract Risperidone, paliperidone, quetiapine, olanzapine, and aripiprazole are antipsychotic drugs approved for treating various psychiatric disorders, including schizophrenia. The objective of this randomized, parallel‐group, open‐label study was to compare finger‐stick‐based capillary with corresponding venous whole‐blood and plasma concentrations for these drugs after administration of a single dose to healthy volunteers. All whole‐blood and plasma drug concentrations were measured with validated liquid chromatography–tandem mass spectrometry methods. Capillary and venous concentrations (both in plasma and whole blood) were in close agreement, although a time‐dependent difference was observed, most obviously for olanzapine and paliperidone, with slightly higher capillary versus venous drug concentrations during the first hours after administering a single dose. The observed difference between capillary and venous plasma drug concentrations is expected not to be relevant in clinical practice, considering the wide window of therapeutic concentrations and the wide range of drug concentrations in the patient population for a given dose. Based on these results, finger‐stick‐based capillary drug concentrations have been shown to approximate venous drug concentrations. PMID:27365164

  13. Changes of human plasma dopamine-beta-hydroxylase activity after intravenous administration of theophylline.

    PubMed

    Aunis, D; Mandel, P; Miras-Portugal, M T; Coquillat, G; Rohmer, F; Warter, J M

    1975-03-01

    The intravenous administration of theophylline to ten healthy human subjects produced either an increase of circulating plasma dopamine-beta-hydroxylase or no change. The rise of plasma enzyme activity may reflect the increased peripheral catecholamine release induced by theophylline.

  14. 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.

  15. 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.

  16. Oral fluid and plasma 3,4-methylenedioxymethamphetamine (MDMA) and metabolite correlation after controlled oral MDMA administration.

    PubMed

    Desrosiers, Nathalie A; Barnes, Allan J; Hartman, Rebecca L; Scheidweiler, Karl B; Kolbrich-Spargo, Erin A; Gorelick, David A; Goodwin, Robert S; Huestis, Marilyn A

    2013-05-01

    Oral fluid (OF) offers a noninvasive sample collection for drug testing. However, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in OF has not been adequately characterized in comparison to plasma. We administered oral low-dose (1.0 mg/kg) and high-dose (1.6 mg/kg) MDMA to 26 participants and collected simultaneous OF and plasma specimens for up to 143 h after dosing. We compared OF/plasma (OF/P) ratios, time of initial detection (t first), maximal concentrations (C max), time of peak concentrations (t max), time of last detection (t last), clearance, and 3,4-methylenedioxyamphetamine (MDA)-to-MDMA ratios over time. For OF MDMA and MDA, C max was higher, t last was later, and clearance was slower compared to plasma. For OF MDA only, t first was later compared to plasma. Median (range) OF/P ratios were 5.6 (0.1-52.3) for MDMA and 3.7 (0.7-24.3) for MDA. OF and plasma concentrations were weakly but significantly correlated (MDMA: R(2) = 0.438, MDA: R(2) = 0.197, p < 0.0001). Median OF/P ratios were significantly higher following high dose administration: MDMA low = 5.2 (0.1-40.4), high = 6.0 (0.4-52.3, p < 0.05); MDA low = 3.3 (0.7-17.1), high = 4.1 (0.9-24.3, p < 0.001). There was a large inter-subject variation in OF/P ratios. The MDA/MDMA ratios in plasma were higher than those in OF (p < 0.001), and the MDA/MDMA ratios significantly increased over time in OF and plasma. The MDMA and MDA concentrations were higher in OF than in plasma. OF and plasma concentrations were correlated, but large inter-subject variability precludes the estimation of plasma concentrations from OF.

  17. 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.

  18. 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.

  19. 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.

  20. 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)

  1. 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

  2. Melatonin administration in diabetes: regulation of plasma Cr, V, and Mg in young male Zucker diabetic fatty rats.

    PubMed

    Navarro-Alarcon, Miguel; Ruiz-Ojeda, Francisco J; Blanca-Herrera, Rosa M; Kaki, Abdullah; Adem, Abdu; Agil, Ahmad

    2014-03-01

    The use of melatonin, a neurohormone present in plants, represents an exciting approach for the maintenance of optimum health conditions. Melatonin administration ameliorates glucose homeostasis in Zucker diabetic fatty (ZDF) rats. The objective of this study was to investigate the effects of melatonin in diabetes in relation to the levels and regulation of plasma chromium (Cr), vanadium (V), and magnesium (Mg) in Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. At the age of 6 weeks, ZDF (n = 30) and ZL (n = 30) groups were each subdivided into three groups: control (C) (n = 10), vehicle-treated (V') (n = 10) and melatonin-treated (M) (10 mg kg(-1) per day; n = 10) groups for a 6 week period. After treatment, plasma mineral concentrations were measured by flame (Mg) and electrothermal (Cr and V) atomic absorption spectrometry. No significant differences were found between the C and V' groups (p > 0.05). Plasma Mg levels were significantly lower in C-ZDF vs. C-ZL rats, demonstrating the presence of hypomagnesemia in this diabetes mellitus model. Plasma V and Cr levels were significantly higher in M-ZDF vs. C-ZDF rats. Plasma Mg levels in ZDF rats were not affected by melatonin treatment (p > 0.05). Melatonin administration ameliorates the diabetic status of ZDF rats by enhancing plasma Cr and V concentrations. This appears to be the first report of a beneficial effect of melatonin treatment on plasma Cr and V regulation in ZDF rats.

  3. 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.

  4. 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.

  5. 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.

  6. Clofibrate-induced reduction of plasma branched-chain amino acid concentrations impairs glucose tolerance in rats.

    PubMed

    Kadota, Yoshihiro; Kazama, Shunsuke; Bajotto, Gustavo; Kitaura, Yasuyuki; Shimomura, Yoshiharu

    2012-05-01

    It has been reported that branched-chain amino acid (BCAA) administration stimulates glucose uptake into muscles and whole body glucose oxidation in rats. The authors examined the effect of decreased plasma BCAA concentrations induced by clofibrate treatment on glucose tolerance in rats. Since clofibrate, a drug for hyperlipidemia (high serum triglyceride concentration), is a potent inhibitor of the branched-chain α-keto acid dehydrogenase kinase, clofibrate treatment (0.2 g/kg body weight) activated the hepatic branched-chain α-keto acid dehydrogenase complex, resulting in decreased plasma BCAA concentrations by 30% to 50% from the normal level. An intraperitoneal glucose tolerance test was conducted after clofibrate administration, and the results showed that peak plasma glucose concentration and the area under the curve of glucose concentration during the intraperitoneal glucose tolerance test were significantly higher in clofibrate-treated rats than in control rats. This impaired glucose tolerance in the clofibrate-treated rats was ameliorated by administration of BCAAs (0.45 g/kg body weight, leucine:isoleucine:valine = 2:1:1), which kept plasma BCAA concentrations at normal levels during the intraperitoneal glucose tolerance test. These results suggest that plasma BCAAs play an important role in maintaining normal glucose tolerance in rats.

  7. Disposition of methylprednisolone acetate in plasma, urine, and synovial fluid following intra-articular administration to exercised thoroughbred horses.

    PubMed

    Knych, H K; Harrison, L M; Casbeer, H C; McKemie, D S

    2014-04-01

    Methylprednisolone acetate (MPA) is commonly administered to performance horses, and therefore, establishing appropriate withdrawal times prior to performance is critical. The objectives of this study were to describe the plasma pharmacokinetics of MPA and time-related urine and synovial fluid concentrations following intra-articular administration to sixteen racing fit adult Thoroughbred horses. Horses received a single intra-articular administration of MPA (100 mg). Blood, urine, and synovial fluid samples were collected prior to and at various times up to 77 days postdrug administration and analyzed using tandem liquid chromatography-mass spectrometry (LC-MS/MS). Maximum measured plasma MPA concentrations were 6.06 ± 1.57 at 0.271 days (6.5 h; range: 5.0-7.92 h) and 6.27 ± 1.29 ng/mL at 0.276 days (6.6 h; range: 4.03-12.0 h) for horses that had synovial fluid collected (group 1) and those that did not (group 2), respectively. The plasma terminal half-life was 1.33 ± 0.80 and 0.843 ± 0.414 days for groups 1 and 2, respectively. MPA was undetectable by day 6.25 ± 2.12 (group 1) and 4.81 ± 2.56 (group 2) in plasma and day 17 (group 1) and 14 (group 2) in urine. MPA concentrations in synovial fluid remained above the limit of detection (LOD) for up to 77 days following intra-articular administration, suggesting that plasma and urine concentrations are not a good indicator of synovial fluid concentrations.

  8. 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

  9. 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.

  10. The effects of allopurinol, uric acid, and inosine administration on xanthine oxidoreductase activity and uric acid concentrations in broilers.

    PubMed

    Settle, T; Carro, M D; Falkenstein, E; Radke, W; Klandorf, H

    2012-11-01

    The purpose of these studies was to determine the effects of uric acid (UA) and inosine administration on xanthine oxidoreductase activity in broilers. In experiment one, 25 broilers were assigned to 5 treatment groups: control, AL (25 mg of allopurinol/kg of body mass), AR (AL for 2 wk followed by allopurinol withdrawal over wk 3), UAF (AL plus 6.25 g of UA sodium salt/kg of feed), and UAI (AL plus 120 mg of UA sodium salt injected daily). The UA administration had no effect on plasma concentration of UA (P > 0.05), and all allopurinol-treated birds had lower (P < 0.05) UA levels than controls. The UA concentrations were restored in both plasma and kidney of AR birds at wk 3, but liver UA concentrations remained lower. Whereas xanthine oxidoreductase (XOR) activity in the liver (LXOR) was reduced (P < 0.05) by allopurinol treatment, XOR activity in the kidney (KXOR) was not affected (P = 0.05). In experiment two, 3 groups of 5 birds each were fed 0 (control), 0.6 M inosine/kg of feed (INO), or INO plus 50 mg of allopurinol/kg of body mass (INOAL). The INOAL birds showed lower total LXOR activity, but KXOR activity was not affected. Both INO and INOAL birds had higher plasma and kidney UA concentrations than controls. The results suggest that regulation of UA production is tissue dependent.

  11. 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

  12. 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.

  13. 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.

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

    PubMed Central

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

    2016-01-01

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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Microdialysis pharmacokinetic study of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration.

    PubMed

    Wei, Yan; Ying, Mingzhen; Xu, Shuai; Wang, Feng; Zou, Aifeng; Cao, Shilei; Jiang, Xinguo; Wang, Yajie

    2016-01-01

    The purpose of this study was to investigate the microdialysis pharmacokinetic of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration. The pharmacokinetic study of subcutaneous and oral administration was also performed in rats. From the in vivo results, scopolamine intranasal administration can avoid hepatic first-pass effect. Tmax plasma samples after intranasal administration were significantly faster than oral administration and subcutaneous injection. The relative bioavailability of intranasal administrations was 51.8-70% when compared with subcutaneous injection. Moreover, one can see that in comparison with scopolamine subcutaneous administration, scopolamine intranasal gel and solutions can increased drug target index (DTI) with olfactory bulb 1.69 and 2.05, vestibule 1.80 and 2.15, respectively. The results indicated that scopolamine can be absorbed directly through the olfactory mucosa into the olfactory bulb, and then transported to various brain tissue after intranasal administration, with the characteristics of brain drug delivery.

  2. GHB Urine Concentrations After Single-Dose Administration in Humans

    PubMed Central

    Haller, Christine; Thai, Dung; Jacob, Peyton; Dyer, Jo Ellen

    2008-01-01

    Gamma-hydroxybutyric acid (GHB) is used as an illicit drug and is implicated in drug-facilitated sexual assault, but it also has some therapeutic uses. Detection of GHB in urine is important for forensic testing and could be of clinical benefit in overdose management. Urine GHB concentration-time profiles have not been well-characterized or correlated with doses used therapeutically. GHB levels were measured by gas chromatography–mass spectrometry in urine collected over 24 h from 16 adults administered single doses of 50 mg/kg GHB (Xyrem®) alone and combined with 0.6 g/kg ethanol. Peak GHB urine concentrations averaged 150–200 mg/L and occurred in the 0–3 h urine collection. Significant variability in GHB urine levels between individuals was observed. Caucasians had lower urine concentrations than other races/ethnicities (p = 0.03). Men had lower GHB levels than women in the first 3 h after dosing (p = 0.038). Coingestion of ethanol did not significantly affect renal clearance of GHB, but urine GHB concentrations were lower in the first 3 h when ethanol and GHB were coingested (p = 0.039). At a proposed cut-off of 10 mg/L to distinguish endogenous versus exogenous GHB levels, 12.5% of the samples collected from 3 to 6 h, 81.3% of samples collected from 6 to 12 h, and 100% of urine specimens collected from 12 to 24 h were below this level. We conclude that the detection time for GHB in urine may be shorter than the previously reported 12-h window in some people taking therapeutic doses of GHB. PMID:16872565

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Natural conditions and administrative settings for concentrating photovoltaics in China

    NASA Astrophysics Data System (ADS)

    Fu, Ling; Chen, Xiaoyuan; Leutz, Ralf

    2012-10-01

    It is an inevitable trend for China to develop green technologies to help the country to produce cleaner energy and to consume it more efficiently, under the pressure of energy security concern, the nation's emissions trajectory and sustainable economic development. The abundant solar resources in West China provide a big potential to utilize the solar energy. Under the promotion of key incentive policies including both feed-in-tariff (FIT) mechanisms and government rebate programs, China has become a major global solar force in photovoltaic (PV) industry both in manufacturing and in the installation of flat-plate products, with 16 GW production and 2.75 GW installation achieved in the year 2011. As a branch of PV technology, concentrating photovoltaics (CPV) technology with several years' development history in China is presently moving from pilot facilities to commercial-scale applications. Several MW-CPV power plants have been installed by both domestic and western companies in China, factories with several hundred-MW production capacity are being planned or built. Sustainable performance and reliability improvement of CPV modules, a vertical integration of supply chain in CPV industry aiming at a cost reduction, a sufficient grid infrastructure for facilitating the West-East and North-South electricity transmission will promote Chinese CPV market to actually initiate, develop and mature.

  9. 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.

  10. Changes of human plasma dopamine-beta-hydroxylase activity after intravenous administration of theophylline.

    PubMed Central

    Aunis, D; Mandel, P; Miras-Portugal, M T; Coquillat, G; Rohmer, F; Warter, J M

    1975-01-01

    The intravenous administration of theophylline to ten healthy human subjects produced either an increase of circulating plasma dopamine-beta-hydroxylase or no change. The rise of plasma enzyme activity may reflect the increased peripheral catecholamine release induced by theophylline. PMID:1137731

  11. 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.

  12. 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

  13. 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

  14. Disposition of isoflupredone acetate in plasma, urine and synovial fluid following intra-articular administration to exercised Thoroughbred horses.

    PubMed

    Knych, Heather K; Harrison, Linda M; White, Alexandria; McKemie, Daniel S

    2016-01-01

    The use of isoflupredone acetate in performance horses and the scarcity of published pharmacokinetic data necessitate further study. The objective of the current study was to describe the plasma pharmacokinetics of isoflupredone acetate as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (8 mg) of isoflupredone acetate into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to and at various times up to 28 days post drug administration. All samples were analyzed using liquid chromatography-Mass Spectrometry. Plasma data were analyzed using a population pharmacokinetic compartmental model. Maximum measured plasma isoflupredone concentrations were 1.76 ± 0.526 ng/mL at 4.0 ± 1.31 h and 1.63 ± 0.243 ng/mL at 4.75 ± 0.5 h, respectively, for horses that had synovial fluid collected and for those that did not. The plasma beta half-life was 24.2 h. Isoflupredone concentrations were below the limit of detection in all horses by 48 h and 7 days in plasma and urine, respectively. Isoflupredone was detected in the right antebrachiocarpal and middle carpal joints for 8.38 ± 5.21 and 2.38 ± 0.52 days, respectively. Results of this study provide information that can be used to regulate the use of intra-articular isoflupredone in the horse.

  15. [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.

  16. Comparative Proteome Analyses of Human Plasma Following in vivo Lipopolysaccharide Administration Using Multidimensional Separations Coupled with Tandem Mass Spectrometry

    PubMed Central

    Qian, Wei-Jun; Jacobs, Jon M.; Camp, David G.; Monroe, Matthew E.; Moore, Ronald J.; Gritsenko, Marina A.; Calvano, Steve E.; Lowry, Stephen F.; Xiao, Wenzhong; Moldawer, Lyle L.; Davis, Ronald W.; Tompkins, Ronald G.; Smith, Richard D.

    2007-01-01

    There is significant interest in characterization of the human plasma proteome due to its potential for providing biomarkers applicable to clinical diagnosis and treatment and for gaining a better understanding of human diseases. We describe here a strategy for the comparative proteome analyses of human plasma, which is applicable to biomarker identifications for various disease states. Multidimensional liquid chromatography-mass spectrometry has been applied to make comparative proteome analyses of plasma samples from an individual prior to and 9 h after lipopolysaccharide (LPS) administration. Peptide peak areas and the number of peptide identifications for each protein were used to evaluate the reproducibility of LC-MS/MS and to compare relative changes in protein concentration between the samples following LPS treatment. A total of 804 distinct plasma proteins (not including immunoglobulins) were confidently identified with 32 proteins observed to be significantly increased in concentration following LPS administration, including several known inflammatory response or acute-phase mediators such as C-reactive protein, serum amyloid A and A2, LPS-binding protein, LPS-responsive and beige-like anchor protein, hepatocyte growth factor activator, and von Willebrand factor, and thus constituting potential biomarkers for inflammatory response. PMID:15627965

  17. Milk and plasma disposition of thymol following intramammary administration of a phytoceutical mastitis treatment.

    PubMed

    McPhee, C S; Anderson, K L; Yeatts, J L; Mason, S E; Barlow, B M; Baynes, R E

    2011-04-01

    Despite the recent growth of the organic dairy industry, organic producers and veterinarians have limited information when choosing mastitis treatments for animals in organic dairy production. Organic producers commonly administer homeopathic or other plant-based products without having research evaluating the efficacy of these products and using estimated or no withholding times to treat mastitis and other health problems in their herds. In this pilot study, we attempted to identify several active ingredients of Phyto-Mast (Penn Dutch Cow Care, Narvon, PA), a plant-based mastitis treatment used on organic dairy farms, and to quantify the product residue in milk and plasma after intramammary administration. We developed an assay to quantify thymol (one of the active ingredients in Phyto-Mast) in milk and plasma using gas chromatography and mass spectrometry (GC-MS). Thymol is a volatile aromatic compound with antiinflammatory properties. As a model for dairy cows, 5 healthy, lactating alpine dairy goats were given 5 mL of Phyto-Mast per udder half. For 10 d following treatment, we analyzed blood and milk samples for thymol residues using GC-MS. The GC-MS assay was very sensitive for thymol detection, to a concentration of 0.01 μg/mL in plasma. Using thymol as a marker, Phyto-Mast was detectable and quantifiable in plasma beginning with the 15-min posttreatment sample, but was no longer detectable in the 4-h posttreatment sample. Thymol residues were only detected in the 12-h posttreatment milk sample. An inflammatory response was not evident in the udder following phytoceutical administration. Although this study provides information about the elimination of thymol, the product contains several other active chemicals, which may have different pharmacokinetic behaviors. Further analysis and additional study animals will help to determine a milk withholding time for Phyto-Mast. Given the recent growth of the organic dairy industry, understanding the pharmacokinetics

  18. Plasma concentrations of pyrimethamine and sulfadoxine and evaluation of pharmaco-kinetic data by computerized curve fitting

    PubMed Central

    Weidekamm, E.; Plozza-Nottebrock, H.; Forgo, I.; Dubach, U. C.

