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Sample records for plasma metabolite levels

  1. Assessing Stress in Arctic Lemmings: Fecal Metabolite Levels Reflect Plasma Free Corticosterone Levels.

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    Fauteux, Dominique; Gauthier, Gilles; Berteaux, Dominique; Bosson, Curtis; Palme, Rupert; Boonstra, Rudy

    Interest in the ecology of stress in wild populations has triggered the development of noninvasive methods for quantifying stress hormones. Measurement of fecal corticosteroid metabolites (FCMs) is one such method, but it is still unclear whether FCMs can be a reliable proxy of free plasma glucocorticoids. To assess the validity of this assumption, we carried out a robust assessment on brown lemmings (Lemmus trimucronatus) from Bylot Island, Nunavut, Canada, that were hand captured and anesthetized and related plasma glucocorticoid levels to fecal metabolite glucocorticoid levels. We examined endogenous factors that could explain interindividual variability. Blood corticosterone was measured from samples obtained on capture and 30 min later, and FCM levels were measured from animals kept in captivity for 72 h. Plasma free corticosterone increased 135-fold over baseline values 30 min after capture, which confirmed that initial handling was perceived as a stressor. We found that FCM levels were highly related with free (marginal [Formula: see text] = 0.53) but not with total ([Formula: see text] = 0.02) corticosterone levels, regardless of age, sex, and reproductive condition. FCM levels started increasing 2 h after capture and reached maximum levels 4 h after capture. No circadian rhythm in FCMs was found. Plasma total corticosterone levels were much higher in adult females compared with adult males, but this difference was much smaller when measuring free corticosterone levels and FCM levels. Our results suggest that FCM levels are good measures of stress by being closely related to plasma free corticosterone levels in brown lemmings.

  2. Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

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    Hagman, R; Kindahl, H; Lagerstedt, A-S

    2006-01-01

    Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α metabolite 15-ketodihydro-PGF2α (PG-metabolite), progesterone and oestradiol (E2-17β) levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra. PMID:16722306

  3. Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

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    Hagman R

    2006-03-01

    Full Text Available Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α metabolite 15-ketodihydro-PGF2α (PG-metabolite, progesterone and oestradiol (E2-17β levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra.

  4. Plasma oxytocin but not prostaglandin F2 alpha metabolite levels at cerclage may predict preterm delivery.

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    Behrens, O; Böhmer, S; Goeschen, K; Fuchs, A R

    1991-06-01

    Plasma oxytocin and prostaglandin F2 alpha metabolite (PGFM) concentrations were measured in 45 patients admitted for cerclage during the second trimester. Samples were collected before, 3 hours after, and 3 days after the Shirodkar procedure. Uterine activity was recorded by external tocography twice daily for 30 minutes. Twenty-eight women with uncomplicated pregnancy and commensurate gestational age served as controls. Cervical length, measured by ultrasonography, was significantly shorter before cerclage (36 +/- 2 mm) than after cerclage (43 +/- 2 mm) or compared with controls (48 +/- 1 mm). Bishop scores ranged from 3-6 (median 4) in the cerclage group and 0-1 (median 0) in controls. Fifteen cerclage patients and one control delivered preterm 5-22 weeks after the procedure. Initial plasma PGFM levels were significantly higher in cerclage patients than in controls. The cerclage procedure caused an immediate rise in plasma PGFM and a subsequent fall below initial levels to control values. Neither the initial levels of PGFM nor the increments 3 hours after cerclage correlated with the outcome of pregnancy. By contrast, plasma oxytocin levels before cerclage were significantly higher in patients who subsequently delivered preterm than in those who delivered at term. Cerclage resulted in a significant fall in plasma oxytocin at 3 hours in patients with preterm delivery, but after 3 days the oxytocin levels had returned to the precerclage values. Patients who had increased uterine contractions had significantly higher plasma oxytocin levels but lower PGFM levels than those without contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Association of plasma IL-6 and Hsp70 with HRV at different levels of PAHs metabolites.

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    Jian Ye

    Full Text Available BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs is associated with reduced heart rate variability (HRV, a strong predictor of cardiovascular diseases, but the mechanism is not well understood. OBJECTIVES: We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function. METHODS: HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6 and heat shock protein 70 (Hsp70 were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs were measured by gas chromatography-mass spectrometry. RESULTS: We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all Ptrend<0.05; and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP and low frequency (LF (Ptrend = 0.014 and 0.006, respectively. In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all Ptrend<0.05, but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN, TP and LF in the low-PAHs metabolites groups (all Ptrend<0.05. We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV. CONCLUSIONS: In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.

  6. Plasma levels of catecholamine metabolites predict the response to sulpiride or fluvoxamine in major depression.

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    Ueda, N; Yoshimura, R; Shinkai, K; Nakamura, J

    2002-09-01

    We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.

  7. Switching antipsychotics to aripiprazole or blonanserin and plasma monoamine metabolites levels in patients with schizophrenia.

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    Miura, Itaru; Shiga, Tetsuya; Katsumi, Akihiko; Kanno-Nozaki, Keiko; Mashiko, Hirobumi; Niwa, Shin-Ichi; Yabe, Hirooki

    2014-03-01

    Blonanserin is a novel atypical antipsychotic drug that has efficacy equal to risperidone. We investigated the effects of aripiprazole and blonanserin on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol in the switching strategy of schizophrenia. Twenty two Japanese patients with schizophrenia were enrolled into this open study. The antipsychotics of all patients were switched to aripiprazole or blonanserin for the improvement of clinical symptoms or side effects. Plasma monoamine metabolites levels were analyzed with high-performance liquid chromatography. There were no significant effects for time (p = 0.346) or time × group interaction (p = 0.27) on the changes of positive and negative syndrome scale (PANSS) total score, although blonanserin decreased PANSS scores. We observed negative correlation between pHVA at baseline and the change in PANSS total score (rs = -0.450, p = 0.046). We also found positive correlation between the changes in pHVA and the changes in PANSS total (rs = 0.536, p = 0.015) and positive (rs = 0.572, p = 0.008) scores. There were no differences between blonanserin and aripiprazole in the improvement of clinical symptoms. Our results suggest that pHVA may be useful indicator for the switching strategy to aripiprazole or blonanserin in schizophrenia. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Dexamethasone decreases plasma levels of the prochiral fenbendazole and its chiral and achiral metabolites in sheep.

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    Sánchez, S; Small, J; Jones, D G; McKellar, Q A

    2003-07-01

    1. The effect of co-administration of either short- or long-acting formulations of DXM on hepatic function and the plasma pharmacokinetic behaviour of prochiral fenbendazole (FBZ) and its metabolites was evaluated in sheep. 2. Neither DXM treatment markedly affected any of the biochemical markers of hepatic function tested. In contrast, both formulations significantly modified the plasma pharmacokinetic behaviour of FBZ and its metabolites. 3. Plasma FBZ concentrations and the associated area under the time-concentration curves were significantly lower, although the plasma detection period was longer (72 versus 48 h) in the DXM pretreated animals compared with those given FBZ alone. 4. DXM also appeared to alter the pattern of FBZ absorption, possibly through effects on abomasal pH. The shape of the plasma concentration-time curves for oxfendazole (OFZ) and fenbendazole sulphone (FBZSO(2)) were similar to FBZ, raising the possibility that DXM treatment may have altered the liver biotransformation of the parent drug. 5. The concentrations of the (+) chiral metabolite of OFZ were significantly lower in DXM pretreated animals compared with those given FBZ alone. The trend was similar for the (-) antipode, although the differences between DXM pretreated and non-pretreated animals were not statistically significant.

  9. Feed deprivation in Senegalese sole (Solea senegalensis Kaup, 1858) juveniles: effects on blood plasma metabolites and free amino acid levels.

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    Costas, Benjamín; Aragão, Cláudia; Ruiz-Jarabo, Ignacio; Vargas-Chacoff, Luis; Arjona, Francisco Jesús; Dinis, Maria Teresa; Mancera, Juan Miguel; Conceição, Luís E C

    2011-09-01

    The effects of prolonged feed deprivation were assessed on blood plasma metabolites and free amino acid levels in Solea senegalensis. Juvenile specimens were maintained at two experimental conditions (24 h fasted and 21 days feed-deprived). In feed-deprived fish, relative growth rate and hepatosomatic index as well as plasma triglycerides and proteins levels were significantly lower. However, plasma cortisol levels were higher in feed-deprived fish, while plasma glucose and lactate values were not significantly different between treatments. Furthermore, feed-deprived fish showed higher levels of total plasma free amino acids than 24 h fasted fish. In 21 days feed-deprived sole, an increase in plasma cortisol levels may suggest a functional role in mobilizing energy due to the catabolic action of this hormone in teleosts. Higher levels of glutamine, arginine and ornithine in 21 days feed-deprived fish may be indicative of a dual role for these amino acids: ammonia detoxification and carbon source for gluconeogenesis. The increased plasma glucogenic and branched-chain amino acid levels, together with the maintenance of plasma glucose in 21 days feed-deprived sole, suggest active liver gluconeogenic processes supported by tissue proteolysis.

  10. Plasma hormones, metabolites, milk production, and cholesterol levels in Murrah buffaloes fed with Asparagus racemosus in transition and postpartum period.

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    Singh, Surendra Pratap; Mehla, Ram Kumar; Singh, Mahendra

    2012-12-01

    Ten dry and pregnant Murrah buffaloes were selected to investigate the effect of Asparagus racemosus feeding on hormones, metabolites, milk yield, and plasma cholesterol levels. The treatment groups of buffaloes were fed with A. racemosus (shatavari) @ 150 g/day/animal during prepartum and @ 300 g/day/animal during the postpartum period. Blood samples collected on -6, -4, -2-week, day of parturition (0), and +2, +4, and +6-week postpartum were analyzed for plasma total cholesterol, triglycerides, HDL, low-density lipoproteins (LDL), prolactin, cortisol, and blood metabolites. Milk samples collected at weekly intervals (+1, +3, +5, and 7 weeks) were analyzed for total milk fat cholesterol. Prepartum plasma cholesterol concentrations were significantly higher in treatment group over the control (P < 0.05). Mean plasma triglycerides, LDL cholesterol, HDL cholesterol, glucose, and nonesterified fatty acid (NEFA) levels varied nonsignificantly between groups. Plasma prolactin and cortisol concentrations were significantly (P < 0.01) more in treatment group than in control group. On day of parturition, plasma prolactin, cortisol, LDL, and plasma total cholesterol were higher (P < 0.01) in treatment group buffaloes in comparison to control group. A. racemosus feeding significantly (P < 0.01) increased plasma prolactin, cortisol (P < 0.01), and milk fat cholesterol (P < 0.05) without affecting total cholesterol, HDL, LDL, glucose, and NEFA concentrations. The buffaloes of treatment group produced more milk (@ 0.526 kg/animal/day) suggesting thereby that A. racemosus is galactopoietic. It was concluded that feeding of A. racemosus increases plasma prolactin and cortisol and decreased plasma total cholesterol and LDL concentration.

  11. Evaluation of plasma reactive oxygen metabolites levels in obese subjects with periodontal disease

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    Snophia Suresh

    2016-01-01

    Result and Conclusion: In this study, obese subjects with chronic periodontitis (Group I had mean plasma ROM levels (442.3 ± 15.65 Carratelli unit [CARR U] showing 100% subjects with high oxidative stress. Obese subjects with chronic gingivitis (Group II had mean plasma ROM levels (358.7 ± 20.61 CARR U indicating 86.7% subjects with oxidative stress. Obese subjects with healthy periodontium (Group III had 46.7% subjects with slight oxidative stress, and the mean ROM level was 320.2 ± 17.57. Nonobese subjects with healthy periodontium (Group IV had 80% of subjects with normal oxidative stress and the mean plasma ROM level was 296.9 ± 20.35 CARR U. The intra- and inter-group comparison showed significant difference (P < 0.001. From our study, we report that obese subjects with periodontitis have more oxidative stress compared to obese subjects with healthy periodontium.

  12. Effect of major and minor surgery on plasma levels of arginine, citrulline, nitric oxide metabolites, and ornithine in humans.

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    Hol, Jaap W; van Lier, Felix; Valk, Madelous; Klimek, Markus; Stolker, Robert J; Fekkes, Durk

    2013-12-01

    To determine the effect of surgical invasiveness on plasma levels of arginine, citrulline, ornithine, and nitric oxide (NO) in humans. Surgical trauma may have a profound effect on the metabolism of NO. However, human studies reported both increased and decreased NO levels after hemorrhagic shock. Arginine, citrulline, and ornithine are key amino acids involved in NO metabolism, but studies evaluating these amino acids together with NO and during 2 types of surgery are lacking. This study tests the hypothesis that major surgery has a more profound effect on plasma levels of arginine, citrulline, NO, and ornithine than minor surgery. Fifteen patients undergoing minor surgery (vulvectomy) and 13 patients undergoing major surgery (laparotomy) were prospectively followed up for 4 days. Plasma was collected for evaluation of levels of arginine, citrulline, NO, and ornithine. Throughout the experiment, arginine levels did not significantly differ between experimental groups. Perioperative plasma citrulline levels were significantly lower in the laparotomy group than in the vulvectomy group, whereas both groups showed a decrease in citrulline levels at the end of the operation and 24 hours postoperatively. Roughly the same pattern was seen for plasma NO and ornithine levels. However, ornithine levels in the laparotomy group showed a more drastic decrease at the end of the operation and 24 hours postoperatively than citrulline and NO levels. The level of surgical invasiveness has the most profound effect on plasma levels of ornithine. In addition, heavier surgical trauma is paired with lower postoperative levels of citrulline and NO metabolites than lighter surgery. It is suggested that surgical trauma stimulates the laparotomy group to consume significantly more ornithine, possibly for use in wound healing.

  13. The metabolite generated by dipeptidyl-peptidase 4 metabolism of glucagon-like peptide-1 has no influence on plasma glucose levels in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Zander, M; Madsbad, S; Deacon, C F

    2006-01-01

    /INTERPRETATION: At approximately similar concentrations of intact GLP-1 (IV, IB, HSC), but with widely ranging metabolite concentrations, the effect on plasma glucose levels was equal, indicating that the presence of the metabolite does not antagonise the glucose-lowering effect of GLP-1....

  14. Effect of colostral fat level on fat deposition and plasma metabolites in the newborn pig.

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    Le Dividich, J; Esnault, T; Lynch, B; Hoo-Paris, R; Castex, C; Peiniau, J

    1991-06-01

    The effects of colostral fat level on fat deposition and plasma concentrations of glucose, insulin, and free fatty acids (FFA) were determined in 28 newborn pigs during the first postnatal day. Soon after birth, pigs were allotted to four treatments groups. Group 1 was killed at birth. The remaining pigs were fed intragastrically sow colostrum that contained high (10.2%; HFC), normal (4.8%; NFC) or low (1.0%; LFC) levels of total fat at the rate of 15 to 18 g/kg birth weight at 65- to 70-min intervals. A total of 21 feedings was provided and pigs were killed 1 h after the last feeding. Body fat deposition increased linearly (P less than .01) with the amount of ingested fat by .32 (+/- .04) g per 1-g increase in fat intake. Fatty acid composition of the pigs changed toward that of the colostrum with increased fat in colostrum. More liver glycogen was lost (P less than .01) in pigs given LFC. Plasma concentrations of glucose and insulin were similar in pigs fed HFC and NFC. After the 11th feeding (14 h postnatal), LFC resulted in lower plasma glucose concentrations (P less than .05) than HFC or NFC. Plasma insulin concentrations also were lower in pigs fed LFC. Plasma FFA concentrations remained unchanged in pigs fed LFC but increased with both fat content in colostrum (P less than .05) and time (P less than .05) in the other two groups. Colostral fat plays a major role in the supply of energy and in glucose homeostasis in the neonatal pig.

  15. Plasma levels of free metanephrines and 3-methoxytyramine indicate a higher number of biochemically active HNPGL than 24-h urinary excretion rates of catecholamines and metabolites

    NARCIS (Netherlands)

    Corssmit, E. P. M.; de Jong, W. H. A.; Brookman, D.; Kema, I. P.; Romijn, J. A.; van Duinen, N.

    2013-01-01

    Context: A substantial number of patients with head and neck paragangliomas (HNPGLs) have biochemically active tumors, evidenced by increased urinary excretion of catecholamines and metabolites, including 3-methoxytyramine (3MT). It is unclear whether plasma levels of these parameters are more sensi

  16. Plasma levels of brain derived-neurotrophic factor and catecholamine metabolites are increased during active phase of psychotic symptoms in CNS lupus: a case report.

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    Ikenouchi, Atsuko; Yoshimura, Reiji; Ikemura, Naomi; Utsunomiya, Kensuke; Mitoma, Masae; Nakamura, Jun

    2006-09-30

    In the present study, the authors reported a case of systemic lupus erythematosus (SLE) with central nervous system involvement (CNS lupus). The authors also longitudinally investigated plasma levels of brain-derived neurotrophic factor (BDNF) and catecholamine metabolites in the patient, and found that plasma levels of BDNF, 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) were raised in accordance with the severity of psychotic symptoms in this case of CNS lupus. These results suggest that it is useful to measure plasma levels of BDNF and the catecholamine metabolites in order to predict the severity of psychotic symptoms in CNS lupus and to provide a differential diagnosis from that of steroid-induced psychosis.

  17. Associations between five-factor model of the Positive and Negative Syndrome Scale and plasma levels of monoamine metabolite in patients with schizophrenia.

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    Watanabe, Kenya; Miura, Itaru; Kanno-Nozaki, Keiko; Horikoshi, Sho; Mashiko, Hirobumi; Niwa, Shin-Ichi; Yabe, Hirooki

    2015-12-15

    The five-factor model of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia symptoms is the most common multiple-factor model used in analyses; its use may improve evaluation of symptoms in schizophrenia patients. Plasma monoamine metabolite levels are possible indicators of clinical symptoms or response to antipsychotics in schizophrenia. We investigated the association between five-factor model components and plasma monoamine metabolites levels to explore the model's biological basis. Plasma levels of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high-performance liquid chromatography in 65 Japanese patients with schizophrenia. Significant negative correlation between plasma 5-HIAA levels and the depression/anxiety component was found. Furthermore, significant positive correlation was found between plasma MHPG levels and the excitement component. Plasma HVA levels were not correlated with any five-factor model component. These results suggest that the five-factor model of the PANSS may have a biological basis, and may be useful for elucidating the psychopathology of schizophrenia. Assessment using the five-factor model may enable understanding of monoaminergic dysfunction, possibly allowing more appropriate medication selection. Further studies of a larger number of first-episode schizophrenia patients are needed to confirm and extend these results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Plasma level monitoring of the major metabolites of diacetylmorphine (heroin) by the "chasing the dragon" route in severe heroin addicts.

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    Dubois, N; Demaret, I; Ansseau, M; Rozet, E; Hubert, Ph; Charlier, C

    2013-01-01

    The objective of the present study was to verify if severe physical health problems frequently encountered in heroin addicts and the concomitant use of alcohol and legal or illegal drugs other than heroin influenced the pharmacokinetics of the major metabolites of heroin. We conducted a 90 minutes follow-up of the plasma concentrations of the pharmaceutical heroin, named diacetylmorphine (DAM), in patients recruited in a DAM assisted treatment centre. TADAM (Traitement Assisté par DiAcétylMorphine) aimed to compare the efficacy of heroin-assisted treatment (HAT) compared with methadone maintenance treatment (MMT) for heroin users considered as treatment resistant patients and who have severe physical and mental health problems. Eleven patients were recruited. Blood samples were collected at baseline and 15, 45 and 90 minutes after DAM administration. All patients received DAM by the "chasing the dragon" route. Plasma samples were analyzed by a previously described ultra-high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS) method. A principal component analysis (PCA) was performed and 8 metabolite concentrations ratios were calculated to evaluate the influence of various factors (DAM dose, patient pathologies, concomitant use of medications, methadone, street heroin, alcohol and cocaine) on heroin metabolite pharmacokinetics. It seemed to be not affected by the DAM dose, patient pathologies and the concomitant use of medications, methadone, street heroin and alcohol. Cocaine use was the only parameter which showed differences in heroin pharmacokinetics.

  19. Effect of prepartal and postpartal dietary fat level on performance and plasma concentration of metabolites in transition dairy cows.

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    Karimian, M; Khorvash, M; Forouzmand, M A; Alikhani, M; Rahmani, H R; Ghaffari, M H; Petit, H V

    2015-01-01

    The objective of this study was to determine the effects of 2 levels of dietary fat (low and high) offered during the prepartal and postpartal periods on dry matter intake (DMI), plasma concentration of metabolites, and milk yield and composition. Twenty-four Holstein dry cows were assigned on d 21 relative to expected parturition date to 1 of 4 treatments in a 2×2 factorial arrangement of 2 levels of fat fed during the prepartal period and 2 levels of fat fed during the postpartal period: prepartal low fat and postpartal low fat (LF-LF), prepartal low fat and postpartal high fat (LF-HF), prepartal high fat and postpartal low fat (HF-LF), or prepartal high fat and postpartal high fat (HF-HF). Prepartal and postpartal LF diets contained no fat supplement. Prepartal HF diets contained 1.60% calcium salts of soybean oil. The proportion of calcium salts of soybean oil was increased to 1.70% of DM for the first 21 d of lactation and to 2.27% of DM from d 21 to 56 of lactation in the HF diet. Diets were fed for ad libitum intake from d 21 before calving until d 56 of gestation. Prepartal DMI was lower for cows fed the HF diet compared with those fed the LF diet (12.6 vs. 16.2kg/d). Postpartum, cows fed the HF-HF and HF-LF diets had, respectively, the lowest and highest DMI, although no significant differences existed between HF-LF and LF-LF. Net energy intake was higher for cows fed the postpartal HF diets compared with those fed the LF diets. Prepartal fat level had no effect on net energy intake. Cows offered the prepartal HF diet had higher milk yield when offered the postpartal LF diet compared with those offered the postpartal HF diet and no effect of the postpartal fat level was detected when cows were fed the prepartal LF diet. Milk composition was similar among treatments. Plasma cholesterol concentration postpartum was higher for cows fed the prepartal LF diet than for those fed the prepartal HF diet (5.16 vs. 3.74mmol/L) and postpartal fat level had no effect

  20. Effect of ACTH and CRH on Plasma Levels of Cortisol and Prostaglandin F2α Metabolite in Cycling Gilts and Castrated Boars

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    Madej A

    2006-12-01

    Full Text Available The present study was designed to evaluate the effects of synthetic ACTH (1–24, tetracosactid and porcine CRH on the plasma levels of cortisol and PGF2α metabolite in cycling gilts (n = 3 and castrated boars (n = 3. The experiments were designed as crossover studies for each gender separately. Each animal received, during three consecutive days; 1 ACTH (Synacthen® Depot at a dose of 10 μg/kg body weight in 5 ml physiological saline, 2 porcine CRH at a dose 0.6 μg/kg body weight in 5 ml physiological saline or 3 physiological saline (5 ml. The test substances were administered via an indwelling jugular cannula in randomized order according to a Latin square. The administration of ACTH to cycling gilts resulted in concomitant elevations of cortisol and PGF2α metabolite with peak levels reached at 70.0 ± 10.0 and 33.3 ± 6.7 min, respectively. Similarly, the administration of ACTH to castrated boars resulted in concomitant elevation of cortisol and PGF2α metabolite with peak levels reached at 60.0 ± 0.0 and 20.0 ± 0.0 min, respectively. Cortisol peaked at 20 min after administration of CRH in both cycling gilts and castrated boars with maximum levels of 149.3 ± 16.5 nmol/1 and 138.3 ± 10.1 nmol/1, respectively. It can be concluded that administration of synthetic ACTH (tetracosactid to pigs caused a concomitant elevation of cortisol and PGF2α metabolite levels in both cycling gilts as well as castrated boars. The administration of CRH to pigs resulted in an elevation of cortisol levels in both cycling gilts and castrated boars. Conversely, PGF2α metabolite levels were not influenced by the administration of CRH either in cycling gilts or in castrated boars.

  1. Effect of ACTH and CRH on Plasma Levels of Cortisol and Prostaglandin F2α Metabolite in Cycling Gilts and Castrated Boars

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    Kindahl H

    2005-12-01

    Full Text Available The present study was designed to evaluate the effects of synthetic ACTH (1–24, tetracosactid and porcine CRH on the plasma levels of cortisol and PGF2α metabolite in cycling gilts (n = 3 and castrated boars (n = 3. The experiments were designed as crossover studies for each gender separately. Each animal received, during three consecutive days; 1 ACTH (Synacthen® Depot at a dose of 10 μg/kg body weight in 5 ml physiological saline, 2 porcine CRH at a dose 0.6 μg/kg body weight in 5 ml physiological saline or 3 physiological saline (5 ml. The test substances were administered via an indwelling jugular cannula in randomized order according to a Latin square. The administration of ACTH to cycling gilts resulted in concomitant elevations of cortisol and PGF2α metabolite with peak levels reached at 70.0 ± 10.0 and 33.3 ± 6.7 min, respectively. Similarly, the administration of ACTH to castrated boars resulted in concomitant elevation of cortisol and PGF2α metabolite with peak levels reached at 60.0 ± 0.0 and 20.0 ± 0.0 min, respectively. Cortisol peaked at 20 min after administration of CRH in both cycling gilts and castrated boars with maximum levels of 149.3 ± 16.5 nmol/1 and 138.3 ± 10.1 nmol/1, respectively. It can be concluded that administration of synthetic ACTH (tetracosactid to pigs caused a concomitant elevation of cortisol and PGF2α metabolite levels in both cycling gilts as well as castrated boars. The administration of CRH to pigs resulted in an elevation of cortisol levels in both cycling gilts and castrated boars. Conversely, PGF2α metabolite levels were not influenced by the administration of CRH either in cycling gilts or in castrated boars.

  2. The levels of zearalenone and its metabolites in plasma, urine and faeces of horses fed with naturally, Fusarium toxin-contaminated oats.

    Science.gov (United States)

    Songsermsakul, P; Böhm, J; Aurich, C; Zentek, J; Razzazi-Fazeli, E

    2013-02-01

    Concentration profile of zearalenone (ZON) and its metabolites in plasma, urine and faeces samples of horses fed with Fusarium toxin-contaminated oats is described. In plasma, β-zearalenol (β-ZOL) was detected at high levels on day 10 of the study (3.21-6.24 μg/l). β-Zearalenol and α-zearalenol were the major metabolites in urine. Zearalenone, α-ZOL and β-ZOL were predominantly found in faeces. Zearalanone could also be detected in urine (1.34-5.79 μg/l) and faeces (1 μg/kg). The degree of glucuronidation was established in all sample types, approximately 100% in urine and plasma. Low per cent of glucuronidation (4-15%) was found in faeces samples. The results indicate the main conversion of ZON into β-ZOL in horse. This finding could explain why horse is not susceptible to ZON in comparison with swine which produce α-ZOL as a predominant metabolite.

  3. A simple LC-MS/MS method to determine plasma and cerebrospinal fluid levels of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in patients with neurocysticercosis.

    Science.gov (United States)

    González-Hernández, Iliana; Ruiz-Olmedo, María Isabel; Cárdenas, Graciela; Jung-Cook, Helgi

    2012-02-01

    The development and validation of an LC-MS/MS method for the simultaneous determination of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in human plasma are described. Samples of 200 μL were extracted with ether-dichloromethane-chloroform (60:30:10, v/v/v). The chromatographic separation was performed using a C(18) column with methanol-formic acid 20 mmol/L (70:30) as the mobile phase. The method was linear in a range of 20-5000 ng/mL for albendazole sulfoxide and 10-1500 ng/mL for albendazole sulfone. For both analytes the method was precise (RSD 90%). The method was successfully applied to determine the plasma and cerebrospinal fluid levels of albendazole sulfoxide and albendazole sulfone in patients with subarachnoidal neurocysticercosis who received albendazole at 30 mg/kg per day for 7 days. This LC-MS/MS method yielded a quick, simple and reliable protocol for determining albendazole sulfoxide and albendazole sulfone concentrations in plasma and cerebrospinal fluid samples and is applicable to therapeutic monitoring.

  4. Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a gut microbiome metabolite associated with CVD risk

    Energy Technology Data Exchange (ETDEWEB)

    Bergeron, Nathalie; Williams, Paul T.; Lamendella, Regina; Faghihnia, Nastaran; Grube, Alyssa; Li, Xinmin; Wang, Zeneng; Knight, Rob; Jansson, Janet K.; Hazen, Stanley L.; Krauss, Ronald M.

    2016-12-20

    Production of trimethylamine-N-oxide (TMAO), a biomarker of CVD risk, is dependent on intestinal microbiota, but little is known of dietary conditions promoting changes in gut microbial communities. Resistant starches (RS) alter the human microbiota. We sought to determine whether diets varying in RS and carbohydrate (CHO) content affect plasma TMAO levels. We also assessed postprandial glucose and insulin responses and plasma lipid changes to diets high and low in RS. In a cross-over trial, fifty-two men and women consumed a 2-week baseline diet (41 percentage of energy (%E) CHO, 40 % fat, 19 % protein), followed by 2-week high- and low-RS diets separated by 2-week washouts. RS diets were assigned at random within the context of higher (51–53 %E)v. lower CHO (39–40 %E) intake. Measurements were obtained in the fasting state and, for glucose and insulin, during a meal test matching the composition of the assigned diet. With lower CHO intake, plasma TMAO, carnitine, betaine andγ-butyrobetaine concentrations were higher after the high-v. low-RS diet (P<0·01 each). These metabolites were not differentially affected by highv. low RS when CHO intake was high. Although the high-RS meal reduced postprandial insulin and glucose responses when CHO intake was low (P<0·01 each), RS did not affect fasting lipids, lipoproteins, glucose or insulin irrespective of dietary CHO content. In conclusion, a lower-CHO diet high in RS was associated with higher plasma TMAO levels. These findings, together with the absence of change in fasting lipids, suggest that short-term high-RS diets do not improve markers of cardiometabolic health.

  5. Differences between human plasma and serum metabolite profiles.

    Directory of Open Access Journals (Sweden)

    Zhonghao Yu

    Full Text Available BACKGROUND: Human plasma and serum are widely used matrices in clinical and biological studies. However, different collecting procedures and the coagulation cascade influence concentrations of both proteins and metabolites in these matrices. The effects on metabolite concentration profiles have not been fully characterized. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the concentrations of 163 metabolites in plasma and serum samples collected simultaneously from 377 fasting individuals. To ensure data quality, 41 metabolites with low measurement stability were excluded from further analysis. In addition, plasma and corresponding serum samples from 83 individuals were re-measured in the same plates and mean correlation coefficients (r of all metabolites between the duplicates were 0.83 and 0.80 in plasma and serum, respectively, indicating significantly better stability of plasma compared to serum (p = 0.01. Metabolite profiles from plasma and serum were clearly distinct with 104 metabolites showing significantly higher concentrations in serum. In particular, 9 metabolites showed relative concentration differences larger than 20%. Despite differences in absolute concentration between the two matrices, for most metabolites the overall correlation was high (mean r = 0.81±0.10, which reflects a proportional change in concentration. Furthermore, when two groups of individuals with different phenotypes were compared with each other using both matrices, more metabolites with significantly different concentrations could be identified in serum than in plasma. For example, when 51 type 2 diabetes (T2D patients were compared with 326 non-T2D individuals, 15 more significantly different metabolites were found in serum, in addition to the 25 common to both matrices. CONCLUSIONS/SIGNIFICANCE: Our study shows that reproducibility was good in both plasma and serum, and better in plasma. Furthermore, as long as the same blood preparation procedure is

  6. [The influence of N-stearoylethanolamine on the activity of antioxidant enzymes and on the level of stable NO metabolites in the rat testes and blood plasma at the early stages of streptozotocine-induced diabetes].

    Science.gov (United States)

    Gorid'ko, T M; Kosiakova, H V; Berdyshev, A H; Bazylians'ka, V R; Margitych, V M; Gula, N M

    2012-01-01

    The influence of N-stearoylethanolamine was investigated on the activity of enzymes of antioxidant protection and content of stable metabolites of nitric oxide (NO) in the testes and plasma of rats at the early stages of development of streptozotocine-induced diabetes mellitus. It was shown that the activity of superoxide dismutase, catalase is reduced in the plasma and testes of animals with streptozotocin-induced (50 mg/kg) diabetes (blood glucose 8-10 mmol/L). A significant increase in the amount of nitrite and nitrate anions was revealed in the plasma of rats, while only the level of nitrite was significantly changed in the testes of animals. The per os administration of the NSE aqueous suspension in a dose of 50 mg/kg during 10 days to the rats with induced diabetes contributed to the normalization of catalase activity in the testis, which correlated with a decrease in the amount of TBA-reacting products and activity of superoxide dismutase and catalase in the blood plasma of animals; the use of NSE also contributed to the reduction of nitrite content in the gonads and to normalization of both nitrite and nitrate in the blood plasma of rats. The NSE administration to intact animals caused an increase in superoxide dismutase activity and significantly reduced the content of stable NO metabolites in the blood plasma of animals.

  7. Plasma metabolites, ions and thyroid hormones levels, and hepatic enzymes׳ activity in Caspian roach (Rutilus rutilus caspicus) exposed to waterborne manganese.

    Science.gov (United States)

    Hoseini, Seyyed Morteza; Hedayati, Aliakbar; Ghelichpour, Melika

    2014-09-01

    To investigate the effect of waterborne manganese on plasma biochemical characteristics in fish, Caspian roach (Rutilus rutilus caspicus) was exposed to 0 (control), 60 (M60), 150 (M150) and 300 (M300) mg/L water manganese for 96h. Thereafter, plasma biochemical characteristics were studied. Plasma glucose level significantly increased in M60 and decreased in M150 and M300 groups, compared to the control. M300 had significantly lower hematocrit compared to the control. Albumin remained unchanged after manganese exposure, however, the manganese-exposed fish showed significant increase in plasma total protein levels. M150 and M300 showed significant increase in the plasma cholesterol and triglyceride levels compared to the control and M60. M60 and M150 had significantly higher alkaline phosphatase (ALP) activity compared to the control. The manganese-exposed groups had significantly higher alanine aminotransferase (ALT) activity compared to the control. M150 and M300 had aspartate aminotransferase (AST) activity significantly higher than those of the control and M60. M300 had significantly higher triiodothyronine (T3) levels than the other groups. All manganese-exposed fish had significantly higher thyroxin (T4) levels than the control. The plasma levels of chloride showed a significant decrease in the manganese-exposed fish, compared to the control. M150 and M300 had significantly lower sodium levels, compared to the control. M60 and M150 had significantly lower plasma calcium levels compared to the other groups. It is concluded that clinical chemistry along with thyroid hormones levels can be the useful tools to monitor manganese toxicity in fish. The possible mechanisms involving in the biochemical changes were discussed.

  8. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Science.gov (United States)

    2010-01-01

    ... metabolites Cutoff level Marijuana metabolites 50 Cocaine metabolites 300 Opiate metabolites 2000... Levels for Drugs and Drug Metabolites Drug or metabolites Cutoff level(ng/mL) Marijuana metabolite 1...

  9. Determination of plasma and urine levels of Delta9-tetrahydrocannabinol and its main metabolite by liquid chromatography after solid-phase extraction.

    Science.gov (United States)

    Mercolini, Laura; Musenga, Alessandro; Comin, Irene; Baccini, Cesare; Conti, Matteo; Raggi, Maria Augusta

    2008-05-12

    Delta9-Tetrahydrocannabinol is the most widespread drug of abuse in the world and it is also currently available as the active principle of formulations for the treatment of chronic pain. Its main metabolite, 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid, is the most important marker of Delta9-tetrahydrocannabinol consumption. An original liquid chromatographic method has been developed for the determination of these two analytes in human plasma and urine. Separation was obtained on a C8 column using a mobile phase with 35% phosphate buffer at pH 2.7 and 65% acetonitrile. The UV detector was set at 220 nm and indomethacin was used as the internal standard. Sample pre-treatment was carried out by solid-phase extraction with C8 cartridges; urine samples were subjected to basic hydrolysis before extraction. Both extraction yields (>91%) and precision values were highly satisfactory. The method was successfully applied to biological samples collected from Cannabis users. Accuracy and selectivity results were satisfactory. This is the first HPLC-UV method developed for the simultaneous quantification of Delta9-tetrahydrocannabinol and 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in both plasma and urine for the monitoring of either therapeutic or recreational use.

  10. Plasma lipid metabolites are associated with gestational age but not bronchopulmonary dysplasia.

    Science.gov (United States)

    Rogers, Lynette K; Young, Christine M; Pennell, Michael L; Tipple, Trent E; Leonhart, Karen L; Welty, Stephen E

    2012-08-01

    To test the hypothesis that plasma lipid metabolite levels in premature infants are associated with the development of bronchopulmonary dysplasia (BPD). The studies also tested a secondary hypothesis that plasma lipid metabolite levels were correlated with gestational age. Infants born <32 weeks' gestation were enrolled during the first 72 h of life. Plasma samples were obtained and lipid levels were measured by LC-MS/MS. Clinical data were collected to determine infant outcomes and BPD diagnosis. Following adjustment for confounders, lipid levels were not associated with BPD; however, levels of specific lipid metabolites were correlated with gestational age. Immature lipid metabolism pathways in premature infants may contribute to the pathogenesis of BPD and other diseases. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

  11. Metabolite profiling of (14)C-omacetaxine mepesuccinate in plasma and excreta of cancer patients.

    Science.gov (United States)

    Nijenhuis, Cynthia M; Lucas, Luc; Rosing, Hilde; Robertson, Philmore; Hellriegel, Edward T; Schellens, Jan H M; Beijnen, And Jos H

    2016-12-01

    Omacetaxine mepesuccinate (hereafter referred to as omacetaxine) is a protein translation inhibitor approved by the US Food and Drug Administration for adult patients with chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors. The objective was to investigate the metabolite profile of omacetaxine in plasma, urine and faeces samples collected up to 72 h after a single 1.25-mg/m(2) subcutaneous dose of (14)C-omacetaxine in cancer patients. High-performance liquid chromatography mass spectrometry (MS) (high resolution) in combination with off-line radioactivity detection was used for metabolite identification. In total, six metabolites of omacetaxine were detected. The reactions represented were mepesuccinate ester hydrolysis, methyl ester hydrolysis, pyrocatechol conversion from the 1,3-dioxole ring. Unchanged omacetaxine was the most prominent omacetaxine-related compound in plasma. In urine, unchanged omacetaxine was also dominant, together with 4'-DMHHT. In feces very little unchanged omacetaxine was found and the pyrocatechol metabolite of omacetaxine, M534 and 4'-desmethyl homoharringtonine (4'-DMHHT) was the most abundant metabolites. Omacetaxine was extensively metabolized, with subsequent renal and hepatic elimination of the metabolites. The low levels of the metabolites found in plasma indicate that the metabolites are unlikely to contribute materially to the efficacy and/or toxicity of omacetaxine.

