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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. 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

  3. Oral administration and younger age decrease plasma concentrations of voriconazole in pediatric patients.

    PubMed

    Kato, Karin; Nagao, Miki; Yamamoto, Masaki; Matsumura, Yasufumi; Takakura, Shunji; Fukuda, Kazuhiko; Ichiyama, Satoshi

    2016-01-01

    Voriconazole is used for treating or preventing invasive aspergillosis and other invasive fungal infections. To minimize adverse reactions and to maximize treatment effects, therapeutic drug monitoring should be performed. However, it is challenging to optimize daily voriconazole dosing because limited data have been published so far on pediatric patients. We retrospectively analyzed voriconazole concentrations in patients aged 0-18 years. In addition, a literature review was conducted. In our study cohort, younger age and oral administration were significantly associated with lower plasma voriconazole concentrations (P < 0.01). An unfavorable outcome was associated with low concentrations of voriconazole (P = 0.01). Reports of voriconazole administration in pediatric patients show that higher doses are required in younger children and in patients receiving oral administration. Hence, the current data suggest that we should escalate both initial and maintenance doses of voriconazole in pediatric patients, particularly in patients of younger age receiving an oral administration of voriconazole. PMID:26538245

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

    PubMed

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

    1987-02-01

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

  5. Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock

    PubMed Central

    Strandberg, G; Larsson, A; Lipcsey, M; Michalek, J; Eriksson, M

    2015-01-01

    Background We aimed to investigate whether comparable antibiotic concentrations could be reached with intraosseous and intravenous administration during septic shock. Methods In this randomized, prospective experimental study conducted at an animal research laboratory at the University Hospital of Uppsala, eight anesthetized pigs, weighing 21.2 to 29.1 kg (mean: 25.2 ± 2.3 kg), received endotoxin infusion at 4 μg/kg/h for 6 h. At the onset of clinical shock, alternatively after 3 h of endotoxemia, they received 75 mg/kg of cefotaxime and 7 mg/kg of gentamicin either in a proximal tibial intraosseous catheter or in a peripheral intravenous catheter. Mixed venous samples were taken after 5, 15, 30, 60, 120 and 180 min and analyzed for antibiotic concentrations. Results For both antibiotics, plasma concentrations after intraosseous and intravenous administration followed similar curves throughout the observation period, and peak concentrations were comparable. Mean concentration area under the curve (AUC mg × h/l) for cefotaxime was 108.1 ± 19.5 after intraosseous and 116.5 ± 11.1 after intravenous administration; ratio 0.93, (95% CI 0.71–1.19). Mean AUC for gentamicin was 28.1 ± 6.8 for intraosseous and 32.2 ± 3.5 for intravenous administration; ratio 0.87 (95% CI 0.62–1.19). Conclusions In this porcine septic shock model, intraosseous and intravenous administration of gentamicin and cefotaxime yielded comparable concentrations. In an emergency, intraosseous administration of these antibiotics may be considered in severe infections when venous access is difficult. PMID:25557933

  6. Plasma concentration and cardiovascular effects of lidocaine during continuous epidural administration in dogs anesthetized with isoflurane.

    PubMed

    Sakonju, Iwao; Maeda, Kenichi; Karasawa, Koichi; Tadokoro, Toshiyuki; Kakuta, Tomoko; Takase, Katsuaki

    2011-03-01

    The cardiovascular effects of continuous epidural administration (CEA) of lidocaine were investigated in anesthetized dogs. Loading epidural injections of 2, 4, or 6 mg/kg of lidocaine were followed by CEA with 1, 2, or 3 mg/kg/hr lidocaine, respectively, for 2 hr under 2.0% isoflurane anesthesia. Heart rate, direct blood pressure, cardiac index, and stroke volume decreased dose-dependently during CEA, whereas systemic vascular resistance did not significantly differ with dose, and no characteristic changes were observed in any groups. Plasma lidocaine concentration reached a steady state during CEA and increased in a dose-dependent manner. Circulatory suppression caused by lidocaine CEA was not attributable to peripheral vasodilation, but rather to the direct cardiac action of systemic lidocaine absorption from the peridural space. PMID:21048393

  7. Plasma and urine concentrations of marbofloxacin following single subcutaneous administration to cats.

    PubMed

    Kietzmann, Manfred; Niedorf, Frank; Kramer, Sabine; Hoffmann, Marina; Schneider, Marc; Vallé, Marc; Pankow, Rüdiger

    2011-01-01

    The pharmacokinetic properties of marbofoxacin, a third generation fluoroquinolone, were investigated in 12 healthy adult cats after single subcutaneous (SC) administration of 2 mg/kg BW (Part I, n=8 cats) and 4 mg/kg BW (Part II, n=4 cats). In each part of the study blood and urine samples were collected before treatment and thereafter for 5 days. The plasma and urine concentrations of marbofloxacin were determined by HPLC with UV detection. Pharmacokinetic calculations were performed for each treated animal using an open one-compartment-model with first-order elimination after SC dosing. Marbofloxacin in plasma (means): Maximum concentrations (Cmax) of about 1.2 and 3.0 microg/ml were measured 2.3 and 4 hours (tmax) after dosing of 2 and 4 mg/kg BW, respectively. Elimination from the body was low with a total clearance (Cl/F) of approximately 0.1 l/h/kg for both dosages. The half-life (t 1/2) for this process was calculated with 8-10 hours. AUC increased almost proportional when doubling the dose, i.e., 19.77 +/- 6.25 microg * h/ml (2 mg/kg BW) and 51.26 +/- 11.83 microg * h/ml (4 mg/kg BW). Plasma kinetics measured were in accordance with data from literature. Marbofloxacin in urine (means): Maximum drug concentrations were detected 4 and 8 hours after dosing with 70 microg/ml (2 mg/kg BW) and 160 microg/ml (4 mg/kg BW), respectively. Inhibitory effects of the urinary matrix on the antimicrobial activity of the drug were taken into account when performing PK/PD calculations. However, a concentration-dependent bactericidal activity (Cmax/MIC > 8-10) which is claimed for fluoroquinolones was sufficiently met with focus on Escherichia (E.) coli (MIC90 0.5 microg/ml). In the same matrix a threshold value of 1.0 microg/ml was undercut 82 and 116 hours after SC dosing, respectively. Hence, a time-dependent bacteria killing kinetic (T > MIC) which may be of relevance for some Gram-positive germs like Staphylococcus spp. (MIC90 1.0 microg/ml) should be covered, too.

  8. Plasma concentrations and sedative effects of a dexmedetomidine, midazolam, and butorphanol combination after transnasal administration in healthy rabbits.

    PubMed

    Santangelo, B; Micieli, F; Marino, F; Reynaud, F; Cassandro, P; Carfora, A; Petrella, R; Borriello, R; Cataldi, M; Vesce, G

    2016-08-01

    Plasma concentrations of dexmedetomidine (D = 0.1 mg/kg), midazolam (M = 2 mg/kg), and butorphanol (B = 0.4 mg/kg) were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) after their simultaneous (DMB) transnasal (TN) administration to healthy rabbits. Time-dependent changes in sedation and antinociception were evaluated by measuring a sedation score based on rabbit's posture, loss of the righting, palpebral and pedal withdrawal reflexes and by instrumental monitoring of rectal temperature, heart rate, arterial blood pressure, pulse-oximetry, and capnometry. The peak plasma concentration (Cmax ) of each drug was reached within 5 min (Tmax ) from DMB-TN administration along with deep sedation and analgesia. Such effects subsided after 45 min into a moderate sedation and analgesia lasting for additional 15 min. All rabbits awakened spontaneously and uneventfully 90 min after DMB-TN administration. During the anesthetic procedure, arterial blood pressure markedly decreased and respiratory depression ensued requiring oxygen supplementation. The results of this study show that all three molecules of the DMB combination were absorbed through the TN route, inducing deep sedation and analgesia suitable for minor surgical procedures. Such combination should be used with caution in rabbits bearing cardiovascular or respiratory diseases because of its ability to induce hypotension and respiratory depression. PMID:26687556

  9. Investigation of low levels of plasma valproic acid concentration following simultaneous administration of sodium valproate and rizatriptan benzoate.

    PubMed

    Hokama, Nobuo; Hobara, Norio; Kameya, Hiromasa; Ohshiro, Susumu; Hobara, Narumi; Sakanashi, Matao

    2007-03-01

    Drug interaction between rizatriptan benzoate, an anti-migraine agent, and sodium valproate (VPA-Na), an anticonvulsant, was studied in rats. When rizatriptan benzoate was administered orally immediately after VPA-Na oral administration, the pharmacokinetic parameters, such as plasma valproic acid (VPA) and area under the plasma concentration-time curve up to 3 h (AUC(0-3)), were significantly decreased compared with those in the control group. However, when rizatriptan benzoate was administered intraperitoneally immediately after VPA-Na orally, these parameters were not changed. In addition, when benzoic acid was administered orally immediately after VPA-Na orally, these were significantly lower compared with the control values. Therefore, it might be possible that VPA transport by monocarboxylate transporter was competitively inhibited by rizatriptan benzoate and thus absorption of VPA was decreased. PMID:17331341

  10. 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. PMID:27234674

  11. A LC-MS-MS method for determination of low doxazosin concentrations in plasma after oral administration to dogs.

    PubMed

    Erceg, Marijana; Cindric, Mario; Pozaic Frketic, Lidija; Vertzoni, Maria; Cetina-Cizmek, Biserka; Reppas, Christos

    2010-02-01

    A rapid and sensitive reversed phase liquid chromatography- tandem mass spectrometry (LC-MS-MS) method is developed for the determination of doxazosin in canine plasma. The samples are prepared by precipitation of proteins using a mixture of methanol and acetonitrile, followed by freezing and evaporation of the organic solvent. The remaining dry residue is redissolved in mobile phase and analyzed by LC-MS-MS with positive electrospray ionization using the selected reactions monitoring mode. An XTerra MS C(18) column, a mobile phase composed of acetonitrile and 2mM ammonium acetate with gradient elution, and a flow rate of 400 microL/min are employed. The elution times for prazosin (internal standard) and doxazosin are approximately 8 and 10 min, respectively. Calibration curves are linear in the 1-20 ng/mL concentration range. Limits of detection and quantification are 0.4 ng/mL and 1.2 ng/mL, respectively. Recovery is higher than 94%. Intra- and inter-day relative standard deviations are below 7% and 8%, respectively. The method is applied for the determination of doxazosin plasma levels following a single administration of doxazosin base and doxazosin mesylate tablets (2 mg dose) to dogs in the fed state. The results indicate possible superiority of the mesylate salt on the plasma input rates of doxazosin.

  12. Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate.

    PubMed

    Ekstrand, C; Bondesson, U; Gabrielsson, J; Hedeland, M; Kallings, P; Olsén, L; Ingvast-Larsson, C

    2015-06-01

    Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03 mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC-MS/MS. Dexamethasone was quantifiable in plasma for 8.3 ± 2.9 days (LLOQ: 0.025 μg/L) and in urine for 9.8 ± 3.1 days (LLOQ: 0.15 μg/L). Maximum observed dexamethasone concentration in plasma was 0.61 ± 0.12 μg/L and in urine 4.2 ± 0.9 μg/L. Terminal plasma half-life was 38.7 ± 19 h. Hydrocortisone was significantly suppressed for 140 h. The plasma half-life of hydrocortisone was 2.7 ± 1.3 h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 ± 0.04 μg/L, 0.95 ± 0.04 and 6.2 ± 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone.

  13. Pharmacokinetics of Cocaine and Metabolites in Human Oral Fluid and Correlation with Plasma Concentrations following Controlled Administration

    PubMed Central

    Scheidweiler, Karl B.; Kolbrich Spargo, Erin A.; Kelly, Tamsin L.; Cone, Edward J.; Barnes, Allan J.; Huestis, Marilyn A.

    2011-01-01

    Oral fluid is an attractive alternative matrix for drug testing, with a non-invasive and directly observed collection, but there are few controlled cocaine administration studies to guide interpretation. Materials and Methods While residing on a closed research unit for up to 10 weeks under constant medical supervision, 19 participants were administered 75 mg/70 kg subcutaneous cocaine and 14 received 150mg/70 kg. The disposition of cocaine, benzoylecgonine (BE) and ecgonine methyl ester (EME) into oral fluid was determined by gas chromatography-mass spectrometry for 0.08–48h after administration. Results In oral fluid collected by citric acid candy stimulated expectoration, cocaine first appeared in oral fluid 0.08–0.32h after dosing and was rapidly eliminated with half-lives of 1.1–3.8h. BE and EME were first detected 0.08–1.0h after dosing, with longer half-lives of 3.4–13.8 (BE) and 2.4–15.5h (EME) (p<0.05). Oral fluid and plasma concentrations were significantly correlated for cocaine, BE and EME (p<0.0001). There were no significant differences (p>0.05) in first and last detection times with the 8 μg/L cutoff proposed by the Substance Abuse and Mental Health Services Administration or the 10 μg/L cutoff from the European initiative, Driving Under the Influence of Drugs, Alcohol and Medicines. Metabolite:cocaine ratios increased after cocaine administration, potentially helpful for interpreting time of last use. Comparison of oral fluid collection via citric acid candy stimulated expectoration, citric acid treated Salivette® and neutral cotton Salivette® devices did not reveal significant differences between devices for areas under the curve for cocaine, BE or EME (p>0.05). Discussion and Conclusion These results provide additional evidence for interpreting cocaine and metabolite concentrations in oral fluid and oral fluid’s usefulness as an alternative matrix for drug testing. PMID:20814350

  14. Plasma luteinizing hormone and progesterone concentrations in goats with estrous cycles of normal or short duration after prostaglandin F2 alpha administration during diestrus or pregnancy.

    PubMed

    Bretzlaff, K N; Weston, P G; Hixon, J E; Ott, R S

    1988-06-01

    Plasma luteinizing hormone (LH) and progesterone concentrations were compared in does experiencing short-duration estrous cycles and in does with estrous cycles of normal duration. The short-duration estrous cycles were observed immediately after induction of abortion in pregnant does by use of prostaglandin (PG) F2 alpha. Intramuscular administration of 5 mg of PGF2 alpha was accomplished in 8 does that were 52 to 63 days into gestation and in 9 cycling does at 7 to 10 days after estrus. In both groups, the mean plasma concentration of progesterone decreased from a luteal phase concentration immediately before to less than 1 ng/ml by 24 hours after PGF2 alpha administration. Of the 8 does that aborted, 6 experienced short-duration estrous cycles, and 4 of these 6 had an LH surge during the time of blood sample collection. The mean time from PGF2 alpha administration to the LH surge was significantly (P less than 0.05) longer in does with short-duration estrous cycles (71 hours) than that in does with estrous cycles of normal duration (58 hours). The mean area under the LH concentration curve was significantly (P less than 0.005) less for does with short-duration estrous cycles. Short-duration estrous cycles were associated with delayed preovulatory LH surges of reduced magnitude. PMID:3165252

  15. 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.

  16. 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. PMID:27324263

  17. 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.

  18. 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. PMID:25786659

  19. 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.

  20. Effects of clozapine administration on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in male C57BL/6 mice: A parallel controlled study

    PubMed Central

    Yuan, Hai-Yan; Liang, Hai-Xia; Liang, Guang-Rong; Zhang, Gui-Xiang; Li, Huan-De

    2008-01-01

    Background: Clozapine has been associated with metabolic adverse events (AEs) (eg, elevated body weight, blood glucose concentrations, cholesterol, triglycerides [TG]), all of which have deleterious effects on health and medication compliance. However, little focus has been directed toward finding a suitable experimental model to study the metabolic AEs associated with clozapine. Objective: The aim of this study was to assess the effects of clozapine administration for 28 days on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in C57BL/6 mice. Methods: C57BL/6 mice were grouped and treated with clozapine 2 or 10 mg/kg or vehicle intraperitoneally QD for 28 days. Body weight was assessed on days 0 (baseline), 7, 14, 21, and 28, and glucose tolerance, blood glucose concentrations, insulin (calculated by insulin resistance index [IRI]), and plasma lipids (including total cholesterol, TG, high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol) were assessed on day 29. Results: Sixty 10-week-old, male C57BL/6 mice were included in the study and were divided into 3 groups (20 mice per group). The body weight significantly decreased in the clozapine 10-mg-treated group on days 14, 21, and 28 compared with the vehicle group (mean [SD] body weight: 21.61 [1.05] vs 22.79 [1.11], 22.53 [1.05] vs 24.17 [1.24], and 22.21 [1.07] vs 24.99 [1.39] g, respectively; all, P < 0.05). In the clozapine 10-mg/kg group, blood glucose concentrations significantly increased 0, 30, 60, and 120 minutes after glucose administration compared with the vehicle group (mean [SD]: 6.67 [1.25], 25.34 [5.85], 12.68 [3.39], and 7.52 [1.45] mmol/L, respectively, vs 4.61 [0.78], 21.54 [6.55], 11.46 [3.46], and 6.55 [1.42] mmol/L, respectively; all P < 0.05). The clozapine 10-mg/kg group also had significant increases in plasma insulin concentrations compared with the vehicle group (12.70 [5.27] vs 7.62 [4.54] μIU/mL; P < 0.05) and

  1. Oral administration of ethanol with aspirin increases the concentration of salicylic acid in plasma and organs, especially the brain, in mice.

    PubMed

    Kato, Hideaki; Yoshimoto, Kanji; Kobayashi, Masaki; Sakabe, Masaaki; Funaki, Hironao; Ikegaya, Hiroshi

    2010-06-10

    Aspirin (acetylsalicylic acid) has been widely used as an over-the-counter drug to relieve pain throughout the world. In suicide attempts, aspirin is one of the most common drugs taken in large quantities. The concentration of salicylic acid shows a low-level distribution in the mouse brain, a site that may be critical regarding the expression of symptoms (e.g. hyperpnea, coma, convulsion and tremor) during acute aspirin toxicity. Therefore, it was suggested that sensitivity to salicylic acid concerning acute toxicity was higher in the brain than in other organs. Moreover, it is thought that it is common for aspirin and ethanol to be ingested at the same time. Therefore, the present study was designed to investigate the influence of ethanol on the distribution of salicylic acid, which is a primary metabolite of aspirin, and its related metabolite, salicyluric acid. The oral co-administration of aspirin (0.5g/kg) and ethanol (2.5g/kg; 10ml/kg of 25% (w/v)) enhanced the concentrations of salicylic acid in the plasma and organs, especially in the brain, compared with the aspirin alone-treated group. On the other hand, ethanol did not influence the concentrations of salicyluric acid in the plasma and kidney compared with the aspirin alone-treated group. These results suggest that ethanol enhances aspirin absorption from the gastrointestinal tract but has no influence on its metabolism. Thus, it is dangerous to ingest the alcohol and aspirin at the same time, as this may exacerbate the acute toxicity of aspirin.

  2. Pharmacokinetics of human activated protein C. 1st communication: plasma concentration and excretion of a lyophilized purified human activated protein C after intravenous administration in the mouse and the rabbit.

    PubMed

    Ishii, S; Mochizuki, T; Nagao, T; Sugiki, S; Kudo, S; Harakawa, N; Taniguchi, K; Igarashi, Y; Kondo, S; Kiyoki, M

    1995-05-01

    Pharmacokinetic studies of human activated protein C (CAS 42617-41-4, APC) were investigated in mice and rabbits with 125I-labeled compound. Plasma levels of APC were determined by three different assays: total radioactivity, APC antigenicity determined by sandwich enzyme-linked immunosorbent assay (ELISA), and the amidolytic activity which was performed by immunologically captured APC. APC concentration obtained from these assays were shown to be correlated well at early times post-dose. After intravenous administration, total radioactivity in the plasma declined tri-exponentially, but antigenicity and amidolytic activity in the plasma declined biexponentially. Plasma AUC increased proportionally with the dose, and the total body clearance and t1/2 did not change significantly. In addition, no significant difference was observed between the pharmacokinetics in male and female mice. In rabbit study, the profiles of times vs APC concentration in the plasma was similar to those in mice after single bolus injection. The plasma concentrations of APC during and after infusion in rabbits were also determined. APC concentration increased during infusion and reached almost steady state at the end of infusion. The profiles of the APC concentration in benzamidine citrate plasma corresponded to the simulated curves which were characterized by the parameters obtained from the single bolus experiment. Plasma disposition profiles of the protein were studied with high performance gel chromatography method. The radioactivity in the unchanged APC was observed at 15 min after administration. At 1 h, most of the radioactivity was observed in larger molecule fraction than the intact APC. These results corresponded to the decrease of amidolytic activity in the plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7612068

  3. 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...

  4. 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...

  5. Plasma concentrations of voriconazole in falcons.

    PubMed

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

    2007-08-25

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

  6. Plasma lipid concentrations for some Brazilian lizards.

    PubMed

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

    1979-01-01

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

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

    PubMed Central

    Lutz, T A; Rand, J S

    1996-01-01

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

  8. 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

  9. 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

  10. Plasma interactions with biased concentrator solar cells

    NASA Astrophysics Data System (ADS)

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

    1986-12-01

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

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

    PubMed

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

    2016-01-01

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

  12. Behavioral alteration of plasma phenylalanine concentration.

    PubMed

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

    1977-11-01

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

  13. Factors influencing lopinavir and atazanavir plasma concentration

    PubMed Central

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

    2010-01-01

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

  14. 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.

  15. 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.

  16. Plasma prolactin concentrations in lead exposed workers.

    PubMed

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

    1987-01-01

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

  17. 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

    2015-01-01

    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

  18. 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

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

    PubMed

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

    2015-08-01

    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

  20. 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

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

    PubMed

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

    2015-08-07

    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.

  2. 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.

  3. Plasma and milk kinetics of eprinomectin following topical or oral administration to lactating Chinese Holstein cows.

    PubMed

    Wen, Huiqiang; Pan, Baoliang; Wang, Yuwan; Wang, Fangfei; Yang, Zhenzhong; Wang, Ming

    2010-11-24

    Chinese Holstein, bred by mating the Holstein-Friesian to Chinese Yellow Cattle, is a major dairy cattle breed in China. Eprinomectin is widely used in the treatment of nematode and ectoparasite infections in lactating cattle. The pharmacokinetics of eprinomectin in the plasma and milk were determined in Chinese Holstein cows following topical (at 0.5 mg kg(-1)) or oral (at 0.2 mg kg(-1)) administration. For topical administration, the concentrations of eprinomectin in plasma reached peak values (C(max)) of 16.16 ± 6.02 ng ml(-1) at 3.20 ± 1.30 days (T(max)). In milk, the C(max) values of 2.28 ± 0.85 ng ml(-1) were obtained at 3.48 ± 0.65 days. The MRT values were 5.00 ± 0.96 days for plasma and 4.65 ± 0.60 days for milk. The AUC values were 91.00 ± 25.32 ng d ml(-1) for plasma and 10.53 ± 1.55 ng d ml(-1) for milk. The ratio of AUC milk/plasma was 0.124 ± 0.041. Significant differences were found in C(max) and AUC of eprinomectin in plasma between Chinese Holstein and Prim Holstein following topical administration. It was probably due to the lower storage of body fat in Chinese Holstein than in Prim Holstein. For oral administration, the concentrations of eprinomectin reach peak values of 30.02 ± 5.73 ng ml(-1) at 1.60 ± 0.55 days in plasma and 3.14 ± 0.88 ng ml(-1) at 1.40 ± 0.27 days in milk. The MRT values for plasma and milk were 3.00 ± 0.46 and 3.18 ± 0.55 days, respectively. The AUC values were 98.46 ± 24.75 ng d ml(-1) for plasma and 10.42 ± 4.22 ng d ml(-1) for milk. The ratio of AUC milk/plasma was 0.104 ± 0.022. Compared with the topical administration, a significantly shorter MRT of eprinomectin in plasma was obtained following oral administration, which would shorten residue time of this compound in faeces and reduce its ecotoxicological effect. The low exposure of eprinomectin in milk would favor the use of eprinomectin in lactating Chinese Holstein for topical or oral administration. PMID:20851527

  4. 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...

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

    PubMed

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

    2015-06-01

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

  6. 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.

  7. Plasma pharmacokinetics of selamectin after a single topical administration in the American bullfrog (Rana catesbeiana).

    PubMed

    D'Agostino, Jennifer J; West, Gary; Boothe, Dawn M; Jayanna, Prashanth K; Snider, Timothy; Hoover, John P

    2007-03-01

    Parasitism is common in wild and captive amphibians; however, pharmacologic data are lacking for anthelmintic drugs. This study was developed to determine the plasma pharmacokinetics of selamectin after topical administration in bullfrogs. Thirty-two adult American bullfrogs (Rana catesbeiana) were randomly assigned into eight groups of four with each group representing a different collection time point. Seven groups received selamectin (6 mg/ kg) topically and the remaining group served as the untreated control group. One group of frogs was euthanized and blood samples immediately collected on days 0 (control), 1, 5, 10, 15, 20, 25, and 30. Plasma was analyzed for selamectin using high performance liquid chromatography with fluorescence detection. Individual samples were analyzed, then data were reported as the mean of the four frogs at each time point. A histologic evaluation of the lung, liver, kidney, and skin tissues was performed and none of the frogs showed histologic evidence of toxicity due to selamectin administration. The mean peak plasma concentration was 162.5 +/- 42.3 ng/ml, area under the curve was 2,856 ng day/ml, mean residence time was 12.2 days, and disappearance half-life was 1.87 days. Based on the plasma pharmacokinetics, bullfrogs appear to absorb selamectin very efficiently, concentrations reach high levels in the plasma, and there were no apparent histologic effects from single dose administration. PMID:17469275

  8. Plasma pharmacokinetics of selamectin after a single topical administration in the American bullfrog (Rana catesbeiana).

    PubMed

    D'Agostino, Jennifer J; West, Gary; Boothe, Dawn M; Jayanna, Prashanth K; Snider, Timothy; Hoover, John P

    2007-03-01

    Parasitism is common in wild and captive amphibians; however, pharmacologic data are lacking for anthelmintic drugs. This study was developed to determine the plasma pharmacokinetics of selamectin after topical administration in bullfrogs. Thirty-two adult American bullfrogs (Rana catesbeiana) were randomly assigned into eight groups of four with each group representing a different collection time point. Seven groups received selamectin (6 mg/ kg) topically and the remaining group served as the untreated control group. One group of frogs was euthanized and blood samples immediately collected on days 0 (control), 1, 5, 10, 15, 20, 25, and 30. Plasma was analyzed for selamectin using high performance liquid chromatography with fluorescence detection. Individual samples were analyzed, then data were reported as the mean of the four frogs at each time point. A histologic evaluation of the lung, liver, kidney, and skin tissues was performed and none of the frogs showed histologic evidence of toxicity due to selamectin administration. The mean peak plasma concentration was 162.5 +/- 42.3 ng/ml, area under the curve was 2,856 ng day/ml, mean residence time was 12.2 days, and disappearance half-life was 1.87 days. Based on the plasma pharmacokinetics, bullfrogs appear to absorb selamectin very efficiently, concentrations reach high levels in the plasma, and there were no apparent histologic effects from single dose administration.

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

    PubMed

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

    2002-04-01

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

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

    PubMed

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

    1987-05-01

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

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

    PubMed

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

    1988-01-01

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

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

    PubMed

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

    2011-03-01

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

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

    PubMed

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

    1996-12-01

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

  14. 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.

  15. Dietary determinants of plasma homocysteine concentrations.

    PubMed

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

    2005-05-01

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

  16. 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.

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

    SciTech Connect

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

    1987-05-01

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

  18. 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

  19. INCREASING AND PROLONGING BLOOD PENICILLIN CONCENTRATIONS FOLLOWING INTRAMUSCULAR ADMINISTRATION.

    PubMed

    Bronfenbrenner, J; Favour, C B

    1945-06-29

    (1) Restriction of fluid intake to 1,500 cc and the salt intake to 3 gm a day doubles the penicillin blood level following interrupted intramuscular [See Figure in the PDF file] injections of penicillin. (2) The administration of benzoic acid to a patient on an unrestricted diet Ilay double the penicillin blood level during similar treatment. (3) The combination of these two procedures results in a four- to eight-fold increase in penicillin blood level with a prolonged effective blood concentration.

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

    SciTech Connect

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

    1990-01-01

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

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

    PubMed

    Sass, J O; Skladal, D

    2000-02-01

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

  2. 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

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

    PubMed

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

    2012-11-01

    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.

  4. 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.

  5. Plasma glutamine concentration in spinal cord injured patients.

    PubMed

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

    2005-09-23

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

  6. Photovoltaic concentrator pointing dynamics and plasma interaction study

    SciTech Connect

    Stern, T.G.

    1984-01-01

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

  7. Laminaria japonica increases plasma exposure of glycyrrhetinic acid following oral administration of Liquorice extract in rats.

    PubMed

    Zhao, Wei-Man; Jiang, Shu-Wen; Chen, Yang; Zhong, Ze-Yu; Wang, Zhong-Jian; Zhang, Mian; Li, Ying; Xu, Ping; Liu, Li; Liu, Xiao-Dong

    2015-07-01

    The present study was designed to investigate the effects of Laminaria japonica (Laminaria) on pharmacokinetics of glycyrrhetinic acid (GA) following oral administration of Liquorice extract in rats. Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract, respectively, plasma samples were obtained at various times and the concentrations of GA, liquiritigenin, and isoliquiritigenin were measured by LC-MS. The effects of Laminaria extract on pharmacokinetics of GA were also investigated, following single-dose and multidose of glycyrrhizic acid (GL). The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model. The metabolism of GL to GA in the contents of small and large intestines was also studied. The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA, accompanied by a shorter Tmax. Similar alteration was observed following multidose administration. However, pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria. Similarly, Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed. The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum, but did not affect the intestinal absorption of GA. It was found that Laminaria enhanced the metabolism of GL to GA in large intestine. In conclusion, Laminaria increased plasma exposures of GA following oral administration of liquorice or GL, which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.

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

    PubMed

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

    1990-03-01

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

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

    PubMed

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

    2002-07-01

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

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

    PubMed Central

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

    1991-01-01

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

  11. Plasma bevantolol concentration and heart rate in rabbits.

    PubMed

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

    1993-05-01

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

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

    PubMed Central

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

    2013-01-01

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

  13. Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats.

    PubMed

    Jia, Xiaoming; Chen, Yanfeng; Zidichouski, Jeffrey; Zhang, Junzeng; Sun, Changhao; Wang, Yanwen

    2008-11-01

    The objective of the present study was to determine the beneficial effects and the safety of oral administration of the combination of berberine (BBR) and plant stanols (PS) on plasma lipid profiles in male Sprague-Dawley rats. Four groups of animals were fed a cornstarch-casein-sucrose-based high-cholesterol (2%, w:w) and high-fat (27.5%) diet. Three treatment groups were supplemented with either BBR (100mgkg(-1)bodyweightd(-1)), PS (1% in diet, w:w), or the combination of both (BBRPS). After 6 wk, animals were sacrificed and followed immediately with the collection of blood and organ samples. Lipid analysis revealed that PS lowered plasma total cholesterol (T-C) by 18% (p=0.067) and non-HDL-cholesterol (non-HDL-C) by 29% (p=0.013) as compared with the control, while BBR had no effect on both T-C and non-HDL-C. The combination treatment of BBRPS reduced plasma T-C by 41% (p=0.0002) and non-HDL-C by 59% (p<0.0001) compared to the control group. BBR reduced plasma TG levels by 31% at a marginal significance relative to the control (p=0.054), whereas PS had no effect. BBRPS showed an additive effect of BBR and PS on plasma TAG. PS and BBRPS both decreased liver cholesterol (p=0.0027 and 0.0002, respectively). BBR and PS, either alone or in combination, did not show any toxic effects as assessed by plasma concentration of hepatic biochemical parameters. These results demonstrate that BBR and PS, when combined, synergistically lower plasma cholesterol levels and significantly reduce liver cholesterol, without the observation of any toxic effects.

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

    PubMed Central

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

    1986-01-01

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

  15. Effects of oral contraceptive and estrogen administration on plasma calcitonin in pre- and postmenopausal women.

    PubMed

    Hurley, D L; Tiegs, R D; Barta, J; Laakso, K; Heath, H

    1989-02-01

    Estrogen (E) therapy and administration of oral contraceptives (OC) reportedly increase plasma calcitonin (CT) concentrations in women, effects said to mediate in part the beneficial actions of E on bone. To further examine this theory, we tested the effects of three cycles of OC therapy in 12 young women, comparing them to 10 healthy women before and after three normal menstrual cycles. We also determined the effects of 3 months of E therapy (ethinyl estradiol, 20 micrograms/day, 25 of 30 days) in 14 healthy postmenopausal women, using a crossover design (studied after 3 months with and 3 months without E). We determined CT by radioimmunoassay (antiserum G-1701) in whole plasma (iCT) and silica cartridge extracts of plasma (exCT) after overnight fasting, after calcium (Ca) infusion (2 mg Ca/kg over 5 minutes), and during a normal day at 0800, 1200, 1700, and 2000 h. In no control study was there a significant diurnal change in iCT or exCT, and neither OC nor E therapy altered this. Similarly, OC administration did not affect basal CT levels or the normal iCT and exCT responses to Ca infusion. E therapy induced expected changes in serum Ca, phosphorus, and alkaline phosphatase and urinary Ca and cAMP excretion; basal and diurnal plasma exCT levels were decreased significantly, consonant with the decrement in serum Ca. E did not alter normal iCT and exCT responses to Ca infusion. Thus, administration of either OC or E has no stimulatory effect on CT secretion, which suggests that the beneficial actions of E on bone are not mediated through CT-induced inhibition of bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. 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.

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

    PubMed Central

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

    2006-01-01

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

  18. 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

  19. 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

  20. 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.

  1. 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.

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

    PubMed

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

    1987-09-01

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

  3. Factors affecting plasma aluminum concentrations in nonexposed workers.

    PubMed

    House, R A

    1992-10-01

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

  4. 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.

  5. 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.

  6. Concentrations of atomoxetine and its metabolites in plasma and oral fluid from paediatric patients with attention deficit/hyperactivity disorder.

    PubMed

    Papaseit, Esther; Marchei, Emilia; Farré, Magí; Garcia-Algar, Oscar; Pacifici, Roberta; Pichini, Simona

    2013-06-01

    Atomoxetine (ATX) is a non-stimulant drug approved for the treatment of children and adolescents with attention deficit/hyperactivity disorder (ADHD). We aimed to study the excretion profile of ATX and its principal metabolites 4-hydroxyatomoxetine (4-OH-ATX) and N-desmethylatomoxetine (desmethyl-ATX) in oral fluid and plasma of ADHD paediatric subjects, after administration of different dosage regimens. Oral fluid and plasma samples were obtained from one child and five adolescents treated with different ATX doses (18-60 mg/day). ATX and its metabolites were measured in oral fluid and plasma by liquid chromatography-mass spectrometry (LC-MS). Apparent pharmacokinetic parameters of ATX in oral fluid and plasma were estimated for each subject. All analytes under investigation were detected in plasma samples with concentrations from 0.6 to 1065.7 ng/ml for ATX, 0.7 to 17.1 ng/ml for 4-OH-ATX and 0.7 to 126.2 ng/ml for desmethyl-ATX. Only ATX and 4-OH-ATX were detected in oral fluid samples with concentrations from 0.5 to 36.0 ng/ml and 0.5 to 4.7 ng/ml, respectively. ATX concentrations in oral fluid were between one and two orders of magnitude lower than those in plasma. 4-OH-ATX was found in oral fluid at a peak concentration approximately one-fourth those in plasma with a mean tmax of 2.3 in plasma and 3.0 h in oral fluid. The correlations between ATX and 4-OH-ATX concentrations in the two biological fluids indicate that oral fluid concentrations of this drug and its principal metabolite may be a predictor of plasma concentrations, even if values are too low and variable to be considered an alternative to plasma.

  7. 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.

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

    PubMed

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

    2001-10-01

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

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

    PubMed

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

    2000-11-01

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

  10. 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

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

    PubMed

    Loft, S; Jensen, V; Rørsgaard, S

    1983-06-01

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

  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. Differential effects of exogenous progesterone administration at different stages of the luteal phase on endogenous oestradiol concentration in cows.