    1982-01-01

    For the determination of the plasma concentration profiles of pyrimethamine and sulfadoxine after the administration of 1 tablet of Fansidar, highly specific analytical methods are needed as the pyrimethamine concentration is low (0.2 - 0.02 mg/litre) and the concentration ratio of the two components in the plasma is high (> 1: 500). The microbiological method described in this paper fulfils these requirements for high specificity and sensitivity (the sensitivity limit for sulfadoxine is 1 mg/litre and for pyrimethamine is 0.013 mg/litre). Pharmacokinetic data were evaluated for 14 volunteers after administration of 1 tablet of Fansidar, and a computer simulation of multiple dosing (1 tablet per week) was performed. PMID:6979415

  19. Variability of serum indomethacin concentrations after oral and intravenous administration to preterm infants.

    PubMed

    Mrongovius, R; Imbeck, H; Wille, L; Müller, H; Seyberth, H W

    1982-03-01

    Fifteen preterm infants with patent ductus arteriosus and respiratory distress syndrome were given indomethacin (0.2 mg/kg) at 12 h intervals up to three times, either orally or intravenously, in an uncontrolled, non-randomized study. Serum indomethacin concentrations were determined in blood samples taken 12 h after dosing. There was considerable variability in the serum indomethacin concentrations, especially after oral administration, although the mean concentrations after each of the three doses were similar after both oral and intravenous administration. The frequency of closures and transient closures of the ductus arteriosus was also similar for both routes of administration. There was, however, no relation between concentration and effect in individual patients. The sustained exposure to indomethacin which appears to be necessary for ductal closure can sometimes be attained by oral administration.

  20. Correlation between the plasma concentration of mepirodipine and its occupancy of Ca2+ antagonist receptors in rats.

    PubMed

    Yamada, S; Matsuoka, Y; Kimura, R

    1993-09-01

    The relationship between the plasma concentration of mepirodipine (1,4-dihydropyridine Ca2+ antagonist) and its occupancy of cardiac and cerebral Ca2+ antagonist receptors in rats has been characterized by a radioreceptor assay technique using (+)-[3H]PN 200-110. Oral administration of mepirodipine in rats produced a dose-dependent and sustained decrease in the number of specific (+)-[3H]PN 200-110 binding sites in both tissues, and the effect was more pronounced in the cardiac tissue than in the cerebral cortex. The occupancy of cardiac and cerebral Ca2+ antagonist receptors by mepirodipine correlated well with its plasma concentration, whereas a 20-fold higher plasma concentration of this drug was necessary to occupy Ca2+ antagonist receptors in the cerebral cortex. Thus, these data suggest that mepirodipine occupies Ca2+ antagonist receptors in cardiovascular tissue selectively over those in brain tissue.

  1. 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

  2. Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

    PubMed

    Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

    2015-12-01

    Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice.

  3. Acute alcohol exposure, acidemia or glutamine administration impacts amino acid homeostasis in ovine maternal and fetal plasma.

    PubMed

    Washburn, Shannon E; Sawant, Onkar B; Lunde, Emilie R; Wu, Guoyao; Cudd, Timothy A

    2013-09-01

    Fetal alcohol syndrome (FAS) is a significant problem in human reproductive medicine. Maternal alcohol administration alters maternal amino acid homeostasis and results in acidemia in both mother and fetus, causing fetal growth restriction. We hypothesized that administration of glutamine, which increases renal ammoniagenesis to regulate acid-base balance, may provide an intervention strategy. This hypothesis was tested using sheep as an animal model. On day 115 of gestation, ewes were anesthetized and aseptic surgery was performed to insert catheters into the fetal abdominal aorta as well as the maternal abdominal aorta and vena cava. On day 128 of gestation, ewes received intravenous administration of saline, alcohol [1.75 g/kg body weight (BW)/h], a bolus of 30 mg glutamine/kg BW, alcohol + a bolus of 30 mg glutamine/kg BW, a bolus of 100 mg glutamine/kg BW, alcohol + a bolus of 100 mg glutamine/kg BW, or received CO2 administration to induce acidemia independent of alcohol. Blood samples were obtained simultaneously from the mother and the fetus at times 0 and 60 min (the time of peak blood alcohol concentration) of the study. Administration of alcohol to pregnant ewes led to a reduction in concentrations of glutamine and related amino acids in plasma by 21-30%. An acute administration of glutamine to ewes, concurrent with alcohol administration, improved the profile of most amino acids (including citrulline and arginine) in maternal and fetal plasma. We suggest that glutamine may have a protective effect against alcohol-induced metabolic disorders and FAS in the ovine model.

  4. Acute alcohol exposure, acidemia or glutamine administration impacts amino acid homeostasis in ovine maternal and fetal plasma

    PubMed Central

    Washburn, Shannon E.; Sawant, Onkar B.; Lunde, Emilie R.; Wu, Guoyao; Cudd, Timothy A.

    2013-01-01

    Fetal alcohol syndrome (FAS) is a significant problem in human reproductive medicine. Maternal alcohol administration alters maternal amino acid homeostasis and results in acidemia in both mother and fetus, causing fetal growth restriction. We hypothesized that administration of glutamine, which increases renal ammoniagenesis to regulate acid-base balance, may provide an intervention strategy. This hypothesis was tested using sheep as an animal model. On day 115 of gestation, ewes were anesthetized and aseptic surgery was performed to insert catheters into the fetal abdominal aorta as well as the maternal abdominal aorta and vena cava. On day 128 of gestation, ewes received intravenous administration of saline, alcohol [1.75 g/kg body weight (BW)/h], a bolus of 30 mg glutamine/kg BW, alcohol + a bolus of 30 mg glutamine/kg BW, a bolus of 100 mg glutamine/kg BW, alcohol + a bolus of 100 mg glutamine/kg BW, or received CO2 administration to induce acidemia independent of alcohol. Blood samples were obtained simultaneously from the mother and the fetus at times 0 and 60 min (the time of peak blood alcohol concentration) of the study. Administration of alcohol to pregnant ewes led to a reduction in concentrations of glutamine and related amino acids in plasma by 21–30%. An acute administration of glutamine to ewes, concurrent with alcohol administration, improved the profile of most amino acids (including citrulline and arginine) in maternal and fetal plasma. We suggest that glutamine may have a protective effect against alcohol-induced metabolic disorders and FAS in the ovine model. PMID:23315157

  5. 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.

  6. Measurement of naphthoxylactic and naphtoxyacetic acid in human plasma following propranolol administration.

    PubMed

    Pritchard, F; Schneck, D; Hayes, A

    1979-02-01

    A method for the quantitative determination of naphthoxylactic acid and naphthoxyacetic acid, two acidic metabolites of propranolol, in human plasma is described. Preliminary data from hypertensive patients receiving chronic propranolol therapy and from normal volunteers who took a single 80 mg oral propranolol dose revealed that naphthoxylactic acid plasma levels were 4 to 20 times that of propranolol whereas naphthoxyacetic acid levels were equivalent to or less than the plasma concentrations of propranolol.

  7. 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.

  8. Different profiles of quercetin metabolites in rat plasma: comparison of two administration methods.

    PubMed

    Kawai, Yoshichika; Saito, Satomi; Nishikawa, Tomomi; Ishisaka, Akari; Murota, Kaeko; Terao, Junji

    2009-03-23

    The bioavailability of polyphenols in human and rodents has been discussed regarding their biological activity. We found different metabolite profiles of quercetin in rat plasma between two administration procedures. A single intragastric administration (50 mg/kg) resulted in the appearance of a variety of metabolites in the plasma, whereas only a major fraction was detected by free access (1% quercetin). The methylated/non-methylated metabolites ratio was much higher in the free access group. Mass spectrometric analyses showed that the fraction from free access contained highly conjugated quercetin metabolites such as sulfo-glucuronides of quercetin and methylquercetin. The metabolite profile of human plasma after an intake of onion was similar to that with intragastric administration in rats. In vitro oxidation of human low-density lipoprotein showed that methylation of the catechol moiety of quercetin significantly attenuated the antioxidative activity. These results might provide information about the bioavailability of quercetin when conducting animal experiments.

  9. BLOOD PLASMA LEVELS AND ELIMINATION OF SALTS OF 2-PAM IN MAN AFTER ORAL ADMINISTRATION,

    DTIC Science & Technology

    salts of 2-PAM in varying amounts. A measurable amount of oxime was found in blood plasma within about 15 minutes; the concentration rose rapidly...level of oxime 3.5 fold. The biological half-life in man of the 2-PAM salts given orally, calculated from blood plasma values and urinary excretion rates

  10. Coenzyme Q10 Administration Increases Brain Mitochondrial Concentrations and Exerts Neuroprotective Effects

    NASA Astrophysics Data System (ADS)

    Matthews, Russell T.; Yang, Lichuan; Browne, Susan; Baik, Myong; Flint Beal, M.

    1998-07-01

    Coenzyme Q10 is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes. Feeding with coenzyme Q10 increased cerebral cortex concentrations in 12- and 24-month-old rats. In 12-month-old rats administration of coenzyme Q10 resulted in significant increases in cerebral cortex mitochondrial concentrations of coenzyme Q10. Oral administration of coenzyme Q10 markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis. These results show that oral administration of coenzyme Q10 increases both brain and brain mitochondrial concentrations. They provide further evidence that coenzyme Q10 can exert neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.

  11. 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.

  12. A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

    NASA Technical Reports Server (NTRS)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

  13. Plasma pharmacokinetics and milk residues of flunixin and 5-hydroxy flunixin following different routes of administration in dairy cattle.

    PubMed

    Kissell, L W; Smith, G W; Leavens, T L; Baynes, R E; Wu, H; Riviere, J E

    2012-12-01

    The objective of this study was to determine if the plasma pharmacokinetics and milk elimination of flunixin (FLU) and 5-hydroxy flunixin (5OH) differ following intramuscular and subcutaneous injection of FLU compared with intravenous injection. Twelve lactating Holstein cows were used in a randomized crossover design study. Cows were organized into 2 groups based on milk production (<20 or >30 kg of milk/d). All cattle were administered 2 doses of 1.1mg of FLU/kg at 12-h intervals by intravenous, intramuscular, and subcutaneous injections. The washout period between routes of administration was 7d. Blood samples were collected from the jugular vein before FLU administration and at various time points up to 36 h after the first dose of FLU. Composite milk samples were collected before FLU administration and twice daily for 5d after the first dose of FLU. Samples were analyzed by ultra-HPLC with mass spectrometric detection. For FLU plasma samples, a difference in terminal half-life was observed among routes of administration. Harmonic mean terminal half-lives for FLU were 3.42, 4.48, and 5.39 h for intravenous, intramuscular, and subcutaneous injection, respectively. The mean bioavailability following intramuscular and subcutaneous dosing was 84.5 and 104.2%, respectively. The decrease in 5OH milk concentration versus time after last dose was analyzed with the nonlinear mixed effects modeling approach and indicated that both the route of administration and rate of milk production were significant covariates. The number of milk samples greater than the tolerance limit for each route of administration was also compared at each time point for statistical significance. Forty-eight hours after the first dose, 5OH milk concentrations were undetectable in all intravenously injected cows; however, one intramuscularly injected and one subcutaneously injected cow had measurable concentrations. These cows had 5OH concentrations above the tolerance limit at the 36-h withdrawal

  14. 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.

  15. 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

  16. Determination of eptifibatide concentration in human plasma utilizing the liquid chromatography-tandem mass spectrometry method.

    PubMed

    Liu, Jia; Duan, Xiaotao; Chen, Xiaoyan; Zhong, Dafang

    2009-02-15

    A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine the concentration of eptifibatide in human plasma. Following protein precipitation, the analyte was separated on a reversed-phase C(18) column. Acetonitrile:5mM ammonium acetate:acetic acid (30:70:0.1, v/v/v) was used at a flow-rate of 0.5mL/min with the isocratic mobile phase. An API 4000 tandem mass spectrometer equipped with a Turbo IonSpray ionization source was used as the detector and was operated in the positive ion mode. "Truncated" multiple reaction monitoring using the transition of m/z 832.6-->m/z 832.6 and m/z 931.3-->m/z 931.3 was performed to quantify eptifibatide and the internal standard (EPM-05), respectively. The method had a lower limit of quantification of 4.61ng/mL for eptifibatide. The calibration curve was demonstrated to be linear over the concentration range of 4.61-2770ng/mL. The intra- and inter-day precisions were less than 10.5% for each QC level, and the inter-day relative errors were 2.0%, 5.6%, and 2.8% for 9.22, 184, and 2490ng/mL, respectively. The validated method was successfully applied to the quantification of eptifibatide concentration in human plasma after intravenous (i.v.) administration of a 270-microg/kg bolus of eptifibatide and i.v. administration of eptifibatide at a constant rate of infusion of 2microg/(kgmin) for 18h in order to evaluate the pharmacokinetics.

  17. 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

  18. Gut mucosal and plasma concentrations of glutamine: a comparison between two enriched enteral feeding solutions in critically ill patients

    PubMed Central

    Preiser, Jean-Charles; Peres-Bota, Daliana; Eisendrath, Pierre; Vincent, Jean-Louis; Van Gossum, André

    2003-01-01

    Background Addition of glutamine to enteral nutrition formulas is consistently associated with a significant decrease in septic morbidity in critically ill patients, possibly related to the attenuation of gut dysfunction. This pilot study was undertaken to compare the effects of enteral administration of two glutamine-enriched formulas containing either additional free glutamine or glutamine-rich proteins, with a standard solution on plasma and mucosal concentrations of glutamine in patients admitted in the Department of Intensive Care. Methods Following randomization, glutamine concentration was determined in endoscopically sampled duodenal biopsies and plasma, before and after a 7-day period of continuous administration of the designated solution. Results The mucosal concentration of glutamine increased in the duodenal biopsies sampled from patients randomized to the solution containing the glutamine-rich proteins (from 3.6 ± 2.2 to 6.7 ± 5.2 micro-mol/g protein), but not from the others. There were no differences between the 3 groups in the plasma concentrations of glutamine, which remained stable over time. Conclusion The source of supplemental glutamine can influence gut mucosal glutamine concentrations, suggesting differences in its availability or utilization. PMID:14613506

  19. 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.

  20. Metabolomic Analyses of Blood Plasma after Oral Administration of D-Glucosamine Hydrochloride to Dogs

    PubMed Central

    Osaki, Tomohiro; Azuma, Kazuo; Kurozumi, Seiji; Takamori, Yoshimori; Tsuka, Takeshi; Imagawa, Tomohiro; Okamoto, Yoshiharu; Minami, Saburo

    2012-01-01

    D-Glucosamine hydrochloride (GlcN∙HCl) is an endogenous amino monosaccharide synthesized from glucose that is useful in the treatment of joint diseases in both humans and animals. The aim of this study was to examine amino acid metabolism in dogs after oral administration of GlcN∙HCl. Accelerated fumarate respiration and elevated plasma levels of lactic acid and alanine were observed after administration. These results suggest that oral administration of GlcN∙HCl induces anaerobic respiration and starvation in cells, and we hypothesize that these conditions promote cartilage regeneration. Further studies are required to evaluate the expression of transforming growth factor-beta (TGF-β). PMID:23015778

  1. Changes in plasma volume during bed rest - Effects of menstrual cycle and estrogen administration

    NASA Technical Reports Server (NTRS)

    Fortney, S. M.; Beckett, W. S.; Carpenter, A. J.; Davis, J.; Drew, H.

    1988-01-01

    The effect of increased blood estrogen concentration, caused either during normal menstrual cycles or by exogenous administration of premarin, on the bed-rest (BR) induced decrease in plasma volume (PV) was investigated. In women who underwent duplicate 11-day BR without estrogen supplementation, the PV was found to decrease significantly, during the first 5 days of BR, to a lower level at which it remained for the rest of the BR period. In women who began BR in the periovulatory stage of the menstrual cycle, the loss of PV was delayed, while women who began BR during other stages of the cycle exhibited the usual trend of the PV decrease during the BR. In women who underwent a single 12-day BR period while taking premarin (1.25 mg/day), PV was found to decrease during the first 4-5 days of BR, but then returned toward the pre-BR level during the remainder of the BR, indicating that estrogens have a role in stabilizing body fluid volume.

  2. The determination of biperiden in plasma using gas chromatography mass spectrometry: pharmacokinetics after intramuscular administration to guinea pigs.

    PubMed

    Capacio, B R; Caro, S T; Smith, J R; Byers, C E

    2002-02-01

    A gas chromatographic-mass spectrometric (GC-MS) method has been developed for the analysis of the biperiden from plasma. The method utilizes 290 microl of plasma and a simple hexane extraction/clean-up procedure. Standard curves were linear over the range of 1.9-250 ng/mL. The range of correlation coefficients for the individual standard curves was 0.9984-0.9999; the largest coefficient of variation expressed as a percentage (% CV) was 11.5%. Precision and accuracy were examined by assessing between-day and within-day variability. For between-day precision, the % CVs ranged from 2.86 to 5.17%. Accuracy as expressed by percentage error ranging from -2.16 to 5.83%. The study for within-day precision demonstrated % CVs from 0.95 to 5.55% with accuracy from -3.37 to 2.45%. Applicability of the method was demonstrated by examining the pharmacokinetics of intramuscular (i.m.) biperiden as an anticonvulsant treatment in a guinea pig model for organophosphate (OP)-induced seizure activity. Mean pharmacokinetic parameter estimates were similar to literature values; selected mean pharmacokinetic parameter estimates were: apparent volume of distribution, 13.9 L/kg; half-life of elimination, 93 min; time to maximal plasma concentration, 27.4 min; and maximal plasma concentration, 32.22 eta g/mL. The time to maximal plasma concentration was found to be similar to the onset time for terminating OP-induced seizure activity in guinea pigs receiving biperiden as an anticonvulsant treatment. The studies indicate that the method affords the required precision, accuracy and sensitivity to assay biperiden at the doses utilized for these pharmacokinetic studies after i.m. administration to guinea pigs.

  3. Analysis of free hydroxytyrosol in human plasma following the administration of olive oil.

    PubMed

    Pastor, Antoni; Rodríguez-Morató, Jose; Olesti, Eulàlia; Pujadas, Mitona; Pérez-Mañá, Clara; Khymenets, Olha; Fitó, Montserrat; Covas, María-Isabel; Solá, Rosa; Motilva, María-José; Farré, Magí; de la Torre, Rafael

    2016-03-11

    Hydroxytyrosol (HT) from olive oil, a potent bioactive molecule with health benefits, has a poor bioavailability, its free form (free HT) being undetectable so far. This fact leads to the controversy whether attained HT concentrations after olive oil polyphenol ingestion are too low to explain the observed biological activities. Due to this, an analytical methodology to determine free HT in plasma is crucial for understanding HT biological activity. Plasma HT instability and low concentrations have been major limitations for its quantification in clinical studies. Here, we describe a method to detect and quantify free HT in human plasma by using liquid chromatography coupled to tandem mass spectrometry. The method encompasses different steps of sample preparation including plasma stabilization, protein precipitation, selective derivatization with benzylamine, and purification by solid-phase extraction. A high sensitivity (LOD, 0.3ng/mL), specificity and stability of HT is achieved following these procedures. The method was validated and its applicability was demonstrated by analyzing human plasma samples after olive oil intake. A pharmacokinetic comparison was performed measuring free HT plasma concentrations following the intake of 25mL of ordinary olive oil (nearly undetectable concentrations) versus an extra-virgin olive oil (Cmax=4.40ng/mL). To our knowledge, this is the first time that an analytical procedure for quantifying free HT in plasma after olive oil dietary doses has been reported. The present methodology opens the door to a better understanding of the relationship between HT plasma concentrations and its beneficial health effects.

  4. 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.

  5. 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.

  6. 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

  7. A comparison of serum antivenom concentrations after intravenous and intramuscular administration of redback (widow) spider antivenom

    PubMed Central

    Isbister, Geoffrey K; O'Leary, Margaret; Miller, Mark; Brown, Simon G A; Ramasamy, Sharmaine; James, Rosemary; Schneider, Jennifer S

    2008-01-01

    AIMS There are no studies measuring antivenom concentrations following intramuscular administration. This study aimed to compare antivenom concentrations following intravenous and intramuscular administration of redback spider antivenom (RBSAV). METHODS Twenty patients recruited to a controlled trial comparing intramuscular and intravenous administration of antivenom had serial blood samples collected at 30 min intervals for 2 h after the administration of one or two doses of antivenom. Antivenom concentration was measured using an enzyme immunoassay. RESULTS Ten patients received intramuscular antivenom but antivenom could not be detected in serum after either one or two vials, at any time point. The median time of the final sample after commencement of antivenom treatment in these patients was 3.2 h (1.8–5 h). Ten patients received intravenous antivenom (three one vial and seven two or more vials) and antivenom was detected in all patients. CONCLUSIONS RBS AV given by the intramuscular route is unlikely to be effective in the treatment of redback (widow) spider bite. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Widow spider antivenoms, including redback spider antivenom, are often given by the intramuscular route. No studies have measured widow spider antivenom following intramuscular or intravenous antivenom. WHAT THIS STUDY ADDS Intramuscular redback spider antivenom is not detectable in serum for at least 3–5 h after treatment. Intravenous antivenom is detectable 30 min after intravenous infusion. Intramuscular antivenom may not be an effective administration route. PMID:18171334

  8. Cremophor EL releases cyclosporin A adsorbed on blood cells and blood vessels, and increases apparent plasma concentration of cyclosporin A.