  12. Tryptophan and its metabolite concentrations in human plasma and breast milk during the perinatal period.

    Directory of Open Access Journals (Sweden)

    Kamimura,Shigehito

    1991-04-01

    Full Text Available Concentrations of tryptophan (free and protein bound and its metabolites in plasma of maternal vein at delivery, umbilical vein, umbilical artery, neonatal vein and breast milk were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in umbilical vein and artery were significantly higher than those in maternal vein. The concentration of total tryptophan in plasma of neonatal vein showed marked decrease at 24 h after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in plasma of neonatal vein. The colostrum contained a high level of total tryptophan. There were high ratios of free to total tryptophan in colostrum, transitional and mature milk. In the blood, ratios of free to total of tryptophan and kynurenine were kept at constant level throughout the perinatal period.

  13. Association between plasma metabolites and gene expression profiles in five porcine endocrine tissues

    Directory of Open Access Journals (Sweden)

    Bassols Anna

    2011-07-01

    Full Text Available Abstract Background Endocrine tissues play a fundamental role in maintaining homeostasis of plasma metabolites such as non-esterified fatty acids and glucose, the levels of which reflect the energy balance or the health status of animals. However, the relationship between the transcriptome of endocrine tissues and plasma metabolites has been poorly studied. Methods We determined the blood levels of 12 plasma metabolites in 27 pigs belonging to five breeds, each breed consisting of both females and males. The transcriptome of five endocrine tissues i.e. hypothalamus, adenohypophysis, thyroid gland, gonads and backfat tissues from 16 out of the 27 pigs was also determined. Sex and breed effects on the 12 plasma metabolites were investigated and associations between genes expressed in the five endocrine tissues and the 12 plasma metabolites measured were analyzed. A probeset was defined as a quantitative trait transcript (QTT when its association with a particular metabolic trait achieved a nominal P value Results A larger than expected number of QTT was found for non-esterified fatty acids and alanine aminotransferase in at least two tissues. The associations were highly tissue-specific. The QTT within the tissues were divided into co-expression network modules enriched for genes in Kyoto Encyclopedia of Genes and Genomes or gene ontology categories that are related to the physiological functions of the corresponding tissues. We also explored a multi-tissue co-expression network using QTT for non-esterified fatty acids from the five tissues and found that a module, enriched in hypothalamus QTT, was positioned at the centre of the entire multi-tissue network. Conclusions These results emphasize the relationships between endocrine tissues and plasma metabolites in terms of gene expression. Highly tissue-specific association patterns suggest that candidate genes or gene pathways should be investigated in the context of specific tissues.

  14. Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

    Science.gov (United States)

    Guo, Li; Tan, Guangguo; Liu, Ping; Li, Huijie; Tang, Lulu; Huang, Lan; Ren, Qian

    2015-10-01

    High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples.

  15. Determination of chlordiazepoxide, diazepam, and their major metabolites in blood or plasma by spectrophotodensitometry.

    Science.gov (United States)

    Stronjny, N; Bratin, K; Brooks, M A; de Silva, J A

    1977-07-01

    An analytical procedure was developed for the determination of chlordiazepoxide, diazepam and their major metabolites in blood or plasma. Demoxepam, a metabolite of chlordiazepoxide, is determined by spectrofluorometry after extraction. The remaining compounds are determined by spectrophotodensitometry after thin-layer chromatographic separation. The sensitivity limit of the spectrofluorometric determination of demoxepam is 0.1 to 0.2 microgram while that of the spectrophotodensitometric determination of chlordiazepoxide, diazepam and their N-desmethyl metabolites is 0.05 to 0.2 microgram. The sensitivity and specificity of the assay renders it suitable for monitoring plasma levels of chlordiazepoxide and its major metabolites following single or chronic oral administration of chlordiazepoxide hydrochloride. The sensitivity limit for diazepam and nordiazepam, its major metabolite, renders the assay useful only for the determination of plasma concentrations resulting from high dosage of diazepam. The assay was used to determine chlordiazepoxide and its metabolites following oral administration of Librium. The data showed a significant correlation to those obtained on the same specimens by differential pulse polarography and by radioimmunoassay.

  16. Impact of nutrient excess and endothelial nitric oxide synthase on the plasma metabolite profile in mice

    Directory of Open Access Journals (Sweden)

    Brian E Sansbury

    2014-11-01

    Full Text Available An increase in calorie consumption is associated with the recent rise in obesity prevalence. However, our current understanding of the effects of nutrient excess on major metabolic pathways appears insufficient to develop safe and effective metabolic interventions to prevent obesity. Hence, we sought to identify systemic metabolic changes caused by nutrient excess and to determine how endothelial nitric oxide synthase (eNOS—which has anti-obesogenic properties—affects systemic metabolism by measuring plasma metabolites. Wild-type (WT and eNOS transgenic (eNOS-TG mice were placed on low fat or high fat diets for six weeks, and plasma metabolites were measured using an unbiased metabolomic approach. High fat feeding in WT mice led to significant increases in fat mass, which was associated with significantly lower plasma levels of 1,5-anhydroglucitol, lysophospholipids, 3-dehydrocarnitine, and bile acids, as well as branched chain amino acids (BCAAs and their metabolites. Plasma levels of several lipids including sphingomyelins, stearoylcarnitine, dihomo-linoleate and metabolites associated with oxidative stress were increased by high fat diet. In comparison with low fat-fed WT mice, eNOS-TG mice showed lower levels of several free fatty acids, but in contrast, the levels of bile acids, amino acids, and BCAA catabolites were increased. When placed on a high fat diet, eNOS overexpressing mice showed remarkably higher levels of plasma bile acids and elevated levels of plasma BCAAs and their catabolites compared with WT mice. Treatment with GW4064, an inhibitor of bile acid synthesis, decreased plasma bile acid levels but was not sufficient to reverse the anti-obesogenic effects of eNOS overexpression. These findings reveal unique metabolic changes in response to high fat diet and eNOS overexpression and suggest that the anti-obesity effects of eNOS are likely independent of changes in the bile acid pool.

  17. Stability of plasma metabolites and hormones in parturient dairy cows.

    Science.gov (United States)

    Athanasiou, V N; Phillips, R W

    1978-06-01

    Metabolic changes that accompany the transition from parturition to lactation in dairy cows were studied. To measure these changes, plasma samples were obtained from 20 mature Holstein-Friesian dairy cows 10 days before through 10 days after parturition. They were analyzed for glucose, free fatty acids (FFA), lactic acid, ketone bodies, glucocorticoids, insulin, and growth hormone concentration. Lactic acid and glucocorticoids remained constant during the experiment, except for the day of parturition itself. In the prepartum period, changes were not detected in concentrations of hormones (glucocorticoids, insulin, and growth hormone), whereas, plasma metabolites began changing prior to parturition. Most evident were prepartum increased in FFA, ketones, and glucose. Postpartum plasma glucose concentration rapidly returned to prepartum concentrations. Plasma concentration of FFA and ketone bodies remained elevated for longer periods.

  18. Blood sampling and hemolysis affect concentration of plasma metabolites

    DEFF Research Database (Denmark)

    Theil, Peter Kappel; Pedersen, Lene Juul; Jensen, Margit Bak;

    2012-01-01

    , a subset of samples from 24 sows fed twice daily in Exp. 1 was combined with data obtained from 30 sows sampled using jugular vein catheters. All sows in Exp. 2 were fed twice daily (0800 h and 1500 h) and blood samples collected repeatedly 1, 4, 11, and 23 h after morning feeding (other conditions were......Two experiments were carried out to reveal and quantify plasma metabolites that are sensitive to hemolysis and animal stress due to the blood sampling procedure (vein puncture vs. catheter). In Exp. 1, 48 sows were fed 4 diets either once (0800 h) or twice daily (0800 h and 1500 h) in a crossover...... design and blood was collected after restraint via vein puncture 1, 4, 11, and 23 h after morning feeding. Plasma samples were categorized as without or with minor or major hemolysis [clear (n = 218), yellow (n = 97), or red (n = 37)] upon centrifugation. Plasma NEFA (P

  19. Stability of plasma metabolites and hormones in lactating dairy cows.

    Science.gov (United States)

    Phillips, R W; Athanasiou, V N

    1978-06-01

    Plasma concentration stability of glucose, free fatty acids, ketone bodies, growth hormone, insulin were determined in lactating dairy cows. Concentrations of these metabolites and hormones were measured during a 36- to 48-hour period in 3 normal, mature dairy cows in the 2nd month of lactation. Samples were taken at 30-minute intervals; also, intensive sampling (every 10 minutes) was done at varying times in relation to feeding and milking. Of the 5 components measured, glucose concentration was the most stable, easiest to assay, and most reliable for use as a diagnostic aid in assessing metabolic carbohydrate disturbances in dairy cattle.

  20. Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort.

    Science.gov (United States)

    Org, Elin; Blum, Yuna; Kasela, Silva; Mehrabian, Margarete; Kuusisto, Johanna; Kangas, Antti J; Soininen, Pasi; Wang, Zeneng; Ala-Korpela, Mika; Hazen, Stanley L; Laakso, Markku; Lusis, Aldons J

    2017-04-13

    The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study. We investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite associated with coronary artery disease and stroke. We further investigate the gut microbiota composition and microbiota-metabolite relationships in subjects with different body mass index and individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state. Our study identifies novel relationships between the composition of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host-gut microbiota relationships.

  1. Untargeted plasma metabolite profiling reveals the broad systemic consequences of xanthine oxidoreductase inactivation in mice.

    Directory of Open Access Journals (Sweden)

    Qiuying Chen

    Full Text Available A major challenge in systems biology is integration of molecular findings for individual enzyme activities into a cohesive high-level understanding of cellular metabolism and physiology/pathophysiology. However, meaningful prediction for how a perturbed enzyme activity will globally impact metabolism in a cell, tissue or intact organisms is precluded by multiple unknowns, including in vivo enzymatic rates, subcellular distribution and pathway interactions. To address this challenge, metabolomics offers the potential to simultaneously survey changes in thousands of structurally diverse metabolites within complex biological matrices. The present study assessed the capability of untargeted plasma metabolite profiling to discover systemic changes arising from inactivation of xanthine oxidoreductase (XOR, an enzyme that catalyzes the final steps in purine degradation. Using LC-MS coupled with a multivariate statistical data analysis platform, we confidently surveyed >3,700 plasma metabolites (50-1,000 Da for differential expression in XOR wildtype vs. mice with inactivated XOR, arising from gene deletion or pharmacological inhibition. Results confirmed the predicted derangements in purine metabolism, but also revealed unanticipated perturbations in metabolism of pyrimidines, nicotinamides, tryptophan, phospholipids, Krebs and urea cycles, and revealed kidney dysfunction biomarkers. Histochemical studies confirmed and characterized kidney failure in xor-nullizygous mice. These findings provide new insight into XOR functions and demonstrate the power of untargeted metabolite profiling for systemic discovery of direct and indirect consequences of gene mutations and drug treatments.

  2. 10 CFR 26.133 - Cutoff levels for drugs and drug metabolites.

    Science.gov (United States)

    2010-01-01

    ... cutoff levels. Otherwise, the following cutoff levels must be used for initial testing of urine specimens... Cocaine metabolites 300 Opiate metabolites 2000 Phencyclidine (PCP) 25 Amphetamines 1000...

  3. Bupropion therapy during pregnancy: the drug and its major metabolites in umbilical cord plasma and amniotic fluid

    Science.gov (United States)

    FOKINA, Valentina M; WEST, Holly; ONCKEN, Cheryl; CLARK, Shannon M; AHMED, Mahmoud S; HANKINS, Gary DV; NANOVSKAYA, Tatiana N

    2017-01-01

    Background Bupropion is used for treatment of depression during pregnancy. However, its use as a smoking cessation aid for pregnant women is currently under evaluation. Objectives The aim of this opportunistic study was to investigate the transfer of bupropion and its major pharmacologically active metabolites, hydroxybupropion and threohydrobupropion, across the placenta in vivo. In addition, the concentrations of the drug and its metabolites were determined in the amniotic fluid. Methods The following samples were collected at deliveries from twenty-two women taking bupropion: maternal blood (n=22), umbilical cord venous blood (n=22), and amniotic fluid (n=9). The concentrations of the drug and its metabolites in blood plasma and amniotic fluid were determined by means of liquid chromatography-mass spectrometry. Placental passage was calculated as a ratio of umbilical cord venous plasma to maternal plasma concentrations. Results The levels of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were invariably lower than their corresponding concentrations in maternal plasma. The concentrations of bupropion in umbilical cord plasma were lower than in maternal plasma in the majority of the maternal-cord blood pairs. The median values of the umbilical cord venous plasma to maternal plasma ratios were: bupropion, 0.53 (interquartile range 0.35, n=18), hydroxybupropion, 0.21 (interquartile range 0.12, n=18), and threohydrobupropion, 0.61 (interquartile range 0.11, n=21). In umbilical cord venous plasma, the median concentration of bupropion was 5.3 ng/ml; hydroxybupropion, 103.6 ng/ml and threohydrobupropion, 59.6 ng/ml. Bupropion and its metabolites were detectable in the amniotic fluid but the concentrations of threohydrobupropion were higher than those in the corresponding umbilical cord venous plasma. Conclusion Bupropion and its active metabolites cross the placenta to the fetal circulation. The concentrations of hydroxybupropion and

  4. NMR identification of endogenous metabolites interacting with fatted and non-fatted human serum albumin in blood plasma: Fatty acids influence the HSA-metabolite interaction

    Science.gov (United States)

    Jupin, Marc; Michiels, Paul J.; Girard, Frederic C.; Spraul, Manfred; Wijmenga, Sybren S.

    2013-03-01

    Metabolites and their concentrations are direct reporters on body biochemistry. Thanks to technical developments metabolic profiling of body fluids, such as blood plasma, by for instance NMR has in the past decade become increasingly accurate enabling successful clinical diagnostics. Human Serum Albumin (HSA) is the main plasma protein (∼60% of all plasma protein) and responsible for the transport of endogenous (e.g. fatty acids) and exogenous metabolites, which it achieves thanks to its multiple binding sites and its flexibility. HSA has been extensively studied with regard to its binding of drugs (exogenous metabolites), but only to a lesser extent with regard to its binding of endogenous (non-fatty acid) metabolites. To obtain correct NMR measured metabolic profiles of blood plasma and/or potentially extract information on HSA and fatty acids content, it is necessary to characterize these endogenous metabolite/plasma protein interactions. Here, we investigate these metabolite-HSA interactions in blood plasma and blood plasma mimics. The latter contain the roughly twenty metabolites routinely detected by NMR (also most abundant) in normal relative concentrations with fatted or non-fatted HSA added or not. First, we find that chemical shift changes are small and seen only for a few of the metabolites. In contrast, a significant number of the metabolites display reduced resonance integrals and reduced free concentrations in the presence of HSA or fatted HSA. For slow-exchange (or strong) interactions, NMR resonance integrals report the free metabolite concentration, while for fast exchange (weak binding) the chemical shift reports on the binding. Hence, these metabolites bind strongly to HSA and/or fatted HSA, but to a limited degree because for most metabolites their concentration is smaller than the HSA concentration. Most interestingly, fatty acids decrease the metabolite-HSA binding quite significantly for most of the interacting metabolites. We further find

  5. Fecal estradiol and progesterone metabolite levels in the three-toed sloth (Bradypus variegatus

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    Mühlbauer M.

    2006-01-01

    Full Text Available The present study was carried out to assess the possibility of measuring fecal steroid hormone metabolites as a noninvasive technique for monitoring reproductive function in the three-toed sloth, Bradypus variegatus. Levels of the estradiol (E2 and progesterone (P4 metabolites were measured by radioimmunoassay in fecal samples collected over 12 weeks from 4 captive female B. variegatus sloths. The validation of the radioimmunoassay for evaluation of fecal steroid metabolites was carried out by collecting 10 blood samples on the same day as defecation. There was a significant direct correlation between the plasma and fecal E2 and P4 levels (P < 0.05, Pearson's test, thereby validating this noninvasive technique for the study of the estrous cycle in these animals. Ovulation was detected in two sloths (SL03 and SL04 whose E2 levels reached 2237.43 and 6713.26 pg/g wet feces weight, respectively, for over four weeks, followed by an increase in P4 metabolites reaching 33.54 and 3242.68 ng/g wet feces weight, respectively. Interestingly, SL04, which presented higher levels of E2 and P4 metabolites, later gave birth to a healthy baby sloth. The results obtained indicate that this is a reliable technique for recording gonadal steroid secretion and thereby reproduction in sloths.

  6. Fecal estradiol and progesterone metabolite levels in the three-toed sloth (Bradypus variegatus).

    Science.gov (United States)

    Mühlbauer, M; Duarte, D P F; Gilmore, D P; Costa, C P da

    2006-02-01

    The present study was carried out to assess the possibility of measuring fecal steroid hormone metabolites as a noninvasive technique for monitoring reproductive function in the three-toed sloth, Bradypus variegatus. Levels of the estradiol (E2) and progesterone (P4) metabolites were measured by radioimmunoassay in fecal samples collected over 12 weeks from 4 captive female B. variegatus sloths. The validation of the radioimmunoassay for evaluation of fecal steroid metabolites was carried out by collecting 10 blood samples on the same day as defecation. There was a significant direct correlation between the plasma and fecal E2 and P4 levels (P sloths (SL03 and SL04) whose E2 levels reached 2237.43 and 6713.26 pg/g wet feces weight, respectively, for over four weeks, followed by an increase in P4 metabolites reaching 33.54 and 3242.68 ng/g wet feces weight, respectively. Interestingly, SL04, which presented higher levels of E2 and P4 metabolites, later gave birth to a healthy baby sloth. The results obtained indicate that this is a reliable technique for recording gonadal steroid secretion and thereby reproduction in sloths.

  7. Plasma appearance and correlation between coffee and green tea metabolites in human subjects.

    Science.gov (United States)

    Renouf, Mathieu; Guy, Philippe; Marmet, Cynthia; Longet, Karin; Fraering, Anne-Lise; Moulin, Julie; Barron, Denis; Dionisi, Fabiola; Cavin, Christophe; Steiling, Heike; Williamson, Gary

    2010-12-01

    Coffee and green tea are two of the most widely consumed hot beverages in the world. Their respective bioavailability has been studied separately, but absorption of their respective bioactive phenolics has not been compared. In a randomised cross-over design, nine healthy subjects drank instant coffee and green tea. Blood samples were collected over 12 h and at 24 h to assess return to baseline. After green tea consumption, (-)-epigallocatechin (EGC) was the major catechin, appearing rapidly in the plasma; (-)-EGC gallate (EGCg) and (-)-epicatechin (EC) were also present, but (-)-EC gallate and C were not detected. Dihydroferulic acid and dihydrocaffeic acid were the major metabolites that appeared after coffee consumption with a long time needed to reach maximum plasma concentration, suggesting metabolism and absorption in the colon. Other phenolic acid equivalents (caffeic acid (CA), ferulic acid (FA) and isoferulic acid (iFA)) were detected earlier, and they peaked at lower concentrations. Summations of the plasma area under the curves (AUC) for the measured metabolites showed 1.7-fold more coffee-derived phenolic acids than green tea-derived catechins (P = 0.0014). Furthermore, we found a significant correlation between coffee metabolites based on AUC. Inter-individual differences were observed, but individuals with a high level of CA also showed a correspondingly high level of FA. However, no such correlation was observed between the tea catechins and coffee phenolic acids. Correlation between AUC and maximum plasma concentration was also significant for CA, FA and iFA and for EGCg. This implies that the mechanisms of absorption for these two classes of compounds are different, and that a high absorber of phenolic acids is not necessarily a high absorber of catechins.

  8. Longitudinal Relationship between Plasma Reactive Oxygen Metabolites and Periodontal Condition in the Maintenance Phase of Periodontal Treatment

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    Tatsuya Machida

    2014-01-01

    Full Text Available Aim. The present cohort study describes the longitudinal relationship between plasma oxidative status and periodontitis progression during the maintenance phase of treatment. Materials and Methods. Forty-five patients (mean age 58.8 years were monitored from 2008 to 2013. Periodontal conditions, including probing pocket depth (PPD and clinical attachment level (CAL, were recorded. Measurements of plasma reactive oxygen metabolites (ROM and biologic antioxidant potential (BAP were performed to evaluate plasma oxidative status. The patients were assigned into 2 groups as low and high plasma ROM level using a cut-off value which was median of plasma ROM level at baseline. Results. In the subjects with low plasma ROM level at baseline, changes in mean CAL were positively correlated with changes in plasma ROM levels, bleeding on probing, and plaque control record, but not with PPD. In the subjects with high plasma ROM at baseline, changes in CAL were significantly associated with only PPD at baseline. On the other hands there were no significant associations between changes in CAL and those in plasma BAP levels. Conclusions. When plasma ROM level in periodontitis patients was low, increases in plasma ROM level were associated with those in CAL during the maintenance phase of treatment.

  9. Synthesis and quantitative analysis of plasma-targeted metabolites of catechin and epicatechin.

    Science.gov (United States)

    Blount, Jack W; Redan, Benjamin W; Ferruzzi, Mario G; Reuhs, Bradley L; Cooper, Bruce R; Harwood, John S; Shulaev, Vladimir; Pasinetti, Giulio; Dixon, Richard A

    2015-03-04

    Grape seed polyphenolic extract (GSPE) rich in the flavan-3-ols (+)-catechin and (-)-epicatechin beneficially modulates Alzheimer's Disease phenotypes in animal models. The parent molecules in the extract are converted to a series of methylated and glucuronidated derivatives. To fully characterize these metabolites and establish a robust quantitative assay of their levels in biological fluids, we have implemented a partial synthetic approach utilizing chemical methylation followed by enzymatic glucuronidation. Liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy were used to assign unequivocal structures to the compounds. An analytical method using solid-phase extraction and LC-MS/MS in selective reaction monitoring mode (SRM) was validated for their quantitation in plasma. These studies provide a basis for improvements in future work on the bioavailability, metabolism, and mechanism of action of metabolites derived from dietary flavan-3-ols in a range of interventions.

  10. Effect of Spirulina supplementation on plasma metabolites in crossbred and purebred Australian Merino lambs

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    A.E.O. Malau-Aduli

    2015-06-01

    Full Text Available The effect of supplementing purebred and crossbred Merino lambs with Arthrospira platensis (Spirulina on plasma metabolite concentrations under pasture-based management system and the influences of sire breed and sex were investigated. A completely randomized experimental design balanced by 4 sire breeds (Merino, White Suffolk, Dorset and Black Suffolk, 3 Spirulina supplementation levels (0, 100 and 200 ml representing the control, low and high, respectively and 2 sexes (ewe and wether lambs was utilised. All lambs had ad libitum access to the basal diet of ryegrass pastures and barley. Lambs in the treatment groups were individually drenched daily with Spirulina prior to being released with the control group of lambs for grazing over a 6-week period following a 3-week adjustment phase. At the start and completion of the feeding trial, blood samples were centrifuged and plasma metabolites measured. Data were analysed with Spirulina supplementation level, sire breed, sex and their second-order interactions fitted as fixed effects and metabolite concentrations as dependent variables. Gamma-glutamyl transferase (GGT concentrations decreased (from 79.40 to 69.25 UI and glucose increased (from 3.81 to 4.19 mmol/L as the level of Spirulina supplementation increased from 0 ml in the control to 200 ml in the high treatment groups (P < 0.05. Lambs supplemented at low Spirulina levels had the highest creatinine concentrations (61.75 μmol/L. Interactions between sex and supplementation level significantly affected glucose, aspartate aminotransferase (AST and Mg concentrations (P < 0.05, while sire breed and supplementation level interactions influenced albumin to globulin (A/G ratio, creatinine and GGT concentrations. It was demonstrated that Spirulina supplementation does not negatively impact lamb health and productivity.

  11. Altered serous levels of monoamine neurotransmitter metabolites in patiens with refractory and non-refractory depression

    Institute of Scientific and Technical Information of China (English)

    Guiqing Zhang; Yanxia Zhang; Jianxia Yang; Min Hu; Yueqi Zhang; Xia Liang

    2012-01-01

    The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression (TRD) and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diagnostic criteria for a depressive episode in accordance with the International Classification of Diseases, Tenth Revision. Before treatment, and at 4, 6, and 8 weeks after treatment, the plasma metabolite products of monoamine neurotransmitters in TRD group, including 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenyl ethylene glycol and homovanillic acid, were significantly lower than those in the non-TRD group. After two types of anti-depressive therapy with 5-serotonin and norepinephrine reuptake inhibitor, combined with psychotherapy, the Hamilton Depression Rating Scale scores were significantly reduced in both groups of patients, and the serous levels of 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenyl ethylene glycol were significantly increased. In contrast, the homovanillic acid level exhibited no significant change. The levels of plasma metabolite products of peripheral monoamine neurotransmitters in depressive patients may predict the degree of depression and the therapeutic effects of treatment.

  12. Concurrent profiling of polar metabolites and lipids in human plasma using HILIC-FTMS

    Science.gov (United States)

    Cai, Xiaoming; Li, Ruibin

    2016-11-01

    Blood plasma is the most popularly used sample matrix for metabolite profiling studies, which aim to achieve global metabolite profiling and biomarker discovery. However, most of the current studies on plasma metabolite profiling focused on either the polar metabolites or lipids. In this study, a comprehensive analysis approach based on HILIC-FTMS was developed to concurrently examine polar metabolites and lipids. The HILIC-FTMS method was developed using mixed standards of polar metabolites and lipids, the separation efficiency of which is better in HILIC mode than in C5 and C18 reversed phase (RP) chromatography. This method exhibits good reproducibility in retention times (CVs < 3.43%) and high mass accuracy (<3.5 ppm). In addition, we found MeOH/ACN/Acetone (1:1:1, v/v/v) as extraction cocktail could achieve desirable gathering of demanded extracts from plasma samples. We further integrated the MeOH/ACN/Acetone extraction with the HILIC-FTMS method for metabolite profiling and smoking-related biomarker discovery in human plasma samples. Heavy smokers could be successfully distinguished from non smokers by univariate and multivariate statistical analysis of the profiling data, and 62 biomarkers for cigarette smoke were found. These results indicate that our concurrent analysis approach could be potentially used for clinical biomarker discovery, metabolite-based diagnosis, etc.

  13. Increased biogenic catecholamine and metabolite levels in two patients with malignant catatonia

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    Nisijima K

    2013-08-01

    Full Text Available Koichi Nisijima Department of Psychiatry, Jichi Medical University, Tochigi, Japan Abstract: The pathophysiology of malignant catatonia, a rare life-threatening psychiatric syndrome, has not yet been elucidated. This paper reports on two patients with malignant catatonia who showed elevated urinary or plasma catecholamine levels. Patient 1 had high catecholamine and metabolite levels in a 24-hour urine sample, and patient 2 had elevated plasma catecholamine levels. These findings indicate the presence of peripheral sympathetic nervous system hyperactivity in malignant catatonia. Symptoms of autonomic dysfunction, including tachycardia, labile blood pressure, and diaphoresis, are typical features of malignant catatonia and may be related to the increased levels of biogenic amines in these cases. Although the findings in the present study cannot entirely explain the pathophysiology of malignant catatonia, they do indicate that hyperactivity of the sympathetic nervous system may be involved in the pathology of this condition. Keywords: malignant catatonia, catecholamine levels, neuroleptic malignant syndrome

  14. Proanthocyanidin metabolites associated with dietary fibre from in vitro colonic fermentation and proanthocyanidin metabolites in human plasma.

    Science.gov (United States)

    Saura-Calixto, Fulgencio; Pérez-Jiménez, Jara; Touriño, Sonia; Serrano, José; Fuguet, Elisabet; Torres, Josep Lluis; Goñi, Isabel

    2010-07-01

    Proanthocyanidins (PAs) or condensed tannins, a major group of dietary polyphenols, are oligomers and polymers of flavan-3-ol and flavan-3, 4-diols widely distributed in plant foods. Most literature data on PAs' metabolic fate deal with PAs that can be extracted from the food matrix by aqueous-organic solvents ( extractable proanthocyanidins). However, there are no data on colonic fermentation of non-extractable proanthocyanidins (NEPAs), which arrive almost intact to the colon, mostly associated to dietary fibre (DF). The aim of the present work was to examine colonic fermentation of NEPAs associated with DF, using a model of in vitro small intestine digestion and colonic fermentation. Two NEPA-rich materials obtained from carob pod (Ceratonia siliqua L. proanthocyanidin) and red grapes (grape antioxidant dietary fibre) were used as test samples. The colonic fermentation of these two products released hydroxyphenylacetic acid, hydroxyphenylvaleric acid and two isomers of hydroxyphenylpropionic acid, detected by HPLC-ESI-MS/MS. Differences between the two products indicate that DF may enhance the yield of metabolites. In addition, the main NEPA metabolite in human plasma was 3,4-dihydroxyphenyl acetic acid. The presence in human plasma of the same metabolites as were detected after in vitro colonic fermentation of NEPAs suggests that dietary NEPAs would undergo colonic fermentation releasing absorbable metabolites with potential healthy effects.

  15. A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer.

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    Haojie Li

    2007-03-01

    Full Text Available BACKGROUND: Vitamin D insufficiency is a common public health problem nationwide. Circulating 25-hydroxyvitamin D3 (25[OH]D, the most commonly used index of vitamin D status, is converted to the active hormone 1,25 dihydroxyvitamin D3 (1,25[OH]2D, which, operating through the vitamin D receptor (VDR, inhibits in vitro cell proliferation, induces differentiation and apoptosis, and may protect against prostate cancer. Despite intriguing results from laboratory studies, previous epidemiological studies showed inconsistent associations of circulating levels of 25(OHD, 1,25(OH2D, and several VDR polymorphisms with prostate cancer risk. Few studies have explored the joint association of circulating vitamin D levels with VDR polymorphisms. METHODS AND FINDINGS: During 18 y of follow-up of 14,916 men initially free of diagnosed cancer, we identified 1,066 men with incident prostate cancer (including 496 with aggressive disease, defined as stage C or D, Gleason 7-10, metastatic, and fatal prostate cancer and 1,618 cancer-free, age- and smoking-matched control participants in the Physicians' Health Study. We examined the associations of prediagnostic plasma levels of 25(OHD and 1,25(OH2D, individually and jointly, with total and aggressive disease, and explored whether relations between vitamin D metabolites and prostate cancer were modified by the functional VDR FokI polymorphism, using conditional logistic regression. Among these US physicians, the median plasma 25(OHD levels were 25 ng/ml in the blood samples collected during the winter or spring and 32 ng/ml in samples collected during the summer or fall. Nearly 13% (summer/fall to 36% (winter/spring of the control participants were deficient in 25(OHD (<20 ng/ml and 51% (summer/fall and 77% (winter/spring had insufficient plasma 25(OHD levels (<32 ng/ml. Plasma levels of 1,25(OH2D did not vary by season. Men whose levels for both 25(OHD and 1,25(OH2D were below (versus above the median had a

  16. Effects of high-fat diet on plasma profiles of eicosanoid metabolites in mice.

    Science.gov (United States)

    Wang, Weicang; Yang, Jun; Yang, Haixia; Sanidad, Katherine Z; Hammock, Bruce D; Kim, Daeyoung; Zhang, Guodong

    2016-12-01

    Obesity is a serious health problem in the US and is associated with increased risks of various human diseases. To date, the mechanisms by which obesity increases the risks of a wide range of human diseases are not well understood. Here we used a LC-MS/MS-based lipidomics, which can analyze >100 bioactive lipid mediators produced by cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes, to analyze plasma profiles of lipid mediators in high-fat diet induced obesity in C57BL/6 mice. Our results show that the plasma concentrations of epoxyoctadecenoic acids (EpOMEs, also termed as leukotoxins) are significantly increased in plasma of high-fat diet-fed mice, in addition, EpOMEs are among the most abundant lipid mediators detected in mouse plasma. Since substantial studies have shown that EpOMEs and their metabolites have a large array of detrimental effects on health, enhanced levels of EpOMEs could contribute to the pathology of obesity.

  17. Identification of novel circulating coffee metabolites in human plasma by liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Redeuil, Karine; Smarrito-Menozzi, Candice; Guy, Philippe; Rezzi, Serge; Dionisi, Fabiola; Williamson, Gary; Nagy, Kornél; Renouf, Mathieu

    2011-07-22

    This study reports a liquid chromatography-mass spectrometry method for the detection of polyphenol-derived metabolites in human plasma without enzymatic treatment after coffee consumption. Separation of available standards was achieved by reversed-phase ultra performance liquid chromatography and detection was performed by high resolution mass spectrometry in negative electrospray ionization mode. This analytical method was then applied for the identification and relative quantification of circulating coffee metabolites. A total of 34 coffee metabolites (mainly reduced, sulfated and methylated forms of caffeic acid, coumaric acid, caffeoylquinic acid and caffeoylquinic acid lactone) were identified based on mass accuracy (<4 ppm for most metabolites), specific fragmentation pattern and co-chromatography (when standard available). Among them, 19 circulating coffee metabolites were identified for the first time in human plasma such as feruloylquinic acid lactone, sulfated and glucuronidated forms of feruloylquinic acid lactone and sulfated forms of coumaric acid. Phenolic acid derivatives such as dihydroferulic acid, dihydroferulic acid 4'-O-sulfate, caffeic acid 3'-O-sulfate, dimethoxycinnamic acid, dihydrocaffeic acid and coumaric acid O-sulfate appeared to be the main metabolites circulating in human plasma after coffee consumption. The described method is a sensitive and reliable approach for the identification of coffee metabolites in biological fluids. In future, this analytical method will give more confidence in compound identification to provide a more comprehensive assessment of coffee polyphenol bioavailability studies in humans.

  18. Serum level of hormone and metabolites in pregnant rabbit does

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    Gabriele Brecchia

    2010-01-01

    Full Text Available The aims of this study were to compare the hormones and metabolites serum levels and the reproductive performances of nulliparous (n=100 and primiparous pregnant does submitted to artificial insemination (AI 11 days post-partum. On the day of AI, all the does were weighed and the sexual receptivity was evaluated. The kits were weaned at 26 day. Blood samples were collect by punc- ture of the marginal ear vein from one day before AI until few days before the kindling and assayed for hormones and metabolites. The higher sexual receptivity and the fertility in nulliparous than in primiparous does confirmed the negative effect of lactation. Nulliparous does showed higher blood con- centration of leptine than primiparous, and in both the groups such level lowered during pregnancy, probably reflecting the reduction of the fat reserve. The insuline level increased during pregnancy in either groups as a consequence of the growing of the foetuses. In nulliparous does the cortisol, NEFA and T3 concentrations were higher than primiparous does. The glucose levels were similar in both the groups probably due to the homeostatic mechanisms controlling the glycemia. Hormonal and metabo- lite analyses represent a good tool for understanding the physiological mechanisms required to meet higher reproductive performance.

  19. Hepatitis C virus infection influences the S-methadone metabolite plasma concentration.

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    Shiow-Ling Wu

    Full Text Available BACKGROUND AND OBJECTIVES: Heroin-dependent patients typically contract hepatitis C virus (HCV at a disproportionately high level due to needle exchange. The liver is the primary target organ of HCV infection and also the main organ responsible for drug metabolism. Methadone maintenance treatment (MMT is a major treatment regimen for opioid dependence. HCV infection may affect methadone metabolism but this has rarely been studied. In our current study, we aimed to test the hypothesis that HCV may influence the methadone dosage and its plasma metabolite concentrations in a MMT cohort from Taiwan. METHODS: A total of 366 MMT patients were recruited. The levels of plasma hepatitis B virus (HBV, HCV, human immunodeficiency virus (HIV antibodies (Ab, liver aspartate aminotransferase (AST and alanine aminotransferase (ALT, as well as methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP were measured along with the urine morphine concentration and amphetamine screening. RESULTS: Of the 352 subjects in our cohort with HCV test records, 95% were found to be positive for plasma anti-HCV antibody. The liver functional parameters of AST (Wilcoxon Rank-Sum test, P = 0.02 and ALT (Wilcoxon Rank-Sum test, P = 0.04, the plasma methadone concentrations (Wilcoxon Rank-Sum test, P = 0.043 and the R-enantiomer of methadone concentrations (Wilcoxon Rank-Sum test, P = 0.032 were significantly higher in the HCV antibody-positive subjects than in the HCV antibody-negative patients, but not the S-EDDP/methadone dose ratio. The HCV levels correlated with the methadone dose (β= 14.65 and 14.13; P = 0.029 and 0.03 and the S-EDDP/methadone dose ratio (β= -0.41 and -0.40; P = 0.00084 and 0.002 in both univariate and multivariate regression analyses. CONCLUSIONS: We conclude that HCV may influence the methadone dose and plasma S-EDDP/methadone dose ratio in MMT patients in this preliminary study.

  20. Aging effect on plasma metabolites and hormones concentrations in riding horses

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    K. Kawasumi

    2015-11-01

    Full Text Available 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.