    PubMed

    Starbuck, G R; Mann, G E

    2010-04-01

    We have investigated the effects administering exogenous progesterone, via insertion of a controlled internal drug release (CIDR) for 4 days, from either day 5 or day 12 of the oestrous cycle on plasma oestradiol concentrations. In study 1, in which progesterone was administered from day 5, measurement of plasma oestradiol in daily samples revealed a significant (p < 0.001) decrease in peripheral oestradiol concentration. In contrast, in study 2, similar administration of progesterone from day 12 had no effect on plasma oestradiol concentration. In study 3, collection of hourly samples following progesterone treatment on day 5 revealed peak progesterone concentrations within 1 h of CIDR insertion and nadir oestradiol concentrations within 4 h. The results demonstrate that treatment with progesterone early in the luteal phase causes a rapid inhibition of oestradiol secretion, while later treatment does not. While improvements in pregnancy rate following progesterone treatment at this time have traditionally been attributed to increases in progesterone, the potential involvement of decreased oestradiol secretion has often been overlooked. PMID:19144035

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

    PubMed

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

    1996-01-01

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

  15. 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.

  16. 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.

  17. Orally administered, insulin-loaded amidated pectin hydrogel beads sustain plasma concentrations of insulin in streptozotocin-diabetic rats.

    PubMed

    Musabayane, C T; Munjeri, O; Bwititi, P; Osim, E E

    2000-01-01

    We report successful oral administration of insulin entrapped in amidated pectin hydrogel beads in streptozotocin (STZ)-diabetic rats, with a concomitant reduction in plasma glucose concentration. The pectin-insulin (PI) beads were prepared by the gelation of humilin-pectin solutions in the presence of calcium. Separate groups of STZ-diabetic rats were orally administered two PI beads (30 micrograms insulin) once or twice daily or three beads (46 micrograms) once daily for 2 weeks. Control non-diabetic and STZ-diabetic rats were orally administered pectin hydrogel drug-free beads. By comparison with control non-diabetic rats, untreated STZ-diabetic rats exhibited significantly low plasma insulin concentration (0.32+/-0. 03 ng/ml, n=6, compared with 2.60+/-0.44 ng/ml in controls, n=6) and increased plasma glucose concentrations (25.84+/-1.44 mmol/l compared with 10.72+/- 0.52 mmol/l in controls). Administration of two PI beads twice daily (60 micrograms active insulin) or three beads (46 micrograms) once a day to STZ-diabetic rats increased plasma insulin concentrations (0.89+/-0.09 ng/ml and 1.85+/- 0.26 ng/ml, respectively), with a concomitant reduction in plasma glucose concentration (15.45+/-1.63 mmol/l and 10.56+/-0.26 mmol/l, respectively). However, a single dose of PI beads (30 micrograms) did not affect plasma insulin concentrations, although plasma glucose concentrations (17.82+/-2.98 mmol/l) were significantly reduced compared with those in untreated STZ-diabetic rats. Pharmacokinetic parameters in STZ-diabetic rats show that the orally administered PI beads (30 micrograms insulin) were more effective in sustaining plasma insulin concentrations than was s.c. insulin (30 micrograms). The data from this study suggest that this insulin-loaded amidated pectin hydrogel bead formulation not only produces sustained release of insulin, but may also reduce plasma glucose concentration in diabetes mellitus.

  18. 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

  19. 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

  20. 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.

  1. Administration of docosahexaenoic acid influences behavior and plasma catecholamine levels at times of psychological stress.

    PubMed

    Hamazaki, T; Sawazaki, S; Nagasawa, T; Nagao, Y; Kanagawa, Y; Yazawa, K

    1999-01-01

    The purpose of the present research was to clarify the effect of docosahexaenoic acid (DHA) intake on behavior and plasma catecholamines (CA). In Study 1, 42 students took either DHA-rich oil capsules containing 1.5-1.8 g DHA/d or control oil capsules containing 97% soybean oil plus 3% of another fish oil for 3 mon in a double-blind fashion. They took a psychological test (PF Study) at the start and end of the study. This study started at the end of summer vacation and ended just before the final exams. In the control group, external aggression (aggression against others) in PF Study was significantly increased at the end of the study as compared with that measured at the start (+8.9%), whereas it was not significantly changed in the DHA group (-1.0%). In a similar double-blind study (Study 2), we measured external aggression under nonstressful conditions. External aggression slightly decreased in the control group, whereas there were no significant changes in the DHA group. In Study 3 with 14 students, plasma CA were measured at the start and end of capsule administration period of 2 mon. Subjects were under continuous stress of the final exams that lasted throughout the whole study period. The ratio of plasma epinephrine to norepinephrine concentrations was significantly increased in the DHA group (78%), whereas it stayed at the same level in the control group. In Study 4, mice were fed either DHA-deficient diet or -sufficient diet for 4 wk, and their rearing frequency (an anxiety index) was measured. In the DHA-sufficient group, the rearing frequency was significantly less than in the other group. These effects of DHA intake may be applied to people in an attempt to ameliorate stress-related diseases. PMID:10419086

  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. PMID:26472183

  3. 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.

  4. 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.

  5. 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.

  6. Cerebrospinal fluid levels of inflammation, oxidative stress and NAD+ are linked to differences in plasma carotenoid concentrations

    PubMed Central

    2014-01-01

    Background The consumption of foods rich in carotenoids that possess significant antioxidant and inflammatory modulating properties has been linked to reduced risk of neuropathology. The objective of this study was to evaluate the relationship between plasma carotenoid concentrations and plasma and cerebrospinal fluid (CSF) markers of inflammation, oxidative stress and nicotinamide adenine dinucleotide (NAD+) in an essentially healthy human cohort. Methods Thirty-eight matched CSF and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of carotenoids and both plasma and cerebrospinal fluid (CSF) levels of NAD(H) and markers of inflammation (IL-6, TNF-α) and oxidative stress (F2-isoprostanes, 8-OHdG and total antioxidant capacity) were quantified. Results The average age of participants was 53 years (SD = 20, interquartile range = 38). Both α-carotene (P = 0.01) and β-carotene (P < 0.001) correlated positively with plasma total antioxidant capacity. A positive correlation was observed between α-carotene and CSF TNF-α levels (P = 0.02). β-cryptoxanthin (P = 0.04) and lycopene (P = 0.02) inversely correlated with CSF and plasma IL-6 respectively. A positive correlation was also observed between lycopene and both plasma (P < 0.001) and CSF (P < 0.01) [NAD(H)]. Surprisingly no statistically significant associations were found between the most abundant carotenoids, lutein and zeaxanthin and either plasma or CSF markers of oxidative stress. Conclusion Together these findings suggest that consumption of carotenoids may modulate inflammation and enhance antioxidant defences within both the central nervous system (CNS) and systemic circulation. Increased levels of lycopene also appear to moderate decline in the essential pyridine nucleotide [NAD(H)] in both the plasma and the CSF. PMID:24985027

  7. 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. PMID:19270373

  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. Pharmacokinetics and effects on plasma retinol concentrations of 13-cis-retinoic acid in melanoma patients.

    PubMed Central

    Formelli, F.; Cavadini, E.; Mascheroni, L.; Belli, F.; Cascinelli, N.

    1997-01-01

    The pharmacokinetics of 13-cis-retinoic acid (13cisRA) and its effects on retinol plasma levels were investigated after the first and the last doses in melanoma patients, who participated in a study run to assess tolerance over a long period of a treatment schedule of 13cisRA associated with recombinant interferon alpha2a (rIFN-alpha2a). Melanoma patients with regional node metastases after radical surgery were randomized to be treated for 3 months with rIFN-alpha2a, 3 x 10(6) IU s.c. every other day, associated with oral 13cisRA at doses of 20 mg day(-1) (five patients) or 40 mg every other day (seven patients). Maximum 13cisRA blood concentrations usually occurred 4 h after drug administration, with average values of 406 and 633 ng ml(-1) (i.e. 1.3 and 2.1 microM) after the 20 and 40 mg dose respectively. The average half-life (t(1/2)) was approximately 30 h. The maximum concentration, the t(1/2) and the area under the concentration-time curves from 0 to 48 h (AUC(0-48)) of 13cisRA did not change after multiple dosing, whereas the AUC(0-48) of its major blood metabolite, 4-oxo-13-cis-retinoic acid, increased. Immediately after 13cisRA treatment, retinol plasma levels started to decline and they reached the lowest values (approximately 20% reduction) shortly after the time of maximum 13cisRA concentrations (i.e. 4-12 h after drug intake). Afterwards, values returned to baseline. The amount of retinol reduction in time was correlated with 13cisRA maximum concentrations. PMID:9413958

  10. 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.

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

    PubMed

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

    2014-03-01

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

  12. Acute arterial baroreflex-mediated changes in plasma catecholamine concentrations in a chronic rat model of myocardial infarction.

    PubMed

    Kawada, Toru; Akiyama, Tsuyoshi; Li, Meihua; Zheng, Can; Turner, Michael J; Shirai, Mikiyasu; Sugimachi, Masaru

    2016-08-01

    While it may be predictable that plasma norepinephrine (NE) concentration changes with efferent sympathetic nerve activity (SNA) in response to baroreceptor pressure inputs, an exact relationship between SNA and plasma NE concentration remains to be quantified in heart failure. We examined acute baroreflex-mediated changes in plasma NE and epinephrine (Epi) concentrations in normal control (NC) rats and rats with myocardial infarction (MI) (n = 6 each). Plasma NE concentration correlated linearly with SNA in the NC group (slope: 2.17 ± 0.26 pg mL(-1) %(-1), intercept: 20.0 ± 18.2 pg mL(-1)) and also in the MI group (slope: 19.20 ± 6.45 pg mL(-1) %(-1), intercept: -239.6 ± 200.0 pg mL(-1)). The slope was approximately nine times higher in the MI than in the NC group (P < 0.01). Plasma Epi concentration positively correlated with SNA in the NC group (slope: 1.65 ± 0.79 pg mL(-1) %(-1), intercept: 115.0 ± 69.5 pg mL(-1)) and also in the MI group (slope: 7.74 ± 2.20 pg mL(-1) %(-1), intercept: 24.7 ± 120.1 pg mL(-1)). The slope was approximately 4.5 times higher in the MI than in the NC group (P < 0.05). Intravenous administration of desipramine (1 mg kg(-1)) significantly increased plasma NE concentration but decreased plasma Epi concentration in both groups, suggesting that neuronal NE uptake had contributed to the reduction in plasma NE concentration. These results indicate that high levels of plasma catecholamine in MI rats were still under the influence of baroreflex-mediated changes in SNA, and may provide additional rationale for applying baroreflex activation therapy in patients with chronic heart failure. PMID:27495297

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

    PubMed Central

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

    1998-01-01

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

  14. Determination of plasma and skin concentrations of orbifloxacin in dogs with clinically normal skin and dogs with pyoderma.

    PubMed

    Kay-Mugford, Patricia A; Weingarten, Allan J; Ngoh, Maureen; Zolynas, Robert; White, Amy; Katz, Terry; Simmons, Robert; Varma, Kanwal J

    2002-01-01

    Plasma and skin concentrations of orbifloxacin (Orbax tablets, Schering-Plough Animal Health) were assessed in 14 clinically normal dogs and 14 dogs with pyoderma following oral administration of the drug at 7.5 mg/kg once daily for 5 to 7 days. Skin biopsies and whole blood samples were obtained before dosing and at the time of the expected maximum concentration in skin (3 hours after dosing) on the first and on the fifth to seventh day of dosing. Skin biopsies and plasma were analyzed for orbifloxacin concentrations by high-performance liquid chromatography. Dogs with pyoderma had significantly higher mean skin concentrations of orbifloxacin within 3 hours of administration (Day 0: 7.80 +/- 3.40 mcg/g, Days 4 to 6: 9.47 +/- 6.23 mcg/g) than did dogs with normal skin (Day 0: 3.85 +/- 1.08 mcg/g, Days 4 to 6: 5.43 +/- 1.02 mcg/g). After dosing on Day 0 and after five to seven daily treatments, dogs with pyoderma had significantly higher mean orbifloxacin skin:plasma ratios (1.40 and 1.44, respectively) than did clinically normal dogs (0.81 and 0.96, respectively). The accumulation of orbifloxacin in diseased skin may contribute to the efficacy of this compound for the treatment of bacterial skin infections.

  15. Plasma concentrations and pharmacokinetics of phenylalanine in rats and mice administered aspartame.

    PubMed

    Hjelle, J J; Dudley, R E; Marietta, M P; Sanders, P G; Dickie, B C; Brisson, J; Kotsonis, F N

    1992-01-01

    Aspartame (L-aspartyl-L-phenylalanine methyl ester) is an esterified, dipeptide sweetener that is rapidly and completely metabolized in the gastrointestinal tract to phenylalanine, aspartic acid and methanol. The pharmacokinetics of phenylalanine (PHE) and tyrosine (TYR) were examined following the administration of oral doses of aspartame (APM) to fasted male Sprague-Dawley rats (0, 50, 100, 200, 500 and 1,000 mg/kg) and CD-1 mice (0, 100, 200, 500, 1,000 and 2,000 mg/kg). Peak plasma PHE/large neutral amino acid (LNAA) ratios were calculated. Maximal plasma PHE and TYR concentrations were observed within 1 h after dosing and returned to baseline within 4-8 h in both species regardless of the dose of APM. Mean PHE Cmaxs ranged from 73.6 to 1,161 nmol/ml in the rat, and from 78.6 to 1,967 nmol/ml in the mouse. TYR Cmaxs ranged from 91.6 to 502 nmol/ml and from 89.2 to 792 nmol/ml in the rat and mouse, respectively. AUCs and Cmaxs were linear with dose in both species. Peak plasma PHE/LNAA ratios ranged from 0.112 to 1.117 in rats and from 0.121 to 1.769 in mice. Comparison of these ratios with those observed previously in humans indicates that rodents require a 2-6 times higher dose of APM than humans to produce similar increases in plasma PHE/LNAA ratios.

  16. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-10-05

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

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

    PubMed

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

    2015-01-01

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

  20. 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

  1. 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

  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. 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.

  4. 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.

  5. Plasma and synovial fluid concentrations of calcium pentosan polysulphate achieved in the horse following intramuscular injection.

    PubMed

    Fuller, C J; Ghosh, P; Barr, A R S

    2002-01-01

    Results from in vitro studies have indicated that calcium pentosan polysulphate (CaPPS) may be of therapeutic value in osteoarthritis (OA) in the horse. However, no controlled clinical trials using this drug in equine OA have yet been reported. If CaPPS is to be developed for such use, the relationship between the proposed i.m. dose of CaPPS to be used and the concentrations of drug attained in plasma and synovial fluid of the target joint should first be established. An investigation was undertaken to determine these concentrations after a single 2 mg/kg i.m. injection of CaPPS. Blood and synovial fluid samples were taken from 6 healthy, sound horses following i.m. CaPPS administration. Concentrations of CaPPS measured in the synovial fluid were, on the basis of published studies, sufficient to elicit a potential therapeutic effect on synoviocyte metabolism, and possibly also to stimulate proteoglycan synthesis and reduce matrix metalloproteinase activities in articular cartilage. It would therefore seem justified to investigate further the therapeutic effect of CaPPS in OA in the horse.

  6. 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.

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

    PubMed

    Orchinik, M; Licht, P; Crews, D

    1988-09-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. Pharmacokinetics of telithromycin in plasma and soft tissues after single-dose administration to healthy volunteers.

    PubMed

    Gattringer, Rainer; Urbauer, Eleonora; Traunmüller, Friederike; Zeitlinger, Markus; Dehghanyar, Pejman; Zeleny, Petra; Graninger, Wolfgang; Müller, Markus; Joukhadar, Christian

    2004-12-01

    By use of microdialysis we assessed the concentrations of telithromycin in muscle and adipose tissue to test its ability to penetrate soft tissues. The ratios of the area under the concentration-versus-time curve from 0 to 24 h to the MIC indicated that free concentrations of telithromycin in tissue and plasma might be effective against Streptococcus pyogenes but not against staphylococci and human and animal bite pathogens. PMID:15561839

  11. Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers

    PubMed Central

    Gattringer, Rainer; Urbauer, Eleonora; Traunmüller, Friederike; Zeitlinger, Markus; Dehghanyar, Pejman; Zeleny, Petra; Graninger, Wolfgang; Müller, Markus; Joukhadar, Christian

    2004-01-01

    By use of microdialysis we assessed the concentrations of telithromycin in muscle and adipose tissue to test its ability to penetrate soft tissues. The ratios of the area under the concentration-versus-time curve from 0 to 24 h to the MIC indicated that free concentrations of telithromycin in tissue and plasma might be effective against Streptococcus pyogenes but not against staphylococci and human and animal bite pathogens. PMID:15561839

  12. 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

  13. 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

    2013-12-01

    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

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

    PubMed

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

    1990-05-01

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

  15. Blood and liver acetaldehyde concentration in rats following acetaldehyde inhalation and intravenous and intragastric ethanol administration

    SciTech Connect

    Watanabe, A.; Hobara, N.; Nagashima, H.

    1986-10-01

    Ethanol is metabolized to acetaldehyde, a highly reactive product of ethanol oxidation. Ethanol might be blended with gasoline and used as a fuel in the future; biohazard of acetaldehyde inhalation must be discussed. Recent improvements in our ability to measure acetaldehyde levels in blood and various tissues have made the assessment of acetaldehyde's role in alcoholic organ intoxication possible. Blood and liver acetaldehyde concentrations in rats were reported as being linearly correlated following intragastric ethanol administration. Acetaldehyde was administered by inhalation to study its toxicity. However, liver concentrations following the inhalation was not investigated. The present communication describes the relationship between blood and liver acetaldehyde concentrations in rats following acetaldehyde inhalation and different routes of ethanol administration.

  16. [HPLC determination of troxerutin in plasma and urine following oral administration in man].

    PubMed

    Dittrich, P; Ostrowski, J; Beubler, E; Schraven, E; Kukovetz, W

    1985-01-01

    A high-performance liquid chromatographic method (HPLC) is described for the analysis of 3',4',7-tri-O-(beta-hydroxy-ethyl)-rutoside (troxerutin) in human plasma and urine. After separation of interfering substances on XAD-2 trihydroxyethylrutoside is converted to tetrahydroxyethylrutoside by 2-chlorethanol in alkaline medium. After HPLC-separation tetrahydroxyethylrutoside is quantified by fluorescence detection. The pharmacokinetics of troxerutin were measured in plasma after oral administration to man. The relative bioavailability of the drug from Venelbin was 97.8 +/- 37.1% compared to an aqueous standard solution.

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

    PubMed Central

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

    1977-01-01

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

  18. 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. PMID:14614525

  19. 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.

  20. Relationship between Sevoflurane Plasma Concentration, Clinical Variables and Bispectral Index Values during Cardiopulmonary Bypass

    PubMed Central

    Nitzschke, Rainer; Wilgusch, Joana; Kersten, Jan Felix; Goepfert, Matthias Sebastian

    2015-01-01

    Background Anesthetic administration is increasingly guided by electroencephalography (EEG)-based monitoring, such as the bispectral index (BIS). However, during cardiopulmonary bypass (CPB), factors other than the administered hypnotic agents may influence EEG signals, and their effects on BIS values are unknown. Methods This report is a secondary analysis of data from a prospective, controlled interventional study comparing the effect of sevoflurane administration guided by BIS monitoring (group SevoBIS) and constant administration of sevoflurane (group Sevo1.8Vol%) during CPB. Sevoflurane plasma concentration (SPC) was measured using gas chromatography. The relationships of BIS to SPC, CPB pump flow, arterial pressure, hematocrit, temperature, time on CPB, and patient characteristics were analysed. Results No association was observed between BIS values and SPC in group SevoBIS. In group Sevo1.8Vol%, a 40 μg ml-1 increase in SPC, which encompassed the entire range of observed values of the SPC in this analysis, was associated with a decrease of 3.6 (95% confidence interval (CI): 1.1–6.1) in BIS values (p = 0.005). Each increase in CPB time of 10 minutes was associated with an increase in BIS values of 0.25 (95%CI: 0.11–0.39, p<0.001). Path analysis revealed that the BIS values of SevoBIS patients were 5.3 (95%CI: 3.2–7.5) units higher than those of Sevo1.8Vol% patients (p<0.001), which was the strongest effect on BIS values. Path analysis revealed a slope of 0.5 (95%CI: 0.3–0.7) BIS units per 1°C body temperature (p<0.001). Conclusion BIS monitoring is insensitive to clinically relevant changes in SPC in individual patients during CPB. PMID:26312484

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

    PubMed

    Lumeij, J T; Remple, J D

    1992-01-01

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

  2. Oral administration of lithium increases tissue magnesium contents but not plasma magnesium level in rats.

    PubMed

    Kiełczykowska, Małgorzata; Musik, Irena; Hordyjewska, Anna; Boguszewska, Anna; Lewandowska, Anna; Pasternak, Kazimierz

    2007-01-01

    The aim of this work was to determine the influence of different doses of lithium on magnesium concentration in plasma and tissues of rats. For a period of eight weeks rats had been provided with aqueous solutions of Li(2)CO(3) whose concentrations were established as follows: 0.7; 1.4; 2.6; 3.6; 7.1; 10.7 mmol Li(+)/l. Magnesium concentration was determined in plasma and tissue supernatants. Lithium caused no changes in magnesium concentration in plasma, whereas Mg concentration in tissues was found to be enhanced, although the degree of the increment depended on the studied tissue. In the liver, brain and heart muscle, the increase was statistically insignificant vs. control. In the kidney, the higher Li doses were required to result in the significant Mg enhancement, whereas in femoral muscle all the used doses caused well-marked Mg increase vs. control. Positive correlations between average daily Li intake and tissue Mg concentration in the kidney (r = 0.650) and femoral muscle (r = 0.696) were found. In conclusion, the present study indicates that the different Li doses disturbed tissue homeostasis of magnesium. The increase in Mg tissue concentration, observed in groups receiving higher Li doses can influence nervous-muscular excitability.

  3. Metabolism and pharmacokinetics of major polyphenol components in rat plasma after oral administration of total flavonoid tablet from Anemarrhenae Rhizoma.

    PubMed

    Xie, Yuan-Yuan; Wang, Xiu-Ming; Wang, Si-Huan; Wang, Yi-Ming; Tian, Hui-Fang; Yuan, Yong-Sheng; Li, Hong-Yan; Liang, Qiong-Lin; Luo, Guo-An

    2016-07-15

    Total flavonoid tablet from Anemarrhenae Rhizoma (Zhimu tablet), which was made of total polyphenol components extracted from the dried rhizome of Anemarrhena asphodeloides Bge. (Zhimu in Chinese), is a novel traditional Chinese medicine prescribed for the treatment of diabetes. Mangiferin (MF) and neomangiferin (NMF) are the two main components detected and determined in Zhimu tablet, accounting for 8.9% of the total weight of each tablet. In the present study, high performance liquid chromatography (HPLC) coupled with time-of-flight (TOF) tandem mass spectrometry (MS) was applied to characterize the metabolites of MF and NMF in rat plasmas collected at different time points after oral administration of Zhimu tablet at a dose of 3.63g/kg (corresponding to 270mg/kg MF). Accurate mass measurement was used to determine the elemental composition of metabolites and thus to confirm the proposed structures of identified metabolites. Time points of appearance of some metabolites, such as isomers, were also taken into account during the structure confirmation. A total of 21 potential metabolites were found in rat plasma at different time points, and the metabolic pathways in vivo were involved in hydrolysis, methylation, glucuronide conjugation, glycoside conjugation, sulphation, dehydration and isomerisation. Furthermore, a selective and accurate LC-MS assay method was developed and validated for the quantification of MF in plasma. Semi-quantification of main conjugated metabolites was also performed in order to describe the dynamic metabolism profiles of polyphenol components in Zhimu tablet. MF concentration in plasma reached 1.36±0.47μgmL(-1) about 5.0h after oral administration of Zhimu tablet, which showed a 3.24- and 4.91-fold increase in plasma maximum concentration and area under the concentration-time curve (AUC) from 0 to 24h of MF compared with those for rats administered with free MF, respectively. The results indicated that the pharmacokinetic processes and

  4. Very High Plasma Concentrations of a Monoclonal Antibody against the Human Insulin Receptor Are Produced by Subcutaneous Injection in the Rhesus Monkey.

    PubMed

    Boado, Ruben J; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Pardridge, William M

    2016-09-01

    Brain penetration of recombinant protein drugs is possible following the re-engineering of the drug as an IgG fusion protein. The IgG domain is a monoclonal antibody (mAb) against an endogenous blood-brain barrier (BBB) receptor transporter, such as the insulin receptor. One such mAb targets the human insulin receptor (HIR) and is active in Rhesus monkeys. Prior work has measured the plasma pharmacokinetics of HIRMAb-derived fusion proteins following intravenous (IV) infusion. However, an alternative method of administration for chronic treatment of brain disease is the subcutaneous (SQ) route. The extent to which an antibody against the insulin receptor undergoes systemic distribution and clearance is unknown. Therefore, in the present study, the rate of plasma clearance of the HIRMAb is measured in Rhesus monkeys following IV or SQ administration of 3, 10, and 30 mg/kg doses of the antibody. The HIRMAb is readily absorbed into the systemic circulation following SQ injection with a 42% plasma bioavailability. The rate of plasma clearance of the antibody, 0.04-0.06 mL/min/kg, is the same following either IV or SQ administration. Owing to the slow rate of plasma clearance of the antibody, high concentrations of the HIRMAb are sustained in plasma for days after the SQ injection. The plasma concentration of the HIRMAb exceeds 0.8 mg/mL, which is 9% of the entire plasma IgG pool in the primate, after the SQ injection of the high dose, 30 mg/kg, of the antibody. In summary, the pharmacokinetics of plasma clearance of the HIRMAb are such that HIRMAb-derived fusion proteins can be developed as protein therapeutics for the brain with chronic SQ administration on a weekly or twice-weekly regimen. PMID:27513815

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

    PubMed

    Hahn, R; Essén, P; Wernerman, J

    1992-01-01

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

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

    SciTech Connect

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

    1991-11-01

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

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

    PubMed

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

    2000-02-01

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

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

    PubMed

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

    1997-01-01

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

  9. 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.

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

    PubMed

    Goldsmith, J C

    2000-03-01

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

  11. Circadian plasma level profile of lisuride in rats and mice after continuous administration via the diet.

    PubMed

    Krause, W; Reissmann, F; Kühne, G; Schöbel, C

    1995-01-01

    Lisuride (Dopergin, CAS 18016-80-3), a dopamine D2 agonist, was administered to male and female rats and mice continuously via the diet for 14 days. The doses were 0.2 mg/kg/d in mice and 1 mg/kg/d in mice and rats. Plasma level profiles (0-22 or 24 h) were determined by measuring lisuride concentrations by radioimmunoassay. At all doses a plateau-like plasma level of lisuride was observed. A clear circadian rhythm of lisuride concentrations (highs during night, low levels during day) was found for male rats (1 mg/kg/d) and for male mice (0.2 mg/kg/d). Female animals did not show this phenomenon as pronounced. At the same dose of 1 mg/kg/d rats showed higher plasma levels than mice. For males the ratio of total AUCs was 1.9 and for female animals 8.6.

  12. 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). PMID:25580397

  13. 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.

  14. Changes in plasma volume during bed rest: effects of menstrual cycle and estrogen administration.

    PubMed

    Fortney, S M; Beckett, W S; Carpenter, A J; Davis, J; Drew, H; LaFrance, N D; Rock, J A; Tankersley, C G; Vroman, N B

    1988-08-01

    Bed rest (BR) is associated with a decrease in plasma volume (PV), which may contribute to the impaired orthostatic and exercise tolerances seen immediately after BR. The purpose of this study was to determine whether increases in blood estrogen concentration, either during normal menstrual cycles or during exogenous estrogen administration, would attenuate this loss of PV. Nineteen healthy women (21-39 yr of age) completed the study. Twelve women underwent duplicate 11-day BR without estrogen supplementation. PV decreased significantly (P less than or equal to 0.01) during both BR's, from 2,531 +/- 113 to 2,027 +/- 102 ml during BR1 and from 2,445 +/- 115 to 2,244 +/- 96 ml during BR2. The women who began BR in the periovulatory stage of the menstrual cycle (n = 3), a time of elevated endogenous estrogens, had a transient delay in loss of PV during the first 5 days of BR. Women who began BR during other stages of the menstrual cycle (n = 17) showed the established trend to decrease PV primarily during the first few days of BR. Seven additional women underwent a single 12-day BR while taking estrogen supplementation (1.25 mg/day premarin). PV decreased during the first 4-5 days of BR, then returned toward the pre-BR level during the remainder of the BR (pre-BR PV, 2,525 +/- 149 ml; post-BR PV, 2,519 +/- 162 ml). Thus menstrual fluctuations in endogenous estrogens appear to have only small transient effects on the loss of PV during BR, whereas exogenous estrogen supplementation significantly attenuates PV loss.

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

    PubMed

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

    2005-01-01

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

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

    PubMed

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

    2006-01-01

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

  17. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    1989-01-01

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

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

    PubMed

    Rana, S K; Sanders, T A

    1986-07-01

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

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

    PubMed

    Rana, S K; Sanders, T A

    1986-07-01

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

  3. 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. PMID:27463546

  4. 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

  5. Intrathecal administration of substance P enhances cutaneous plasma protein extravasation in pentobarbital anaesthetized rats.

    PubMed

    Kérouac, R; Jacques, L; Couture, R

    1987-01-13

    In pentobarbital-anaesthetized rats, the intrathecal administration of substance P (SP) at T9 spinal cord level enhances plasma protein extravasation (PE) in cutaneous tissues of the back, the hind paws and the ears. This vascular response is maximum at 15 min after administration of SP (6.5 nmol), and the most striking in the skin of the hind paws. Contrary to SP, neurotensin (NT) administered intrathecally failed to enhance PE. Both peptides are however potent enhancers of PE following intravenous injection. PE elicited by intrathecal administration of SP is significantly reduced in both spinal rats and in capsaicin treated animals. These results suggest that SP but not NT may play a role as a spinal chemical mediator in peripheral vascular permeability through a supraspinal reflex mechanism involving sensory afferents.

  6. 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. PMID:26492539

  7. 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.

  8. 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.

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

    PubMed

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

    2006-04-01

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

  10. High plasma coenzyme Q10 concentration is correlated with good left ventricular performance after primary angioplasty in patients with acute myocardial infarction

    PubMed Central

    Huang, Ching-Hui; Kuo, Chen-Ling; Huang, Ching-Shan; Tseng, Wan-Min; Lian, Ie Bin; Chang, Chia-Chu; Liu, Chin-San

    2016-01-01

    Abstract Exogenous administration of coenzyme Q10 (CoQ10) has been shown in experimental models to have a protective effect against ischemia–reperfusion injury. However, it is unclear whether follow-up plasma CoQ10 concentration is prognostic of left ventricular (LV) performance after primary balloon angioplasty in patients with acute ST segment elevation myocardial infarction (STEMI). We prospectively recruited 55 patients with STEMI who were treated with primary coronary balloon angioplasty. Plasma CoQ10 concentrations were measured before primary angioplasty (baseline) and 3 days, 7 days, and 1 month after STEMI using high-performance liquid chromatography. Echocardiography was performed at baseline and at 6-month follow-up. The control group comprised 54 healthy age- and sex-matched volunteers. Serial circulating CoQ10 concentrations significantly decreased with time in the STEMI group. The LV ejection fraction at 6-month follow-up positively correlated with the 1-month plasma CoQ10 tertile. Higher plasma CoQ10 concentrations at 1 month were associated with favorable LV remodeling and systolic function 6 months after STEMI. Multiple linear regression analysis showed that changes in CoQ10 concentrations at 1-month follow-up were predictive of LV systolic function 6 months after STEMI. Changes in CoQ10 concentrations correlated negatively with baseline oxidized low-density lipoprotein and fibrinogen concentrations and correlated positively with leukocyte mitochondrial copy number at baseline. Patients with STEMI who had higher plasma CoQ10 concentrations 1 month after primary angioplasty had better LV performance at 6-month follow-up. In addition, higher plasma CoQ10 concentration was associated with lower grade inflammatory and oxidative stress status. Therefore, plasma CoQ10 concentration may serve as a novel prognostic biomarker of LV systolic function after revascularization therapy for acute myocardial infarction. PMID:27495100

  11. Tear film concentrations of doxycycline following oral administration in ophthalmologically normal dogs.

    PubMed

    Collins, Sean P; Labelle, Amber L; Dirikolu, Levent; Li, Zhong; Mitchell, Mark A; Hamor, Ralph E

    2016-09-01

    OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration. DESIGN Crossover study. ANIMALS 10 privately owned dolichocephalic or mesaticephalic dogs free of ophthalmic disease. PROCEDURES Dogs were randomly assigned to receive doxycycline hyclate first at 5 mg/kg (2.3 mg/lb) or 10 mg/kg (4.5 mg/lb), PO, every 12 hours for 5 days, beginning on day 1. Doxycycline was administered 1 hour prior to feeding. Tear samples were collected from days 1 through 10 approximately 3 hours after the morning dose was administered. Following a 3-week washout period, dogs received the alternative dose in the same conditions. Doxycycline concentration in tear samples from 1 eye (same eye used for both sessions) was measured via liquid chromatography-mass spectrometry and compared between the 2 doxycycline doses. RESULTS Doxycycline was detected in tear samples of all dogs from days 1 through 10 for both doxycycline doses. Median peak doxycycline concentrations for the 5 mg/kg and 10 mg/kg doses were 2.19 ng/mL on day 3 and 4.32 ng/mL on day 4, respectively. Concentrations differed significantly with time, but this difference was not influenced by dose, dose order, or eye. A significant positive correlation was identified between doxycycline concentration and body weight (r = 0.22). CONCLUSIONS AND CLINICAL RELEVANCE Detectable doxycycline concentrations were achieved in the tear film of ophthalmologically normal dogs following oral administration of doxycycline at 5 or 10 mg/kg, every 12 hours. Dose had no significant effect on tear film concentration of the drug. PMID:27556265

  12. The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients.

    PubMed

    Melis, Gerdien C; Boelens, Petra G; van der Sijp, Joost R M; Popovici, Theodora; De Bandt, Jean-Pascal; Cynober, Luc; van Leeuwen, Paul A M

    2005-07-01

    Enhancement of depressed plasma concentrations of glutamine and arginine is associated with better clinical outcome. Supplementation of glutamine might be a way to provide the patient with glutamine, and also arginine, because glutamine provides the kidney with citrulline, from which the kidney produces arginine when plasma levels of arginine are low. The aim of the present study was to investigate the parenteral and enteral response of the administered dipeptide Ala-Gln, glutamine, citrulline and arginine. Therefore, seven patients received 20 g Ala-Gln, administered over 4 h, parenterally or enterally, on two separate occasions. Arterial blood samples were taken before and during the administration of Ala-Gln. ANOVA and a paired t test were used to test differences (P<0.05). Ala-Gln was undetectable with enteral administration, whereas Ala-Gln remained stable at a plasma concentration of 268 micromol/l throughout parenteral infusion and rapidly decreased towards zero after infusion was stopped. The highest level of glutamine was observed with parenteral infusion of the dipeptide, although enteral infusion also significantly increased plasma levels of glutamine. The highest plasma response of citrulline was observed with the enteral administration of the dipeptide, although parenteral administration also increased plasma levels of citrulline. Plasma arginine increased significantly with parenteral infusion, but not with enteral administration of Ala-Gln. In conclusion, administrations of Ala-Gln, parenteral or enteral, resulted in an increased plasma glutamine response, as compared with baseline. Interestingly, in spite of the high availability of citrulline with enteral administration of the dipeptide, only parenteral infusion of Ala-Gln increased plasma arginine concentration.

  13. [Hplc estimation of coenzyme Q(10) redox status in plasma after intravenous coenzyme Q(10) administration].