    PubMed

    Jin, Mingji; Shimada, Tsutomu; Yokogawa, Koichi; Nomura, Masaaki; Mizuhara, Yasuharu; Furukawa, Hiroyuki; Ishizaki, Junko; Miyamoto, Ken-Ichi

    2005-04-11

    We examined the influence of cremophor EL (crEL) on the disposition kinetics of CyA in rats. A dose of 10mg/kg of CyA in a volume of 750 microL containing 4.3, 16 or 30% concentration of crEL was intravenously administered over 1 min to rats. The values of distribution volume at the steady-state (Vd(ss)) and total clearance (CL(tot)) of CyA in the presence of increasing amounts of crEL were decreased to about 1/3-1/5 of those with 4.3% crEL, in a crEL concentration-dependent manner. The values of blood to plasma concentration ratio (RBP) and the apparent tissue to plasma concentration ratio (K(p,app)) of CyA with 30% crEL were both only about 1/2 of those of CyA with 4.3% crEL. Next, rats were intravenously given 30% crEL solution at 30 min after an intravenous administration of CyA (10 mg/kg) with 4.3% crEL. Subsequently, the blood and plasma concentrations of CyA rose significantly to 2.4 and 4.7 times those seen when i.v. 30% crEL was not given, respectively. In an in vitro study, we found that the uptake of CyA by red blood cells is inhibited by crEL, and that CyA adsorbed on the inner surface of blood vessels after the administration of CyA is released by crEL. The disposition kinetics of CyA is altered by i.v. administration in combination with the surfactant vehicle crEL, in a crEL concentration-dependent manner.

  9. Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration.

    PubMed

    Freeman, Willard M; Vanguilder, Heather D; Guidone, Elizabeth; Krystal, John H; Grant, Kathleen A; Vrana, Kent E

    2011-08-01

    Objective diagnostics of excessive alcohol use are valuable tools in the identification and monitoring of subjects with alcohol use disorders. A number of potential biomarkers of alcohol intake have been proposed, but none have reached widespread clinical usage, often due to limited diagnostic sensitivity and specificity. In order to identify novel potential biomarkers, we performed proteomic biomarker target discovery in plasma samples from non-human primates that chronically self-administer high levels of ethanol. Two-dimensional difference in-gel electrophoresis (2D-DIGE) was used to quantify plasma proteins from within-subject samples collected before exposure to ethanol and after 3 months of excessive ethanol self-administration. Highly abundant plasma proteins were depleted from plasma samples to increase proteomic coverage. Altered plasma levels of serum amyloid A4 (SAA4), retinol-binding protein, inter-alpha inhibitor H4, clusterin, and fibronectin, identified by 2D-DIGE analysis, were confirmed in unmanipulated, whole plasma from these animals by immunoblotting. Examination of these target plasma proteins in human subjects with excessive alcohol consumption (and control subjects) revealed increased levels of SAA4 and clusterin and decreased levels of fibronectin compared to controls. These proteins not only serve as targets for further development as biomarker candidates or components of biomarker panels, but also add to the growing understanding of dysregulated immune function and lipoprotein metabolism with chronic, excessive alcohol consumption.

  10. Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration

    PubMed Central

    Freeman, Willard M.; VanGuilder, Heather D.; Guidone, Elizabeth; Krystal, John H.; Grant, Kathleen A.; Vrana, Kent E.

    2011-01-01

    Objective diagnostics of excessive alcohol use are valuable tools in the identification and monitoring of subjects with alcohol use disorders. A number of potential biomarkers of alcohol intake have been proposed, but none have reached widespread clinical usage, often due to limited diagnostic sensitivity and specificity. In order to identify novel potential biomarkers, we performed proteomic biomarker target discovery in plasma samples from non-human primates that chronically self-administer high levels of ethanol. 2-dimensional in-gel electrophoresis (2D-DIGE) was used to quantify plasma proteins from within subject samples collected before exposure to ethanol and after three months of excessive ethanol self-administration. Highly abundant plasma proteins were depleted from plasma samples to increase proteomic coverage. Altered plasma levels of SAA4, RBP, ITIH4, clusterin, and fibronectin, identified by 2D-DIGE analysis, were confirmed in unmanipulated, whole plasma from these animals by immunoblotting. Examination of these target plasma proteins in human subjects with excessive alcohol consumption (and control subjects) revealed increased levels of SAA4 and clusterin and decreased levels of fibronectin compared to controls. These proteins not only serve as targets for further development as biomarker candidates or components of biomarker panels, but also add to the growing understanding of dysregulated immune function and lipoprotein metabolism with chronic, excessive alcohol consumption. PMID:21303580

  11. Posaconazole plasma concentration in pediatric patients receiving antifungal prophylaxis after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Heinz, Werner J; Cabanillas Stanchi, Karin M; Klinker, Hartwig; Blume, Olivia; Feucht, Judith; Hartmann, Ulrike; Feuchtinger, Tobias; Lang, Peter; Handgretinger, Rupert; Döring, Michaela

    2016-02-01

    Posaconazole has been proven to be effective for antifungal prophylaxis in adults after hematopoietic stem cell transplantation (HSCT). Due to low gastrointestinal resorption of posaconazole suspension, bioavailability is impaired. Fatty food improves the uptake of posaconazole, but insufficient data on the pharmacokinetics of posaconazole in pediatric patients are available so far. The single-center analysis investigated 161 posaconazole serum concentrations in 27 pediatric patients after HSCT receiving 12 mg·kg BW(-1)·d(-1) posaconazole suspension depending on age, gender, and intestinal graft-versus-host (iGvHD) disease, and the influence of posaconazole on cyclosporine A plasma concentrations. To improve the uptake of posaconazole, one patient cohort received higher fat nutrition with the drug administration. A comparison of the regular nutrition and higher-fat nutrition groups revealed the following values: 31 (27.4%) versus 8 (16.7%) < 500 ng/ml; 12 (10.6%) versus 7 (14.6%) 500-700 ng/ml; 8 (7.1%) versus 6 (12.5%) 700-1000 ng/ml; 51 (45.1%) versus 21 (43.8%) 1000-2000 ng/ml; and 11 (9.7%) versus 6 (12.5%) > 2000 ng/ml. The mean posaconazole concentrations in patients with regular nutrition was 1123 ± 811 ng/ml and with higher-fat nutrition was 1191 ± 673 ng/ml. Posaconazole levels in patients with iGvHD were significantly lower (P = 0.0003) than in patients without GvHD. The majority of samples showed a sufficient posaconazole concentration above 700 ng/ml. Posaconazole levels were slightly higher in patients with higher-fat nutrition and significantly lower in patients with iGvHD. Cyclosporine A levels were not significantly higher during posaconazole administration.

  12. LH release and ovulatory response after intramuscular, intravenous, and intrauterine administration of β-nerve growth factor of seminal plasma origin in female llamas.

    PubMed

    Silva, M; Fernández, A; Ulloa-Leal, C; Adams, G P; Berland, M A; Ratto, M H

    2015-10-15

    The objective of the study was to compare the pituitary and ovarian responses after intramuscular, intravenous, or intrauterine administration of β-nerve growth factor (β-NGF) of seminal plasma origin (SP-NGF) in llamas. In experiment 1, mature female llamas with a growing follicle of 7 mm or greater were assigned randomly to four groups (n = 7/group) and given 2 mg of purified SP-NGF in a volume of 2 mL by (1) intramuscular administration, (2) intravenous administration, and (3) intrauterine infusion, or (4) intrauterine infusion of 2 mL of PBS (negative control). Because ovulations were not detected after intrauterine infusion in experiment 1, a second experiment was done to determine if a higher dose of SP-NGF given by intrauterine infusion, similar to a natural dose during copulation, will elicit an ovulatory response. In experiment 2, llamas with a growing follicle of 7 mm or greater were assigned randomly to three groups (n = 6/per group) given an intrauterine infusion of (1) 4 mL of raw seminal plasma, (2) 4 mL of PBS containing 20 mg of purified llama SP-NGF, or 3) 4 mL of PBS (negative control). In both experiments, the ovaries were examined daily by transrectal ultrasonography using a B-mode scanner and power Doppler mode to detect ovulation and to monitor CL growth, regression, and vascularization. Blood samples were collected to determine plasma LH and progesterone concentrations. In experiment 1, only llamas treated by intramuscular or intravenous administration of SP-NGF ovulated (7 of 7 and 6 of 7, respectively). Plasma LH concentration did not differ between the intramuscular and intravenous SP-NGF-treated groups, nor did CL diameter, CL vascularization, or plasma progesterone concentration profiles. In experiment 2, the ovulation rate was 100% for llamas treated by intrauterine infusion of raw seminal plasma or llama SP-NFG, whereas no ovulations were detected in females treated with PBS. Plasma LH concentrations did not differ between groups

  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. Leptin concentrations in plasma and follicular fluid from prepubertal gilts as influenced by fasting, refeeding and insulin.

    PubMed

    Govoni, N; Galeati, G; Castellani, G; Tamanini, C

    2005-03-01

    This study's aim was to examine whether fasting and refeeding would influence leptin levels in both plasma and follicular fluid from prepubertal gilts, and whether insulin affects leptin levels in fasting gilts. In experiment 1, four gilts were fasted for 72 h and then refed. Blood samples were withdrawn during normoalimentation, at the end of fasting, and for 4 h after refeeding. All samples were assayed for leptin; alternate samples were assayed for insulin, glucose and non-esterified fatty acids (NEFA). Fasting caused a decrease in leptin, glucose and insulin levels in plasma, while NEFA concentrations increased. In experiment 2, four gilts were given insulin as a bolus (0.2 IU/kg body weight) after 68 h of fasting. Blood samples were collected every 15 min around insulin administration and were assayed for leptin, insulin and glucose. This experiment shows that insulin administration increases leptin levels during fasting. In experiment 3, gilts were ovariectomized during normal alimentation (n=4), after 48 h of fasting (n=4), and after 48 h of realimentation following 48 h of fasting (n=4). Leptin levels in both plasma and follicular fluid collected after 48 h of fasting were significantly lower than those observed during normoalimentation or refeeding. In conclusion, a transient increase in insulin during fasting is effective in restoring leptin concentrations; in addition, leptin levels in follicular fluid parallel those in plasma.

  15. Long-term melatonin administration increases polyunsaturated fatty acid percentage in plasma lipids of hypercholesterolemic rats.

    PubMed

    Pita, Maria L; Hoyos, Marta; Martin-Lacave, Inés; Osuna, Carmen; Fernández-Santos, Jose M; Guerrero, Juan M

    2002-04-01

    This study was designed to investigate the effect of melatonin on the fatty acid composition of plasma and tissue lipids. Melatonin administration to rats fed with a standard diet only increased long-chain n-6 polyunsaturated fatty acids (PUFA) in total plasma lipids and liver phospholipids but induced significant changes in hypercholesterolemic rats. In plasma, palmitoleic and oleic acids increased and n-6 and n-3 PUFA decreased in hypercholesterolemic rats; theses changes were reversed by melatonin administration. The analysis of lipid fractions revealed that only the cholesteryl ester fraction was affected by melatonin. Histological studies of the carotid artery intima revealed the appearance, in hypercholesterolemic rats, of fatty streaks produced by a mass of foam cells covered by the endothelium and by a thin layer of mononucleated cells. These changes were prevented by melatonin. We conclude that long-term melatonin administration modifies the fatty acid composition of rat plasma and liver lipids and ameliorates the arterial fatty infiltration induced by cholesterol.

  16. 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 time interval defined by the lowest and highest 95

  17. [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.

  18. Sex-dependent effects of maternal separation on plasma corticosterone and brain monoamines in response to chronic ethanol administration.

    PubMed

    Kawakami, S E; Quadros, I M H; Machado, R B; Suchecki, D

    2013-12-03

    Prolonged and repeated periods of maternal separation produce behavioral phenotype of increased vulnerability to neuropsychiatric disorders and drug abuse. Most of the changes in behavior, corticosterone (CORT) and monoamine levels induced by long maternal separation (LMS) are observed after a challenge, but not in basal conditions. LMS increases ethanol-induced locomotor response and self-administration, possibly due to changes in CORT release and/or monoamine concentrations. This study examined the effects of LMS in association with chronic ethanol treatment on plasma CORT and brain monoamine concentrations in male and female Swiss mice, which were kept undisturbed (animal facility rearing - AFR) or separated from their mothers for 3h/day, from 2 to 14 days of age (LMS). As adults, one set of male and female mice received no drug treatment to assess the effect of LMS per se. Another set of animals received saline injections for 20 days and one ethanol injection (2.2g/kg, i.p.) on day 21 (acute) or ethanol for 21 days (chronic). Locomotor activity, plasma CORT levels and monoamines in the frontal cortex, striatum and hippocampus of AFR and LMS mice were evaluated in non-treated, acute and chronic ethanol-treated animals. In non-treated mice, no differences were found in CORT or locomotor activity, with small changes in monoamines content. In LMS females, chronic ethanol increased dopamine and serotonin concentrations in the frontal cortex, relative to acute ethanol LMS and to chronic ethanol-treated AFR groups (p<0.05). In LMS males, chronic ethanol increased hippocampal noradrenaline, dopamine, serotonin and metabolites when compared to respective AFR controls, as well as acute LMS. Moreover, chronic ethanol treatment resulted in higher CORT concentrations in LMS than in AFR males. Overall, these results indicate that LMS mice were more susceptible to the effects of chronic ethanol administration on CORT and brain monoamine concentrations, and that these effects

  19. 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.

  20. Digitoxin plasma half-life in the dog after administration of toxic doses.

    PubMed

    Bluschke, V; Viana, A P

    1976-04-01

    Digitoxin plasma levels were determined in the dog by radioimmunoassy after i.v. infusion of this cardenolide in toxic amounts (388 +/- 13 mug/kg). Plasma values found immediately after the administration of this dose were 588.5 +/- 91 ng/ml and attained very low levels (10 ng/ml) 96 h later. The dominant half-life of digitoxin in the dog was found to be 49.6 +/- 6.5 h, but this value was attained only in the final part of our study. The results found are compared with previous data and controversial aspects are discussed.

  1. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels.

    PubMed

    Rasmussen, D D; Boldt, B M; Wilkinson, C W; Yellon, S M; Matsumoto, A M

    1999-02-01

    Human and rat pineal melatonin secretion decline with aging, whereas visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. Accordingly, we investigated the effects of daily melatonin supplementation to male Sprague-Dawley rats, starting at middle age (10 months) and continuing into old age (22 months). Melatonin was added to the drinking water (92% of which was consumed at night) at a dosage (4 microg/ml) previously reported to attenuate the aging-associated decrease in survival rate in male rats, as well as at a 10-fold lower dosage. The higher dosage produced nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged rats receiving the lower dosage were not significantly different from young or middle-aged controls. Relative (% of body wt) retroperitoneal and epididymal fat, as well as plasma insulin and leptin levels, were all significantly increased at middle age when compared to young rats. All were restored within 10 weeks to youthful (4 month) levels in response to both dosages of melatonin. Continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels were not significantly altered by aging or melatonin treatment. Plasma testosterone, insulin-like growth factor I (IGF-I) and total triiodothyronine (T3) decreased by middle age; these aging-associated decreases were not significantly altered by melatonin treatment. Thus, visceral fat, insulin and leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral fat is associated with increased insulin resistance, diabetes, and cardiovascular disease, these results

  2. [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

  3. Human plasma concentrations of cytochrome P450 probes extrapolated from pharmacokinetics in cynomolgus monkeys using physiologically based pharmacokinetic modeling.

    PubMed

    Shida, Satomi; Utoh, Masahiro; Murayama, Norie; Shimizu, Makiko; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-01-01

    1. Cynomolgus monkeys are widely used in preclinical studies as non-human primate species. Pharmacokinetics of human cytochrome P450 probes determined in cynomolgus monkeys after single oral or intravenous administrations were extrapolated to give human plasma concentrations. 2. Plasma concentrations of slowly eliminated caffeine and R-/S-warfarin and rapidly eliminated omeprazole and midazolam previously observed in cynomolgus monkeys were scaled to human oral biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Results of the simplified human PBPK models were consistent with reported experimental PK data in humans or with values simulated by a fully constructed population-based simulator (Simcyp). 3. Oral administrations of metoprolol and dextromethorphan (human P450 2D probes) in monkeys reportedly yielded plasma concentrations similar to their quantitative detection limits. Consequently, ratios of in vitro hepatic intrinsic clearances of metoprolol and dextromethorphan determined in monkeys and humans were used with simplified PBPK models to extrapolate intravenous PK in monkeys to oral PK in humans. 4. These results suggest that cynomolgus monkeys, despite their rapid clearance of some human P450 substrates, could be a suitable model for humans, especially when used in conjunction with simple PBPK models.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Effects of radioiodine administration on serum concentrations of matrix metalloproteinases, adiponectin and thrombospondin-1

    PubMed Central

    2013-01-01

    Background In order to assess safety of radioactive iodine administration in the treatment of thyrotoxicosis, we measured concentrations of matrix metalloproteinase-2 (MMP-2), its main inhibitor – TIMP-2 (tissue inhibitor of MMP-2), matrix metalloproteinase-9 (MMP-9), its main inhibitor – TIMP-1, adiponectin, as well as pro-inflammatory and procancerogenic thrombospondin-1 (TSP-1). Design and patients The study involved 23 patients treated with radioiodine for thyrotoxicosis. Serum concentrations of TSH, free T4, free T3, MMP-2, MMP-9, TIMP-1, TIMP-2, total adiponectin and TSP-1 were measured by immunoassays just before radioiodine administration (visit 1), and subsequently, after 7 days (visit 2), 3 months (visit 3), 6 to 8 months (visit 4) and 15–18 months after radioiodine administration (visit 5). Results There were no acute changes in serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, adiponectin and TSP-1 (visit 1 vs. 2). Subsequently, there was an increase in MMP-2 (from 393±106 ng/ml to 774±424 ng/ml), TIMP-1 (from 177±76 ng/ml to 296±118 ng/ml), and adiponectin (from 16442±9490 ng/ml to 23518±9840 ng/ml), visit 1 to 5, respectively (p < 0.01). Further analysis revealed no significant change in MMP-2/TIMP-2 ratio, but there was a significant decrease in MMP-9/TIMP-1 ratio (p < 0.05), suggestive of possible decrease in free MMP-9 concentrations. Conclusions Our data reveal a significant and sustained increase in serum adiponectin, as well as possible decrease of free MMP-9 concentration after radioiodine administration. In contrast, there was no significant change of TSP-1. This might indicate overall safety of radioiodine treatment of thyrotoxicosis in terms of the risks of subsequent cardiovascular and neoplastic disease. PMID:23919647

  10. Strategic administration of enrofloxacin in poultry to achieve higher maximal serum concentrations.

    PubMed

    Sumano, L H; Gutierrez, O L; Zamora, Q M

    2003-03-01

    To achieve a higher maximal serum concentration (Cs(max)) of enrofloxacin after oral administration of 10mg/kg/day of three commercial preparations of enrofloxacin to chickens, two concentrations of the drug were tested (0.1 and 0.2%), under controlled laboratory conditions. A single oral bolus dose was delivered directly into the proventriculus of each of 240 chickens, which were equally divided into six groups: three received the customary concentration (0.1%), and three received the higher concentration. A quantitative/qualitative microbiological analytical method to determine serum concentrations of enrofloxacin and a software program to obtain pharmacokinetic variables, revealed that time vs. concentration relationships best fitted double peak shape curves, Cs(max1) and Cs(max2). Statistically significant (P>0.01) increments were obtained when 0.2% enrofloxacin oral solutions from the three different commercial preparations were administered. The increments ranged from 175% to 338% for Cs(max1) and 69% to 342% for Cs(max2). Optimal bactericidal concentrations of enrofloxacin are usually twice the value of their minimal inhibitory concentration. Although clinical trials are now required, it would appear that increments in the serum concentration of enrofloxacin may reduce to the rate at which bacterial resistance occurs and so increase clinical efficacy without affecting the cost per treatment.