  1. In vitro antioxidative activity of (-)-epicatechin glucuronide metabolites present in human and rat plasma.

    Science.gov (United States)

    Natsume, Midori; Osakabe, Naomi; Yasuda, Akiko; Baba, Seigo; Tokunaga, Takashi; Kondo, Kazuo; Osawa, Toshihiko; Terao, Junji

    2004-12-01

    Recently we identified four conjugated glucuronide metabolites of epicatechin, (-)-epicatechin-3'-O-glucuronide (E3'G), 4'-O-methyl-(-)-epicatechin-3'-O-glucuronide (4'ME3'G), (-)-epicatechin-7-O-glucuronide (E7G) and 3'-O-methyl-(-)-epicatechin-7-O-glucuronide (3'ME7G) from plasma and urine. E3'G and 4'ME3'G were isolated from human urine, while E7G and 3'ME7G were isolated from rats that had received oral administration of (-)-epicatechin (Natsume et al. (2003), Free Radic. Biol. Med. 34,840-849). It has been suggested that these metabolites possess considerable in vivo activity, and therefore we carried out a study to compare the antioxidant activities of the metabolites with that of the parent compound. This was achieved by measuring superoxide scavenging activity, reduction of plasma TBARS production and reduced susceptibility of low-density-lipoprotein (LDL) to oxidation. (-)-Epicatechin was found to have more potent antioxidant activity than the conjugated glucuronide metabolites. Both (-)-epicatechin and E7G had marked antioxidative properties with respect to superoxide radical scavenging activity, plasma oxidation induced by 2,2'-azobis-(2-aminopropane) dihydrochloride (AAPH) and LDL oxidation induced by copper ions or 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (MeO-AMVN). In contrast, the other metabolites had light antioxidative activities over the range of physiological concentrations found in plasma.

  2. High-performance liquid chromatography determination of dipotassium clorazepate and its major metabolite nordiazepam in plasma.

    Science.gov (United States)

    Colin, P; Sirois, G; Lelorier, J

    1983-04-08

    A rapid and sensitive high-performance liquid chromatographic method is described for the quantitative analysis of dipotassium clorazepate (CZP) and its major metabolite nordiazepam (ND) in fresh human and dog plasma. The method consists of two separate selective ND extractions from a plasma sample without and with conversion of all the CZP to ND. For quantitation, diazepam (DZP) is used as the internal standard. The chromatographic phase utilized in a reversed-phase Hibar EC-RT analytical column prepacked with LiChrosolv RP-18 with a solvent system consisting of acetonitrile-0.05 M sodium acetate buffer, pH 5.0 (45:55). The UV absorbance is monitored at 225 nm using a variable-wavelength detector. The mean assay coefficient of variation over a concentration range of 20-400 ng per ml of plasma is less than 3% for the within-day precision. Recoveries of ND, DZP and CZP (as ND) are essentially quantitative at all levels investigated. The calibration curves of ND are rectilinear (r2 = 0.99) from the lower limit of sensitivity (2 ng/ml) to at least 2000 ng/ml in plasma. Applicability of the method to CZP and ND disposition studies in the anaesthetized mongrel dog is illustrated. When the two separate selective nordiazepam extractions from plasma cannot be performed immediately after blood sampling, an extrapolation kinetic method is suggested for the estimation of CZP concentration. In all previous in vivo studies, CZP has been determined only with gas-liquid chromatographic methods.

  3. Changes in concentrations of insulin, growth hormone and metabolites in plasma with spontaneous feeding in lactating dairy cows.

    Science.gov (United States)

    Vasilatos, R; Wangsness, P J

    1980-07-01

    Changes in plasma levels of growth hormone (GH), insulin and metabolites and their relationships to spontaneous feeding in four lactating dairy cows were studied. Cows were fed a 60:40 (concentrate:silage) mixed ration through 100 days postpartum. Jugular blood samples were withdrawn at 10-minute intervals for 24 hours at day 90 postpartum; feeding behavior was monitored by time-lapse photography during this period. Insulin concentration increased immediately upon feeding and remained elevated for up to 50 minutes after meal termination, despite no significant change in plasma glucose levels. Plasma GH was depressed at 20 minutes postmeal and rose thereafter. Feeding appeared to dampen the fluctuations in free fatty acids (FFA) observed during premeal intervals. Time spent eating during a meal was not correlated with concentrations of these humoral factors at any premeal interval. The correlations of GH/glucose and GH/FFA were significant during eating, noneating and all other intervals during 24 hours. Correlation coefficients of other hormone/metabolite relationships were lower during eating as compared to non-eating periods. The consistent GH/metabolite relationships and rapid, feeding-induced changes in insulin, suggest their importance in the control of feed intake and energy balance.

  4. Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions.

    Science.gov (United States)

    Melcangi, Roberto Cosimo; Giatti, Silvia; Calabrese, Donato; Pesaresi, Marzia; Cermenati, Gaia; Mitro, Nico; Viviani, Barbara; Garcia-Segura, Luis Miguel; Caruso, Donatella

    2014-02-01

    Progesterone is synthesized and actively metabolized in the central and peripheral nervous system, into neuroactive steroid metabolites, such as dihydroprogesterone, allopregnanolone and isopregnanolone. Progesterone and/or its metabolites exert a variety of effects acting as physiological regulators of neuronal and glial development and plasticity, controlling reproduction, neuroendocrine events, mood and affection. In addition, these neuroactive steroids maintain neural homeostasis and exert neuroprotective actions. In agreement, metabolic pathways of progesterone are affected by modifications in the level of gonadal hormones and by pathology or injury with a regional specificity and in a sex-dimorphic way. Therefore, observations here summarized may provide a background to design sex-specific therapies based on progesterone metabolites. On this point of view, considering that one of the major limits of a therapy based on neuroactive steroids could be modifications in their plasma levels and their consequent peripheral effects, pharmacological treatments aimed to increase their levels in the nervous system could provide an interesting therapeutic option.

  5. Rapid and sensitive electron-capture gas chromatographic method for the determination of pinazepam and its metabolites in human plasma, urine and milk.

    Science.gov (United States)

    Pacifici, G M; Placidi, G F

    1977-05-11

    A rapid, sensitive and specific gas-liquid chromatographic method for the measurement of pinazepam and its metabolites in biological fluids is reported. After a single extraction of the sample with toluene, the organic phase is concentrated and, after chromatography on a 3% OV-17 column, measured with an electron-capture detector. The sensitivity was 1.0 ng/ml for pinazepam and 5.0 ng/ml for its metabolites. Plasma levels and urinary excretion in human volunteers and plasma and milk levels in women suffering from anxiety during breastfeeding are reported.

  6. Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa.

    Science.gov (United States)

    Näsström, Elin; Parry, Christopher M; Vu Thieu, Nga Tran; Maude, Rapeephan R; de Jong, Hanna K; Fukushima, Masako; Rzhepishevska, Olena; Marks, Florian; Panzner, Ursula; Im, Justin; Jeon, Hyonjin; Park, Seeun; Chaudhury, Zabeen; Ghose, Aniruddha; Samad, Rasheda; Van, Tan Trinh; Johansson, Anders; Dondorp, Arjen M; Thwaites, Guy E; Faiz, Abul; Antti, Henrik; Baker, Stephen

    2017-05-09

    Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.

  7. LC-MS/MS quantitation of antimalarial drug piperaquine and metabolites in human plasma.

    Science.gov (United States)

    Aziz, Mohd Yusmaidie; Hoffmann, Kurt-Jürgen; Ashton, Michael

    2017-09-15

    This study aimed to develop a sensitive, quantitative assay for the antimalarial piperaquine (PQ) and its metabolites M1 and M2 in human plasma. Analytes were gradiently separated on a C18 column and detected with a Sciex API 4000 MS/MS with an ESI source operated in the positive ion mode with deuterated PQ as internal standard. The response was linear in the range 3.9-2508nM with a runtime of 7.0min per sample. The method was applied to clinical samples from healthy volunteers. This LC-MS/MS method for the simultaneous quantitation of PQ and two of its metabolites in plasma may prove helpful for assessment of metabolite safety issues in vivo. Copyright © 2017. Published by Elsevier B.V.

  8. GMP-compliant radiosynthesis of [{sup 18}F]altanserin and human plasma metabolite studies

    Energy Technology Data Exchange (ETDEWEB)

    Hasler, F. [University Hospital of Psychiatry, Heffter Research Center, Zurich (Switzerland)], E-mail: fehasler@bli.uzh.ch; Kuznetsova, O.F.; Krasikova, R.N. [Institute of the Human Brain, Russian Academy of Science, St. Petersburg (Russian Federation); Cservenyak, T. [Center for Radiopharmaceutical Sciences of ETH, PSI and University Hospital Zurich (Switzerland); Quednow, B.B.; Vollenweider, F.X. [University Hospital of Psychiatry, Heffter Research Center, Zurich (Switzerland); Ametamey, S.M.; Westera, G. [Center for Radiopharmaceutical Sciences of ETH, PSI and University Hospital Zurich (Switzerland)

    2009-04-15

    [{sup 18}F]altanserin is the preferred radiotracer for in-vivo labeling of serotonin 2A receptors by positron emission tomography (PET). We report a modified synthesis procedure suited for reliable production of multi-GBq amounts of [{sup 18}F]altanserin useful for application in humans. We introduced thermal heating for drying of [{sup 18}F]fluoride as well as for the reaction instead of microwave heating. We furthermore describe solid phase extraction and HPLC procedures for quantitative determination of [{sup 18}F]altanserin and metabolites in plasma. The time course of arterial plasma activity with and without metabolite correction was determined. 90 min after bolus injection, 38.4% of total plasma activity derived from unchanged [{sup 18}F]altanserin. Statistical comparison of kinetic profiles of [{sup 18}F]altanserin metabolism in plasma samples collected in the course of two ongoing studies employing placebo, the serotonin releaser dexfenfluramine and the hallucinogen psilocybin, revealed the same tracer metabolism. We conclude that metabolite analysis for correction of individual plasma input functions used in tracer modeling is not necessary for [{sup 18}F]altanserin studies involving psilocybin or dexfenfluramine treatment.

  9. Effects of Dietary Protein Levels for Gestating Gilts on Reproductive Performance, Blood Metabolites and Milk Composition

    Science.gov (United States)

    Jang, Y. D.; Jang, S. K.; Kim, D. H.; Oh, H. K.; Kim, Y. Y.

    2014-01-01

    This experiment was conducted to evaluate the effects of dietary CP levels in gestation under equal lysine content on reproductive performance, blood metabolites and milk composition of gilts. A total of 25 gilts (F1, Yorkshire×Landrace) were allotted to 4 dietary treatments at breeding in a completely randomized design, and fed 1 of 4 experimental diets containing different CP levels (11%, 13%, 15%, or 17%) at 2.0 kg/d throughout the gestation. Body weight of gilts at 24 h postpartum tended to increase linearly (p = 0.09) as dietary CP level increased. In lactation, backfat thickness, ADFI, litter size and weaning to estrus interval (WEI) did not differ among dietary treatments. There were linear increases in litter and piglet weight at 21 d of lactation (p<0.05) and weight gain of litter (p<0.01) and piglet (p<0.05) throughout the lactation as dietary CP level increased. Plasma urea nitrogen levels of gilts in gestation and at 24 h postpartum were linearly elevated as dietary CP level increased (p<0.05). Free fatty acid (FFA) levels in plasma of gestating gilts increased as dietary CP level increased up to 15%, and then decreased with quadratic effects (15 d, p<0.01; 90 d, p<0.05), and a quadratic trend (70 d, p = 0.06). There were no differences in plasma FFA, glucose levels and milk composition in lactation. These results indicate that increasing dietary CP level under equal lysine content in gestation increases BW of gilts and litter performance but does not affect litter size and milk composition. Feeding over 13% CP diet for gestating gilts could be recommended to improve litter growth. PMID:25049930

  10. 1H NMR-based metabolite profiling of plasma in a rat model of chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Ju-Ae Kim

    Full Text Available Chronic kidney disease (CKD is characterized by the gradual loss of the kidney function to excrete wastes and fluids from the blood. (1H NMR-based metabolomics was exploited to investigate the altered metabolic pattern in rats with CKD induced by surgical reduction of the renal mass (i.e., 5/6 nephrectomy (5/6 Nx, particularly for identifying specific metabolic biomarkers associated with early of CKD. Plasma metabolite profiling was performed in CKD rats (at 4- or 8-weeks after 5/6 Nx compared to sham-operated rats. Principle components analysis (PCA, partial least squares-discriminant analysis (PLS-DA and orthogonal partial least squares-discriminant analysis (OPLS-DA score plots showed a significant separation between the groups. The resulting metabolic profiles demonstrated significantly increased plasma levels of organic anions, including citrate, β-hydroxybutyrate, lactate, acetate, acetoacetate, and formate in CKD. Moreover, levels of alanine, glutamine, and glutamate were significantly higher. These changes were likely to be associated with complicated metabolic acidosis in CKD for counteracting systemic metabolic acidosis or increased protein catabolism from muscle. In contrast, levels of VLDL/LDL (CH2n and N-acetylglycoproteins were decreased. Taken together, the observed changes of plasma metabolite profiles in CKD rats provide insights into the disturbed metabolism in early phase of CKD, in particular for the altered metabolism of acid-base and/or amino acids.

  11. High-performance liquid chromatographic assay for metamizol metabolites in rat plasma: application to pharmacokinetic studies.

    Science.gov (United States)

    Domínguez-Ramírez, Adriana Miriam; Calzadilla, Patricia Carrillo; Cortés-Arroyo, Alma Rosa; Hurtado Y de la Peña, Marcela; López, José Raúl Medina; Gómez-Hernández, Martín; López-Muñoz, Francisco Javier

    2012-12-01

    In order to evaluate the pharmacokinetics of metamizol in the presence of morphine in arthritic rats, after subcutaneous administration of the drugs, an easy, rapid, sensitive and selective analytical method was proposed and validated. The four main metamizol metabolites (4-methylaminoantipyrine, 4-aminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine) were extracted from plasma samples (50-100μl) by a single solid-phase extraction method prior to reverse-phase high performance liquid chromatography with diode-array detection. Standard calibration graphs for all metabolites were linear within a range of 1-100μg/ml (r(2)≥0.99). The intra-day coefficients of variation (CV) were in the range of 1.3-8.4% and the inter-day CV ranged from 1.5 to 8.4%. The intra-day assay accuracy was in the range of 0.6-9.6% and the inter-day assay accuracy ranged from 0.9 to 7.5% of relative error. The lower limit of quantification was 1μg/ml for all metabolites using a plasma sample of 100μl. Plasma samples were stable at least for 4 weeks at -20°C. This method was found to be suitable for studying metamizol metabolites pharmacokinetics in arthritic rats, after simultaneous administration of metamizol and morphine, in single dose. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Methodology for the analysis of fenbendazole and its metabolites in plasma, urine, feces, and tissue homogenates.

    Science.gov (United States)

    Barker, S A; Hsieh, L C; Short, C R

    1986-05-15

    New methodology for the extraction and analysis of the anthelmintic fenbendazole and its metabolites from plasma, urine, liver homogenates, and feces from several animal species is presented. Quantitation of fenbendazole and its metabolites was conducted by high-pressure liquid chromatography using ultraviolet detection at 290 nm. The combined extraction and analysis procedures give excellent recoveries in all of the different biological matrices examined. High specificity, low limits of detection, and excellent linearity, accuracy, and inter- and intrasample variability were also obtained. The study of fenbendazole pharmacokinetics in vitro and in vivo should be greatly enhanced through the utilization of these methods.

  13. Quantitative monitoring of tamoxifen in human plasma extended to 40 metabolites using liquid-chromatography high-resolution mass spectrometry: new investigation capabilities for clinical pharmacology.

    Science.gov (United States)

    Dahmane, Elyes; Boccard, Julien; Csajka, Chantal; Rudaz, Serge; Décosterd, Laurent; Genin, Eric; Duretz, Bénédicte; Bromirski, Maciej; Zaman, Khalil; Testa, Bernard; Rochat, Bertrand

    2014-04-01

    Liquid-chromatography (LC) high-resolution (HR) mass spectrometry (MS) analysis can record HR full scans, a technique of detection that shows comparable selectivity and sensitivity to ion transitions (SRM) performed with triple-quadrupole (TQ)-MS but that allows de facto determination of "all" ions including drug metabolites. This could be of potential utility in in vivo drug metabolism and pharmacovigilance studies in order to have a more comprehensive insight in drug biotransformation profile differences in patients. This simultaneous quantitative and qualitative (Quan/Qual) approach has been tested with 20 patients chronically treated with tamoxifen (TAM). The absolute quantification of TAM and three metabolites in plasma was realized using HR- and TQ-MS and compared. The same LC-HR-MS analysis allowed the identification and relative quantification of 37 additional TAM metabolites. A number of new metabolites were detected in patients' plasma including metabolites identified as didemethyl-trihydroxy-TAM-glucoside and didemethyl-tetrahydroxy-TAM-glucoside conjugates corresponding to TAM with six and seven biotransformation steps, respectively. Multivariate analysis allowed relevant patterns of metabolites and ratios to be associated with TAM administration and CYP2D6 genotype. Two hydroxylated metabolites, α-OH-TAM and 4'-OH-TAM, were newly identified as putative CYP2D6 substrates. The relative quantification was precise (<20 %), and the semiquantitative estimation suggests that metabolite levels are non-negligible. Metabolites could play an important role in drug toxicity, but their impact on drug-related side effects has been partially neglected due to the tremendous effort needed with previous MS technologies. Using present HR-MS, this situation should evolve with the straightforward determination of drug metabolites, enlarging the possibilities in studying inter- and intra-patients drug metabolism variability and related effects.

  14. Effects of vitamin D3 supplementation and UVb exposure on the growth and plasma concentration of vitamin D3 metabolites in juvenile bearded dragons (Pogona vitticeps)

    NARCIS (Netherlands)

    Oonincx, D.G.A.B.; Stevens, Y.; Borne, van den J.J.G.C.; Leeuwen, van J.P.T.M.; Hendriks, W.H.

    2010-01-01

    The effectiveness of dietary vitamin D3 and UVb exposure on plasma vitamin D metabolites in growing bearded dragons (Pogona vitticeps) was studied. A total of 84 (40 males and 44 females) newly hatched bearded dragons were allocated to six levels of oral vitamin D3 supplementation (0 to 400%) or six

  15. Determination of clobazam, N-desmethylclobazam and their hydroxy metabolites in plasma and urine by high-performance liquid chromatography.

    Science.gov (United States)

    Tomasini, J L; Bun, H; Coassolo, P; Aubert, C; Cano, J P

    1985-10-11

    Owing to the pharmacological and clinical importance of the determination of plasma and urine levels of the hydroxy metabolites of clobazam and N-desmethylclobazam in healthy volunteers and in epileptic patients, a high-performance liquid chromatographic (HPLC) method was developed that permits the determination of all these compounds in the same plasma or urine sample. The method involved ether extraction at pH 13 with diazepam as internal standard for the measurement of clobazam and N-desmethylcobazam, followed by ether extraction at pH 9 with nitrazepam as internal standard for the measurement of the hydroxy derivatives. The limit of detection was about 10-20 ng/ml for each of these compounds. Applications to patients were limited by chromatographic interferences between the hydroxy metabolites and some medications currently associated with clobazam in the treatment of epilepsy. The only interference in clobazam and N-desmethylclobazam analysis was from N-desmethyldiazepam. Despite these inconveniences, this HPLC procedure appears to be the only available method for the simultaneous quantification of clobazam and its three main metabolites.

  16. Modulation of plasma fibrinogen levels by medication

    NARCIS (Netherlands)

    Maat, M.P.M. de; Kodex, M.; Kastelein, J.J.P.

    1996-01-01

    Elevated plasma fibrinogen levels represent an increased risk for cardiac events. This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels. Agents that have this capacity are the lipid lowering fibric acid derivatives (e.g. ciprofibrate) and the plate

  17. Glucose kinetics, plasma metabolites, and endocrine responses during experimental ketosis in steers.

    Science.gov (United States)

    Lyle, R R; deBoer, G; Mills, S E; Russell, R W; Beitz, D C; Young, J W

    1984-10-01

    Phlorizin and 1,3-butanediol were used to determine effects of glucosuria and ketonemia on concentrations of metabolites in blood plasma and on kinetics of glucose metabolism. Four steers received four treatments (control; control plus dietary 1,3-butanediol; control plus phlorizin injections; and control plus phlorizin and 1,3-butanediol) in a Latin square design. Treatments lasted 14 days. All steers received a 30% grain, 70% forage ration in equal meals every 2 h. Metabolite concentrations in blood plasma and urine and glucose kinetics were measured on each of the last 3 days of each treatment period. Phlorizin caused glucosuria; decreased plasma glucose, glucose total entry rate, and glucose recycling; and increased plasma free fatty acids and glucose irreversible loss. Glucose pool size was increased by 1,3-butanediol. Phlorizin plus 1,3-butanediol caused glucosuria and ketonuria; decreased plasma glucose; and increased blood ketone bodies, plasma free fatty acids, glucose irreversible loss, and glucose pool size. Growth hormone, insulin, and glucagon were not affected by treatment. Physiological perturbations in these steers were characteristic of some of those in ketotic cows.

  18. Effects of dietary protein levels for gestating gilts on reproductive performance, blood metabolites and milk composition.

    Science.gov (United States)

    Jang, Y D; Jang, S K; Kim, D H; Oh, H K; Kim, Y Y

    2014-01-01

    This experiment was conducted to evaluate the effects of dietary CP levels in gestation under equal lysine content on reproductive performance, blood metabolites and milk composition of gilts. A total of 25 gilts (F1, Yorkshire×Landrace) were allotted to 4 dietary treatments at breeding in a completely randomized design, and fed 1 of 4 experimental diets containing different CP levels (11%, 13%, 15%, or 17%) at 2.0 kg/d throughout the gestation. Body weight of gilts at 24 h postpartum tended to increase linearly (p = 0.09) as dietary CP level increased. In lactation, backfat thickness, ADFI, litter size and weaning to estrus interval (WEI) did not differ among dietary treatments. There were linear increases in litter and piglet weight at 21 d of lactation (pPlasma urea nitrogen levels of gilts in gestation and at 24 h postpartum were linearly elevated as dietary CP level increased (pplasma of gestating gilts increased as dietary CP level increased up to 15%, and then decreased with quadratic effects (15 d, pplasma FFA, glucose levels and milk composition in lactation. These results indicate that increasing dietary CP level under equal lysine content in gestation increases BW of gilts and litter performance but does not affect litter size and milk composition. Feeding over 13% CP diet for gestating gilts could be recommended to improve litter growth.

  19. Buspirone, fexofenadine, and omeprazole: Quantification of probe drugs and their metabolites in human plasma

    OpenAIRE

    Gor, Parul; Alnouti, Yazen; Reed, Gregory A.

    2011-01-01

    Probe drugs are critical tools for the measurement of drug metabolism and transport activities in human subjects. Often several probe drugs are administered simultaneously in a —cocktail . This cocktail approach requires efficient analytical methods for the simultaneous quantitation of multiple analytes. We have developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three probe drugs and their metabolites in human plasma. The anal...

  20. Determination of Duloxetine and Its Major Metabolites in Rabbit Plasma by High-Performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    T. K. Laha

    2015-03-01

    Full Text Available A rapid and sensitive high performance liquid chromatographic method is described for simultaneous determination of duloxetine and its major metabolites, such as 4- hydroxy duloxetine (M7, Glucuronide conjugate of 5-hydroxy-6-methoxy duloxetine (M6 and Glucuronide conjugate of dihydrodiol duloxetine (M12 in rabbit plasma. HPLC analysis was carried out on a µ-Bondapak C18 column (250 mm × 4.6 mm, 5µm particle size using methanol: phosphate buffer (pH 7.9, 50 mM (7:3 v/v as the mobile phase at a flow rate of 1.5 ml/min. Detection was carried out at 224 nm with an UV detector. The above metabolites present in the rabbit plasma were characterized by retro-synthesis followed by NMR and MS study for structure confirmation and finally injected separately into the HPLC system. All the three retention time matches with the metabolites present in the plasma sample.

  1. Supplementation with l-arginine stabilizes plasma arginine and nitric oxide metabolites, suppresses elevated liver enzymes and peroxidation in sickle cell anaemia.

    Science.gov (United States)

    Jaja, S I; Ogungbemi, S O; Kehinde, M O; Anigbogu, C N

    2016-06-01

    The effect of l-arginine on liver function in SCD has received little or no attention. The effect of a chronic, oral, low-dose supplementation with l-arginine (1gm/day for 6 weeks) on some liver enzymes, lipid peroxidation and nitric oxide metabolites was studied in 20 normal (non-sickle cell anaemia; NSCA) subjects and 20 sickle cell anaemia (SCA) subjects. Ten milliliters of blood was withdrawn from an ante-cubital vein for the estimation of plasma arginine concentration ([R]), alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and alkaline phosphatase (ALP), plasma total bilirubin concentration [TB], malondialdehyde concentration [MDA] and nitric oxide metabolites concentration [NOx]. Before supplementation, ALT, AST, ALP (pconcentration and nitric oxide metabolites levels in NSCA and SCA subjects. Responses in SCA subjects to l-arginine were more sensitive than in NSCA subjects.

  2. Plasma substance P levels in fibrositis.

    Science.gov (United States)

    Reynolds, W J; Chiu, B; Inman, R D

    1988-12-01

    The mechanism of pain in the fibrositis syndrome is unknown. We measured plasma levels of substance P in 32 patients with fibrositis and 26 sex and age matched controls using a radioimmunoassay. The mean plasma level of substance P in the patients with fibrositis was 371 +/- 91 pg/ml and in controls 397 +/- 84 pg/ml (p = NS). We conclude that determination of plasma levels of substance P in fibrositis is of no diagnostic value. This does not exclude the possible role of substance P as a neurotransmitter in the fibrositis syndrome.

  3. Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants

    NARCIS (Netherlands)

    J. Bouwmeester (Nancy); J.N. van den Anker (John); W.C.J. Hop (Wim); K.J.S. Anand (Kanwaljeet); D. Tibboel (Dick)

    2003-01-01

    textabstractBACKGROUND: To investigate clinical variables such as gestational age, sex, weight, the therapeutic regimens used and mechanical ventilation that might affect morphine requirements and plasma concentrations of morphine and its metabolites. METHODS: In a double-blind stu

  4. Microminiature Monitor for Vital Electrolyte and Metabolite Levels of Astronauts

    Science.gov (United States)

    Tohda, Koji; Gratzl, Miklos

    2004-01-01

    Ions, such as proton (pH) and potassium, play a crucial role in body fluids to maintain proper basic functioning of cells and tissues. Metabolites, such as glucose, control the energy available to the entire human body in normal as well as stress situations, and before, during, and after meals. These molecules diffuse easily between blood in the capillaries and the interstitial fluid residing between cells and tissues. We have developed and approach to monitoring of critical ions (called electrolytes) and glucose in the interstitial fluid under the human skin. Proton and potassium levels sensed using optode technology that translates the respective ionic concentrations into variable colors of corresponding ionophore/dye/polymeric liquid membranes. Glucose is monitored indirectly, by coupling through immobilized glucose oxidase with local pH that is then detected using a similar color scheme. The monitor consists of a tiny plastic bar, 100-200 microns wide and 1-2 mm long, placed just under the skin, with color changing spots for each analyte as well as blanks. The colors are read and translated into concentration values by a CCD camera. Direct optical coupling between the in vivo sensing bar and the ex vivo detector device requires no power, and thus eliminates the need for wires or optical fibers crossing the skin. The microminiature bar penetrates the skin easily and painlessly, so that astronauts could insert it themselves. The approach is fully compatible with telemetry in space, and thus, in vivo clinical data will be available real time in the Earth based command center once the device is fully developed. The information provided can be used for collecting hitherto unavailable vital data on clinical effects of space travel. Managing clinical emergencies in space with the sensor already in place should also become much more efficient than without a continuous monitor, as is currently the case. Civilian applications may include better glucose control of

  5. Microminiature Monitor for Vital Electrolyte and Metabolite Levels of Astronauts

    Science.gov (United States)

    Tohda, Koji; Gratzl, Miklos

    2004-01-01

    Ions, such as proton (pH) and potassium, play a crucial role in body fluids to maintain proper basic functioning of cells and tissues. Metabolites, such as glucose, control the energy available to the entire human body in normal as well as stress situations, and before, during, and after meals. These molecules diffuse easily between blood in the capillaries and the interstitial fluid residing between cells and tissues. We have developed and approach to monitoring of critical ions (called electrolytes) and glucose in the interstitial fluid under the human skin. Proton and potassium levels sensed using optode technology that translates the respective ionic concentrations into variable colors of corresponding ionophore/dye/polymeric liquid membranes. Glucose is monitored indirectly, by coupling through immobilized glucose oxidase with local pH that is then detected using a similar color scheme. The monitor consists of a tiny plastic bar, 100-200 microns wide and 1-2 mm long, placed just under the skin, with color changing spots for each analyte as well as blanks. The colors are read and translated into concentration values by a CCD camera. Direct optical coupling between the in vivo sensing bar and the ex vivo detector device requires no power, and thus eliminates the need for wires or optical fibers crossing the skin. The microminiature bar penetrates the skin easily and painlessly, so that astronauts could insert it themselves. The approach is fully compatible with telemetry in space, and thus, in vivo clinical data will be available real time in the Earth based command center once the device is fully developed. The information provided can be used for collecting hitherto unavailable vital data on clinical effects of space travel. Managing clinical emergencies in space with the sensor already in place should also become much more efficient than without a continuous monitor, as is currently the case. Civilian applications may include better glucose control of

  6. Antioxidant enzyme activities, plasma hormone levels and serum metabolites of finishing broiler chickens reared under high ambient temperature and fed lemon and orange peel extracts and Curcuma xanthorrhiza essential oil.

    Science.gov (United States)

    Akbarian, A; Golian, A; Kermanshahi, H; De Smet, S; Michiels, J

    2015-02-01

    The negative effects of high ambient temperature during some months of the year on poultry production have been of great concern in many countries. Dietary modifications are among the most practical ways to alleviate the effects of high temperature. Possible effects of dietary supplementation with 200 or 400 mg/kg feed of lemon peel extract (LPE), orange peel extract (OPE) and Curcuma xanthorrhiza essential oil (CXEO) under hot conditions (34 °C with 50% relative humidity for 5 h daily starting from day 28 until day 38 of age) on blood antioxidant enzyme activities, biochemical parameters and antibody titres of broiler chickens were investigated. All extracts are rich in phenolic compounds and highly available. Compared to control, supplementation with OPE at 400 mg/kg and CXEO significantly increased erythrocyte glutathione peroxidase and superoxide dismutase activity, plasma growth hormone concentrations and serum phosphorus, total protein and chloride concentrations and decreased serum low-density lipoprotein and cholesterol concentrations in chickens at 38 days of age. Regarding antibody titres, CXEO supplementation at 400 mg/kg caused a significant increase in bronchitis antibody titres. Supplementation with LPE and OPE gave more inconsistent results. Most interesting, 400 mg/kg LPE significantly increased 3,5,3'-triiodothyronine and GH concentration as compared to the control. In conclusion, the herbal extracts tested in this study, in particular CXEO at 400 mg/kg, may relieve some of the changes in blood composition induced by increased ambient temperatures. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  7. Simultaneous detection of five one-carbon metabolites in plasma using stable isotope dilution liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Adaikalakoteswari, Antonysunil; Webster, Craig; Goljan, Ilona; Saravanan, Ponnusamy

    2016-02-15

    Disturbance in one-carbon (1-C) cycle occurs due to nutritional deficiencies (vitamin B12/folate) or specific genetic polymorphisms. This leads to altered levels of key 1-C metabolites such as SAM (s-adenosyl methionine), SAH (s-adenosyl homocysteine), methionine, homocysteine and MMA (methyl malonic acid). These 1-C metabolites are determinants of cellular methylation potential and epigenetic modifications of DNA which impairs metabolic pathways in several pathological diseases and developmental programming. Though methods were able to measure these analytes only independently, none of the methods detect simultaneously. Therefore we developed a method to measure these five 1-C metabolites in a single run using liquid chromatography tandem mass spectrometry (LC-MS/MS). We used stable isotopes dilution LC-MS/MS to measure the 1-C metabolites in human plasma. Blood samples were collected from pregnant women (n=30) at early gestation in the ongoing, multicentre, prospective PRiDE study. Linearity exhibited across the calibration range for all the analytes with the limit of detection (LOD) of 1.005nmol/l for SAM, 0.081nmol/l for SAH, 0.002μmol/l for methionine, 0.046μmol/l for homocysteine and 3.920nmol/l for MMA. The average recovery for SAM was 108%, SAH-110%, methionine-97%, homocysteine-91% and MMA-102%. The inter-assay CV for SAM was 7.3, SAH-5.6%, methionine-3.5%, homocysteine-7.0% and MMA-4.0%. The intra-assay CV for SAM was 8.7%, SAH-4.7%, methionine-5.4%, homocysteine-8.1% and MMA-6.1%. Pregnant women at early gestation with low B12 levels had significantly higher homocysteine, MMA, lower levels of methionine, SAM and SAM:SAH ratio and higher triglycerides. We developed a simple and rapid method to simultaneously quantify 1-C metabolites such as SAM, SAH, methionine, homocysteine and MMA in plasma by stable isotope dilution LC-MS/MS which would be useful to elucidate the epigenetic mechanisms related in the gene-nutrient interactions.

  8. Milk decreases urinary excretion but not plasma pharmacokinetics of cocoa flavan-3-ol metabolites in humans.

    Science.gov (United States)

    Mullen, William; Borges, Gina; Donovan, Jennifer L; Edwards, Christine A; Serafini, Mauro; Lean, Michael E J; Crozier, Alan

    2009-06-01

    Cocoa drinks containing flavan-3-ols are associated with many health benefits, and conflicting evidence exists as to whether milk adversely affects the bioavailability of flavan-3-ols. The objective was to determine the effect of milk on the bioavailability of cocoa flavan-3-ol metabolites. Nine human volunteers followed a low-flavonoid diet for 2 d before drinking 250 mL of a cocoa beverage, made with water or milk, that contained 45 micromol (-)-epicatechin and (-)-catechin. Plasma and urine samples were collected for 24 h, and flavan-3-ol metabolites were analyzed by HPLC with photodiode array and mass spectrometric detection. Milk affected neither gastric emptying nor the transit time through the small intestine. Two flavan-3-ol metabolites were detected in plasma and 4 in urine. Milk had only minor effects on the plasma pharmacokinetics of an (epi)catechin-O-sulfate and had no effect on an O-methyl-(epi)catechin-O-sulfate. However, milk significantly lowered the excretion of 4 urinary flavan-3-ol metabolites from 18.3% to 10.5% of the ingested dose (P = 0.016). Studies that showed protective effects of cocoa and those that showed no effect of milk on bioavailability used products that have a much higher flavan-3-ol content than does the commercial cocoa used in the present study. Most studies of the protective effects of cocoa have used drinks with a very high flavan-3-ol content. Whether similar protective effects are associated with the consumption of many commercial chocolate and cocoa products containing substantially lower amounts of flavan-3-ols, especially when absorption at lower doses is obstructed by milk, remains to be determined.

  9. Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa

    Science.gov (United States)

    Näsström, Elin; Parry, Christopher M; Vu Thieu, Nga Tran; Maude, Rapeephan R; de Jong, Hanna K; Fukushima, Masako; Rzhepishevska, Olena; Marks, Florian; Panzner, Ursula; Im, Justin; Jeon, Hyonjin; Park, Seeun; Chaudhury, Zabeen; Ghose, Aniruddha; Samad, Rasheda; Van, Tan Trinh; Johansson, Anders; Dondorp, Arjen M; Thwaites, Guy E; Faiz, Abul; Antti, Henrik; Baker, Stephen

    2017-01-01

    Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics. DOI: http://dx.doi.org/10.7554/eLife.15651.001 PMID:28483042

  10. Buspirone, fexofenadine, and omeprazole: quantification of probe drugs and their metabolites in human plasma.

    Science.gov (United States)

    Gor, Parul; Alnouti, Yazen; Reed, Gregory A

    2011-07-15

    Probe drugs are critical tools for the measurement of drug metabolism and transport activities in human subjects. Often several probe drugs are administered simultaneously in a "cocktail". This cocktail approach requires efficient analytical methods for the simultaneous quantitation of multiple analytes. We have developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three probe drugs and their metabolites in human plasma. The analytes include omeprazole and its metabolites omeprazole sulfone and 5'-hydroxyomeprazole; buspirone and its metabolite 1-[2-pyrimidyl]-piperazine (1PP); and fexofenadine. These analytes and the internal standard lansoprazole were extracted from plasma using protein precipitation with acetonitrile. Gradient reverse-phase chromatography was performed with 7.5mM ammonium bicarbonate and acetonitrile, and the analytes were quantified in positive ion electrospray mode with multiple reaction monitoring. The method was validated to quantify the concentration ranges of 1.0-1000ng/ml for omeprazole, omeprazole sulfone, 5'-hydroxyomeprazole, and fexofenadine; 0.1-100ng/ml for buspirone, and 1.0-100ng/ml for 1PP. These linear ranges span the plasma concentrations for all of the analytes from probe drug studies. The intra-day precision was between 2.1 and 16.1%, and the accuracy ranged from 86 to 115% for all analytes. Inter-day precision and accuracy ranged from 0.3 to 14% and from 90 to 110%, respectively. The lower limits of quantification were 0.1ng/ml for buspirone and 1ng/ml for all other analytes. This method provides a fast, sensitive, and selective analytical tool for quantification of the six analytes in plasma necessary to support the use of this probe drug cocktail in clinical studies.