    PubMed

    Kalenikova, E I; Kharitonova, E V; Gorodetskaya, E A; Tokareva, O G; Medvedev, O S

    2015-01-01

    The pharmacokinetics of the total pool of coenzyme Q(10) (Co(10)), its oxidized (ubiquinone) and reduced (ubiquinol, CoQ(10)H₂) forms have been investigated in rats plasma during 48 h after a single intravenous injection of a solution of solubilized CoQ(10) (10 mg/kg) to rats. Plasma levels of CoQ(10) were determined by HPLC with spectrophotometric and coulometric detection. In plasma samples taken during the first minutes after the CoQ(10) intravenous injection, the total pool of coenzyme Q(10) and proportion of CoQ(10)H₂ remained unchanged during two weeks of storage at -20°C. The kinetic curve of the total pool of coenzyme Q(10) corresponds to a one-part model (R² = 0.9932), while the corresponding curve of its oxidized form fits to the two-part model. During the first minutes after the injection a significant portion of plasma ubiquinone undergoes reduction, and after 7 h the concentration of ubiquinol predominates. The decrease in the total plasma coenzyme Q(10) content was accompanied by the gradual increase in plasma ubiquinol, which represented about 90% of total plasma CoQ(10) by the end of the first day. The results of this study demonstrate the ability of the organism to transform high concentrations of the oxidized form of CoQ(10) into the effective antioxidant (reduced) form and justify prospects of the development of parenteral dosage forms of CoQ(10) for the use in the treatment of acute pathological conditions.

  14. 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.

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

    PubMed

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

    2013-10-01

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

  16. 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

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

    PubMed

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

    2010-03-01

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

  18. 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

  19. 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.

  20. Therapeutic efficacy of artesunate-amodiaquine combinations and the plasma and saliva concentrations of desethylamodiaquine in children with acute uncomplicated Plasmodium falciparum malaria.

    PubMed

    Sowunmi, Akintunde; Gbotosho, Grace O; Happi, Christian T; Okuboyejo, Titilope M; Sijuade, Abayomi O; Michael, Obaro S; Adewoye, Elsie O; Folarin, Onikepe

    2013-01-01

    The treatment efficacy of artesunate-amodiaquine (AQ) coformulated or copackaged, and the plasma and saliva concentrations of desethylamodiaquine (DEAQ), the active metabolite of AQ, were evaluated in 120 and 7 children, respectively, with uncomplicated Plasmodium falciparum malaria treated with oral daily doses of the 2 formulations for 3 days. All children recovered clinically. Fever clearance (1.1 ± 0.2 vs 1.0 ± 0 days) and parasite clearance times (21.1 ± 10.2 vs 19.0 ± 7.0 hours) in artesunate-AQ coformulated and artesunate-AQ copackaged treated children, respectively, were similar. All children remained aparasitemic for at least 28 days. Blood and saliva samples were collected over 35 days and DEAQ in plasma and saliva was determined by high-performance liquid chromatography. DEAQ was detectable in plasma and saliva within 40 minutes of oral administration of artesunate-AQ. DEAQ concentrations 7 days after the start of therapy were 247.8 and 125.1 ng/mL in plasma and saliva, respectively. The concentration-time curves of plasma and saliva in declining phases were approximately parallel giving a similar half-life of 169.1 ± 16.4 and 142.8 ± 6.5 hours in plasma and saliva, respectively. Clearance from plasma and saliva was also similar (335.6 and 443.4 mL·h·kg, respectively). Area under concentration-time curves (AUC0-35d) for plasma and saliva were 94,744.9 and 74,004.2 ng·mL·h, respectively. In general, Saliva-plasma concentration ratio was 0.25-0.4. DEAQ concentrations in saliva may be useful for monitoring therapy and for the evaluation of the disposition of AQ in children with falciparum malaria treated with AQ-based combination.

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

    PubMed

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

    1981-02-01

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

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

    USGS Publications Warehouse

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

    1981-01-01

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

  3. Plasma and interstitial fluid pharmacokinetics of enrofloxacin, its metabolite ciprofloxacin, and marbofloxacin after oral administration and a constant rate intravenous infusion in dogs.

    PubMed

    Bidgood, T L; Papich, M G

    2005-08-01

    Enrofloxacin and marbofloxacin were administered to six healthy dogs in separate crossover experiments as a single oral dose (5 mg/kg) and as a constant rate IV infusion (1.24 and 0.12 mg/h.kg, respectively) following a loading dose (4.47 and 2 mg/kg, respectively) to achieve a steady-state concentration of approximately 1 microg/mL for 8 h. Interstitial fluid (ISF) was collected with an in vivo ultrafiltration device at the same time period as plasma to measure protein unbound drug concentrations at the tissue site and assess the dynamics of drug distribution. Plasma and ISF were analyzed for enrofloxacin, its active metabolite ciprofloxacin, and for marbofloxacin by high performance liquid chromatography (HPLC). Lipophilicity and protein binding of enrofloxacin were higher than for marbofloxacin and ciprofloxacin. Compared to enrofloxacin, marbofloxacin had a longer half-life, higher Cmax, and larger AUC(0-infinity) in plasma and ISF after oral administration. Establishing steady state allowed an assessment of the dynamics of drug concentrations between plasma and ISF. The ISF and plasma-unbound concentrations were similar during the steady-state period despite differences in lipophilicity and pharmacokinetic parameters of the drugs.

  4. Flurbiprofen concentration in soft tissues is higher after topical application than after oral administration

    PubMed Central

    Kai, Shuken; Kondo, Eiji; Kawaguchi, Yasuyuki; Kitamura, Nobuto; Yasuda, Kazunori

    2013-01-01

    Aim To compare tissue concentrations of flurbiprofen resulting from topical application and oral administration according to the regulatory approved dosing guidelines. Method Sixteen patients were included in this study. Each patient was randomly assigned to the topical application or oral administration group. In each group, a pair of tapes or a tablet, containing a total of 40 mg flurbiprofen, was administered twice at 16 and 2 h before the surgery. Results The flurbiprofen concentration in the fat, tendon, muscle and periosteum tissues was significantly higher (P < 0.0330) after topical application (992 ng g−1 [95% CI 482, 1503], 944 [95% CI 481, 1407], 492 [95% CI 248, 735], and 455 [95% CI 153, 756], respectively) than after oral administration (150 ng g−1 [95% CI 84, 217], 186 [95% CI 118, 254], 82 [95% CI 49, 116],and 221 [95% CI, 135, 307], respectively). Conclusion Topical application is an effective method to deliver flurbiprofen to the human body, particularly to soft tissues near the body surface. PMID:22822928

  5. Kinetic profiles of tianeptine and its MC5 metabolite in plasma, blood and brain after single and chronic intraperitoneal administration in the rat.

    PubMed

    Couet, W; Girault, J; Latrille, F; Salvadori, C; Fourtillan, J B

    1990-01-01

    This study was conducted to determine kinetic profiles of the antidepressant tianeptine and its main metabolite (named MC5) in plasma, blood and brain after single (10 mg.kg-1) and chronic (10 mg.kg-1.day-1 and 2 x 10 mg.kg-1.day-1 for 15 days) intraperitoneal administration in Wistar rats. In plasma, tianeptine and MC5 reached a peak very quickly (5 and 15 min post administration respectively). Following the peak, disappearance of tianeptine was faster than that of MC5 with terminal half-lives close to 2.5 and 6.5 h respectively. During chronic treatment, accumulation of tianeptine was negligible, that of MC5 was slight as indicated by accumulation ratios equal to 1.28 (once daily administration) and 1.73 (twice daily administration). Tianeptine and MC5 rapidly appeared in brain tissue but at concentrations less than those observed in plasma. Peak concentrations of tianeptine in brain were higher than those of MC5. A very low penetration of tianeptine and MC5 into erythrocytes was observed.

  6. 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.

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

    PubMed

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

    1985-08-01

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

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

    PubMed

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

    2014-03-01

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

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

    PubMed

    Geelen, M J; Beynen, A C

    2000-05-01

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

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

    PubMed

    Sorondo, María L; Cirio, Alberto

    2009-05-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2012-01-01

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

  13. 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.

  14. 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. PMID:17312724

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2010-04-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. In vitro efficacy of lufenuron against filamentous fungi and blood concentrations after PO administration in horses.

    PubMed

    Scotty, Nicole C; Evans, Tim J; Giuliano, Elizabeth; Johnson, Philip J; Rottinghaus, George E; Fothergill, Annette W; Cutler, Tim J

    2005-01-01

    Lufenuron is a benzoylphenyl urea-derived insecticide that has been recently introduced as a novel treatment for fungal infections in horses. The purposes of this study were to determine (1) the in vitro efficacy of lufenuron against Aspergillus and Fusarium spp. and (2) the ability of lufenuron to reach efficacious blood concentrations after PO administration in horses. Fungal colonies isolated from diseased equine corneas were tested against lufenuron solutions up to 700 microg/mL. Twenty-one adult horses received 1 of 3 PO lufenuron treatment regimens: 5 mg/kg body weight (BW) q24h for 3 days, 20 mg/kg BW q24h for 3 days, or 60 mg/ kg BW q24h for 1 day. Blood samples were collected up to 96 hours after drug administration and analyzed by high-performance liquid chromatography. Statistical analyses of lufenuron blood concentrations were performed by analysis of variance and Fischer's Least Significant Difference test, with statistical significance set at P < .05. Lufenuron showed no effect on the in vitro growth of Aspergillus or Fusarium spp. Lufenuron was detected in the blood of all but 1 horse and showed no adverse effects. The maximum blood lufenuron concentration (83.5 +/- 58.7 microg/L) was lower than the concentrations proven to be ineffective in vitro in this study. Further therapeutic use of lufenuron as an antifungal agent in horses should be based on proven efficacy against specific strains of clinically relevant fungi with pharmacokinetic data demonstrating sufficient lufenuron concentrations in target tissues. PMID:16355684

  19. 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. PMID:26851651

  20. Salivary and urinary excretion and plasma-saliva concentration ratios of isoniazid in the presence of Co-administered ciprofloxacin.

    PubMed

    Ofoefule, Sabinus I; Obodo, Chioma E; Orisakwe, Orish E; Afonne, Johnson O; Ilondu, Ndidiamaka A; Agbasi, Patrick U; Anusiem, Chikere A; Maduka, Steve O; Ilo, Cajetan E

    2002-01-01

    Salivary and urinary excretion and plasma-saliva concentration ratios of isoniazid (INH) in the absence and presence of ciprofloxacin (CP) were investigated in healthy female volunteers. Results obtained indicated an absorption form of interaction between INH and CP. This led to delay in gastric emptying and onset of absorption of INH in the upper part of the gastrointestinal tract, resulting in a corresponding delay in the onset of salivary and urinary excretion of the drugs. There was a 1-hour reduction in the time to attain peak saliva concentration of INH (tmax), an insignificant difference in peak saliva concentration (Cmax), and a significant (P = 0.05) increase in AUC(0-24h) of INH in the presence of CP. Cumulative amount of INH excreted in the urine increased approximately 38% in the presence of CP. The calculated plasma-saliva concentration ratios of INH were reduced in the presence of CP and were slightly lower than the experimental values. This indicates increased amount of the drug secreted into saliva in the presence of CP and possible buccal partitioning of the drug. Overall, results of the current study indicate that CP delayed the onset but not the extent of INH absorption. Therefore, concurrent administration of the two drugs was considered relatively safe, and the absorption interaction that may have occurred may not be of reasonable clinical consequence.

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

    PubMed Central

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

    2012-01-01

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

  2. 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.

  3. Comparison of plasma concentrations of estradiol-17β and progesterone, and conception in dairy cows with cystic ovarian diseases between Ovsynch and Ovsynch plus CIDR timed AI protocols.

    PubMed

    Kawate, Noritoshi; Watanabe, Kensuke; Uenaka, Kazuhiro; Takahashi, Masahiro; Inaba, Toshio; Tamada, Hiromichi

    2011-04-01

    The objectives of this study were 1) to determine the effects of adding a CIDR to the Ovsynch protocol on plasma concentrations of estradiol-17β and progesterone and conception in dairy cows with cystic ovarian diseases and 2) to examine associations among the estradiol-17β and progesterone concentrations and conception. Cows were diagnosed as having cystic ovarian diseases if they were found to have a cystic follicle (diameter ≥25 mm) without a corpus luteum by two palpations per rectum with an interval for 7 to 14 days. They were treated with either the Ovsynch (GnRH on Day 0, PGF(2α) on Day 7 and GnRH on Day 9, with AI on Day 10; n=15) or Ovsynch+CIDR protocol (Ovsynch protocol plus a CIDR from Day 0 to Day 7; n=23). Plasma estradiol-17β concentrations were determined on Days 0, 7 and 9, and plasma progesterone concentrations were determined on Days 0, 7, 9 and 17. The plasma estradiol-17β and progesterone concentrations at all of the days examined and conception rates did not differ significantly between the two timed AI protocols. The progesterone concentrations on Day 17 and conception rates were lower (P<0.05) for cows with low concentrations of estradiol-17β (<2 pg/ml) on Day 9 than for cows with high concentrations of estradiol-17β (≥2 pg/ml). The present study suggests that, in dairy cows with cystic ovarian diseases, addition of a CIDR to the Ovsynch protocol had no remarkable effects on plasma estradiol-17β and progesterone concentrations during and after the treatments or on conception after timed AI. This study indicates that the low plasma estradiol-17β concentration at the second administration of GnRH in the protocols can be a predictor for impaired luteal formation and lower likelihood of pregnancy in dairy cows with cystic ovarian diseases.

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

    PubMed

    Svennebring, Andreas Mats

    2016-01-01

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

  5. Reversal of medetomidine-induced sedation in reindeer (Rangifer tarandus tarandus) with atipamezole increases the medetomidine concentration in plasma.

    PubMed

    Ranheim, B; Horsberg, T E; Nymoen, U; Søli, N E; Tyler, N J; Arnemo, J M

    1997-10-01

    The pharmacokinetics of two potent alpha 2-adrenoceptor agents that can be used for immobilization (medetomidine) and reversal (atipamezole) of the sedation in mammals, were studied in three reindeer (Rangifer tarandus tarandus) in winter and again in summer. Medetomidine (60 micrograms/kg) was injected intravenously (i.v.), followed by atipamezole (300 micrograms/kg) intravenously 60 min later. Drug concentrations in plasma were measured by HPLC. The administration of atipamezole resulted in an immediate 2.5-3.5 fold increase in the medetomidine concentration in plasma. Clearance for medetomidine (median 19.3 mL/min.kg) was lower than clearance for atipamezole (median 31.0 mL/min.kg). The median elimination half-lives of medetomidine and atipamezole in plasma were 76.1 and 59.9 min, respectively. The animals became resedated 0.5-1 h after the reversal with atipamezole. Resedation may be explained by the longer elimination half-life of medetomidine compared to atipamezole. PMID:9350254

  6. Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults.

    PubMed

    Obeid, Rima; Kirsch, Susanne H; Kasoha, Mariz; Eckert, Rudolf; Herrmann, Wolfgang

    2011-05-01

    Folate deficiency can cause age-related disease. Folic acid (FA) has been used in studies aiming at disease prevention. Recently, unmetabolized FA in plasma raised public health concerns; but numerous studies used FA for disease prevention. Concentrations of the folate forms FA, 5-methyltetrahydrofolate (5-MTHF), and tetrahydrofolate (THF) were measured before and after 3-week placebo or FA 5 mg, vitamin B6 40 mg, and cyanocobalamin 2 mg per day administrated to 74 older adults (median age, 82 years). Concentrations of 5-MTHF and total homocysteine (tHcy) (r = -0.392) and S-adenosylmethionine (r = 0.329) were correlated at baseline. Twenty-six percent of the elderly subjects had unmetabolized FA in plasma at the start, and concentrations of FA were increased after 3 weeks of FA treatment (median FA = 0.08 nmol/L at baseline and 15.3 nmol/L at the end of the treatment in the vitamin group). Folic acid caused a 10- and a 5-fold increase in 5-MTHF and THF, respectively, and lowered tHcy (median tHcy = 17.2 μmol/L at baseline vs 9.0 μmol/L after treatment). Concentrations of unmetabolized FA were positively related to those of 5-MTHF and THF. People showed wide variations in folate forms at baseline, but these were reduced after FA treatment. Folic acid given to older adults is mostly converted to THF and 5-MTHF and lowered concentrations of tHcy, but caused a substantial increase in unmetabolized FA in the plasma.

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

    PubMed

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

    1987-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  9. 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.

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

    PubMed

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

    1998-01-01

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

  11. 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.

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

    PubMed

    Lumeij, J T; Remple, J D

    1991-03-01

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

  13. 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.

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

    PubMed

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

    2006-01-01

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

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

    PubMed

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

    1980-11-01

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed

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

    1984-03-01

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

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

    PubMed

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

    2013-09-01

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

  19. Pharmacokinetics of anthraquinones in rat plasma after oral administration of a rhubarb extract.

    PubMed

    Wu, Wenjin; Yan, Ru; Yao, Meicun; Zhan, Ying; Wang, Yitao

    2014-04-01

    A sensitive and specific LC-MS/MS method was developed for simultaneous determination of aloe-emodin, rhein, emodin, chrysophanol and physcion and their conjugates in rat plasma. The lower limit of quantitation of each anthraquinone was 0.020-0.040 µm. Intra-day and inter-day accuracies were 90.1-114.3% and the precisions were <14.6%. The matrix effects were 104.0-113.2%. The method was successfully applied to a pharmacokinetic study in rats receiving a rhubarb extract orally. The area under the concentration-time curve (AUC0-t ) and peak concentration (Cmax ) of free aloe-emodin and emodin in rat plasma were much lower than those of rhein. The amounts of chrysophanol and physcion were too low to be continuously detected. After treating the plasma samples with β-glucuronidases, each anthraquinone was detectable throughout the experimental period (36 h) and showed much higher plasma concentrations and AUC0-t . The free/total ratios of aloe-emodin, rhein and emodin were 6.5, 49.0 and 1.7% for Cmax and 3.7, 32.5 and 1.1% for AUC0-t , respectively. The dose-normalized AUC0-t and Cmax of the total of each anthraquinone were in the same descending order: rhein > emodin > chrysophanol > physcion > aloe-emodin. These findings reveal phase II conjugates as the dominant in vivo existing forms of rhubarb antharquinones and warrant a further study to evaluate their contribution to the herbal activity.

  20. Plasma and Tissue Concentrations of α-Tocopherol and δ-Tocopherol Following High Dose Dietary Supplementation in Mice

    PubMed Central

    Baxter, Laura L.; Marugan, Juan J.; Xiao, Jingbo; Incao, Art; McKew, John C.; Zheng, Wei; Pavan, William J.

    2012-01-01

    Vitamin E isoforms are essential nutrients that are widely used as dietary supplements and therapeutic agents for a variety of diseases. However, their pharmacokinetic (PK) properties remain poorly characterized, and high dosage animal studies may provide further information on their in vivo functions and pharmacological effects. In this study, alpha-tocopherol (α-toc) and delta-tocopherol (δ-toc) levels were measured in mouse plasma and tissues following their high dosage dietary supplementation. Average α-toc levels at 5, 10 and 20 g α-toc/kg diet increased over baseline levels 6-fold in plasma, 1.6-fold in brain, and 4.9-fold in liver. These elevated α-toc concentrations remained constant from 5 to 20 g α-toc/kg diet, rather than showing further increases across these dosages. No α-toc-related toxicity occurred at these high dosages, and strain-specific differences in liver and brain α-toc levels between Balb/cJ and C57Bl/6J mice were observed. Relatively high-dosage administration of dietary δ-toc for 1 or 4 weeks resulted in 6–30-fold increases in plasma and liver levels between dosages of 0.33 and 1.67 g δ-toc/kg diet. Co-administration of sesamin with δ-toc further increased δ-toc levels between 1.3- and 14-fold in plasma, liver, and brain. These results provide valuable PK information on high dosage α-toc and δ-toc in mouse and show that supplementation of sesamin with δ-toc further increases δ-toc levels over those seen with δ-toc supplementation alone. PMID:22822447

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

    PubMed

    Stangier, Joachim; Feuring, Martin

    2012-03-01

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

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

    PubMed

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

    2008-04-01

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

  3. 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.

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

    PubMed

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

    2010-04-01

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

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

    PubMed

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

    2010-04-01

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

  6. LC determination and pharmacokinetic study of the main phenolic components of Portulaca oleracea L. extract in rat plasma after oral administration.

    PubMed

    Cheng, Zhongzhe; Wang, Dong; Zhang, Wenjie; Du, Yang; Wang, Yunjiao; Zhai, Yanjun; Ying, Xixiang; Kang, Tingguo

    2012-01-01

    This study investigated the pharmacokinetics of hesperidin (HP), ferulic acid (FA) and p-coumaric acid (CA) in rat plasma after oral administration of Portulaca oleracea L. extract (POE). The plasma concentrations were determined by HPLC with vitexin-2″-O-rhamnoside (VR) as internal standard. The calibration curves were linear over the range 0.1-5 µg mL(-1), 0.1-5 µg mL(-1)and 0.015-3 µg mL(-1) for HP, FA and CA, respectively. The validated method was suitable to the pharmacokinetic study of HP, FA and CA in rats after oral administration at a single dose of POE. PMID:22250700

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

    PubMed

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

    1988-03-01

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

  8. Oral and Intraperitoneal Administration of Quercetin Decreased Lymphocyte DNA Damage and Plasma Lipid Peroxidation Induced by TSA In Vivo

    PubMed Central

    Chan, Shu-Ting; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

    2014-01-01

    Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation. PMID:24868531

  9. Controlled Systemic Delivery by Polymeric Implants Enhances Tissue and Plasma Curcumin Levels Compared with Oral Administration

    PubMed Central

    Bansal, Shyam S.; Kausar, Hina; Vadhanam, Manicka V.; Ravoori, Srivani; Gupta, Ramesh C.

    2012-01-01

    Curcumin possess potent anti-inflammatory and anti-proliferative activities but with poor biopharmaceutical attributes. To overcome these limitations, curcumin implants were developed and tissue (plasma, brain and liver) curcumin concentrations were measured in female ACI rats for 3 months. Biological efficacy of tissue levels achieved was analyzed by modulation of hepatic cytochromes. Curcumin implants exhibited diffusion-mediated biphasic release pattern with ~2-fold higher in vivo release as compared to in vitro. Plasma curcumin concentration from implants was ~3.3 ng/ml on day 1 which dropped to ~0.2 ng/ml after 3 months whereas only 0.2–0.3 ng/ml concentration was observed from 4–12 days with diet and was undetected subsequently. Almost 10 fold higher curcumin levels were observed in brain on day 1 from implants compared with diet (30.1±7.3 vs 2.7±0.8 ng/g) and were higher even after 90 days (7.7±3.8 vs 2.2±0.8 ng/g). Although, curcumin levels were similar in liver from both the routes (~25–30 ng/g from day 1–4 and ~10–15 ng/g at 90 days), implants were more efficacious in altering hepatic CYP1A1 levels and CYP3A4 activity at ~28 fold lower doses. Curcumin implants provided much higher plasma and tissue concentrations and are a viable alternative for delivery of curcumin to various organs like brain. PMID:22227368

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

    PubMed Central

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

    1978-01-01

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

  11. 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.

  12. 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

  13. 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

  14. 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

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

    PubMed Central

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

    2016-01-01

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

  16. Aspartame ingestion with and without carbohydrate in phenylketonuric and normal subjects: effect on plasma concentrations of amino acids, glucose, and insulin.

    PubMed

    Wolf-Novak, L C; Stegink, L D; Brummel, M C; Persoon, T J; Filer, L J; Bell, E F; Ziegler, E E; Krause, W L

    1990-04-01

    Seven subjects homozygous for phenylketonuria (PKU) and seven normal subjects were administered four beverage regimens after an overnight fast: unsweetened beverage, beverage providing carbohydrate (CHO), beverage providing aspartame (APM), and beverage providing APM plus CHO. The APM dose (200 mg) was the amount provided in 12 oz of diet beverage; the CHO was partially hydrolyzed starch (60 g). Plasma amino acid concentrations were determined after dosing and the molar plasma phenylalanine (Phe) to large neutral amino acid (LNAA) ratio calculated. APM administration without CHO did not increase plasma Phe concentrations over baseline values in either normal or PKU subjects (5.48 +/- 0.85 and 150 +/- 23.0 mumols/dL, respectively). Similarly, the Phe/LNAA did not increase significantly. Ingestion of beverage providing APM and CHO did not significantly increase plasma Phe concentrations over baseline values in either normal or PKU subjects. However, ingestion of beverage providing CHO (with or without APM) significantly decreased plasma levels of valine, isoleucine, and leucine 1.5 to 4 hours after dosing in both normal and PKU subjects, thereby increasing the Phe/LNAA ratio significantly. These data indicate that changes noted in Phe/LNAA values after ingestion of beverage providing APM plus CHO were due to CHO. The plasma insulin response to beverage providing CHO (with or without APM) was significantly higher in PKU subjects than in normals.

  17. 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

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

    PubMed Central

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

    2010-01-01

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

  19. 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.

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

    PubMed

    Sanders, T A; Key, T J

    1987-06-01

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

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

    PubMed

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

    2000-06-01

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

  2. 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.

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

    PubMed

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

    2007-11-01

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

  4. 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

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

    PubMed

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

    2014-09-15

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

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

    PubMed

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

    1990-08-01

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

  7. Effect of repeated ingestion of aspartame-sweetened beverage on plasma amino acid, blood methanol, and blood formate concentrations in normal adults.

    PubMed

    Stegink, L D; Filer, L J; Bell, E F; Ziegler, E E; Tephly, T R

    1989-04-01

    Aspartame (APM) is a widely used dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester). It has been suggested that excessive use of APM might elevate plasma aspartate, phenylalanine, and/or methanol concentrations to levels that are potentially harmful. Six normal young adults ingested eight successive servings of unsweetened and APM-sweetened beverage at one-hour intervals in a balanced crossover design. In one part, the beverage was not sweetened. In the other, each serving of beverage provided 600 mg APM, a dose equivalent to the amount provided by 36 oz of APM-sweetened diet beverage. Plasma aspartate concentration was not significantly increased after ingestion of unsweetened or APM-sweetened beverage. Similarly, ingestion of the unsweetened beverage had no significant effect on plasma phenylalanine concentration. However, ingestion of APM-sweetened beverage significantly increased plasma phenylalanine levels 1.41 to 2.35 mumol/dL above baseline 30 minutes after ingestion. Plasma phenylalanine values reached a steady state after administration of four to five servings and did not exceed normal postprandial values at any time. Blood methanol and formate concentrations remained within normal limits. The data indicate ready metabolism of APM when administered at levels that may be ingested by normal individuals who are heavy users of diet beverages.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2013-11-01

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

  12. Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.

    PubMed

    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

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2010-01-01

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

  15. Is there evidence that fresh frozen plasma is superior to antithrombin administration to treat heparin resistance in cardiac surgery?

    PubMed

    Beattie, Gwyn W; Jeffrey, Robert R

    2014-01-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was, 'in [patients with heparin resistance] is [treatment with FFP] superior [to antithrombin administration] in [achieving adequate anticoagulation to facilitate safe cardiopulmonary bypass]?' More than 29 papers were found using the reported search, of which six represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Antithrombin (AT) binds to heparin and increases the rate at which it binds to thrombin. The levels of antithrombin in the blood are an important aspect of the heparin dose-response curve. When the activated clotting time (ACT) fails to reach a target >480, this is commonly defined as heparin resistance (HR). Heparin resistance is usually treated with a combination of supplementary heparin, fresh frozen plasma (FFP) or antithrombin III concentrate. There is a paucity of evidence on the treatment of heparin resistance with FFP, with only five studies identified, including one retrospective study, one in vitro trial and three case reports. AT has been studied more extensively with multiple studies, including a crossover trial comparing AT to supplemental heparin and a multicentre, randomized, double blind, placebo-controlled trial. Antithrombin (AT) concentrate is a safe and efficient treatment for heparin resistance to elevate the activated clotting time (ACT). It avoids the risk of transfusion-related acute lung injury (TRALI), volume overload, intraoperative time delay and viral or vCJD transmission. Antithrombin concentrates are more expensive than fresh frozen plasma and may put patients at risk of heparin rebound in the early postoperative period. Patients treated with AT have a lower risk of further FFP transfusions during their stay in hospital. We conclude that the treatment of

  16. 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.

  17. 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

  18. Plasma cinnarizine levels resulting from oral administration as capsule or tablet formulation investigated by gas-liquid chromatography.

    PubMed Central

    Morrison, P J; Bradbrook, I D; Rogers, H J

    1979-01-01

    1 A gas chromatographic assay for the estimation of therapeutic concentrations of cinnarizine in plasma is described. 2 Cinnarizine (75 mg) was administered orally to twelve healthy subjects in the form of capsules and tablets on two separate occasions. No difference was found in the plasma levels or absorption of cinnarizine from these formulations. 3 The mean plasma elimination half-life of cinnarizine was 3.24 h. PMID:444354

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

    Frawley, G; Ragg, P; Hack, H

    2000-01-01

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

  2. 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.

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

    SciTech Connect

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

    2006-01-15

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

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

    PubMed

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

    1989-03-01

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

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

    PubMed

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

    2013-08-01

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

  6. 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

  7. 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

  8. Rapid determination of apixaban concentration in human plasma by liquid chromatography/tandem mass spectrometry: application to pharmacokinetic study.

    PubMed

    Delavenne, Xavier; Mismetti, Patrick; Basset, Thierry

    2013-05-01

    We described the development and full validation of a rapid, high throughput sensible and accurate LC method using tandem mass spectrometry detection for determining apixaban concentration with [(¹³C, ²H₇]-apixaban as internal standard in human plasma. Plasma pretreatment involved a one-step protein precipitation with methanol. The separation was performed by reverse-phase chromatography on a Luna MercuryMS C18 column (20 mm × 4 mm × 3 μm) column. The multiple reaction monitoring transitions used for quantification were m/z 460.20→443.27 and 460.20→198.99 for apixaban, 468.22→451.30 for [(¹³C, ²H₇]-apixaban in the electrospray positive ionization mode. The method was linear over the concentration range of 5-500 μg/L. The intra- and inter-day precision values were below 14% and accuracy was from 90.0 to 105.8% at all quality control levels. Sample analysis time was less than 10 min including sample preparation. The present method was successfully applied to a pharmacokinetic study following oral administration of apixaban. PMID:23499913

  9. 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.

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

    PubMed

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

    2012-08-01

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

  11. 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.

  12. A simple liquid chromatography-tandem mass spectrometry method for determination of plasma fentanyl concentration in rats and patients with cancer pain.

    PubMed

    Hisada, Tatsuya; Katoh, Miki; Hitoshi, Kotaro; Kondo, Yuya; Fujioka, Miho; Toyama, Yukio; Ieda, Hideaki; Gocho, Saori; Nadai, Masayuki

    2013-01-01

    A fentanyl patch is widely used for the treatment of cancer pain. Its few adverse effects include constipation and drowsiness. The absorption volume of transdermally applied fentanyl may differ according to its site of application and variability in patch adhesion. Since fentanyl is predominantly metabolized by the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 in the liver, its concentration may vary in cases of physiologically reduced CYP3A4 activity in the liver (liver disease and aging) or on co-administration of drugs. The clinical significance of measuring plasma concentration of fentanyl is high, but conventional methods require complicated processes such as solid-phase extraction and liquid-liquid extraction before the sample is injected into an HPLC system. In this study, a simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determining plasma fentanyl concentrations by deproteinization with acetonitrile. A recovery test was conducted using an absolute calibration curve to confirm the method's linearity and inter- and intra-day reproducibility. The required plasma volume for detection was reduced from 1 mL in the conventional method to 20 µL in the present study, and a good calibration curve was obtained in the concentration range from 0.05 to 5 ng/mL. These findings suggest that the method for sample preparation and quantification developed in this study are appropriate for measuring fentanyl concentration in human plasma in clinical settings.

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

    PubMed

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

    2012-06-01

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

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

    PubMed

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

    2016-01-01

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

  15. 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.

  16. Effect of repeated administration of cadmium, captopril and its combination on plasma renin activity in rats.

    PubMed

    Nath, P V; Vivek, T

    1997-11-01

    The effects of normal saline (1 ml kg-1, i.p. for 5 days), cadmium acetate (1 mg kg-1, i.p. for 5 days), captopril (20 mg kg-1, p.o. for 5 days), or captopril (20 mg kg-1, p.o. for 5 days) plus cadmium acetate (1 mg kg-1, i.p. for 5 days) on blood pressure (BP), heart rate (HR), plasma renin activity (PRA) and respiratory rate (RR) were examined in male Sprague-Dawley (S-D) rats. Repeated administration of cadimum acetate produced a hypertensive response (P < 0.01) without significant changes in PRA, HR or RR. The captopril group was associated with hypotension (P < 0.01) but again PRA, HR and RR were not significantly altered. In the group receiving captopril p.o. and cadmium i.p., BP rose significantly compared with captopril alone but PRA, HR, RR were not altered. Cadmium-induced hypertension cannot be obviously accounted for on its basis of augmented plasma or tissue renin angiotensin involvement.

  17. 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

  18. Effects of Gn-RH, TRH, and CRF administration on plasma leptin levels in lean and obese women.

    PubMed

    Komorowski, J; Jankiewicz-Wika, J; Stepień, H

    2000-04-01

    Leptin, a hormone which is produced by adipose tissue, has been shown to inhibit food intake, increase energy expenditure and influence the function of hypothalamo-pituitary-gonadal, -thyroid, and -adrenal systems. We have examined the association between leptin concentrations (RIA method) and levels of different hormones using standard Gn-RH, TRH and CRF tests (at 0, 30, 60, and 120 min) in regularly menstruating 10 lean and 10 obese premenopausal women in follicular phase. FSH, LH, estradiol (E2) and progesterone (P) concentrations in Gn-RH test; TSH, PRL, fT3, fT4 in TRH test; ACTH, DHEA-S, cortisol in CRF test were measured by RIA, ELISA or IRMA methods. The obese subjects had thicker four skinfolds, higher fat content in the body, and bigger BMI, compared to the lean females. Gn-RH test: We have noted higher basal leptin values in obese women than in lean subjects, which was stable during the Gn-RH test. In the same blood specimen, basal insulin concentrations did not differ between the tested groups of patients. There were no correlations between E(2), P, or gonadotropins and plasma leptin concentrations between both groups of patients. We have revealed the negative correlation between LH mobilization (maximal incremental values over basal levels; Delta%) and baseline leptin concentrations in all observed subjects. TRH test: In both groups of patients the leptin levels decreased at 120 min of TRH administration. We have noted diminished PRL and TSH mobilisation in obese subjects in comparison to the controls. In all females (n = 20) the correlations between TSH or PRL mobilization and BMI, skinfold thickness and the mass of body fat in kg were negative. In obese subjects only we observed the positive correlations between fT(3)concentrations at 60 and 120 min of the test or Delta% of fT(3)and leptin levels. CRF test: In obese females, we noted higher basal ACTH and cortisol concentrations with decreased mobilization (Delta%) of ACTH or cortisol, as compared to

  19. 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

  20. 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

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

    PubMed Central

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

    2015-01-01

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

  2. 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

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

    SciTech Connect

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

    2007-12-15

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

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

    PubMed Central

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

    1988-01-01

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

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

    PubMed

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

    1991-10-01

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

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

    PubMed

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

    1998-12-01

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

  7. Repeated Administration of a Mutant Cocaine Esterase: Effects on Plasma Cocaine Levels, Cocaine-Induced Cardiovascular Activity, and Immune Responses in Rhesus Monkeys

    PubMed Central

    Collins, Gregory T.; Brim, Remy L.; Noon, Kathleen R.; Narasimhan, Diwahar; Lukacs, Nicholas W.; Sunahara, Roger K.; Woods, James H.