  11. Analysis and distribution of esculetin in plasma and tissues of rats after oral administration.

    PubMed

    Kim, Ji-Sun; Ha, Tae-Youl; Ahn, Jiyun; Kim, Suna

    2014-12-01

    In this study, we developed a method to quantify esculetin (6,7-dihydroxycoumarin) in plasma and tissues using HPLC coupled with ultraviolet detection and measured the level of esculetin in rat plasma after oral administration. The calibration curve for esculetin was linear in the range of 4.8 ng/mL to 476.2 ng/mL, with a correlation coefficient (r(2)) of 0.996, a limit of detection value of 33.2 ng/mL, and a limit of quantification value of 100.6 ng/mL. Recovery rates for the 95.2 ng/mL and 190.5 ng/mL samples were 95.2% and 100.3%, within-runs and 104.8% and 101.0% between-runs, respectively. The relative standard deviation was less than 7% for both runs. In the pharmacokinetic analysis, the peak plasma esculetin level was reached 5 min after administration (Cmax=173.3 ng/mL; T1/2=45 min; AUC0 ~180 min=5,167.5 ng · min/mL). At 180 min post-administration (i.e., after euthanasia), esculetin was only detectable in the liver (30.87±11.33 ng/g) and the kidney (20.29±7.02 ng/g).

  12. 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.

  13. 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

  14. Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

    PubMed

    Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

    2015-04-01

    Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally.

  15. 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

  16. Steady-state maternal and fetal plasma concentrations of glyceryl trinitrate (GTN) in the preterm sheep.

    PubMed

    Bustard, Mark A; Farley, Anne E; Bennett, Brian M; Smith, Graeme N

    2003-09-01

    The administration of glyceryl trinitrate (GTN; nitroglycerin) is increasing during preterm pregnancies, yet its disposition and, importantly, the extent of fetal exposure remain to be elucidated. When used as a tocolytic (pharmacological agent that stops uterine contractions), it is administered transdermally (24-48 h). Here, we quantified the maternal and fetal steady-state plasma concentrations of maternal intravenous GTN in preterm sheep and continuously monitored maternal and fetal vascular parameters to observe possible dose-dependent vascular effects. Preterm (120 days gestation) pregnant sheep (n = 6) were instrumented with maternal femoral arterial (MA) and venous (MV) and fetal femoral arterial (FA) and umbilical venous (UV) polyethylene blood-sampling catheters. During maternal GTN infusion (3.0 micro g.kg-1.min-1, 60-min duration) the steady-state GTN concentrations ([GTN]) were as follows: MA, 98.6 +/- 9.0 nM; UV, 17.4 +/- 7.6 nM; and FA, <5 nM. There were no changes in maternal and fetal mean arterial pressure and heart rate or in uterine activity. Overall, the steady-state [GTN] was established by 5 min, and the UV/MA ratio of [GTN] was 0.18. The FA [GTN] (<5 nM) indicates that the fetus cleared essentially all GTN in the UV, and the maternal and fetal heart rate and mean arterial pressure appear to be independent of maternal GTN infusion.

  17. Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir.

    PubMed

    Sebbag, Lionel; Thomasy, Sara M; Woodward, Andrew P; Knych, Heather K; Maggs, David J

    2016-08-01

    OBJECTIVES To determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS 7 male domestic shorthair cats. PROCEDURES In a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTS Compared with penciclovir concentrations, BRL42359 concentrations were 5- to 11-fold greater in plasma and 4- to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCE In cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting. The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. Cocaine and metabolite concentrations in DBS and venous blood after controlled intravenous cocaine administration

    PubMed Central

    Ellefsen, Kayla N; da Costa, Jose Luiz; Concheiro, Marta; Anizan, Sebastien; Barnes, Allan J; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A

    2015-01-01

    Background: DBS are an increasingly common clinical matrix. Methods & results: Sensitive and specific methods for DBS and venous blood cocaine and metabolite detection by LC–HRMS and 2D GC–MS, respectively, were validated to examine correlation between concentrations following controlled intravenous cocaine administration. Linear ranges from 1 to 200 µg/l were achieved, with acceptable bias and imprecision. Authentic matched specimens’ (392 DBS, 97 venous blood) cocaine and benzoylecgonine concentrations were qualitatively similar, but DBS had much greater variability (21.4–105.9 %CV) and were lower than in blood. Conclusion: DBS offer advantages for monitoring cocaine intake; however, differences between capillary and venous blood and DBS concentration variability must be addressed. PMID:26327184

  8. 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

  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. Hematologic and plasma biochemical changes associated with fenbendazole administration in Hermann's tortoises (testudo hermanni).

    PubMed

    Neiffer, Donald L; Lydick, Dianna; Burks, Kyle; Doherty, Donna

    2005-12-01

    Toxicosis associated with benzimidazole anthelmintics has been reported with increasing frequency in zoologic collections. Clinical signs, clinicopathologic abnormalities, and gross and histologic lesions are primarily the result of damage to the gastrointestinal and hematopoietic systems. Profound leukopenia, especially granulocytopenia, is the most common and severe clinicopathologic change associated with benzimidazole administration. Death usually occurs from overwhelming systemic bacterial and/or fungal infections secondary to severe immunosuppression. In this 125-day study, six male Hermann's tortoises (Testudo hermanni) were treated orally with two 5-day courses of fenbendazole 2 wk apart at a dosage of 50 mg/kg. Serial blood samples were used to assess hematologic and plasma biochemical changes before, during, and following the treatment period. Although the tortoises remained healthy, blood sampling indicated an extended heteropenia with transient hypoglycemia, hyperuricemia, hyperphosphatemia, and equivocal hyperproteinemia/hyperglobulinemia, which were considered to be in response to fenbendazole administration. Changes in several other clinicopathologic parameters appeared to correlate with fenbendazole administration. The hematologic and biochemical changes seen in the healthy animals in this study should be considered when treating compromised tortoises with fenbendazole. Hematologic and plasma biochemical status of tortoises/reptiles should be determined before treatment and monitored during the treatment period. The risk of mortality of an individual from nematode infection should be assessed relative to the potential for metabolic alteration and secondary septicemia following damage to hematopoietic and gastrointestinal systems by fenbendazole.

  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. Simulation of Human Plasma Concentrations of Thalidomide and Primary 5-Hydroxylated Metabolites Explored with Pharmacokinetic Data in Humanized TK-NOG Mice.

    PubMed

    Nishiyama, Sayako; Suemizu, Hiroshi; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

    2015-11-16

    Plasma concentrations of thalidomide and primary 5-hydroxylated metabolites including 5,6-dihydroxythalidomide and glutathione (GSH) conjugate(s) were investigated in chimeric mice with highly "humanized" liver cells harboring cytochrome P450 3A5*1. Following oral administration of thalidomide (100 mg/kg), plasma concentrations of GSH conjugate(s) of 5-hydroxythalidomide were higher in humanized mice than in controls. Simulation of human plasma concentrations of thalidomide were achieved with a simplified physiologically based pharmacokinetic model in accordance with reported thalidomide concentrations. The results indicate that the pharmacokinetics in humans of GSH conjugate and/or catechol primary 5-hydroxylated thalidomide contributing in vivo activation can be estimated for the first time.

  14. Topographic localization of gastric lesions and key role of plasma bicarbonate concentration in dogs with experimentally induced gastric dilatation.

    PubMed

    Pfeiffer, C J; Keith, J C; April, M

    1987-02-01

    The canine gastric response to acute dilatation, its correlation with selected systemic cardiovascular changes, and preliminary study of its modulation by membrane-stabilizing agents were studied in 21 Beagle dogs. Gastric mucosal damage and adverse cardiovascular sequelae were induced by inflation of an intragastric balloon to 60 mm of Hg in each anesthetized dog for 2.5 hours. At this time, dogs were given 1 of 4 treatments: control; lidocaine HCl, 2.2 mg bolus + 66 micrograms/min, IV; prednisolone succinate, 6.6 mg, IV; and zinc sulfate, 2.2 mg bolus + 66 micrograms/min, IV. After treatments were given, there was a 4-hour deflation period. Throughout the 6.5 hours, continuous measurements were made of stroke volume, arterial blood pressure, PaO2, PaCO2, and plasma HCO3- concentration. Gastric lesions, assessed by planimetric analysis of ulcer indices, were limited to the fundus and corpus and were significantly decreased by lidocaine administration. As seen by histopathologic examination, a sharply delineated transverse area bordering the corporeal-antral junction near the lesser curvature demonstrated minimal resistance to ulceration and showed mucus depletion. Plasma HCO3- concentration, base excess, and CO2 values were negatively correlated with development of gastric damage, indicating that plasma HCO3- concentration has a key role in mucosal resistance to ulcerogenesis.

  15. 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

  16. 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.

  17. A comparison of dexmedetomidine and placebo on the plasma concentrations of NGF, BDNF, GDNF, and epinephrine during severe alcohol withdrawal.

    PubMed

    Reynolds, Paul M; Mueller, Scott W; MacLaren, Robert

    2015-02-01

    Alcohol withdrawal and therapies may affect nerve growth factor (NGF), brain-derived neurotrophic growth factor (BDNF), glial-derived neurotrophic growth factor (GDNF), and epinephrine (EPI). This study evaluated dexmedetomidine (DEX) on NGF, BDNF, GDNF, and EPI in severe alcohol withdrawal and related their plasma concentrations to DEX concentrations. Twenty-four subjects were randomized to DEX 1.2 mcg/kg/hour (high dose [HD]), 0.4 mcg/kg/hour (low dose [LD]), or placebo. Blood was collected at 0 (T0), 48 (T48), and 96-120 (T96) hours after starting the study drug, and concentrations of these transmitters and DEX were determined. Similar NGF suppression occurred at T48 and T96 across all groups. BDNF and GDNF levels increased insignificantly at T48 in the placebo group but steadily declined in both DEX groups, with a trend toward significance in the HD group at T48. EPI concentrations declined significantly in the HD group at T48, only to increase at T96. Median DEX concentrations during the study were insignificantly higher in HD than LD. T0 values of BDNF (r = -0.47, p = 0.02) and GDNF (r = -0.37, p = 0.05) were inversely associated with the need for mechanical ventilation before study enrollment. No other clinical parameter was associated with the plasma concentrations of these transmitters. Daily lorazepam requirements were associated with the severity of withdrawal (r = 0.7, p < 0.0001) and DEX concentrations were inversely related to daily lorazepam requirements (r = -0.33, p = 0.008). DEX utilization suppressed EPI (r = -0.57, p = 0.004). EPI concentrations were associated with BDNF values at T0 (r = 0.55, p = 0.04) and throughout the study (r = 0.25, p = 0.04). In summary, the plasma concentrations of NGF, BDNF, GDNF, and EPI during alcohol withdrawal are variable and the effects of DEX were marginal. DEX administration and higher DEX concentrations attenuated lorazepam administration in the short-term and suppressed EPI.

  18. 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.

  19. 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.

  20. Oral fluid cocaine and benzoylecgonine concentrations following controlled intravenous cocaine administration.

    PubMed

    Ellefsen, Kayla N; Concheiro, Marta; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A

    2016-03-01

    Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze(®) (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE observed Cmax median (range) concentrations were 932 (394-1574)μg/L for cocaine and 248 (96.9-953)μg/L for BE. SS observed cocaine and BE Cmax median (range) concentrations trended lower at 732 (83.3-1892)μg/L and 360 (77.2-836)μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs.

  1. UHPLC-MS/MS Determination, Pharmacokinetic, and Bioavailability Study of Taxifolin in Rat Plasma after Oral Administration of its Nanodispersion.

    PubMed

    Yang, Chun-Juan; Wang, Zhi-Bin; Mi, Ying-Ying; Gao, Ming-Jie; Lv, Jin-Nan; Meng, Yong-Hai; Yang, Bing-You; Kuang, Hai-Xue

    2016-04-14

    A rapid and sensitive LC-MS/MS method based on the Triple Quad system has been developed and validated for the determination and pharmacokinetics of taxifolin and its nanodispersion in rat plasma. Taxifolin plasma samples along with butylparaben (internal standard) were pre-treated by liquid-liquid extraction with ethyl acetate, and then separated on a SB-C18 RRHD column (150 mm × 2.1 mm × 1.8 μm) using isocratic elution with a run time of 3.0 min. The mobile phase was acetonitrile-water (90:10, v/v) containing 5 mM ammonium acetate at a flow rate of 0.4 mL/min. Quantification of taxifolin was performed by the electrospray ionization tandem mass spectrometry in the multiple reaction monitoring (MRM) mode with negative atmospheric ionization at m/z 303.0→285.0 for taxifolin and 193.1→92.0 for I.S., respectively. The calibration curve of taxifolin showed good linearity over a concentration range of 5.0-4280 ng/mL with a correlation coefficient of 0.9995. The limit of quantification (LLOQ) was 5.0 ng/mL. Intra-day, inter-day precision and accuracy (percent relative to standard deviation) were all within 8% at three concentration levels. A total recovery of taxifolin and I.S. was beyond 75%. The present LC-MS/MS method was successfully applied to pharmacokinetic studies of taxifolin after intravenous administration of taxifolin, oral administration of its physical mixture and nanodispersion. The absolute bioavailability of taxifolin was calculated as 0.75% for taxifolin nanodispersion and 0.49% for taxifolin, respectively.

  2. Identification of Recent Cannabis Use: Whole-Blood and Plasma Free and Glucuronidated Cannabinoid Pharmacokinetics following Controlled Smoked Cannabis Administration

    PubMed Central

    Schwope, David M.; Karschner, Erin L.; Gorelick, David A.; Huestis, Marilyn A.

    2013-01-01

    BACKGROUND Δ9-Tetrahydrocannabinol (THC) is the most frequently observed illicit drug in investigations of accidents and driving under the influence of drugs. THC-glucuronide has been suggested as a marker of recent cannabis use, but there are no blood data following controlled THC administration to test this hypothesis. Furthermore, there are no studies directly examining whole-blood cannabinoid pharmacokinetics, although this matrix is often the only available specimen. METHODS Participants (9 men, 1 woman) resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. We quantified THC, 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), cannabinol (CBN), THC-glucuronide and THCCOOH-glucuronide directly in whole blood and plasma by liquid chromatography/ tandem mass spectrometry within 24 h of collection to obviate stability issues. RESULTS Median whole blood (plasma) observed maximum concentrations (Cmax) were 50 (76), 6.4 (10), 41 (67), 1.3 (2.0), 2.4 (3.6), 89 (190), and 0.7 (1.4) μg/L 0.25 h after starting smoking for THC, 11-OH-THC, THCCOOH, CBD, CBN, and THCCOOH-glucuronide, respectively, and 0.5 h for THC-glucuronide. At observed Cmax, whole-blood (plasma) detection rates were 60% (80%), 80% (90%), and 50% (80%) for CBD, CBN, and THC-glucuronide, respectively. CBD and CBN were not detectable after 1 h in either matrix (LOQ 1.0 μg/L). CONCLUSIONS Human whole-blood cannabinoid data following cannabis smoking will assist whole blood and plasma cannabinoid interpretation, while furthering identification of recent cannabis intake. PMID:21836075

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Determination of thalidomide concentration in human plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Bai, Nan; Cui, Xiang-Yong; Wang, Jin; Sun, Chun-Guang; Mei, He-Kun; Liang, Bei-Bei; Cai, Yun; Song, Xiu-Jie; Gu, Jing-Kai; Wang, Rui

    2013-02-01

    A rapid, sensitive and specific analytical method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of thalidomide concentration in human plasma. The analyte and internal standard were extracted by liquid-liquid extraction with ether-dichloromethane (3:2, v/v) and separated on a TC-C(18) column using methanol-10 mM ammonium acetate-formic acid (60:40:0.04, v/v/v) as the mobile phase at a flow rate of 0.9 ml/min. The detection was performed using an API 4000 triple quadrupole mass spectrometer in the positive electrospray ionization (ESI) mode and completed within 3.0 min. The multiple reaction monitoring (MRM) transitions were m/z 259.1→84.0 for the analyte and m/z 195.9→138.9 for temozolomide. The calibration curve exhibited a linear dynamic range of 2-1500 ng/ml (r>0.9991). The intra-and inter-day precisions (as relative standard deviation; RSD) were 6.8-13.5% and 4.3-5.0% respectively and the accuracy (as relative error; RE) was 2.0-3.5%. The recoveries and matrix effects were satisfactory in all the biological matrices examined. This method was successfully used in a pharmacokinetic study of thalidomide in healthy male volunteers receiving an oral administration of a 200-mg dose.

  9. 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.

  10. 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.

  11. Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration.

    PubMed

    Dumont, G J H; Sweep, F C G J; van der Steen, R; Hermsen, R; Donders, A R T; Touw, D J; van Gerven, J M A; Buitelaar, J K; Verkes, R J

    2009-01-01

    MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in animals has suggested that the neuropeptide oxytocin may induce these effects. In a double blind, randomized, crossover, and placebo-controlled study in 15 healthy volunteers we assessed blood oxytocin and MDMA concentrations and subjective prosocial effects after oral administration of 100 mg MDMA or placebo. MDMA induced a robust increase of blood oxytocin concentrations and an increase of subjective prosocial feelings. Within subjects, the variations in these feelings were significantly and positively correlated with variation in oxytocin levels, and the correlations between these feelings and oxytocin were significantly stronger than those between these feelings and blood MDMA levels. MDMA induces oxytocin release in humans, which may be involved in the characteristic prosocial effects of ecstasy.

  12. Pharmacokinetics of Enrofloxacin and Danofloxacin in Plasma, Inflammatory Exudate, and Bronchial Secretions of Calves following Subcutaneous Administration

    PubMed Central

    McKellar, Quintin; Gibson, Ian; Monteiro, Ana; Bregante, Miguel

    1999-01-01

    Enrofloxacin (2.5 mg/kg of body weight) and danofloxacin (1.25 mg/kg) were administered subcutaneously to ruminating calves (n = 8) fitted with subcutaneous tissue cages. Concentrations of enrofloxacin, its metabolite ciprofloxacin, and danofloxacin in blood (plasma), tissue cage exudate (following intracaveal injection of 0.3 ml of 1% [vol/wt] carrageenan), and bronchial secretions were measured by high-performance liquid chromatography (HPLC) and microbiological assay (enrofloxacin plus ciprofloxacin and danofloxacin). Mean maximum concentrations (Cmax) ± standard deviations of enrofloxacin (0.24 ± 0.08 μg/ml), ciprofloxacin (0.11 ± 0.03 [total, 0.34 ± 0.10] μg/ml), and danofloxacin (0.23 ± 0.05 μg/ml) were detected in the plasma of calves by HPLC. The Cmax were 0.49 ± 0.17 μg/ml (enrofloxacin equivalents) and 0.24 ± 0.03 μg/ml (danofloxacin) when they were measured by microbiological assay. Mean Cmax in exudate (HPLC) were 0.18 ± 0.07 μg/ml (enrofloxacin), 0.10 ± 0.04 μg/ml (ciprofloxacin), 0.27 ± 0.09 μg/ml (enrofloxacin plus ciprofloxacin), and 0.19 ± 0.05 μg/ml (danofloxacin), and concentrations in exudate exceeded those in plasma from 8 h (enrofloxacin and ciprofloxacin) or 6 h (danofloxacin) after drug administration. The Cmax were 0.34 ± 0.09 μg/ml (enrofloxacin equivalents) and 0.22 ± 0.04 μg/ml (danofloxacin) in exudate when they were measured by the microbiological assay. The maximum mean concentration achieved in bronchial secretions (HPLC) were 0.07 ± 0.04 μg/ml (enrofloxacin), 0.04 ± 0.07 μg/ml (ciprofloxacin), 0.10 ± 0.05 μg/ml (enrofloxacin plus ciprofloxacin), and 0.12 ± 0.09 μg/ml (danofloxacin). The maximum mean concentration in bronchial secretions from a limited number of animals from which samples were available for microbiological assay were 0.27 ± 0.11 μg/ml (n = 4 [enrofloxacin equivalents]) and 0.14 ± 0.02 μg/ml (n = 3 [danofloxacin]). With predictive models of efficacy (Cmax/MIC and area under the

  13. 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.

  14. No effect of route of exposure (oral; subcutaneous injection) on plasma bisphenol A throughout 24h after administration in neonatal female mice.