  11. Clinical relevance of plasma prostaglandin F2α metabolite concentrations in patients with idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Kensaku Aihara

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis (IPF is a devastating lung disease of unknown etiology with few current treatment options. Recently, we determined an important role of prostaglandin F2α (PGF2α in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF2α in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF2α in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF2α, a stable metabolite of PGF2α. METHODS: We measured plasma concentrations of 15-keto-dihydro PGF2α in 91 IPF patients and compared these values with those of controls (n = 25. We further investigated the relationships of plasma 15-keto-dihydro PGF2α concentrations with disease severity and mortality. RESULTS: Plasma concentrations of 15-keto-dihydro PGF2α were significantly higher in IPF patients than controls (p<0.001. Plasma concentrations of this metabolite were significantly correlated with forced expiratory volume in 1 second (Rs [correlation coefficient] = -0.34, p = 0.004, forced vital capacity (Rs = -0.33, p = 0.005, diffusing capacity for carbon monoxide (Rs = -0.36, p = 0.003, the composite physiologic index (Rs = 0.40, p = 0.001, 6-minute walk distance (Rs = -0.24, p = 0.04 and end-exercise oxygen saturation (Rs = -0.25, p = 0.04 when patients with emphysema were excluded. Multivariate analysis using stepwise Cox proportional hazards model showed that a higher composite physiologic index (relative risk = 1.049, p = 0.002 and plasma 15-keto-dihydro PGF2α concentrations (relative risk = 1.005, p = 0.002 were independently associated with an increased risk of mortality. CONCLUSIONS: We demonstrated significant associations of plasma concentrations of PGF2α metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF2α in human IPF.

  12. Pharmacokinetic study of tramadol and its three metabolites in plasma, saliva and urine

    Directory of Open Access Journals (Sweden)

    M.R Rouini

    2009-12-01

    Full Text Available "nBackground and the purpose of the study: Pharmacokinetic parameters of tramadol and its three metabolites in plasma, saliva and urine following administration of 100 mg single oral dose were investigated in 24 healthy volunteers.Materials and Methods: 12 male and 12 female healthy volunteers received a single oral dose of tramadol and Plasma, mixed saliva -secreted samples without any stimulation and urine were analyzed for Tramadol and its main metabolites by HPLC method.Results and Disscusion: Almost 16.2% of tramadol and 11.2, 1.1 and 5.0% of O-desmethyltramadol (M1, N-desmethyltramadol (M2 and N,O-didesmethyltramadol (M5 respectively were recovered in 30 hrs collected urine. Renal clearance of tramadol, M1, M2 and M5 were 114.7 ± 44.5, 193.9 ± 67.6, 116.1 ± 61.8 and 252.0 ± 91.5 (mL/min respectively. The maximum plasma concentration of tramadol, M1, M2 and M5 were 349.3 ± 76.7, 88.7±30.3, 23.1 ± 11.4 and 30.0 ± 11.7 (ng/mL at 1.6 ± 0.4, 2.4 ± 0.7, 2.8 ± 1.0 and 2.7 ± 1.4 hrs after drug administration respectively. Tramadol and its metabolites appeared in a significant amount in saliva with the saliva/plasma ratios of 9.0, 1.6, 12.3 and 2.8 for tramadol, M1, M2 and M5 according to AUC(0-24 respectively. Conclusion: Conclusion Strong correlations were found between plasma and saliva concentrations for all studied compounds and a dissection to pre and post absorption components improved these correlations. Results o f this study suggests that saliva is a suitable alternative to plasma for clinical and toxicological studies of tramadol and in addition to passive diffusion, a possible active transport is also suggested to describe the elevated saliva/plasma ratios for these compounds.

  13. Effect of fasting on plasma metabolites and hormones in lactating dairy cows.

    Science.gov (United States)

    Athanasiou, V N; Phillips, R W

    1978-06-01

    Metabolic and pathophysiologic changes of secondary ketosis were studied. Plasma samples were obtained from a group of 8 mature, lactating dairy cows before, during, and after a 48-hour fast. These samples were analyzed for glucose, free fatty acids (FFA), lactic acid, ketone bodies, glucocorticoids, insulin, and growth hormone concentrations. In the prefasting period, metabolites and hormones remained constant. Lactic acid and glucocorticoids also remained stable during the entire experiment, except on the 1st day after termination of the fast, when glucocorticoids increased significantly (P less than 0.05). Glucose values decreased significantly (P less than 0.01) with the onset of fasting, began to rise halfway through the fast, and were elevated following termination of the fast. Plasma glucose concentration returned to normal by the end of the experiment. Plasma FFA concentrations increased during the early portions of the fast and decreased thereafter. Plasma ketone body concentration responded similarly, but the change occurred approximately 12 hours after the plasma FFA changes. A value determined as ketotic was reached during the fast (14.6 +/- 1.3 mg/dl). Insulin concentrations remained low during the fast and increased after fasting. Plasma growth hormone concentration increased to a new plateau in response to fasting and then decreased somewhate after fasting was ended.

  14. Sensitive quantification of omeprazole and its metabolites in human plasma by liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Hofmann, Ute; Schwab, Matthias; Treiber, Gerd; Klotz, Ulrich

    2006-02-02

    A sensitive method was developed for the simultaneous determination of omeprazole and its major metabolites 5-hydroxyomeprazole and omeprazole sulfone in human plasma by HPLC-electrospray mass spectrometry. Following liquid-liquid extraction HPLC separation was achieved on a ProntoSil AQ, C18 column using a gradient with 10 mM ammonium acetate in water (pH 7.25) and acetonitrile. The mass spectrometer was operated in the selected ion monitoring mode using the respective MH(+) ions, m/z 346 for omeprazole, m/z 362 for 5-hydroxy-omeprazole and omeprazol-sulfone and m/z 300 for the internal standard (2-{[(3,5-dimethylpyridine-2-yl)methyl]thio}-1H-benzimidazole-5-yl)methanol. The limit of quantification (LOQ) achieved with this method was 5 ng/ml for 5-hydroxyomeprazole and 10 ng/ml for omeprazole and omeprazole-sulfone using 0.25 ml of plasma. Intra- and inter-assay variability was below 11% over the whole concentration range from 5 to 250 ng/ml for 5-hydroxyomeprazol and from 10 to 750 ng/ml for omeprazole and omeprazole-sulfone. The method was successfully applied to the determination of pharmacokinetic parameters of esomeprazole and the two major metabolites after a single dose and under steady state conditions.

  15. The Relationship between Mitochondrial Respiratory Chain Activities in Muscle and Metabolites in Plasma and Urine: A Retrospective Study

    Science.gov (United States)

    Alban, Corinne; Fatale, Elena; Joulani, Abed; Ilin, Polina; Saada, Ann

    2017-01-01

    The relationship between 114 cases with decreased enzymatic activities of mitochondrial respiratory chain (MRC) complexes I-V (C I-V) in muscle and metabolites in urine and plasma was retrospectively examined. Less than 35% disclosed abnormal plasma amino acids and acylcarnitines, with elevated alanine and low free carnitine or elevated C4-OH-carnitine as the most common findings, respectively. Abnormal urine organic acids (OA) were detected in 82% of all cases. In CI and CII defects, lactic acid (LA) in combination with other metabolites was the most common finding. 3-Methylglutaconic (3MGA) acid was more frequent in CIV and CV, while Tyrosine metabolites, mainly 4-hydroxyphenyllactate, were common in CI and IV defects. Ketones were present in all groups but more prominent in combined deficiencies. There was a significant strong correlation between elevated urinary LA and plasma lactate but none between urine Tyrosine metabolites and plasma Tyrosine or urinary LA and plasma Alanine. All except one of 14 cases showed elevated FGF21, but correlation with urine OA was weak. Although this study is limited, we conclude that urine organic acid test in combination with plasma FGF21 determination are valuable tools in the diagnosis of mitochondrial diseases. PMID:28287425

  16. Effects of anesthesia and blood sampling techniques on plasma metabolites and corticosterone in the rat.

    Science.gov (United States)

    Arnold, Myrtha; Langhans, Wolfgang

    2010-04-19

    Blood is routinely sampled from laboratory animals in biomedical research, and many of the commonly applied sampling techniques require anesthesia. Acute effects of many sampling and anesthesia procedures may confound the results, but those effects are incompletely characterized. We here compare the effects of four common anesthesia procedures (inhalation anesthesia with ether (EA) or isoflurane (IA) and intraperitoneal injection anesthesia with xylazin/ketamine (XKA) or medetomidine/midazolam/fentanyl (MMFA)) on plasma concentrations of glucose, lactate, non-esterified fatty acids (NEFAs), and corticosterone in blood obtained from a previously implanted jugular vein (JV) catheter with the effect of JV blood sampling from non-anesthetized, freely-moving rats (JV-NA). Also, we included in the comparison two other blood sampling procedures usually performed without anesthesia (NA), i.e., puncture of the saphenic vein (SV) and tail incision (TI). Whereas the control procedure (JV-NA) did not significantly affect any of the target parameters, plasma glucose increased from 14 (JV-IA) to 44 (JV-MMFA) % (all Ps=0.05 when compared with the control procedure) in all blood samples collected in anesthesia and was 12 and 14% lower (both Pssamples, respectively. Plasma lactate increased from 74 (JV-IA) to 226% (SV-NA) (all Pssampling and anesthesia procedures except for JV-XKA and JV-MMF. Plasma NEFAs increased to 52% (P0.05). Finally, only the JV-EA and the JV-MMFA procedures increased plasma corticosterone (+525 and +353%, respectively, both Pssampling procedures can have profound acute effects on plasma metabolite and hormone concentrations. This must be considered for the design and interpretation of blood sampling experiments in laboratory animals. (c) 2010. Published by Elsevier Inc.

  17. Radioreceptor assay to study the affinity of benzodiazepines and their receptor binding activity in human plasma including their active metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Dorow, R.G.; Seidler, J.; Schneider, H.H. (Schering A.G., Berlin (Germany, F.R.))

    1982-04-01

    A radioreceptor assay has been established to measure the receptor affinities of numerous benzodiazepines in clinical use. The time course of receptor binding activity was studied by this method in the plasma of eight healthy subjects randomly treated with 1mg lormetazepam (Noctamid(R)), 2mg flunitrazepam (Rohypnol(R)), and 10mg diazepam (Valium(R)), and placebo on a cross-over basis. Blood samples were collected up to 154h after treatment. Receptor affinities of numerous benzodiazepines in vitro show good correlation with therapeutic human doses (r=0.96) and may be predictive of drug potency in man. Mean peak plasma levels of lormetazepam binding equivalents were 4.8+-1 ng/ml at 2h after lormetazepam, 7.2+-1.8 ng/ml at 8h after flunitrazepam, and 17.9+-2.7 ng/ml at 15h after diazepam. Plasma elimination halflives of benzodiazepine binding equivalents were 9.3, 23 and 63h, respectively. Slow elimination of benzodiazepine binding equivalents following flunitrazepam and diazepam may be due to persistent active metabolites.

  18. Fasting plasma hormones and metabolites in feral and domestic newborn pigs.

    Science.gov (United States)

    Kasser, T R; Martin, R J; Gahagan, J H; Wangsness, P J

    1981-08-01

    Newborn Yorkshire and Ossabaw (feral) pigs were examined under thermoneutral conditions to determine whether survival rate during fasting differs between these breeds and whether any blood-borne factors are associated with improved survival. Newborn pigs were removed from the sow before suckling. Body composition was determined on 10 newborn Ossabaw and 12 newborn Yorkshire pigs. Another group of animals (eight Ossabaw, 12 Yorkshire) was fasted for 72 hr, with blood samples drawn at birth and 12 and 24 hr into fasting. Glucose, free fatty acid (FFA), growth hormone (GH), insulin, thyroxine (T4), triiodothyronine (T3), cortisol and glucagon concentrations were measured in plasma of fasted pigs. Concentrations of carcass lipid, dry matter and ash were higher in newborn Ossabaw pigs than in newborn Yorkshire pigs. Survival through 72 hr of fasting was lower among Yorkshire pigs. Yorkshire and Ossabaw pigs had similar concentrations of metabolites and hormones at birth, with the exceptions of lower plasma GH and higher T3 concentrations in Ossabaw pigs. Higher plasma T3 concentrations would indicate a greater potential for fatty acid oxidation. During fasting, Ossabaw pigs had lower plasma GH and T4 concentrations and higher glucagon and FFA concentrations. Increased survival among newborn Ossabaw pigs may have been due to increased availability of FFA during fasting, and to a greater potential for gluconeogenesis through increased oxidation of fatty acids and higher plasma glucagon concentrations. This would suggest that maternal treatments that would increase storage of fat and(or) increase the capacity for oxidation of fat in utero would improve survival of newborn pigs.

  19. NMR metabolomics profiling of blood plasma mimics shows that medium- and long-chain fatty acids differently release metabolites from human serum albumin

    Science.gov (United States)

    Jupin, M.; Michiels, P. J.; Girard, F. C.; Spraul, M.; Wijmenga, S. S.

    2014-02-01

    Metabolite profiling by NMR of body fluids is increasingly used to successfully differentiate patients from healthy individuals. Metabolites and their concentrations are direct reporters of body biochemistry. However, in blood plasma the NMR-detected free-metabolite concentrations are also strongly affected by interactions with the abundant plasma proteins, which have as of yet not been considered much in metabolic profiling. We previously reported that many of the common NMR-detected metabolites in blood plasma bind to human serum albumin (HSA) and many are released by fatty acids present in fatted HSA. HSA is the most abundant plasma protein and main transporter of endogenous and exogenous metabolites. Here, we show by NMR how the two most common fatty acids (FAs) in blood plasma - the long-chain FA, stearate (C18:0) and medium-chain FA, myristate (C14:0) - affect metabolite-HSA interaction. Of the set of 18 common NMR-detected metabolites, many are released by stearate and/or myristate, lactate appearing the most strongly affected. Myristate, but not stearate, reduces HSA-binding of phenylalanine and pyruvate. Citrate signals were NMR invisible in the presence of HSA. Only at high myristate-HSA mole ratios 11:1, is citrate sufficiently released to be detected. Finally, we find that limited dilution of blood-plasma mimics releases HSA-bound metabolites, a finding confirmed in real blood plasma samples. Based on these findings, we provide recommendations for NMR experiments for quantitative metabolite profiling.

  20. Simultaneous determination of clobazam and its major metabolite in human plasma by a rapid HPLC method.

    Science.gov (United States)

    Rouini, Mohammadreza; Ardakani, Yalda H; Hakemi, Lida; Mokhberi, Maryam; Badri, Gheise

    2005-09-05

    A rapid and specific HPLC method has been developed and validated for simultaneous determination of clobazam, the anticonvulsant agent, and its major metabolite in human plasma. The sample preparation was a liquid-liquid extraction with tuloene yielding almost near 100% recoveries of two compounds. Chromatographic separation was achieved with a Chromolith Performance RP-18e 100 mm x 4.6mm column, using a mixture of a phosphate buffer (pH 3.5; 10mM)-acetonitrile (70:30, v/v), in isocratic mode at 2 ml/min at a detection wave-length of 228 nm. The calibration curves were linear (r(2)>0.998) in the concentration range of 5-450 ng ml(-1). The lower limit of quantification was 5 ng ml(-1) for two compounds studied. The within- and between-day precisions in the measurement of QC samples at four tested concentrations were in the range of 0.89-9.1% and 2.1-10.1% R.S.D., respectively. The developed procedure was applied to assess the pharmacokinetics of clobazam and its major metabolite following administration of a single 10mg oral dose of clobazam to healthy volunteers.

  1. Detection and identification of plasma progesterone metabolites in the female Florida manatee (Trichechus manatus latirostris) using GC/MS/MS.

    Science.gov (United States)

    Tripp, K M; Dubois, M; Delahaut, P; Verstegen, J P

    2009-08-01

    Florida manatees (Trichechus manatus latirostris) have relatively low peripheral concentrations of progesterone (P4). The objective of this study was to determine if these relatively low P4 concentrations are associated with a high ratio of progestin metabolites and to document metabolite concentrations from individual blood samples obtained from manatees during diestrus or pregnancy. Metabolites known to exist in elephants-terrestrial manatee relatives-were targeted. These included 5alpha-reduced progestins (5alpha-pregnane-3,20-dione [5alpha-DHP] and 3alpha-hydroxy-5alpha-pregnan-20-one [5alpha-P3-OH]) and 17alpha-hydroxyprogesterone (17alpha-OHP), which occurs in Asian elephants. An additional, inactive metabolite, 20alpha-hydroxyprogesterone (20alpha-OHP), indicative of P4 overproduction, was also targeted. Progesterone itself was the predominant progestin detected in pregnant and nonpregnant manatee plasma (n = 10) using gas chromatography-mass spectrometry with tandem quadrupole detectors (GC/MS/MS). Progesterone concentrations in pregnant females varied from early (moderate to high) through mid and late (low) pregnancy. Progesterone concentrations ranged from low to high in nonpregnant, nonlactating females. The most commonly detected metabolite was 5alpha-P3-OH (n = 7), which occurred in pregnant (lower limit of detection [LLOD] to high) and nonpregnant (trace to high) females. The 5alpha-DHP metabolite was also detected in pregnant (LLOD to moderate) and nonpregnant (low) females. The 17alpha-OHP metabolite was not detected in any tested female. The 20alpha-OHP metabolite was detected in one nonpregnant, nonlactating, captive female (LLOD). Metabolites were most prevalent during early pregnancy, concurrent with maximum P4 concentrations. Based on their concentrations in peripheral circulation, we inferred that these metabolites may have, opposite to elephants, a limited physiologic role during luteal, pregnant, and nonpregnant phases in the manatee.

  2. Evaluation of the Ecstasy influence on tramadol and its main metabolite plasma concentration in rats.

    Science.gov (United States)

    Jamali, Bardia; Sheikholeslami, Behjat; Hosseinzadeh Ardakani, Yalda; Lavasani, Hoda; Rouini, Mohammad-Reza

    2017-09-26

    Tramadol is prone to be abused alone, or in combination with 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). It was reported that 95% of people with a history of substance abuse in the United States used tramadol in 2004. According to the WHO report in 2016, there was a growing number of tramadol abusers alone or in combination with psychoactive substances such as MDMA in particular in some Middle East countries. Higher concentrations of tramadol in plasma may lead to adverse drug reactions or lethal intoxication. In this study, the effect of MDMA on the pharmacokinetics of tramadol was examined in male rats. The effect of MDMA on Tmax, Cmax, area under the curve, elimination rate, and half-life of tramadol and its metabolites was examined. Two control and two treatment groups were designed. The treatment groups received MDMA 18 h before the administration of tramadol. Jugular vein blood samples were analyzed by high-performance liquid chromatography with fluorescent detector to determine the concentrations of tramadol and its metabolites. Independent-sample t-test was used to define the differences between pharmacokinetic parameters of control and treatment groups. When tramadol administered intraperitoneally, the absorption rate of this drug was reduced, and a lower Cmax (40%) with longer Tmax (eight-fold) was achieved. MDMA exerted greater inhibitory effects on cytochrome P450 3A4 (CYP3A4) than on cytochrome P450 2D6 (CYP2D6). The M2 metabolite ratio was reduced by half, and because of the inhibition of M2 production, the M1 plasma concentration slightly increased. According to the obtained data, MDMA treatment affected the absorption, distribution and metabolism phases of tramadol. This treatment increased the concentration of tramadol if administered intravenously and can latent the absorption of tramadol in oral route. However, MDMA was introduced as CYP2D6 inhibitor; in this study, MDMA inhibited CYP3A4 isoenzymes as well. This finding is important for

  3. Identification of 4-hydroxyheptachlorostyrene in polar bear plasma and its binding affinity to transthyretin : a metabolite of octachlorostyrene?

    NARCIS (Netherlands)

    Standau, C.D.; Meerts, I.A.T.M.; Letcher, R.J.; McAlees, A.J.; Chittim, B.; Brouwer, A.; Norstrom, R.J.

    2000-01-01

    A new compound, 4-hydroxyheptachlorostyrene (4-OH-HpCS), was identified as a major component in the chlorinated phenolic compound fraction of polar bear plasma. The structure was hypothesized to be 4-OH-HpCS based on mass spectral interpretation, the assumption that it was a metabolite of octachloro

  4. Identification of 4-hydroxyheptachlorostyrene in polar bear plasma and its binding affinity to transthyretin : a metabolite of octachlorostyrene?

    NARCIS (Netherlands)

    Standau, C.D.; Meerts, I.A.T.M.; Letcher, R.J.; McAlees, A.J.; Chittim, B.; Brouwer, A.; Norstrom, R.J.

    2000-01-01

    A new compound, 4-hydroxyheptachlorostyrene (4-OH-HpCS), was identified as a major component in the chlorinated phenolic compound fraction of polar bear plasma. The structure was hypothesized to be 4-OH-HpCS based on mass spectral interpretation, the assumption that it was a metabolite of

  5. Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with Type 2 diabetes mellitus

    NARCIS (Netherlands)

    Pena, M. J.; Lambers Heerspink, H. J.; Hellemons, M. E.; Friedrich, T.; Dallmann, G.; Lajer, M.; Bakker, S. J. L.; Gansevoort, R. T.; Rossing, P.; de Zeeuw, D.; Roscioni, S. S.

    Aims Early detection of individuals with Type 2 diabetes mellitus or hypertension at risk for micro- or macroalbuminuria may facilitate prevention and treatment of renal disease. We aimed to discover plasma and urine metabolites that predict the development of micro-or macroalbuminuria. Methods

  6. Optical sensors for monitoring dynamic changes of intracellular metabolite levels in mammalian cells.

    Science.gov (United States)

    Hou, Bi-Huei; Takanaga, Hitomi; Grossmann, Guido; Chen, Li-Qing; Qu, Xiao-Qing; Jones, Alexander M; Lalonde, Sylvie; Schweissgut, Oliver; Wiechert, Wolfgang; Frommer, Wolf B

    2011-10-27

    Knowledge of the in vivo levels, distribution and flux of ions and metabolites is crucial to our understanding of physiology in both healthy and diseased states. The quantitative analysis of the dynamics of ions and metabolites with subcellular resolution in vivo poses a major challenge for the analysis of metabolic processes. Genetically encoded Förster resonance energy transfer (FRET) sensors can be used for real-time in vivo detection of metabolites. FRET sensor proteins, for example, for glucose, can be targeted genetically to any cellular compartment, or even to subdomains (e.g., a membrane surface), by adding signal sequences or fusing the sensors to specific proteins. The sensors can be used for analyses in individual mammalian cells in culture, in tissue slices and in intact organisms. Applications include gene discovery, high-throughput drug screens or systematic analysis of regulatory networks affecting uptake, efflux and metabolism. Quantitative analyses obtained with the help of FRET sensors for glucose or other ions and metabolites provide valuable data for modeling of flux. Here we provide a detailed protocol for monitoring glucose levels in the cytosol of mammalian cell cultures through the use of FRET glucose sensors; moreover, the protocol can be used for other ions and metabolites and for analyses in other organisms, as has been successfully demonstrated in bacteria, yeast and even intact plants. The whole procedure typically takes ∼4 d including seeding and transfection of mammalian cells; the FRET-based analysis of transfected cells takes ∼5 h.

  7. A unique automation platform for measuring low level radioactivity in metabolite identification studies.

    Directory of Open Access Journals (Sweden)

    Joel Krauser

    Full Text Available Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using (14C or (3H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector.

  8. A Unique Automation Platform for Measuring Low Level Radioactivity in Metabolite Identification Studies

    Science.gov (United States)

    Krauser, Joel; Walles, Markus; Wolf, Thierry; Graf, Daniel; Swart, Piet

    2012-01-01

    Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using 14C or 3H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector. PMID:22723932

  9. A unique automation platform for measuring low level radioactivity in metabolite identification studies.

    Science.gov (United States)

    Krauser, Joel; Walles, Markus; Wolf, Thierry; Graf, Daniel; Swart, Piet

    2012-01-01

    Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using (14)C or (3)H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector.

  10. Effects of acute and chronic heat stress on plasma metabolites, hormones and oxidant status in restrictedly fed broiler breeders.

    Science.gov (United States)

    Xie, Jingjing; Tang, Li; Lu, Lin; Zhang, Liyang; Lin, Xi; Liu, Hsiao-Ching; Odle, Jack; Luo, Xugang

    2015-07-01

    Heat tolerance can be improved by feed restriction in broiler chickens. It is unknown whether the same is true for broiler breeders, which are restrictedly fed. Therefore, the current study was conducted to study the effects of heat stress on plasma metabolites, hormones, and oxidative status of restricted fed broiler breeders with special emphases on the temperature and latency of heat exposure. In trial 1, 12 broiler breeders were kept either in a thermoneutral chamber (21°C, control, n = 6) or in a chamber with a step-wise increased environmental temperature from 21 to 33°C (21, 25, 29, 33°C, heat-stressed, n = 6). Changes in plasma total cholesterol, glucose, and triiodothyronine (T3) were closely related to the environmental temperature. When the temperature reached 29°C, plasma T3 (P stressed birds, whereas plasma glucose (P stressed birds than controls regardless of the temperatures applied. In Trial 2, 24 broiler breeders were divided into 2 groups and raised under 21°C and 32°C for 8 weeks, respectively. Total cholesterol was increased in chronic heat-stressed broiler breeders after 4 weeks. Plasma lactate dehydrogenase (LDH, P = 0.047) and glutamic-oxaloacetic transaminase (GOT, P = 0.036) was up-regulated after 6 weeks of thermal treatment, whereas plasma CK (P = 0.009) was increased at the end of thermal treatment. Plasma malonaldehyde, protein carbonyl content, activity of total superoxide dismutase (SOD), and corticosterone content were not altered after acute and prolonged heat challenges. Taken together, acute heat stress primarily resulted in disturbance of plasma metabolites, whereas chronic heat stress caused tissue damage reflected by increased plasma LDA, GOT, and CK. During acute heat stress, plasma metabolites were minimally disturbed in broiler breeders until the environmental temperature reached 33°C. © 2015 Poultry Science Association Inc.

  11. Eicosanoid and cytokine levels in plasma of patients during mesenteric infarction.

    Science.gov (United States)

    Nathan, N; Denizot, Y; Feiss, P

    1997-01-01

    Multible organ failure (MOF) induced by mesenteric infarction is associated with a high mortality rate. This study reports eicosanoid and cytokine levels in the blood of three atherosclerotic patients who ultimately died from MOF induced by mesenteric infarction. High plasma levels of 6- keto-prostaglandin (PG) F(1alpha) (the stable metabolite of PGI(2)), interleukin (IL)-6 and IL-8 are observed whereas plasma tumour necrosis factor alpha (TNFalpha), TxB(2) (the stable metabolite of TxA(2)), PGE(2), leukotrienes (LT)B(4) and LTC(4), and whole blood platelet-activating factor levels are not different from values obtained in similarly severe atherosclerotic patients. This short report questioned the clinical involvement of TNFalpha during such a pathology where a persistent translocation of endotoxin has been observed through the gut endothelial barrier. Activation of phospholipase A(2) is suggested by the increase in the stable metabolite of PGI(2) and might be by itself or through lipidic metabolites, a major systemic stimulus of IL-6 and IL-8 production.

  12. Eicosanoid and cytokine levels in plasma of patients during mesenteric infarction

    Directory of Open Access Journals (Sweden)

    N. Nathan

    1997-01-01

    Full Text Available Multible organ failure (MOF induced by mesenteric infarction is associated with a high mortality rate. This study reports eicosanoid and cytokine levels in the blood of three atherosclerotic patients who ultimately died from MOF induced by mesenteric infarction. High plasma levels of 6- keto-prostaglandin (PG F1α (the stable metabolite of PGI2, interleukin (IL-6 and IL-8 are observed whereas plasma tumour necrosis factor alpha (TNFα, TxB2 (the stable metabolite of TxA2, PGE2, leukotrienes (LTB4 and LTC4, and whole blood platelet-activating factor levels are not different from values obtained in similarly severe atherosclerotic patients. This short report questioned the clinical involvement of TNFα during such a pathology where a persistent translocation of endotoxin has been observed through the gut endothelial barrier. Activation of phospholipase A2 is suggested by the increase in the stable metabolite of PGI2 and might be by itself or through lipidic metabolites, a major systemic stimulus of IL-6 and IL-8 production.

  13. Correlation of thiamine metabolite levels with cognitive function in the non-demented elderly.

    Science.gov (United States)

    Lu, Jingwen; Pan, Xiaoli; Fei, Guoqiang; Wang, Changpeng; Zhao, Lei; Sang, Shaoming; Liu, Huimin; Liu, Meng; Wang, Hui; Wang, Zhiliang; Zhong, Chunjiu

    2015-12-01

    Thiamine metabolism is critical for glucose metabolism and also vital for brain function, which is susceptible to decline in the elderly. This study aimed to investigate whether thiamine metabolites correlate with cognitive function in the non-demented elderly and their impact factors. Volunteers >60 years old were recruited and their blood thiamine metabolites and Mini-Mental State Examination (MMSE) scores were measured. The apolipoprotein E (APOE) genotype, routine blood parameters, liver and kidney function, and levels of fasting blood glucose and triglycerides were also measured. The results showed that the thiamine diphosphate (TDP) level weakly correlated with MMSE score in the non-demented elderly. Participants with high TDP levels performed better in Recall and Attention and Calculation than those with low TDP. TDP levels were associated with the APOE ε2 allele, body mass index, hemoglobin level, fasting blood glucose, and triglycerides. Our results suggest that TDP, which is easily affected by many factors, impacts cognitive function in the elderly.

  14. Single oral doses of (±) 3,4-methylenedioxymethamphetamine ('Ecstasy') produce lasting serotonergic deficits in non-human primates: relationship to plasma drug and metabolite concentrations.

    Science.gov (United States)

    Mueller, Melanie; Yuan, Jie; McCann, Una D; Hatzidimitriou, George; Ricaurte, George A

    2013-05-01

    Repeated doses of the popular recreational drug methylenedioxymethamphetamine (MDMA, 'Ecstasy') are known to produce neurotoxic effects on brain serotonin (5-HT) neurons but it is widely believed that typical single oral doses of MDMA are free of neurotoxic risk. Experimental and therapeutic trials with MDMA in humans are underway. The mechanisms by which MDMA produces neurotoxic effects are not understood but drug metabolites have been implicated. The aim of the present study was to assess the neurotoxic potential of a range of clinically relevant single oral doses of MDMA in a non-human primate species that metabolizes MDMA in a manner similar to humans, the squirrel monkey. A secondary objective was to explore the relationship between plasma MDMA and metabolite concentrations and lasting serotonergic deficits. Single oral doses of MDMA produced lasting dose-related serotonergic neurochemical deficits in the brains of squirrel monkeys. Notably, even the lowest dose of MDMA tested (5.7 mg/kg, estimated to be equivalent to 1.6 mg/kg in humans) produced significant effects in some brain regions. Plasma levels of MDMA engendered by neurotoxic doses of MDMA were on the order of those found in humans. Serotonergic neurochemical markers were inversely correlated with plasma concentrations of MDMA, but not with those of its major metabolites, 3,4-dihydroxymethamphetamine and 4-hydroxy-3-methoxymethamphetamine. These results suggest that single oral doses of MDMA in the range of those used by humans pose a neurotoxic risk and implicate the parent compound (MDMA), rather than one of its metabolites, in MDMA-induced 5-HT neural injury.

  15. Combined supercritical fluid extraction/solid-phase extraction with octadecylsilane cartridges as a sample preparation technique for the ultratrace analysis of a drug metabolite in plasma.

    Science.gov (United States)

    Liu, H; Cooper, L M; Raynie, D E; Pinkston, J D; Wehmeyer, K R

    1992-04-01

    Supercritical fluid extraction was coupled with solid-phase extraction using octadecylsilane cartridges for the selective isolation of ultratrace levels of a drug metabolite, mebeverine alcohol, from plasma. Plasma was directly applied to the extraction cartridge, the cartridge was washed to remove protein and then extracted under supercritical conditions using CO2/5% methanol. The effluent from the extraction cell was bubbled through a small volume of 2-propanol to trap the extracted mebeverine alcohol. The effects of extraction pressure and temperature on analyte recovery were examined. The absolute recovery, selectivity, precision, and accuracy of the combined supercritical fluid extraction/solid-phase extraction approach were compared to those of conventional solid-phase extraction using gas chromatography/mass spectrometry in the selected-ion monitoring mode. Mebeverine alcohol was used as a model compound, and dog plasma was employed as the biological matrix for these studies.

  16. Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Yosuke Matsubara

    2017-02-01

    Full Text Available Insufficient detoxification and/or overproduction of reactive oxygen species (ROS induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs in plasma. ROS-scavenging and lipid hydroperoxide (LPO generation assays revealed that gallic acid, 3-O-methylgallic acid, (+-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases.

  17. Influence of a ketogenic diet, fish-oil, and calorie restriction on plasma metabolites and lipids in C57BL/6J mice

    Science.gov (United States)

    2014-01-01

    Background Diet therapies including calorie restriction, ketogenic diets, and fish-oil supplementation have been used to improve health and to treat a variety of neurological and non-neurological diseases. Methods We investigated the effects of three diets on circulating plasma metabolites (glucose and β-hydroxybutyrate), hormones (insulin and adiponectin), and lipids over a 32-day period in C57BL/6J mice. The diets evaluated included a standard rodent diet (SD), a ketogenic diet (KD), and a standard rodent diet supplemented with fish-oil (FO). Each diet was administered in either unrestricted (UR) or restricted (R) amounts to reduce body weight by 20%. Results The KD-UR increased body weight and glucose levels and promoted a hyperlipidemic profile, whereas the FO-UR decreased body weight and glucose levels and promoted a normolipidemic profile, compared to the SD-UR. When administered in restricted amounts, all three diets produced a similar plasma metabolite profile, which included decreased glucose levels and a normolipidemic profile. Linear regression analysis showed that circulating glucose most strongly predicted body weight and triglyceride levels, whereas calorie intake moderately predicted glucose levels and strongly predicted ketone body levels. Conclusions These results suggest that biomarkers of health can be improved when diets are consumed in restricted amounts, regardless of macronutrient composition. PMID:24910707

  18. Acute post-exercise oxygen uptake, hormone and plasma metabolite response in obese men.

    Science.gov (United States)

    Lanzi, S; Codecasa, F; Cornacchia, M; Maestrini, S; Salvadori, A; Fanari, P; Brunani, A; Malatesta, D

    2014-06-01

    This study aimed to compare oxygen uptake (  VO2), hormone and plasma metabolite responses during the 30 min after submaximal incremental exercise (Incr) performed at the same relative/absolute exercise intensity and duration in lean (L) and obese (O) men. Eight L and 8 O men (BMI: 22.9 ± 0.4; 37.2 ± 1.8 kg · m(-2)) completed Incr and were then seated for 30 min.   VO2 was monitored during the first 10 min and from the 25-30(th) minutes of recovery. Blood samples were drawn for the determination of hormone (catecholamines, insulin) and plasma metabolite (NEFA, glycerol) concentrations. Excess post-exercise oxygen consumption (EPOC) magnitude during the first 10 min was similar in O and in L (3.5 ± 0.4; 3.4 ± 0.3 liters, respectively, p=0.86). When normalized to percent change (  VO2END=100%), %   VO2END during recovery was significantly higher from 90-120 s in O than in L (p ≤ 0.04). There were no significant differences in catecholamines (p ≥ 0.24), whereas insulin was significantly higher in O than in L during recovery (p=0.01). The time-course of glycerol was similar from 10-30 min of recovery (-42% for L; -41% for O, p=0.85), whereas significantly different patterns of NEFA were found from 10-30 min of recovery between groups (-18% for L; +8% for O, p=0.03). Despite similar EPOC, a difference in   VO2 modulation between groups was observed, likely due to faster initial rates of   VO2 decline in L than in O. The different patterns of NEFA between groups may suggest a lower NEFA reesterification during recovery in O, which was not involved in the rapid EPOC component. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Personal care product use and urinary levels of phthalate metabolites in Mexican women.

    Science.gov (United States)

    Romero-Franco, Michelle; Hernández-Ramírez, Raúl U; Calafat, Antonia M; Cebrián, Mariano E; Needham, Larry L; Teitelbaum, Susan; Wolff, Mary S; López-Carrillo, Lizbeth

    2011-07-01

    Sources of phthalates other than Polyvinyl chloride (PVC) related products are scarcely documented in Mexico. The objective of our study was to explore the association between urinary levels of nine phthalate metabolites and the use of personal care products. Subjects included 108 women who participated as controls in an ongoing population-based case-control study of environmental factors and genetic susceptibility to breast cancer in northern Mexico. Direct interviews were performed to inquire about sociodemographic characteristics, reproductive history, use of personal care products, and diet. Phthalate metabolites measured in urine by high performance liquid chromatography-isotope dilution tandem mass spectrometry were monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-3-carboxypropyl phthalate (MCPP) as well as mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP) that are metabolites of di-ethylhexyl phthalate (DEHP). Detectable urinary concentrations of phthalate metabolites varied from 75% (MEHP) to 100% (MEP, MBP, MEOHP, MEHHP and MECPP). Medians of urinary concentrations of some phthalate metabolites were significantly higher among users of the following personal care products compared to nonusers: body lotion (MEHHP, MECPP and sum of DEHP metabolites (ΣDEHP)), deodorant (MEHP and ΣDEHP), perfume (MiBP), anti-aging facial cream (MEP, MBP and MCPP) and bottled water (MCPP, MEHHP and MEOHP). Urinary concentrations of MEP showed a positive relationship with the number of personal care products used. Our results suggest that the use of some personal care products contributes to phthalate body burden that deserves attention due to its potential health impact.