    2012-01-01

    Previous studies have demonstrated the capacity of a long-acting mutant form of a naturally occurring bacterial double mutant cocaine esterase (DM CocE) to antagonize the reinforcing, discriminative, convulsant, and lethal effects of cocaine in rodents and reverse the increases in mean arterial pressure (MAP) and heart rate (HR) produced by cocaine in rhesus monkeys. This study was aimed at characterizing the immunologic responses to repeated dosing with DM CocE and determining whether the development of anti-CocE antibodies altered the capacity of DM CocE to reduce plasma cocaine levels and ameliorate the cardiovascular effects of cocaine in rhesus monkeys. Under control conditions, intravenous administration of cocaine (3 mg/kg) resulted in a rapid increase in the plasma concentration of cocaine (n = 2) and long-lasting increases in MAP and HR (n = 3). Administration of DM CocE (0.32 mg/kg i.v.) 10 min after cocaine resulted in a rapid hydrolysis of cocaine with plasma levels below detection limits within 5 to 8 min. Elevations in MAP and HR were significantly reduced within 25 and 50 min of DM CocE administration, respectively. Although slight (10-fold) increases in anti-CocE antibodies were observed after the fourth administration of DM CocE, these antibodies did not alter the capacity of DM CocE to reduce plasma cocaine levels or ameliorate cocaine's cardiovascular effects. Anti-CocE titers were transient and generally dissipated within 8 weeks. Together, these results suggest that highly efficient cocaine esterases, such as DM CocE, may provide a novel and effective therapeutic for the treatment of acute cocaine intoxication in humans. PMID:22518021

  8. Repeated administration of a mutant cocaine esterase: effects on plasma cocaine levels, cocaine-induced cardiovascular activity, and immune responses in rhesus monkeys.

    PubMed

    Collins, Gregory T; Brim, Remy L; Noon, Kathleen R; Narasimhan, Diwahar; Lukacs, Nicholas W; Sunahara, Roger K; Woods, James H; Ko, Mei-Chuan

    2012-07-01

    Previous studies have demonstrated the capacity of a long-acting mutant form of a naturally occurring bacterial double mutant cocaine esterase (DM CocE) to antagonize the reinforcing, discriminative, convulsant, and lethal effects of cocaine in rodents and reverse the increases in mean arterial pressure (MAP) and heart rate (HR) produced by cocaine in rhesus monkeys. This study was aimed at characterizing the immunologic responses to repeated dosing with DM CocE and determining whether the development of anti-CocE antibodies altered the capacity of DM CocE to reduce plasma cocaine levels and ameliorate the cardiovascular effects of cocaine in rhesus monkeys. Under control conditions, intravenous administration of cocaine (3 mg/kg) resulted in a rapid increase in the plasma concentration of cocaine (n = 2) and long-lasting increases in MAP and HR (n = 3). Administration of DM CocE (0.32 mg/kg i.v.) 10 min after cocaine resulted in a rapid hydrolysis of cocaine with plasma levels below detection limits within 5 to 8 min. Elevations in MAP and HR were significantly reduced within 25 and 50 min of DM CocE administration, respectively. Although slight (10-fold) increases in anti-CocE antibodies were observed after the fourth administration of DM CocE, these antibodies did not alter the capacity of DM CocE to reduce plasma cocaine levels or ameliorate cocaine's cardiovascular effects. Anti-CocE titers were transient and generally dissipated within 8 weeks. Together, these results suggest that highly efficient cocaine esterases, such as DM CocE, may provide a novel and effective therapeutic for the treatment of acute cocaine intoxication in humans. PMID:22518021

  9. 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.

  10. Lack of association between plasma levels of non-nucleoside reverse transcriptase inhibitors & virological outcomes during rifampicin co-administration in HIV-infected TB patients

    PubMed Central

    Ramachandran, Geetha; Kumar, A.K. Hemanth; Ponnuraja, C.; Ramesh, K.; Rajesh, Lakshmi; Chandrasekharan, C.; Swaminathan, Soumya

    2013-01-01

    Background & objectives: Among patients with HIV-associated tuberculosis (TB), reduced plasma non-nucleoside reverse transcriptase inhibitors (NNRTI) concentrations during rifampicin (RMP) co-administration could lead to HIV treatment failure. This study was undertaken to examine the association between plasma nevirapine (NVP) and efavirenz (EFV) concentrations and virological outcomes in patients infected with HIV-1 and TB. Methods: This was a nested study undertaken in a clinical trial of patients with HIV-1 and TB, randomized to two different once-daily antiretroviral treatment (ART) regimens along with anti-TB treatment (ATT). Trough concentrations of plasma NVP and EFV were estimated at months 1 (during ATT and ART) and 6 months (ART only) by HPLC. Plasma HIV-1 RNA level >400 copies/ml or death within 6 months of ART were considered as unfavourable outcomes. Genotyping of CYP2B6 516G>T polymorphism was performed. Results: Twenty nine per cent of patients in NVP arm had an unfavourable outcome at 6 months compared to 9 per cent in EFV arm (P<0.08). The mean NVP and EFV levels estimated at 1 and 6 months did not significantly differ between favourable and unfavourable responders. Logistic regression analysis showed CYP2B6 516G>T polymorphism significantly associated with virologic outcome in patients receiving EFV–based regimen. Interpretation & conclusions: Trough plasma concentrations of NVP and EFV did not show any association with response to ART in patients on ATT and once-daily ART. CYP2B6 516G>T polymorphism was associated with virologic outcome among patients on EFV. PMID:24521642

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

    PubMed Central

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

    2014-01-01

    Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA) levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6) in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase) in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro. PMID:24675707

  12. Resistin in dairy cows: plasma concentrations during early lactation, expression and potential role in adipose tissue.

    PubMed

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

    2014-01-01

    Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA) levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6) in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase) in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro. PMID:24675707

  13. 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

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

    PubMed

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

    2013-01-01

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

  15. 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.

  16. 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.

  17. Plasma osmotic and electrolyte concentrations of largemouth bass from some acidic Florida lakes

    SciTech Connect

    Canfield, D.E. Jr.; Maceina, M.J.; Nordlie, F.G.; Shireman, J.V.

    1985-05-01

    Five acidic clear (pH 3.7-4.9), three acidic colored (pH 4.1-4.6), and three neutral (pH 6.9-7.3) north-central Florida lakes were surveyed in 1983 to determine plasma osmotic and electrolyte concentrations, growth, and coefficients of condition for largemouth bass Micropterus salmoides floridanus. Plasma osmotic concentrations averaged greater than 273 milliosmoles/kg in fish from acidic colored and circumneutral lakes, but averaged less than 269 milliosmoles/kg in four of the acidic clear lakes. Growth and coefficients of condition of largemouth bass > 305 mm total length in the acidic lakes were significantly lower than in the neutral lakes. Reductions in fish growth and condition, however, could be related to either acidic conditions or lake trophic status. 29 references, 3 tables.

  18. Plasma and urine diketopiperazine concentrations in normal adults ingesting large quantities of aspartame.

    PubMed

    Cho, E S; Coon, J D; Stegink, L D

    1987-07-01

    In aqueous solution, aspartame can cyclicize to form its corresponding diketopiperazine (3-carboxymethyl-6-benzyl-2,5-diketopiperazine; DKP) and methanol. We measured plasma and urinary concentrations of DKP in samples obtained from six normal adult subjects ingesting 2.2 mg DKP/kg body weight. The DKP was administered as part of a dose of 200 mg aspartame/kg body weight. DKP concentrations in plasma were below the detection limit (less than 1 microgram/ml) of the high-pressure liquid chromatographic method at each time interval after ingestion at which they were measured. Mean (+/- SD) total urinary DKP excreted during the first 24-hr period after dosing was 6.68 +/- 1.30 mg (4.83 +/- 0.23% of the ingested DKP dose). Approximately 44% of the total DKP excreted was excreted in the first 4 hr after dosing.

  19. Plasma pharmacokinetics, bioavailability and tissue distribution of agnuside following peroral and intravenous administration in mice using liquid chromatography tandem mass spectrometry.

    PubMed

    Ramakrishna, Rachumallu; Bhateria, Manisha; Singh, Rajbir; Puttrevu, Santosh Kumar; Bhatta, Rabi Sankar

    2016-06-01

    Agnuside (AGN), an iridoid glycoside, is the chemotaxonomic marker of the genus Vitex which has gained enormous attention by virtue of its potential health benefits. Regardless of claiming many therapeutic applications reports demonstrating its pharmacokinetics or quantification in biomatrices are lacking. This is the first report which presents a sensitive liquid chromatography coupled to a tandem mass spectrometry (LC-MS/MS) method for the quantification of AGN in mice plasma and various tissues (including liver, intestine, spleen, kidney, heart, lungs and brain). AGN was extracted from the biological samples using protein precipitation followed by liquid-liquid extraction and the separation was achieved on C18 reversed phase column with a mobile phase consisted of 0.1% formic acid in acetonitrile-0.1% formic acid in triple distilled water (92:8, v/v) at a flow rate of 0.7mL/min. The MS/MS detection was performed by electrospray ionization (ESI) using multiple reaction monitoring (MRM) in negative scan mode. The bioanalytical method was found linear over the concentration range of 1-4000ng/mL for plasma and tissue homogenates (r(2)≥0.990). The lower limit of quantitation (LLOQ) for all matrices was 1ng/mL. Intra-day and inter-day variance and accuracy ranged from 90 to 110% and 1-10%, respectively. Matrix effect and recoveries were well within the satisfactory limits. The validated method was applied successfully to measure AGN concentrations in plasma and tissues following intravenous (i.v.) and peroral (p.o.) administration to mice. Maximal AGN concentrations in plasma and tissues were reached within 30-45min. The mean absolute bioavailability (%F) of AGN was∼0.7%. After oral administration, AGN was most abundant in intestine, followed by kidney, liver, spleen, brain, lungs and heart. The identified target tissues of AGN may help in understanding its pharmacological action in vivo.

  20. Association between dietary factors and plasma fetuin-A concentrations in the general population.

    PubMed

    Nimptsch, Katharina; Janke, Jürgen; Pischon, Tobias; Linseisen, Jakob

    2015-10-28

    Circulating fetuin-A, a novel marker for hepatic fat accumulation, has been related to a higher risk of type 2 diabetes and cardiovascular diseases in a growing number of prospective studies. However, little is known about dietary determinants of fetuin-A concentrations in the general population. Therefore, we aimed to investigate the association between dietary intake of energy, energy-providing nutrients, alcohol and major food groups and plasma fetuin-A concentrations in the Bavarian Food Consumption Survey II. Dietary intake was assessed by three 24-h dietary recalls, and plasma concentrations of fetuin-A were measured in 558 adults (18-81 years). After multivariable adjustment for lifestyle factors and body fatness, higher energy intake was nonsignificantly associated with higher fetuin-A concentrations (per 2092 kJ/d (500 kcal/d) 3·7 µg/ml, 95 % CI -0·5, 7·8 µg/ml). There was no clear association between energy-providing nutrients and fetuin-A concentrations. Higher alcohol intake was associated with lower fetuin-A concentrations (P trend 0·003): mean fetuin-A concentrations were 324 (95 % CI 313, 335) µg/ml in non-drinkers, and with 293 (95 % CI 281, 306) µg/ml significantly lower in participants who drank ≥30 g alcohol per d. Mean fetuin-A concentrations decreased across quintiles of milk and dairy product intake (lowest quintile 319 (95 % CI 309, 330) µg/ml; highest quintile 304 (95 % CI 293, 314) µg/ml; P trend 0·03), and each 150-g increment in milk/dairy products per d was associated with 5·6 (95 % CI -9·6, -1·5) µg/ml lower fetuin-A. Dietary intakes of vegetables, meat or fish were not associated with fetuin-A concentrations. Because of the preventive potential of our findings, further exploration is warranted. PMID:26316198

  1. 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.

  2. Modifications of plasma 5-HT concentrations during the allergic bronchoconstriction in guinea pigs.

    PubMed

    Arreola-Ramírez, José Luis; Vargas, Mario H; Manjarrez-Gutiérrez, Gabriel; Alquicira, Jesús; Gutiérrez, Julio; Córdoba, Guadalupe; Campos-Bedolla, Patricia; Segura-Medina, Patricia

    2013-09-01

    Several contractile mediators involved in the antigen-induced airway obstruction have been identified, but the role of 5-HT (5-hydroxytryptamine or serotonin) has been scantily investigated. In this work, the potential role of 5-HT in the allergic bronchoconstriction was evaluated through a pharmacological approach and plasma 5-HT measurement in blood samples from the right and left ventricles of anesthetized guinea-pigs. Intravenous 5-HT caused a dose-dependent increase of the lung resistance in anesthetized, nonsensitized guinea pigs. Likewise, in sensitized animals the antigenic challenge with ovalbumin also caused a transient bronchoconstriction (356 ± 60% the basal value), which was largely inhibited by the blockade of serotonergic receptors with methiothepin plus tropisetron (134 ± 10%, P = .007). Sensitized animals tended to have plasma 5-HT concentrations higher than nonsensitized controls, and shortly after the peak of the allergic bronchoconstriction the 5-HT levels in the left ventricle (blood flowing out from lungs) tended to be higher than in the right ventricle (blood entering the lungs), although data dispersion precluded the obtaining of statistical significance. Interestingly, the degree of bronchoconstriction highly correlated with the concentrations of 5-HT found in the left ventricle and measured either in platelet-rich plasma (r = 0.97 P = .007) or platelet-poor plasma (r = 0.97, P = .006). After the obstructive response subsided these correlations were lost, but now the degree of bronchoconstriction turned to be correlated with 5-HT concentration in platelet concentrate (r = 0.76, P = .03). In conclusion, our results suggested that 5-HT is actively released from lungs during the antigenic challenge and that this autacoid is involved in the generation of the airway obstruction.

  3. 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.

  4. 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

  5. Evidence that plasma concentration rather than dose per kilogram body weight predicts ribavirin-induced anaemia.

    PubMed

    Lindahl, K; Schvarcz, R; Bruchfeld, A; Ståhle, L

    2004-01-01

    Ribavirin in combination with interferon alpha-2 or pegylated interferon is the standard treatment for chronic hepatitis C. The current dosage recommendations for ribavirin are based on body weight (bw). Ribavirin is mainly eliminated by the kidneys and we have recently shown that ribavirin plasma concentrations are determined primarily by renal function. It is therefore reasonable to hypothesize that side-effects of ribavirin, i.e. anaemia, should be more closely related to plasma concentrations of ribavirin than to the dose per kg bw. A total of 108 consecutive patients eligible for treatment of chronic hepatitis C were studied. Ribavirin concentrations in plasma were measured by high-performance liquid chromatography (HPLC)-UV after solid-phase extraction in trough samples taken 4, 8 and 12 weeks after the treatment commenced. A total of 213 samples were obtained and the change in the haemoglobin level and the creatinine concentration was measured in addition to ribavirin. The dose of ribavirin per kg bw did not correlate with the drop in haemoglobin level induced by ribavirin. The concentration of ribavirin was non-linearly related to the drop in the haemoglobin level as revealed by fitting a standard Hill equation type dose-response curve. The half maximal drop in haemoglobin was obtained at 4.4 microm. The results from this study suggest that the anaemia induced by ribavirin depends primarily on the concentration of ribavirin, and not on the dose per kg bw. This lends further support to the idea that ribavirin should be dosed according to renal function.

  6. Effect of extracorporeal shockwave lithotripsy on plasma and urine endothelin concentrations.

    PubMed

    Esen, A A; Gezer, S; Gemalmaz, A; Kirkali, G; Kirkali, Z

    1996-08-01

    Since the first reports of extracorporeal shockwave lithotripsy (SWL), there have been increasing numbers of articles in the literature documenting renal blood flow impairment and blood pressure elevation as complications. However, little is known about the pathophysiology and prevention of these complications. In this prospective study, the influence of high-energy shockwaves on plasma and urine endothelin concentrations was investigated in 20 patients with renal stones. The patients were randomly assigned to receive a calcium channel blocker, 10 mg of nitrendipine (Bypress; Bayer) (N = 10) 2 hours before SWL or no medication (control group; N = 10). Blood samples were taken just before and 1 minute after application of 3000 shocks. Urine samples were collected by ureteral catheters. The plasma endothelin-1 concentrations were significantly elevated after SWL in the control group (P = 0.003). On the other hand, nitrendipine significantly reduced plasma endothelin concentrations after SWL (P = 0.003). No significant change was observed in urine samples and blood pressure measurements. These results suggest that endothelin release after SWL may be a cause for lithotripsy-induced hemodynamic changes. Medical prevention with calcium channel blockers warrants further investigation.

  7. Plasma membrane calcium ATPase is concentrated in the head of sea urchin spermatozoa.

    PubMed

    Gunaratne, Herath Jayantha; Neill, Anna T; Vacquier, Victor D

    2006-05-01

    Plasma membrane Ca2+ATPases (PMCAs) export Ca2+ from cells in a highly regulated manner, providing fine-tuning to the maintenance of intracellular Ca2+ concentrations. There are few studies of PMCAs in spermatozoa, which is surprising considering the importance of this enzyme in all cell types. Here we describe the primary structure and localization of the PMCA of sea urchin spermatozoa (suPMCA). The suPMCA is 1,154 amino acids and has 56% identity and 76% similarity to all 4 human PMCA isoforms. The suPMCA shares the features of a typical PMCA, including domains for calmodulin binding, ATP binding, ATPase phosphorylation, and 10 putative transmembrane segments with two large cytoplasmic loops. Southern blots show that suPMCA is a single copy gene. Treatment of live sea urchin sperm with the PMCA inhibitor, 5-(-6)-carboxyeosin, results in elevations of intracellular Ca2+ and loss of flagellar motility. Immunoblotting and immunoflorescence show that suPMCA is concentrated in the sperm head plasma membrane. In previous work, we showed that a plasma membrane K+ dependent Na+/Ca2+ exchanger (suNCKX), which also keeps Ca2+ low in these cells, is concentrated in the sperm flagellum. Thus, the sperm head and flagellum localize different gene products, both functioning to keep intracellular Ca2+ low, while the sperm swims in seawater containing 10 mM Ca2+. PMID:16358326

  8. 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

  9. 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.

  10. Plasma volumes, blood volumes, and plasma protein concentrations after moderate haemodilution with fluosol-DA or normal saline in the rat.

    PubMed

    Shrewsbury, R P

    1991-05-01

    Plasma volumes, blood volumes, and plasma total protein, albumin, and bilirubin concentrations have been determined in rats for 72 h following 20 or 40 mL kg-1 haemodilution with Fluosol-DA or 0.9% NaCl. Haemodilution with 20 mL kg-1 of either haemodiluent had no influence on the measured values. Plasma and blood volumes did not change after Fluosol-DA haemodilution at 40 mL kg-1, but albumin and bilirubin concentrations were decreased for 72 h. Only bilirubin concentrations were decreased for 72 h following haemodilution with 40 mL kg-1 of 0.9% NaCl. It was concluded that changes in a drug's plasma protein binding, and not the plasma or blood volume, are responsible for the reported alterations in a drug's apparent volume of distribution after haemodilution.

  11. 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

  12. 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

  13. Estimation of electron concentration in plasma and plasma frequency in the vicinity of a hypersonic aircraft that moves in atmosphere and analysis of propagation frequencies of electromagnetic waves in such plasma

    NASA Astrophysics Data System (ADS)

    Fedorov, V. A.

    2016-05-01

    Electron concentration in plasma and plasma frequency are estimated for the plasma that is formed in the vicinity of a hypersonic aircraft that moves in atmosphere. The frequencies of electromagnetic waves that may propagate in plasma emerging in the vicinity of the aircraft are determined. Formulas that make it possible to analytically (rather than graphically) calculate electron concentration in plasma at altitudes of 30, 60, and 90 km are derived for two speeds. Several specific features of variations in the electron concentration in plasma depending on the above altitudes and speeds are presented. Quasi-periodic variations in the plasma concentration can be obtained using an increase and decrease in the speed of aircraft.

  14. Positive correlations of age and parity with plasma concentration of macrophage migration inhibitory factor in Japanese black cows

    PubMed Central

    KOIZUMI, Motoya; NAHAR, Asrafun; YAMABE, Ryusei; KADOKAWA, Hiroya

    2016-01-01

    Plasma Macrophage migration inhibitory factor (MIF) concentration correlates positively with age, and negatively with self-rated health in women, and optimal MIF concentration may promote proper reproductive function. This study was conducted to evaluate the hypotheses that plasma MIF concentration changes with parturition or postpartum first ovulation, and that age in months and parity correlate with plasma MIF concentration in Japanese black cows. Western blotting utilizing an anti-MIF mouse monoclonal antibody of various tissues and plasma from females indicated that MIF expression was stronger in the anterior pituitary than in other tissues. We developed a competitive EIA utilizing the same anti-MIF mouse monoclonal antibody with sufficient sensitivity and reliable performance for measuring bovine plasma samples. We then measured MIF concentrations in bovine plasma collected from 4 weeks before parturition to 4 weeks after postpartum first ovulation. There was no significant difference in plasma MIF concentration pre- and post-parturition, or before and after the postpartum first ovulation. Plasma MIF concentrations were positively correlated (P < 0.01) with parity (r = 0.703), age in months on the day of parturition (r = 0.647), and age in months on the day of the postpartum first ovulation (r = 0.553) when we used almost all data, except for that from a third-parity cow with an abnormally high plasma MIF concentration. We therefore concluded that plasma MIF concentrations may increase with age in months and parity, but do not change either before and after parturition or before and after postpartum first ovulation in Japanese black cows. PMID:26853787

  15. Arginines Plasma Concentration and Oxidative Stress in Mild to Moderate COPD

    PubMed Central

    Zinellu, Angelo; Fois, Alessandro Giuseppe; Sotgia, Salvatore; Sotgiu, Elisabetta; Zinellu, Elisabetta; Bifulco, Fabiana; Mangoni, Arduino A; Pirina, Pietro; Carru, Ciriaco

    2016-01-01

    Background Elevated plasma concentrations of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) have been observed in respiratory conditions such as asthma and cystic fibrosis. Since oxidative stress has been shown to increase the activity of arginine methylating enzymes, hence increased ADMA synthesis, and to reduce ADMA degrading enzymes, hence increased ADMA concentrations, we assessed methylated arginines concentrations in chronic obstructive pulmonary disease (COPD), a disease characterized by increased oxidative stress. Methods Plasma arginine, ADMA and symmetric dimethylarginine (SDMA), oxidative stress markers (thiobarbituric acid reactive substances, TBARS, and plasma proteins SH, PSH) and antioxidants (taurine and paraoxonase 1, PON1, activity) were measured in 43 COPD patients with mild (n = 29) or moderate (n = 14) disease and 43 age- and sex-matched controls. Results TBARS significantly increased with COPD presence and severity (median 2.93 vs 3.18 vs 3.64 μmol/L, respectively in controls, mild and moderate group, p<0.0001 by ANOVA) whereas PSH decreased (6.69±1.15 vs 6.04±0.85 vs 5.33±0.96 μmol/gr prot, p<0.0001 by ANOVA). Increased ADMA/arginine ratio, primarily due to reduced arginine concentrations, was also observed with COPD presence and severity (median 0.0067 vs 0.0075 vs 0.0100, p<0.0001 by ANOVA). In multiple logistic regression analysis, only TBARS (OR 0.44, 95% CI 0.25–0.77; p = 0.0045) and ADMA/Arginine ratio (OR 1.72, 95% CI 2.27–13.05; p = 0.02) were independently associated with COPD severity. Conclusion COPD presence and severity are associated with increased oxidative stress and alterations in arginine metabolism. The reduced arginine concentrations in COPD may offer a new target for therapeutic interventions increasing arginine availability. PMID:27479314

  16. 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.

  17. Plasma Cannabinoid Pharmacokinetics following Controlled Oral Δ9-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration

    PubMed Central

    Karschner, Erin L.; Darwin, W. David; Goodwin, Robert S.; Wright, Stephen; Huestis, Marilyn A.

    2013-01-01

    BACKGROUND Sativex®, a cannabis extract oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC’s effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. METHODS Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board–approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. RESULTS Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (Cmax) and areas under the curve from 0–10.5 h postdose (AUC0→10.5) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in Cmax, time to maximum concentration or in the AUC0→10.5 between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. CONCLUSION These data suggest that CBD modulation of THC’s effects is not due to a pharmacokinetic interaction at these therapeutic doses. PMID:21078841

  18. Determinants of plasma concentrations of perfluoroalkyl substances in pregnant Norwegian women

    PubMed Central

    Whitworth, KW; Ydersbond, TA; Haug, LS; Haugen, M; Knutsen, HK; Thomsen, C; Meltzer, HM; Becher, G; Sabaredzovic, A; Hoppin, JA; Eggesbø, M; Longnecker, MP

    2013-01-01

    Background Perfluoroalkyl substances (PFASs) are widespread pollutants that have been associated with adverse health effects although not on a consistent basis. Diet has been considered the main source of exposure. The aim of the present study was to identify determinants of four plasma PFASs in pregnant Norwegian women. Methods This study is based in the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Our sample included 487 women who enrolled in MoBa from 2003–2004. A questionnaire regarding sociodemographic, medical, and reproductive history was completed at 17 weeks gestation and a dietary questionnaire was completed at 22 weeks gestation. Maternal plasma samples were obtained around 17 weeks of gestation. Plasma concentrations of four PFASs (perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA)) were examined in relation to demographic, lifestyle, dietary, and pregnancy-related covariates. Predictors were identified by optimizing multiple linear regression models using Akaike’s information criterion (AIC). Results Parity was the determinant with the largest influence on plasma PFAS concentrations, with r2 between 0.09 and 0.32 in simple regression models. In optimal multivariate models, when compared to nulliparous women, parous women had 46%, 70%, 19%, and 62% lower concentrations of PFOS, PFOA, PFHxS, and PFNA respectively (p<0.001 except for PFHxS, p<0.01). In all these models, duration of breastfeeding was associated with reduced PFAS levels. PFOA showed the largest reduction from breastfeeding, with a 2–3% reduction per month of breastfeeding in typical cases. Levels of PFOS, PFOA, and PFNA increased with time since most recent pregnancy. While pregnancy-related factors were the most important predictors, diet was a significant factor explaining up to 4% of the variance. One quartile increase in estimated dietary PFAS intake

  19. Plasma catecholamine concentrations in rainbow trout (Salmo gairdneri) at rest and after anesthesia and surgery

    USGS Publications Warehouse

    Gingerich, W.H.; Drottar, K.R.

    1989-01-01

    The effects of surgery and anesthesia on concentrations of plasma epinephrine (E), norepinephrine (NE), and dopamine (DA) were investigated in rainbow trout fitted with dorsal aorta cannulae. Baseline catecholamines (CA) concentrations, established in resting rainbow trout, were 1.55 ± 0.90 ϱmol/ml (X ± SD) for E, 2.07 ± 1.26 for NE, and 1.33 ± 0.87 for DA. These values were based on the pooled analyses of five individual fish taken over seven different sampling periods. The E:NE ratio in resting fish was always less than 1.0. In a second experiment, fish were subjected to dorsal aorta cannulation and sequential blood samples were taken immediately after surgery, and 6, 24, and 48 hr later. Plasma E concentrations were 36 times greater than baseline values in the first sample; NE was 15 times greater and DA was 41 times greater. After surgery, plasma concentrations of all CAs fell rapidly but values were still higher than baseline 6 hr after surgery, then were near baseline at 24 and 48 hr after surgery. The E:NE ratio was about 3.0 immediately after surgery, dropped to 1.8 at 6 hr, and was about 1.0 at 24 and 48 hr. In a third experiment, plasma CAs were determined in a group of five animals anesthetized with tricaine methanesulfonate (100 mg/ml) to advanced anesthesia, and then allowed to recover in flowing well water over a 12-hr observation period. Plasma E and NE concentrations in the fish during early anes-thesia (1.14 ± 0.14 min) were not significantly different from preanesthesia values. During advanced anesthesia (2.31 ± 0.21 min), values for E and NE were significantly greater and continued to be elevated during the 12-hr recovery period. The E:NE ratio exceeded 1.0 during advanced anesthesia and for the rest of the experiment.

  20. The effects of exercise training programs on plasma concentrations of proenkephalin Peptide F and catecholamines.

    PubMed

    Kraemer, William J; Gordon, Scott E; Fragala, Maren S; Bush, Jill A; Szivak, Tunde K; Flanagan, Shawn D; Hooper, David R; Looney, David P; Triplett, N Travis; DuPont, William H; Dziados, Joseph E; Marchitelli, Louis J; Patton, John F

    2015-02-01

    To determine if exercise training alters the pattern and magnitude of plasma concentrations of proenkephalin Peptide F and epinephrine, plasma proenkephalin [107-140] Peptide F(ir) and catecholamines were examined pre-training (T-1), and after 4- (T-2), 8- (T-3), and 12-weeks (T-4) of training. 26 healthy men were matched and randomly assigned to one of three groups: heavy resistance strength training (Strength, n=9), high intensity endurance training (Endurance, n=8), or both training modalities combined (Combined, n=9). Blood was collected using a syringe with a cannula inserted into a superficial arm vein with samples collected at rest, after each 7 min stage and 5 and 15 min into recovery. With training, all groups observed shifted plasma Peptide F responses to graded exercise, where significant increases were observed at lower exercise intensities. Increases in plasma epinephrine with exercise were observed in all groups. The Combined group saw increases at 25% at T-3 and for 50% at T-2, T-3, and T-4 which was higher than T-1. The Endurance group demonstrated increases for 50% at T-1, T-2, T-3 but not at T-4. The plasma epinephrine response to graded exercise was reduced in the Strength group. Increases in plasma norepinephrine above rest were observed starting at 50% . The Strength group demonstrated a significant reduction in norepinephrine observed at 100% at T-3 and T-4. Peptide F and catecholamines responses to graded exercise can be altered by different types of physical exercise training. Simultaneous high intensity training may produce adrenal medulla exhaustion when compared to single mode training.

  1. Increased Nutrient Sensitivity and Plasma Concentrations of Enteral Hormones during Duodenal Nutrient Infusion in Functional Dyspepsia

    PubMed Central

    Bharucha, Adil E.; Camilleri, Michael; Burton, Duane D.; Thieke, Shannon L.; Feuerhak, Kelly J.; Basu, Ananda; Zinsmeister, Alan R.

    2015-01-01

    Objectives Functional dyspepsia is predominantly attributed to gastric sensorimotor dysfunctions. The contribution of intestinal chemosensitivity to symptoms is not understood. We evaluated symptoms and plasma hormones during enteral nutrient infusion and the association with impaired glucose tolerance and quality-of-life (QOL) scores in functional dyspepsia vs health. Design Enteral hormonal responses and symptoms were measured during isocaloric and isovolumic dextrose and lipid infusions into the duodenum in 30 patients with functional dyspepsia (n=27) or nausea and vomiting (n=3) and 35 healthy controls. Infusions were administered in randomized order over 120 minutes each, with a 120-minute washout. Cholecystokinin, glucose-dependent insulinotropic peptide, glucagonlike peptide 1 (GLP1), and peptide YY were measured during infusions. Results Moderate or more severe symptoms during lipid (4 controls vs 14 patients) and dextrose (1 control vs 12 patients) infusions were more prevalent in patients than controls (P≤.01), associated with higher dyspepsia symptom score (P=.01), worse QOL (P=.01), and greater plasma hormone concentrations (eg, GLP1 during lipid infusion). Moderate or more severe symptoms during enteral infusion explained 18%, and depression score explained 21%, of interpatient variation in QOL. Eight patients had impaired glucose tolerance, associated with greater plasma GLP1 and peptide YY concentrations during dextrose and lipid infusions, respectively. Conclusions Increased sensitivity to enteral dextrose and lipid infusions was associated with greater plasma enteral hormone concentrations, more severe daily symptoms, and worse QOL in functional dyspepsia. These observations are consistent with the hypothesis that enteral hormones mediate increased intestinal sensitivity to nutrients in functional dyspepsia. PMID:25403365

  2. 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.

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

    PubMed

    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

  4. 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

  5. Variability and determinants of total homocysteine concentrations in plasma in an elderly population.

    PubMed

    Clarke, R; Woodhouse, P; Ulvik, A; Frost, C; Sherliker, P; Refsum, H; Ueland, P M; Khaw, K T

    1998-01-01

    The variability of plasma total homocysteine (tHcy) was examined in 96 individuals over a 1-yr period. Blood tHcy concentrations varied from 7.1 micromol/L in the bottom quintile to 14.5 micromol/L in the top quintile. The mean tHcy was 10.4 micromol/L, the between-person SD was 2.5 micromol/L, and the within-person SD was 0.93 micromol/L. There was little seasonal variation, and the reliability coefficient was 0.88. Mean tHcy concentrations were inversely related to mean plasma folate (r = -0.36) and vitamin B12 (r = -0.35) concentrations. Median tHcy concentrations were approximately 1 micromol/L higher in men than in women and in older (70 to 74 years) than in younger (65 to 69 years) individuals and higher in those with the TT and CT genotypes for the methylenetetrahydrofolate reductase polymorphism than in those with the CC genotype (10.7 and 10.6 vs 9.6 micromol/L). Epidemiological studies based on single tHcy measurements may underestimate the magnitude of any risk associations with disease by 10-15%. PMID:9550566

  6. Variability and determinants of total homocysteine concentrations in plasma in an elderly population.

    PubMed

    Clarke, R; Woodhouse, P; Ulvik, A; Frost, C; Sherliker, P; Refsum, H; Ueland, P M; Khaw, K T

    1998-01-01

    The variability of plasma total homocysteine (tHcy) was examined in 96 individuals over a 1-yr period. Blood tHcy concentrations varied from 7.1 micromol/L in the bottom quintile to 14.5 micromol/L in the top quintile. The mean tHcy was 10.4 micromol/L, the between-person SD was 2.5 micromol/L, and the within-person SD was 0.93 micromol/L. There was little seasonal variation, and the reliability coefficient was 0.88. Mean tHcy concentrations were inversely related to mean plasma folate (r = -0.36) and vitamin B12 (r = -0.35) concentrations. Median tHcy concentrations were approximately 1 micromol/L higher in men than in women and in older (70 to 74 years) than in younger (65 to 69 years) individuals and higher in those with the TT and CT genotypes for the methylenetetrahydrofolate reductase polymorphism than in those with the CC genotype (10.7 and 10.6 vs 9.6 micromol/L). Epidemiological studies based on single tHcy measurements may underestimate the magnitude of any risk associations with disease by 10-15%.

  7. Plasma lactate concentration increases as a parabola with delay during ramp exercise.

    PubMed

    Péronnet, F; Morton, R H

    1994-01-01

    This study presents an elementary model of a system which relates plasma lactate concentration ([La-]) during ramp exercise to its rate of accumulation (Rc) within its extramuscular distribution space (S). Under the parsimonious assumptions that Rc increases linearly with time (t) with a kinetic delay (delta), and that the volume of S is constant, it is shown that plasma [La-] increases as a parabola with the kinetic delay delta when t increases. This elementary system model describes changes in plasma [La-] observed in five healthy young subjects during ramp exercise on the cycle ergometer (1 W every 2 s) with great accuracy (r > 0.99) with very small residuals (average value less than 0.01 mmol.l-1), randomly distributed around the fitting curves. The delay between the beginning of exercise and the onset of increase in Rc could be due to the fact that at the corresponding work rates: (1) rate of lactate appearance (Ra), which is equal to the rate of lactate disappearance (Rd), is not modified from rest, since the exercising muscles work in fully aerobic conditions (hypothesis of the anaerobic threshold); or (2) the increase in Ra is associated with a similar increase in Rd. An alternate or complementary hypothesis is that, during ramp exercise, plasma [La-] could reflect metabolic events within the muscles, with a significant delay.

  8. A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

    PubMed Central

    Chouraki, V; De Bruijn, RFAG; Chapuis, J; Bis, JC; Reitz, C; Schraen, S; Ibrahim-Verbaas, CA; Grenier-Boley, B; Delay, C; Rogers, R; Demiautte, F; Mounier, A; Fitzpatrick, AL; Berr, C; Dartigues, J-F; Uitterlinden, AG; Hofman, A; Breteler, M; Becker, JT; Lathrop, M; Schupf, N; Alpérovitch, A; Mayeux, R; van Duijn, CM; Buée, L; Amouyel, P; Lopez, OL; Ikram, MA; Tzourio, C; Lambert, J-C

    2014-01-01

    Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides’ functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1–40 and Aβ1–42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10−5). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1–42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1–42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites. PMID:24535457

  9. Impurity identifications, concentrations and particle fluxes from spectral measurements of the EXTRAP T2R plasma

    NASA Astrophysics Data System (ADS)

    Menmuir, S.; Kuldkepp, M.; Rachlew, E.