    PubMed

    Taylor, Julia A; Welshons, Wade V; Vom Saal, Frederick S

    2008-02-01

    Route of administration of chemicals in adults is an important factor in pharmacokinetics of chemicals such as bisphenol A (BPA), the monomer with estrogenic activity used to make polycarbonate plastic products and to line food and beverage cans. Based on findings in adults it has been proposed (CERHR, 2007) that non-oral routes of administration in newborn rodents would also lead to high exposure relative to oral administration. However, in fetuses and neonates, the enzyme that conjugates BPA (UDP-glucuronosyltransferase) is expressed at low levels, suggesting that there may be no differences in pharmacokinetics between oral and non-oral dosing. We thus conducted an analysis of plasma concentrations of unconjugated 3H-BPA after HPLC separation in postnatal day 3 female mice throughout the 24h after administering 3H-BPA orally or via subcutaneous injection at doses above and below the current EPA reference dose. We found no significant difference in plasma BPA based on route of administration in neonatal mice at either dose. However, compared to data from other studies conducted with adults, there was a markedly higher plasma BPA level after oral administration of BPA in newborn mice. This finding sets aside the belief that non-oral administration of BPA renders data as not suitable for consideration of the hazard posed by low-dose exposure to BPA during neonatal life. Therefore the large numbers of BPA studies that used non-oral administration at very low doses during the neonatal period should not be dismissed by scientists or the regulatory community based on route of administration.

  15. Plasma angiopoietin-2 concentrations are related to impaired lung function, and organ failure in a clinical cohort receiving high dose interleukin-2 therapy

    PubMed Central

    Gores, Kathryn M.; Delsing, Angela S.; Kraus, Sara J.; Powers, Linda; Vaena, Daniel A.; Milhem, Mohammed M.; Monick, Martha; Doerschug, Kevin C.

    2015-01-01

    Introduction The pathophysiology and therapeutic options in sepsis-induced lung injury remain elusive. High Dose Interleukin-2 therapy (HDIL-2) is an important protocol for advanced malignancies but is limited by systemic inflammation and pulmonary edema that is indistinguishable from sepsis. In pre-clinical models, IL-2 stimulates angiopoietin-2 secretion, which increases endothelial permeability and causes pulmonary edema. However, these relationships have not been fully elucidated in humans. Further, the relevance of plasma angiopoietin-2 to organ function is not clear. We hypothesized that plasma angiopoietin-2 concentrations increase during HDIL-2, and are relevant to clinical pathophysiology. Methods We enrolled 13 subjects with metastatic melanoma or renal cell carcinoma admitted to receive HDIL-2, and collected blood and spirometry data daily. The plasma concentrations of angiopoietin-2 and interleukin-6 were measured with ELISA. Results At baseline, the mean angiopoietin-2 concentration was 2.5 ng/mL (SD 1.0 ng/mL). Angiopoietin-2 concentrations increased during treatment: the mean concentration on the penultimate day was 16.0 ng/mL (SD 4.5 ng/mL) and increased further to 18.6 ng/mL (SD 4.9 ng/mL; p < 0.05 vs penultimate) during the last day of therapy. The Forced Expiratory Volume in one second (FEV-1) decreased during treatment. Interestingly, plasma angiopoietin-2 concentrations correlated negatively with FEV-1 (Spearman r=−0.78, p < 0.0001). Plasma angiopoietin-2 concentrations also correlated with plasma interleukin-6 concentrations (r = 0.61, p < 0.0001) and Sequential Organ Failure Assessment (SOFA) scores (r = 0.68, p < 0.0001). Conclusions Plasma angiopoietin-2 concentrations increase during HDIL-2 administration, and correlate with pulmonary dysfunction. HDIL-2 may serve as a clinical model of sepsis and acute lung injury. Further investigation is warranted. PMID:24727870

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Concentrations of nandrolone metabolites in urine after the therapeutic administration of an ophthalmic solution.

    PubMed

    Avois, Lidia; Mangin, Patrice; Saugy, Martial

    2007-05-09

    Nandrolone, an anabolic steroid, is used for the treatment of several diseases and is available in various pharmaceutical formulations. The most widely used pharmaceutical formulation is Deca-Durabolin, but other products, such as Keratyl eye drops solution, are also currently administered. Nandrolone is one of the most abused anabolic steroid in sports. Analyses for this anabolic steroid according to the World Anti-Doping Agency (WADA) protocol are based on the identification of the nandrolone two main urinary metabolites which, in humans, are glucuronides of 19-norandrosterone and 19-noretiocholanolone. A positive cut off limit of 2 ng/mL has been set by the anti-doping code for the first metabolite, 19-norandrosterone. In this preliminary study, an eye drops solution (Keratyl) containing a therapeutic dose of a nandrolone sodium sulphate was administered to several male volunteers during 3 days and urines were collected during 3 weeks. Surprisingly, contrary to all expectations, the urinary concentrations measured in urines reached 450 ng/mL and 70 ng/mL for norandrosterone and noretiocholanolone, respectively. Moreover, concentration levels near to 2 ng/mL were found, more than 2 weeks after the last administration, depending on individual metabolism. Inter-variability as well as intra-variability of nandrolone excretion kinetic, regarding this particular administration mode, were also evaluated. Quantification of nandrolone metabolites was performed by GC-MS. The method was previously validated in terms of specificity, precision, linearity, LOD, LOQ, robustness, accuracy and the expanded uncertainty was also evaluated.

  3. Short-term administration of tall oil phytosterols improves plasma lipid profiles in subjects with different cholesterol levels.

    PubMed

    Jones, P J; Howell, T; MacDougall, D E; Feng, J Y; Parsons, W

    1998-06-01

    To assess the short-term cholesterol-lowering potential of sitostanol-containing tall oil plant sterols, 22 subjects consumed fixed-food diets over two 10-day periods with or without 21.2 mg/kg body weight/d tall oil phytosterols (sitosterol 62%, sitostanol 21%, campesterol 16%, and campestanol 1%) in a randomized crossover study design. On day 10 of each diet, plasma lipoprotein cholesterol levels, plasma phytosterol concentrations, and cholesterol biosynthesis rates were determined. Total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels were lower (P < .01) after administration of tall oil phytosterol (4.7 +/- 0.3 and 3.0 +/- 0.3 mmol/L, respectively) versus placebo (5.0 +/- 0.3 and 3.2 +/- 0.3 mmol/L, respectively). Tall oil treatment had no effect on the plasma high-density lipoprotein (HDL) cholesterol level (1.1 +/- 0.1 mmol/L) versus placebo (1.1 +/- 0.1 mmol/L). Similarly, plasma triglyceride (TG) levels did not differ between tall oil (1.3 +/- 0.2 mmol/L) and placebo (1.4 +/- 0.2 mmol/L) treatments. Plasma campesterol (15.8 +/- 3.7 mmol/mol cholesterol) and sitosterol (6.0 +/- 2.1 mmol/mol cholesterol) levels were not different after tall oil treatment versus placebo treatment (15.4 +/- 2.3 and 6.4 +/- 2.0 mmol/mol cholesterol, respectively). Plasma sitostanol levels were essentially undetectable. No difference was observed in cholesterol biosynthesis between tall oil (0.045 +/- 0.004 pools/d) and placebo (0.034 +/- 0.004 pools/d) treatments; however, the effect of treatments in subjects with different cholesterol levels varied. In subjects with lower cholesterol values, the red blood cell cholesterol fractional synthesis rate (FSR) increased from 0.0291 +/- 0.0054 pools/d after placebo to 0.0509 +/- 0.0049 pools/d (P < .05) after phytosterol treatment. In subjects with higher cholesterol values, the red blood cell cholesterol FSR did not change significantly after treatment. These results demonstrate the short-term efficacy of tall

  4. 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.

  5. 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.

  6. Comparison of jet injector and insulin pen in controlling plasma glucose and insulin concentrations in type 2 diabetic patients.

    PubMed

    Guo, Lixin; Xiao, Xinhua; Sun, Xue; Qi, Cuijuan

    2017-01-01

    This study is conducted to investigate efficacy of an insulin jet injector and an insulin pen in treatment of type 2 diabetic patients. Sixty patients with type 2 diabetes were treated with rapid-acting insulin (regular insulin) and insulin analog (insulin aspart) using the jet injector and the pen in 4 successive test cycles. Postprandial glucose and insulin concentrations in blood were measured over time. Areas under curves of glucose and the insulin were calculated, and efficacy of 2 injection methods in treatment of the diabetes was compared. Regular insulin and insulin aspart administration by the jet injector showed significant decreases in plasma glucose levels as compared to the pen injection (P < 0.05). Postprandial plasma glucose excursions at the time points of 0.5 to 3 hours were obviously lower in the jet-treated patients than the pen-treated ones (P < 0.05). Postprandial plasma insulin levels were markedly higher in the jet-treated patients than the pen-treated ones (P < 0.05). Area under the glucose curve in the pen-treated patients was significantly increased as compared to the jet-treated ones (P < 0.01). Efficacy of the insulin jet injector in treatment of type 2 diabetic patients is obviously superior to the insulin pen in regulating plasma glucose and insulin levels.

  7. Comparison of jet injector and insulin pen in controlling plasma glucose and insulin concentrations in type 2 diabetic patients

    PubMed Central

    Guo, Lixin; Xiao, Xinhua; Sun, Xue; Qi, Cuijuan

    2017-01-01

    Abstract This study is conducted to investigate efficacy of an insulin jet injector and an insulin pen in treatment of type 2 diabetic patients. Sixty patients with type 2 diabetes were treated with rapid-acting insulin (regular insulin) and insulin analog (insulin aspart) using the jet injector and the pen in 4 successive test cycles. Postprandial glucose and insulin concentrations in blood were measured over time. Areas under curves of glucose and the insulin were calculated, and efficacy of 2 injection methods in treatment of the diabetes was compared. Regular insulin and insulin aspart administration by the jet injector showed significant decreases in plasma glucose levels as compared to the pen injection (P < 0.05). Postprandial plasma glucose excursions at the time points of 0.5 to 3 hours were obviously lower in the jet-treated patients than the pen-treated ones (P < 0.05). Postprandial plasma insulin levels were markedly higher in the jet-treated patients than the pen-treated ones (P < 0.05). Area under the glucose curve in the pen-treated patients was significantly increased as compared to the jet-treated ones (P < 0.01). Efficacy of the insulin jet injector in treatment of type 2 diabetic patients is obviously superior to the insulin pen in regulating plasma glucose and insulin levels. PMID:28072690

  8. Biodistribution of boron concentration on melanoma-bearing hamsters after administration of p-, m-, o-boronophenylalanine.

    PubMed

    Hiratsuka, J; Yoshino, K; Kondoh, H; Imajo, Y; Mishima, Y

    2000-04-01

    Although p-boronophenylalanine (p-BPA), a boronate analogue of tyrosine, has proven to be one of the most successful compounds for boron neutron capture therapy (BNCT) of malignant melanoma, the selective uptake mechanism of this compound into melanoma cells is not well understood. Therefore, the relationship between the structure of BPA and its specific affinity to melanoma cells appears worthy of investigation. In the present study, m- and o-boronophenylalanine (m- and o-BPA) were administered to melanoma-bearing hamsters and their uptake was measured. The time courses (0.5, 2.0, 4.0 and 48.0 h) of boron concentrations in melanoma, normal skin, and blood were determined in male Syrian (golden) hamsters bearing Greene's melanomas following a single intraperitoneal injection of either p-, m- or o-BPA (100 mg/kg of BPA fructose in 1.0 ml of saline). The boron concentrations in these tissues were measured by inductively coupled plasma-atomic emission spectrometry (ICP-AES). In melanoma, the order of boron uptake was p- > m- > o-BPA at all time points, and the boron concentrations obtained with p-BPA and m-BPA resembled each other in that they had a peak at 2 h after administration and decreased with time. The melanoma/skin boron concentration ratio of p-BPA had a peak at 4 h after administration and the ratio ranged between 7/1 and 8/1. On the other hand, m-BPA and o-BPA had a peak at 2 h and their ratios ranged between 4/1 and 5/1. The difference in the accumulations of p-BPA and m-BPA could be due to a difference in the property of p-BPA as a tyrosine analogue for melanin synthesis. The accumulation of m-BPA into melanoma might indicate the baseline level of metabolism-related amino acid transport. Our experimental findings indicate that this melanin synthesis, or the structural analogy between the boron compound and tyrosine as a precursor of melanin, is an important factor in the increased accumulation of p-BPA in melanoma cells.

  9. Plasma and cerebrospinal fluid concentrations of linezolid in neurosurgical critically ill patients with proven or suspected central nervous system infections.

    PubMed

    Luque, S; Grau, S; Alvarez-Lerma, F; Ferrández, O; Campillo, N; Horcajada, J P; Basas, M; Lipman, J; Roberts, J A

    2014-11-01

    Linezolid is a valuable treatment option for central nervous system (CNS) infections caused by multidrug-resistant Gram-positive micro-organisms. Data regarding its penetration into the CNS have shown wide variability. The aim of this study was to describe the population pharmacokinetics of linezolid in plasma and cerebrospinal fluid (CSF) in critically ill patients with external CSF drainage and proven or suspected CNS infections. This was an observational pharmacokinetic (PK) study in 11 critically ill patients with proven or suspected CNS infection receiving linezolid. Serial blood and CSF samples were taken and were subject to population PK analysis. The median (interquartile range) of AUC(0-12h) was 47.6 (17.9-58.6) mgh/L in plasma and 21.1 (18.8-30.4) mgh/L in CSF, with a median CSF/plasma ratio of 0.77. At pre-dose at steady state, a strong positive correlation was observed between linezolid concentrations in CSF and plasma (Spearman's rho=0.758; P=0.011). For a minimum inhibitory concentration (MIC) of 2 mg/L, the median AUC(0-24h)/MIC values in plasma and CSF were <80 in all patients. A three-compartment linear model was found to be most appropriate. The mean value for linezolid clearance was 16.6L/h and mean volume of distribution was 101.3 L. No covariate relationships could be supported on any of the parameters. Linezolid demonstrated good penetration into the CNS but high interindividual PK variability. Administration of higher than standard doses of linezolid and therapeutic drug monitoring should therefore be considered as options to optimise linezolid dosing in critically ill patients with CNS infections.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.

    PubMed

    Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; LoDico, Charles; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

    2014-08-01

    Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45 g oral poppy seed doses 8 h apart, each containing 15.7 mg morphine and 3mg codeine. Urine was collected ad libitum up to 32 h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2000 and 300 μg/L cutoffs, and the ThermoFisher CEDIA(®) heroin metabolite (6-acetylmorphine, 6-AM) and Lin-Zhi 6-AM immunoassays with 10 μg/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32 h following dosing; 26.6% and 83.4% were positive for morphine at 2000 and 300 μg/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7522 μg/L with a median peak concentration of 5239 μg/L. The median first morphine-positive urine sample at 2000 μg/L cutoff concentration occurred at 6.6 h (1.2-12.1), with the last positive from 2.6 to 18 h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2000 μg/L, but 20.2% exceeded 300 μg/L, with peak concentrations of 658 μg/L (284-1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300 μg/L cutoffs. The CEDIA 6-AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results.

  19. Morphine and Codeine Concentrations in Human Urine following Controlled Poppy Seeds Administration of Known Opiate Content

    PubMed Central

    Smith, Michael L.; Nichols, Daniel C.; Underwood, Paula; Fuller, Zachary; Moser, Matthew A.; LoDico, Charles; Gorelick, David A.; Newmeyer, Matthew N.; Concheiro, Marta; Huestis, Marilyn A.

    2014-01-01

    Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45g oral poppy seed doses 8h apart, each containing 15.7mg morphine and 3mg codeine. Urine was collected ad libitum up to 32h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2,000 and 300μg/L cutoffs, and the ThermoFisher CEDIA® Heroin Metabolite (6-acetylmorphine, 6AM) and Lin-Zhi 6AM immunoassays with 10μg/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32h following dosing; 26.6% and 83.4% were positive for morphine at 2,000 and 300μg/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7,522μg/L with a median peak concentration of 5,239μg/L. The median first morphine-positive urine sample at 2,000μg/L cutoff concentration occurred at 6.6h (1.2-12.1), with the last positive from 2.6 to 18h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2,000μg/L, but 20.2% exceeded 300μg/L, with peak concentrations of 658 μg/L (284-1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300μg/L cutoffs. The CEDIA 6AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results. PMID:24887324

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. [Serum gamma globulin concentration in goat kids after colostrum administration: effect of time of administration, volume and type of colostrum].

    PubMed

    Orsel, K; van Amerongen, J J; Zadoks, R N; van Doorn, D C; Wensing, T

    2000-12-01

    In this study, which was performed on a Dutch dairy goat farm, several aspects of the administration of colostrum to new-born goat kids were examined. Time of colostrum administration and amount and type of colostrum administered were compared. Effectiveness was measured as total serum protein content and gamma globulin fraction. No significant differences in serum gamma globulin titre were observed between kids that received colostrum at 30 or 60-90 minutes post partum, respectively. Titres were significantly lower in kids that received 100 ml of colostrum instead of 150-200 ml. The effect of sheep colostrum replacer or cow colostrum was also examined. Gamma globulin titres were significantly high with goat colostrum than with cow colostrum or sheep colostrum replacer, and titres were higher with cow colostrum than with sheep colostrum replacer. Based on the results of this experiment, the following protocol is suggested for colostrum administration to goat kids: single administration of 150-200 ml of goat colostrum within 90 minutes of birth. Use of cow colostrum is not advised because it may lead to transmission of paratuberculosis. Use of sheep colostrum replacer as a source of passive immunity is not recommended.

  6. 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

  7. 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.

  8. 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

  9. Oral Fluid Cocaine and Benzoylecgonine Concentrations Following Controlled Intravenous Cocaine Administration

    PubMed Central

    Ellefsen, Kayla N.; Concheiro, Marta; Pirard, Sandrine; Gorelick, David A.; Huestis, Marilyn A.

    2016-01-01

    Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze® (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25 mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE median observed Cmax (range) was 932 (394–1,574) μg/L for cocaine and 248 (96.9–953) μg/L for BE. SS median (range) observed cocaine and BE Cmax trended lower at 732 (83.3–1,892) μg/L and 360 (77.2–836) μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5 h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs. PMID:26851651

  10. Urinary excretion of copper, zinc and iron with and without D-penicillamine administration in relation to hepatic copper concentration in dogs.

    PubMed

    Fieten, H; Hugen, S; van den Ingh, T S G A M; Hendriks, W H; Vernooij, J C M; Bode, P; Watson, A L; Leegwater, P A J; Rothuizen, J

    2013-08-01

    Hereditary copper-associated hepatitis in dogs resembles Wilson's disease, a copper storage disease in humans. Values for urinary copper excretion are well established in the diagnostic protocol of Wilson's disease, whereas in dogs these have not been evaluated. The objectives of this study were to characterize both basal and D-penicillamine induced urinary copper, zinc and iron excretion in dogs in relation to hepatic copper concentration. Beagles, Beagle-Bedlington terrier cross-breeds homozygous for the COMMD1 gene mutation that causes copper toxicosis, and Labrador retrievers with normal or increased hepatic copper concentrations were investigated. The hepatic copper phenotype was determined by histological evaluation of liver biopsies and measurement of the hepatic copper concentration by instrumental neutron activation analysis. Urinary excretion of copper, iron and zinc was measured via inductively coupled plasma optical emission spectrometry under basal conditions and after oral administration of a single dose (20mg/kg bodyweight) of the chelator D-penicillamine. There was a rapid increase in urinary excretion of copper and zinc, but not iron after D-penicillamine administration. This increase was not different between dogs with high or normal hepatic copper concentrations. D-penicillamine-induced urinary copper excretion and the copper/creatinine ratio did not correlate with hepatic copper concentrations in the dogs studied, although basal urinary copper/zinc ratios did correlate with hepatic copper concentrations in Labrador retrievers. The latter parameter may be useful in diagnostic and follow-up protocols for copper-associated hepatitis in Labrador retrievers.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

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

    PubMed

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

    2013-01-01

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

  17. Pharmacokinetics of Repeated Sodium Salicylate Administration to Laying Hens: Evidence for Time Dependent Increase in Drug Elimination from Plasma and Eggs

    PubMed Central

    Poźniak, Błażej; Grabowski, Tomasz; Motykiewicz-Pers, Karolina; Bobrek, Kamila; Rak, Lech; Bobusia, Katarzyna; Gaweł, Andrzej; Świtała, Marcin

    2015-01-01

    Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs) to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus) salicylate (SA) may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS) to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT), minimal plasma concentration (Cmin, C16h) and elimination half-life (T1/2el) of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB) increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment. PMID:25893240

  18. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.

    PubMed

    Sumi, H; Hamada, H; Nakanishi, K; Hiratani, H

    1990-01-01

    The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced.

  19. Assessing plasma lipid levels, body weight, and hepatic and renal toxicity following chronic oral administration of a water soluble phytostanol compound, FM-VP4, to gerbils.