  20. The time course of metabolites in human plasma after 6-[(18)F]fluoro-l-m-tyrosine administration.

    Science.gov (United States)

    Wahl, L M; Chen, J J; Thompson, M; Chirakal, R; Nahmias, C

    1999-11-01

    For the investigation of intracerebral dopamine metabolism, 6-[(18)F]fluoro-l-m-tyrosine (FmT) has been proposed as an alternative tracer that, unlike 6-[(18)F]fluoro-l-dopa, is not subjected to O-methylation. We have studied the time course of FmT and its labelled metabolites in plasma after intravenous injection into humans, employing a method that we have developed and validated to analyze labelled metabolites of FmT in plasma. The study population comprised 38 subjects, 14 of whom were taking an aromatic amino acid decarboxylase inhibitor (carbidopa), and obtained arterialized venous blood samples at various times after an intravenous injection of between 185 and 370 MBq of FmT. The major metabolite of FmT present in plasma was 6-[(18)F]fluoro-3-hydroxyphenylacetic acid. The time course of the fraction of radioactivity in plasma attributable to FmT was fitted well by the decay of two exponential functions. The fast component of the decay accounted for 40%-50% of the radioactivity and had a half-life of about 5 min. The slow component of the decay had a half-life of about 6 h in the subjects not taking carbidopa and 20 h in the patients taking carbidopa. When the total available FmT was calculated for each individual subject and expressed as a proportion of total radioactivity, this quantity did not differ significantly from that determined from the corresponding population mean. There was significantly more (15% on average) FmT available over the course of the 2-h experiment in the group pretreated with carbidopa. Our results demonstrate that the major metabolite in plasma after an intravenous injection of FmT is 6-[(18)F]fluoro-3-hydroxyphenylacetic acid. The clearance of FmT from plasma compares well with the clearance of intravenously administered levodopa. Carbidopa increases significantly the availability of FmT in plasma. These results verify, in a large number of human subjects, earlier analyses of FmT metabolism in other species. We validate a

  1. Feeding motivation and plasma metabolites in pregnant sows fed diets rich in dietary fiber either once or twice daily.

    Science.gov (United States)

    Jensen, M B; Pedersen, L J; Theil, P K; Yde, C C; Bach Knudsen, K E

    2012-06-01

    The present study investigated the effects of source and level of dietary fiber (DF) and feeding frequency (once vs. twice daily) on feeding motivation and plasma metabolites at 4 different time points post feeding. Sixty pregnant sows (Sus scrofa, 4 blocks of 15 sows) were allocated to 1 of 5 diets within blocks. Four diets were restricted (approximately 35 MJ ME/d): a barley and wheat control diet (171 g DF/kg DM; 12 g DF/MJ ME), and 3 fiber diets formulated to contain 35% DF by including pectin residue (323 g DF/kg DM; 25 g DF/MJ ME), potato pulp (404 g DF/kg DM; 29 g DF/MJ ME), or sugar beet pulp (367 g DF/kg DM; 25 g DF/MJ ME). The fifth diet was a mixture including an equal amount of the 3 fiber diets offered semi ad libitum (ad libitum access to feed during 6 periods of 1 h starting at 0300, 0600, 1100, 1500, 1800, and 2300; 354 g DF/kg DM; 25 g DF/MJ ME). The experimental period included 2 periods of 4 wk each. Restricted-fed sows were fed once daily (0800 h) during the first period and twice daily (0800 and 1500 h) during the second period, or vice versa. Semi ad libitum fed sows had access to feed 6 times a day in both periods. In each period, the feeding motivation was assessed in an operant conditioning test, and samples of peripheral blood were taken in a balanced design, at 0900, 1200, 1900, and 0700 h, corresponding to 1, 4, 11, and 23 h after feeding for restricted sows fed once daily. No differences in the feeding motivation were found between the 4 restricted diets at any of the time points post feeding, but semi ad libitum fed sows had a decreased feeding motivation (P fiber diets compared with the control (P = 0.02). Nonesterified fatty acid was least in sows on the control diet and greatest in sows on the potato diet, whereas sows on the pectin and sugar beet diets were intermediate (P fiber diets. In spite of the found effects on plasma metabolites, the applied level of fiber in the diet of restrictedly fed sows did not reduce their feeding

  2. Catechol O-methyltransferase and monoamine oxidase A genotypes, and plasma catecholamine metabolites in bipolar and schizophrenic patients.

    Science.gov (United States)

    Zumárraga, Mercedes; Dávila, Ricardo; Basterreche, Nieves; Arrue, Aurora; Goienetxea, Biotza; Zamalloa, María I; Erkoreka, Leire; Bustamante, Sonia; Inchausti, Lucía; González-Torres, Miguel A; Guimón, José

    2010-01-01

    Metabolites of dopamine and norepinephrine measured in the plasma have long been associated with symptomatic severity and response to treatment in schizophrenic, bipolar and other psychiatric patients. Plasma concentrations of catecholamine metabolites are genetically regulated. The genes encoding enzymes that are involved in the synthesis and degradation of these monoamines are candidate targets for this genetic regulation. We have studied the relationship between the Val158Met polymorphism in catechol O-methyltransferase gene, variable tandem repeat polymorphisms in the monoamine oxidase A gene promoter, and plasma concentrations of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid in healthy control subjects as well as in untreated schizophrenic and bipolar patients. We found that the Val158Met substitution in catechol O-methyltransferase gene influences the plasma concentrations of homovanillic and 3,4-dihydroxyphenylacetic acids. Although higher concentrations of plasma homovanillic acid were found in the high-activity ValVal genotype, this mutation did not affect the plasma concentration of 3-methoxy-4-hydroxyphenylglycol. 3,4-dihydroxyphenylacetic acid concentrations were higher in the low-activity MetMet genotype. Interestingly, plasma values 3-methoxy-4-hydroxyphenylglycol were greater in schizophrenic patients and in bipolar patients than in healthy controls. Our results are compatible with the previously reported effect of the Val158Met polymorphism on catechol O-methyltransferase enzymatic activity. Thus, our results suggest that this polymorphism, alone or associated with other polymorphisms, could have an important role in the genetic control of monoamine concentration and its metabolites.

  3. Performance and plasma concentration of metabolites in transition dairy cows supplemented with vitamin E and fat

    Institute of Scientific and Technical Information of China (English)

    Rohollah Amirifard; Mohammad Khorvash; Masiholla Forouzmand; Hamid-Reza Rahmani; Ahmad Riasi; Mohammad Malekkhahi; Mojtaba Yari; Morteza Hosseini-Ghaffari

    2016-01-01

    The objective of this study was to evaluate the effects of vitamin E (VE; 1500 or 3000 international units (IU) d–1) and fat (2% of dry matter calcium salt of soybean oil) supplementation during the transition period on feed intake, milk yield and composition and blood metabolites of dairy cows. 48 multiparous Holstein cows were randomly assigned into one of four treatments in a 2×2 factorial arrangement of vitamin E and supplemental dietary fat during the transition period. Treatments were: 1) 1500 IU d–1 vitamin E without fat supplementation (1500VE–F); 2) 1500 IU d–1 vitamin E with fat supplement (1500VE+F); 3) 3000 IU d–1 vitamin E without fat supplementation (3000VE–F); and 4) 3000 IU d–1 vitamin E with fat supplement (3000VE+F). Dietary treatments were initiated at approximately 28 d before expected calving dates and con-tinued through 28 d postpartum. Dry matter intake (DMI) was unaffected (P>0.05) by prepartum treatment. Regardless of vitamin E supplementation, DMI was greater (P0.05) by treatments. Postpartum diets had no signiifcant effect on milk yield or milk composition. Plasma concentra-tions of non-esteriifed fatty acids, glucose, and insulin were not affected (P>0.05) by treatments. Regardless of vitamin E supplementation, plasma β-hydroxybutyrate concentration was greater (P<0.05) in fat-supplemented cows compared with un-supplemented cows during the postpartum period. These results showed no indication of positive effects on lactation performance associated with vitamin E and dietary fat supplement in transition cows.

  4. Dairy products and plasma cholesterol levels

    Directory of Open Access Journals (Sweden)

    Lena Ohlsson

    2010-08-01

    Full Text Available Cholesterol synthesized in the body or ingested is an essential lipid component for human survival from our earliest life. Newborns ingest about 3–4 times the amount per body weight through mother's milk compared to the dietary intake of adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4–4.5 mmol/L during the nursing period and continue to increase from adulthood around 40% throughout life. Coronary artery disease and other metabolic disorders are strongly associated with low-density lipoprotein (LDL and high-density lipoprotein (HDL cholesterol as well as triacylglycerol concentration. Milk fat contains a broad range of fatty acids and some have a negative impact on the cholesterol rich lipoproteins. The saturated fatty acids (SFAs, such as palmitic acid (C16:0, myristic acid (C14:0, and lauric acid (C12:0, increase total plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans-fatty acids with polyunsaturated fatty acids decreases plasma cholesterol, especially LDL cholesterol, and is associated with a reduced risk of cardiovascular disease. Available data shows different effects on lipoproteins for different dairy products and there is uncertainty as to the impact a reasonable intake amount of dairy items has on cardiovascular risk. The aim of this review is to elucidate the effect of milk components and dairy products on total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent randomized controlled trials of parallel or cross-over design and recent reviews it can be concluded that replacement of saturated fat mainly (but not exclusively derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in polar lipids, and techniques such as fermentation, or fortification of cows feeding can be used

  5. Determination of omeprazole and its metabolites in human plasma by liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Kanazawa, Hideko; Okada, Akiko; Matsushima, Yoshikazu; Yokota, Hiromitsu; Okubo, Shigeo; Mashige, Fumiko; Nakahara, Kazuhiko

    2002-03-08

    Omeprazole is a benzimidazole compound that acts as a proton-pump inhibitor. Because the metabolism of omeprazole is mainly catalyzed by cytochrome P-450 (CYP) 3A4 and CYP2C19. the genetic polymorphism of CYP2C19 could be of clinical concern in the treatment of acid-related diseases with omeprazole. Therefore, a reliable method for omeprazole phenotyping is desirable in clinical situations. This study has demonstrated the determination of omeprazole and its metabolites in human plasma by liquid chromatography-three-dimensional quadrupole mass spectrometry with a sonic spray ionization interface. The analytical column was YMC-Pack Pro C18(50x2.0 mm I.D.) using acetonitrile-50 mM ammonium acetate (pH 7.25) (1:4) at a flow-rate of 0.2 ml/min. The drift voltage was 30 V. The sampling aperture was heated at 110 degrees C and Shield temperature was 230 degrees C. In the mass spectrum, the molecular ions of omeprazole, hydroxyomeprazole and omeprazole sulfone were clearly observed as base peaks. This method is sufficiently sensitive and accurate for pharmacokinetic studies of omeprazol.

  6. Effects of vitamin D3 supplementation and UVb exposure on the growth and plasma concentration of vitamin D3 metabolites in juvenile bearded dragons (Pogona vitticeps).

    Science.gov (United States)

    Oonincx, D G A B; Stevens, Y; van den Borne, J J G C; van Leeuwen, J P T M; Hendriks, W H

    2010-06-01

    The effectiveness of dietary vitamin D3 and UVb exposure on plasma vitamin D metabolites in growing bearded dragons (Pogona vitticeps) was studied. A total of 84 (40 males and 44 females) newly hatched bearded dragons were allocated to six levels of oral vitamin D3 supplementation (0 to 400%) or six UVb exposure times (2 to 12 h). At 3 and 6 months of age, blood samples were obtained from each animal and analysed for 25(OH)D3 and 1,25(OH)2D3. At 3 months of age, plasma concentrations of 25(OH)D3 did not increase with increasing vitamin D3 supplementation unlike the 1,25(OH)2D3. At 6 months of age, plasma concentrations of both 25(OH)D(3) and 1,25(OH)2D3 increased with increasing vitamin D(3) supplementation. Plasma concentrations in UVb-exposed animals were 18 times higher for 25(OH)D3 (178.4+/-9.0 vs. 9.9+/-1.3 nmol/L) and 5.3 times higher for 1,25(OH)2D3 (1.205+/-0.100 vs. 0.229+/-0.025 nmol/L) than in vitamin D(3) supplemented animals at 6 months of age. This study shows that 2h of UVb exposure enables adequate physiological concentrations of plasma vitamin D metabolites to be maintained in growing bearded dragons. Oral supplementation of vitamin D(3) is ineffective in raising plasma concentrations of 25(OH)D3 and 1,25(OH)2D3 to concentrations observed in UVb-exposed animals. 2010 Elsevier Inc. All rights reserved.

  7. Impacts of rising tropospheric ozone on photosynthesis and metabolite levels on field grown soybean.

    Science.gov (United States)

    Sun, Jindong; Feng, Zhaozhong; Ort, Donald R

    2014-09-01

    The response of leaf photosynthesis and metabolite profiles to ozone (O3) exposure ranging from 37 to 116 ppb was investigated in two soybean cultivars Dwight and IA3010 in the field under fully open-air conditions. Leaf photosynthesis, total non-structural carbohydrates (TNC) and total free amino acids (TAA) decreased linearly with increasing O3 levels in both cultivars with average decrease of 7% for an increase in O3 levels by 10 ppb. Ozone interacted with developmental stages and leaf ages, and caused higher damage at later reproductive stages and in older leaves. Ozone affected yield mainly via reduction of maximum rate of Rubisco carboxylation (Vcmax) and maximum rates of electron transport (Jmax) as well as a shorter growing season due to earlier onset of canopy senescence. For all parameters investigated the critical O3 levels (∼50 ppb) for detectable damage fell within O3 levels that occur routinely in soybean fields across the US and elsewhere in the world. Strong correlations were observed in O3-induced changes among yield, photosynthesis, TNC, TAA and many metabolites. The broad range of metabolites that showed O3 dose dependent effect is consistent with multiple interaction loci and thus multiple targets for improving the tolerance of soybean to O3.

  8. Measurement of caffeine and its three primary metabolites in human plasma by HPLC-ESI-MS/MS and clinical application.

    Science.gov (United States)

    Chen, Feng; Hu, Zhe-Yi; Parker, Robert B; Laizure, S Casey

    2017-06-01

    Caffeine is a mild stimulant with significant potential for abuse, being consumed in larger doses with the widespread availability of energy drinks and by novel routes of administration such as inspired powder, oral sprays and electronic cigarettes. How these recent changes in caffeine consumption affecting caffeine disposition and abuse potential is of growing concern. In the study of caffeine disposition in humans, it is common to only measure the caffeine concentration; however, caffeine's three major metabolites (paraxanthine, theobromine and theophylline) retain central nervous system stimulant activity that may contribute to the overall pharmacological activity and toxicity. Therefore, it would be scientifically more rigorous to measure caffeine and its major metabolites in the evaluation of caffeine disposition in human subjects. Herein, we report a method for the simultaneous quantification of caffeine and its three major metabolites in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Human plasma samples were treated by simple protein precipitation and the analytes were separated using a 6 min gradient program. Precision and accuracy were well within in the 15% acceptance range. The simple sample preparation, short runtime, sensitivity and the inclusion of caffeine's major metabolites make this assay methodology optimal for the study of caffeine's pharmacokinetics and pharmacodynamics in human subjects. Copyright © 2016 John Wiley & Sons, Ltd.

  9. High grain diets perturb rumen and plasma metabolites and induce inflammatory responses in early lactation dairy cows

    Directory of Open Access Journals (Sweden)

    B. N. Ametaj

    2010-04-01

    Full Text Available Immediately after parturition dairy cows are fed diets containing high proportions of grain which are associated with high incidence of metabolic disorders. However, the reason behind these effects is not clear. The goal of this study was to investigate metabolic and immune responses of early postpartum dairy cows to feeding increasing proportions of barley grain in the diet. Rumen endotoxin content increased several fold and rumen fluid pH was lower in cows fed the highest amount of barley grain. Results indicate that feeding high proportions of barley grain in early lactation dairy cows was associated with induction of an acute phase response and changes in multiple plasma metabolites. Further research is warranted to understand the mechanism(s by which feeding of barley grain causes disturbances in plasma metabolites and stimulates an inflammatory response in dairy cows.

  10. An examination of the role of feeding regimens in regulating metabolism during the broiler breeder grower period. 2. Plasma hormones and metabolites.

    Science.gov (United States)

    de Beer, M; McMurtry, J P; Brocht, D M; Coon, C N

    2008-02-01

    A trial was conducted to determine the effects of different feeding regimens on plasma hormone and metabolite levels in 16-wk-old broiler breeder pullets. A flock of 350 Cobb 500 breeder pullets was divided in 2 at 28 d of age and fed either every day (ED, 5 pens of 35 birds) or skip-a-day (SKIP, 5 pens of 35 birds) from 28 to 112 d of age. Total feed intake did not differ between the 2 groups. At 112 d, 52 randomly selected pullets from the larger flock of ED-fed pullets, and 76 from the SKIP-fed pullets were individually caged and fed a meal of 74 g (ED) or 148 g (SKIP). Blood samples were collected from 4 pullets in each group by cardiac puncture at intervals after feeding. Plasma was analyzed for insulin, glucagon, insulin-like growth factor-I and insulin-like growth factor-II, triiodothyronine and thyroxine, corticosterone, leptin, glucose, nonesterified fatty acids, triglycerides, and uric acid. Feed retention in the crop was also noted at each interval. In ED birds, the crop was empty by 12 h and in SKIP birds, the crop was empty by 24 h after feeding. The physiological responses to fasting, such as increased glucagon and corticosterone and reduced plasma triglyceride, occurred at times coincidental with crop emptying in both ED and SKIP birds. Overall, mean insulin-like growth factor-I levels were higher (P birds. Triiodothyronine was higher (P = 0.09) in SKIP birds. Overall mean plasma corticosterone was 2-fold higher in SKIP-fed birds, which may be related to the increased length of fasting periods, hunger, and stress. Plasma leptin was consistently higher in ED-fed birds, which was indicative of their more consistent food supply and more stable energy status. In summary, the experiment reported here shows that different feeding regimens can alter hormone and metabolite profiles, in spite of total feed intakes being equal.

  11. Plasma cortisol and faecal cortisol metabolites concentrations in stereotypic and non-stereotypic horses: do stereotypic horses cope better with poor environmental conditions?

    Directory of Open Access Journals (Sweden)

    Fureix Carole

    2013-01-01

    Full Text Available Abstract Background Stereotypic behaviours, i.e. repetitive behaviours induced by frustration, repeated attempts to cope and/or brain dysfunction, are intriguing as they occur in a variety of domestic and captive species without any clear adaptive function. Among the different hypotheses, the coping hypothesis predicts that stereotypic behaviours provide a way for animals in unfavourable environmental conditions to adjust. As such, they are expected to have a lower physiological stress level (glucocorticoids than non-stereotypic animals. Attempts to link stereotypic behaviours with glucocorticoids however have yielded contradictory results. Here we investigated correlates of oral and motor stereotypic behaviours and glucocorticoid levels in two large samples of domestic horses (NStudy1 = 55, NStudy2 = 58, kept in sub-optimal conditions (e.g. confinement, social isolation, and already known to experience poor welfare states. Each horse was observed in its box using focal sampling (study 1 and instantaneous scan sampling (study 2. Plasma samples (collected in study 1 but also non-invasive faecal samples (collected in both studies were retrieved in order to assess cortisol levels. Results Results showed that 1 plasma cortisol and faecal cortisol metabolites concentrations did not differ between horses displaying stereotypic behaviours and non-stereotypic horses and 2 both oral and motor stereotypic behaviour levels did not predict plasma cortisol or faecal cortisol metabolites concentrations. Conclusions Cortisol measures, collected in two large samples of horses using both plasma sampling as well as faecal sampling (the latter method minimizing bias due to a non-invasive sampling procedure, therefore do not indicate that stereotypic horses cope better, at least in terms of adrenocortical activity.

  12. Plasma homocysteine levels in female patients with eating disorders.

    NARCIS (Netherlands)

    Levine, J.; Gur, E.; Loewenthal, R.; Vishne, T.; Dwolatzky, T.; Beijnum, I.M. van; Sela, B.A.; Vered, I.; Yosef, G.; Stein, D.

    2007-01-01

    OBJECTIVE: To examine plasma homocysteine, vitamin B(12), and folate levels in females with restricting and bingeing/purging eating disorders (EDs). METHOD: Adolescent and adult female patients were compared to appropriate control groups with regard to plasma homocysteine levels. RESULTS: The plasma

  13. Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with Type 2 diabetes mellitus.

    Science.gov (United States)

    Pena, M J; Lambers Heerspink, H J; Hellemons, M E; Friedrich, T; Dallmann, G; Lajer, M; Bakker, S J L; Gansevoort, R T; Rossing, P; de Zeeuw, D; Roscioni, S S

    2014-09-01

    Early detection of individuals with Type 2 diabetes mellitus or hypertension at risk for micro- or macroalbuminuria may facilitate prevention and treatment of renal disease. We aimed to discover plasma and urine metabolites that predict the development of micro- or macroalbuminuria. Patients with Type 2 diabetes (n = 90) and hypertension (n = 150) were selected from the community-cohort 'Prevention of REnal and Vascular End-stage Disease' (PREVEND) and the Steno Diabetes Center for this case-control study. Cases transitioned in albuminuria stage (from normo- to microalbuminuria or micro- to macroalbuminuria). Controls, matched for age, gender, and baseline albuminuria stage, remained in normo- or microalbuminuria stage during follow-up. Median follow-up was 2.9 years. Metabolomics were performed on plasma and urine. The predictive performance of a metabolite for albuminuria transition was assessed by the integrated discrimination index. In patients with Type 2 diabetes with normoalbuminuria, no metabolites discriminated cases from controls. In patients with Type 2 diabetes with microalbuminuria, plasma histidine was lower (fold change = 0.87, P = 0.02) and butenoylcarnitine was higher (fold change = 1.17, P = 0.007) in cases vs. controls. In urine, hexose, glutamine and tyrosine were lower in cases vs. controls (fold change = 0.20, P diabetes. Type 2 diabetes-specific plasma and urine metabolites were discovered that predict the development of macroalbuminuria beyond established renal risk markers. These results should be confirmed in a large, prospective cohort. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  14. Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood prolactin levels

    NARCIS (Netherlands)

    Knegtering, R; Baselmans, P; Castelein, S; Bosker, F; Bruggeman, R; van den Bosch, RJ

    2005-01-01

    Objective: The atypical antipsychotic risperidone significantly raises plasma prolactin levels in patients, but clozapine, olanzapine, and quetiapine do not. The differences in neuroendocrine response may be connected with the metabolism of the medications. The authors examined the contributory role

  15. Rapid quantification of the metabolite of valacyclovir hydrochloride in human plasma by liquid chromatography-tandem mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To establish a rapid,sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of acyclovir (the metabolite of valacyclovir hydrochloride) in human plasma. Methods After addition of ganciclovir as internal standard (IS),plasma samples were prepared by one-step protein precipitation using acetonitrile as precipitant,followed by an isocratic elution with 0.1% formic acid solution-methanol (95∶5,v/v) on an Agilent ZORBAX SB-C18 (150mm×2.1mm i.d.,3....

  16. Levels of dichloro-dyphenyl-trichloroethane (DDT) metabolites in maternal milk and their determinant factors.

    Science.gov (United States)

    Torres-Arreola, L; López-Carrillo, L; Torres-Sánchez, L; Cebrián, M; Rueda, C; Reyes, R; López-Cervantes, M

    1999-01-01

    To document the levels and the determinants of dichloro-dyphenyl-trichloroethane (DDT) metabolites in maternal milk, we conducted a cohort study of 50 adult females who lived in Mexico City. We measured social and dietary characteristics via interview. Levels of DDT metabolites were determined by gas-liquid chromatography. The mean values (lipid milk basis) were 0.162 ppm p,p'-DDT; 0.138 ppm o,p'-DDT; and 0.594 ppm 2,2(bis)p-chlorophyenyl-1-1-dichloroethylene (DDE). The main determinants of DDT metabolites were maternal age, lifetime lactation, history of living in an agricultural area, and consumption of salted meat and fish. We estimated that 6.0% of the breast-fed babies had daily intakes of DDT above the level of 0.005 mg/kg d recommended by the World Health Organization/Food and Agriculture Organization of the United Nations (WHO/FAO). Health-outcomes research among children is needed, and investigators should design or adjust current surveillance programs.

  17. Feeding motivation and plasma metabolites in pregnant sows fed diets rich in dietary fiber either once or twice daily

    DEFF Research Database (Denmark)

    Jensen, Margit Bak; Pedersen, Lene Juul; Theil, Peter Kappel

    2012-01-01

    The present study investigated the effects of source and level of dietary fiber (DF) and feeding frequency (once vs. twice daily) on feeding motivation and plasma metabolites at 4 different time points post feeding. Sixty pregnant sows (Sus scrofa, 4 blocks of 15 sows) were allocated to 1 of 5...... diets within blocks. Four diets were restricted (approximately 35 MJ ME/d): a barley and wheat control diet (171 g DF/kg DM; 12 g DF/MJ ME), and 3 fiber diets formulated to contain 35% DF by including pectin residue (323 g DF/kg DM; 25 g DF/MJ ME), potato pulp (404 g DF/kg DM; 29 g DF/MJ ME), or sugar...... beet pulp (367 g DF/kg DM; 25 g DF/MJ ME). The fifth diet was a mixture including an equal amount of the 3 fiber diets offered semi ad libitum (ad libitum access to feed during 6 periods of 1 h starting at 0300, 0600, 1100, 1500, 1800, and 2300; 354 g DF/kg DM; 25 g DF/MJ ME). The experimental period...

  18. GLC determination of plasma drug levels after oral administration of clorazepate potassium salts.

    Science.gov (United States)

    Hoffman, D J; Chun, A H

    1975-10-01

    Plasma nordiazepam levels resulting from the oral administration of clorazepate potassium salts were determined by a sensitive GLC assay. Nordiazepam and the internal standard (diazepam) were selectively extracted into ether at pH 9.2, hydrolyzed to their respective benzophenones, and quantified by electron-capture detection. The assay was used in a comparative bioavailability study of single equimolar oral doses of monopotassium and dipotassium salts of clorazepate in dogs. Both clorazepate salts were rapidly absorbed and exhibited mean peak total drug levels after 1 hr. Clorazepate levels accounted for about 50% of the total drug levels present. No statistical difference in the plasma drug levels of clorazepate mono- and dipotassium salts and the metabolite was found in dogs.

  19. Effects of profession on urinary PAH metabolite levels in the US population.

    Science.gov (United States)

    Liu, Bian; Jia, Chunrong

    2016-01-01

    Although exposure to polycyclic aromatic hydrocarbons (PAHs) is common in both environmental and occupational settings, few studies have compared PAH exposure among people with different professions. The purpose of this study was to investigate the variations in recent PAH exposure among different occupational groups over time using national representative samples. The study population consisted of 4162 participants from the 2001 to 2008 National Health and Nutrition Examination Survey, who had both urinary PAH metabolites and occupational information. Four corresponding monohydroxy-PAH urine metabolites: naphthalene (NAP), fluorene (FLUO), phenanthrene (PHEN), and pyrene (PYR) among seven broad occupational groups were analyzed using weighted linear regression models, adjusting for creatinine levels, sociodemographic factors, smoking status, and sampling season. The overall geometric mean concentrations of NAP, FLUO, PHEN, and PYR were 6927, 477, 335, and 87 ng/L, respectively. All four PAH metabolites were elevated in the "extractive, construction, and repair (ECR)" group, with 21-42 % higher concentrations than those in the reference group of "management." Similar trends were seen in the "operators, fabricators, and laborers (OFL)" group for FLUO, PHEN, and PYR. In addition, both "service" and "support" groups had elevated FLUO. Significant (p job categories exist at the population level. The upward temporal trends in NAP and PYR warrant reduction in PAH exposure, especially among those with OFL and ECR occupations.

  20. Performance and plasma metabolites of dairy calves fed starter containing sodium butyrate, calcium propionate or sodium monensin.

    Science.gov (United States)

    Ferreira, L S; Bittar, C M M

    2011-02-01

    This study was conducted to examine the influence of supplementation of sodium butyrate, sodium monensin or calcium propionate in a starter diet on the performance and selected plasma metabolites (plasma glucose, non-esterified fatty acids and β-hydroxybutyrate) of Holstein calves during pre- and post-weaning periods. Twenty-four newborn Holstein calves were housed in individual hutches until 10 weeks of life, receiving water free choice, and fed four liters of milk daily. Calves were blocked according to weight and date of birth, and allocated to one of the following treatments, according to the additive in the starter: (i) sodium butyrate (150 g/kg); (ii) sodium monensin (30 mg/kg); and (iii) calcium propionate (150 g/kg). During 10 weeks, calves received starter ad libitum, while coast cross hay (Cynodon dactylon (L.) pers.) was offered after weaning, which occurred at the 8th week of age. Weekly, calves were weighted and evaluated for body measurements. Blood samples were taken weekly after the fourth week of age, 2 hours after the morning feeding, for determination of plasma metabolites. No differences were observed among treatments for starter or hay intake, BW and daily gain of the animals. Mean concentrations of selected plasma metabolites were similar in calves fed a starter supplemented with sodium butyrate, sodium monensin and calcium propionate. There was significant reduction in the concentrations of plasma glucose as calves aged. The inclusion of sodium butyrate, calcium propionate or sodium monensin as additives in starter feeds resulted in equal animal performance, before and after weaning, suggesting that sodium monensin may be replaced by organic acid salts.

  1. Monitoring nicotine intake from e-cigarettes: measurement of parent drug and metabolites in oral fluid and plasma.

    Science.gov (United States)

    Papaseit, Esther; Farré, Magí; Graziano, Silvia; Pacifici, Roberta; Pérez-Mañá, Clara; García-Algar, Oscar; Pichini, Simona

    2017-03-01

    Electronic cigarettes (e-cig) known as electronic nicotine devices recently gained popularity among smokers. Despite many studies investigating their safety and toxicity, few examined the delivery of e-cig-derived nicotine and its metabolites in alternative biological fluids. We performed a randomized, crossover, and controlled clinical trial in nine healthy smokers. Nicotine (NIC), cotinine (COT), and trans-3'-hydroxycotinine (3-HCOT) were measured in plasma and oral fluid by liquid chromatography-tandem mass spectrometry after consumption of two consecutive e-cig administrations or two consecutive tobacco cigarettes. NIC and its metabolites were detected both in oral fluid and plasma following both administration conditions. Concentrations in oral fluid resulted various orders of magnitude higher than those observed in plasma. Oral fluid concentration of tobacco cigarette and e-cig-derived NIC peaked at 15 min after each administration and ranged between 1.0 and 1396 μg/L and from 0.3 to 860 μg/L; those of COT between 52.8 and 110 μg/L and from 33.8 to 94.7 μg/L; and those of 3-HCOT between 12.4 and 23.5 μg/L and from 8.5 to 24.4 μg/L. The oral fluid to plasma concentration ratio of both e-cig- and tobacco cigarette-derived NIC peaked at 15 min after both administrations and correlated with oral fluid NIC concentration. The obtained results support the measurement of NIC and metabolites in oral fluid in the assessment of intake after e-cig use and appear to be a suitable alternative to plasma when monitoring nicotine delivery from e-cig for clinical and toxicological studies.

  2. Influence of CYP2D6 Polymorphisms on Serum Levels of Tamoxifen Metabolites in Spanish Women with Breast Cancer

    Science.gov (United States)

    Zafra-Ceres, Mercedes; de Haro, Tomas; Farez-Vidal, Esther; Blancas, Isabel; Bandres, Fernando; de Dueñas, Eduardo Martinez; Ochoa-Aranda, Enrique; Gomez-Capilla, Jose A.; Gomez-Llorente, Carolina

    2013-01-01

    Background Estrogen receptor-positive breast cancer tumors depend on estrogen signaling for their growth and replication and can be treated by anti-estrogen therapy with tamoxifen. Polymorphisms of the CYP2D6 and CYP2C19 genes are associated with an impaired response to tamoxifen. The study objective was to investigate the impact of genetic polymorphisms in CYP2D6 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Spanish women with estrogen receptor-positive breast cancer who were candidates for tamoxifen therapy. Methods: We studied 90 women with estrogen receptor-positive breast cancer, using the AmpliChip CYP450 test to determine CYP2D6 and CYP2C19 gene variants. Plasma levels of tamoxifen and its metabolites were quantified by high-performance liquid chromatography. Results The CYP2D6 phenotype was extensive metabolizer in 80%, intermediate metabolizer in 12.2%, ultra-rapid metabolizer in 2.2%, and poor metabolizer in 5.6% of patients, and the allele frequency was 35.0% for allele *1, 21.0% for *2, and 18.9% for *4. All poor metabolizers in this series were *4/*4, and their endoxifen and 4-hydroxy tamoxifen levels were 25% lower than those of extensive metabolizers. CYP2C19*2 allele, which has been related to breast cancer outcomes, was detected in 15.6% of the studied alleles. Conclusion CYP2D6*4/*4 genotype was inversely associated with 4-hydroxy tamoxifen and endoxifen levels. According to these results, CYP2D6 and CYP2C19 genotyping appears advisable before the prescription of tamoxifen therapy. PMID:23781139

  3. Quantitative Metabolite Profiling of an Amino Group Containing Pharmaceutical in Human Plasma via Precolumn Derivatization and High-Performance Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry.

    Science.gov (United States)

    Li, Sanwang; Klencsár, Balázs; Balcaen, Lieve; Cuyckens, Filip; Lynen, Frederic; Vanhaecke, Frank

    2017-02-07

    Quantitative determination of the candidate drug molecule and its metabolites in biofluids and tissues is an inevitable step in the development of new pharmaceuticals. Because of the time-consuming and expensive nature of the current standard technique for quantitative metabolite profiling, i.e., radiolabeling followed by high-performance liquid chromatography (HPLC) with radiodetection, the development of alternative methodologies is of great interest. In this work, a simple, fast, sensitive, and accurate method for the quantitative metabolite profiling of an amino group containing drug (levothyroxine) and its metabolites in human plasma, based on precolumn derivatization followed by HPLC-inductively coupled plasma mass spectrometry (ICPMS), was developed and validated. To introduce a suitable "heteroelement" (defined here as an element that is detectable with ICPMS), an inexpensive and commercially available reagent, tetrabromophthalic anhydride (TBPA) was used for the derivatization of free NH2-groups. The presence of a known number of I atoms in both the drug molecule and its metabolites enabled a cross-validation of the newly developed derivatization procedure and quantification based on monitoring of the introduced Br. The formation of the derivatives was quantitative, providing a 4:1 stoichiometric Br/NH2 ratio. The derivatives were separated via reversed-phase HPLC with gradient elution. Bromine was determined via ICPMS at a mass-to-charge ratio of 79 using H2 as a reaction gas to ensure interference-free detection, and iodine was determined at a mass-to-charge ratio of 127 for cross-validation purposes. The method developed shows a fit-for-purpose accuracy (recovery between 85% and 115%) and precision (repeatability <15% RSD). The limit of quantification (LoQ) for Br was approximately 100 μg/L.

  4. Effect of the long-term regular intake of virgin olive oil on the phenolic metabolites in human fasting plasma.

    Science.gov (United States)

    Valls, Rosa-Maria; Soler, Aranzazu; Girona, Josefa; Heras, Mercedes; Romero, Maria-Paz; Covas, Maria-Isabel; Solà, Rosa; Masana, Lluis; Motilva, Maria-Jose

    2010-09-21

    The effect of repeated consumption of virgin olive oil on endogenous phenolic metabolites of fasting plasma is unknown. For this reason, we hypothesized that regular long-term virgin olive oil intake could have an indirect protection effect on the endogenous phenols. Thus, the aim of the study was to determine the phenolic profile of human plasma in a fasting state of long-term regular virgin olive oil consumers, using the fasting plasma of non-consumers as a natural control. Forty participants living in the area of Reus (Catalonia, Spain) were selected, 20 life-long regular consumers of virgin olive oil and a natural control of 20 non-consumers, the latter being Rumanians who dislike the taste of olive oil. The diet was obtained from 3-day food records. The results showed similar phenolic composition of fasting plasmas of the two volunteer groups. Of special interest is that more of the compounds quantified showed higher concentration in fasting plasma from habitual virgin olive oil consumers. The compounds were semi-quantified using caffeic acid as the calibration standard. The quantification of fasting consumer's plasma showed higher concentration of a hydroxyflavanone type compound (2.90+/-0.04 microM vs 1.5+/-0.04 microM) and a catecholamine derivative (0.70+/-0.03 microM vs 0.56+/-0.03 microM) than the plasma of non-consumers (Polive oil consumption related to the protection of the endogenous antioxidant system.

  5. Effects of feeding metabolite combinations from lactobacillus plantarum on plasma and breast meat lipids in Broiler Chickens

    Directory of Open Access Journals (Sweden)

    TC Loh

    2013-12-01

    Full Text Available The effects of feeding different doses of metabolite combination of L. plantarum RS5, RI11, RG14 and RG11 strains (Com3456 on cholesterol reduction in plasma and breast meat in broiler chickens and the possible mechanism was studied. A total of 504 male Ross broilers were grouped into 7 treatments and offered with different diets: (i standard corn-soybean based diet (-ve control; (ii standard cornsoybean based diet + neomycin and oxytetracycline (+ve control; (iii standard corn-soybean based diet + 0.1% metabolite combination of L. plantarum RS5, RI11, RG14 and RG11 strains (Com3456; (iv standard corn-soybean based diet + 0.2% of Com3456; (v standard cornsoybean based diet + 0.3% of Com3456 (vi standard corn-soybean based diet + 0.4% of Com3456 and (vii standard corn-soybean based diet + 0.5% of Com3456. The metabolite combinations supplemented in the diet of broilers reduced protein, cholesterol esters concentration in very low-density lipoprotein particles. The present of organic acids and proteinaceous compound in the metabolite combinations as found in previous study also increased lactic acid bacteria count in small intestine digesta and improved bile salts deconjugation ability of lactic acid bacteria.

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

    Science.gov (United States)

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

    2013-12-01

    A rapid, sensitive, simple and accurate LC-MS/MS method for the simultaneous quantitation of caffeine, and its three primary metabolites, theobromine, paraxanthine, and theophylline, in rat plasma was developed and validated. Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18 column using 1 μg/mL acetaminophen as an internal standard. Each sample was run at 0.5 mL/min for a total run time of 7 min/sample. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with positive electrospray ionization. The lower limit of quantification was 5 ng/mL for all analytes with linear ranges up to 5000 ng/mL for caffeine and 1000 ng/mL for its metabolites. The coefficient of variation for assay precision was less than 12.6%, with an accuracy of 93.5-114%. The assay was successfully applied to determine plasma concentrations of caffeine, theobromine, paraxanthine, and theophylline in rat administered various energy drinks containing the same caffeine content. Various energy drinks exhibited considerable variability in the pharmacokinetic profiles of caffeine and its three primary metabolites, even containing the same caffeine. Different additives of energy drinks might contribute to these results. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. A novel LC-MS/MS method for the simultaneous quantification of topiramate and its main metabolites in human plasma.