    2006-10-01

    An absolute intensity calibrated 0.5 m spectrometer with optical multi-channel analyser detector was used to observe the visible-UV radiation from the plasma in the EXTRAP T2R reversed field pinch experiment. Spectral lines were identified indicating the presence of oxygen, chromium, iron and molybdenum impurities in the hydrogen plasma. Certain regions of interest were examined in more detail and at different times in the plasma discharge. Impurity concentration calculations were made using the absolute intensities of lines of OIV and OV measured at 1-2 ms into the discharge generating estimates of the order of 0.2% of ne in the central region rising to 0.7% of ne at greater radii for OIV and 0.3% rising to 0.6% for OV. Edge electron temperatures of 0.5-5 eV at electron densities of 5-10×1011 cm-3 were calculated from the measured relative intensities of hydrogen Balmer lines. The absolute intensities of hydrogen lines and of multiplets of neutral chromium and molybdenum were used to determine particle fluxes (at 4-5 ms into the plasma) of the order 1×1016, 7×1013 and 3×1013 particles cm-2 s-1, respectively.

  10. A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly.

    PubMed

    Chouraki, V; De Bruijn, R F A G; Chapuis, J; Bis, J C; Reitz, C; Schraen, S; Ibrahim-Verbaas, C A; Grenier-Boley, B; Delay, C; Rogers, R; Demiautte, F; Mounier, A; Fitzpatrick, A L; Berr, C; Dartigues, J-F; Uitterlinden, A G; Hofman, A; Breteler, M; Becker, J T; Lathrop, M; Schupf, N; Alpérovitch, A; Mayeux, R; van Duijn, C M; Buée, L; Amouyel, P; Lopez, O L; Ikram, M A; Tzourio, C; Lambert, J-C

    2014-12-01

    Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1-40 and Aβ1-42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10(-)(5)). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1-42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1-42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.

  11. Different changes of plasma membrane beta-adrenoceptors in rat heart after chronic administration of propranolol, atenolol and bevantolol.

    PubMed

    Horinouchi, Takahiro; Morishima, Shigeru; Tanaka, Takashi; Suzuki, Fumiko; Tanaka, Yoshio; Koike, Katsuo; Miwa, Soichi; Muramatsu, Ikunobu

    2007-07-12

    Recently, tissue segment binding method with a hydrophilic radioligand [(3)H]-CGP12177 was developed to detect plasma membrane beta-adrenoceptors in rat heart (Horinouchi et al., 2006). In the present study, propranolol (40 mg kg(-1) day(-1)), atenolol (40 mg kg(-1) day(-1)) and bevantolol (200 mg kg(-1) day(-1)) were administered to rats for 6 weeks, and the changes of plasma membrane beta-adrenoceptors and their mRNA expression in rat ventricle were examined. Chronic administration of propranolol increased the beta(1)-adrenoceptors but decreased the beta(2)-adrenoceptors without changing total amount of plasma membrane beta-adrenoceptors. Atenolol increased both plasma membrane beta(1)- and beta(2)-adrenoceptors, whereas bevantolol had no effect on the beta-adrenoceptor density and their subtype proportions. In contrast, the density of beta-adrenoceptors detected in conventional homogenate binding study was extremely low (approximately 60% of plasma membrane beta-adrenoceptors detected with the tissue segment binding method) and the effects of chronic administration of beta-adrenoceptor antagonists were not necessarily in accord with those at the plasma membrane beta-adrenoceptors. The mRNA levels of beta(1)- and beta(2)-adrenoceptors were not altered by propranolol treatment, while beta(1)-adrenoceptor mRNA significantly decreased after administration of atenolol or bevantolol without changing the level of beta(2)-adrenoceptor mRNA. The present binding study with intact tissue segments clearly shows that the plasma membrane beta(1)- and beta(2)-adrenoceptors of rat heart, in contrast to the homogenate binding sites and the mRNA levels, are differently affected by chronic treatment with three beta-adrenoceptor antagonists; up- and down-regulations of beta(1)- and beta(2)-adrenoceptors, respectively, by propranolol, and up-regulation of both the subtypes by atenolol, but no significant change in both the subtypes by bevantolol.

  12. Plasma cytokine concentration changes induced by the antitumor agents dipterinyl calcium pentahydrate (DCP) and related calcium pterins.

    PubMed

    Moheno, Phillip; Pfleiderer, Wolfgang; Fuchs, Dietmar

    2009-01-01

    Analysis of plasma cytokine concentration changes determined that oral dosing with the antitumor agent (1:4 mol:mol) calcium pterin (CaPterin) increased plasma IL-10, decreased plasma IL-6, and decreased plasma IFN-gamma concentrations in nude mice with MDA-MB-231 xenograph tumors [Moheno, P., Pfleiderer, W., Dipasquale, A.G., Rheingold, A.L., Fuchs, D., 2008. Cytokine and IDO metabolite changes effected by calcium pterin during inhibition of MDA-MB-231 xenograph tumors in nude mice. Int. J. Pharm. 355, 238-248]. A further analysis, reported here, of plasma cytokine concentration changes in nude mice with the same tumor xenographs treated with dipterinyl calcium pentahydrate (DCP), (1:2 mol:mol) calcium pterin, and CaCl(2).2H(2)O has been carried out. The measured cytokines included: IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-gamma, and TNF-alpha. The major preliminary findings from the analyses of these data are that (1) the overall relative tumor volumes for the treatments correlated significantly with a full study antitumor plasma cytokine pattern (fsAPCP), a composite measure consisting of decreased plasma IL-6 and increased IL-4 concentrations, and (2) DCP induces a significant threshold antitumor response strongly correlated to a derived DCP antitumor plasma cytokine pattern (DCP/APCP) consisting of plasma IL-12, IL-6, and IL-4 concentration changes. This DCP/APCP composite measure identifies plasma IL-12 concentration increases, plasma IL-6 concentration decreases, and plasma IL-4 concentration increases correlated to relative tumor volume decreases caused by DCP dosing. The finding that the novel calcium pterins and CaCl(2).2H(2)O treatments decrease plasma IL-6 concentrations corroborates the previous finding that CaPterin dosing decreases plasma IL-6 concentrations in this mouse/tumor system [Moheno, P., Pfleiderer, W., Dipasquale, A.G., Rheingold, A.L., Fuchs, D., 2008. Cytokine and IDO metabolite changes effected by calcium pterin during inhibition

  13. Effect of training on blood volume and plasma hormone concentrations in the elderly

    NASA Technical Reports Server (NTRS)

    Carroll, J. F.; Convertino, V. A.; Wood, C. E.; Graves, J. E.; Lowenthal, D. T.; Pollock, M. L.

    1995-01-01

    The purpose of this investigation was to determine the effects of 6 months of endurance training on resting plasma (PV) and blood volume (BV), and resting hormone and electrolyte concentrations in the elderly. Thirty-eight elderly men and women (ages 60-82 yr) were assigned to endurance exercise training (N = 29) or to control (N = 9) groups. Resting plasma levels of adrenocorticotropic hormone, vasopressin, aldosterone, norepinephrine, epinephrine, sodium, potassium, and protein were measured at the start (T1) and end (T2) of 26 wk of training. PV measurement was performed using the Evan's blue dye technique. Endurance training consisted of uphill treadmill walking or stairclimbing exercise 3 times.wk-1, 30-45 min.d-1, at 75-84% of maximal heart rate reserve. The exercise group increased VO2max by 11.2% (P < or = 0.05) and increased resting PV and BV by 11.2% and 12.7% (P < or = 0.05), respectively. Hormone and electrolyte levels in the exercise group remained unchanged; all variables were unchanged in the control group. These results are similar to findings in younger individuals. Because plasma hormone concentrations were maintained despite a chronically elevated BV, endurance training in healthy, elderly subjects may be associated with a resetting of volume receptors.

  14. Measurement of plasma and tissue triiodothyronine concentration in the rat by radioimmunoassay.

    PubMed

    Nejad, I; Bollinger, J; Mitnick, M A; Sullivan, P; Reichlin, S

    1975-03-01

    This paper reports a radioimmunoassay method for triiodothyronine (T3) and the application of this assay to the study of plasma and tissue T3 concentration in the rat. Several antisera formed to a T3-bovine fibrogen complex in guinea pigs and T3-thyroglobulin complex in rabbits are shown to have low or no cross reactivity with T4, monoiodotyrosine, diiodotyrosine, tetraiodothyroacetic acid (TETRAC) and reverse T3. Cross reactivity with T3 derivatives, triiodothyroacetic acid (TRIAC), and triiodothyropropionic (TRIPROP) was variable, some antisera differentiating moderately well and others not at all. An extraction method is described which removes approximately 85% of added 125I-T3 or unlabelled T3 from tissues and in the final step represents 57% of total tissue T3. Mean plasma T3 in 5 normal male rats was 58 plus or minus 6.0 ng/100 ml (SEM), in liver 769 plus or minus 56 ng/100 g, and kidney 627 plus or minus 39 ng/100 g. Tissue to plasma concentration gradients for liver and kidney were 13.3 and 10.8, respectively.

  15. Effect of intravenous lipid emulsion on bupivacaine plasma concentration in humans.

    PubMed

    Litonius, E; Tarkkila, P; Neuvonen, P J; Rosenberg, P H

    2012-06-01

    Intravenous lipid emulsion is the recommended treatment for severe local anaesthetic intoxication. Lipid emulsion may entrap lipid soluble drugs by functioning as a 'lipid sink', but its effect on bupivacaine pharmacokinetics remains unknown. In this randomised, double-blind, crossover study, eight healthy male volunteers were infused bupivacaine 0.5mg.kg(-1) intravenously over 20 min, followed by an infusion of either intravenous lipid emulsion or Hartmann's solution for 30 min. At 20 and 30 min after the start of the infusion, the total plasma bupivacaine concentration was lower while receiving lipid emulsion than Hartmann's solution (mean difference 111 (95% CI 55-167) μg.l(-1) and 75 (95% CI 26-124 μg.l(-1) at 20 and 30 min, respectively; p<0.02). However, there were no differences in un-entrapped (non-lipid bound) or free (non-protein bound) bupivacaine plasma concentrations during the infusion. Intravenous lipid emulsion infusion reduced the context-sensitive half-life of total plasma bupivacaine from 45 (95% CI 32-76)min to 25 (95% CI 20-33)min; p=0.01. We observed no significant adverse effects of lipid emulsion. In conclusion, lipid emulsion may slightly increase the rate of bupivacaine tissue distribution. No 'lipid sink' effect was observed with the non-toxic dose of bupivacaine used.

  16. Removal of low-concentration BTX in air using a combined plasma catalysis system.

    PubMed

    Fan, X; Zhu, T L; Wang, M Y; Li, X M

    2009-06-01

    The behavior of non-thermal plasma (NTP) and combined plasma catalysis (CPC) was investigated for removal of low-concentration benzene, toluene and p-xylene (BTX mixture) in air using a link tooth wheel-cylinder plasma reactor. Combining NTP with MnO(x)/Al(2)O(3) catalyst after the discharge zone (CPC) significantly promoted BTX conversion and improved the energy efficiency. For a specific input energy (SIE) of 10 JL(-1), the conversion of benzene, toluene and p-xylene reached 94%, 97% and 95%, respectively. The introduction of MnO(x)/Al(2)O(3) catalyst also moved the BTX conversion towards total oxidation and reduced the emission of O(3) and NO(2) as compared to NTP alone. For an SIE of 10 JL(-1), the O(3) outlet concentration decreased from 46.7 for NTP alone to 1.9 ppm for CPC, while the NO(2) emission correspondingly decreased from 1380 to 40 ppb.

  17. Higher Plasma S100B Concentrations in Schizophrenia Patients, and Dependently Associated with Inflammatory Markers

    PubMed Central

    Hong, Wu; Zhao, Min; Li, Haozhe; Peng, Fanglan; Wang, Fan; Li, Ningning; Xiang, Hui; Su, Yousong; Huang, Yueqi; Zhang, Shengyu; Zhao, Guoqin; Zhou, Rubai; Mao, Ling; Lin, Zhiguang; Fang, Yiru; Zhang, Qinting; Xie, Bin

    2016-01-01

    Glial damage and immune dysfunction are involved in pathogenesis of schizophrenia. However, interaction between glial damage and immune dysfunction in schizophrenia is undefined. This study aims to compare plasma S100 calcium binding protein (S100B) levels between schizophrenia patients and healthy participants, and to determine if immune markers are independently related with concentration of S100B in schizophrenia patients. Forty-one schizophrenia patients and thirty-three healthy volunteers were enrolled. Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of plasma S100B and inflammatory markers. We found that concentrations of S100B were elevated in schizophrenia patients than healthy participants (p < 0.05), and were negatively related with the severity of symptoms (p = 0.046). Receiver operating characteristic (ROC) curve analysis showed that different S100B levels between schizophrenia and healthy participants can be used as a clinical diagnostic factor (predictive value: 0.666, p = 0.015). Multiple linear regression analysis found that length of illness (Beta = −0.161), plasma levels of inflammatory regulation factors (including TGF-β1, logIL-23 and logIL-10) (Beta = 0.119, 0.475, 0.514) were independently associated with concentrations of S100B (Adjusted R2 = 0.897, p < 0.001). Therefore, our results suggest the possible function of S100B in pathogenesis of schizophrenia, and implicate the important role of autoimmune response and balance to glial dysfunction in patients with schizophrenia. PMID:27279465

  18. Plasma catecholamine concentration during sedation in ventilated patients requiring intensive therapy.

    PubMed

    Kong, K L; Willatts, S M; Prys-Roberts, C; Harvey, J T; Gorman, S

    1990-01-01

    The effects of isoflurane and midazolam sedation on the catecholamine responses of ventilated patients were studied over a 24-h period. Sixty ventilated patients admitted to our intensive therapy unit were allocated randomly to receive either isoflurane or midazolam sedation. Arterial blood samples for plasma catecholamine concentrations were taken at baseline, 6 h after starting sedation and at the end of the study period. Patients sedated with isoflurane showed a progressive reduction in both adrenaline and noradrenaline concentrations during the period of sedation which reached statistical significance for adrenaline at 6 h (p less than 0.02) and at the end of the study (p less than 0.001). Patients sedated with midazolam showed no significant changes of adrenaline or noradrenaline concentrations. Overall, a more satisfactory degree of sedation was achieved with isoflurane.

  19. Concentrations of Methadone in Breast Milk and Plasma in the Immediate Perinatal Period

    PubMed Central

    Jansson, Lauren M.; Choo, Robin E.; Harrow, Cheryl; Velez, Martha; Schroeder, Jennifer R.; Lowe, Ross; Huestis, Marilyn A.

    2009-01-01

    This study evaluates concentrations of methadone in breast milk and plasma among a sample of methadone-maintained women in the immediate perinatal period. Twelve methadone-maintained, lactating women provided blood and breast milk specimens 1, 2, 3, and 4 days after delivery. Specimens were collected at the time of trough (just before methadone dose) and peak (3 hours after dosing) maternal methadone levels. Paired specimens of foremilk (prefeed) and hindmilk (postfeed) were obtained at each sampling time. Although there was a significant increase in methadone concentration in breast milk over time for the peak postfeed sampling time, t(22) = 2.40, P = .0255, methadone concentrations in breast milk were small, ranging from 21 to 314 ng/mL, and were unrelated to maternal methadone dose. Results obtained from this study contribute to the recommendation of breastfeeding for methadone-maintained women regardless of methadone dose. PMID:17478871

  20. The Effect of Topiramate Plasma Concentration on Linguistic Behavior, Verbal Recall and Working Memory

    PubMed Central

    Marino, S.E.; Pakhomov, S.V.S.; Han, S.; Anderson, K.L.; Ding, M.; Eberly, L.E.; Loring, D.W.; Hawkins-Taylor, C.; Rarick, J.O.; Leppik, I.E.; Cibula, J.E.; Birnbaum, A.K.

    2012-01-01

    This is the first study of the effect of topiramate on linguistic behavior and verbal recall using a computational linguistics system for automated language and speech analysis to detect and quantify drug-induced changes in speech recorded during discourse level tasks. Healthy volunteers were administered a single, 100 mg oral dose of topiramate in two double-blind, randomized, placebo-controlled, crossover studies. Subjects’ topiramate plasma levels ranged from 0.23–2.81ug/mL. We found a significant association between topiramate levels and impairment on measures of verbal fluency elicited during a picture description task, correct number of words recalled on a paragraph recall test, and reaction time recorded during a working memory task. Using the tools of clinical pharmacology and computational linguistics, we elucidated the relationship between the determinants of a drug’s disposition as reflected in plasma concentrations and their impact on cognitive functioning as reflected in spoken language discourse. PMID:22658432

  1. Histological changes, rhinoscopical findings and nickel concentration in plasma and urine in retired nickel workers.

    PubMed

    Boysen, M; Solberg, L A; Torjussen, W; Poppe, S; Høgetveit, A C

    1984-01-01

    Histological examination of nasal biopsy specimens, rhinoscopical evaluation and nickel analysis in plasma and urine were performed on 59 retired nickel workers. The histological characteristics were graded according to a numerical classification table. Workers with short employment and short retirement time had a significantly lower mean histological scores than those with long employment and long retirement. Thirteen persons (22%) showed epithelial dysplasia, possibly representing precancerous lesions. Also included in the material were four cases of nasal carcinoma. Presence of hyperplastic/polypoid nasal mucosa was inversely related to the duration of retirement, possibly reflecting gradual regression of the mucosal swelling after termination of the irritation. The nickel concentration in plasma and urine was significantly higher among former roasting/smelting workers than in former electrolysis and non-process workers. This is probably a consequence of the slow release of heavy soluble nickel compounds that have accumulated in the organism at the former place of work. PMID:6689819

  2. Histological changes, rhinoscopical findings and nickel concentration in plasma and urine in retired nickel workers.

    PubMed

    Boysen, M; Solberg, L A; Torjussen, W; Poppe, S; Høgetveit, A C

    1984-01-01

    Histological examination of nasal biopsy specimens, rhinoscopical evaluation and nickel analysis in plasma and urine were performed on 59 retired nickel workers. The histological characteristics were graded according to a numerical classification table. Workers with short employment and short retirement time had a significantly lower mean histological scores than those with long employment and long retirement. Thirteen persons (22%) showed epithelial dysplasia, possibly representing precancerous lesions. Also included in the material were four cases of nasal carcinoma. Presence of hyperplastic/polypoid nasal mucosa was inversely related to the duration of retirement, possibly reflecting gradual regression of the mucosal swelling after termination of the irritation. The nickel concentration in plasma and urine was significantly higher among former roasting/smelting workers than in former electrolysis and non-process workers. This is probably a consequence of the slow release of heavy soluble nickel compounds that have accumulated in the organism at the former place of work.

  3. 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

  4. Plasma Amino Acid Concentrations Predict Mortality in Patients with End-Stage Liver Disease

    PubMed Central

    Kinny-Köster, Benedict; Bartels, Michael; Becker, Susen; Scholz, Markus; Thiery, Joachim

    2016-01-01

    Background The liver plays a key role in amino acid metabolism. In former studies, a ratio between branched-chain and aromatic amino acids (Fischer’s ratio) revealed associations with hepatic encephalopathy. Furthermore, low concentrations of branched-chain amino acids were linked to sarcopenia in literature. Encephalopathy and sarcopenia are known to dramatically worsen the prognosis. Aim of this study was to investigate a complex panel of plasma amino acids in the context of mortality in patients with end-stage liver disease. Methods 166 patients evaluated for orthotopic liver transplantation were included. 19 amino acids were measured from citrated plasma samples using mass spectrometry. We performed survival analysis for plasma amino acid constellations and examined the relationship to established mortality predictors. Results 33/166 (19.9%) patients died during follow-up. Lower values of valine (p<0.001), Fischer’s ratio (p<0.001) and valine to phenylalanine ratio (p<0.001) and higher values of phenylalanine (p<0.05) and tyrosine (p<0.05) were significantly associated with mortality. When divided in three groups, the tertiles discriminated cumulative survival for valine (p = 0.016), phenylalanine (p = 0.024) and in particular for valine to phenylalanine ratio (p = 0.003) and Fischer’s ratio (p = 0.005). Parameters were also significantly correlated with MELD and MELD-Na score. Conclusions Amino acids in plasma are valuable biomarkers to determine increased risk of mortality in patients with end-stage liver disease. In particular, valine concentrations and constellations composed of branched-chain and aromatic amino acids were strongly associated with prognosis. Due to their pathophysiological importance, the identified amino acids could be used to examine individual dietary recommendations to serve as potential therapeutic targets. PMID:27410482

  5. Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response.

    PubMed

    Mauri, Massimo C; Volonteri, Lucia S; Colasanti, Alessandro; Fiorentini, Alessio; De Gaspari, Ilaria F; Bareggi, Silvio R

    2007-01-01

    In the past, the information about the dose-clinical effectiveness of typical antipsychotics was not complete and this led to the risk of extrapyramidal adverse effects. This, together with the intention of improving patients' quality of life and therapeutic compliance, resulted in the development of atypical or second-generation antipsychotics (SGAs). This review will concentrate on the pharmacokinetics and metabolism of clozapine, risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole and sertindole, and will discuss the main aspects of their pharmacodynamics. In psychopharmacology, therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding adverse effects by keeping long-term exposure to the minimal effective blood concentration. The rationale for using therapeutic drug monitoring in relation to SGAs is still a matter of debate, but there is growing evidence that it can improve efficacy, especially when patients do not respond to therapeutic doses or when they develop adverse effects. Here, we review the literature concerning the relationships between plasma concentrations of SGAs and clinical responses by dividing the studies on the basis of the length of their observation periods. Studies with clozapine evidenced a positive relationship between plasma concentrations and clinical response, with a threshold of 350-420 ng/mL associated with good clinical response. The usefulness of therapeutic drug monitoring is well established because high plasma concentrations of clozapine can increase the risk of epileptic seizures. Plasma clozapine concentrations seem to be influenced by many factors such as altered cytochrome P450 1A4 activity, age, sex and smoking. The pharmacological effects of risperidone depend on the sum of the plasma concentrations of risperidone and its 9-hydroxyrisperidone metabolite, so monitoring the plasma concentrations of the parent compound alone can lead to erroneous

  6. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24975958

  8. 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.

  9. Experience of stress in childhood negatively correlates with plasma oxytocin concentration in adult men.

    PubMed

    Opacka-Juffry, Jolanta; Mohiyeddini, Changiz

    2012-01-01

    Early life experience is known to affect responses to stress in adulthood. Adverse experience in childhood and/or adolescence sensitises to life events that precipitate depression in later life. Published evidence suggests a relationship between depression and oxytocin (OT), but the extent to which early life experience influences OT disposition in adulthood deserves further exploration. This study hypothesised that early life stress (ELS) has a long-term negative effect on OT system activity. The study was performed on 90 male volunteers (18-56 years; mean ± standard deviation = 27.7 ± 7.09 years). Several questionnaires were used to assess: health, early life stressful experiences in childhood (ELS-C, up to 12 years) and early life stressful adolescence (13-18 years), recent stressful life events, depressive symptoms, state-trait anxiety and social desirability. Plasma OT concentration was estimated by means of a competitive enzyme immunoassay. Lower OT concentrations were significantly associated with higher levels of ELS-C (p < 0.01), and with depressive symptoms and trait anxiety (both p < 0.05). The interaction between ELS-C and trait anxiety was significant (p < 0.05), indicating that the link between ELS-C and plasma OT concentration is moderated by trait anxiety. These results contribute to the evidence that early life adverse experience is negatively associated with OT system activity in adulthood, and offer further insight into mediator and moderator effects on this link.

  10. 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.

  11. 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.

  12. 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.

  13. Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract.

    PubMed

    Wen, Zhiming; Dumas, Todd E; Schrieber, Sarah J; Hawke, Roy L; Fried, Michael W; Smith, Philip C

    2008-01-01

    Silymarin, a mixture of polyphenolic flavonoids extracted from milk thistle (Silybum marianum), is composed mainly of silychristin, silydianin, silybin A, silybin B (SB(B)), isosilybin A (ISB(A)), and isosilybin B. In this study, the plasma concentrations of free (unconjugated), conjugated (sulfated and glucuronidated), and total (free and conjugated) silymarin flavonolignans were measured using liquid chromatography-electrospray ionization-mass spectrometry, after a single oral dose of 600 mg of standardized milk thistle extracts to three healthy volunteers. Pharmacokinetic analysis indicated that silymarin flavonolignans were rapidly eliminated with short half-lives (1-3 and 3-8 h for free and conjugated, respectively). The AUC(0-->infinity) values of the conjugated silymarin flavonolignans were 4- to 30-fold higher than those of their free fractions, with SB(B) (mean AUC(0-->infinity) = 51 and 597 microg x h/l for free and conjugated, respectively) and ISB(A) (mean AUC(0-->infinity) = 30 and 734 microg x h/l for free and conjugated, respectively) exhibiting higher AUC(0-->infinity) values in comparison with other flavonolignans. Near the plasma peak times (1-3 h), the free, sulfated, and glucuronidated flavonolignans represented approximately 17, 28, and 55% of the total silymarin, respectively. In addition, the individual silymarin flavonolignans exhibited quite different plasma profiles for both the free and conjugated fractions. These data suggest that, after oral administration, silymarin flavonolignans are quickly metabolized to their conjugates, primarily forming glucuronides, and the conjugates are primary components present in human plasma.

  14. Plasma prolactin, growth hormone and progesterone concentrations in pseudopregnant, hysterectomized and pregnant goats.

    PubMed

    Kornalijnslijper, J E; Kemp, B; Bevers, M M; van Oord, H A; Taverne, M A

    1997-12-01

    Jugular plasma prolactin (PRL), growth hormone (GH) and progesterone (P4) levels were estimated in goats under three different conditions with prolonged luteal function (P4 > or = 1 ng/ml): pseudopregnant animals (n = 4), goats hysterectomized during early pregnancy (n = 4) and does with normal pregnancy (n = 4). Mean duration (+/- S.E.M.) of luteal phases were 189 +/- 20, 171 +/- 10, and 147 +/- 2 days in the three groups, respectively. Until day 120, mean PRL levels were below 150 ng/ml in each group. After day 120 of the luteal phase, PRL concentrations were significantly higher than before, but continued to increase up to 800 ng/ml only in pregnant animals around parturition. Mean GH levels varied between 2 and 3 ng/ml in animals of each group during the luteal phase. Only after parturition, a significant elevation occurred. P4 levels in pseudopregnant animals were significantly lower than in the other two groups between days 10 and 55, and showed a gradual but continuous decline towards the end of the luteal phase. After hysterectomy of early pregnant animals, P4 concentrations decreased to levels measured in pseudopregnant animals but were significantly higher again as compared to pseudopregnant animals between days 121 and 150. It is concluded that a pseudopregnant condition, characterized by intrauterine fluid accumulation, is not related to increased plasma PRL and GH concentrations. The low and gradually decreasing plasma progesterone levels in the pseudopregnant animals probably reflect the absence of a luteotrophic stimulus by the conceptus. The progesterone profile in the animals that were hysterectomized during early pregnancy suggests that the corpora lutea of these does have been permanently changed by the presence of the conceptus during the first weeks of the luteal phase. PMID:9505110

  15. 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.

  16. Manifestation of cryptic fibroblast tissue factor occurs at detergent concentrations which dissolve the plasma membrane.

    PubMed

    Carson, S D

    1996-04-01

    Cultured fibroblasts treated with increasing concentrations of detergents expressed only encrypted levels of tissue factor activity (measured by fX activation in the presence of fVIIa), characteristic of undamaged cells, until each detergent reached a critical concentration at which the cryptic tissue factor activity was manifested. Beyond the narrow ranges of concentrations over which the detergents stimulated tissue factor activity, the detergents were inhibitory. Studies with Triton X-100 and octyl glucoside revealed that manifestation of tissue factor activity coincided with breakdown of the plasma membrane. The magnitude of the increased tissue factor activity differed among detergents, with octyl glucoside giving the largest response. The tissue factor that was active after Triton X-100 treatment remained mostly associated with the insoluble cell residue, whereas the concentration of octyl glucoside which stimulated activity released tissue factor activity into the supernatant. Radiolabeled antibody against human tissue factor was used to show that a small percentage of the total accessible tissue factor remained in the insoluble fraction after treatment with either non-ionic detergent. Chromatographic analysis of lipids extracted from cells treated with detergents and dansyl chloride showed dansyl-reactivity of phosphatidylserine on intact cells, and solubilization of membrane lipids at sublytic concentrations of detergents. These findings reveal that there is a critical level of detergent-induced membrane damage at which tissue factor activity is maximally expressed, in essentially an all-or-none manner. The results are consistent with a major role for phospholipid asymmetry in regulation of tissue factor specific activity, but require either maintenance of asymmetry during sublytic detergent perturbation of the plasma membrane or additional control mechanisms.

  17. Comprehensive Profiling of Plasma Fatty Acid Concentrations in Young Healthy Canadian Adults

    PubMed Central

    Abdelmagid, Salma A.; Clarke, Shannon E.; Nielsen, Daiva E.; Badawi, Alaa; El-Sohemy, Ahmed; Mutch, David M.; Ma, David W. L.

    2015-01-01

    Circulating fatty acids (FA) are associated with a multitude of chronic diseases. However, a major gap in establishing such relationships is the lack of accepted fatty acid reference ranges representing healthy individuals. Data on validated FA reference ranges would provide a better understanding of study baseline measures and aid in the evaluation and interpretation of pharmaceutical or dietary interventions. Reference ranges for plasma FA levels have been reported in a few small studies and on a limited number of FA. Therefore, we determined the average and percentiles of a broad set of 61 FA (C14 - C24:1) from plasma total lipids from an ethnically diverse population of healthy young Canadian males and females (Total n = 826). Plasma concentrations of some of the major FA ranged from 0.3 to 4.1 mmol/L for palmitic acid, 0.1 to 1.0 mmol/L for stearic acid, 0.03 to 3.2 mmol/L for oleic acid, 0.2 to 5.0 mmol/L for linoleic acid (LA), 12.0 to 186.9 μmol/L for α-linolenic acid, and 7.2 to 237.5 μmol/L for docosahexaenoic acid (DHA). Males had significantly higher plasma concentrations of γ-linolenic acid (GLA) and n-3 docosapentaenoic acid and lower concentrations of palmitoleic acid, LA and DHA than females. Comparison of FA concentrations between Caucasians, East Asians and South Asians revealed that South Asians had significantly lower levels of palmitoleic acid (p < 0.01) and oleic acid (p = 0.01) while East Asians had lower levels of GLA (p = 0.02) and dihomo-γ-linolenic acid (p = 0.03). Overall, these data provide a comprehensive set of quantitative values that profiles a small cohort of Canadians which highlights the utility of establishing validated FA reference ranges that may be used to understand how deficient, suboptimal, or excess amounts of a given FA may be associated with chronic disease. PMID:25675440

  18. [Isolation, extractive concentration, and determination of caffeine in the studies of blood plasma].

    PubMed

    Korenman, Ia I; Shormanov, V K; Mokshina, N Ia; Krivosheeva, O A; Golubitskiĭ, G B

    2012-01-01

    The optimal conditions for the isolation of caffeine from human blood by means of acetone extraction are described with special reference to the peculiarities of extraction from aqueous solutions. The possibility of concentration and purification of caffeine from blood plasma using acetone and aceton-chlorophorm mixture (2:8) as the solvents is illustrated. In addition, purification by silica-gel thin layer chromatography is discussed. Thin layer chromatography, UV-spectrophotometry, and high performance liquid chromatography are considered as potential methods for the identification and quantitative determination of caffeine.

  19. Therapeutic drug monitoring of cerebrospinal fluid vancomycin concentration during intraventricular administration.

    PubMed

    Popa, D; Loewenstein, L; Lam, S W; Neuner, E A; Ahrens, C L; Bhimraj, A

    2016-02-01

    Limited data are available on intraventricular vancomycin dosing for meningitis. This study explored clinical characteristics that correlated with cerebrospinal fluid (CSF) concentrations. Over a nine-year period, 13 patients with 34 CSF vancomycin concentrations were evaluated. CSF output and time from dose correlated with CSF vancomycin concentration. No relationship was seen with regards to CSF protein, white blood cell count or glucose.

  20. Concentrations of oestradiol-17 beta in plasma and milk and progesterone in plasma during the oestrus cycle and in early pregnancy in goats.

    PubMed

    Abeyawardene, S A; Pope, G S

    1990-01-01

    Pre-ovulatory peaks in oestradiol-17 beta concentrations were observed on days 1 or 2 and post-ovulatory peaks between days 4 and 7, both in jugular venous plasma and defatted milk, day 1 being the day of the onset of oestrus in the goats. Mean values of the magnitudes of these concentration peaks and of their timing (relative to oestrus) during the oestrus cycle did not differ significantly (P greater than 0.05) from those when the goats were mated and became pregnant. Pre-ovulatory oestradiol-17 beta peaks were invariably greater than the corresponding post-ovulatory peaks, as were peak concentrations in plasma relative to those in defatted milk collected on the same day. Mean intervals between the pre- and post-ovulatory peaks in oestradiol-17 beta concentrations were respectively 4.2 days for plasma and 4.0 days for defatted milk. Concentrations of oestradiol-17 beta in jugular venous plasma and defatted milk were strongly correlated: rank correlation coefficients for the three goats studied were 0.871, 0.668 and 0.739. It is suggested that in goats, as in cattle, ovarian follicular oestradiol-17 beta secretion approaching pre-ovulatory level is restored by 4 days after oestrus and its rapid decline after this time may be due to the inhibitory influence of the rapidly rising plasma progesterone concentration. PMID:2331587

  1. Spectroscopic measurements of temperature and plasma impurity concentration during magnetic reconnection at the Swarthmore Spheromak Experiment

    SciTech Connect

    Chaplin, V. H.; Brown, M. R.; Cohen, D. H.; Gray, T.; Cothran, C. D.

    2009-04-15

    Electron temperature measurements during counterhelicity spheromak merging studies at the Swarthmore Spheromak Experiment (SSX) [M. R. Brown, Phys. Plasmas 6, 1717 (1999)] are presented. VUV monochromator measurements of impurity emission lines are compared with model spectra produced by the non-LTE excitation kinematics code PRISMSPECT[J. J. MacFarlane et al., in Proceedings of the Third Conference on Inertial Fusion Science and Applications (2004)] to yield the electron temperature in the plasma with 1 {mu}s time resolution. Average T{sub e} is seen to increase from 12 to 19 eV during spheromak merging. Average C III ion temperature, measured with a new ion Doppler spectrometer (IDS) [C. D. Cothran et al., Rev. Sci. Instrum. 77, 063504 (2006)], likewise rises during spheromak merging, peaking at {approx}22 eV, but a similar increase in T{sub i} is seen during single spheromak discharges with no merging. The VUV emission line measurements are also used to constrain the concentrations of various impurities in the SSX plasma, which are dominated by carbon, but include some oxygen and nitrogen. A burst of soft x-ray emission is seen during reconnection with a new four-channel detector (SXR). There is evidence for spectral changes in the soft x-ray emission as reconnection progresses, although our single-temperature equilibrium spectral models are not able to provide adequate fits to all the SXR data.

  2. 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.