    PubMed

    Wasan, K M; Najafi, S; Wong, J; Kwong, M; Pritchard, P H

    2001-01-01

    The purpose of this project was to determine the effect of a FM-VP4 when incorporated into the diet or drinking water on plasma lipids, body weight, and hepatic and renal function following chronic oral administration to gerbils. Gerbils were administered water and food daily containing either no FM-VP4 (controls; n=6), 2% or 4% FM-VP4 incorporated into the gerbil diet (n=6 each treatment group) or 2% or 4% FM-VP4 dissolved in the drinking water (n=6 each treatment group). Body weight and food and water intake were monitored weekly. Following 8 weeks of this regiment blood was obtained via a cardiac puncture and all animals were sacrificed humanely. Plasma obtained from this blood was analyzed for total cholesterol, total triglyceride and high-density lipoprotein (HDL)-cholesterol levels by standard enzymatic and precipitation techniques. Low-density lipoprotein (LDL)-cholesterol levels were determined by the Friedewald equation. The plasma was also analyzed for changes in hepatic enzyme (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and plasma creatinine (renal function) concentrations. 2% and 4% FM-VP4 administration incorporated both into the diet and in the drinking water resulted in a significant decrease in total plasma cholesterol and LDL cholesterol concentration compared to controls. Animals administered 4% FM-VP4 in either their diet or drinking water had significantly lower body weight following the 8 weeks of treatment compared to the other groups. Significant differences in daily water intake was observed in all treatment groups with the exception of the 2% FM-VP4 in diet group compared to controls. Significant differences in daily food intake were observed in gerbils administered 2% FM-VP4 in the drinking water and 4% FM-VP4 in the diet and drinking water groups compared to controls. A significant decrease in total plasma triglyceride concentration was observed in gerbils administered 4% FM-VP4 in their drinking water compared

  20. 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

  1. 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.

  2. A supersulfated low-molecular-weight heparin (IK-SSH) increases plasma levels of free and total tissue factor pathway inhibitor after intravenous and subcutaneous administration in humans.

    PubMed

    Kaiser, B; Glusa, E; Hoppensteadt, D A; Breddin, H K; Amiral, J; Fareed, J

    1998-09-01

    Unfractionated as well as low-molecular-weight heparins (LMWH) are known to cause an increase in blood levels of tissue factor pathway inhibitor (TFPI). To study the effect of a newly developed supersulfated LMWH (IK-SSH, Iketon Farmaceutici) on TFPI concentrations in human plasma, the compound was injected into volunteers at doses of 0.14, 0.33 and 0.66 mg/kg intravenously or 0.33, 0.66 and 1.0 mg/kg subcutaneously. At certain known times blood was drawn and plasma levels of both total and free TFPI were measured using enzyme-linked immunosorbent assay methodology. Baseline plasma concentrations of TFPI were 72.2+/-3.1 ng/ml for total and 10.8+/-0.8 ng/ml for free TFPI. Intravenous or subcutaneous injection of IK-SSH led to a strong and long-lasting rise in TFPI levels which were increased more than 5-fold for total TFPI and more than 30-fold for free TFPI. Maximum TFPI levels were reached 5-10 min after intravenous and 60 min after subcutaneous administration. IK-SSH caused prolongation of ex-vivo clotting times in the APTT and Heptest assay, whereas thrombin time was not affected. Anticoagulant actions of IK-SSH showed a significant correlation to plasma concentrations of TFPI and they are thought to be based at least partially on the release of TFPI from vascular sites.

  3. Plasma protein binding of amphotericin B and pharmacokinetics of bound versus unbound amphotericin B after administration of intravenous liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate.

    PubMed

    Bekersky, Ihor; Fielding, Robert M; Dressler, Dawna E; Lee, Jean W; Buell, Donald N; Walsh, Thomas J

    2002-03-01

    Unilamellar liposomal amphotericin B (AmBisome) (liposomal AMB) reduces the toxicity of this antifungal drug. The unique composition of liposomal AMB stabilizes the liposomes, producing higher sustained drug levels in plasma and reducing renal and hepatic excretion. When liposomes release their drug payload, unbound, protein-bound, and liposomal drug pools may exist simultaneously in the body. To determine the amounts of drug in these pools, we developed a procedure to measure unbound AMB in human plasma by ultrafiltration and then used it to characterize AMB binding in vitro and to assess the pharmacokinetics of nonliposomal pools of AMB in a phase IV study of liposomal AMB and AMB deoxycholate in healthy subjects. We confirmed that AMB is highly bound (>95%) in human plasma and showed that both human serum albumin and alpha(1)-acid glycoprotein contribute to this binding. AMB binding exhibited an unusual concentration dependence in plasma: the percentage of bound drug increased as the AMB concentration increased. This was attributed to the low solubility of AMB in plasma, which limits the unbound drug concentration to <1 microg/ml. Subjects given 2 mg of liposomal AMB/kg of body weight had lower exposures (as measured by the maximum concentration of drug in serum and the area under the concentration-time curve) to both unbound and nonliposomal drug than those receiving 0.6 mg of AMB deoxycholate/kg. Most of the AMB in plasma remained liposome associated (97% at 4 h, 55% at 168 h) after liposomal AMB administration, so that unbound drug concentrations remained at <25 ng/ml in all liposomal AMB-treated subjects. Although liposomal AMB markedly reduces the total urinary and fecal recoveries of AMB, urinary and fecal clearances based on unbound AMB were similar (94 to 121 ml h(-1) kg(-1)) for both formulations. Unbound drug urinary clearances were equal to the glomerular filtration rate, and tubular transit rates were <16% of the urinary excretion rate, suggesting

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

    PubMed

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

    2002-04-01

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

  5. 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

  6. 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

  7. Phenytoin blood concentrations in hospitalized geriatric patients: oral versus nasogastric feeding tube administration.

    PubMed

    Lubart, Emilia; Berkovitch, Matitiahu; Leibovitz, Arthur; Orly, Dafni; Segal, Refael

    2010-04-01

    Many medications administered to frail geriatric patients are not in a liquid form, but are crushed and dissolved in water before their administration through a nasogastric tube (NGT). Some medications are enteric coated and others are extended release. Only sparse information is available on their pharmacokinetics when administered through NGT. The aim of our study was to evaluate the pharmacokinetics of phenytoin administered through an NGT and to compare these with the pharmacokinetics of a group of patients receiving the drug orally. Twenty patients were studied in a stable clinical condition, from the long-term care ward of the Geriatric Medical Center Shmuel Harofeh. They were consistently treated with phenytoin for the prevention of seizure disorders. Patients in group 1 (n = 12) had oropharyngeal dysphagia and received feeding and medications by NGT. Group 2 (n = 8), included age-matched orally fed patients from the same department, who received phenytoin orally. Blood samples for phenytoin concentration were taken at baseline, time 0, and at 1, 3, 4, 6, and 8 hours postdrug administration; phenytoin was measured using the AxSYM assay. The mean daily dose was not statistically different between the 2 groups: 291 +/- 28 (200-300) mg/d and 300 +/- 53 (200-400) mg/d, in the NGT, and the orally fed group, respectively, in one dose. Pharmacokinetic parameters of phenytoin were not significantly different between the 2 groups; trough concentrations, 1.9 +/- 1.7 (0.5-4.9) versus 2.2 +/- 1.8 (1.0-6.5) microg/mL; Cmax, 6.6 +/- 3.4 (2.5-9.1) versus 7.3 +/- 6.7 (2.7-8.4) microg/mL; tmax, 5.1 +/- 3.1 (3.1-8.2) versus 4.6 +/- 2.7 (2.3-8.4) hours; area under the curve, 52.2 +/- 40.1 (41.1-61.2) versus 62.3 +/- 84.7 (30.2-77.2) microg/h/mL, in the NGT fed versus the oral fed, respectively. Phenytoin pharmacokinetic parameters are not significantly different between patients receiving the drug through NGT as compared with those who received it orally, but the implication

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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) ...

  16. 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.

  17. 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.

  18. [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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Gait Changes Vary among Horses with Naturally Occurring Osteoarthritis Following Intra-articular Administration of Autologous Platelet-Rich Plasma

    PubMed Central

    Mirza, Mustajab H.; Bommala, Prakash; Richbourg, Heather A.; Rademacher, Nathalie; Kearney, Michael T.; Lopez, Mandi J.

    2016-01-01

    Mechanisms to reduce lameness associated with osteoarthritis (OA) are vital to equine health and performance. This study was designed to quantify response to autologous, intra-articular platelet-rich plasma (PRP) in horses with OA. Kinetic gait analysis was performed on 12 horses with unilateral forelimb lameness and OA in the same limb before and after intra-articular anesthesia (IAA). Radiographs and kinetic data were obtained before and 6 and 16 weeks after PRP administration to same joint, 4 weeks after IAA. Statistical evaluations included filtration effect on platelet concentration, relationship between kinetic variable changes after IAA versus PRP in the affected limb, and associations between response to PRP and response to IAA, platelet concentration, and radiographic OA. A positive response to IAA or PRP was defined as ≥5% improvement in peak vertical force, vertical impulse, or breaking impulse of the affected limb. Out of 10 horses that responded to IAA, 3 responded to PRP at both time points and 4 responded at one. Of the two horses that did not respond to IAA, one responded to PRP at both time points. Filtration increased platelet concentration significantly. The relationship between kinetic variable alterations of the affected limb after IAA and PRP was not significant, and response to PRP was not associated with response to IAA, platelet concentration, or radiographic OA. Changes in kinetic variables following IAA in joints with naturally occurring OA provide a custom standard to assess intra-articular therapy. Kinetic gait changes after intra-articular PRP are variable in horses with moderate to severe forelimb OA. PMID:27148544

  4. Effects of a newly developed transdermal clonidine delivery system (M-5041T) on EEG sleep-wake cycle in relation to plasma concentration in rabbits.

    PubMed

    Kimura, K; Ishihara, K; Tagawa, T; Sakurai, M; Fujii, Y; Dote, S; Naruse, T; Sasa, M; Namba, K

    1996-01-01

    1. The effects of a transdermal clonidine delivery system (M-5041T) on EEG sleep pattern with relation to plasma concentrations in unrestrained rabbits were investigated and compared with those of intravenous (i.v.) administration of clonidine. 2. Although M-5041T did not affect the EEG recorded from cortex and hippocampus at doses up to 2.5 mg/kg, slow theta waves in hippocampal EEG accompanied by low-voltage slow waves in cortex were induced at a higher dose of 12.5 mg/kg. On i.v. injection (0.25 mg/kg), EEG tracings with bursts of high-voltage slow waves in cortical EEG and slow theta waves in hippocampus were observed. 3. At doses of 0.5 and 2.5 mg/kg, M-5041T did not cause any alterations of the sleep-wake cycle, and plasma concentrations of 1-2 ng/ml were maintained for an 8-hr observation period. However, this delivery system significantly suppressed the incidence of rapid-eye movement sleep (REMS) from 11.9 to 4.7% and enhanced drowsiness (DW) from 9.0 to 21.0% during the 8-hr recording period at 12.5 mg/kg with a plasma concentration of up to 10 ng/ml. Contrary to transdermal administration, i.v. clonidine (0.25 mg/kg) completely blocked light and deep slow wave sleep as well as REMS with a plasma concentration indicated more than 10 ng/ml at 2 hr post administration. Recovery to a normal sleep-wake cycle was eventually established thereafter. The incidence of REMS and DW were significantly decreased from 11.9 to 6.3% and increased from 9.0 to 25.5%, respectively. 4. Concurrent monitoring of clonidine concentrations in cerebrospinal fluid (CSF) indicated that CSF concentrations after patching M-5041T, as well as i.v. clonidine, were almost equal to plasma levels. 5. These results suggest that alteration of the sleep-wake cycle with clonidine occurs depending upon brain concentrations, which increase to a level similar to that in plasma after administration, and that M-5041T at doses of less than 2.5 mg/kg could establish effective hypertensive therapy

  5. 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.

  6. UHPLC-MS/MS determination and pharmacokinetic study of plantamajoside in rat plasma after oral administration of single plantamajoside and Plantago asiatica extract.

    PubMed

    Bai, Lizhi; Han, Li; Lu, Xiaoguang; Kang, Xin; Fan, Zhiwei; Xing, Rong; Zhou, Dangxia

    2017-05-01

    A sensitive and reliable ultra-high performance liquid chromatography coupled with tandem quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for quantitation of plantamajoside in rat plasma. First, this study compared the pharmacokinetic properties of plantamajoside after oral administration of Plantago asiatica extract and pure plantamajoside in rat plasma with approximately the same dosage of 8.98 mg/kg. Second, chromatographic separation was performed on an Acquity HSS C18 column (50 × 2.1 mm, p.d.1.7 μm) with isocratic elution using methanol-water (80:20, v/v) as mobile phase at a flow rate of 0.25 mL/min. The calibration curves were linear over the range of 0.1-100 ng/mL for plantamajoside. At different time points (0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6 and 8 h) after administration, the concentrations of plantamajoside in plasma were measured and the main pharmacokinetic parameters were estimated. The study indicates that the pharmacokinetics of plantamajoside in rat plasma have significant differences between two groups.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. [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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Rising taurine and ethanol concentrations in nucleus accumbens interact to produce dopamine release after ethanol administration.

    PubMed

    Ericson, Mia; Chau, PeiPei; Clarke, Rhona B; Adermark, Louise; Söderpalm, Bo

    2011-07-01

    We have previously demonstrated that glycine receptors in the nucleus accumbens (nAc) are involved in modulating both basal and ethanol-induced dopamine output in the same brain region. Ethanol is known to induce a release of both taurine and dopamine in the nAc, but the relationship between these two neuromodulators has not been investigated thoroughly. In vivo microdialysis was used to measure the effects of systemic ethanol diluted in isotonic (0.9% NaCl) or hypertonic (3.6% NaCl) saline on accumbal taurine and dopamine levels. We found that ethanol given in a hypertonic solution, contrary to an isotonic solution, failed to increase concentrations both of taurine and dopamine in the nAc. However, a modest, non-dopamine elevating concentration of taurine in the nAc disclosed a dopamine-elevating effect of systemic ethanol also when given in a hypertonic solution. In a second experiment, we investigated the effects of ethanol on taurine and dopamine in normal rats and rats with decreased levels of endogenous taurine. Lowering the level of taurine, approximately 40% by adding 5% β-alanine in the drinking water, did not influence taurine or dopamine output over time. We conclude that the elevations of taurine and dopamine in the nAc are closely related, and that in order for ethanol to induce dopamine release, a simultaneous increase of extracellular taurine levels in the nAc is required. These data also provide support for the notion that the nAc is the primary target for ethanol in its dopamine-activating effect after systemic administration.

  18. Methamphetamine and Amphetamine Isomer Concentrations in Human Urine Following Controlled Vicks VapoInhaler Administration

    PubMed Central

    Smith, Michael L.; Nichols, Daniel C.; Underwood, Paula; Fuller, Zachary; Moser, Matthew A.; Flegel, Ron; Gorelick, David A.; Newmeyer, Matthew N.; Concheiro, Marta; Huestis, Marilyn A.

    2014-01-01

    Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography–mass spectrometry (GC–MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC–MS method with >99% purity of R-(−)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC–MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0–1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT® II Plus, KIMS® II and DRI® had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT® II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation. PMID:25217541

  19. Methamphetamine and amphetamine isomer concentrations in human urine following controlled Vicks VapoInhaler administration.

    PubMed

    Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; Flegel, Ron; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

    2014-10-01

    Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography-mass spectrometry (GC-MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC-MS method with >99% purity of R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC-MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0-1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤ 4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT(®) II Plus, KIMS(®) II and DRI(®) had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT(®) II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. Intrathecal Morphine Plus General Anesthesia in Cardiac Surgery: Effects on Pulmonary Function, Postoperative Analgesia, and Plasma Morphine Concentration

    PubMed Central

    dos Santos, Luciana Moraes; Santos, Verônica Cavani Jorge; Santos, Silvia Regina Cavani Jorge; Malbouisson, Luiz Marcelo Sá; Carmona, Maria José Carvalho

    2009-01-01

    OBJECTIVES: To evaluate the effects of intrathecal morphine on pulmonary function, analgesia, and morphine plasma concentrations after cardiac surgery. INTRODUCTION: Lung dysfunction increases morbidity and mortality after cardiac surgery. Regional analgesia may improve pulmonary outcomes by reducing pain, but the occurrence of this benefit remains controversial. METHODS: Forty-two patients were randomized for general anesthesia (control group n=22) or 400 μg of intrathecal morphine followed by general anesthesia (morphine group n=20). Postoperative analgesia was accomplished with an intravenous, patient-controlled morphine pump. Blood gas measurements, forced vital capacity (FVC), forced expiratory volume (FEV), and FVC/FEV ratio were obtained preoperatively, as well as on the first and second postoperative days. Pain at rest, profound inspiration, amount of coughing, morphine solicitation, consumption, and plasma morphine concentration were evaluated for 36 hours postoperatively. Statistical analyses were performed using the repeated measures ANOVA or Mann-Whiney tests (*p<0.05). RESULTS: Both groups experienced reduced FVC postoperatively (3.24 L to 1.38 L in control group; 2.72 L to 1.18 L in morphine FEV1 (p=0.085), group), with no significant decreases observed between groups. The two groups also exhibited similar results for FEV1/FVC (p=0.68) and PaO2/FiO2 ratio (p=0.08). The morphine group reported less pain intensity (evaluated using a visual numeric scale), especially when coughing (18 hours postoperatively: control group= 4.73 and morphine group= 1.80, p=0.001). Cumulative morphine consumption was reduced after 18 hours in the morphine group (control group= 20.14 and morphine group= 14.20 mg, p=0.037). The plasma morphine concentration was also reduced in the morphine group 24 hours after surgery (control group= 15.87 ng.mL−1 and morphine group= 4.08 ng.mL−1, p=0.029). CONCLUSIONS: Intrathecal morphine administration did not significantly alter

  12. Development of a Rat Plasma and Brain Extracellular Fluid Pharmacokinetic Model for Bupropion and Hydroxybupropion Based on Microdialysis Sampling, and Application to Predict Human Brain Concentrations.

    PubMed

    Cremers, Thomas I F H; Flik, Gunnar; Folgering, Joost H A; Rollema, Hans; Stratford, Robert E

    2016-05-01

    Administration of bupropion [(±)-2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one] and its preformed active metabolite, hydroxybupropion [(±)-1-(3-chlorophenyl)-2-[(1-hydroxy-2-methyl-2-propanyl)amino]-1-propanone], to rats with measurement of unbound concentrations by quantitative microdialysis sampling of plasma and brain extracellular fluid was used to develop a compartmental pharmacokinetics model to describe the blood-brain barrier transport of both substances. The population model revealed rapid equilibration of both entities across the blood-brain barrier, with resultant steady-state brain extracellular fluid/plasma unbound concentration ratio estimates of 1.9 and 1.7 for bupropion and hydroxybupropion, respectively, which is thus indicative of a net uptake asymmetry. An overshoot of the brain extracellular fluid/plasma unbound concentration ratio at early time points was observed with bupropion; this was modeled as a time-dependent uptake clearance of the drug across the blood-brain barrier. Translation of the model was used to predict bupropion and hydroxybupropion exposure in human brain extracellular fluid after twice-daily administration of 150 mg bupropion. Predicted concentrations indicate that preferential inhibition of the dopamine and norepinephrine transporters by the metabolite, with little to no contribution by bupropion, would be expected at this therapeutic dose. Therefore, these results extend nuclear imaging studies on dopamine transporter occupancy and suggest that inhibition of both transporters contributes significantly to bupropion's therapeutic efficacy.

  13. Relationship between plasma concentrations and cardiac beta-adrenoceptor blockade--a study with oral and intravenous bopindolol.