    Science.gov (United States)

    Milosheska, Daniela; Roškar, Robert

    2017-05-10

    The aim of the present report was to develop and validate simple, sensitive and reliable LC-MS/MS method for quantification of topiramate (TPM) and its main metabolites: 2,3-desisopropylidene TPM, 4,5-desisopropylidene TPM, 10-OH TPM and 9-OH TPM in human plasma samples. The most abundant metabolite 2,3-desisopropylidene TPM was isolated from patients urine, characterized and afterwards used as an authentic standard for method development and validation. Sample preparation method employs 100μL of plasma sample and liquid-liquid extraction with a mixture of ethyl acetate and diethyl ether as extraction solvent. Chromatographic separation was achieved on a 1290 Infinity UHPLC coupled to 6460 Triple Quad Mass Spectrometer operated in negative MRM mode using Kinetex C18 column (50×2.1mm, 2.6μm) by gradient elution using water and methanol as a mobile phase and stable isotope labeled TPM as internal standard. The method showed to be selective, accurate, precise and linear over the concentration ranges of 0.10-20μg/mL for TPM, 0.01-2.0μg/mL for 2,3-desisopropylidene TPM, and 0.001-0.200μg/mL for 4,5-desisopropylidene TPM, 10-OH TPM and 9-OH TPM. The described method is the first fully validated method capable of simultaneous determination of TPM and its main metabolites in plasma over the selected analytical range. The suitability of the method was successfully demonstrated by the quantification of all analytes in plasma samples of patients with epilepsy and can be considered as reliable analytical tool for future investigations of the TPM metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Associations between vitamin D-binding protein isotypes, circulating 25(OH)D levels, and vitamin D metabolite uptake in colon cancer cells.

    Science.gov (United States)

    Hibler, Elizabeth A; Jacobs, Elizabeth T; Stone, Angelika Dampf; Sardo, Christine L; Galligan, Michael A; Jurutka, Peter W

    2014-04-01

    Vitamin D metabolites have been extensively studied as cancer chemopreventive agents. Gc-globulin (GC) isotypes, based on rs7041 and rs4588 diplotypes, have varying affinities for 1α,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25(OH)D), which may affect circulating metabolite concentration as well as delivery at the cellular level. We evaluated associations between GC isotype and circulating vitamin D metabolite concentrations in 403 ursodeoxycholic acid (UDCA) clinical trial participants. Metabolite uptake was evaluated in human colon cancer (HCT-116) cells treated with ethanol vehicle, 1,25(OH)2D, or 25(OH)D, and with plasma from individuals with known GC isotype. Mammalian-2-hybrid and vitamin D-responsive element-based luciferase assays were used to measure the vitamin D receptor pathway activation as a marker for metabolite uptake. Regression analysis demonstrated significantly lower serum 25(OH)D concentration for clinical trial participants with 1F_2, 1S_2, or 2_2 isotypes (P OH)D uptake varied less by GC isotype only at the higher concentration tested (P = 0.05), while 1,25(OH)2D uptake differed markedly by GC isotype across concentration and assay (P OH)2D treatment and, while activation varied less with 25(OH)D, the 2_2 isotype demonstrated increased induction at the lower concentration. These results suggest that vitamin D metabolite concentration and delivery to colon cells may vary not only by GC isotype, but also that certain isotypes may more effectively deliver 1,25(OH)2D versus 25(OH)D. Overall, these results may help identify populations at risk for cancer and potential recipients of targeted chemoprevention.

  9. Plasma and semen ascorbic levels in spermatogenesis

    African Journals Online (AJOL)

    were significant decreases in the seminal and plasma ascorbic acid concentrations ... maintenance of sperm cell lipid membrane has generated increasing interest. .... function and its association with the genesis of reactivc oxygen species.

  10. [Identification of the metabolites of Sinisan extract in rat plasma, urine, feces and bile after intragastric administration].

    Science.gov (United States)

    Lu, Lin-ling; Shu, Yan; Qian, Da-wei; Su, Shu-lan; Duan, Jin-ao; Qian, Ye-fei; Xue, Cai-fu

    2011-11-01

    Sinisan is a widely used traditional Chinese medicine (TCM) in treating various diseases; however, the in vivo metabolic profile of its multiple components remains unknown. In this paper, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was applied to identify the metabolites of Sinisan extract in rat plasma, urine, feces and bile after intragastric administration. Using MS(E) and mass defect filter techniques, 41 metabolites of 10 parent compounds (naringin, naringenin, hesperidin, neohesperidin, liquiritin, liquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, saikosaponin a and saikosaponin d) were detected and tentatively identified. It was shown by our results that these compounds was metabolized to the forms of hydroxylation, glucuronidation, sulfation, glucuronidation with sulfation and glucuronidation with hydroxylation in vivo.

  11. [Metabolites of R, S-1-(2-methoxyphenyl)-4-[3-(naphtha-1-yl-oxy)-2-hydroxypropyl]-piperazin in rat plasma].

    Science.gov (United States)

    Li, Li; Zhou, Xin; Yuan, Mu; Zhou, Hong; Wang, Dao-Ping

    2006-01-01

    To study the metabolites of R, S-1-(2-methoxypheyl)-4-[3-(naphthal-yl-oxy)-2-hydroxypropyl] -piperazine, (naftopidil, NAF), a novel antihypertensive drug in rat plasma. The rat plasma samples were analyzed by LC/MS after oral administration of NAF. According to MS relativity of metabolites and parent compound (NAF) and metabolic rule of compound with similar structure, the structure of potential metabolites were postulated. Phase I metabolites were identified by HPLC/MS and by comparison with authentic standards, phase II conjugates were indirectly identified with beta-D-glucuronidase in presence or absence of glucuronidase selective inhibitor D-saccharric acid beta-1,4-Lactone. Phase I metabolites desmethyl-naftopidil (DMN), (phenyl) hydroxynaftopidil (PHN), (naphthyl) -hydroxy-naftopidil (NHN) were separated and identified in rat plasma by comparison with reference substances, phase II conjugates, NAF and NHN glucuronide conjugates were separated and tentatively identified by hydrolysis with glucuronidase, the aglycones, NAF and NHN, were identified in rat plasma. The major metabolic pathway of NAF in rat plasma should be the hydroxylation of the phenyl or nephthyl moiety of NAF and demethylation of NAF. Therefore, (naphthyl) hydroxyl-metabolite and NAF followed by conjugation with beta-glueuronic acid.

  12. Reduction of thyroid hormone levels by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Yoshihisa; Shibahara, Tomoo; Kimura, Ryohei [School of Pharmaceutical Sciences, University of Shizuoka (Japan); Haraguchi, Koichi; Masuda, Yoshito [Daiichi College of Pharmaceutical Sciences, Fukuoka (Japan)

    1998-07-01

    Male Sprague-Dawley rats received four consecutive intraperitoneal doses of four kinds of methylsulfonyl (MeSO{sub 2}) metabolites of polychlorinated biphenyl (PCB) congeners: 3-MeSO{sub 2}-2,2`,3`,4`,5,6-hexachlorobiphenyl (3-MeSO{sub 2}-CB132); 3-MeSO{sub 2}-2,2`,3`,4`, 5,5`-hexachlorobiphenyl (3-MeSO{sub 2}-CB141); 3-MeSO{sub 2}-2,2`,4`,5,5`,6-hexachlorobiphenyl (3-MeSO{sub 2}-CB149) and 4-MeSO{sub 2}-2,2`,4`,5,5`,6-hexachlorobiphenyl (4-MeSO{sub 2}-CB149). The congeners were major MeSO{sub 2}-PCBs determined in human milk, liver and adipose tissue, and the aim was to determine their effect on thyroid hormone levels. All four tested MeSO{sub 2} metabolites (20 {mu}mol/kg once daily for 4 days) reduced serum total thyroxine levels by 22-44% at a much lower dose than phenobarbital (PB; 431 {mu}mol/kg once daily for 4 days) on days 2, 3, 4 and 7 after the final doses. Total triiodothyronine levels were reduced 37% by treatment with 4-MeSO{sub 2}-CB149 at day 7. A 30% increase in thyroid weight was produced by 3-MeSO{sub 2}-CB141 treatment. Total cytochrome P450 content was increased by 3-MeSO{sub 2}-CB132, 3-MeSO{sub 2}-CB141 and 3-MeSO{sub 2}-CB149, but not by 4-MeSO{sub 2}-CB149. Thus, it is likely that the 3-MeSO{sub 2}-hexachlorobiphenyls and 4-MeSO{sub 2}-CB149 could influence the thyroid hormone metabolism by different mechanism(s). The results show that tested 3- and 4-MeSO{sub 2} metabolites of PCB congeners reduce thyroid hormone levels much more than PB in rats. Our finding suggests that the metabolites may act as endocrine-disrupters. (orig.) With 2 figs., 1 tab., 25 refs.

  13. Plasma concentrations of cortisol and PGF2α metabolite in Danish sows during mating, and intrauterine and conventional insemination

    Directory of Open Access Journals (Sweden)

    Kindahl Hans

    2007-12-01

    Full Text Available Abstract Background The aims of the present work was to study whether there are any relationships between cortisol and PG-metabolite in mated sows or inseminated with the intrauterine technique and compare these to changes occurring in conventionally inseminated sow. Methods Thirty three crossbred sows (Danish Landrace × Danish Large White were fitted with jugular vein catheters through vena auricularis from one of the ears. The sows were randomly divided into three groups (Boar-, IUI- and AI-group and blood samples were collected before, during and after service. In a final evaluation only 25 sows that became pregnant and farrowed piglets at full term were used. Results Cortisol concentrations increased in all groups but Boar-group (n = 8 had a significantly higher cortisol during 10 to 20 min after service than sows in AI-group (n = 8. In mated sows cortisol concentrations peaked at 15 minutes after service. The Boar-group (n = 8 showed no ascending PG-metabolite levels during the whole experiment, while both IUI- and AI-groups (n = 9 and n = 8, respectively had a 2.5-fold increase in PG-metabolite 15 minutes after service. Conclusion In conclusion, mating of sows by a boar results in a greater increase of cortisol than AI and without an elevation of PG-metabolite levels, which was seen in both the inseminated groups. It was also demonstrated that IUI-group had an earlier significant increase of PG-metabolite levels than sows inseminated conventionally. Further investigation using different semen extenders or even different type of insemination catheters might be helpful in understanding the reason for an immediate increase of PG-metabolite after insemination but not after mating.

  14. Simultaneous determination of blonanserin and its four metabolites in human plasma using ultra-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Zhou, Ying; Liu, Ming; Jiang, Ji; Wang, Hongyun; Hu, Pei

    2013-11-15

    A sensitive and rapid method based on ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the simultaneous determination of blonanserin, its major active metabolite (N-deethyl form) and other three metabolites (N-oxide form, Ethylenediamine form and Carboxylate form) in human plasma. Plasma samples were pre-purified by solid-phase extraction (SPE) and analyzed using a gradient chromatographic separation over an Acquity UPLC CSH C18 column. The mobile phase consisted of acetonitrile-water containing 5mM ammonium formate and 0.1% formic acid at a flow rate of 0.5mL/min. Positive electrospray ionization was employed as the ionization source in the multiple reaction monitoring (MRM) mode. The analysis time was about 3.5min. The method was fully validated over the concentration range of 0.01-1ng/mL for all analytes. The lower limit of quantification (LLOQ) was 0.01ng/mL. Inter- and intra-batch precision was less than 15% and the accuracy was within 85-115%. The mean extraction recoveries of all analytes at two concentration levels were consistent. Selectivity, matrix effect and stability were also validated. The method was applied to the pharmacokinetic study of blonanserin in Chinese healthy subjects. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Paradoxical sleep deprivation increases plasma endothelin levels

    Directory of Open Access Journals (Sweden)

    B.D. Palma

    2002-01-01

    Full Text Available The endothelins (ET-1, 2 and 3 constitute a family of 21 amino acid peptides with potent biological activities. ET-1 is one of the most potent endogenous vasoconstrictors so far identified and its increased concentration in plasma appears to be closely related to the pathogenesis of arterial hypertension as well as to obstructive sleep apnea (OSA. OSA patients exhibit repetitive episodes of apnea and hypopnea that result in hypoxia and consecutive arousals. These patients are chronically sleep deprived, which may aggravate the hypertensive features, since literature data show that sleep deprivation results in hypertension both in humans and in animals. Based on the reported relationship between ET-1, hypertension and sleep deprivation consequences, the purpose of the present study was to determine plasma ET concentrations in paradoxical sleep-deprived animals. Male Wistar rats, 3 to 4 months old (N = 10 per group, were deprived of sleep for 24 and 96 h by the platform technique and plasma ET-1/2 was measured by radioimmunoassay. Analysis of plasma revealed that 96 h of sleep deprivation induced a significant increase in ET-1/2 release (6.58 fmol/ml compared to control (5.07 fmol/ml. These data show that sleep deprivation altered plasma ET-1/2 concentrations, suggesting that such an increase may participate in the genesis of arterial hypertension and cardiorespiratory changes observed after sleep deprivation.

  16. Low arginine plasma levels in patients after thoracoabdominal aortic surgery.

    Science.gov (United States)

    Nijveldt, R J; Prins, H A; Siroen, M P; Rauwerda, J A; Teerlink, T; van Leeuwen, P A

    2000-08-01

    Thoracoabdominal aortic surgery is a high-risk procedure and associated with a significant morbidity and mortality. Ischemia reperfusion of visceral organs and lower extremities is one of the most important determinants of this morbidity. Arginine is the precursor of nitric oxide and arginine plasma levels are important in maintaining organ blood flow. Furthermore, arginine is important in wound healing and the immune system. Because of increased utilization of arginine, low arginine plasma levels could be expected after thoracoabdominal aortic surgery. We therefore measured arginine plasma levels in these patients. Six patients with thoracoabdominal aortic aneurysm were included in this study. University Hospital Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands. Six patients undergoing thoracoabdominal aortic surgery. Plasma levels of arginine were measured by high-performance liquid chromatography. Very low arginine plasma levels were seen on the first postoperative day. From day 1 arginine slowly increased, but did not reach normal plasma levels on day 6. A significant decrease of arginine plasma levels was found and because of the fact that arginine has multiple functions, it may be important to keep these arginine plasma levels at normal or even higher levels in patients undergoing major vascular surgery. European Journal of Clinical Nutrition (2000) 54, 615-617.

  17. Metabolomic analysis reveals differences in umbilical vein plasma metabolites between normal and growth-restricted fetal pigs during late gestation.

    Science.gov (United States)

    Lin, Gang; Liu, Chuang; Feng, Cuiping; Fan, Zhiyong; Dai, Zhaolai; Lai, Changhua; Li, Zhen; Wu, Guoyao; Wang, Junjun

    2012-06-01

    Intrauterine growth restriction (IUGR) remains a major problem for both human health and animal production due to its association with high rates of neonatal morbidity and mortality, low efficiency of food utilization, permanent adverse effects on postnatal growth and development, and long-term health and productivity of the offspring. However, the underlying mechanisms for IUGR are largely unknown. In this study, one IUGR fetus and one normal body weight (NBW) fetus were obtained from each of 9 gilts at each of 2 gestational ages (d 90 and 110). Metabolomes of umbilical vein plasma in IUGR and NBW fetuses were determined by MS, while hormones, amino acids, and related metabolites in maternal and fetal plasma were measured using assay kits and chromatographic methods. Metabolites (including glucose, urea, ammonia, amino acids, and lipids) in umbilical vein plasma exhibited a cluster of differences between IUGR and NBW fetuses on d 90 and 110 of gestation. These changes in the IUGR group are associated with disorders of nutrient and energy metabolism as well as endocrine imbalances, which may contribute to the retardation of fetal growth and development. The findings help provide information regarding potential mechanisms responsible for IUGR in swine and also have important implications for the design of effective strategies to prevent, diagnose, and treat IUGR in other mammalian species, including humans.

  18. Plasma levels of acylated ghrelin in patients with functional dyspepsia

    Institute of Scientific and Technical Information of China (English)

    Yeon Soo Kim; Joon Seong Lee; Tae Hee Lee; Joo Young Cho; Jin Oh Kim; Wan Jung Kim; Hyun Gun Kim; Seong Ran Jeon; Hoe Su Jeong

    2012-01-01

    AIM:To investigate the relationship between plasma acylated ghrelin levels and the pathophysiology of functional dyspepsia.METHODS:Twenty-two female patients with functional dyspepsia and twelve healthy volunteers were recruited for the study.The functional dyspepsia patients were each diagnosed based on the Rome Ⅲ criteria.Eligible patients completed a questionnaire concerning the severity of 10 symptoms.Plasma acylated ghrelin levels before and after a meal were determined in the study participants using a commercial human acylated enzyme immunoassay kit; electrogastrograms were performed for 50 min before and after a standardized 10-min meal containing 265 kcal.RESULTS:There were no significant differences in plasma acylated ghrelin levels between healthy volunteers and patients with functional dyspepsia.However,in patients with functional dyspepsia,there was a negative correlation between fasting plasma acylated ghrelin levels and the sum score of epigastric pain (r =-0.427,P =0.047) and a positive correlation between the postprandial/fasting plasma acylated ghrelin ratio and the sum score of early satiety (r =0.428,P =0.047).Additionally,there was a negative correlation between fasting acylated ghrelin plasma levels and fasting normogastria (%) (r =-0.522,P =0.013).Interestingly,two functional dyspepsia patients showed paradoxically elevated plasma acylated ghrelin levels after the meal.CONCLUSION:Abnormal plasma acylated ghrelin levels before or after a meal may be related to several of the dyspeptic symptoms seen in patients with functional dyspepsia.

  19. Determination of two mebeverine metabolites, mebeverine alcohol and desmethylmebeverine alcohol, in human plasma by a dual stable isotope-based gas chromatographic-mass spectrometric method.

    Science.gov (United States)

    Tulich, L J; Randall, J L; Kelm, G R; Wehmeyer, K R

    1996-07-12

    A dual stable isotope-based GC-MS method was developed for the simultaneous determination of two metabolites of mebeverine, mebeverine alcohol and desmethylmebeverine alcohol, in human plasma. Plasma samples were treated with beta-glucuronidase to cleave the glucuronide conjugates of both compounds prior to analysis. The treated plasma was prepared for analysis by solid-phase extraction using octadecylsilane cartridges. The isolated metabolites were derivatized and analyzed by GC-MS using selected-ion monitoring. Plots of peak-area ratio were linear with metabolite concentration from 2 to 200 ng/ml and the limit of detection for both metabolites was 0.5 ng/ml. The GC-MS methodology was applied to the analysis of plasma from human subjects following peroral administration of mebeverine. Pharmacokinetic parameters for both metabolites were determined and suggest that relative systemic mebeverine exposure may potentially be assessed using metabolite kinetics, if the latter subsequently are demonstrated to be linear with mebeverine dose.

  20. A new HILIC-MS/MS method for the simultaneous analysis of carbidopa, levodopa, and its metabolites in human plasma.

    Science.gov (United States)

    Vilhena, Raquel de Oliveira; Pontes, Flávia Lada Degaut; Marson, Breno Maurício; Ribeiro, Rômulo Pereira; de Carvalho, Katherine Athayde Teixeira; Cardoso, Marco André; Pontarolo, Roberto

    2014-09-15

    Monitoring of the plasmatic levels of levodopa (LEV) and carbidopa (CAR) is necessary to adjust the dose of these drugs according to the individual needs of Parkinson's disease patients. To support drug therapeutic monitoring, a method using HILIC mode and LC-MS/MS was developed for the simultaneous determination of carbidopa, levodopa, and its metabolites (3-o-methyldopa (3-OMD) and dopamine (DOPA)) in human plasma. A triple quadrupole mass spectrometry was operated under the multiple reaction-monitoring mode (MRM) using the electrospray ionization technique. After straightforward sample preparation via protein precipitation, an Atlantis HILIC (150 × 2.1 mm, 3 μm, Waters, USA) column were used for separation under the isocratic condition of acetonitrile/water (79:21, v/v) containing 0.05% formic acid and 3 mmol/L ammonium formate and the total run time was 7 min. Deuterated LEV was used as internal standard for quantification. The developed method was validated in human plasma with a lower limit of quantitation of 75 ng/mL for LEV, 65 ng/mL for CAR and 3-OMD, and 20 ng/mL for DOPA. The calibration curve was linear within the concentration range of 75-800 ng/mL for LEV, 65-800 ng/mL for CAR and 3-OMD, and 20-400 ng/mL for DOPA (r>0.99). The assay was accurate and precise, with inter-assay and intra-assay accuracies within ±13.44% of nominal and inter-assay and intra-assay precision≤13.99%. All results were within the acceptance criteria of the US FDA and ANVISA guidelines for method validation. LEV, CAR, 3-OMD and DOPA were stable in the battery of stability studies, long-term, bench-top, autosampler, and freeze/thaw cycles. Samples from patients undergoing treatment were analyzed, and the results indicated that this new method is suitable for therapeutic drug monitoring in Parkinson's disease patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Plasma glutamine levels and falciparum malaria.

    Science.gov (United States)

    Cowan, G; Planche, T; Agbenyega, T; Bedu-Addo, G; Owusu-Ofori, A; Adebe-Appiah, J; Agranoff, D; Woodrow, C; Castell, L; Elford, B; Krishna, S

    1999-01-01

    Glutamine deficiency is associated with increased rates of sepsis and mortality, which can be prevented by glutamine supplementation. Changes in glutamine concentration were examined in Ghanaian children with acute falciparum malaria and control cases. The mean (SD) plasma glutamine concentration was lower in patients with acute malaria (401 (82) mumol/L, n = 50) than in control patients (623 (67) mumol/L, n = 7; P sepsis and dyserythropoeisis.

  2. Prenatal urinary phthalate metabolites levels and neurodevelopment in children at two and three years of age

    Science.gov (United States)

    Téllez-Rojo, Martha M.; Cantoral, Alejandra; Cantonwine, David E.; Schnaas, Lourdes; Peterson, Karen; Hu, Howard; Meeker, John D.

    2013-01-01

    Background Previous studies suggest that prenatal phthalate exposure affects neurodevelopment and behavior during the first years of life. Objectives To evaluate the effect of maternal urinary concentrations of phthalate metabolites during pregnancy on mental and psychomotor development in children 24-36 months of age. Methods This analysis was conducted on the first three years of life among a subsample of 136 mother-child pairs from the ELEMENT cohort studies conducted in Mexico City. Maternal urine samples collected during the third trimester of pregnancy were analyzed for 9 phthalate metabolites: Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), Mono-3-carboxypropyl phthalate (MCPP), and four di-2-ethylhexyl phthalate (DEHP) metabolites [mono-2-ethylhexyl-phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)]. Among the 136 children, 135 (99.3%) completed the study period. Child neurodevelopment was assessed using mental and psychomotor development indexes (MDI and PDI) from a Bayley (BSID II) test at 24, 30, and 36 months of age. The effect of prenatal phthalate exposure on neurodevelopment was estimated using linear regression models for longitudinal data clustered at the individual level. Results No significant associations were observed among all children combined, but differential effects by gender were found. Among girls, there was a negative association between MDI and DEHP metabolites MEHP (β = −2.11 [95% CI: −3.73, −0.49]), MEHHP (β = −1.89 [95% CI: −3.64, −0.15]), MEOHP (β = −1.80 [95% CI: −3.58, −0.03]) MECPP (β = −2.52 [95% CI: −4.44, −0.61]), and DEHP (β = −3.41 [95% CI: −5.26, −1.55]); there was no significant effect among boys. Male PDI was positively related to MBzP (β = 1.79 [95% CI: 0.14, 3.45]) and MCPP (β = 1.64 [95% CI: 0

  3. Development and validation of a liquid chromatographic method for the simultaneous determination of four anthracyclines and their respective 13-S-dihydro metabolites in plasma and saliva.

    Science.gov (United States)

    Maudens, Kristof E; Stove, Christophe P; Cocquyt, Veronique F J; Denys, Hannelore; Lambert, Willy E

    2009-11-15

    A quantitative HPLC method with fluorescence detection has been developed for the simultaneous determination of four anthracyclines (doxorubicin, epirubicin, daunorubicin and idarubicin) and their respective 13-S-dihydro metabolites (doxorubicinol, epirubicinol, daunorubicinol and idarubicinol) in plasma and saliva, using epidaunorubicin as internal standard. A progressive optimization matrix led to a two-step extraction based on a protein precipitation with ethanol followed by a liquid-liquid extraction with dichloromethane after pH adjustment to 8.5. The chromatographic separation was performed in 14min on a C18 column, applying gradient elution with a mixture of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. The analytes were detected and quantified at an excitation and emission wavelength of 480 and 555nm, respectively. Limit of detection (LOD) and lower limit of quantification (LLOQ) were 0.3 or 0.75, and 1 or 2.5ng/mL, respectively. Linearity by means of weighted (1/x) regression was obtained from the LLOQ up to 1000 or 2500ng/mL for the parent drugs and up to 400 or 1000ng/mL for the metabolites. Intra-assay and inter-assay relative standard deviation values were all less than 14% at low, medium and high levels, and below 17% at the LLOQ. Accuracy ranged between 91 and 113% at low, medium and high concentrations and between 83 and 118% at the LLOQ. Absolute recoveries were between 78 and 88% in plasma, and between 70 and 79% in saliva, respectively. Autosampler, benchtop, freeze-thaw and long-term stability samples fulfilled acceptance criteria. This selective method was applied successfully to the analysis of plasma and saliva samples from patients administered epirubicin intravenously.

  4. Simultaneous analysis of oxybutynin and its active metabolite N-desethyl oxybutynin in human plasma by stable isotope dilution LC-MS/MS to support a bioequivalence study.

    Science.gov (United States)

    Sharma, Primal; Patel, Daxesh P; Sanyal, Mallika; Berawala, Hiren; Guttikar, Swati; Shrivastav, Pranav S

    2013-10-01

    An isotope dilution high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of oxybutynin and its pharmacologically active metabolite N-desethyl oxybutynin in human plasma. Extraction of oxybutynin, its metabolite and their deuterated analogs as internal standards (ISs) from 300 μL human plasma was carried out by liquid-liquid extraction with methyl tert-butyl ether-ethyl acetate solvent mixture. Chromatographic separation of analytes was performed on Cosmosil C18 (150 mm × 4.6 mm, 5 μm) column under isocratic conditions with acetonitrile-1.0mM ammonium acetate (90:10, v/v) as the mobile phase. Six endogenous plasma phospholipids (496.3/184.0, 524.3/184.0, 758.5/184.0, 786.5/184.0, 806.5/184.0 and 810.5/184.0) were monitored to determine the extraction efficiency under different extraction conditions. The precursor→product ion transition for both the analytes and ISs were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring and positive ionization mode. The method was validated over a concentration range of 0.050-10.0 ng/mL for oxybutynin and 0.500-100 ng/mL for N-desethyl oxybutynin. The mean extraction recovery for analytes (80.4%) and ISs (76.9%) was consistent across five QC levels. Bench top, wet and dry extract, freeze-thaw and long term stability was evaluated for both the analytes. The method was applied to support a bioequivalence study of 5mg tablet formulation in 74 healthy Indian subjects. Assay reproducibility was demonstrated by reanalysis of 344 incurred samples.

  5. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

    Directory of Open Access Journals (Sweden)

    W. B. Mattes

    2013-01-01

    Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

  6. Simultaneous determination of the peptide-mitomycin KW-2149 and its metabolites in plasma by high-performance liquid chromatography.

    Science.gov (United States)

    Zhang, Z D; Guetens, G; De Boeck, G; Van Cauwenberghe, K; Maes, R A; Ardiet, C; van Oosterom, A T; Highley, M; de Bruijn, E A; Tjaden, U R

    2000-03-10

    A gradient high-performance liquid chromatographic (HPLC) method is described for the quantification of KW-2149 and its two major metabolites in plasma. The method involves a sample clean-up by solid-phase extraction on C18 columns, separation of the respective compounds by HPLC on a YMC ODS-AQ column (5-microm particle size, 150x6 mm I.D.), using a methanol-water gradient system as an eluent, and measurement by UV absorbance detection at 375 nm. The limits of quantitation were 10 ng/ml for KW-2149 and M-16, and 15 ng/ml for M-18. Recoveries from plasma were higher than 92% on C18 extraction columns. Intra-day precision, expressed as %C.V., was between 1.4 and 6.5%. Intra-day accuracy ranged from 94 to 107%. Precision and accuracy of variability of inter-assays increased somewhat; however, were still within acceptable ranges. The ability of the method to quantify KW-2149 and two major metabolites simultaneously, with precision, accuracy and sensitivity, make it useful in monitoring the fate of this new mitomycin in cancer patients.

  7. [LC-LTQ-Orbitrap analysis on chemical constituents in Scrophulariae Radix extract and their metabolites in rat plasma].

    Science.gov (United States)

    Xu, Duo-Duo; Pang, Huan-Huan; Jiang, Mei-Fang; Jian, Wei-Jie; Wang, Qin-Hui; Sun, Lu; Dong, Zi-Yi; Huang, Jian-Mei

    2016-02-01

    Chemical constituents in extract of Scrophulariae Radix and their metabolites in rat plasma after oral administration were identified by HPLC-LTQ-Orbitrap. Samples were separated by a Venusil MP C₁₈ column using a binary gradient elution. The information on the total ion chromatogram, the extraction chromatogram and the mass spectrogram in a negative mode were synthetically analyzed by comparing the retention time, MS and MS/MS spectra with literature data and some of reference standards to conduct a qualitative study on constituents of Radix Scrophulariae extract in vivo and in vitro. Totally 37 compounds from Scrophularia ningpoensis extract were detected including 12 iridoid glycosides, 20 phenylpropanoids and 5 unknown compounds. In vivo, harpagide, harpagoside and angoroside C were confirmed to enter into the blood in prototype forms. Besides, another 2 prototype compounds and 2 metabolites were detected in rat plasma after oral administration of S. ningpoensis extract. The results are beneficial for the determination of bioactive substances of S. ningpoensis and significant for further studies on S. ningpoensis. Copyright© by the Chinese Pharmaceutical Association.

  8. Methodological Studies on Plasma Endotoxin Level and Endotoxin Inactivation Capacity

    Institute of Scientific and Technical Information of China (English)

    姚国相; 杨乃发; 薛新波; 赵玉沛; 蒋朱明

    2004-01-01

    To establish stable methods for detecting plasma endotoxin level and endotoxin inactivation capacity in a normal population and general surgical patients and evaluate their perioperative changes, 50 healthy people and 50 patients receiving gastrointestinal operation were enrolled, their plasma endotoxin levels and plasma endotoxin inactivation capacity were assayed. Our results showed that plasma endotoxin levels were 0.044±0.009 EU/ml in the normal population and 0.044±0.023 EU/ml in the preoperative patients. Endotoxin level peaked 3 h after the operation (0.223±0.041 EU/ml), and then decreased rapidly on the first day after the operation (0.134±0.164EU/ml). Endotoxin inactivation capacity also had the same time course as endotoxin level. Systemic inflammatory response syndrome and infection induced another elevation in the time course. It is concluded that establishing the endotoxin standard curve by using pyrogenic free water is better than by using plasma. Plasma endotoxin inactivation capacity can be used as an indirect indicator of postoperative immune depression. Plasma endotoxin level and endotoxin inactivation capacity peaked shortly after operation, indicating surgical stress is closely related with the changes.

  9. [Plasma homocysteine levels in patients with ischemic heart disease].

    Science.gov (United States)

    Márk, L; Erdei, F; Márki-Zay, J; Nagy, E; Kondacs, A; Katona, A

    2001-07-29

    In the latest years it became clear that beside traditional cardiovascular risk factors the high plasma homocysteine level increases the risk of atherosclerotic diseases too. Metaanalysis of 27 papers found that 10% of population's coronary risk is attributable to homocysteine and a 5 mumol/l increase in its plasma level elevates the coronary risk by as much as 0.5 mumol/l cholesterol increase. Recent studies have shown an inverse relation between the levels of plasma homocysteine and that of folic acid, vitamin B6, vitamin B12. The latters are cofactors and substrates of the homocysteine and methionin metabolism. The plasma total cholesterol, HDL-cholesterol, triglyceride, lipoprotein(a), Apo A1, Apo B and homocysteine concentrations were examined in 39 patients suffering from coronary artery disease treated in the Cardiac Rehabilitation Department of our hospital. Twenty of them were treated by folic acid and vitamin B6 for a three week period. The mean (+/- SD) plasma homocysteine concentration was 15.60 +/- 6.14 mumol/l. In the treated subgroup the mean (+/- SD) plasma homocysteine concentration was 17.3 +/- 7.00 mumol/l, the mean (+/- SD) plasma folic acid level was 8.58 +/- 4.6 mumol/l. After the three week treatment period (folic acid and vitamin B6) the plasma homocysteine level decreased by 26.5% (p = 0.012), that of folic acid increased by 68.7% (p = 0.002). From the plasma lipids the level of total- and LDL-cholesterol decreased significantly (6.7% and 10.4%, P gen of the metylenetetrahydrofolate-reductase (MTHFR) enzyme there was a significant correlation with homocysteine level (r = 0.436, p = 0.010), and a negative, but not significant correlation with the folic acid level (r = -0.354).

  10. Feasibility of hair sampling to assess levels of organophosphate metabolites in rural areas of Sri Lanka

    Science.gov (United States)

    Knipe, D.W.; Jayasumana, C.; Siribaddana, S.; Priyadarshana, C.; Pearson, M.; Gunnell, D.; Metcalfe, C.; Tzatzarakis, M.N.; Tsatsakis, A.M.

    2016-01-01

    Measuring chronic pesticide exposure is important in order to investigate the associated health effects. Traditional biological samples (blood/urine) are difficult to collect, store and transport in large epidemiological studies in settings such as rural Asia. We assessed the acceptability of collecting hair samples from a rural Sri Lankan population and found that this method of data collection was feasible. We also assessed the level of non-specific metabolites (DAPS) of organophosphate pesticides in the hair samples. The median concentration (pg/mg) of each DAP was: diethyl phosphate: 83.3 (IQI 56.0, 209.4); diethyl thiophosphate: 34.7 (IQI 13.8, 147.9); diethyl dithiophosphate: 34.5 (IQI 23.4, 55.2); and dimethyl phosphate: 3 (IQI 3, 109.7). Total diethylphosphates were recovered in >80% of samples and were positively correlated with self-reported pesticide exposure. PMID:26894816

  11. Assessment of the levels of DDT and its metabolites in soil and dust samples from Chiapas, Mexico.

    Science.gov (United States)

    Martínez-Salinas, Rebeca I; Díaz-Barriga, Fernando; Batres-Esquivel, Lilia E; Pérez-Maldonado, Iván N

    2011-01-01

    The aim of this study was to assess the levels of DDT and its metabolites in two environmental matrices (soil and dust) in five communities in Chiapas, Mexico. DDT and its metabolites were analyzed by gas chromatography/mass spectrometry. The soil levels of total DDT ranged from non detectable (levels ranged from non detectable (

  12. Challenges and solutions in the bioanalysis of BMS-986094 and its metabolites including a highly polar, active nucleoside triphosphate in plasma and tissues using LC-MS/MS.

    Science.gov (United States)

    Liu, Ang; Lute, John; Gu, Huidong; Wang, Bonnie; Trouba, Kevin J; Arnold, Mark E; Aubry, Anne-Françoise; Wang, Jian

    2015-09-01

    BMS-986094, a nucleotide polymerase inhibitor of the hepatitis C virus, was withdrawn from clinical trials because of a serious safety issue. To investigate a potential association between drug/metabolite exposure and toxicity in evaluations conducted after the termination of the BMS-986094 development program, it was essential to determine the levels of BMS-986094 and its major metabolites INX-08032, INX-08144 and INX-09054 in circulation and the active nucleoside triphosphate INX-09114 in target and non-target tissues. However, there were many challenges in the bioanalysis of these compounds. The chromatography challenge for the extremely polar nucleoside triphosphate was solved by applying mixed-mode chromatography which combined anion exchange and reversed-phase interactions. The LC conditions provided adequate retention and good peak shape of the analyte and showed good robustness. A strategy using simultaneous extraction but separate LC analysis of the prodrug BMS-986094 and its major circulating metabolites was used to overcome a carryover issue of the hydrophobic prodrug while still achieving good chromatography of the polar metabolites. In addition, the nucleotide analytes were not stable in the presence of endogenous enzymes. Low pH and low temperature were required for blood collection and plasma sample processing. However, the use of phosphatase inhibitor and immediate homogenization and extraction were critical for the quantitative analysis of the active triphosphate, INX-09114, in tissue samples. To alleviate the bioanalytical complexity caused by multiple analytes, different matrices, and various species, a fit-for-purpose approach to assay validation was implemented based on the needs of drug safety assessment in non-clinical (GLP or non-GLP) studies. The assay for INX-08032 was fully validated in plasma of toxicology species. The lower limit of quantification was 1.00ng/mL and the linear curve range was 1.00-500.00ng/mL using a weighted (1/x(2

  13. Modulation of plasma metabolite biomarkers of MAPK pathway with the MEK inhibitor RO4987655: pharmacodynamic and predictive potential in metastatic melanoma.

    Science.gov (United States)

    Ang, Joo Ern; Pal, Akos; Asad, Yasmin J; Henley, Alan T; Valenti, Melanie; Box, Gary; de Haven Brandon, Alexis; Revell, Victoria; Skene, Debra J; Venturi, Miro; Rueger, Ruediger; Meresse, Valerie; Eccles, Suzanne A; de Bono, Johann S; Kaye, Stanley B; Workman, Paul; Banerji, Udai; Raynaud, Florence I

    2017-06-21

    MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based metabolomics, we identified in preclinical models 21 plasma metabolites including amino acids, propionylcarnitine, phosphatidylcholines and sphingomyelins that were significantly altered in two B-RAF mutant melanoma xenografts and that were reversed following a single dose of the potent and selective MEK inhibitor RO4987655. Treatment of non-tumour bearing animals and mice bearing the PTEN null U87MG human glioblastoma xenograft elicited plasma changes only in amino acids and propionylcarnitine. In patients with advanced melanoma treated with RO4987655, on-treatment changes of amino acids were observed in patients with disease progression and not in responders. In contrast, changes in phosphatidylcholines and sphingomyelins were observed in responders. Furthermore, pre-treatment levels of 7 lipids identified in the preclinical screen were statistically significantly able to predict objective responses to RO4987655. The RO4987655 treatment-related changes were greater than baseline physiological variability in non-treated individuals. This study provides evidence of a translational exo-metabolomic plasma readout predictive of clinical efficacy together with pharmacodynamic utility following treatment with a signal transduction inhibitor. Copyright ©2017, American Association for Cancer Research.