  3. Plasma mitomycin C concentrations determined by HPLC coupled to solid-phase extraction.

    PubMed

    Paroni, R; Arcelloni, C; De Vecchi, E; Fermo, I; Mauri, D; Colombo, R

    1997-04-01

    The aim of this study was to set up a method for quantification of plasma mitomycin C (MMC) concentrations during intravesical chemotherapy delivered in the presence of local bladder hyperthermia (HT). In comparison with existing methods, this assay, characterized by relative simplicity and efficiency, resulted in the facilitation of performance with nondedicated instrumentation or nonspecialized staff. Purification from plasma matrix was carried out by solid-phase extraction under vaccuum. The purified drug was then collected directly into the vials of the HPLC autosampler. Chromatographic analysis was performed on a reversed-phase C18 column with water:acetonitrile (85:15 by vol) as the mobile phase and the UV detector set at 365 nm. The use of porfiromycin as internal standard provided a method with good within-day precision (CV 6.0% at 5 micrograms/L, n = 6), linearity (0.5-50 micrograms/L), and specificity. The lower limit of detection (< or = 0.5 microgram/L) proved to be suitable for plasma pharmacokinetics monitoring in two tested patients treated with MMC + HT for superficial bladder cancer. PMID:9105262

  4. Dietary fat type and energy restriction interactively influence plasma leptin concentration in rats.

    PubMed

    Cha, M C; Jones, P J

    1998-08-01

    To investigate whether dietary fat source and energy restriction interactively influence plasma leptin levels and its association of leptin with insulin action, rats were fed diets containing either fish, safflower oil, or beef tallow (20% wt/wt) for 10 weeks. Groups of rats consumed each diet ad libitum or at 85% or 70% of ad libitum energy intake in a design that held fat intake constant. Graded levels of energy restriction caused body weight to decrease (P < 0.001) differently according to the dietary fat provided. Plasma leptin concentrations were 60% higher (P < 0.05) in the groups fed fish oil and safflower oil ad libitum compared with those in the beef tallow group, despite smaller perirenal fat mass and fat cell size in the fish oil-fed animals. Energy restriction resulted in a 62% decrease (P < 0.05) in leptin levels in fish oil- and safflower oil-fed rats, whereas no changes were observed in beef tallow-fed animals. Plasma insulin levels were lower (P < 0.05) in the fish oil group fed ad libitum compared with those in the two other diet groups. These data demonstrate a hyperleptinemic effect in animals consuming diets rich in polyunsaturated fatty acid, which can be normalized to the level of saturated fat consumption by mild energy restriction. Thus, dietary fatty acid composition, independent of adipose tissue mass, is an important determinant of circulating leptin level in diet-induced obesity.

  5. A prospective study of plasma 25-hydroxyvitamin D concentration and prostate cancer risk.

    PubMed

    Deschasaux, Mélanie; Souberbielle, Jean-Claude; Latino-Martel, Paule; Sutton, Angela; Charnaux, Nathalie; Druesne-Pecollo, Nathalie; Galan, Pilar; Hercberg, Serge; Le Clerc, Sigrid; Kesse-Guyot, Emmanuelle; Ezzedine, Khaled; Touvier, Mathilde

    2016-01-28

    Mechanistic hypotheses suggest that vitamin D and the closely related parathyroid hormone (PTH) may be involved in prostate carcinogenesis. However, epidemiological evidence is lacking for PTH and inconsistent for vitamin D. Our objectives were to prospectively investigate the association between vitamin D status, vitamin D-related gene polymorphisms, PTH and prostate cancer risk. A total of 129 cases diagnosed within the Supplémentation en Vitamines et Minéraux Antioxydants cohort were included in a nested case-control study and matched to 167 controls (13 years of follow-up). 25-Hydroxyvitamin D (25(OH)D) and PTH concentrations were assessed from baseline plasma samples. Conditional logistic regression models were computed. Higher 25(OH)D concentration was associated with decreased risk of prostate cancer (ORQ4 v. Q1 0·30; 95 % CI 0·12, 0·77; P trend=0·007). PTH concentration was not associated with prostate cancer risk (P trend=0·4) neither did the studied vitamin D-related gene polymorphisms. In this prospective study, prostate cancer risk was inversely associated with 25(OH)D concentration but not with PTH concentration. These results bring a new contribution to the understanding of the relationship between vitamin D and prostate cancer, which deserves further investigation. PMID:26568368

  6. Plasma 24,25-dihydroxyvitamin D concentration of Dahl salt-sensitive rats decreases during high salt intake

    NASA Technical Reports Server (NTRS)

    Thierry-Palmer, Myrtle; Tewolde, Teclemicael K.; Forte, Camille; Wang, Min; Bayorh, Mohamed A.; Emmett, Nerimiah L.; White, Jolanda; Griffin, Keri

    2002-01-01

    Dahl salt-sensitive rats, but not salt-resistant rats, develop hypertension in response to high salt intake. We have previously shown an inverse relationship between plasma 25-hydroxyvitamin D (25-OHD) concentration and blood pressure of Dahl salt-sensitive rats during high salt intake. In this study, we report on the relationship between high salt intake and plasma 24,25-dihydroxyvitamin D (24,25-(OH)(2)D) concentration of Dahl salt-sensitive and salt-resistant rats. Rats were fed a high salt diet (8%) and sacrificed at day 2, 7, 14, 21, and 28. Plasma 24,25-(OH)(2)D concentrations of salt-sensitive rats were reduced to 50% of that at baseline at day 2-when blood pressure and plasma 25-OHD concentration were unchanged, but 25-OHD content in the kidney was 81% of that at baseline. Plasma 24,25-(OH)(2)D concentration was reduced further to 10% of that at baseline from day 7 to 14 of high salt intake, a reduction that was prevented in rats switched to a low salt (0.3%) diet at day 7. Exogenous 24,25-dihydroxycholecalciferol (24,25-(OH)(2)D(3)), administered at a level that increased plasma 24,25-(OH)(2)D concentration to five times normal, did not attenuate the salt-induced hypertension of salt-sensitive rats. Plasma 24,25-(OH)(2)D concentration of salt-resistant rats was gradually reduced to 50% of that at baseline at day 14 and returned to baseline value at day 28 of high salt intake. We conclude that the decrease in plasma 24,25-(OH)(2)D concentration in salt-sensitive rats during high salt intake is caused by decreased 25-OHD content in the kidney and also by another unidentified mechanism.

  7. Pharmacokinetics of oritavancin in plasma and skin blister fluid following administration of a 200-milligram dose for 3 days or a single 800-milligram dose.

    PubMed

    Fetterly, Gerald J; Ong, Christine M; Bhavnani, Sujata M; Loutit, Jeffrey S; Porter, Steven B; Morello, Lisa G; Ambrose, Paul G; Nicolau, David P

    2005-01-01

    Oritavancin is a novel glycopeptide currently being developed for the treatment of complicated skin and skin structure infections (cSSSI), including those caused by multidrug resistant gram-positive pathogens. The disposition of oritavancin in skin structures was investigated using a cantharide-induced blister fluid model. Seventeen healthy male subjects received oritavancin, but only 16 subjects were evaluated after one subject discontinued study drug. Each subject (eight per dose group) received 200 mg of oritavancin once a day for 3 days (group A) or 800 mg as one single dose (group B). Group A plasma samples and exudates from blister fluid were collected on days 3, 4, 7, 9, and 12 and on days 3, 4, 7, and 9, respectively. Group B samples and exudates were collected on days 1, 2, 5, 7, and 10 and on days 1, 2, 5, and 7, respectively. Drug concentrations were determined using a liquid chromatography-tandem mass spectrometry assay and, subsequently, pharmacokinetic analysis was performed. Differences between treatment groups in ratios for area under the concentration-time curve for blister fluid and plasma (AUC(blister fluid)/AUC(plasma) ratios) were evaluated using a t test (alpha = 0.05). Mean maximum concentration of drug in plasma or blister fluid was approximately 8-fold and 11-fold higher in plasma than in blister fluid following the 200- or 800-mg doses of oritavancin, respectively. Mean AUC(blister fluid)/AUC(plasma) ratios at 24 h were 0.190 (standard deviation [SD], 0.052) and 0.182 (SD, 0.062) for groups A and B, respectively (P = 0.791). To place these results in a clinical context, mean drug concentrations in blister fluid exceed the oritavancin MIC at which 90% of strains are inhibited of Staphylococcus aureus (2 microg/ml) by approximately 2- to 5.5-fold at 12 h and 1.5- to 3-fold at 24 h following administration of both dosing regimens. These results support the potential use of oritavancin for the treatment of cSSSI.

  8. Effect of the excipient concentration on the pharmacokinetics of PM181104, a novel antimicrobial thiazolyl cyclic peptide antibiotic, following intravenous administration to mice

    PubMed Central

    Yemparala, Vijayaphanikumar; Damre, Anagha A.; Manohar, Venkat; Sharan Singh, Kishori; Mahajan, Girish B.; Sawant, Satish N.; Deokule, Tanaji; Sivaramakrishnan, H.

    2014-01-01

    Thiazolyl cyclic peptide antibiotics are known for their poor aqueous solubility and unfavorable pharmacokinetics (PK) and hence pose challenging tasks in developing these antibiotics as clinical candidates. In the current paper, we report a possible way to address these challenges with exemplification of our antibiotic PM181104. The approach was to prepare formulations with known excipients, Polysorbate 80 (Tween 80, T-80) and PEG 400 through their varied stiochiometric combination in appropriate ratio to achieve acceptable osmolarity, pH and particle size of the formulation. Two different sets of formulations were prepared with two distinct average particle diameters ranging from 32.8 to 465.4 nm. First, semi-transparent solutions with a particle size of >100 nm were achieved by keeping concentration of PEG 400 constant at 8% (w/v) and decreasing the amounts of T-80. Second, clear colorless solutions with a particle size of <100 nm were achieved by keeping concentration of T-80 constant at 8% (w/v) and decreasing the amounts of PEG 400. In PK studies, intravenous administration of formulation with particle size <100 nm to mice resulted in a two-fold increase in area under the plasma concentration-time curve (AUClast) and concentration at time zero (C0), there by facilitating the selection of suitable formulation for further efficacy studies. PMID:25756005

  9. Effect of the excipient concentration on the pharmacokinetics of PM181104, a novel antimicrobial thiazolyl cyclic peptide antibiotic, following intravenous administration to mice.

    PubMed

    Yemparala, Vijayaphanikumar; Damre, Anagha A; Manohar, Venkat; Sharan Singh, Kishori; Mahajan, Girish B; Sawant, Satish N; Deokule, Tanaji; Sivaramakrishnan, H

    2014-01-01

    Thiazolyl cyclic peptide antibiotics are known for their poor aqueous solubility and unfavorable pharmacokinetics (PK) and hence pose challenging tasks in developing these antibiotics as clinical candidates. In the current paper, we report a possible way to address these challenges with exemplification of our antibiotic PM181104. The approach was to prepare formulations with known excipients, Polysorbate 80 (Tween 80, T-80) and PEG 400 through their varied stiochiometric combination in appropriate ratio to achieve acceptable osmolarity, pH and particle size of the formulation. Two different sets of formulations were prepared with two distinct average particle diameters ranging from 32.8 to 465.4 nm. First, semi-transparent solutions with a particle size of >100 nm were achieved by keeping concentration of PEG 400 constant at 8% (w/v) and decreasing the amounts of T-80. Second, clear colorless solutions with a particle size of <100 nm were achieved by keeping concentration of T-80 constant at 8% (w/v) and decreasing the amounts of PEG 400. In PK studies, intravenous administration of formulation with particle size <100 nm to mice resulted in a two-fold increase in area under the plasma concentration-time curve (AUClast) and concentration at time zero (C 0), there by facilitating the selection of suitable formulation for further efficacy studies.

  10. 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.

  11. Midlife plasma vitamin D concentrations and performance in different cognitive domains assessed 13 years later.

    PubMed

    Assmann, Karen E; Touvier, Mathilde; Andreeva, Valentina A; Deschasaux, Mélanie; Constans, Thierry; Hercberg, Serge; Galan, Pilar; Kesse-Guyot, Emmanuelle

    2015-05-28

    25-Hydroxyvitamin D (25(OH)D) insufficiency is very common in many countries. Yet, the extent to which 25(OH)D status affects cognitive performance remains unclear. The objective of the present study was to evaluate the cross-time association between midlife plasma 25(OH)D concentrations and subsequent cognitive performance, using a subsample from the French 'SUpplémentation en Vitamines et Minéraux AntioXydants' randomised trial (SU.VI.MAX, 1994-2002) and the SU.VI.MAX 2 observational follow-up study (2007-9). 25(OH)D concentrations were measured in plasma samples drawn in 1994-5, using an electrochemoluminescent immunoassay. Cognitive performance was evaluated in 2007-9 with a neuropsychological battery including phonemic and semantic fluency tasks, the RI-48 (rappel indicé-48 items) cued recall test, the Trail Making Test and the forward and backward digit span. Cognitive factors were extracted via principal component analysis (PCA). Data from 1009 individuals, aged 45-60 years at baseline, with available 25(OH)D and cognitive measurements were analysed by multivariable linear regression models and ANCOVA, stratified by educational level. PCA yielded two factors, designated as 'verbal memory' (strongly correlated with the RI-48 and phonemic/semantic fluency tasks) and 'short-term/working memory' (strongly correlated with the digit span tasks). In the fully adjusted regression model, among individuals with low education, there was a positive association between 25(OH)D concentrations and the 'short-term/working memory' factor (P=0.02), mainly driven by the backward digit span (P=0.004). No association with either cognitive factor was found among better educated participants. In conclusion, higher midlife 25(OH)D concentrations were linked to better outcomes concerning short-term and working memory. However, these results were specific to subjects with low education, suggesting a modifying effect of cognitive reserve. PMID:25864611

  12. Risk Factors for a Low Linezolid Trough Plasma Concentration in Acute Infections

    PubMed Central

    Morata, Laura; Cuesta, Marta; Rojas, Jhon F.; Rodriguez, Sebastian; Brunet, Merce; Casals, Gregori; Cobos, Nazareth; Hernandez, Cristina; Martínez, José A.; Mensa, Josep

    2013-01-01

    Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (Cmin) and to determine factors associated with a Cmin < 2 mg/liter and other clinically relevant thresholds. Characteristics of 78 patients receiving 600 mg/12 h of linezolid with a Cmin determination at the steady state and within the first 10 days of treatment were retrospectively reviewed. Concentrations were measured using high-pressure liquid chromatography. Univariate and multivariate analysis were performed to identify risk factors of low Cmin. A total of 29.5% of patients had a Cmin < 2 mg/liter. The percentage was significantly higher in patients with an estimated glomerular filtration (eGF) > 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of Cmin < 2 mg/liter were an eGF > 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P = 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P = 0.006). A linezolid Cmin of <2 mg/liter was found in 29.5% of cases, and the risk was significantly higher among those with an eGF > 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy. PMID:23403416

  13. Nasal midazolam in children, plasma concentrations and the effect on respiration.

    PubMed

    Fösel, T; Hack, C; Knoll, R; Kraus, G B; Larsen, R

    1995-01-01

    Twenty ASA 1 children, one to six years old, weighing 10-20 kg, scheduled for a combination of general and caudal anaesthesia received at random midazolam 0.2, 0.4, or 0.6 mg.kg-1 or NaCl 0.9% (control group) intranasally. Drug or NaCl 0.9% were administered in one nostril, after inhalation induction of anaesthesia, intubation without relaxant and caudal anaesthesia. Spontaneous respiration was via a circle system and fresh gas flow of 6 l.min-1 (N2O/O2 = 2:1), PEEP 5 cm H2O, endtidal halothane 0.4%. Immediately before and 2, 5, 8, 12, 16, 20, 30, 60 and 120 min after application of the drug 2.5 ml blood was sampled for plasma levels of midazolam. Endtidal CO2, respiratory rate, and oxygen saturation were recorded as long as the children were intubated. Endtidal CO2 and respiratory rate showed no statistical difference between the groups at any time, however, in the group receiving 0.6 mg.kg-1, endtidal CO2 increased significantly from 5.3 kPa (41 mm Hg) at the start to 5.9 kPa (45.5 mm Hg) after 30 min. Plasma levels of midazolam were detected 2 min after application in 10 of 15 patients. Median peak levels were found between 12 and 16 min. Medians of peak plasma levels showed no statistical difference between the three groups (0.2 mg.kg-1:111 ng.ml-1, 0.4 mg.kg-1:136 ng.ml-1, 0.6 mg.kg-1:277 ng.ml-1). After 30, 60 and 120 min medians of midazolam plasma concentration were significantly higher in the group 0.6 mg.kg-1.

  14. Fasting plasma carotenoids concentrations in Crohn's and pancreatic cancer patients compared to control subjects.

    PubMed

    Drai, J; Borel, P; Faure, H; Galabert, C; Le Moël, G; Laromiguière, M; Fayol, V

    2009-03-01

    Carotenoids are colored molecules that are widespread in the plant kingdom, but animals cannot synthesize them. Carotenes are long, apolar molecules which require fully functioning digestive processes to be absorbed properly. Hence they could be interesting markers of intestinal absorption and digestion. Indeed, only few tests are available to assess these processes and only the D-xylose tolerance test is routinely used. However D-xylose is a sugar that tests only the absorption of water-soluble compounds and it only tests duodenal absorption. In this study, we have evaluated carotenoids as markers of digestion and absorption. We compared fasting plasma carotenoids concentrations in 21 control subjects, 20 patients with Crohn's disease, and 18 patients with pancreatic cancer. Crohn's disease alters intestinal absorption while pancreatic cancer decreases pancreatic enzyme secretion thus impairing digestion. Results show that all carotenoids are significantly lower in Crohn's and cancer patients as compared to control subjects and the multifactorial analysis shows that this decrease is mostly independent of dietary intake. Interestingly, maldigestion as seen in pancreatic cancer more strongly influences plasma lutein and lycopene concentrations while malabsorption in Crohn's disease acts on other carotenoids. Thus carotenoids could be interesting alternatives for testing and following patients that are suspected of having malabsorption or maldigestion syndromes. PMID:20108210

  15. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

    PubMed

    Chambers, John C; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Van der Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E; Coin, Lachlan J; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L; Hottenga, Jouke-Jan; Kühnel, Brigitte; Kumar, Vinod; Lagou, Vasiliki; Liang, Liming; Luan, Jian'an; Vidal, Pedro Marques; Mateo Leach, Irene; O'Reilly, Paul F; Peden, John F; Rahmioglu, Nilufer; Soininen, Pasi; Speliotes, Elizabeth K; Yuan, Xin; Thorleifsson, Gudmar; Alizadeh, Behrooz Z; Atwood, Larry D; Borecki, Ingrid B; Brown, Morris J; Charoen, Pimphen; Cucca, Francesco; Das, Debashish; de Geus, Eco J C; Dixon, Anna L; Döring, Angela; Ehret, Georg; Eyjolfsson, Gudmundur I; Farrall, Martin; Forouhi, Nita G; Friedrich, Nele; Goessling, Wolfram; Gudbjartsson, Daniel F; Harris, Tamara B; Hartikainen, Anna-Liisa; Heath, Simon; Hirschfield, Gideon M; Hofman, Albert; Homuth, Georg; Hyppönen, Elina; Janssen, Harry L A; Johnson, Toby; Kangas, Antti J; Kema, Ido P; Kühn, Jens P; Lai, Sandra; Lathrop, Mark; Lerch, Markus M; Li, Yun; Liang, T Jake; Lin, Jing-Ping; Loos, Ruth J F; Martin, Nicholas G; Moffatt, Miriam F; Montgomery, Grant W; Munroe, Patricia B; Musunuru, Kiran; Nakamura, Yusuke; O'Donnell, Christopher J; Olafsson, Isleifur; Penninx, Brenda W; Pouta, Anneli; Prins, Bram P; Prokopenko, Inga; Puls, Ralf; Ruokonen, Aimo; Savolainen, Markku J; Schlessinger, David; Schouten, Jeoffrey N L; Seedorf, Udo; Sen-Chowdhry, Srijita; Siminovitch, Katherine A; Smit, Johannes H; Spector, Timothy D; Tan, Wenting; Teslovich, Tanya M; Tukiainen, Taru; Uitterlinden, Andre G; Van der Klauw, Melanie M; Vasan, Ramachandran S; Wallace, Chris; Wallaschofski, Henri; Wichmann, H-Erich; Willemsen, Gonneke; Würtz, Peter; Xu, Chun; Yerges-Armstrong, Laura M; Abecasis, Goncalo R; Ahmadi, Kourosh R; Boomsma, Dorret I; Caulfield, Mark; Cookson, William O; van Duijn, Cornelia M; Froguel, Philippe; Matsuda, Koichi; McCarthy, Mark I; Meisinger, Christa; Mooser, Vincent; Pietiläinen, Kirsi H; Schumann, Gunter; Snieder, Harold; Sternberg, Michael J E; Stolk, Ronald P; Thomas, Howard C; Thorsteinsdottir, Unnur; Uda, Manuela; Waeber, Gérard; Wareham, Nicholas J; Waterworth, Dawn M; Watkins, Hugh; Whitfield, John B; Witteman, Jacqueline C M; Wolffenbuttel, Bruce H R; Fox, Caroline S; Ala-Korpela, Mika; Stefansson, Kari; Vollenweider, Peter; Völzke, Henry; Schadt, Eric E; Scott, James; Järvelin, Marjo-Riitta; Elliott, Paul; Kooner, Jaspal S

    2011-10-16

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.

  16. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

    PubMed

    Chambers, John C; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Van der Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E; Coin, Lachlan J; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L; Hottenga, Jouke-Jan; Kühnel, Brigitte; Kumar, Vinod; Lagou, Vasiliki; Liang, Liming; Luan, Jian'an; Vidal, Pedro Marques; Mateo Leach, Irene; O'Reilly, Paul F; Peden, John F; Rahmioglu, Nilufer; Soininen, Pasi; Speliotes, Elizabeth K; Yuan, Xin; Thorleifsson, Gudmar; Alizadeh, Behrooz Z; Atwood, Larry D; Borecki, Ingrid B; Brown, Morris J; Charoen, Pimphen; Cucca, Francesco; Das, Debashish; de Geus, Eco J C; Dixon, Anna L; Döring, Angela; Ehret, Georg; Eyjolfsson, Gudmundur I; Farrall, Martin; Forouhi, Nita G; Friedrich, Nele; Goessling, Wolfram; Gudbjartsson, Daniel F; Harris, Tamara B; Hartikainen, Anna-Liisa; Heath, Simon; Hirschfield, Gideon M; Hofman, Albert; Homuth, Georg; Hyppönen, Elina; Janssen, Harry L A; Johnson, Toby; Kangas, Antti J; Kema, Ido P; Kühn, Jens P; Lai, Sandra; Lathrop, Mark; Lerch, Markus M; Li, Yun; Liang, T Jake; Lin, Jing-Ping; Loos, Ruth J F; Martin, Nicholas G; Moffatt, Miriam F; Montgomery, Grant W; Munroe, Patricia B; Musunuru, Kiran; Nakamura, Yusuke; O'Donnell, Christopher J; Olafsson, Isleifur; Penninx, Brenda W; Pouta, Anneli; Prins, Bram P; Prokopenko, Inga; Puls, Ralf; Ruokonen, Aimo; Savolainen, Markku J; Schlessinger, David; Schouten, Jeoffrey N L; Seedorf, Udo; Sen-Chowdhry, Srijita; Siminovitch, Katherine A; Smit, Johannes H; Spector, Timothy D; Tan, Wenting; Teslovich, Tanya M; Tukiainen, Taru; Uitterlinden, Andre G; Van der Klauw, Melanie M; Vasan, Ramachandran S; Wallace, Chris; Wallaschofski, Henri; Wichmann, H-Erich; Willemsen, Gonneke; Würtz, Peter; Xu, Chun; Yerges-Armstrong, Laura M; Abecasis, Goncalo R; Ahmadi, Kourosh R; Boomsma, Dorret I; Caulfield, Mark; Cookson, William O; van Duijn, Cornelia M; Froguel, Philippe; Matsuda, Koichi; McCarthy, Mark I; Meisinger, Christa; Mooser, Vincent; Pietiläinen, Kirsi H; Schumann, Gunter; Snieder, Harold; Sternberg, Michael J E; Stolk, Ronald P; Thomas, Howard C; Thorsteinsdottir, Unnur; Uda, Manuela; Waeber, Gérard; Wareham, Nicholas J; Waterworth, Dawn M; Watkins, Hugh; Whitfield, John B; Witteman, Jacqueline C M; Wolffenbuttel, Bruce H R; Fox, Caroline S; Ala-Korpela, Mika; Stefansson, Kari; Vollenweider, Peter; Völzke, Henry; Schadt, Eric E; Scott, James; Järvelin, Marjo-Riitta; Elliott, Paul; Kooner, Jaspal S

    2011-11-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function. PMID:22001757

  17. Therapeutic drug monitoring of cerebrospinal fluid vancomycin concentration during intraventricular administration.

    PubMed

    Popa, D; Loewenstein, L; Lam, S W; Neuner, E A; Ahrens, C L; Bhimraj, A

    2016-02-01

    Limited data are available on intraventricular vancomycin dosing for meningitis. This study explored clinical characteristics that correlated with cerebrospinal fluid (CSF) concentrations. Over a nine-year period, 13 patients with 34 CSF vancomycin concentrations were evaluated. CSF output and time from dose correlated with CSF vancomycin concentration. No relationship was seen with regards to CSF protein, white blood cell count or glucose. PMID:26654472

  18. Determining the Volume of Additive Solution and Residual Plasma in Whole Blood Filtered and Buffy Coat Processed Red Cell Concentrates

    PubMed Central

    Jordan, Andrew; Acker, Jason P.

    2016-01-01

    Summary Background Residual plasma in transfused red cell concentrates (RCCs) has been associated with adverse transfusion outcomes. Despite this, there is no consensus on the standard procedure for measuring residual plasma volume. Methods The volumes of residual plasma and additive solution were measured in RCCs processed using two separation methods: whole blood filtration (WBF) and buffy coat (BC)/RCC filtration. The concentration of mannitol and albumin in RCC components was measured using colorimetric assays. Mannitol concentration was used to calculate additive solution volume. Residual plasma volume was calculated using two methods. Results Calculated RCC supernatant volumes were much lower in BC-processed components compared to WBF-processed components (BC = 97 ± 6 ml, WBF = 109 ± 4 ml; p < 0.05). Calculated additive solution volumes were greater in WBF- than in BC-processed components (BC = 81 ± 4 ml, WBF = 105 ± 2 ml; p < 0.05). Absolute residual plasma volume varied significantly based on the calculation method used. Conclusion Disparity between plasma volume calculation methods was observed. Efforts should be made to standardize residual plasma volume measurement methods in order to accurately assess the impact of residual plasma on transfusion outcomes. PMID:27330533

  19. Comparison of Oseltamivir and Oseltamivir Carboxylate Concentrations in Venous Plasma, Venous Blood, and Capillary Blood in Healthy Volunteers

    PubMed Central

    Instiaty, Insti; Lindegardh, Niklas; Jittmala, Podjanee; Hanpithakpong, Warunee; Blessborn, Daniel; Pukrittayakamee, Sasithon; White, Nicholas J.

    2013-01-01

    Oseltamivir and oseltamivir carboxylate concentrations were measured in venous plasma, venous blood, and capillary blood taken simultaneously from 24 healthy volunteers. Median (range) venous-blood-to-plasma ratios were 1.42 (0.920 to 1.97) for oseltamivir and 0.673 (0.564 to 0.814) for oseltamivir carboxylate. Capillary blood/venous plasma ratios were 1.32 (0.737 to 3.16) for oseltamivir and 0.685 (0.502 to 1.34) for oseltamivir carboxylate. Oseltamivir concentrations in venous and capillary blood were similar. Oseltamivir carboxylate showed a time-dependent distribution between venous and capillary blood. PMID:23507284

  20. Serum and plasma concentration of oxidant and antioxidants in patients of Helicobacter pylori gastritis and its correlation with gastric cancer.

    PubMed

    Khanzode, Shruti S; Khanzode, Suchet D; Dakhale, Ganesh N

    2003-05-30

    Serum superoxide dismutase, plasma ascorbic acid and lipid peroxidation in H. pylori gastritis and gastric cancer patients were compared with values for age matched healthy subjects. Serum superoxide dismutase and serum malondialdehyde were analyzed spectrophotometrically whereas plasma ascorbic acid was determined by colorimetric method. Significant increase in serum superoxide dismutase and serum malondialdehyde and significant decrease in plasma ascorbic acid were observed in H. pylori gastritis and gastric cancer patients compared to control subjects. The concentration of serum superoxide dismutase and serum malondialdehyde was significantly higher and plasma ascorbic acid was significantly lower in gastric cancer as compared to H. pylori gastritis patients. Our results demonstrate that a correlation existed between the concentration of serum superoxide dismutase, plasma ascorbic acid and lipid peroxidation in H. pylori gastritis and gastric cancer patients.

  1. 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 Central

    Zimmermann, Estevan Sonego; Laureano, João Victor; dos Santos, Camila Neris; Schmidt, Stephan; Lagishetty, Chakradhar V.; de Castro, Whocely Victor

    2015-01-01

    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

  2. Simultaneous determination and pharmacokinetics of five rhubarb anthraquinones in dog plasma by HPLC after orally administration the rhubarb extract.

    PubMed

    Feng, Su-xiang; Li, Jian-sheng; Wang, Shu-mei; Yang, Ran; Zhou, Ti-qiang; Li, Xiao-yu; Qu, Ling-bo

    2014-07-01

    Rhubarb is widely used in the treatment of obstipation, gastrointestinal indigestion and other diseases in China and other Asian countries for thousands of years. Anthraquinones are the major group of polyphenol constituents including aloe-emodin, rhein, emodin, chrysophanol and physcion. In order to evaluate the pharmacokinetics of five rhubarb anthraquinones, a high-performance liquid chromatography with fluorescence detection (HPLC-FLD) method for simultaneous determination of aloe-emodin, rhein, emodin, chrysophanol and physcion in dog plasma was established. Solid phase extraction (SPE) was applied to the extraction and purification of samples. The calibration curves of five anthraquinones showed good linearity with r greater than 0.9925. The average extraction recoveries, examined at three concentration levels, carried from 92.1% to 102.3%, and the accuracies ranged from 87.7% to 102.5% with precision (RSD) <10%. The pharmacokinetic paremeters of five anthraquinones were investigated systematically after orally administration the rhubarb extract. Five anthraquinones were rapidly absorbed and Tmax for aloe-emodin, rhein, emodin, chrysophanol and physcion was at 0.75, 1.50, 0.75, 1.0 and 2.0 h respectively. The Cmax of five anthraquinones was 0.031, 3.39, 0.27, 0.036 and 0.032 μg/mL while the AUC of five anthraquinones was 0.35 ± 0.058, 32.22 ± 8.29, 2.97 ± 0.66, 0.43 ± 0.10 and 0.41 ± 0.12 mg h/L, respectively.

  3. Effects of aspartame and glucose administration on brain and plasma levels of large neutral amino acids and brain 5-hydroxyindoles.

    PubMed

    Yokogoshi, H; Roberts, C H; Caballero, B; Wurtman, R J

    1984-07-01

    Administration of the artificial sweetener aspartame (L-aspartylphenylalanylmethyl ester; 200 mg/kg) by gavage to rats caused large increments in brain and plasma levels of phenylalanine and its product tyrosine. Glucose administration (3 g/kg, by gavage, a dose sufficient to cause insulin-mediated reductions in plasma levels of the large neutral amino acids leucine, isoleucine, and valine) also elevated brain phenylalanine and tyrosine, and enhanced the increments caused by the aspartame, nearly doubling the rise in brain phenylalanine. Each animal's brain phenylalanine or tyrosine levels were highly correlated (r = 0.97 and 0.99, respectively) with its plasma phenylalanine or tyrosine ratios, affirming that aspartame's effects on the brain amino acids result from the changes it produces in plasma composition. As described previously, glucose consumption increased brain tryptophan levels, and consequently, brain levels of the 5-hydroxyindoles serotonin and 5-hydroxyindoleacetic acid. Aspartame alone had no effect on these compounds but completely blocked the changes in 5-hydroxyindoles caused by glucose. Each animal's brain level of tryptophan (r = 0.89) and 5-hydroxyindoles (r = 0.74) was also significantly correlated with its plasma tryptophan ratio, affirming that the effects of glucose or aspartame on these brain constituents also result from the changes they produce in plasma composition. The aspartame-glucose combination also reduced brain levels of leucine, isoleucine, and valine to a significantly greater extent than aspartame or glucose alone. These observations indicate that high aspartame doses can generate major neurochemical changes in rats, especially when consumed along with carbohydrate-containing foods. However, they should not in any way be interpreted as demonstrating that aspartame significantly affects the human brain.

  4. Effect of vacuum conditions and plasma concentration on the chemical composition and adhesion of vacuum-plasma coatings

    NASA Astrophysics Data System (ADS)

    Borisov, D. P.; Kuznetsov, V. M.; Slabodchikov, V. A.

    2015-11-01

    The paper reports on the chemical composition of titanium nitride (TiN) and silicon (Si) coatings deposited with a new technological vacuum plasma setup which comprises magnetron sputtering systems, arc evaporators, and an efficient plasma generator. It is shown that due to highly clean vacuum conditions and highly clean surface treatment in the gas discharge plasma, both the coating-substrate interface and the coatings as such are almost free from oxygen and carbon. It is found that the coating-substrate interface represents a layer of thickness ≥ 60 nm formed through vacuum plasma mixing of the coating and substrate materials. The TiN coatings obtained on the new equipment display a higher adhesion compared to brass coatings deposited by industrial technologies via intermediate titanium oxide layers. It is concluded that the designed vacuum plasma equipment allows efficient surface modification of materials and articles by vacuum plasma immersion processes.

  5. Prognostic and diagnostic value of plasma soluble ST2 concentrations in Acute Respiratory Distress Syndrome

    PubMed Central

    Bajwa, Ednan K.; Volk, Jessica A.; Christiani, David C.; Harris, R. Scott; Matthay, Michael A.; Thompson, B. Taylor; Januzzi, James L.

    2013-01-01

    Objective Soluble ST2 (sST2) is a biomarker of myocardial strain and inflammation. The characteristics of acute respiratory distress syndrome (ARDS) include inflammation and cardiovascular dysfunction. We sought to determine whether plasma sST2 concentration is associated with outcome and response to conservative fluid management, and whether sST2 concentration discriminates ARDS from decompensated heart failure (HF). Design, Setting, and Patients We assayed plasma sST2 concentrations in 826 patients in the Fluid and Catheter Treatment Trial (FACTT), a multi-center randomized controlled trial of conservative fluid management in ARDS, as well as a cohort of patients with decompensated HF. We tested whether sST2 was associated with outcome, response to therapy, and diagnostic utility for ARDS vs. HF. Measurements and Main Results Non-survivors had higher day 0 (P<.0001) and day 3 (P<.0001) sST2 concentrations. After adjustment for severity of illness, higher sST2 concentration was associated with mortality, with odds ratio (ORadj) 1.47 (95% confidence interval [CI] 0.99 – 2.20, P=.06) at day 0, 2.94 (95% CI 2.00 – 4.33, P<.0001) at day 3, and 3.63 (95% CI 2.38 – 5.53, P<.0001) if sST2 increased between days. Cumulative fluid balance was more positive among patients with higher day 0 (median 5212 mL, interquartile range [IQR] 200 – 12284 vs. 2020 mL, −2034 – 7091; P<0.0001), and day 3 sST2 (median 7678 mL, IQR 2217 – 14278 vs. 1492 mL, −2384 – 6239; P<0.0001). sST2 showed excellent discriminative ability between the FACTT and HF populations (Area under ROC curve=0.98, P<0.0001). Conclusions Higher sST2 concentrations are associated with worse outcome in ARDS and may have value for discriminating ARDS from heart failure. PMID:23939353

  6. Choice of anesthetic technique on plasma concentrations of interleukins and cell adhesion molecules

    PubMed Central

    2013-01-01

    Background Whether inflammatory responses to surgery are comparably activated during total intravenous anesthesia (TIVA) and during volatile anesthesia remains unclear. We thus compared the perioperative effects of TIVA and isoflurane anesthesia on plasma concentrations of proinflammatory and anti-inflammatory interleukins and cell adhesion molecules. Methods Patients having laparoscopic cholecystectomies were randomly allocated to two groups: 44 were assigned to TIVA and 44 to isoflurane anesthesia. IL-1β, IL-6, IL-8, IL-10, IL-13, and the cellular adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were determined preoperatively, before incision, and at 2 and 24 hours postoperatively. Our primary outcomes were area-under-the-curve cytokine and adhesion molecule concentrations over 24 postoperative hours. Results The only statistically significant difference in area-under-the-curve concentrations was for IL-6, which was greater in patients given isoflurane:78 (95% confidence interval (CI): 52 to 109) pg/ml versus 33 (22 to 50) pg/ml, P= 0.006. Two hours after surgery, IL-6 was significantly greater than baseline in patients assigned to isoflurane: 47 (95% CI: 4 to 216, P<0.001) pg/ml versus 18 (95%CI: 4 to 374, P<0.001) pg/ml in the TIVA group. In contrast, IL-10 was significantly greater in patients assigned to TIVA: 20 (95% CI: 2 to 140, P<0.001) pg/ml versus 12 (95% CI: 3 to 126, P<0.001) pg/ml. By 24 hours after surgery, concentrations were generally similar between study groups and similar to baseline values. Conclusion The only biomarker whose postoperative area-under-the-curve concentrations differed significantly as a function of anesthetic management was IL-6. Two hours after surgery, IL-6 concentrations were significantly greater in patients given isoflurane than TIVA. However, the differences were modest and seem unlikely to prove clinically important. Further studies are needed. PMID:24472144

  7. Effects of storage time on total protein and globulin concentrations in bovine fresh frozen plasma obtained for transfusion.