    PubMed Central

    Aellig, W H; Nüesch, E; Engel, G; Grevel, J; Niederberger, W; Rosenthaler, J

    1986-01-01

    Bopindolol, an esterified beta-adrenoceptor blocking drug, was administered to nine healthy male volunteers in oral (1 mg and 4 mg) and intravenous (1 mg) doses. Plasma concentrations determined using a radio-receptor assay (RRA) and high pressure liquid chromatography (h.p.l.c.) yielded almost identical results, indicating that hydrolysed bopindolol, the major metabolite, is responsible for the pharmacological activity of the drug. After intravenous administration the half-life for the formation of the hydrolysis product was about 0.3 h. The elimination of hydrolysed bopindolol from the plasma, determined with a one-compartment model occurred with a half-life of about 4 h. There were indications for a longer beta phase of elimination with a half-life of about 8 h, which, owing to the relative insensitivity of the method for concentrations present after more than 24 h, could not be determined exactly. The absolute bioavailability of the active compound is about 70%. Cardiac beta-adrenoceptor blockade was determined as the reduction in exercise-induced tachycardia. With oral doses the maximum effect was reached after 3 h (-29 beats min-1 after 1 mg, -40 beats min-1 after 4 mg). After intravenous administration most of the effect was present after 0.5 h but the maximum effect (-33 beats min-1) was only reached at 3 h. Bopindolol possesses a long duration of action: after 48 h 33% of the maximum effect of the oral dose of 4 mg was still present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2868747

  14. Relationship between plasma concentrations and cardiac beta-adrenoceptor blockade--a study with oral and intravenous bopindolol.

    PubMed

    Aellig, W H; Nüesch, E; Engel, G; Grevel, J; Niederberger, W; Rosenthaler, J

    1986-01-01

    Bopindolol, an esterified beta-adrenoceptor blocking drug, was administered to nine healthy male volunteers in oral (1 mg and 4 mg) and intravenous (1 mg) doses. Plasma concentrations determined using a radio-receptor assay (RRA) and high pressure liquid chromatography (h.p.l.c.) yielded almost identical results, indicating that hydrolysed bopindolol, the major metabolite, is responsible for the pharmacological activity of the drug. After intravenous administration the half-life for the formation of the hydrolysis product was about 0.3 h. The elimination of hydrolysed bopindolol from the plasma, determined with a one-compartment model occurred with a half-life of about 4 h. There were indications for a longer beta phase of elimination with a half-life of about 8 h, which, owing to the relative insensitivity of the method for concentrations present after more than 24 h, could not be determined exactly. The absolute bioavailability of the active compound is about 70%. Cardiac beta-adrenoceptor blockade was determined as the reduction in exercise-induced tachycardia. With oral doses the maximum effect was reached after 3 h (-29 beats min-1 after 1 mg, -40 beats min-1 after 4 mg). After intravenous administration most of the effect was present after 0.5 h but the maximum effect (-33 beats min-1) was only reached at 3 h. Bopindolol possesses a long duration of action: after 48 h 33% of the maximum effect of the oral dose of 4 mg was still present.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. 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.

  16. Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration.

    PubMed

    Lee, Dayong; Vandrey, Ryan; Milman, Garry; Bergamaschi, Mateus; Mendu, Damodara R; Murray, Jeannie A; Barnes, Allan J; Huestis, Marilyn A

    2013-09-01

    Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.

  17. 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

  18. Effects of ambroxol hydrochloride on concentrations of paclitaxel and carboplatin in lung cancer patients at different administration times.

    PubMed

    Li, J; Yi, W; Jiang, P; Sun, R; Li, T

    2016-11-30

    Our previous preliminary study revealed a synergistic effect of ambroxol hydrochloride with chemotherapeutic agents such as paclitaxel and carboplatin in lung cancer. However, the optimal conditions such as administration time and drug concentration of ambroxol hydrochloride to achieve the maximum synergistic effect remained unclear. Therefore, concentration changes of the chemotherapy drugs paclitaxel and carboplatin in the sputum were observed after ambroxol hydrochloride administration at different times in order to determine the most effective time frame of ambroxol hydrochloride administration. In this study, 470 cases of non-small cell lung cancer (NSCLC) were divided into different groups with ambroxol hydrochloride administered at different time points prior to chemotherapy, while another 171 cases received no ambroxol hydrochloride prior to chemotherapy. The results showed the concentrations of paclitaxel and carboplatin in sputum of patients treated with ambroxol hydrochloride were significantly higher than those of the control group, suggesting that ambroxol hydrochloride significantly increased the local concentrations of chemotherapeutic agents in lung tissues of NSCLC. Furthermore, the intravenous administration of ambroxol hydrochloride more than 48 hours before chemotherapy showed an optimized schedule and much greater efficacy in increasing drug concentrations than that of the control group. No statistical differences were found in the rates of grade 2 or above myelosuppression between the ambroxol intervention and control groups. Taken together, these results demonstrate that ambroxol hydrochloride administered intravenously more than 48 hours prior to chemotherapy optimally increased the concentrations of paclitaxel and carboplatin in lung tissue without significantly increasing hematologic toxicity.

  19. 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.

  20. 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

  1. 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.

  2. Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations?

    PubMed

    Öbrink-Hansen, Kristina; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob

    2015-11-01

    Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.).

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. Comparison of the Peak-to-trough Fluctuation in Plasma Concentration of Long-acting Injectable Antipsychotics and Their Oral Equivalents

    PubMed Central

    Sheehan, John J.; Reilly, Kristin R.; Fu, Dong-Jing

    2012-01-01

    Background: Small peak-to-trough drug levels have been suggested to be related to improved tolerability. The aim of this study is to review the steady-state, peak-to-trough, plasma-concentration fluctuation of long-acting injectable antipsychotics and equivalent oral formulations. Methods: A review of published literature and clinical study reports identified references that reported, depicted, or permitted derivation of the steady-state, peak-to-trough, plasma-concentration fluctuation of antipsychotics (the ratio of maximum concentration to minimum concentration following administration according to the recommended dosing interval) over the dosing interval. Suitable references were identified for haloperidol decanoate, olanzapine pamoate, paliperidone palmitate, risperidone long-acting injectable, and zuclopenthixol decanoate and their oral equivalents except zuclopenthixol. The single-dose time to maximum plasma concentration (Tmax) and half-life (t1/2) were also identified. Results: The steady-state, peak-to-trough, plasma-concentration ratios of oral antipsychotics varied from 1.47 (paliperidone extended-release, once daily) to 3.30 (active-moiety risperidone, once daily). Among long-acting injectable antipsychotics, the ratios varied from 1.56 (paliperidone palmitate, once monthly) to approximately 4 (olanzapine pamoate, once every four weeks). Among drugs with similar dosing intervals, longer Tmax and/or t1/2 generally correlated with less peak-to-trough fluctuation. Conclusion: Peak-to-trough fluctuations in plasma concentrations vary widely and may be affected by differences in dosing, pharmacokinetic sampling, subjects’ phenotypes, concomitant medications, comorbid diseases, and formulation. These fluctuations may affect clinical response and tolerability. Along with other patient-specific and drug-specific factors, these fluctuations warrant consideration when selecting an antipsychotic and antipsychotic formulation. Further study is needed with more

  10. 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.

  11. 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.

  12. 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.

  13. Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study

    PubMed Central

    Daughters, Katie; Manstead, Antony S. R.; Hubble, Kelly; Rees, Aled; Thapar, Anita; van Goozen, Stephanie H. M.

    2015-01-01

    The use of intranasal oxytocin (OT) in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration ‘wait-time’ prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups. PMID:26669935

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. [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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Plasma concentrations of endotoxin and platelet activation in the developmental stage of oligofructose-induced laminitis.

    PubMed

    Bailey, S R; Adair, H S; Reinemeyer, C R; Morgan, S J; Brooks, A C; Longhofer, S L; Elliott, J

    2009-06-15

    The link between the fermentation of carbohydrate in the equine large intestine and the development of acute laminitis is poorly understood. Absorption of endotoxin (lipopolysaccharide; LPS) into the plasma has been observed in one experimental model of laminitis, but does not cause laminitis when administered alone. Thus, the potential role of endotoxin is unclear. Platelet activation has previously been demonstrated in the developmental stage of laminitis. Equine platelets are more sensitive than leukocytes to activation by endotoxin, and can be activated directly by LPS in the low pg/ml range, activating p38 MAP kinase and releasing serotonin (5-HT) and thromboxane. The objectives of this study were firstly to determine whether endotoxin and platelet activation could be measured in the plasma of horses in the developmental phase of laminitis induced with oligofructose. Secondly, the time course of events involving platelet activation and platelet-derived vasoactive mediator production was investigated. Laminitis was induced in six Standardbred horses by the administration of 10 g/kg bwt of oligofructose. Plasma samples were obtained every 4h, and platelet pellets were obtained by centrifugation. LPS was measured using a kinetic limulus amebocyte lysate assay, and platelet activation was assessed by Western blotting for the phosphorylated form of p38 MAP kinase. Plasma 5-HT was assayed by HPLC with electrochemical detection and thromboxane B(2) was measured by radioimmunoassay. Clinical signs of laminitis and histopathologic changes were observed in lamellar sections from five of the six horses. Onset of lameness was between 20 and 30 h after the administration of oligofructose. LPS increased above the limit of detection (0.6 pg/ml) to reach a peak of 2.4+/-1.0 pg/ml at 8 h. TNFalpha was also detectable in the plasma from 12 to 24 h. There was a time-dependent increase in platelet p38 MAPK phosphorylation, which peaked at approximately 12 h (3.8+/-1.3 fold

  7. 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

  8. Simultaneous Determination and Pharmacokinetic Study of Quercetin, Luteolin, and Apigenin in Rat Plasma after Oral Administration of Matricaria chamomilla L. Extract by HPLC-UV

    PubMed Central

    Dong, Xiaoxv; Lan, Wei; Yin, Xingbin; Yang, Chunjing; Wang, Wenping

    2017-01-01

    A simple and sensitive HPLC-UV method has been developed for the simultaneous determination of quercetin, luteolin, and apigenin in rat plasma after oral administration of Matricaria chamomilla L. extract. The flow rate was set at 1.0 ml/min and the detection wavelength was kept at 350 nm. The calibration curves were linear in the range of 0.11–11.36 μg/ml for quercetin, 0.11–11.20 μg/ml for luteolin, and 0.11–10.60 μg/ml for apigenin, respectively. The intraday and interday precisions (RSD) were less than 8.32 and 8.81%, respectively. The lower limits of quantification (LLOQ) of the three compounds were 0.11 μg/ml. The mean recoveries for quercetin, luteolin, and apigenin were 99.11, 95.62, and 95.21%, respectively. Stability studies demonstrated that the three compounds were stable in the preparation and analytical process. The maximum plasma concentration (Cmax) was 0.29 ± 0.06, 3.04 ± 0.60, and 0.42 ± 0.10 μg/ml, respectively. The time to reach the maximum plasma concentration (Tmax) was 0.79 ± 0.25, 0.42 ± 0.09, and 0.51 ± 0.13 h, respectively. The validated method was successfully applied to investigate the pharmacokinetics study of quercetin, luteolin, and apigenin in rat plasma after oral administration of M. chamomilla extract. PMID:28373891

  9. Simultaneous Determination and Pharmacokinetic Study of Quercetin, Luteolin, and Apigenin in Rat Plasma after Oral Administration of Matricaria chamomilla L. Extract by HPLC-UV.

    PubMed

    Dong, Xiaoxv; Lan, Wei; Yin, Xingbin; Yang, Chunjing; Wang, Wenping; Ni, Jian

    2017-01-01

    A simple and sensitive HPLC-UV method has been developed for the simultaneous determination of quercetin, luteolin, and apigenin in rat plasma after oral administration of Matricaria chamomilla L. extract. The flow rate was set at 1.0 ml/min and the detection wavelength was kept at 350 nm. The calibration curves were linear in the range of 0.11-11.36 μg/ml for quercetin, 0.11-11.20 μg/ml for luteolin, and 0.11-10.60 μg/ml for apigenin, respectively. The intraday and interday precisions (RSD) were less than 8.32 and 8.81%, respectively. The lower limits of quantification (LLOQ) of the three compounds were 0.11 μg/ml. The mean recoveries for quercetin, luteolin, and apigenin were 99.11, 95.62, and 95.21%, respectively. Stability studies demonstrated that the three compounds were stable in the preparation and analytical process. The maximum plasma concentration (Cmax) was 0.29 ± 0.06, 3.04 ± 0.60, and 0.42 ± 0.10 μg/ml, respectively. The time to reach the maximum plasma concentration (Tmax) was 0.79 ± 0.25, 0.42 ± 0.09, and 0.51 ± 0.13 h, respectively. The validated method was successfully applied to investigate the pharmacokinetics study of quercetin, luteolin, and apigenin in rat plasma after oral administration of M. chamomilla extract.

  10. 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.

  11. 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

  12. Simultaneous determination of seven alkaloids in rat plasma by UFLC-MS/MS and its application to a pharmacokinetic study after oral administration of Cerebralcare Granule.

    PubMed

    Xiaowen, Li; Ling, Tong; Yunfei, Li; Guoxiang, Sun; Dailin, Yang; Herry, Sun

    2016-04-01

    An ultra fast liquid chromatography-tandem mass sepectrometry (UFLC-MS/MS) method was developed for simultaneous determination of seven active alkaloid components (tetrahydropalmatine, corydaline, α-allocryptopine, tetrahydroberberine, tetrahydrocoptisine, tetrahydrocolumbamine and dehydrocorydaline) in rat plasma after oral administration of Cerebralcare Granule. Plasma samples were pretreated by protein precipitation with acetronitrile containing the internal standard diazepam. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with gradient elution using mobile phase consisting of acetonitrile -0.1% formic acid in water at a flow rate of 0.3mL/min. The detection was performed on an electrospray ionization triple quadrupole tandem mass spectrometer using multiple reaction monitoring (MRM) with positive ionization mode. The established method was fully validated and proved to be sensitive and specific with lower limits of quantification (LLOQs) all less than 0.0265ng/mL in rat plasma. Good linearities of seven alkaloids were obtained in respective concentration ranges (r>0.9923). The intra- and inter-day precisions were below of 15% for all the seven alkaloids in terms of relative standard deviation (RSD), and the accuracies were ranged from -2.7% to 8.3% in terms of relative error (RE). Extraction recovery, matrix effect and stability were within the required limits in rat plasma. The validated method was successfully applied to investigate the pharmacokinetics of the seven alkaloids in rat plasma after oral administration of Cerebralcare Granule (CG).

  13. Assessment of chronic administration of Aloe vera gel on haematology, plasma biochemistry, lipid profiles and erythrocyte osmotic resistance in Wistar rats.

    PubMed

    Iji, O T; Oyagbemi, A A; Azeez, O I

    2010-11-28

    The study was designed to investigate the effects of chronic administration of Aloe vera gel extract on markers of hepatic damage, lipid profiles and erythrocyte osmotic fragility using the Wistar rats. Forty male Wistar rats divided into four groups of ten rats per group were used in the study. Group I which served as the control received 0.9% physiological saline while those in groups II, III and IV received Aloe vera gel (100, 250 and 500mg/kg), respectively, for four weeks. There was significant increase in the haemoglobin concentration while the PCV, RBC count, MCH and MCHC though showed some marginal increases but the increases were not significant in all the treated rats. No significant change was also observed in the erythrocyte osmotic fragility. However, there were significant reductions in plasma ALT, AST and ALP levels in animals that received the gel compared with the control while the plasma albumin and total protein values were higher than those of the control. All the animals that received the gel also showed significant reduction in plasma total cholesterol, triglycerides and LDL-cholesterol ratio compared with the control. In a similar manner, those animals that were administered with 500mg/kg gel had significantly higher HDL-cholesterol ratio than those of the control. This study showed that, chronic administration of Aloe vera gel extract had no significant effects on the haematological parameters of the rats and did not affect erythrocyte osmotic resistance. It however showed some cholesterol lowering action.

  14. Buccal mucosal delivery of a potent peptide leads to therapeutically-relevant plasma concentrations for the treatment of autoimmune diseases.

    PubMed

    Jin, Liang; Boyd, Ben J; White, Paul J; Pennington, Michael W; Norton, Raymond S; Nicolazzo, Joseph A

    2015-02-10

    Stichodactyla helianthus neurotoxin (ShK) is an immunomodulatory peptide currently under development for the treatment of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis by parenteral administration. To overcome the low patient compliance of conventional self-injections, we have investigated the potential of the buccal mucosa as an alternative delivery route for ShK both in vitro and in vivo. After application of fluorescent 5-Fam-ShK to untreated porcine buccal mucosa, there was no detectable peptide in the receptor chamber using an in vitro Ussing chamber model. However, the addition of the surfactants sodium taurodeoxycholate hydrate or cetrimide, and formulation of ShK in a chitosan mucoadhesive gel, led to 0.05-0.13% and 1.1% of the applied dose, respectively, appearing in the receptor chamber over 5h. Moreover, confocal microscopic studies demonstrated significantly enhanced buccal mucosal retention of the peptide (measured by mucosal fluorescence associated with 5-Fam-ShK) when enhancement strategies were employed. Administration of 5-Fam-ShK to mice (10mg/kg in a mucoadhesive chitosan-based gel (3%, w/v) with or without cetrimide (5%, w/w)) resulted in average plasma concentrations of 2.6-16.2nM between 2 and 6h, which were substantially higher than the pM concentrations required for therapeutic activity. This study demonstrated that the buccal mucosa is a promising administration route for the systemic delivery of ShK for the treatment of autoimmune diseases.

  15. Effects of prolonged elevation of plasma adrenaline concentration in vivo on insulin-sensitivity in soleus muscle of the rat.

    PubMed Central

    Budohoski, L; Challiss, R A; Dubaniewicz, A; Kaciuba-Usciłko, H; Leighton, B; Lozeman, F J; Nazar, K; Newsholme, E A; Porta, S

    1987-01-01

    1. Prolonged elevation of the plasma adrenaline concentration was produced in rats by implantation of adrenaline-releasing retard-tablets. With this technique, a hyperadrenalinaemic state is maintained for at least 5 days. 2. At 6 h after implantation of the retard-tablet it was found that plasma glucose and fatty acid concentrations increased and insulin concentration decreased compared with values obtained from placebo-tablet-implanted rats. Administration of a subcutaneous glucose load demonstrated an impaired glucose tolerance in vivo, and incubation of soleus muscle strips from 6 h-hyperadrenalinaemic rats in vitro demonstrated a decreased sensitivity of the rates of glycolysis and glucose transport to insulin. 3. The sensitivities of the rates of glycolysis, glucose transport and glycogen synthesis to insulin were determined for the incubated soleus muscle preparation isolated from animals after 48 h, 72 h and 120 h duration of hyperadrenalinaemia. At 48 h after retard-tablet implantation, the sensitivity of the processes of glucose transport and glycolysis was decreased; at 72 h, the insulin-sensitivities of the rates of glycolysis and glucose transport in skeletal muscle were similar to those determined for control animals; at 120 h, however, the sensitivities of the processes of glucose transport and glycolysis were both statistically significantly increased. In contrast, no changes in the sensitivity of the process of glycogen synthesis were observed at any of the time intervals studied. 4. The possible biochemical basis for the observed changes in skeletal-muscle insulin-sensitivity with prolonged hyperadrenalinaemia is discussed. PMID:3328612

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Effect of long term-administration with Gymnema sylvestre R. BR on plasma and liver lipid in rats.

    PubMed

    Shigematsu, N; Asano, R; Shimosaka, M; Okazaki, M

    2001-06-01

    Extract of Gymnema sylvestre leaves was administered to rats receiving either a high fat diet or normal fat diet for 10 weeks to investigate its influence on plasma and liver lipids and on visceral fat accumulation. In addition, its effect was compared with those of chitosan and the influence of combined use of these two substances was also evaluated. Within the high fat diet groups, the extract suppressed body weight gain and accumulation of liver lipids to the same extent as chitosan and the combined use. In addition, intraperitoneal fat and fat drop vacuoles on the epithelium of renal tubules, noted in the high fat diet group, were scattered by administration of the extract with the same results as for chitosan and combined use. Within the normal fat diet groups, plasma triglyceride levels decreased by administration of the extract, with similar results as chitosan and combined use. Concerning plasma total cholesterol, there was no decreasing effects with the extract, as found with chitosan and combined use. However, the effect of chitosan on plasma total cholesterol tended to be enhanced when used in combination with the extract. In addition, long-term administration of the extract did not show any influence on hematological and blood chemical parameters.

  2. Plasma corticosterone of city and desert Curve-billed Thrashers, Toxostoma curvirostre, in response to stress-related peptide administration.