  14. Effects of chlordiazepoxide, diazepam and oxazepam on the antitumor activity, the lethality and the blood level of active metabolites of cyclophosphamide and cyclophosphamide oxidase activity in mice.

    Science.gov (United States)

    Sasaki, K; Furusawa, S; Takayanagi, G

    1983-10-01

    Effects of chlordiazepoxide, diazepam and oxazepam on the antitumor activity and acute toxicity of cyclophosphamide and the level of its active metabolites in the plasma were investigated in mice. Cyclophosphamide was administered 24 h after the final injection of chlordiazepoxide, diazepam or oxazepam (100 mg/kg/d for 3 d, i.p.). Pretreatment with these drugs increased the acute toxicity of cyclophosphamide (300 or 450 mg/kg, i.p.), whereas drugs had no effect on the antitumor activity of cyclophosphamide (100 mg/kg, i.p.) against Ehrlich solid carcinoma. A high level of active metabolites of cyclophosphamide in the plasma after the administration of cyclophosphamide (300 or 450 mg/kg, i.p.) was observed in chlordiazepoxide-, diazepam- or oxazepam-treated mice. On the other hand, chlordiazepoxide, diazepam or oxazepam enhanced significantly the activity of cyclophosphamide oxidase in hepatic microsomes. It is concluded that potentiation of the acute toxicity at a high dose of cyclophosphamide by chlordiazepoxide, diazepam and oxazepam is due to an induction of microsomal drug-metabolizing enzyme which are responsible for the in vivo activation of cyclophosphamide.

  15. Human plasma DNP level after severe brain injury

    Institute of Scientific and Technical Information of China (English)

    GAO Yi-lu; XIN Hui-ning; FENG Yi; FAN Ji-wei

    2006-01-01

    Objective: To determine the relationship between DNP level after human severe brain injury and hyponatremia as well as isorrhea.Methods: The peripheral venous plasma as control was collected from 8 volunteers. The peripheral venous plasma from 14 severe brain injury patients were collected in the 1, 3, 7 days after injury. Radioimmunoassay was used to detect the DNP concentration. Meanwhile, daily plasma and urine electrolytes, osmotic pressure as well as 24 h liquid intake and output volume were detected.Results: The normal adult human plasma DNP level was 62. 46 pg/ml ± 27. 56 pg/ml. In the experimental group, the plasma DNP levels were higher from day 1 today 3 in 8 of the 14 patients than those in the control group (P1 =0.05, P3 =0.03). Negative fluid balance occurred in 8 patients and hyponatremia in 7 patients. The increase of plasma DNP level was significantly correlated with the development of a negative fluid balance (r=-0.69,P<0.01) and hyponatremia (x2 =4.38, P<0.05).Conclusions: The increase of plasma DNP level is accompanied by the enhancement of natriuretic and diuretic responses in severe brain-injured patients, which is associated with the development of a negative fluid balance and hyponatremia after brain injury.

  16. EFFECT OF ACUPUNCTURE ON PLASMA GLUCOSE LEVEL IN HUMAN VOLUNTEERS

    Institute of Scientific and Technical Information of China (English)

    Amit Kumar Chakraborty; Mrigendranath Gantait; Biswapati Mukherjee

    2006-01-01

    Objective To observe the changes of plasma glucose level (PGL) in human volunteers after acupuncture. Methods Seventy-seven human volunteers were taken up from the acupuncture clinic. All of pletion of acupuncture. All cases were at four hours abstinence from food before doing acupuncture. Results Plasma glucose level varied 5 mg% or more in 62 cases (80.51%) and only those were considered for computation. PGL increased in cases who had generally plasma glucose level below 90 mg% before acupuncture;and PGL decreased in cases who had plasma glucose 90 mg% or above. In 10 control cases there was no variation of the considerable level of 5 mg% in any case. Conclusion Bi-directional variation of PGL after acupuncture indicates that acupuncture can be used to maintain optimum PGL through endogenous mechanism,suggesting that it is applicable in controlling hyperglycemia in diabetes mellitus patients.

  17. Assessing plasma glucose and lipid levels, body weight and acute ...

    African Journals Online (AJOL)

    Assessing plasma glucose and lipid levels, body weight and acute toxicity following oral ... Diabetes was induced in male and female Wistar rats with alloxan ... had good hypoglycemic activity and good effects on cardiovascular risk factors.

  18. Determination of multiple human arsenic metabolites employing high performance liquid chromatography inductively coupled plasma mass spectrometry

    Science.gov (United States)

    Stice, Szabina; Liu, Guangliang; Matulis, Shannon; Boise, Lawrence H.; Cai, Yong

    2016-01-01

    During the metabolism of different arsenic-containing compounds in human, a variety of metabolites are produced with significantly varying toxicities. Currently available analytical methods can only detect a limited number of human metabolites in biological samples during one run due to their diverse characteristics. In addition, co-elution of species is often unnoticeable with most detection techniques leading to inaccurate metabolic profiles and assessment of toxicity. A high performance liquid chromatography inductively coupled mass spectrometry (HPLC-ICP-MS) method was developed that can identify thirteen common arsenic metabolites possibly present in human with special attention dedicated to thiolated or thiol conjugated arsenicals. The thirteen species included in this study are arsenite (AsIII), arsino-glutathione (As(GS)3), arsenate (AsV), monomethylarsonous acid (MMAIII), monomethylarsino-glutathione (MMAIII(GS)2), monomethylarsonic acid (MMAV), dimethylarsinous acid (DMAIII (from DMAIIII)), S-(dimethylarsinic)cysteine (DMAIII(Cys)), dimethylarsino-glutathione (DMAIII(GS)), dimethylarsinic acid (DMAV), dimethylmonothioarsinic acid (DMMTAV), dimethyldithioarsinic acid (DMDTAV), dimethylarsinothioyl glutathione (DMMTAV(GS)). The developed method was applied for the analysis of cancer cells that were incubated with Darinaparsin (DMAIII(GS)), a novel chemotherapeutic agent for refractory malignancies, and the arsenic metabolic profile obtained was compared to results using a previously developed method. This method provides a useful analytical tool which is much needed in unequivocally identifying the arsenicals formed during the metabolism of environmental arsenic exposure or therapeutic arsenic administration. PMID:26708625

  19. Levels of Urinary Metabolites of Organophosphate Flame Retardants, TDCIPP, and TPHP, in Pregnant Women in Shanghai

    Directory of Open Access Journals (Sweden)

    Liping Feng

    2016-01-01

    Full Text Available Flame retardants are widely used in consumer products to reduce their flammability. Previously used flame retardants have been sequentially banned due to their environmental and human toxicity. Currently, tris(1,3-dichloropropyl phosphate (TDCIPP and triphenyl phosphate (TPHP are among the most commonly used flame retardants. TDCIPP and TPHP are reproductive toxins and have carcinogenic, neurotoxic, and endocrine-disrupting properties. Although high levels of TDCIPP and TPHP have been found in drinking water, seawater, and office air in China, data regarding human exposure are lacking. In this study, we assessed the level of urinary TPHP and TDCIPP metabolites (DPHP and BDCIPP, resp. in a cohort of pregnant women (N=23 from Shanghai, China, using liquid chromatography-tandem mass spectrometry. DPHP were detected in 100% urine samples, while only four urine samples had detectable level of BDCIPP in this cohort (17% detected. Geometric means of DPHP and BDCIPP concentrations were 1.1 ng/mL (interquartile range [IQR]: 0.6, 1.5 ng/mL and 1.2 ng/mL (IQR: 0.6, 2.2 ng/mL, respectively. In this small cohort, urinary DPHP and BDCIPP levels were not significantly correlated with miscarriages, neonatal birthweight, gestational diabetes, or maternal age. These data suggest that exposure to TPHP is widespread, and they demonstrate the feasibility of using urinary biomarkers to measure exposures to modern flame-retardant chemicals.

  20. Optimization and validation of bioanalytical SPE – HPLC method for the simultaneous determination of carbamazepine and its main metabolite, carbamazepine-10, 11-epoxide, in plasma

    Directory of Open Access Journals (Sweden)

    Jasmina Tonic – Ribarska

    2012-03-01

    Full Text Available Carbamazepine is widely used as an antiepileptic drug in the treatment of partial and generalized tonic-clonic seizures. Carbamazepine 10,11-epoxide is the most important metabolite of carbamazepine, because it is a pharmacologically active compound with anticonvulsant properties. According to that, the routine analysis of carbamazepine 10,11-epoxide along with carbamazepine may provide optimal therapeutic monitoring of carbamazepine treatment. The aim of this study was to optimize and validate a simple and reliable solid - phase extraction method followed by RP-HPLC for the simultaneous determination of plasma levels of carbamazepine and carbamazepine-10,11-epoxide, in order to assure the implementation of the method for therapeutic monitoring. The extraction of the analytes from the plasma samples was performed by means of a solid-phase extraction procedure. The separation was carried out on a reversed-phase column using isocratic elution with acetonitrile and water (35:65, v/v as a mobile phase. The temperature was 30°C and UV detection was set at 220 nm. The extraction yield values were more than 98% for all analytes, measured at four concentration levels of the linear concentration range. The method displayed excellent selectivity, sensitivity, linearity, precision and accuracy. Stability studies indicate that stock solutions and plasma samples were stabile under different storage conditions at least during the observed period. The method was successfully applied to determine the carbamazepine and carbamazepine-10,11-epoxide in plasma of epileptic patients treated with carbamazepine as monotherapy and in polytherapy. In conclusion, the proposed method is suitable for application in therapeutic drug monitoring of epileptic patients undergoing treatment with carbamazepine.

  1. Drought Responses of Leaf Tissues from Wheat Cultivars of Differing Drought Tolerance at the Metabolite Level

    Institute of Scientific and Technical Information of China (English)

    Jairus B.Bowne; Tim A.Erwin; Juan Juttner; Thorsten Schnurbusch; Peter Langridge; Antony Bacic; Ute Roessner

    2012-01-01

    Drought has serious effects on the physiology of cereal crops.At the cellular and specifically the metabolite level,many individual compounds are increased to provide osmoprotective functions,prevent the dissociation of enzymes,and to decrease the number of reactive oxygen species present in the cell.We have used a targeted GC-MS approach to identify compounds that differ in three different cultivars of bread wheat characterized by different levels of tolerance to drought under drought stress (Kukri,intolerant; Excalibur and RAC875,tolerant).Levels of amino acids,most notably proline,tryptophan,and the branched chain amino acids leucine,isoleucine,and valine were increased under drought stress in all cultivars.In the two tolerant cultivars,a small decrease in a large number of organic acids was also evident.Excalibur,a cultivar genotypically related to Kukri,showed a pattern of response that was more similar to Kukri under well-watered conditions.Under drought stress,Excalibur and RAC875 had a similar response; however,Excalibur did not have the same magnitude of response as RAC875.Here,the results are discussed in the context of previous work in physiological and proteomic analyses of these cultivars under drought stress.

  2. A high performance liquid chromatographic method for the determination of febantel and its major metabolites in lamb plasma.

    Science.gov (United States)

    Landuyt, J; Debackere, M; Delbeke, F; McKellar, Q

    1993-01-01

    A high performance liquid chromatographic (HPLC) method for the determination of the anthelminthic pro-benzimidazole febantel and its major metabolites in lamb plasma has been developed. Samples were extracted after addition of albendazole as internal standard, NH4OH and distilled diethyl ether. The extracted phase was dried under a stream of nitrogen redissolved in methanol and chromatographed by HPLC. Detection was by UV absorbance at 292 nm. Recovery from the plasma was 97.2, 97.1, 54.5 and 88.0% for febantel, fenbendazole, oxfendazole and oxfendazole sulphone respectively, and within-day and between-day coefficients of variation were 4.03, 4.69, 3.57 and 5.06% and 4.25, 3.73, 5.12 and 4.12%, respectively, for febantel, fenbendazole, oxfendazole and oxfendazole sulphone. The specificity and sensitivity of this method (limit of detection in plasma 0.025 micrograms/mL and doses to sheep.

  3. Reduced Levels of Nitric Oxide Metabolites in Cerebrospinal Fluid Are Associated with Equine Protozoal Myeloencephalitis

    Science.gov (United States)

    Njoku, Chinedu J.; Saville, William J. A.; Reed, Stephen M.; Oglesbee, Michael J.; Rajala-Schultz, Päivi J.; Stich, Roger W.

    2002-01-01

    Equine protozoal myeloencephalitis (EPM) is a disease of horses that is primarily associated with infection with the apicomplexan Sarcocystis neurona. Infection with this parasite alone is not sufficient to induce the disease, and the mechanism of neuropathogenesis associated with EPM has not been reported. Nitric oxide (NO) functions as a neurotransmitter, a vasodilator, and an immune effector and is produced in response to several parasitic protozoa. The purpose of this work was to determine if the concentration of NO metabolites (NOx−) in the cerebrospinal fluid (CSF) is correlated with the development of EPM. CSF NOx− levels were measured before and after transport-stressed, acclimated, or dexamethasone-treated horses (n = 3 per group) were experimentally infected with S. neurona sporocysts. CSF NOx− levels were also compared between horses that were diagnosed with EPM after natural infection with S. neurona and horses that did not have clinical signs of disease or that showed no evidence of infection with the parasite (n = 105). Among the experimentally infected animals, the mean CSF NOx− levels of the transport-stressed group, which had the most severe clinical signs, was reduced after infection, while these values were found to increase after infection in the remaining groups that had less severe signs of EPM. Under natural conditions, horses with EPM (n = 65) had a lower mean CSF NOx− concentration than clinically normal horses with antibodies (Abs) against S. neurona (n = 15) in CSF, and horses that developed ataxia (n = 81) had a significantly lower mean CSF NOx− concentration than horses that did not have neurologic signs (n = 24). In conclusion, lower CSF NOx− levels were associated with clinical EPM, suggesting that measurement of CSF NOx− levels could improve the accuracy of diagnostic tests that are based upon detection of S. neurona-specific Abs in CSF alone and that reduced NO levels could be causatively related to the development

  4. Major Metabolite Levels of Preoperative Proton Magnetic Resonance Sectroscopy and Intraoperative Fluorescence Intensity in Glioblastoma.

    Science.gov (United States)

    Tian, Hai-Long; Zu, Yu-Liang; Wang, Chao-Chao; Lin, Tao; Guo, Zhen-Tao; Jiang, Bin; Yin, Xin; Guo, Wen-Qiang; Wang, Zhi-Gang

    2017-08-20

    Objective To compare the intraoperative major metabolite level of preoperative proton magnetic resonance spectroscopy((1)H-MRS)and fluorescence intensity marked with fluorescein sodium(FLs)in glioblastoma(GBM)and thus provide an objective basis for fluorescence surgical treatment of GBM. Methods All newly diagnosed patients by plain and enhanced magnetic resonance imaging from the April 1,2014 to December 31,2015 were enrolled in this study.All of them received (1)H-MRS and marked with FLs.The expression of Ki67 in tumor boundary were confirmed by postoperative pathology and determined by immunostaining assay.The relationship between (1)H-MRS metabolite levels and tumor fluorescence intensity was analyzed. Results Totally 33 patients were included in the study.Preoperative (1)H-MRS revealed high-grade gliomas in 25 cases.The N-acetylaspartate(NAA)decreased significantly and choline(Cho)increased significantly in high-grade gliomas.The ratios of Cho/NAA,NAA/creatine(Cr),and Cho/Cr significantly differed in different tumor regions(P=0.02,P=0.01,and P=0.00,respectively).Surgical results were marked with FLs intraoperatively.Tissue fluorescence were clearly seen.There were 29 patients undergoing total resection and 4 cases undergoing subtotal resection.No acute encephalocele occured after operation,while 2 patients suffered from epilepsy.Postoperative pathology results included:28 cases were diagnosed as GBM(22 cases consistent with (1)H-MRS diagnosis).The results of GBM fluorescence imaging included:the level of fluorescence intensity in tumor parenchyma was significantly higher than that in tumor boundary and peritumoral edema(P=0.01).The result of (1)H-MRS metabolite analysis included:The kurtosis of NAA and of Cho and the ratio of Cho/NAA were significantly different according the fluorescence intensity in tumor parenchyma(P=0.01,P=0.02,and P=0.01).While there was no difference in the kurtosis of NAA,the kurtosis of Cho and the ratio of Cho/NAA were significantly

  5. The relation of cerebrospinal fluid and plasma glycine levels in propionic acidaemia, a 'ketotic hyperglycinaemia'.

    Science.gov (United States)

    Scholl-Bürgi, S; Korman, S H; Applegarth, D A; Karall, D; Lillquist, Y; Heinz-Erian, P; Davidson, A G F; Haberlandt, E; Sass, J O

    2008-06-01

    The characteristic elevation of plasma glycine concentrations observed in propionic acidaemia (PA) and other 'ketotic hyperglycinaemias' has been attributed to secondary inhibition of the hepatic glycine cleavage system (GCS) by accumulating CoA derivatives of branched-chain amino acid metabolites. In nonketotic hyperglycinaemia (NKH), cerebrospinal fluid (CSF) and plasma glycine levels and their ratio are increased due to primary deficiency of central nervous system (CNS) as well as hepatic GCS. Whether the GCS in the CNS is also inhibited in PA is unclear, as there are scant data available on CSF glycine levels in this disorder. We studied the relation of CSF and plasma glycine levels in 6 paired samples from 4 PA patients, including one PA patient with bacterial meningitis who underwent ventriculoperitoneal shunting and multiple CSF analyses (n = 26). In contrast to the CSF glycine levels which were generally elevated in all four PA patients, the CSF/plasma glycine concentration ratios in paired samples were normal (0.016-0.029), with the exception of a single sample (0.132) with extremely high CSF protein concentration (2010 mg/L) during the course of meningitis indicating a disturbed blood-brain barrier. This finding of normal CSF/plasma glycine ratio in PA suggests that the observed elevations of CSF glycine levels are a reflection of the concurrent hyperglycinaemia resulting from secondary inhibition of hepatic GCS, but that brain GCS is not affected, in contrast to the situation in NKH. The neurological sequelae in PA are therefore unlikely to be related to disturbed glycine metabolism.

  6. Concentrations in plasma clozapine levels in schizophrenic and schizoaffective patients.

    Science.gov (United States)

    Iglesias García, Celso; Iglesias Alonso, Ana; Bobes, Julio

    2017-08-22

    There is great variability in plasma levels of clozapine. The objective of this study is to know the characteristics of patients treated with clozapine and the relationship between them and the variability of plasma levels. Descriptive, cross-sectional study of all patients currently treated with clozapine in a Psychiatric Service with a diagnosis of schizophrenic psychosis or schizoaffective disorder. The present study assessed physical situation, psychopathology and functionality of the patients and explored the associations and correlations between clinical variables and plasma levels. We studied 39 patients, predominantly men, with negative and depressive symptoms and cardiovascular risk factors (metabolic syndrome and smoking). Significant variability in dose and even greater in clozapine levels were observed. The levels of clozapine at equal doses/kg of body weight were higher in non-smokers, they had positive correlation with BMI and negative correlation with systolic BP, disruptive behaviors and number of cigarettes consumed. Plasma level monitoring clozapine is an important tool to avoid clozapine plasma levels monitoring and minimize undesirable clinical situations (metabolic syndrome, sedation, negative symptoms and functional impairment). It is also important to control the effects of a smoking habit for optimum drug bioavailability. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Plasma obestatin levels in normal weight, obese and anorectic women.

    Science.gov (United States)

    Zamrazilová, H; Hainer, V; Sedlácková, D; Papezová, H; Kunesová, M; Bellisle, F; Hill, M; Nedvídková, J

    2008-01-01

    Obestatin is a recently discovered peptide produced in the stomach, which was originally described to suppress food intake and decrease body weight in experimental animals. We investigated fasting plasma obestatin levels in normal weight, obese and anorectic women and associations of plasma obestatin levels with anthropometric and hormonal parameters. Hormonal (obestatin, ghrelin, leptin, insulin) and anthropometric parameters and body composition were examined in 15 normal weight, 21 obese and 15 anorectic women. Fasting obestatin levels were significantly lower in obese than in normal weight and anorectic women, whereas ghrelin to obestatin ratio was increased in anorectic women. Compared to leptin, only minor differences in plasma obestatin levels were observed in women who greatly differed in the amount of fat stores. However, a negative correlation of fasting obestatin level with body fat indexes might suggest a certain role of obestatin in the regulation of energy homeostasis. A significant relationship between plasma obestatin and ghrelin levels, independent of anthropometric parameters, supports simultaneous secretion of both hormones from the common precursor. Lower plasma obestatin levels in obese women compared to normal weight and anorectic women as well as increased ghrelin to obestatin ratio in anorectic women might play a role in body weight regulation in these pathologies.

  8. Increased metabolite levels of glycolysis and pentose phosphate pathway in rabbit atherosclerotic arteries and hypoxic macrophage.

    Directory of Open Access Journals (Sweden)

    Atsushi Yamashita

    Full Text Available AIMS: Inflammation and possibly hypoxia largely affect glucose utilization in atherosclerotic arteries, which could alter many metabolic systems. However, metabolic changes in atherosclerotic plaques remain unknown. The present study aims to identify changes in metabolic systems relative to glucose uptake and hypoxia in rabbit atherosclerotic arteries and cultured macrophages. METHODS: Macrophage-rich or smooth muscle cell (SMC-rich neointima was created by balloon injury in the iliac-femoral arteries of rabbits fed with a 0.5% cholesterol diet or a conventional diet. THP-1 macrophages stimulated with lipopolysaccharides (LPS and interferon-γ (INFγ were cultured under normoxic and hypoxic conditions. We evaluated comprehensive arterial and macrophage metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using (18F-fluorodeoxyglucose ((18F-FDG and pimonidazole, a marker of hypoxia. RESULTS: The levels of many metabolites increased in the iliac-femoral arteries with macrophage-rich neointima, compared with those that were not injured and those with SMC-rich neointima (glycolysis, 4 of 9; pentose phosphate pathway, 4 of 6; tricarboxylic acid cycle, 4 of 6; nucleotides, 10 of 20. The uptake of (18F-FDG in arterial walls measured by autoradiography positively correlated with macrophage- and pimonidazole-immunopositive areas (r = 0.76, and r = 0.59 respectively; n = 69 for both; p<0.0001. Pimonidazole immunoreactivity was closely localized with the nuclear translocation of hypoxia inducible factor-1α and hexokinase II expression in macrophage-rich neointima. The levels of glycolytic (8 of 8 and pentose phosphate pathway (4 of 6 metabolites increased in LPS and INFγ stimulated macrophages under hypoxic but not normoxic condition. Plasminogen activator inhibitor-1 protein levels in the supernatant were closely

  9. Benzene metabolite levels in blood and bone marrow of B6C3F{sub 1} mice after low-level exposure

    Energy Technology Data Exchange (ETDEWEB)

    Bechtold, W.E.; Strunk, M.R.; Thornton-Manning, J.R. [and others

    1995-12-01

    Studies at the Inhalation Toxicology Research Institute (ITRI) have explored the species-specific uptake and metabolism of benzene. Results have shown that metabolism is dependent on both dose and route of administration. Of particular interest were shifts in the major metabolic pathways as a function of exposure concentration. In these studies, B6C3F{sub 1} mice were exposed to increasing levels of benzene by either gavage or inhalation. As benzene internal dose increased, the relative amounts of muconic acid and hydroquinone decreased. In contrast, the relative amount of catechol increased with increasing exposure. These results show that the relative levels of toxic metabolites are a function of exposure level. Based on these results and assuming a linear relationship between exposure concentration and levels of bone marrow metabolites, it would be difficult to detect an elevation of any phenolic metabolites above background after occupational exposures to the OSHA Permissible Exposure Limit of 1 ppm benzene.

  10. Simultaneous determination of borneol and its metabolite in rat plasma by GC-MS and its application to pharmacokinetic study

    Institute of Scientific and Technical Information of China (English)

    Xiu-Man Sun; Qiong-Feng Liao; Yu-Ting Zhou; Xue-Jiao Deng; Zhi-Yong Xie

    2014-01-01

    A gas chromatography mass spectrometry (GC-MS) method has been developed and fully validated for the simultaneous determination of natural borneol (NB) and its metabolite, camphor, in rat plasma. Following a single liquid-liquid extraction, the analytes were separated using an HP-5MS capillary column (0.25 mm ? 30 m ? 0.25μm) and analyzed by MS in the selected ion monitoring mode. Selected ion monitor (m/z) of borneol, camphor and internal standard was 95, 95 and 128, respectively. Linearity, accuracy, precision and extraction recovery of the analytes were all satisfactory. The method was successfully applied to pharmacokinetic studies of NB after oral administration to Wistar rats.

  11. Determination of psilocin, bufotenine, LSD and its metabolites in serum, plasma and urine by SPE-LC-MS/MS.

    Science.gov (United States)

    Martin, Rafaela; Schürenkamp, Jennifer; Gasse, Angela; Pfeiffer, Heidi; Köhler, Helga

    2013-05-01

    A validated method for the simultaneous determination of psilocin, bufotenine, lysergic acid diethylamide and its metabolites in serum, plasma and urine using liquid chromatography-electrospray ionization/tandem mass spectrometry was developed. During the solid-phase extraction procedure with polymeric mixed-mode cation exchange columns, the unstable analytes were protected by ascorbic acid, drying with nitrogen and exclusion of light. The limits of detection and quantitation for all analytes were low. Recovery was ≥86 % for all analytes and no significant matrix effects were observed. Interday and intraday imprecisions at different concentrations ranged from 1.1 to 8.2 % relative standard deviation, bias was within ±5.3 %. Processed samples were stable in the autosampler for at least 2 days. Furthermore, freeze/thaw and long-term stability were investigated. The method was successfully applied to authentic serum and urine samples.

  12. Simultaneous determination of borneol and its metabolite in rat plasma by GC–MS and its application to pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Xiu-Man Sun

    2014-10-01

    Full Text Available A gas chromatography mass spectrometry (GC–MS method has been developed and fully validated for the simultaneous determination of natural borneol (NB and its metabolite, camphor, in rat plasma. Following a single liquid–liquid extraction, the analytes were separated using an HP-5MS capillary column (0.25 mm×30 m×0.25 μm and analyzed by MS in the selected ion monitoring mode. Selected ion monitor (m/z of borneol, camphor and internal standard was 95, 95 and 128, respectively. Linearity, accuracy, precision and extraction recovery of the analytes were all satisfactory. The method was successfully applied to pharmacokinetic studies of NB after oral administration to Wistar rats.

  13. Clinical significance of plasma metastin level in pancreatic cancer patients.

    Science.gov (United States)

    Katagiri, Fumihiko; Nagai, Kazuyuki; Kida, Atsushi; Tomita, Kenji; Oishi, Shinya; Takeyama, Masaharu; Doi, Ryuichiro; Fujii, Nobutaka

    2009-03-01

    Metastin, which is a 54-residue peptide coded by KiSS-1 gene, is an endogenous ligand to a G-protein-coupled receptor GPR54. Metastin suppresses a malignant tumor to metastasize and regulates secretion of gonadotropine releasing hormone. Physiological action of metastin has been focused on in oncology. It is reported that less KiSS-1 gene and more hOT7T175 gene which codes GPR54 are expressed in pancreatic cancers than in normal pancreatic tissues; however, there is no study that investigates the relationship between clinicopathological characteristics and plasma metastin concentration in pancreatic cancer patients. The purpose of this study was to investigate the relationship between plasma metastin-like immunoreactive substance (LI) levels and clinical characteristics in pancreatic cancer patients. Thirty-three patients with pathologically confirmed pancreatic cancer before or just after treatments and 24 healthy volunteers were included in the study. Patients were grouped according to the International Union Against Cancer TNM classification. Plasma metastin-LI was measured by enzyme immunoassay. The plasma metastin-LI levels of cancer patients were significantly higher when compared with healthy volunteers. Significant relationship was not found between the plasma metastin-LI levels and the clinicopathological factors such as tumor size, invasion, lymph node metastasis and distant metastasis. The plasma metastin levels may be a significant biomarker to predict the presence of pancreatic cancer and could be used in pancreatic cancer screening.

  14. Association of plasma manganese levels with chronic renal failure.

    Science.gov (United States)

    Sánchez-González, Cristina; López-Chaves, Carlos; Gómez-Aracena, Jorge; Galindo, Pilar; Aranda, Pilar; Llopis, Juan

    2015-01-01

    Manganese (Mn) is an essential trace element involved in the formation of bone and in amino acid, lipid and carbohydrate metabolism. Mn excess may be neurotoxic to humans, affecting specific areas of the central nervous system. However, relatively little is known about its physiological and/or toxicological effects, and very few data are available concerning the role of Mn in chronic renal failure (CRF). This paper describes a 12-month study of the evolution of plasma Mn levels in predialysis patients with CRF and the relationship with energy and macronutrient intake. The participants in this trial were 64 patients with CRF in predialysis and 62 healthy controls. Plasma levels of creatinine, urea, uric acid, total protein and Mn were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients had higher plasma levels of creatinine, urea, uric acid and Mn and a lower GFR than the controls. Plasma Mn was positively correlated with creatinine, plasma urea and plasma uric acid and was negatively correlated with the GFR and the intake of energy and macronutrients. In conclusion, CRF in predialysis patients is associated with increases in circulating levels of Mn.

  15. Optical sensors for measuring dynamic changes of cytosolic metabolite levels in yeast.

    Science.gov (United States)

    Bermejo, Clara; Haerizadeh, Farzad; Takanaga, Hitomi; Chermak, Diane; Frommer, Wolf B

    2011-10-27

    Optical sensors allow dynamic quantification of metabolite levels with subcellular resolution. Here we describe protocols for analyzing cytosolic glucose levels in yeast using genetically encoded Förster resonance energy transfer (FRET) sensors. FRET glucose sensors with different glucose affinities (K(d)) covering the low nano- to mid- millimolar range can be targeted genetically to the cytosol or to subcellular compartments. The sensors detect the glucose-induced conformational change in the bacterial periplasmic glucose/galactose binding protein MglB using FRET between two fluorescent protein variants. Measurements can be performed with a single sensor or multiple sensors in parallel. In one approach, cytosolic glucose accumulation is measured in yeast cultures in a 96-well plate using a fluorimeter. Upon excitation of the cyan fluorescent protein (CFP), emission intensities of CFP and YFP (yellow fluorescent protein) are captured before and after glucose addition. FRET sensors provide temporally resolved quantitative data of glucose for the compartment of interest. In a second approach, reversible changes of cytosolic free glucose are measured in individual yeast cells trapped in a microfluidic platform, allowing perfusion of different solutions while FRET changes are monitored in a microscope setup. By using the microplate fluorimeter protocol, 96 cultures can be measured in less than 1 h; analysis of single cells of a single genotype can be completed in <2 h. FRET-based analysis has been performed with glucose, maltose, ATP and zinc sensors, and it can easily be adapted for high-throughput screening using a wide spectrum of sensors.

  16. Plasma 25-hydroxyvitamin D2 and D3 levels and incidence of postoperative atrial fibrillation.

    Science.gov (United States)

    Skuladottir, G V; Cohen, A; Arnar, D O; Hougaard, D M; Torfason, B; Palsson, R; Indridason, O S

    2016-01-01

    Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study.

  17. Impact of Extracorporeal Detoxification on the Serum Levels of Microbial Aromatic Acid Metabolites in Sepsis

    Directory of Open Access Journals (Sweden)

    S. E. Khoroshilov

    2015-01-01

    Full Text Available A search for low molecular weight biomarkers to objectively evaluate the efficiency of extracorporeal detoxification methods is extremely relevant. For this purpose, the investigation is to verify whether metabolites, the production of which from aromatic amino acids in the human body can be of microbial ori gin, may be used. Objective: to evaluate the efficiency of extracorporeal detoxification methods on the serum level of phenyl carboxylic acids in patients with sepsis associated renal failure. Subjects and methods. Ten patients with acute or chronic (end stage renal failure that had developed in the presence of severe sepsis, infective and toxic shock, long term extracorporeal circulation, postresuscitation disease, etc. were prospectively examined and treated. All the patients underwent extracorporeal detoxification; the choice of its technique was determined from their past medical history and intoxication patterns. The investigators eval uated organ dysfunctions using the Sequential Organ Failure Assessment (SOFA scale, estimated body tempera ture, leukocyte count, and leukocyte index of intoxication, and assessed the results of a procalcitonin test. Hemodiafiltration was done as extrarenally indicated to ameliorate a systemic inflammatory response in septic shock, by applying an EMiC2 superhigh permeability dialyzer. Low flux Diacap LO PS dialyzers were employed for hemodialysis. Blood samples were taken to estimate changes in the serum concentrations of phenylcarboxylic acid, benzoic acid, 3 phenylpropionic acid, phenyllactic acid, para hydroxyphenylacetic acid (p HPAA, and para hydroxyphenyllactic acid (p HPLA directly before and immediately after extracorporeal detoxification. Results. The severity of organ dysfunctions by SOFA score was 10—22 (mean 16 scores; 10 day mortality rates were 40%. In all the patients, the baseline serum levels of some phenylcarboxylic acids were considerably above normal. After hemodiafiltration, the

  18. Simultaneous determination of blonanserin and its metabolite in human plasma and urine by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study.

    Science.gov (United States)

    Wen, Yu-Guan; Ni, Xiao-Jia; Zhang, Ming; Liu, Xia; Shang, De-Wei

    2012-08-15

    Blonanserin is a novel atypical antipsychotic with highly selective receptor antagonist activity to dopamine D₂ and 5-HT(2A). N-desethyl blonanserin (blonanserin C) is its major active metabolite in human plasma. Herein we report a new highly sensitive, selective, and rapid liquid chromatography-tandem mass spectrometry method to determine blonanserin and blonanserin C simultaneously in human plasma and urine, with N-desethyl-chlor-blonanserin (blonanserin D) as internal standard (IS). Blonanserin and blonanserin C were extracted from aliquots of plasma and urine with ethyl acetate and dichloromethane (4:1) as the solvent and chromatographic separation was performed using an Agilent Eclipse Plus C₁₈ column. The mobile phase was composed of: acetonitrile and ammonium formate-formic acid buffer containing 5mM ammonium formate and 0.1% formic acid (87:13, v/v). To quantify blonanserin, blonanserin C, and blonanserin D, respectively, multiple reaction monitoring (MRM) transition of m/z 368.2→297.2, m/z 340.2→297.1, and m/z 356.2→313.3 was performed in positive mode. The analysis time was about 5.5 min. The calibration curve was linear in the concentration range of 0.01-2 ng/ml. The lower limit of quantification reached 0.01 ng/ml. The intra and inter-day precision and relative errors were less than 8.0% and 6.6% for three QC levels in plasma and urine. The current LC-MS/MS method was validated as simple, sensitive, and accurate and has been successfully applied to investigate the pharmacokinetics of blonanserin and blonanserin C in humans. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Plasma Adiponectin Levels in Acute Liver Failure Patients Treated with Plasma Filtration with Dialysis and Plasma Exchange.

    Science.gov (United States)

    Yamamoto, Hiroshi; Nakae, Hajime; Uji, Yoshitaka; Maeda, Kazuhisa; Tani, Tohru; Eguchi, Yutaka

    2015-08-01

    Plasma filtration with dialysis (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside of the hollow fibers. Improvement of hypoadiponectinemia is considered to be a useful therapeutic approach for ameliorating fatal conditions including cardio-metabolic and infectious disease. We investigated the effects of PDF in comparison to PE in terms of plasma adiponectin (APN) changes in patients with acute liver failure. Seventeen patients with liver failure were studied; PDF was performed 55 times and PE 14 times. Plasma APN levels increased significantly after PDF, while decreasing significantly after PE. PDF appears to be among the most useful blood purification therapies in acute liver failure cases in terms of increasing APN levels.

  20. Use of physiologically based kinetic (PBK) modeling to study interindividual human variation and species differences in plasma concentrations of quercetin and its metabolites.

    Science.gov (United States)

    Boonpawa, Rungnapa; Moradi, Nooshin; Spenkelink, Albertus; Rietjens, Ivonne M C M; Punt, Ans

    2015-12-15

    Biological activities of flavonoids in vivo ultimately depend on the systemic bioavailability of the aglycones and their metabolites. We aimed to develop physiologically based kinetic (PBK) models to predict plasma concentrations of the flavonoid quercetin and its metabolites in individual human subjects and to define species differences compared with male rat. The human models were developed based on in vitro metabolic parameters derived from incubations with pooled and 20 individual human tissue fractions and by fitting kinetic parameters to available in vivo data. The outcomes obtained were compared to a previously developed model for quercetin and its metabolites formation in male rat. Quercetin-3'-O-glucuronide was predicted to be the major circulating metabolite in 19 out of 20 individuals, while in male rat di- and tri-conjugates of quercetin containing a glucuronic acid, sulfate and/or methyl moieties are the major metabolites. Significant species differences occur in major circulating metabolites of quercetin suggesting that rat is not an adequate model to study effects of quercetin in man. The defined PBK models can be used to guide the experimental design of in vitro experiments with flavonoids, especially to better take into account the relevance of metabolism and the contribution of metabolites to the biological activity in humans.