    PubMed

    Proverbio, D; Spada, E; Baggiani, L; Bagnagatti De Giorgi, G; Roggero, N; Belloli, A; Pravettoni, D; Perego, R

    2015-01-01

    To evaluate the effects of storage conditions on total protein (TP) and globulin fractions in fresh frozen bovine plasma units prepared and stored for transfusion, TP and globulin fractions were evaluated in fresh plasma and at 1 month and 6 and 12 months after blood collection in plasma stored at -20°C. Significant differences in concentrations were found in the median concentration of total protein (P=0.0336), between 0 months and 1 month (P=0.0108), 0 and 6 months (P=0.0023), and 0 and 12 months (P=0.0027), in mean concentration (g/dL) of albumin (P=0.0394), between 0 months and 1 month (P=0.0131), 0 and 6 months (P=0.0035), and 0 and 12 months (P=0.0038), and beta-2 fraction (P=0.0401), between 0 and 6 months (P=0.0401) and 0 and 12 months (P=0.0230). This study suggests that total gamma globulin concentration in bovine frozen plasma is stable for 12 months at -20°C. Total protein, ALB, and beta-2 fraction have significantly different concentrations (g/dL) when compared to prestorage. This study has shown IgG protein fraction stability in bovine fresh frozen plasma collected for transfusion; therefore, bovine fresh frozen plasma seems to be suitable for the treatment of hypogammaglobulinemia (failure of passive transfer) in calves when stored for 12 months at -20°C.

  8. Plasma progesterone and prolactin concentrations in overtly pseudopregnant bitches: a clinical study.

    PubMed

    Tsutsui, T; Kirihara, N; Hori, T; Concannon, P W

    2007-03-15

    Plasma concentrations of progesterone (P(4)) and prolactin (PRL) were measured in 35 bitches presented at veterinary clinics for symptoms of overt pseudopregnancy (PSP) between 50 and 95 days after the onset of proestrus. Results were compared to those from samples collected from 35 control bitches at comparable stages of the ovarian cycle (expressed as days after the onset of observed signs of proestrus). In the PSP bitches at 71.4+/-1.6 (mean+/-S.E.M.) days of the cycle, P(4) (1.5+/-0.2ng/mL) was lower (P<0.01) and PRL (16.0+/-1.9ng/mL) was higher (P<0.01), compared to P(4) (2.7+/-0.4ng/mL) and PRL (2.9+/-0.6ng/mL) in control bitches at 70.6+/-1.5 days of the cycle. Low P(4) was not a prerequisite for elevated PRL. Although elevated (> or =10ng/mL) PRL (20.9+/-2.0ng/mL) occurred more often with low (<2ng/mL) P(4) (20 of 24 cases) it also occurred with P(4) above 3ng/mL in two affected bitches and in two control bitches. Whether the occurrence of relatively low PRL concentrations (<4ng/mL) in samples obtained from 4 of the 35 pseudopregnant bitches reflected variable and often elevated PRL secretion or increased sensitivity to PRL in the absence of elevated prolactin in those animals was not determined. We inferred that elevated plasma PRL was often involved in the etiology of overt PSP; furthermore, a premature decline in circulating P(4) concentrations may be a factor in some instances.

  9. Concentrations, metabolic clearance rates, production rates and plasma binding of cortisol in Antarctic phocid seals.

    PubMed

    Liggins, G C; France, J T; Schneider, R C; Knox, B S; Zapol, W M

    1993-10-01

    We have reported previously that plasma of the Weddell seal, a member of the phocid family, contains a very high concentration of cortisol. The present study was undertaken to determine whether high cortisol levels were common to seals in the Antarctic environment, or to other phocidae, and to determine the mechanism of the hypercortisolaemia. High levels of cortisol (0.82-2.38 mumol/l) were found in 4 phocidae (Weddell, crabeater, leopard and Southern elephant seals), whereas levels in a member of the otariid family (Antarctic fur seal) were similar to human values. Metabolic clearance rates (MCR) and production rates (PR) of cortisol were determined in the field in Weddell (N = 1), crabeater (N = 3) and leopard (N = 3) seals following bolus injections of [3H] cortisol. The MCR and PR did not differ between the three phocids, but whereas the MCR of 410-590 1/day was twice that of human values, the PR of 460-1180 mumol.m-2 x d-1 was up to 40-fold greater. The binding capacity of corticosteroid-binding globulin (CBG) was equal to or greater than the plasma concentrations of cortisol, resulting in relatively low concentrations of free cortisol. We conclude that hypercortisolaemia is maintained in phocid seals mainly by a high production rate--the highest (corrected for surface area) reported in any species. The relatively low cortisol levels in otariid seals studied in the same environment suggest that the high PR in phocidae is unrelated to the harsh climatic conditions, but may be part of their adaptation for diving to extreme depths.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Effects of coenzyme Q(10) administration on its tissue concentrations, mitochondrial oxidant generation, and oxidative stress in the rat.

    PubMed

    Kwong, Linda K; Kamzalov, Sergey; Rebrin, Igor; Bayne, Anne-Cécile V; Jana, Chandan K; Morris, Paul; Forster, Michael J; Sohal, Rajindar S

    2002-09-01

    Coenzyme Q (CoQ(10)) is a component of the mitochondrial electron transport chain and also a constituent of various cellular membranes. It acts as an important in vivo antioxidant, but is also a primary source of O(2)(-*)/H(2)O(2) generation in cells. CoQ has been widely advocated to be a beneficial dietary adjuvant. However, it remains controversial whether oral administration of CoQ can significantly enhance its tissue levels and/or can modulate the level of oxidative stress in vivo. The objective of this study was to determine the effect of dietary CoQ supplementation on its content in various tissues and their mitochondria, and the resultant effect on the in vivo level of oxidative stress. Rats were administered CoQ(10) (150 mg/kg/d) in their diets for 4 and 13 weeks; thereafter, the amounts of CoQ(10) and CoQ(9) were determined by HPLC in the plasma, homogenates of the liver, kidney, heart, skeletal muscle, brain, and mitochondria of these tissues. Administration of CoQ(10) increased plasma and mitochondria levels of CoQ(10) as well as its predominant homologue CoQ(9). Generally, the magnitude of the increases was greater after 13 weeks than 4 weeks. The level of antioxidative defense enzymes in liver and skeletal muscle homogenates and the rate of hydrogen peroxide generation in heart, brain, and skeletal muscle mitochondria were not affected by CoQ supplementation. However, a reductive shift in plasma aminothiol status and a decrease in skeletal muscle mitochondrial protein carbonyls were apparent after 13 weeks of supplementation. Thus, CoQ supplementation resulted in an elevation of CoQ homologues in tissues and their mitochondria, a selective decrease in protein oxidative damage, and an increase in antioxidative potential in the rat.

  11. Practical approach to self-administration of intravenous C1-INH concentrate: a nursing perspective.

    PubMed

    Symons, C; Rossi, O; Magerl, M; Andritschke, K

    2013-01-01

    At an international hereditary angioedema (HAE) expert meeting, results from a survey were used to guide discussion on how best to advise patients on self-administering intravenous C1 esterase inhibitor therapy. Treatment differences across Europe were highlighted, together with the practicalities of self-administration and useful resources for patients in the future. The international HAE experts noted an increase in the uptake of self-administration, with patients being trained by nursing staff. All patients who are willing and able to self-administer should be offered this treatment option and patients should be encouraged to treat attacks early. Several initiatives were suggested regarding support for patients who self-administer therapy, including a 24-hour helpline and home care agencies.

  12. An fMRI study on variation of visuospatial cognitive performance of young male due to highly concentrated oxygen administration

    NASA Astrophysics Data System (ADS)

    Chung, Soon Cheol; Kim, Ik Hyeon; Tack, Gye Rae; Sohn, Jin Hun

    2004-04-01

    This study investigated the effects of 30% oxygen administration on the visuospatial cognitive performance using fMRI. Eight college students (right-handed, average age 23.5) were selected as subjects for this study. Oxygen supply equipment which gives 21% and 30% oxygen at a constant rate of 8L/min was developed for this study. To measure the performance of visuospatial cognition, two questionnaires with similar difficulty containing 20 questions each were also developed. Experiment was designed as two runs: run for visuospatial cognition test with normal air (21% of oxygen) and run for visuospatial cognition test with highly concentrated air (30% of oxygen). Run consists of 4 blocks and each block has 8 control problems and 5 visuospatial problems. Functional brain images were taken from 3T MRI using single-shot EPI method. Activities of neural network due to performing visuospatial cognition test were identified using subtraction procedure, and activation areas while performing visuospatial cognition test were extracted using double subtraction procedure. Activities were observed at occipital lobe, parietal lobe, and frontal lobe when performing visuospatial cognition test following both 21% and 30% oxygen administration. But in case of only 30% oxygen administration there were more activities at left precuneus, left cuneus, right postcentral gyrus, bilateral middle frontal gyri, right inferior frontal gyrus, left superior frontal gyrus, bilateral uvula, bilateral pyramis, and nodule compared with 21% oxygen administration. From results of visuospatial cognition test, accuracy rate increased in case of 30% oxygen administration. Thus it could be concluded that highly concentrated oxygen administration has positive effects on the visuospatial cognitive performance.

  13. Glucose tolerance, blood lipid, insulin and glucagon concentration after single or continuous administration of aspartame in diabetics.

    PubMed

    Okuno, G; Kawakami, F; Tako, H; Kashihara, T; Shibamoto, S; Yamazaki, T; Yamamoto, K; Saeki, M

    1986-04-01

    A nutritive sweetener, aspartame (L-aspartyl-L-phenylalanine methylester) was administered orally to normal controls and diabetic patients in order to evaluate effects on blood glucose, lipids and pancreatic hormone secretion. An oral glucose tolerance test was also performed in the same subjects as a control study of aspartame administration. In 7 normal controls and 22 untreated diabetics, a single dose of 500 mg aspartame, equivalent to 100 g glucose in sweetness, induced no increase in blood glucose concentration. Rather, a small but significant decrease in blood glucose was noticed 2 or 3 h after administration. The decrease in blood glucose was found to be smallest in the control and became greater as the diabetes increased in severity. No significant change in blood insulin or glucagon concentration during a 3-h period was observed in either the controls or the diabetics. The second study was designed to determine the effects of 2 weeks' continuous administration of 125 mg aspartame, equal in sweetness to the mean daily consumption of sugar (20-30 g) in Japan, to 9 hospitalized diabetics with steady-state glycemic control. The glucose tolerance showed no significant change after 2 weeks' administration. Fasting, 1 h and 2 h postprandial blood glucose, blood cholesterol, triglyceride and HDL-cholesterol were also unaffected. From these and other published results, aspartame would seem to be a useful alternative nutrient sweetener for patients with diabetes mellitus.

  14. Comparison of blood lead and blood and plasma δ-aminolevulinic acid concentrations as biomarkers for lead poisoning in cattle.

    PubMed

    Kang, Hwan Goo; Bischoff, Karyn; Ebel, Joseph G; Cha, Sang Ho; McCardle, James; Choi, Cheong Up

    2010-11-01

    Lead (Pb) concentrations in whole blood and δ-aminolevulinic acid (ALA) concentrations in plasma and whole blood from 37 cattle with suspected Pb exposure were determined in order to investigate the usefulness of ALA as a biological indicator for Pb poisoning in cattle. Cows were divided into 4 groups based on blood Pb, as follows: <30 ppb (group 1), 30-100 ppb (group 2), 100-300 ppb (group 3), and >300 ppb (group 4). The derivatization reaction for ALA was improved by a greater than 2-fold measure in whole blood and by a 10-fold measure in plasma by adding 75 and 50 µl of 0.1 N HCl, respectively. Blood Pb concentrations ranged from <25 ppb to 1,006 ppb (185.5 ± 254.9 ppb), with 17 samples containing >50 ppb Pb. Delta-aminolevulinic acid concentrations in whole blood and plasma ranged from <62.7 ppb to 96.9 ppb (77.4 ± 8.4 ppb) and from <5.0 ppb to 24.0 ppb (4.6 ± 3.8 ppb), respectively. Whole blood ALA did not correlate with blood lead concentrations in any group. Increase in plasma ALA concentration was dependent on blood Pb concentration. There was no correlation between blood Pb concentration and plasma ALA concentration in group 2 (n  =  4), but correlation coefficients were 0.736 in group 3 and 0.807 in group 4, respectively. The correlation coefficient was increased to 0.851 when groups 3 and 4 were combined. Based on these observations, in cattle, plasma ALA is a more reliable biological biomarker for Pb exposure than is blood ALA.

  15. New method of tracing blood hemoglobin concentration to hematocrit ratio for monitoring plasma dilution and osmotic origin shifts in blood.

    PubMed

    Andrijauskas, Audrius; Ivaskevicius, Juozas

    2006-01-01

    Blood hemoglobin concentration and hematocrit are probably the most widely used parameters for outpatient and inpatient examination. In addition to their inherent significance for evaluation of blood viscosity and oxygen carrying capacity, these parameters are traditionally used as tracers of plasma dilution. Blood test derived results are conventionally recorded on multiple pages in patient's medical records making dynamical investigations tedious and time-consuming. In addition, research results describing plasma dilution by means of hemoglobin or hematocrit are presented in a clinically unpractical way. A new method, referred to as HBS Graphics (patent pending--USA serial # 60/712809) is introduced for the first time in this article. This method of evaluation of dynamical hemoglobin concentration, hematocrit and mean corpuscular hemoglobin concentration value deploys interfering parameter shifts for the evaluation of plasma dilution in relation to osmotic dynamics. The HBS Graphics complements two coordinate systems--hemoglobin concentration and hematocrit--with incorporated mean corpuscular hemoglobin concentration value specific trends referred to as radiating lines. Isosmotic plasma dilution and erythrocyte volume shifts follow radiating lines, while osmotic shifts induce intertrend shifts. This article also reviews other methods of tracing plasma dilution by means of blood hemoglobin concentration and hematocrit dynamics.

  16. The Concentrations of Circulating Plasma Oxytocin and the Pattern of Oxytocin Release in Mare during Oestrus and after Ovulation

    NASA Astrophysics Data System (ADS)

    Bae, Sung Eun

    Mares susceptible to persistent mating-induced endometritis (PMIE) accumulate intrauterine fluid after mating. One of the factors causing delayed uterine clearance is thought to be impaired uterine contractility. Oxytocin is central in controlling myometrial contractility. The objective of the present study was to describe peripheral oxytocin release during estrus and in the early postovulatory period in reproductively-normal mares and to compare the baseline circulating oxytocin concentrations in reproductively-normal mares and mares with PMIE. Blood samples were collected from reproductively-normal mares (n=5) from day -5 of estrus to day 2 postovulation and every 5 min for 30 min from reproductively-normal mares (n=5) and mares with PMIE (n=5) on day 3 of estrus. Pulsatile secretion of oxytocin was observed in all mares. Mean plasma oxytocin concentrations were significantly higher (P<0.05) in estrus (day -5 to day -2) than on the day of ovulation (day 0). After ovulation, plasma oxytocin concentrations tended to increase. On day 3 of estrus, plasma oxytocin concentrations were significantly higher (P<0.01) in reproductively-normal mares than in mares with PMIE. The results showed there is a significant difference in plasma oxytocin concentrations between mares to PMIE. The low plasma oxytocin concentrations in mares with PMIE may contribute to predisposing factors in their poor uterine clearance in these mares.

  17. Variability of plasma HDL subclass concentrations in men and women over time.

    PubMed

    Williams, P T; Dreon, D M; Blanche, P J; Krauss, R M

    1997-04-01

    Plasma HDL subclasses were examined by gradient gel electrophoresis in repeated samples to assess variability over time. Absorbance of the protein stain was used as an index of mass concentrations at 0.01-nm intervals within five HDL subclasses: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 nm). Three separate longitudinal studies of men showed that repeated samples of HDL over time were correlated most strongly within HDL2b, somewhat less within HDL2a, and more weakly within HDL3a, HDL3b, and HDL3c. As in men, repeated samples in women from two studies were significantly correlated within the HDL2b, HDL2a, and HDL3b intervals. Plasma HDL2b levels were significantly more stable in men than in women. Although the variability of HDL subclass measurements includes both methodological and physiological sources, differences in laboratory measurement error do not appear to explain the differences in correlations among subclasses. Specifically, analysis of 288 replications from frozen aliquots suggested that laboratory error had the least effect on correlations involving HDL3 subclasses and only slightly greater effect on correlations involving HDL2 subclasses. Our results suggest that for plasma sampled over time, the stability of HDL subclass levels increases with particle size. Prior reports of subclass-specific correlations between HDL and other variables (eg, diet, exercise, and other lipids) are unlikely to be artifacts of laboratory precision but could arise from subclass differences in variability that are physiological.

  18. Physiologically relevant plasma d,l-homocysteine concentrations mobilize Cd from human serum albumin.

    PubMed

    Sagmeister, Peter; Gibson, Matthew A; McDade, Kyle H; Gailer, Jürgen

    2016-08-01

    Although low-level chronic exposure of humans to cadmium (Cd(2+)) can result in a variety of adverse health effects, little is known about the role that its interactions with plasma proteins and small molecular weight (SMW) ligands in the bloodstream may play in delivering this metal to its target organs. To gain insight, a Cd-human serum albumin (HSA) 1:1 (molar ratio) complex was analyzed by size exclusion chromatography (SEC) coupled on-line to a flame atomic absorption spectrometer (FAAS). Using a phosphate buffered saline (PBS)-buffer mobile phase, the stability of the Cd-HSA complex was investigated in the presence of 2.0mM of SMW ligands, including taurine, acetaminophen, l-methionine, l-cysteine (Cys), d,l-homocysteine (hCys) or l-cysteine methyl-ester (Cys-Me). While taurine, acetaminophen and l-methionine did not affect its integrity, Cys, hCys and Cys-Me completely abstracted Cd from HSA. Subsequent investigations into the effect of 1.5, 1.0 and 0.5mM Cys and hCys on the integrity of the Cd-HSA complex revealed clear differences with regard to the nature of the eluting SMW-Cd species between these structurally related endogenous thiols. Interestingly, the Cd-specific chromatograms that were obtained for 0.5mM hCys revealed the elution of an apparent mixture of the parent Cd-HSA complex with a significant contribution of a structurally uncharacterized CdxhCysy species. Since this hCys concentration is encountered in blood plasma of hyperhomocysteinemia patients and since previous studies by others have revealed that a SH-containing carrier mediates the uptake of Cd into hepatocytes, our results suggest that plasma hCys may play a role in the toxicologically relevant translocation of Cd from the bloodstream to mammalian target organs. PMID:27294530

  19. Physiologically relevant plasma d,l-homocysteine concentrations mobilize Cd from human serum albumin.

    PubMed

    Sagmeister, Peter; Gibson, Matthew A; McDade, Kyle H; Gailer, Jürgen

    2016-08-01

    Although low-level chronic exposure of humans to cadmium (Cd(2+)) can result in a variety of adverse health effects, little is known about the role that its interactions with plasma proteins and small molecular weight (SMW) ligands in the bloodstream may play in delivering this metal to its target organs. To gain insight, a Cd-human serum albumin (HSA) 1:1 (molar ratio) complex was analyzed by size exclusion chromatography (SEC) coupled on-line to a flame atomic absorption spectrometer (FAAS). Using a phosphate buffered saline (PBS)-buffer mobile phase, the stability of the Cd-HSA complex was investigated in the presence of 2.0mM of SMW ligands, including taurine, acetaminophen, l-methionine, l-cysteine (Cys), d,l-homocysteine (hCys) or l-cysteine methyl-ester (Cys-Me). While taurine, acetaminophen and l-methionine did not affect its integrity, Cys, hCys and Cys-Me completely abstracted Cd from HSA. Subsequent investigations into the effect of 1.5, 1.0 and 0.5mM Cys and hCys on the integrity of the Cd-HSA complex revealed clear differences with regard to the nature of the eluting SMW-Cd species between these structurally related endogenous thiols. Interestingly, the Cd-specific chromatograms that were obtained for 0.5mM hCys revealed the elution of an apparent mixture of the parent Cd-HSA complex with a significant contribution of a structurally uncharacterized CdxhCysy species. Since this hCys concentration is encountered in blood plasma of hyperhomocysteinemia patients and since previous studies by others have revealed that a SH-containing carrier mediates the uptake of Cd into hepatocytes, our results suggest that plasma hCys may play a role in the toxicologically relevant translocation of Cd from the bloodstream to mammalian target organs.

  20. Association of plasma 25-hydroxyvitamin D concentrations and pathogenic oral bacteria in postmenopausal women

    PubMed Central

    Sahli, Michelle W; Wactawski-Wende, Jean; Ram, Pavani K; LaMonte, Michael J.; Hovey, Kathleen M.; Genco, Robert J.; Andrews, Christopher A.; Millen, Amy E.

    2014-01-01

    Background Previous findings of an association between 25-hydroxyvitamin D (25(OH)D) concentrations and periodontal disease, may be partially explained by vitamin D’s antimicrobial properties. To our knowledge, no study has investigated the association between 25(OH)D and pathogenic oral bacteria, a putative cause of periodontal disease. Methods We examined the association between plasma 25(OH)D concentrations and pathogenic oral bacteria among postmenopausal women in the Buffalo Osteoporosis and Periodontal Disease Study (1997–2000), an ancillary study of the Women’s Health Initiative Observational Study. Subgingival plaque samples were assessed using immunofluorescence for the presence of Porphyromonas gingivalis, Tannerella forsythensis, Fusobacterium nucleatum, Prevotella intermedia and Campylobacter rectus. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for prevalent bacteria by quintile (Q) of 25(OH)D concentrations adjusting for age and body mass index. Results Of the 855 participants, 288 (34%) had deficient/inadequate (<50 nmol/L) 25(OH)D concentrations and 497 (58%) had at least one species of pathogenic bacteria. No significant association was found between 25(OH)D and presence of any of these bacteria (adjusted OR for high (Q5) compared to low (Q1) 25(OH)D=0.96; 95% CI: 0.61–1.50, p for trend=0.50). Inverse, although not statistically significant, associations were found between 25(OH)D and more than one species of pathogenic bacteria (adjusted OR for adequate compared to deficient/inadequate 25(OH)D=0.85; 95% CI: 0.60–1.19). Conclusions No association was observed between pathogenic oral bacteria and 25(OH)D concentrations in postmenopausal women. This may be due to the species of bacteria assessed, small effect size or a true absence of an association. PMID:24261910

  1. Effects in vivo of decreased plasma and intracellular muscle glutamine concentration on whole-body and hindquarter protein kinetics in rats.

    PubMed

    Olde Damink, S W; de Blaauw, I; Deutz, N E; Soeters, P B

    1999-06-01

    Glutamine is considered to be a 'conditionally' essential amino acid. During situations of severe stress like sepsis or after trauma there is a fall in plasma glutamine levels, enhanced glutamine turnover and intracellular muscle glutamine depletion. Under these conditions, decreased intramuscular glutamine concentration correlates with reduced rates of protein synthesis. It has therefore been hypothesized that intracellular muscle glutamine levels have a regulatory role in muscle protein turnover rates. Administration of the glutamine synthetase inhibitor methionine sulphoximine (MSO) was used to decrease glutamine levels in male Wistar rats. Immediately after the MSO treatment (t=0 h), and at t=6 h and t=12 h, rats received intraperitoneal injections (10 ml/100 g body weight) with glutamine (200 mM) to test whether this attenuated the fall in plasma and intracellular muscle glutamine. Control animals received alanine and saline after MSO treatment, while saline was also given to a group of normal rats. At t=18 h rats received a primed constant infusion of L-[2,6-3H]phenylalanine. A three-pool compartment tracer model was used to measure whole-body protein turnover and muscle protein kinetics. Administration of MSO resulted in a 40% decrease in plasma glutamine and a 60% decrease in intracellular muscle glutamine, both of which were successfully attenuated by glutamine infusions. The decreased intracellular muscle glutamine levels had no effect on whole-body protein turnover or muscle protein kinetics. Also, glutamine supplementation did not alter these parameters. Alanine supplementation increased both hindquarter protein synthesis and breakdown but the net balance of phenylalanine remained unchanged. In conclusion, our results show that decreased plasma and muscle glutamine levels have no effect on whole-body protein turnover or muscle protein kinetics. Therefore, it is unlikely that, in vivo, the intracellular muscle concentration of glutamine is a major

  2. UHPLC-MS simultaneous determination and pharmacokinetic study of three aromatic acids and one monoterpene in rat plasma after oral administration of Shaofu Zhuyu decoction.

    PubMed

    Su, Shulan; Cui, Wenxia; Duan, Jin-Ao; Hua, Yongqing; Guo, Jianming; Shang, Erxin; Liu, Pei; Tang, Yuping

    2013-01-01

    We developed a sensitive and rapid method for determination of ferulic acid, caffeic acid, vanillic acid, and paeoniflorin in rat plasma based on ultra high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The separation of the four compounds was carried out on an AcQuity UHPLC™ BEH C18 column using a mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). Electrospray ionization in positive and negative ion mode and multiple reaction monitoring was used to identify and quantify active components. All calibration curves gave good linearity (r > 0.991) over the concentration range from 4.24-2875 ngmL(-1) for all components. The precision of the in vivo study was evaluated by intraday and interday assays and the percentages of RSD were all within 10.6%. The recovery ranged from 60.2 to 77.9%. The method was successfully applied to pharmacokinetic study of all three aromatic acids and one monoterpene in rat plasma. Furthermore, we compared the pharmacokinetics profile of the four compounds in normal and primary dysmenorrhea rats' plasma following oral administration of Shaofu Zhuyu decoction (SFZYD) and its ethanol supernatant extract (SFE). PMID:23711150

  3. Evolution of a Langmuir Wave in a Weakly Inhomogeneous Plasma with a Positive Concentration Gradient

    SciTech Connect

    Matveev, A.I.

    2005-11-01

    Spatial evolution of a Langmuir wave excited by external sources in a weakly inhomogeneous electron plasma without external sources is considered for a small positive gradient of the plasma concentration in the direction of propagation of the wave. At the first state of the evolution, the dispersion of the wave is close to linear. When the phase velocity is doubled, the second stage of the evolution begins. The wave loses its individuality and becomes a hybrid of two waves. Its profile acquires the shape of an alternating sequence of fragments of these waves. The wave dispersion is determined by the dispersion of each fragment. In the course of evolution, the spacing between the equilibrium values of the wave fragments increases; as a result, the wave decays into two waves, which are also loaded by trapped electrons. Prior to decay, the humps of the wave become steeper; as a result, at the instant of the decay, the wave is transformed into a sequence of solitons with different polarities.

  4. Wheat germ policosanol failed to lower plasma cholesterol in subjects with normal to mildly elevated cholesterol concentrations.

    PubMed

    Lin, Yuguang; Rudrum, Mike; van der Wielen, Reggy P J; Trautwein, Elke A; McNeill, Gerald; Sierksma, Aafje; Meijer, Gert W

    2004-10-01

    Sugar cane policosanol, a mixture of long-chain primary alcohols (approximately 67% as octacosanol), has been reported to lower plasma low-density lipoprotein (LDL)-cholesterol. We investigated the effect of wheat germ policosanol (WGP) on plasma lipid profiles in 58 adults (30 men and 28 women, aged 49 +/- 11 years) with normal to mildly elevated plasma cholesterol concentrations in a double-blind, randomized, parallel placebo-controlled study. Subjects consumed chocolate pellets with or without 20 mg/d WGP for 4 weeks. Plasma lipid concentrations, routine blood chemistry and hematology were determined at the start and the end of the study. The initial plasma total, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triacylglycerol concentrations in the WGP and the control groups were identical. Over the 4 weeks, neither the WGP nor the control treatment significantly changed plasma total cholesterol, LDL- and HDL-cholesterol, or triacylglycerol concentrations when compared to baseline values. In addition, there was no significant difference in plasma lipid profiles between the WGP and the control groups at the end of the study. WGP did not result in any adverse effects as indicated by plasma activities of L-gamma-glutamyltransferase (gamma-GT), ALT, AST, bilirubin concentrations, and blood cell profiles. Chemical analysis showed that WGP consists of 8% hexacosanol, 67% octacosanol, 12% triacosanol, and 13% other long-chain alcohols, which is similar to the composition of sugar cane policosanol. In conclusion, WGP at 20 mg/d had no beneficial effects on blood lipid profiles. It therefore seems unlikely that the long chain (C24-34) alcohols have any cholesterol-lowering activity.

  5. Do ambulatory-use Platelet-Rich Plasma (PRP) concentrates present risks?

    PubMed

    Martinez-Gonzalez, J M; Cano-Sanchez, J; Gonzalo-Lafuente, J C; Campo-Trapero, J; Esparza-Gomez, G; Seoane, J

    2002-01-01

    Platelet-Rich Plasma (PRP) concentrates have been widely used in the past decade as a complement to tissue regeneration procedures. The authors who have clinically used PRP refer no risk of infection, disease transmission, or undesirable effects. Nevertheless, there have been reports on the over-expression of growth factors (GFs) and their receptors related to tumour and dysplastic tissues. This has led to evaluation of the possible coincidences between carcinogenesis and the mitogenic pathways employed by GFs. The present study provides a review of the literature on the possible effects of the therapeutic uses of GFs (including PRP) in relation to carcinogenesis, their influence upon tissues with epithelial dysplasia or oral carcinoma, and their relation to tumour growth and infiltration.

  6. Daylength influences pelage and plasma prolactin concentrations but not reproduction in the prairie vole, Microtus ochrogaster.

    PubMed

    Smale, L; Nelson, R J; Zucker, I

    1988-05-01

    Short daylengths did not affect testes weight or spermatogenic index in male voles or uterine weight in female voles. Short daylengths did stimulate the growth of a winter pelage in both sexes; short-day voles had longer underhairs and guard hairs and a thicker, more dense pelage than did long-day voles. Plasma prolactin concentrations were five times higher in long-day than in short-day females and 25% higher in long-day males than in short-day males. The effect of short daylength on pelage was prevented by pinealectomy. We suggest that the growth of a winter coat is an obligate adaptation for winter survival, stimulated by exposure to short daylengths, but that changes in breeding activity are facultative and dependent to a greater extent on other cues for seasonal synchronization. PMID:3294399

  7. Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women

    SciTech Connect

    Swahn, M.L.; Wang, G.; Aedo, A.R.; Cekan, S.Z.; Bygdeman, M.

    1986-11-01

    RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy.

  8. Amoxicillin concentrations in serum, jaw cyst, and jawbone following a single oral administration.

    PubMed

    Akimoto, Y; Kaneko, K; Tamura, T

    1982-05-01

    Forty-four patient who underwent enucleation of jaw cysts were administered amoxicillin preoperatively. Specimens of venous blood (44), walls and fluids from periodontal (31) and dentigerous (13) cysts, and jawbone (26) were obtained during the operation and assayed for amoxicillin content. Measurable concentrations were found in all specimens. The levels were higher in periodontal cysts than in dentigerous cysts, and higher in maxillary bone than in mandibular bone. Since amoxicillin can easily and rapidly pass through the epithelial lining according to the change in concentration, the penetration by amoxicillin of blood/cyst wall/cyst fluid probably depends on simple diffusion.

  9. Pituitary progesterone receptor expression and plasma gonadotrophin concentrations in the reproductively dysfunctional mutant restricted ovulator chicken.

    PubMed

    Ocón-Grove, Olga M; Maddineni, Sreenivasa; Hendricks, Gilbert L; Elkin, Robert G; Proudman, John A; Ramachandran, Ramesh

    2007-04-01

    Female mutant restricted ovulator (RO) chickens of the White Leghorn strain carry a naturally occurring single nucleotide mutation in the very low density lipoprotein receptor (VLDLR) gene. Due to this mutation, RO hens fail to express a functional VLDLR protein on the oocyte membrane, which results in an impaired uptake of circulating yolk precursor macromolecules. Mutant RO hens subsequently develop hyperlipidemia and generally fail to lay eggs due to follicular atresia. Since RO hens also reportedly have three-fold higher basal plasma estrogen concentrations, combined with four-fold lower levels of circulating progesterone as compared to wild-type (WT) hens, we hypothesized that RO hens would have an increased abundance of pituitary progesterone receptor (PR) mRNA and PR isoforms A and B as well as alterations in circulating gonadotrophin levels. Quantitative PCR assays revealed significantly greater (Pplasma concentrations of luteinizing hormone, follicle stimulating hormone, estrone, and estradiol, but lower circulating progesterone levels. Collectively, elevated circulating estrogen and/or decreased progesterone levels may have contributed to the upregulation of PR mRNA and PR isoforms A and B in the RO hen pituitary gland. Lastly, in order to gain a more complete understanding of why RO hens are reproductively dysfunctional, a model is proposed that links humoral and ovarian factors to observed and putative changes in the hypothalamic-pituitary axis.

  10. Effects of Intraduodenal Administration of HCl and Glucose on Circulating Immunoreactive Secretin and Insulin Concentrations

    PubMed Central

    Boden, Guenther; Essa, Noorjehan; Owen, Oliver E.; Reichle, Frederick A.; Saraga, Walter

    1974-01-01

    A new radioimmunoassay for secretin was used to investigate (a) serum secretin responses to intraduodenally infused HCl and glucose, (b) the metabolic half-life and the volume of distribution of exogenous secretin and (c) the effect of endogenously released secretin on insulin secretion in 25 anesthetized dogs. Portal and femoral venous blood samples were taken simultaneously before, during, and after intraduodenal infusion of HCl (21 meq/30 min) and glucose (131 ml/30 min). Control experiments were performed with intraduodenal infusion of saline. Mean portal venous immunoreactive secretin concentration of six dogs rose from 313 μU/ml before to 1,060 μU/ml 10 min after initiation of the intestinal acidification (P < 0.005). Femoral venous immunoreactive secretin concentration rose from 220 μU/ml before to 567 μU/ml 15 min after intestinal acidification (P < 0.01). Secretin concentrations remained elevated during the remainder of the infusion. In the same six dogs mean portal venous immunoreactive insulin concentration rose from 38 μU/ml before to 62 μU/ml at the end of the infusion (P < 0.05). Peripheral immunoreactive insulin, glucose, and free fatty acid concentrations, however, did not change significantly. Pancreatic exocrine function was studied in four dogs. The rise in secretin concentration was followed promptly by a highly significant increase in exocrine pancreatic flow rate and bicarbonate secretion, indicating biological activity of the circulating immunoreactive secretin. The effect of intraduodenal infusion of glucose on immunoreactive secretin concentration was studied in 12 dogs. Glucose in concentrations ranging from 2.5% to 10% had no detectable influence on portal or peripheral secretin concentration. Infusion of 50% glucose caused a slight decline in secretin concentration. The metabolic clearance rate, half-life of disappearance, and volume of distribution of exogenous secretin was studied in three dogs by the constant infusion technic

  11. Effects of induced parturition in goats on immunoglobulin G and chitotriosidase activity in colostrum and plasma and on plasma concentrations of prolactin.