    PubMed

    Fokidis, H Bobby; Deviche, Pierre

    2011-05-01

    We compared the activity and responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis of an urban (Phoenix, Arizona) and desert population of a male songbird species (Curve-billed Thrasher, Toxostoma curvirostre), by measuring plasma corticosterone in response to acute administration of corticotropin-releasing factor, arginine vasotocin, or adrenocorticotropin hormone. Urban adult male thrashers showed greater responsiveness than desert birds to an injection of arginine vasotocin or adrenocorticotropin hormone, suggesting a population difference in pituitary and adrenal gland sensitivity. Plasma corticosterone in response to corticotropin-releasing factor injection did, however, not differ between populations. The differential corticosterone response to arginine vasotocin and corticotropin-releasing factor may reflect effects of chronic stress or habituation, which are known to favor arginine vasotocin over corticotropin-releasing factor sensitivity. Efficacy of HPA negative feedback by glucocorticoids was determined by measuring plasma corticosterone in response to acute administration of the synthetic glucocorticoid dexamethasone. This administration decreased plasma corticosterone similarly in urban and desert thrashers, suggesting that the negative feedback of glucocorticoids on the HPA axis in the two populations was equally effective. The higher sensitivity of urban than desert thrashers to adrenocorticotropin hormone and arginine vasotocin may result from up-regulation of the HPA axis in urban birds. This up-regulation may in turn make it easier for city birds to cope with urban environment-associated stressors.

  3. The hormonal response to stress is not modified by the dramatic decrease in prolactin plasma concentration during surgery for microprolactinoma

    PubMed Central

    Guieu, R; Dufour, H; Devaux, C; Brue, T; Rosso, J; Grisoli, F; Grino, M; Enjalbert, A; Begoud, D; Broder, N; Rochat, H; Jaquet, P

    1998-01-01

    OBJECTIIVES—To determine the endocrine response to surgical stress in a homogeneous population of 36 women with microprolactinomas, particularly to evaluate the effect of the sharp decrease in plasma prolactin on stress induced hormonal secretion. In addition, the effects of exogenous opiates on prolactin secretion were studied.
METHODS—The plasma kinetics of cortisol, prolactin, ACTH, GH, and β-endorphin like immunoreactivity (β-ELI) were analysed by including patients operated on with strict anaesthetic and surgical protocols, and by sampling blood every 10 minutes, starting at premedication up to 3 hours after induction.
RESULTS AND CONCLUSIONS—(a) Surgical stress or opiate administration did not induce prolactin release in patients with microprolactinoma. (b) The dramatic decrease in prolactin concentrations have apparently no effect on the release of other hormones involved in stress. (c) The existence of an early GH peak, independently of any surgical procedure, strongly suggests that GH is released by surgical stress whereas β-endorphin is secreted in response to pain. Thus GH may be a useful marker of surgical stress.

 PMID:9771773

  4. 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

  5. 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.

  6. The effect of acute stress and long-term corticosteroid administration on plasma metabolites in an urban and desert songbird.

    PubMed

    Davies, Scott; Rodriguez, Natalie S; Sweazea, Karen L; Deviche, Pierre

    2013-01-01

    In response to stressful stimuli, animals activate the hypothalamic-pituitary-adrenal axis, which can result in transition to the "emergency life history stage." A key adaptive characteristic of this life history stage is the mobilization of energy stores. However, few data are available on the metabolic response to acute stress in wild-caught, free-ranging birds. We quantified the effect of acute capture and restraint stress on plasma glucose, free fatty acid, and uric acid in free-ranging Abert's towhees Melozone aberti. Furthermore, birds were caught from urban and desert localities of Phoenix, Arizona, to investigate potential effects of urban versus desert habitats on the corticosterone (CORT) and metabolic response to acute stress. Complementing work on free-ranging birds, captive towhees received CORT-filled Silastic capsules to investigate the response of urban and desert conspecifics to long-term CORT administration. We quantified the effect of CORT administration on baseline plasma glucose and uric acid, liver and pectoralis muscle glycogen stores, kidney phosphoenolpyruvate carboxykinase (PEPCK-C, a key gluconeogenic enzyme), and body mass. Acute stress increased plasma CORT and glucose and decreased plasma uric acid but had no effect on plasma free fatty acid. There was no difference between urban and desert localities in body mass, fat scores, and the response to acute stress. CORT administration decreased body mass but had no effect on glucose and uric acid, pectoral muscle glycogen, or kidney PEPCK-C. However, liver glycogen of CORT-treated urban birds increased compared with corresponding controls, whereas glycogen decreased in CORT-treated desert birds. This study suggests that Abert's towhees principally mobilize glucose during acute stress but urban and desert towhees do not differ in their CORT and metabolic response to acute stress or long-term CORT administration.

  7. Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes.

    PubMed

    Liu, Chi; Kurokawa, Ryosuke; Fujino, Masayuki; Hirano, Shinichi; Sato, Bunpei; Li, Xiao-Kang

    2014-06-30

    Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS), and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using high-quality sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Pharmacokinetic comparison of berberine in rat plasma after oral administration of berberine hydrochloride in normal and post inflammation irritable bowel syndrome rats.

    PubMed

    Gong, Zipeng; Chen, Ying; Zhang, Ruijie; Wang, Yinghan; Guo, Yan; Yang, Qing; Zhang, Haixian; Dong, Yu; Weng, Xiaogang; Gao, Shuangrong; Zhu, Xiaoxin

    2014-01-02

    In the present study, post inflammation irritable bowel syndrome (PI-IBS) rats were firstly established by intracolonic instillation of acetic acid with restraint stress. Then the pharmacokinetics of berberine in the rat plasma were compared after oral administration of berberine hydrochloride (25 mg/kg) to normal rats and PI-IBS rats. Quantification of berberine in the rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. Compared with the normal group, area under the plasma concentration vs. time curve from zero to last sampling time (AUC0-t) and total body clearance (CL/F) in the model group significantly increased or decreased, (2039.49 ± 492.24 vs. 2763.43 ± 203.14; 4999.34 ± 1198.79 vs. 3270.57 ± 58.32) respectively. The results indicated that the pharmacokinetic process of berberine could be altered in PI-IBS pathological conditions.

  15. Determination of hydroxysafflor yellow A in rat plasma and tissues by high-performance liquid chromatography after oral administration of safflower extract or safflor yellow.

    PubMed

    Li, Yi; Zhang, Zhao-Yang; Zhang, Jin-Lan

    2007-03-01

    A simple and reproducible HPLC method for quantification of hydroxysafflor yellow A (HSYA) in rat plasma and tissues after oral administration of safflower extract or safflor yellow (SY) was developed. Sample preparation was achieved by protein precipitation of plasma and tissue homogenates with three volumes of methanol. p-Hydroxybenzaldehyde was used as the internal standard (IS). HSYA and IS were separated on a Hypersil BDS-C(18) column with a gradient elution system composed of acetonitrile and aqueous acetic acid. UV detection was used at 320 nm. The calibration curves were linear in all matrices (r(2) > 0.999) in the concentration ranges 0.51-101.36 microg/mL for plasma, 12.27-2454.46 microg/g for intestines and 0.96-192.20 microg/g for lung. The intra-day and inter-day precision were all less than 12.5%, and the extract recovery was in the range 64.1-103.7% with RSD less than 15.6% for HSYA in all matrices. The method was used successfully to quantify HSYA in rat plasma and tissue samples to support a pharmacokinectic study.

  16. Studies of various biochemical parameters of rat plasma following chronic administration of "Rohitakarista"-an Ayurvedic formulation.

    PubMed

    Ullah, M Obayed; Uddin, M Jashim; Hamid, K; Kabir, S; Rahman, M Azizur; Choudhuri, M S K

    2008-08-15

    The study was carried out to investigate the safety profile as well as the effect of "Rohitakarista" (RHT) on various biochemical parameters of rats' plasma after chronic administration. RHT, a classical Ayurvedic preparation used in hepatosplenic disorders, was administered per oral route at a dose of 100 mg kg(-1) body weight, once daily, up to 46 days for all the experiments. Forty albino rats (Rattus novergicus: Sprague-Dawley strains), equally of both sexes, were randomly grouped into four where each group had ten animal/sex. One male and one female group were used as control and other groups were used as test. In the male, rats there was a statistically insignificant increase (p = 0.763) in the total protein but there was a statistically significant increase (p = 0.022) in the total protein content of the plasma of female rats. Statistically very high significant increase (male: p = 0.001 and female: p = 0.001) in the albumin content of the plasma was noted in both sexes. In case of bilirubin, interestingly it was decreased very high significantly (p = 0.001) in plasma of male rats but increased very high significantly (p = 0.001) in the plasma of female rats. In the male rats, statistically there was a very high significant decrease (sGPT: p = 0.001, sGOT: p = 0.001 and ALP: p = 0.001) in the sGPT, sGOT and ALP activities in the plasma. On the other hand, statistically there was a very highly significant increase (sGPT: p = 0.001, sGOT: p = 0.001 and ALP: p = 0.001) in the sGPT, sGOT and ALP activities in the plasma of female rats. Very high significant decrease (male: p = 0.001 and female: p = 0.001) in creatinine in plasma of both sexes were observed after chronic administration of RHT. Urea in the plasma was decreased very high significantly (p = 0.001) in plasma of male rats but increased very high significantly (p = 0.001) in the plasma of female rats. There was high significant increase (p = 0.002) in uric acid in male rats. On the contrary, no

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. Plasma N-POMC, ACTH and cortisol concentrations in a psychogeriatric population.

    PubMed

    Leake, A; Charlton, B G; Lowry, P J; Jackson, S; Fairbairn, A; Ferrier, I N

    1990-05-01

    Elderly patients with depression and Alzheimer-type dementia (ATD) were compared with age-matched control subjects using a protocol which measured cortisol, adrenocorticotrophic hormone (ACTH) and N-terminal pro-opiomelanocortin (N-POMC) to determine diurnal variation and the effect of dexamethasone administration. Depressed patients had significantly elevated cortisol concentrations both before and after dexamethasone administration. Basal ACTH and N-POMC concentrations were normal in depressed patients but were both elevated, compared with controls, after dexamethasone. By contrast, in ATD patients, cortisol was elevated only after dexamethasone, as was ACTH, but not N-POMC. This may imply that the pattern of secretion of POMC-derived peptides underlying increased cortisol secretion is different in ATD from that in depression.

  4. 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.

  5. Delta(9)-tetrahydrocannabinol, 11-hydroxy-delta(9)-tetrahydrocannabinol and 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in human plasma after controlled oral administration of cannabinoids.

    PubMed

    Goodwin, Robert S; Gustafson, Richard A; Barnes, Allan; Nebro, Wesenyalsh; Moolchan, Eric T; Huestis, Marilyn A

    2006-08-01

    A clinical study to investigate the pharmacokinetics and pharmacodynamics of oral tetrahydrocannabinol was performed. This randomized, double-blind, placebo-controlled, within-subject, inpatient study compared the effects of THC-containing hemp oils in liquid and capsule form to dronabinol (synthetic THC) in doses used for appetite stimulation. The National Institute on Drug Abuse Institutional Review Board approved the protocol and each participant provided informed consent. Detection times and concentrations of THC, 11-hydroxy-Delta-tetrahydrocannabinol (11-OH-THC), and 11-nor-9-carboxy-Delta-tetrahydrocannabinol (THCCOOH) in plasma were determined by gas chromatography-mass spectrometry [limits of quantification (LOQ)=0.5, 0.5, and 1.0 ng/mL, respectively] after oral THC administration. Six volunteers ingested liquid hemp oil (0.39 and 14.8 mg THC/d), hemp oil in capsules (0.47 mg THC/d), dronabinol capsules (7.5 mg THC/d), and placebo. Plasma specimens were collected during and after each dosing condition. THC and 11-OH-THC concentrations were low and never exceeded 6.1 ng/mL. Analytes were detectable 1.5 hour after initiating dosing with the 7.5 mg THC/d regimen and 4.5 hour after starting the 14.8 mg THC/d sessions. THCCOOH was detected 1.5 hour after the first dose, except for the 0.47 mg THC/d session, which required 4.5 hour for concentrations to reach the LOQ. THCCOOH concentrations peaked at 3.1 ng/mL during dosing with the low-dose hemp oils. Plasma THC and 11-OH-THC concentrations were negative for all participants at all doses within 15.5 hours after the last THC dose. Plasma THCCOOH persisted for at least 39.5 hours after the end of dosing and at much higher concentrations (up to 43.0 ng/mL). This study demonstrated that subjects who used high THC content hemp oil (347 mug/mL) as a dietary supplement had THC and metabolites in plasma in quantities comparable to those of patients using dronabinol for appetite stimulation. There was a significant

  6. 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

  7. 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

  8. Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

    PubMed

    Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

    2015-01-01

    We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

  9. 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.

  10. 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.

  11. The concentrations of SH-groups in some radiosensitive tissues after the administration of radioprotectors in rats.

    PubMed

    Stoklasová, A; Krízala, J; Ledvina, M

    1980-03-01

    The changes in the concentrations of total, nonprotein and protein SH-groups were spectrophotometrically determined in the small intestine and bone marrow of the rats 10, 20, 30 and 60 min after the administration of protective doses of cystamine (50 mg/kg), mexamine (10 mg/kg) or of a mixture of cystamine with mexamine (20 + 10 mg/kg). Cystamine caused an increase in the concentration of mainly nonprotein thiols, whereas the mexamine administration increased the protein SH-groups (mainly between the 20th and 30th min after treatment). The radioprotective mixture led to the most pronounced increase at the 10-min interval. This increase at the 10- and 20-min intervals was more pronounced (or identical) than after cystamine or mexamine administered as a single agent. If the SH-concentration should correspond to the degree of radioprotection, then the phenomenon observed would indicate the usefulness of the mixture administered.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet

    PubMed Central

    Sivak, Olena; Darlington, Jerry; Gershkovich, Pavel; Constantinides, Panayiotis P; Wasan, Kishor M

    2009-01-01

    The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS) on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE) deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE) deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w), untreated control and 2% (w/w) stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w) and stigmastanol at 2% (w/w) treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w) NSAS and 2% (w/w) stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model. PMID:19638223

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. [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.

  7. 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.

  8. Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration.

    PubMed

    Zimmermann, Estevan Sonego; Laureano, João Victor; Dos Santos, Camila Neris; Schmidt, Stephan; Lagishetty, Chakradhar V; de Castro, Whocely Victor; Dalla Costa, Teresa

    2016-02-01

    Levofloxacin (LEV) is a broad-spectrum fluoroquinolone used to treat pneumonia, urinary tract infections, chronic bacterial bronchitis, and prostatitis. Efflux transporters, primarily P-glycoprotein (P-gp), are involved in LEV's tissue penetration. In the present work, LEV free lung and prostate interstitial space fluid (ISF) concentrations were evaluated by microdialysis in Wistar rats after intravenous (i.v.) and intratracheal (i.t.) administration (7 mg/kg of body weight) with and without coadministration of the P-gp inhibitor tariquidar (TAR; 15 mg/kg administered i.v.). Plasma and tissue concentration/time profiles were evaluated by noncompartmental analysis (NCA) and population pharmacokinetics (popPK) analysis. The NCA showed significant differences in bioavailability (F) for the control group (0.4) and the TAR group (0.86) after i.t. administration. A four-compartment model simultaneously characterized total plasma and free lung (compartment 2) and prostate (compartment 3) ISF concentrations. Statistically significant differences in lung and prostate average ISF concentrations and levels of kidney active secretion in the TAR group from those measured for the control group (LEV alone) were observed. The estimated population means were as follows: volume of the central compartment (V1), 0.321 liters; total plasma clearance (CL), 0.220 liters/h; TAR plasma clearance (CLTAR), 0.180 liters/h. The intercompartmental distribution rate constants (K values) were as follows: K12, 8.826 h(-1); K21, 7.271 h(-1); K13, 0.047 h(-1); K31, 7.738 h(-1); K14, 0.908 h(-1); K41, 0.409 h(-1); K21 lung TAR (K21LTAR), 8.883 h(-1); K31 prostate TAR (K31PTAR), 4.377 h(-1). The presence of P-gp considerably impacted the active renal secretion of LEV but had only a minor impact on the efflux from the lung following intratracheal dosing. Our results strongly support the idea of a role of efflux transporters other than P-gp contributing to LEV's tissue penetration into the prostrate.

  9. Absolute bioavailability of hydromorphone after peroral and rectal administration in humans: saliva/plasma ratio and clinical effects.

    PubMed

    Ritschel, W A; Parab, P V; Denson, D D; Coyle, D E; Gregg, R V

    1987-09-01

    The absolute bioavailability of hydromorphone was investigated in eight healthy male subjects by a cross-over design (with washout period of two weeks) after intravenous (2 mg), peroral (4 mg) and rectal (3 mg) administration of hydromorphone. The use of saliva hydromorphone concentrations as a noninvasive technique in pharmacokinetic evaluation was investigated, and the clinical effects after the three routes of administration were determined. Hydromorphone has an absolute bioavailability of 51.35 +/- 29.29% and 36.33 +/- 29.60% after peroral and rectal administration, respectively. More side effects were observed after intravenous administration of hydromorphone than after rectal or peroral dosing. The saliva sampling for the hydromorphone concentration was found to be a useful noninvasive technique for the estimation of the elimination half-life of hydromorphone.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM®)-guided administration of fibrinogen concentrate and prothrombin complex concentrate

    PubMed Central

    2010-01-01

    Introduction The appropriate strategy for trauma-induced coagulopathy management is under debate. We report the treatment of major trauma using mainly coagulation factor concentrates. Methods This retrospective analysis included trauma patients who received ≥ 5 units of red blood cell concentrate within 24 hours. Coagulation management was guided by thromboelastometry (ROTEM®). Fibrinogen concentrate was given as first-line haemostatic therapy when maximum clot firmness (MCF) measured by FibTEM (fibrin-based test) was <10 mm. Prothrombin complex concentrate (PCC) was given in case of recent coumarin intake or clotting time measured by extrinsic activation test (EXTEM) >1.5 times normal. Lack of improvement in EXTEM MCF after fibrinogen concentrate administration was an indication for platelet concentrate. The observed mortality was compared with the mortality predicted by the trauma injury severity score (TRISS) and by the revised injury severity classification (RISC) score. Results Of 131 patients included, 128 received fibrinogen concentrate as first-line therapy, 98 additionally received PCC, while 3 patients with recent coumarin intake received only PCC. Twelve patients received FFP and 29 received platelet concentrate. The observed mortality was 24.4%, lower than the TRISS mortality of 33.7% (P = 0.032) and the RISC mortality of 28.7% (P > 0.05). After excluding 17 patients with traumatic brain injury, the difference in mortality was 14% observed versus 27.8% predicted by TRISS (P = 0.0018) and 24.3% predicted by RISC (P = 0.014). Conclusions ROTEM®-guided haemostatic therapy, with fibrinogen concentrate as first-line haemostatic therapy and additional PCC, was goal-directed and fast. A favourable survival rate was observed. Prospective, randomized trials to investigate this therapeutic alternative further appear warranted. PMID:20374650

  20. Effects of plant stanol ester consumption on fasting plasma oxy(phyto)sterol concentrations as related to fecal microbiota characteristics.

    PubMed

    Baumgartner, Sabine; Mensink, Ronald P; Smet, Els De; Konings, Maurice; Fuentes, Susana; de Vos, Willem M; Plat, Jogchum

    2016-03-03

    Information regarding dietary effects on plasma oxyphytosterol concentrations as well as on the origin of oxyphytosterols is scarce. We hypothesized that plant sterols are oxidized in the intestinal lumen, mediated by microbial activity, followed by uptake into the circulation. To address this hypothesis, we carried out, a randomized, double blind, crossover study in 13 healthy subjects, who consumed for 3 weeks control and plant stanol ester enriched margarines (3.0g/d plant stanols) separated by a 4-week wash-out period. Plasma oxy(phyto)sterols were determined via GC-MS/MS, while microbiota analyses were performed on fecal DNA using a phylogenetic microarray to assess microbial composition and diversity. Plasma plant sterol concentrations did not correlate with plasma oxyphytosterols concentrations at baseline. Plant stanol consumption reduced serum sitosterol and campesterol concentrations (-37% and -38%), respectively (p<0.001), as well as plasma concentrations of 7β-OH-campesterol (-24%; p<0.05), 7β-OH-sitosterol (-17%; p<0.05) and 7-keto-sitosterol (-13%; p<0.05). Although the intestinal microbiota composition and diversity of the faecal contents were not different between the two periods, we observed significant correlations between several specific bacterial groups and plasma plant sterol, but not with plasma oxyphytosterol concentrations. In conclusion, plant stanol ester consumption reduced serum plant sterol and plasma oxyphytosterol concentrations, while intestinal microbiota composition and diversity were not changed. To definitely answer the effects of microbiota on oxyphytosterol formation, future studies could examine oxyphytosterol concentrations after changing intestinal microbial composition or by measuring intestinal oxyphytosterol formation after providing labelled non-oxidized plant sterols.