    PubMed

    Castro, N; Capote, J; Batista, M; Bruckmaier, R M; Argüello, A

    2011-05-01

    The effect of induction of parturition with a PGF(2)α analog on plasma concentration of prolactin (PRL) and its effects on colostrum concentration of IgG and chitotriosidase (ChT) activity were studied in 16 pregnant Majorera goats. Treated goats, those in which parturition was induced, had greater concentrations of PRL than control goats 24 h before parturition (P < 0.05) and 48 h after parturition (P < 0.05). Control goats had greater concentrations of PRL than treated goats 96 h after parturition (P < 0.05). Plasma concentration of IgG did not differ between groups during the experimental period, but colostrum concentrations of IgG were greater in control goats than in treated goats at parturition (P < 0.05). Plasma ChT activity decreased during the period 72 h before parturition to 24 h after parturition in control and treated goats. Time evolution after partum affected the colostrum ChT activity, being greater at parturition than after parturition in both groups (P < 0.05). In summary, concentration of IgG in colostrum is slightly diminished if parturition is induced. Induction of parturition causes an early increase in PRL, which is most likely responsible for preterm suppression of IgG transport into mammary secretions.

  12. CYP2B6 Variants and Plasma Efavirenz Concentrations during Antiretroviral Therapy in Port-au-Prince, Haiti

    PubMed Central

    Leger, Paul; Dillingham, Rebecca; Beauharnais, Carole Anne; Kashuba, Angela D. M.; Rezk, Naser L.; Fitzgerald, Daniel W.; Pape, Jean William; Haas, David W.

    2009-01-01

    Background Polymorphisms in CYP2B6 are known to predict increased steady-state plasma concentrations of efavirenz. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations among 45 Haitians who initiated antiretroviral therapy in Port-au-Prince. Methods An observational study characterized relationships between clinical factors, pharmacokinetics, and treatment response among antiretroviral-naïve patients initiating once-daily efavirenz plus twice-daily AZT/3TC. Plasma drug concentrations were determined at weeks 2 and 4. Drug doses were directly observed by field workers or designated family members. We retrospectively characterized relationships between efavirenz concentrations and 50 single nucleotide polymorphisms in CYP2B6, and several polymorphisms in CYP2A6, CYP3A4, CYP3A5 and ABCB1. Results Plasma for efavirenz assay was obtained 13.9 ±1.6 hours (mean ± SD) post-dose. As expected, CYP2B6 516G→T was associated with increased plasma efavirenz concentrations (Spearman’s rho=0.71, P<0.0001), as were 10 polymorphisms in linkage disequilibrium with 516G→T. Distinct CYP2B6 polymorphisms were associated with decreased plasma efavirenz concentrations (greatest absolute rho=0.48, P=0.0008). Associations were replicated by results from a recent pharmacokinetic study involving 34 healthy, HIV-negative African Americans. Conclusions Relatively frequent CYP2B6 polymorphisms may predict decreased plasma efavirenz exposure in patients of African descent. If replicated in other cohorts, the implications of these novel associations for treatment response warrant further study. PMID:19659438

  13. Baseline Plasma C-Reactive Protein Concentrations and Motor Prognosis in Parkinson Disease

    PubMed Central

    Umemura, Atsushi; Oeda, Tomoko; Yamamoto, Kenji; Tomita, Satoshi; Kohsaka, Masayuki; Park, Kwiyoung; Sugiyama, Hiroshi; Sawada, Hideyuki

    2015-01-01

    Background C-reactive protein (CRP), a blood inflammatory biomarker, is associated with the development of Alzheimer disease. In animal models of Parkinson disease (PD), systemic inflammatory stimuli can promote neuroinflammation and accelerate dopaminergic neurodegeneration. However, the association between long-term systemic inflammations and neurodegeneration has not been assessed in PD patients. Objective To investigate the longitudinal effects of baseline CRP concentrations on motor prognosis in PD. Design, Setting, and Participants Retrospective analysis of 375 patients (mean age, 69.3 years; mean PD duration, 6.6 years). Plasma concentrations of high-sensitivity CRP were measured in the absence of infections, and the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) scores were measured at five follow-up intervals (Days 1–90, 91–270, 271–450, 451–630, and 631–900). Main Outcome Measure Change of UPDRS-III scores from baseline to each of the five follow-up periods. Results Change in UPDRS-III scores was significantly greater in PD patients with CRP concentrations ≥0.7 mg/L than in those with CRP concentrations <0.7 mg/L, as determined by a generalized estimation equation model (P = 0.021) for the entire follow-up period and by a generalized regression model (P = 0.030) for the last follow-up interval (Days 631–900). The regression coefficients of baseline CRP for the two periods were 1.41 (95% confidence interval [CI] 0.21–2.61) and 2.62 (95% CI 0.25–4.98), respectively, after adjusting for sex, age, baseline UPDRS-III score, dementia, and incremental L-dopa equivalent dose. Conclusion Baseline plasma CRP levels were associated with motor deterioration and predicted motor prognosis in patients with PD. These associations were independent of sex, age, PD severity, dementia, and anti-Parkinsonian agents, suggesting that subclinical systemic inflammations could accelerate neurodegeneration in PD. PMID:26308525

  14. Concentrations of some antibiotics in synovial fluid after oral administration, with special reference to antistaphylococcal activity.

    PubMed

    Sattar, M A; Barrett, S P; Cawley, M I

    1983-02-01

    One of 4 antibiotics with antistaphylococcal activity was given in a conventional oral dose for one day to each of 20 hospitalised patients with synovial effusion of a knee joint requiring aspiration. Serial synchronous samples of serum and synovial fluid (SF) were taken over 36 hours through indwelling cannulae. No morbidity was experienced either during or after this procedure. Satisfactory antistaphylococcal concentrations in SF were achieved with sodium fusidate (500 mg 8 hourly) and amoxycillin (250 mg 8 hourly). Cephradine (500 mg 6 hourly) frequently failed to reach the minimum inhibitory concentration for Staphylococcus aureus in the SF, and flucloxacillin (250 mg 6 hourly) was unpredictable in its penetration of the synovial space. Wide interpatient variation of both serum and SF concentrations was found. Our results indicate that sodium fusidate is an appropriate early treatment for a nonresistant staphylococcal joint infection. Amoxycillin is a suitable alternative or second antistaphylococcal drug and would also be appropriate initial therapy when the infecting organism is unknown. We strongly recommend that SF antibiotic concentrations be measured, to ensure adequate penetration of the synovial cavity, in the treatment of septic arthritis.

  15. Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis

    PubMed Central

    White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

    2016-01-01

    Summary Background Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. Methods We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. Findings In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04–1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08–1·29), 1·10 (1·00–1·22), and 1·05 (0·92–1·20), respectively, per 1 SD increment in plasma urate. Interpretation Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for

  16. Plasma buprenorphine concentrations after the application of a 70 microg/h transdermal patch in dogs. Preliminary report.

    PubMed

    Andaluz, A; Moll, X; Ventura, R; Abellán, R; Fresno, L; García, F

    2009-10-01

    The objective of the present study was to evaluate the plasma concentrations and pharmacokinetics of buprenorphine after transdermal application in dogs (n = 4). A 70 microg/h transdermal buprenorphine patch was applied to the ventral abdomen of four healthy beagles. Blood samples were collected through a preplaced jugular catheter before and at 1, 2, 4, 8, 12, 24, 36, 48 and every 6 h until 108 h after the patch application. Plasma buprenorphine concentrations were measured using a (125)I-labelled radioimmunoassay (RIA) assay. No adverse effects were observed in any of the dogs. Concentrations of buprenorphine were detected in plasma after the application of the transdermal buprenorphine patch on the four experimental animals. Buprenorphine plasma concentrations increased during the first 36 h and then remained in the 0.7-1.0 ng/mL range during the study period. A decrease in plasma buprenorphine concentration was not observed during the study. Although analgesia could not be demonstrated the present study shows the ability of buprenorphine transdermal delivery systems developed for human use to deliver measurable concetrations of buprenorphine in dogs.

  17. Plasma amino acid concentrations in normal adults fed meals with added monosodium L-glutamate and aspartame.

    PubMed

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

    1983-09-01

    Aspartame is a dipeptide sweetener containing aspartate. It has been suggested that aspartame addition to meals containing large amounts of monosodium L-glutamate (MSG) would result in a rapid rise in plasma glutamate and/or aspartate concentrations and increase the potential for dicarboxylic amino acid--induced toxicity. Sic normal adult subjects were fed three hamburger and milk shake meals providing protein at 1 g/kg body weight in a Latin square design. One meal had no additions, the second provided MSG at 150 mg/kg body weight, and the third provided MSG at 150 mg/kg body weight and aspartame at 23 mg/kg body weight. The addition of MSG alone significantly increased plasma glutamate + aspartate concentration above values noted after ingestion of the meal alone. Aspartame addition to meals already containing MSG did not further significantly increase plasma glutamate + aspartate concentration above values noted when only MSG was added. However, aspartame addition did significantly increase the mean plasma phenylalanine concentration above values noted after ingestion of the meal alone or the meal with added MSG, reflecting aspartame's phenylalanine content. The data do not support the suggestion that aspartame addition to high protein meals already containing large amounts of MSG, will promote a rapid and dangerous rise in plasma glutamate and aspartate concentrations.

  18. Effect of a defined lacto-ovo-vegetarian diet and oral creatine monohydrate supplementation on plasma creatine concentration.

    PubMed

    Lukaszuk, Judith M; Robertson, Robert J; Arch, Judith E; Moyna, Niall M

    2005-11-01

    This study examined the effects that preceding creatine supplementation with a lacto-ovo-vegetarian diet would have on plasma creatine concentration. Twenty-six healthy moderately fit omnivorous men were assigned to either a 26-day lacto-ovo-vegetarian (LOV; n = 12) or omnivorous (Omni; n = 14) diet. On day 22, subjects were also assigned in a double-blind manner either creatine monohydrate (CM; 0.3 g.kg(-1).day(-1) + 20 g Polycose) or an equivalent dose of placebo (PL) for 5 days. Blood samples were taken on days 1, 22 and 27. Consuming a LOV diet for 21 days was effective in reducing plasma creatine concentration (p < 0.01) in the LOV group. Regardless of diet, the CM group showed an increase in plasma creatine concentrations from day 22 to 27, whereas the PL group's levels remained the same (p < 0.05). Although the LOV diet caused a deprivation effect in plasma creatine concentration relative to the Omni diet, concurrent supplementation with creatine resulted in no difference in plasma creatine concentrations between the LOV and Omni diet groups. Dietary advice should be provided to LOV athletes that supplementation with creatine may help to increase their muscle stores of creatine, and thus their ATP resynthesis capabilities, to levels similar to those of omnivores.

  19. Preliminary study to assay plasma amethocaine concentrations after topical application of a new local anaesthetic cream containing amethocaine.

    PubMed

    Mazumdar, B; Tomlinson, A A; Faulder, G C

    1991-10-01

    Plasma concentrations of amethocaine were measured after topical application of amethocaine cream 2 g (5% w/w) to the dorsum of the right hand of 10 adult volunteers. The cream was applied for 240 min and plasma was assayed for amethocaine and its metabolite p-n-butylaminobenzoic acid at 0, 30, 60, 90, 120 and 240 min in all 10 volunteers, and at 360 min in seven volunteers, by high pressure liquid chromatography. No amethocaine was detected in the plasma of seven volunteers. Plasma concentrations of amethocaine up to 0.20 mg litre-1 were observed in three volunteers. No significant side effects were seen and pain scores on insertion of a 16-gauge cannula were 0 in all subjects. We conclude that the absence of clinical toxicity in the 10 healthy volunteers was a reflection of slow absorption and tissue hydrolysis of amethocaine after topical dermal application.

  20. Pregnancy-associated glycoprotein (PAG) concentration in plasma and milk samples for early pregnancy diagnosis in Lacaune dairy sheep.

    PubMed

    El Amiri, B; Sousa, N M; Alvarez Oxiley, A; Hadarbach, D; Beckers, J F

    2015-04-01

    In the present study, four RIA systems (RIA-1 to -4) based on two antisera raised against ovine pregnancy-associated glycoproteins (ovPAGs), combined with an ovine or a bovine PAG tracer were used to measure PAG concentrations in plasma and milk samples of dairy ewes. Blood and milk samples were collected on different days of gestation: 0, 18, 20, 22, 25, 28, 32, 42, and 49. From day 20 onward, the PAG in plasma could be detected in all pregnant ewes using the four RIA systems. By using milk, except for RIA-1, the other systems showed a sensitivity of 100% from day 28 of gestation onward. In plasma, PAG concentrations were higher in multiple than in single pregnancies, while no clear relationship was observed in milk. In conclusion, milk is a good alternative to plasma for early pregnancy diagnosis in sheep from day 28 to day 42.

  1. A comparison of fasting plasma insulin and growth hormone concentrations in marasmic, kwashiorkor, marasmic-kwashiorkor and underweight children.

    PubMed

    Robinson, H; Picou, D

    1977-05-01

    Fasting plasma insulin and growth hormone concentrations were measured in 24 marasmic, 11 kwashiorkor, 16 marasmic-kwashiorkor, and 4 underweight children. Hormone measurements were made by a special modification of the Hales and Randle double antibody immunoassay with increased sensitivity in the concentration range 0-25 micronU/ml. Fasting plasma insulin was low in marasmus, kwashiorkor, and marasmic-kwashiorkor children, and increased to normal levels after recovery. Fasting plasma growth hormone was elevated in all groups during malnutrition and was significantly decreased to normal levels after recovery. There were no significant differences in plasma insulin or growth hormone levels between the different clinical types of severe protein energy malnutrition. These hormonal changes in severe protein energy malnutrition are of complex and not fully understood etiology. However, recovered children appear to have a hormonal pattern similar to that described in normal control infants and children.

  2. The effect of morphine consumption on plasma corticosteron concentration and placenta development in pregnant rats

    PubMed Central

    Kazemi, Masoomeh; Sahraei, Hedayat; Azarnia, Mahnaz; Dehghani, Leila; Bahadoran, Hossein; Tekieh, Elaheh

    2011-01-01

    Background: Previous studies have shown that morphine consumption during pregnancy may delay embryo development or cause abnormal nervous system function. Objective: The present study focused on the effect of maternal morphine consumption on development of placenta and blood corticosteron concentration in addictive pregnant mothers. Materials and Methods: 24 female rats, 170-200g weight, were used. The experimental groups after pregnancy received an oral dose of 0.05 mg/ml of morphine by tap water while the control group received only tap water. On 10th and 14th day of pregnancy, rats were anesthetized and placenta removed surgically, 1ml blood was collected from each pregnant mother from retro-orbital sinus, the concentration of blood corticosteron was determined by corticosteron Elisa kit after centrifugation. The fixed tissue was processed, sectioned and stained with hematoxylin and eosin. Placenta was studied microscopically according to the thickness of layers, area of blood cisterns, and the number of cells. Results: Comparing the plasma corticosteron concentration of the treatment and the control groups, not only a severe increase in the treatment group was detected, but also the thickness of maternal and embryonic portions of the placenta at day 10th and 14th of gestation was different significantly (p≤0.05). Furthermore, an increase in number of cells in maternal and embryonic portion of placenta and a decrease in blood cistern area were demonstrated in both the experimental and the control groups. Conclusion: The effects of morphine, including an increase in blood concentration of corticosteron, in dependent pregnant mothers were seen. Development of placenta in the experimental group was delayed. PMID:25587250

  3. PON-1 Activity and Plasma 8-Isoprostane Concentration in Patients with Angiographically Proven Coronary Artery Disease

    PubMed Central

    Kuchta, Agnieszka; Strzelecki, Adrian; Ćwiklińska, Agnieszka; Totoń, Magdalena; Gruchała, Marcin; Zdrojewski, Zbigniew; Kortas-Stempak, Barbara; Gliwińska, Anna; Dąbkowski, Kamil; Jankowski, Maciej

    2016-01-01

    The aim of the study was to estimate association of the extent of angiographically proven coronary artery disease (CAD) with plasma 8-isoprostane F2 (8-iso-PGF2α) levels as a reliable marker of lipid peroxidation and serum activity of paraoxonase-1, which demonstrates the ability to protect against lipid oxidation. The study included 105 patients with angiographically documented CAD (CAD+) and 45 patients with negative results of coronary angiography (CAD−). Compared to the control group CAD+ patients were characterized by increased 8-iso-PGF2α levels (P = 0.007) and reduced activity of PON-1 towards paraoxon (PONase, P = 0.002) and phenyl acetate (AREase, P = 0.037). Univariate correlation analysis indicated that 8-iso-PGF2α concentrations were positively associated with the severity of CAD as evaluated by the Gensini score (R = 0.41, P < 0.001) while PONase activity (R = −0.26, P < 0.05) and AREase activity (R = −0.23, P < 0.05) were inversely correlated with CAD severity. PONase activity and 8-iso-PGF2α concentration remained independent determinant of atherosclerosis severity in multiple linear regression after adjusting for age, gender, smoking habits, hypertension, type 2 diabetes, statin therapy, and HDL-C and TAG concentration (β coefficients −0.267; P < 0.05 and 0.368; P < 0.001, resp.). The results suggest that PON-1 activity and 8-iso-PGF2α concentration are associated with the presence and extent of coronary stenosis and may be considered additional markers of coronary artery disease. PMID:26697134

  4. Elevated anthranilic acid plasma concentrations in type 1 but not type 2 diabetes mellitus

    PubMed Central

    Oxenkrug, Gregory; van der Hart, Marieke; Summergrad, Paul

    2015-01-01

    Experimental data suggested involvement of tryptophan (Trp) – kynurenine (Kyn) pathway (TKP) in mechanisms of autoimmune, type 1 (T1D), and metabolic, type 2 (T2D), diabetes. However, clinical evaluations of TKP metabolites were limited to T2D. We assessed Trp, Kyn and TKP metabolites: anthranilic (AA), kynurenic (KYNA) and xanthurenic (XA) acids, in plasma samples of fifteen T1D, thirty T2D patients and twenty eight non-diabetic subjects by HPLC-mass spectrometry. Trp concentrations were higher in T1D than in T2D and controls while Kyn concentrations were not changed suggesting down-regulation of indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme of TKP, in T1D. AA concentrations were 2.3-fold higher in T1D than in T2D and in controls. KYNA and XA concentrations were higher in T1D than in controls, and in previously reported T2D. AA elevation might be a specific feature of T1D. TKP shift towards AA formation in T1D may result from riboflavin deficiency, that increases AA in rats and baboons, and is highly associated with T1D but not T2D. AA augments autoimmune-induced apoptosis of pancreatic cells (PC) by increasing formation of antibodies to PC auto-antigen. Marked increase of AA was reported in rheumatoid arthritis, another autoimmune disorder. Trp, an essential amino acid for humans, is synthesized from AA by diabetogenic intestinal microbiome. AA down-regulates IDO by inhibition of Trp entry into cells. Resulting elevation of Trp attenuates Trp depletion-induced protection of PC against autoimmunity. Further studies of TKP might offer new tools for prevention and treatment of T1D and other autoimmune disorders. PMID:26523229

  5. Human urine and plasma concentrations of bisphenol A extrapolated from pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and semi-physiological pharmacokinetic modeling.

    PubMed

    Miyaguchi, Takamori; Suemizu, Hiroshi; Shimizu, Makiko; Shida, Satomi; Nishiyama, Sayako; Takano, Ryohji; Murayama, Norie; Yamazaki, Hiroshi

    2015-06-01

    The aim of this study was to extrapolate to humans the pharmacokinetics of estrogen analog bisphenol A determined in chimeric mice transplanted with human hepatocytes. Higher plasma concentrations and urinary excretions of bisphenol A glucuronide (a primary metabolite of bisphenol A) were observed in chimeric mice than in control mice after oral administrations, presumably because of enterohepatic circulation of bisphenol A glucuronide in control mice. Bisphenol A glucuronidation was faster in mouse liver microsomes than in human liver microsomes. These findings suggest a predominantly urinary excretion route of bisphenol A glucuronide in chimeric mice with humanized liver. Reported human plasma and urine data for bisphenol A glucuronide after single oral administration of 0.1mg/kg bisphenol A were reasonably estimated using the current semi-physiological pharmacokinetic model extrapolated from humanized mice data using algometric scaling. The reported geometric mean urinary bisphenol A concentration in the U.S. population of 2.64μg/L underwent reverse dosimetry modeling with the current human semi-physiological pharmacokinetic model. This yielded an estimated exposure of 0.024μg/kg/day, which was less than the daily tolerable intake of bisphenol A (50μg/kg/day), implying little risk to humans. Semi-physiological pharmacokinetic modeling will likely prove useful for determining the species-dependent toxicological risk of bisphenol A.

  6. Differential effects of L-tryptophan and L-leucine administration on brain resting state functional networks and plasma hormone levels

    PubMed Central

    Zanchi, Davide; Meyer-Gerspach, Anne Christin; Suenderhauf, Claudia; Janach, Katharina; le Roux, Carel W.; Haller, Sven; Drewe, Jürgen; Beglinger, Christoph; Wölnerhanssen, Bettina K.; Borgwardt, Stefan

    2016-01-01

    Depending on their protein content, single meals can rapidly influence the uptake of amino acids into the brain and thereby modify brain functions. The current study investigates the effects of two different amino acids on the human gut-brain system, using a multimodal approach, integrating physiological and neuroimaging data. In a randomized, placebo-controlled trial, L-tryptophan, L-leucine, glucose and water were administered directly into the gut of 20 healthy subjects. Functional MRI (fMRI) in a resting state paradigm (RS), combined with the assessment of insulin and glucose blood concentration, was performed before and after treatment. Independent component analysis with dual regression technique was applied to RS-fMRI data. Results were corrected for multiple comparisons. In comparison to glucose and water, L-tryptophan consistently modifies the connectivity of the cingulate cortex in the default mode network, of the insula in the saliency network and of the sensory cortex in the somatosensory network. L-leucine has lesser effects on these functional networks. L-tryptophan and L-leucine also modified plasma insulin concentration. Finally, significant correlations were found between brain modifications after L-tryptophan administration and insulin plasma levels. This study shows that acute L-tryptophan and L-leucine intake directly influence the brain networks underpinning the food-reward system and appetite regulation. PMID:27760995

  7. Simultaneous determination of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside, senkyunolide I in Beagle dogs plasma by UPLC-MS/MS and its application to a pharmacokinetic study after Oral Administration of Shaofu Zhuyu Decoction.

    PubMed

    Huang, Xiaochen; Su, Shulan; Cui, Wenxia; Liu, Pei; Duan, Jin-ao; Guo, Jianming; Li, Zhenhao; Shang, Erxin; Qian, Dawei; Huang, Zhijun

    2014-07-01

    In this present study, a sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside and senkyunolide I in Beagle dog plasma after oral administration of the Shao-Fu-Zhu-Yu Decoction. Chloramphenicol and clarithromycin were used as internal standards. Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100mm×2.1mm, 1.7μm) at a flow-rate of 0.4mL/min, using 0.1% formic acid-acetonitrile as mobile phase. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. After validation, this method was successfully applied to a pharmacokinetic study. The results showed that the apparent plasma clearance of paeoniflorin, albiflorin, typhaneoside and senkyunolide I were significantly higher than others. Double peak was observed in plasma concentration curves of tetrahydropalmatine, the ferulic acid had a good absorption in Beagle dog plasma, and senkyunolide I was detected in plasma from the first blood sampling time (15min) and rapidly reached Tmax. The compound of typhaneoside has a low bioavailability according to the results. PMID:24907546

  8. Pharmacokinetic studies of phellodendrine in rat plasma and tissues after intravenous administration using ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Yi; Liu, Xin-Guang; Wang, Hui-Ying; Dong, Xin; Gao, Wen; Xu, Xiao-Jun; Li, Ping; Yang, Hua

    2016-09-01

    Phellodendrine, a quaternary ammonium alkaloid extracted from the dried bark of Phellodendrom chinensis Schneid and Phellodendrom amurense Rupr, has the effect of suppressing cellular immune response, reducing blood pressure and antinephritis. However, few investigations have been conducted for the pharmacokinetic study of phellodendrine. Thus, a rapid, simple and reliable ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-QQQ MS/MS) method has been established for quantification of phellodendrine in rat plasma and tissues by using magnoflorine as internal standard. The chromatographic separation was achieved on an Agilent ZORBAX SB-C18 column (4.6mm×50mm, 1.8μm) by gradient elution using 0.1% aqueous formic acid (A) and methanol (B). Triple quadrupole mass detection with multiple reaction monitoring mode was used to monitor the ion transitions, at m/z 342.20→192.20 for phellodendrine and m/z 342.20→58.20 for internal standard, respectively. The developed method was fully validated and successfully applied to the pharmacokinetics and tissue distribution study of phellodendrine after intravenous administration. The lower limits of quantification were 0.5ng/mL for plasma samples, 2.5ng/g for brain and 1ng/g for other tested tissues. Precisions and accuracy values were within the Food and Drug Administration acceptance criteria, the recovery and matrix effects were between 87.8-113.5%. The area under the curve (AUC0-t) ranged from 15.58 to 57.41mg/L min and Cmax were between 1.63-4.93mg/L. The results showed that phellodendrine was eliminated in 120min in plasma and most of tissues and the highest concentrations of phellodendrine were found in the kidney. This study may provide a basis for the further study of phellodendrine.

  9. Alterations in amino acid concentrations in the plasma and muscle in human subjects during 24 h of simulated adventure racing.

    PubMed

    Borgenvik, Marcus; Nordin, Marie; Mikael Mattsson, C; Enqvist, Jonas K; Blomstrand, Eva; Ekblom, Björn

    2012-10-01

    This investigation was designed to evaluate changes in plasma and muscle levels of free amino acids during an ultra-endurance exercise and following recovery. Nine male ultra-endurance trained athletes participated in a 24-h standardized endurance trial with controlled energy intake. The participants performed 12 sessions of running, kayaking and cycling (4 × each discipline). Blood samples were collected before, during and after exercise, as well as after 28 h of recovery. Muscle biopsies were taken before the test and after exercise, as well as after 28 h of recovery. During the 24-h exercise, plasma levels of branched-chain (BCAA), essential amino acids (EAA) and glutamine fell 13, 14 and 19% (P < 0.05), respectively, whereas their concentrations in muscle were unaltered. Simultaneously, tyrosine and phenylalanine levels rose 38 and 50% (P < 0.05) in the plasma and 66 and 46% (P < 0.05) in muscle, respectively. After the 24-h exercise, plasma levels of BCAA were positively correlated with muscle levels of glycogen (r (2) = 0.73, P < 0.05), as was the combined concentrations of muscle tyrosine and phenylalanine with plasma creatine kinase (R (2) = 0.55, P < 0.05). Following 28-h of recovery, plasma and muscle levels of amino acids had either returned to their initial levels or were elevated. In conclusion, ultra-endurance exercise caused significant changes elevations in plasma and muscle levels of tyrosine and phenylalanine, which suggest an increase in net muscle protein breakdown during exercise. There was a reduction in plasma concentrations of EAA and glutamine during exercise, whereas no changes were detected in their muscle concentration after exercise. PMID:22350359

  10. Activation of ENaC by AVP contributes to the urinary concentrating mechanism and dilution of plasma.

    PubMed

    Mironova, Elena; Chen, Yu; Pao, Alan C; Roos, Karl P; Kohan, Donald E; Bugaj, Vladislav; Stockand, James D

    2015-02-01

    Arginine vasopressin (AVP) activates the epithelial Na(+) channel (ENaC). The physiological significance of this activation is unknown. The present study tested if activation of ENaC contributes to AVP-sensitive urinary concentration. Consumption of a 3% NaCl solution induced hypernatremia and plasma hypertonicity in mice. Plasma AVP concentration and urine osmolality increased in hypernatremic mice in an attempt to compensate for increases in plasma tonicity. ENaC activity was elevated in mice that consumed 3% NaCl solution compared with mice that consumed a diet enriched in Na(+) with ad libitum tap water; the latter diet does not cause hypernatremia. To determine whether the increase in ENaC activity in mice that consumed 3% NaCl solution served to compensate for hypernatremia, mice were treated with the ENaC inhibitor benzamil. Coadministration of benzamil with 3% NaCl solution decreased urinary osmolality and increased urine flow so that urinary Na(+) excretion increased with no effect on urinary Na(+) concentration. This decrease in urinary concentration further increased plasma Na(+) concentration, osmolality, and AVP concentration in these already hypernatremic mice. Benzamil similarly compromised urinary concentration in water-deprived mice and in mice treated with desmopressin. These results demonstrate that stimulation of ENaC by AVP plays a critical role in water homeostasis by facilitating urinary concentration, which can compensate for hypernatremia or exacerbate hyponatremia. The present findings are consistent with ENaC in addition to serving as a final effector of the renin-angiotensin-aldosterone system and blood pressure homeostasis, also playing a key role in water homeostasis by regulating urine concentration and dilution of plasma. PMID:25391898

  11. Concentrations of besifloxacin, gatifloxacin, and moxifloxacin in human conjunctiva after topical ocular administration

    PubMed Central

    Torkildsen, Gail; Proksch, Joel W; Shapiro, Aron; Lynch, Stephanie K; Comstock, Timothy L

    2010-01-01

    Purpose To evaluate the pharmacokinetic properties of besifloxacin, gatifloxacin, and moxifloxacin in the conjunctival tissue of healthy volunteers after topical application. Methods One-hundred eight (108) subjects were randomly assigned to receive one drop of besifloxacin (0.6% suspension), gatifloxacin (0.3% solution), or moxifloxacin (0.5% solution) ophthalmic formulations in one eye prior to conjunctival biopsy. Conjunctival samples were taken from subjects at either 15 minutes, 30 minutes, 2 hours, 6 hours, 12 hours, or 24 hours after dosing. Results All three fluoroquinolones reached a peak mean concentration 15 minutes after dosing. The mean concentrations of besifloxacin, gatifloxacin, and moxifloxacin at 15 minutes were 2.30 ± 1.42 μg/g, 4.03 ± 3.84 μg/g, and 10.7 ± 5.89 μg/g, respectively. Concentrations decreased with each subsequent time point. At 24 hours after dosing, concentrations of besifloxacin were measurable in 4 of 6 subjects, compared with 3 of 6 subjects for gatifloxacin and 2 of 6 subjects for moxifloxacin. Besifloxacin had the greatest mean residence time (4.7 hours) in the conjunctival tissue. With regard to methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis, besifloxacin had the greatest area-under-the-curve (AUC) to MIC90 ratio. Nine percent (9%) of study subjects (N = 7) experienced a transient reduction in visual acuity. Conclusion All three fluoroquinolones were well tolerated and reached levels in the conjunctiva above the MIC90s of methicillin-sensitive S. aureus and S. epidermidis for at least 2 hours. PMID:20463802

  12. Azithromycin Concentrations in Blood and Gingival Crevicular Fluid after Systemic Administration

    PubMed Central

    Lai, Pin-Chuang; Ho, Weiting; Jain, Nidhi; Walters, John D.

    2011-01-01

    Background Azithromycin is a macrolide antibiotic that is active against several periodontal pathogens. Macrolides are taken up and concentrated inside gingival fibroblasts, which could influence their pharmacokinetics. This study tested the hypothesis that steady-state levels of azithromycin are higher and more sustained in gingival crevicular fluid (GCF) than in serum. Methods Four healthy subjects received an initial dose of 500 mg azithromycin followed by 250 mg doses on each of the next 2 days. Serum and GCF samples were obtained 2 hours after the last dose (day 2) and on days 4 and 7. GCF samples were collected from maxillary posterior sites with paper strips. The strips were pooled and eluted with high purity water. After extraction, the azithromycin content of the serum samples and GCF eluates was determined with an agar diffusion bioassay. Results On days 2, 4 and 7, the concentrations of azithromycin in blood serum were 0.22 ± 0.02, 0.08 ± 0.02 and 0.04 ± 0.01 μg/ml, respectively. The concentrations in GCF were 8.82 ± 1.25, 7.90 ± 1.72 and 7.38 ± 1.15 μg/ml, respectively. Mean GCF levels were significantly higher than mean serum levels (P ≤ 0.02, paired t-test). Conclusion The findings demonstrate that the pharmacokinetic profiles of azithromycin are different in GCF and serum. At steady state, azithromycin concentrations in GCF were higher and more sustained than those in serum. Based on previous studies, the levels observed in GCF were above the MIC for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia. PMID:21417585

  13. An investigation into the vancomycin concentration in the cerebrospinal fluid due to vancomycin intraventricular administration in newborns: a study of 13 cases.

    PubMed

    Matsunaga, Nobuaki; Hisata, Ken; Shimizu, Toshiaki

    2015-06-01

    Treatment against shunt infection by transvenous antimicrobial treatment is difficult, with a high risk of relapse. Consequently, to maintain a sufficient cerebrospinal fluid (CSF) concentration, intraventricular administration is utilized in combination with the transvenous administration of vancomycin (VCM). Few studies have so far investigated the optimum administration dose for newborns and the concentration in the CSF. Therefore, we chronologically measured the VCM concentration in the CSF after VCM intraventricular administration in newborns and attempted to elucidate the optimum administration method.The participants consisted of newborns admitted to Juntendo University Neonatal intensive care unit from March 2007 to June 2011 who underwent interventricular shunting placement. VCM was intraventricularly administered to 10 patients for a total of 13 cases. The CSF concentration of VCM was chronologically measured at 12 to 120  hours following the intraventricular administration of VCM.The intraventricular administration groups with VCM of 20 (n = 6) and 10  mg (n = 2) had a high concentration in the CSF at 24  hours following administration (95-168  mg/L), with the concentration remaining high at 72  hours (13.2-72  mg/L). At the same time, in the 5  mg group (n = 5), the concentration in the CSF 24  hours following VCM administration was sufficiently maintained (33.2-62.9  mg/L), with a sufficient trough concentration still maintained at 72  hours (11.7-16.5  mg/L).The concentration in the CSF is prolonged in newborns, thus allowing a sufficient therapeutic range to be maintained even at an intraventricular administration of 5  mg. It is therefore believed that the monitoring of the CSF is very important regarding the administration interval because the VCM concentration in the CSF differs depending on the case.

  14. Circadian rhythms in the concentration of plasma thyroxine in vitamin A-deprived calves.

    PubMed

    Bridge, P S; Abrams, J T; Curtis, R J; Spratling, F R

    1977-01-01

    Over a period of approximately 11 months, a total of 57 24 hour experiments was performed on 5 calves. The animals were fed a vitamin A-free diet and showed the common signs of vitamin A deficiency. During each experiment blood samples were taken hourly and the plasma iodoprotein content of each sample was determined. Each set of 24 values was subjected to Fourier analysis in an attempt to elucidate 24 hour, sinusoidal rhythms in iodoprotein concentration. A rhythm was deemed to be present where the chance of random sampling producing the observed pattern of concentration was less than or equal to 0.05. 25 such rhythms were detected. As the probability of random sampling giving rise to 25 rhythms in 57 tests is extremely small, circadian rhythms are assumed to exist in vitamin A-deficient, as in normal, calves. Rhythms, the characteristics of which are described here, were observed under natural conditions of day and night, and with controlled light and darkness. It is suggested that the occurrence of the rhythms, in relation to the environmental patterns of light and darkness, is better related to other aspects of brain activity than to those concerned with vision. PMID:563385

  15. Effect of heat stress and drinking water salt supplements on plasma electrolytes and aldosterone concentration in broiler chickens

    NASA Astrophysics Data System (ADS)

    Deyhim, F.; Teeter, R. G.

    1995-12-01

    An experiment was conducted to evaluate the effects of supplementing drinking water with isomolar (0.067 mol/l) KCl or NaCl on mass gain, food and water consumption, rectal temperature, and plasma concentrations of aldosterone, Na+, and K+ in broiler chickens reared in thermoneutral and cycling heat stressing environments. Heat stress decreased ( P≤0.05) mass gain, food consumption, and plasma concentrations of Na+ and K+, while increases ( P≤0.05) in plasma concentrations of aldosterone, rectal temperature, and water consumption were observed. Drinking water supplemented with either KCl or NaCl increased ( P≤0.05) broiler mass gain and water consumption, but had no effect ( P>0.1) on the other variables evaluated. The results of this study indicate that broiler chickens in a heat stress environment are under osmotic stress and supplementing drinking water with 0.067 mo