  1. Liquid chromatography determination of clobazam and its major metabolite N-desmethylclobazam in human plasma.

    Science.gov (United States)

    Brachet-Liermain, A; Jarry, C; Faure, O; Guyot, M; Loiseau, P

    1982-01-01

    A specific procedure for the analysis of clobazam and N-desmethylclobazam in plasma is described. Reversed-phase liquid chromatography was performed on a Radial-pak cartridge using a mixture of 45% acetonitrile and 55% buffer solution (pH 7); the ultraviolet detector was set at 254 nm. The method used diazepam as internal standard and diethylether as extraction solvent. The calibration curves are linear between 50 and 500 ng/ml for clobazam and between 100 and 1000 ng/ml for N-desmethylclobazam. The day-to-day precision of the procedure at clobazam plasma concentrations of 50, 250, and 500 ng/ml generated coefficients of variation of 2.2, 6.6, and 11.3%, respectively. No interference occurred in plasma from patients treated with various drugs. The method has been used to study the pharmacokinetics of clobazam and N-desmethylclobazam in patients receiving oral clobazam.

  2. In vivo evidence that Agxt2 can regulate plasma levels of dimethylarginines in mice.

    Science.gov (United States)

    Kittel, Anja; Maas, Renke; König, Jörg; Mieth, Maren; Weiss, Norbert; Jarzebska, Natalia; Hohenstein, Bernd; Martens-Lobenhoffer, Jens; Bode-Böger, Stefanie M; Rodionov, Roman N

    2013-01-01

    Elevated plasma concentrations of the asymmetric (ADMA) and symmetric (SDMA) dimethylarginine have repeatedly been linked to adverse cardiovascular clinical outcomes. Both dimethylarginines can be degraded by alanine-glyoxylate aminotransferase 2 (Agxt2), which is also the key enzyme responsible for the degradation of endogenously formed β-aminoisobutyrate (BAIB). In the present study we wanted to investigate the effect of BAIB on Agxt2 expression and Agxt2-mediated metabolism of dimethylarginines. We infused BAIB or saline intraperitoneally for 7days in C57/BL6 mice via minipumps. Expression of Agxt2 was determined in liver and kidney. The concentrations of BAIB, dimethylarginines and the Agxt2-specific ADMA metabolite α-keto-δ-(N(G),N(G)-dimethylguanidino)valeric acid (DMGV) was determined by LC-MS/MS in plasma and urine. As compared to controls systemic administration of BAIB increased plasma and urine BAIB levels by a factor of 26.5 (p<0.001) and 25.8 (p<0.01), respectively. BAIB infusion resulted in an increase of the plasma ADMA and SDMA concentrations of 27% and 31%, respectively, (both p<0.05) and a 24% decrease of plasma DMGV levels (p<0.05), while expression of Agxt2 was not different. Our data demonstrate that BAIB can inhibit Agxt2-mediated metabolism of dimethylarginines and show for the first time that endogenous Agxt2 is involved in the regulation of systemic ADMA, SDMA and DMGV levels. The effect of BAIB excess on endogenous dimethylarginine levels may have direct clinical implications for humans with the relatively common genetic trait of hyper-β-aminoisobutyric aciduria.

  3. Level crossings, excess times and transient plasma-wall interactions in fusion plasmas

    CERN Document Server

    Theodorsen, Audun

    2016-01-01

    Based on a stochastic model for intermittent fluctuations in the boundary region of magnetically confined plasmas, an expression for the level crossing rate is derived from the joint distribution of the process and its derivative. From this the average time spent by the process above a certain threshold level is obtained. This provides novel predictions of plasma-wall interactions due to transient transport events associated with radial motion of blob-like structures in the scrape-off layer.

  4. [Simultaneous determination of erdosteine and its active metabolite in human plasma by liquid chromatography-tandem mass spectrometry with pre-column derivatization].

    Science.gov (United States)

    Jin, Jing; Chen, Xiao-Yan; Zhang, Yi-Fan; Ma, Zhi-Yu; Zhong, Da-Fang

    2013-03-01

    A sensitive, rapid and accurate liquid chromatography-tandem mass spectrometric (LC-MS/MS) method with pre-column derivatization was developed for the simultaneous determination of erdosteine and its thiol-containing active metabolite in human plasma. Paracetamol and captopril were chosen as the internal standard of erdosteine and its active metabolite, respectively. Aliquots of 100 microL plasma sample were derivatized by 2-bromine-3'-methoxy acetophenone, then separated on an Agilent XDB-C18 (50 mm x 4.6 mm ID, 1.8 microm) column using 0.1% formic acid methanol--0.1% formic acid 5 mmol x L(-1) ammonium acetate as mobile phase, in a gradient mode. Detection of erdosteine and its active metabolite were achieved by ESI MS/MS in the positive ion mode. The linear calibration curves for erdosteine and its active metabolite were obtained in the concentration ranges of 5-3 000 ng x mL(-1) and 5-10 000 ng x mL(-1), respectively. The lower limit of quantification of erdosteine and its active metabolite were both 5.00 ng x mL(-1). The pharmacokinetic results of erdosteine and its thiol-containing active metabolite showed that the area under curve (AUC) of the thiol-containing active metabolite was 6.2 times of that of erdosteine after a single oral dose of 600 mg erdosteine tables in 32 healthy volunteers, The mean residence time (MRT) of the thiol-containing active metabolite was (7.51 +/- 0.788) h, which provided a pharmacokinetic basis for the rational dosage regimen.

  5. Ultra high performance liquid chromatography-quadrupole-time of flight analysis for the identification and the determination of resveratrol and its metabolites in mouse plasma

    Energy Technology Data Exchange (ETDEWEB)

    Menet, M.C., E-mail: marie-claude.menet@parisdescartes.fr [Universite Paris Descartes, Sorbonne Paris cite, EA 4463, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); Cottart, C.H. [APHP, Groupe hospitalier Pitie-Salpetriere, Charles Foix, Service de Biochimie, 7 avenue de la Republique, Ivry sur Seine 94205 (France); Universite Paris Descartes, Sorbonne Paris cite, EA 4466, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); Taghi, M. [Universite Paris Descartes, Sorbonne Paris cite, EA 4463, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); Nivet-Antoine, V. [Universite Paris Descartes, Sorbonne Paris cite, EA 4466, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); APHP, Hopital Europeen Georges Pompidou, Service de Biochimie, 20 rue Leblanc, Paris 75015 (France); Dargere, D. [Universite Paris Descartes, Sorbonne Paris cite, EA 4463, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); and others

    2013-01-25

    Graphical abstract: Simultaneous identification and determination of new resveratrol metabolites in mice by UHPLC-Q-TOF in full scan mode. Highlights: Black-Right-Pointing-Pointer Fast method to quantify resveratrol and its main metabolites in the mouse plasma. Black-Right-Pointing-Pointer Isotope-labeled standards to build a linear calibration curve. Black-Right-Pointing-Pointer Linear calibration curve on a wide range of concentrations. Black-Right-Pointing-Pointer Simultaneous identification and quantification of metabolites by using full scan mode. Black-Right-Pointing-Pointer Detection of uncommon metabolites not yet described in mice. - Abstract: Resveratrol is a polyphenol that has numerous interesting biological properties, but, per os, it is quickly metabolized. Some of its metabolites are more concentrated than resveratrol, may have greater biological activities, and may act as a kind of store for resveratrol. Thus, to understand the biological impact of resveratrol on a physiological system, it is crucial to simultaneously analyze resveratrol and its metabolites in plasma. This study presents an analytical method based on UHPLC-Q-TOF mass spectrometry for the quantification of resveratrol and of its most common hydrophilic metabolites. The use of {sup 13}C- and D-labeled standards specific to each molecule led to a linear calibration curve on a larger concentration range than described previously. The use of high resolution mass spectrometry in the full scan mode enabled simultaneous identification and quantification of some hydrophilic metabolites not previously described in mice. In addition, UHPLC separation, allowing run times lower than 10 min, can be used in studies that requiring analysis of many samples.

  6. Enhancing effect of lipids and emulsifiers on the accumulation of quercetin metabolites in blood plasma after the short-term ingestion of onion by rats.

    Science.gov (United States)

    Azuma, Keiko; Ippoushi, Katsunari; Ito, Hidekazu; Horie, Hideki; Terao, Junji

    2003-12-01

    The effects of co-ingested lipids and emulsifiers on the accumulation of quercetin metabolites in blood plasma after the short-term ingestion of onion by rats were investigated. Plasma extracts of rats that had been fed onion-containing diets for one and two weeks were analyzed by HPLC with electrochemical detection after a treatment with sulfatase/beta-glucuronidase. Almost all of the quercetin metabolites in the plasma were sulfate/glucuronide conjugates of quercetin and isorhamnetin. More than 4.6% (w/w) of soybean oil in the diets significantly enhanced the accumulation of quercetin metabolites in the plasma. Fish oil and beef tallow increased this to an extent similar to that with soybean oil, and lecithin was more effective than the other three lipids. Two emulsifiers, sodium caseinate and sucrose fatty acid ester, also showed an enhancing effect on the accumulation of quercetin metabolites. These results indicate that co-ingested lipids and emulsifiers could enhance the bioavailability of quercetin glucosides in onion.

  7. A simple and sensitive fully validated HPLC-UV method for the determination of 5-fluorouracil and its metabolite 5.6-dihydrofluorouracil in plasma

    NARCIS (Netherlands)

    Maring, JG; Greijdanus, B; de Vries, EGE; Uges, DRA

    2005-01-01

    The authors developed a simple and sensitive, fully validated HPLC-UV method for the determination of both 5-FU and its metabolite DHFU in small-volume plasma samples. The analytes were separated on a 4.6 X 250 mm ID Atlantis dC18 5-mum column with isocratic elution at room temperature. Chlorouracil

  8. Peroxisome Proliferator-Activated Receptor Activation is Associated with Altered Plasma One-Carbon Metabolites and B-Vitamin Status in Rats.

    Science.gov (United States)

    Lysne, Vegard; Strand, Elin; Svingen, Gard F T; Bjørndal, Bodil; Pedersen, Eva R; Midttun, Øivind; Olsen, Thomas; Ueland, Per M; Berge, Rolf K; Nygård, Ottar

    2016-01-05

    Plasma concentrations of metabolites along the choline oxidation pathway have been linked to increased risk of major lifestyle diseases, and peroxisome proliferator-activated receptors (PPARs) have been suggested to be involved in the regulation of key enzymes along this pathway. In this study, we investigated the effect of PPAR activation on circulating and urinary one-carbon metabolites as well as markers of B-vitamin status. Male Wistar rats (n = 20) received for 50 weeks either a high-fat control diet or a high-fat diet with tetradecylthioacetic acid (TTA), a modified fatty acid and pan-PPAR agonist with high affinity towards PPARα. Hepatic gene expression of PPARα, PPARβ/δ and the enzymes involved in the choline oxidation pathway were analyzed and concentrations of metabolites were analyzed in plasma and urine. TTA treatment altered most biomarkers, and the largest effect sizes were observed for plasma concentrations of dimethylglycine, nicotinamide, methylnicotinamide, methylmalonic acid and pyridoxal, which were all higher in the TTA group (all p Pparα mRNA was increased after TTA treatment, but genes of the choline oxidation pathway were not affected. Long-term TTA treatment was associated with pronounced alterations on the plasma and urinary concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats.

  9. Acute effect of smoking on plasma Obestatin levels

    Directory of Open Access Journals (Sweden)

    Saroglou Maria

    2010-01-01

    Full Text Available Abstract Background Smoking and smoking cessation are considered to be associated with weight changes. We have recently shown that smoking acutely increases plasma levels of ghrelin, a known orexigenic hormone. Obestatin is a peptide encoded by the ghrelin gene, which opposes ghrelin effects on food intake. We conducted a study in adult volunteers measuring plasma levels of obestatin immediately after initiation of smoking. Methods 31 volunteers (mean age 32.2 ± 9.2 years and mean BMI 25.7 ± 4.1, 17 smokers and 14 non-smokers, were enrolled in our study. The 2 groups were matched in age and BMI. Plasma obestatin concentrations were determined at baseline (T0, 2 (T2, 5 (T5, 15 (T15, and 60 (T60 minutes after the initiation of smoking. Results In all 31 subjects, no significant difference in the mean values of plasma obestatin levels was observed from baseline at T2, T5, T15 and T60 after initiation of smoking (overall p = 0.15. However, a trend for higher obestatin levels was noted in smokers vs non-smokers (overall p = 0.069, which was not related to the pack-years. Conclusion On the contrary with ghrelin's response after smoking initiation, there is no such an acute response of plasma obestatin levels.

  10. Protozoan growth rates on secondary-metabolite-producing Pseudomonas spp. correlate with high-level protozoan taxonomy

    DEFF Research Database (Denmark)

    Pedersen, Annette L.; Winding, Anne; Altenburger, Andreas

    2011-01-01

    Different features can protect bacteria against protozoan grazing, for example large size, rapid movement, and production of secondary metabolites. Most papers dealing with these matters focus on bacteria. Here, we describe protozoan features that affect their ability to grow on secondary...... with membrane-bound metabolites. Interestingly, protozoan response seemed to correlate with high-level protozoan taxonomy, and amoeboid taxa tolerated a broader range of Pseudomonas strains than did the non-amoeboid taxa. This stresses the importance of studying both protozoan and bacterial characteristics...

  11. Plasma and urine catecholamine levels in cosmonauts during long-term stay on Space Station Salyut-7

    Science.gov (United States)

    Kvetn̆anský, R.; Davydova, N. A.; Noskov, V. B.; Vigas̆, M.; Popova, I. A.; Us̆akov, A. C.; Macho, L.; Grigoriev, A. I.

    The activity of the sympathetic adrenal system in cosmonauts exposed to a stay in space lasting for about half a year has so far been studied only by measuring catecholamine levels in plasma and urine samples taken before space flight and after landing. The device "Plasma 01", specially designed for collecting and processing venous blood from subjects during space flight on board the station Salyut-7 rendered it possible for the first time to collect and freeze samples of blood from cosmonauts in the course of a long-term 237-day space flight. A physician-cosmonaut collected samples of blood and urine from two cosmonauts over the period of days 217-219 of their stay in space. The samples were transported to Earth frozen. As indicators of the sympathetic adrenal system activity, plasma and urine concentrations of epinephrine and norepinephrine as well as urine levels of the catecholamine metabolites metanephrine, normetanephrine, and vanillylmandelic acid were determined before, during and after space flight. On days 217-219 of space flight plasma epinephrine and norepinephrine levels were slightly increased, yet not substantially different from normal. During stress situations plasma norepinephrine and epinephrine levels usually exhibit a manifold increase. On days 217-219 of space flight norepinephrine and epinephrine levels in urine were comparable with pre-flight values and the levels of their metabolites were even significantly decreased. All the parameters studied, particularly plasma norepinephrine as well as urine norepinephrine, normetanephrine, and vanillylmandelic acid, reached the highest values 8 days after landing. The results obtained suggest that, in the period of days 217-219 of the cosmonauts' stay in space in the state of weightlessness, the sympathetic adrenal system is either not activated at all or there is but a slight activation induced by specific activities of the cosmonauts, whereas in the process of re-adaptation after space flight on

  12. Ameliorating effects of Mango (Mangifera indica L.) fruit on plasma ethanol level in a mouse model assessed with 1H-NMR based metabolic profiling

    Science.gov (United States)

    Kim, So-Hyun; K. Cho, Somi; Min, Tae-Sun; Kim, Yujin; Yang, Seung-Ok; Kim, Hee-Su; Hyun, Sun-Hee; Kim, Hana; Kim, Young-Suk; Choi, Hyung-Kyoon

    2011-01-01

    The ameliorating effects of Mango (Mangifera indica L.) flesh and peel samples on plasma ethanol level were investigated using a mouse model. Mango fruit samples remarkably decreased mouse plasma ethanol levels and increased the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase. The 1H-NMR-based metabolomic technique was employed to investigate the differences in metabolic profiles of mango fruits, and mouse plasma samples fed with mango fruit samples. The partial least squares-discriminate analysis of 1H-NMR spectral data of mouse plasma demonstrated that there were clear separations among plasma samples from mice fed with buffer, mango flesh and peel. A loading plot demonstrated that metabolites from mango fruit, such as fructose and aspartate, might stimulate alcohol degradation enzymes. This study suggests that mango flesh and peel could be used as resources for functional foods intended to decrease plasma ethanol level after ethanol uptake. PMID:21562641

  13. Ameliorating effects of Mango (Mangifera indica L.) fruit on plasma ethanol level in a mouse model assessed with H-NMR based metabolic profiling.

    Science.gov (United States)

    Kim, So-Hyun; K Cho, Somi; Min, Tae-Sun; Kim, Yujin; Yang, Seung-Ok; Kim, Hee-Su; Hyun, Sun-Hee; Kim, Hana; Kim, Young-Suk; Choi, Hyung-Kyoon

    2011-05-01

    The ameliorating effects of Mango (Mangifera indica L.) flesh and peel samples on plasma ethanol level were investigated using a mouse model. Mango fruit samples remarkably decreased mouse plasma ethanol levels and increased the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase. The (1)H-NMR-based metabolomic technique was employed to investigate the differences in metabolic profiles of mango fruits, and mouse plasma samples fed with mango fruit samples. The partial least squares-discriminate analysis of (1)H-NMR spectral data of mouse plasma demonstrated that there were clear separations among plasma samples from mice fed with buffer, mango flesh and peel. A loading plot demonstrated that metabolites from mango fruit, such as fructose and aspartate, might stimulate alcohol degradation enzymes. This study suggests that mango flesh and peel could be used as resources for functional foods intended to decrease plasma ethanol level after ethanol uptake.

  14. Plasma and ear tissue concentrations of enrofloxacin and its metabolite ciprofloxacin in dogs with chronic end-stage otitis externa after intravenous administration of enrofloxacin.

    Science.gov (United States)

    Cole, Lynette K; Papich, Mark G; Kwochka, Kenneth W; Hillier, Andrew; Smeak, Daniel D; Lehman, Amy M

    2009-02-01

    The purpose of this study was to measure the concentrations of enrofloxacin and its metabolite ciprofloxacin following intravenous administration of enrofloxacin in the plasma and ear tissue of dogs with chronic end-stage otitis undergoing a total ear canal ablation and lateral bulla osteotomy. The goals were to determine the relationship between the dose of enrofloxacin and the concentrations of enrofloxacin and ciprofloxacin, and determine appropriate doses of enrofloxacin for treatment of chronic otitis externa and media. Thirty dogs were randomized to an enrofloxacin-treatment group (5, 10, 15 or 20 mg kg(-1)) or control group (no enrofloxacin). After surgical removal, ear tissue samples (skin, vertical ear canal, horizontal ear canal, middle ear) and a blood sample were collected. Concentrations of enrofloxacin and ciprofloxacin in the plasma and ear tissue were measured by high performance liquid chromatography. Repeated measures models were applied to log-transformed data to assess dosing trends and Pearson correlations were calculated to assess concentration associations. Ear tissue concentrations of enrofloxacin and ciprofloxacin were significantly (P ciprofloxacin concentrations, respectively. For bacteria with an minimal inhibitory concentration of 0.12-0.15 or less, 0.19-0.24, 0.31-0.39 and 0.51-0.64 microg mL(-1), enrofloxacin should be dosed at 5, 10, 15 and 20 mg kg(-1), respectively. Treatment with enrofloxacin would not be recommended for a bacterial organism intermediate or resistant in susceptibility to enrofloxacin since appropriate levels of enrofloxacin would not be attained.

  15. High-throughput LC-MS/MS assay for 6-methoxy-2-naphthylacetic acid, an active metabolite of nabumetone in human plasma and its application to bioequivalence study.

    Science.gov (United States)

    Patel, Bhavin N; Sharma, Naveen; Sanyal, Mallika; Prasad, Arpana; Shrivastav, Pranav S

    2008-11-01

    A simple, precise and accurate assay for the determination of 6-methoxy-2-naphthylacetic acid (6-MNA), an active metabolite of nabumetone in human plasma, was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analyte (6-MNA) and propranolol (internal standard, IS) were extracted from 200 microL aliquot of human plasma via solid-phase extraction employing HLB Oasis cartridges and separated on a Discovery HS C18 (50 x 4.6 mm, 5 microm) column. Detection of analyte and IS was done by tandem mass spectrometry with a turbo ion spray interface operating in positive ion and multiple reaction monitoring acquisition mode. The total chromatographic runtime was 3.0 min with retention time for 6-MNA and IS at 1.97 and 1.26 min, respectively. The method was validated over a dynamic linear range of 0.20-60.00 microg/mL for 6-MNA with mean correlation coefficient r > or = 0.9986. The intra-batch and inter-batch precision (%CV) across five validation runs (lower limit of quantiation, low-, medium- and high-quality controls and upper limit of quantitation) was less than 7.5%. The accuracy determined at these levels was within -5.8 to +0.2% in terms of percentage bias. The method was successfully applied for a bioequivalence study of 750 mg nabumetone tablet formulation in 12 healthy Indian male subjects under fasted condition.

  16. 3,4-Methylenedioxypyrovalerone (MDPV) and metabolites quantification in human and rat plasma by liquid chromatography-high resolution mass spectrometry.

    Science.gov (United States)

    Anizan, Sebastien; Ellefsen, Kayla; Concheiro, Marta; Suzuki, Masaki; Rice, Kenner C; Baumann, Michael H; Huestis, Marilyn A

    2014-05-27

    Synthetic cathinones are recreational drugs that mimic the effects of illicit stimulants like cocaine, amphetamine or Ecstasy. Among the available synthetic cathinones in the United States, 3,4-methylenedioxypyrovalerone (MDPV) is commonly abused and associated with dangerous side effects. MDPV is a dopamine transporter blocker 10-fold more potent than cocaine as a locomotor stimulant in rats. Previous in vitro and in vivo studies examining MDPV metabolism reported 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) as the two primary metabolites. We developed and validated a liquid chromatography-high resolution mass spectrometry method to quantify MDPV and its primary metabolites in 100 μL human and rat plasma. Plasma hydrolysis was followed by protein precipitation before analysis. Limits of detection were 0.1 μg L(-1), with linear ranges from 0.25 to 1000 μg L(-1). Process efficiency, matrix effect, total imprecision (%CV) and accuracy (%target) were 36-93%, from -8 to 12%, 2.1 to 7.3% and 86 to 109%, respectively. MDPV and metabolites were stable at room temperature for 24 h, 4 °C for 72 h and after 3 freeze-thaw cycles with less than 10% variability. Human-rat plasma cross validation demonstrated that rat plasma could be accurately quantified against a human plasma calibration curve. As proof of this method, rat plasma specimens were analyzed after intraperitoneal and subcutaneous dosing with MDPV (0.5 mg kg(-1)). MDPV, 3,4-catechol-PV and 4-OH-3-MeO-PV concentrations ranged from not detected to 107.5 μg L(-1) prior to and up to 8h after dosing. This method provides a simultaneous quantification of MDPV and two metabolites in plasma with good selectivity and sensitivity. Published by Elsevier B.V.

  17. Plasminogen and fibrinogen plasma levels in coronary artery disease

    Science.gov (United States)

    Lima, Luciana Moreira; Carvalho, Maria das Graças; Sousa, Marinez de Oliveira

    2012-01-01

    Objective The formation of thrombi at the site of atherosclerotic lesions plays a central role in atherothrombosis. Impaired fibrinolysis may exacerbate pre-existing coronary artery disease and potentiate its evolution. While the fibrinogen plasma level has been strongly associated with the severity of coronary artery disease, its relevance in the evaluation of plasminogen in coronary artery disease patients remains unclear. This study evaluated fibrinogen and plasminogen levels in subjects with coronary artery disease as diagnosed by angiography. Methods This is a cross-sectional study. Blood samples obtained from 17 subjects with angiographically normal coronary arteries (controls), 12 with mild/moderate atheromatosis and 28 with severe atheromatosis were evaluated. Plasma plasminogen and fibrinogen levels were measured by chromogenic and coagulometric methods, respectively. Results Fibrinogen levels were significantly higher in the severe atheromatosis group compared to the other groups(p-value < 0.0001). A significant positive correlation was observed between the severity of coronary artery diseaseand increasing fibrinogen levels (r = 0.50; p-value < 0.0001) and between fibrinogen and plasminogen levels (r =0.46; p-value < 0.0001). There were no significant differences in the plasminogen levels between groups. Conclusion Plasma fibrinogen, but not plasminogen levels were higher in patients with coronary artery disease compared to angiographically normal subjects. The plasma fibrinogen levels also appear to be associated with the severity of the disease. The results of this study provide no evidence of a significant correlation between plasma plasminogen levels and the progress of coronary stenosis in the study population. PMID:23049444

  18. Simultaneous analysis of diazepam and its metabolites in rat plasma and brain tissue by HPLC-UV and SPE.

    Science.gov (United States)

    Mercolini, Laura; Mandrioli, Roberto; Iannello, Carmelina; Matrisciano, Francesco; Nicoletti, Ferdinando; Raggi, Maria Augusta

    2009-11-15

    Diazepam is frequently used as an adjuvant during antidepressant therapy. Recently, some studies have suggested that the treatment with benzodiazepines could have different efficacy in depressed patients as opposed to non-depressed ones. To clarify the matter, a study is currently underway, regarding the drug metabolism in rats. In order to obtain a more complete and significant set of data, the main diazepam metabolites have also been considered, namely: nordiazepam, temazepam and oxazepam. A feasible and reliable HPLC method has been developed for the simultaneous determination of these compounds in plasma and brain tissue of rats. The method has been applied to "normal" rats and to genetic rat models of depression in order to estimate drug metabolism in different breeds. Analyte separation was achieved on a C8 reversed phase column using an acidic phosphate buffer/acetonitrile mixture as the mobile phase. The detection wavelength was 238 nm. An original sample pre-treatment, based on solid-phase extraction (SPE) was developed in order to eliminate endogenous interference, using only 250 microL of matrix (brain homogenate or plasma) for a complete analysis. The method has been validated with good results in terms of precision, extraction yield, sensitivity, selectivity and accuracy on both matrices and has been successfully applied to samples from some rats subjected to the preliminary study. The obtained data will hopefully contribute to the clarification of possible differences between depressed and non-depressed subjects with respect to benzodiazepine biotransformation.

  19. Simultaneous quantitation of acetylsalicylic acid and clopidogrel along with their metabolites in human plasma using liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Chhonker, Yashpal S; Pandey, Chandra P; Chandasana, Hardik; Laxman, Tulsankar Sachin; Prasad, Yarra Durga; Narain, V S; Dikshit, Madhu; Bhatta, Rabi S

    2016-03-01

    The interest in therapeutic drug monitoring has increased over the last few years. Inter- and intra-patient variability in pharmacokinetics, plasma concentration related toxicity and success of therapy have stressed the need of frequent therapeutic drug monitoring of the drugs. A sensitive, selective and rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of acetylsalicylic acid (aspirin), salicylic acid, clopidogrel and carboxylic acid metabolite of clopidogrel in human plasma. The chromatographic separations were achieved on Waters Symmetry Shield(TM) C18 column (150 × 4.6 mm, 5 µm) using 3.5 mm ammonium acetate (pH 3.5)-acetonitrile (10:90, v/v) as mobile phase at a flow rate of 0.75 mL/min. The present method was successfully applied for therapeutic drug monitoring of aspirin and clopidogrel in 67 patients with coronary artery disease.

  20. Plasma BDNF levels following weight recovery in anorexia nervosa.

    Science.gov (United States)

    Phillips, Kathryn E; Jimerson, David C; Pillai, Anilkumar; Wolfe, Barbara E

    2016-10-15

    Preclinical studies have implicated brain-derived neurotrophic factor (BDNF) in the regulation of eating behavior and body weight. As reviewed in this report, prior studies of BDNF levels in anorexia nervosa have yielded variable results, perhaps reflecting effects of malnutrition and psychiatric comorbidity. The goal of the current report was to assess plasma BDNF as a biomarker in weight-recovered individuals with a history of anorexia nervosa (ANWR). Study groups included women meeting criteria for ANWR and healthy female controls. Participants were in a normal weight range, free of current major psychiatric disorder, and free of medication. Self-ratings included eating disorder symptoms, depression and anxiety. Plasma BDNF levels were measured by enzyme linked immunoassay. Plasma BDNF levels were not significantly different for ANWR and control groups. Plasma BDNF levels were inversely correlated with anxiety ratings in controls (p<0.02) but not in the ANWR group. This report provides new evidence that circulating BDNF concentrations do not differ in healthy controls and ANWR free of psychiatric comorbidity. Additionally, the data provide new information on the relationship between plasma BDNF and anxiety in these two study groups. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Simultaneous determination of a novel calcium entry blocker, monatepil maleate, and its metabolites in rat plasma by means of solid-phase extraction and reversed-phase liquid chromatography with electrochemical detection.

    Science.gov (United States)

    Kurono, M; Suzuki, K; Yoshida, K; Naruto, S

    1997-02-21

    A reversed-phase LC method with electrochemical detection is described for the simultaneous determination of monatepil maleate (AJ-2615, AJ), a novel calcium entry blocker, and its three S-oxidized metabolites in plasma. These compounds were extracted from plasma by solid-phase extraction and injected onto an ODS column. The determination limit in plasma (0.5 ml) was 10 ng/ml for AJ and 5 ng/ml for the three metabolites. The method was applied to the determination of AJ and the metabolites in rat plasma samples.

  2. Effect of peripartum nutritional management on plasma profile of steroid hormones, metabolites, and postpartum fertility in buffaloes

    Directory of Open Access Journals (Sweden)

    R. M. Kalasariya

    2017-03-01

    Full Text Available Aim: The aim of this study was to evaluate the influence of peripartum protein and minerals supplementation on plasma profile of steroid hormones, metabolites, and fertility in rural buffaloes. Material and Methods: A total of 85 advanced pregnant (~8 months pluriparous buffaloes selected at farmers’ doorstep in three tribal villages of Middle Gujarat were randomly divided into two groups, viz., control (n=45 and nutrients treatment (40. The buffaloes of treatment group (n=40, in addition to farmers feeding schedule/control, received daily 1.5 kg compound concentrate mixture (22% CP and 50 g of chelated ASMM for 2 months each pre- and post-partum. Further, 15 buffaloes, each of control and treatment group, were injected parentrally (deep i/m with 5 ml of micro-minerals (each ml containing Se, Zn, Cu and Mn at 5, 40, 15 and 10 mg, respectively, twice 2 months before and on the day of calving, keeping rest of the animals (control, n=30 and treatment, n=25 as controls. Blood sampling was done on days −60, −30, −15, 0, 15, 30, 45, and 60 peripartum for estimation of plasma progesterone and estradiol by standard RIA techniques and other metabolites using assay kits on biochemistry analyzer. The puerperal events and postpartum fertility were monitored through history and by fortnightly palpation per rectum till day 45 and then again at 120 days postpartum for both the groups and subgroups. Results: The mean plasma progesterone concentrations in all groups declined significantly (p0.05. The micro-minerals injection appreciably reduced the incidence of RFMs and significantly (p<0.05 reduced the placental expulsion time over non-injected controls. In treatment group, the period for involution of uterus was significantly shorter (29.39±0.50 vs. 32.12±0.82 days, p<0.05, with early onset of first postpartum estrus (67.65±1.67 vs. 79.43±3.06 days, p<0.01, shorter service period (90.89±4.41 vs. 105.09±4.76 days, p<0.05 and higher conception rate

  3. Cerebrospinal fluid levels of catecholamine metabolites in Parkinson’s disease and L-DOPA-induced dyskinesia

    DEFF Research Database (Denmark)

    Dammann Andersen, Andreas; Binzer, Michael; Stenager, Egon;

    Levodopa (L-DOPA) is effective in the symptomatic treatment of Parkinson’s disease (PD), but chronic use is associated with L-DOPA-induced dyskinesia (LID). In the 6-hydroxydopamine rat model of PD, L-DOPA treatment increases dopamine, its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC...... fasting and 1 hour after intake of medication. Results and conclusion: PD patients receiving levodopa had 10-20 fold higher L-DOPA levels and about 100 fold higher levels of 3-OMD than age-matched controls or PD not receiving L-DOPA. DOPAC levels were not different among controls and subgroups of PD. HVA...... levels were significantly lower in non-DOPA-treated PD. Ratios of DOPAC/DOPA or HVA/DOPA were much lower in levodopa-treated patients, not distinguishing dyskinetic (N=6) from non-dyskinetic PD patients (N=5). More patients need to be included. Tryptophan/kynurenine metabolites will be analysed using LC...

  4. Near-infrared spectroscopy and plasma homovanillic acid levels in bipolar disorder: a case report

    Directory of Open Access Journals (Sweden)

    Miura I

    2014-03-01

    Full Text Available Itaru Miura,1,2 Soichi Kono,1 Sachie Oshima,1 Keiko Kanno-Nozaki,1 Hirobumi Mashiko,1 Shin-Ichi Niwa,1 Hirooki Yabe11Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, Japan; 2Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USAAbstract: Misdiagnosis of bipolar disorder is a serious, but not unusual problem for patients. Nevertheless, there are few biomarkers for distinguishing unipolar and bipolar disorder. Near-infrared spectroscopy (NIRS is a noninvasive and useful method for the measurement of hemoglobin concentration changes in the cortical surface area, which enables the assessment of brain function. We measured NIRS and plasma monoamine metabolite levels in a patient with bipolar disorder. A 22-year-old man was admitted due to major depression. At admission, NIRS findings showed oxygenated hemoglobin reincrease in the posttask period, which is characteristic of schizophrenia. After treatment with paroxetine, he became manic with psychotic symptoms. His plasma level of homovanillic acid just before the manic switch was ten times higher than that just after paroxetine initiation. Treatment with lithium and antipsychotics was successful, and plasma homovanillic acid decreased after treatment. In this case, the NIRS findings may predict a possible risk of a manic switch, which is likely induced by paroxetine. NIRS may be able to help distinguish unipolar and bipolar disorder in clinical settings.Keywords: near-infrared spectroscopy, bipolar disorder, homovanillic acid, diagnosis, biomarker

  5. Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours.

    Science.gov (United States)

    Seeram, Navindra P; Henning, Susanne M; Zhang, Yanjun; Suchard, Marc; Li, Zhaoping; Heber, David

    2006-10-01

    Ellagitannins (ETs) from pomegranate juice (PJ) are reported to have numerous biological properties, but their absorption and metabolism in humans are poorly understood. To investigate the pharmacokinetics of pomegranate ETs, 18 healthy volunteers were given 180 mL of PJ concentrate, and blood samples were obtained for 6 h afterwards. Twenty-four-hour urine collections were obtained on the day before (-1), the day of (0), and the day after (+1) the study. Ellagic acid (EA) was detected in plasma of all subjects with a maximum concentration of 0.06 +/- 0.01 micromol/L, area under concentration time curve of 0.17 +/- 0.02 (micromol x h) x L(-1), time of maximum concentration of 0.98 +/- 0.06 h, and elimination half-life of 0.71 +/- 0.08 h. EA metabolites, including dimethylellagic acid glucuronide (DMEAG) and hydroxy-6H-benzopyran-6-one derivatives (urolithins), were also detected in plasma and urine in conjugated and free forms. DMEAG was found in the urine obtained from 15 of 18 subjects on d 0, but was not detected on d -1 or +1, demonstrating its potential as a biomarker of intake. Urolithin A-glucuronide was found in urine samples from 11 subjects on d 0 and in the urine from 16 subjects on d +1. Urolithin B-glucuronide was found in the urine of 3 subjects on d 0 and in the urine of 5 subjects on d +1. Urolithins, formed by intestinal bacteria, may contribute to the biological effects of PJ as they may persist in plasma and tissues and account for some of the health benefits noted after chronic PJ consumption. Whether genetic polymorphisms in EA-metabolizing enzymes (e.g., catechol-O-methyl transferase and glucuronosyl transferase) are related to variations in response to PJ remains to be established.

  6. Plasma Actin, Gelsolin and Orosomucoid Levels after Eccentric Exercise.

    Science.gov (United States)

    Tékus, Éva; Váczi, Márk; Horváth-Szalai, Zoltán; Ludány, Andrea; Kőszegi, Tamás; Wilhelm, Márta

    2017-02-01

    The present study investigated the acute effect of eccentric exercise on blood plasma actin, gelsolin (GSN) and orosomucoid (AGP) levels in untrained and moderately trained individuals, and their correlation with exercise induced muscle damage (EIMD) markers (CK, intensity of muscle soreness and maximal voluntary contraction torque deficit). Healthy physical education students (6 untrained, 12 moderately trained) participated in this research. Actin, GSN, AGP and CK levels were measured in blood plasma at baseline, immediately, 1 h, 6 h and 24 h post-exercise comprising 90 eccentric quadriceps contractions performed on a dynamometer. There was significant time main effect for GSN, AGP, CK and significant difference was found between baseline and the lowest value of post-exercise GSN (p exercise AGP (p exercise and CK activity at 6 h, p exercise, p eccentric exercise do not seem sensitive to training status. The plasma actin level is used as an indicator of injury, however, our results suggest that it is not an accurate marker of EIMD, while plasma GSN concentrations show a better relationship with EIMD and the post-exercise inflammatory process. The elevated plasma AGP and the correlation between GSN and AGP seem to be promising for assessment of exercise-induced muscle injury.

  7. Use of a column-switching high-performance liquid chromatography method to assess the presence of specific binding of (R)- and (S)-[{sup 11}C]rolipram and their labeled metabolites to the phosphodiesterase-4 enzyme in rat plasma and tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kenk, Miran; Greene, Michael [Cardiovascular PET Molecular Imaging Program, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); Lortie, Mireille; Kemp, Robert A. de [Cardiovascular PET Molecular Imaging Program, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Beanlands, Rob S. [Cardiovascular PET Molecular Imaging Program, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); DaSilva, Jean N. [Cardiovascular PET Molecular Imaging Program, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada)], E-mail: jdasilva@ottawaheart.ca

    2008-05-15

    Introduction: To complement recent studies using the high-affinity {sup 11}C-labeled phosphodiesterase-4 (PDE4) inhibitor (R)-rolipram and the less active enantiomer (S)-[{sup 11}C]rolipram for in vivo quantification of PDE4 levels, we evaluated the presence of radiolabeled metabolites and their potential binding to PDE4 in the rat plasma, brain, heart, pancreas, skeletal muscle and brown adipose tissue. Methods: A reverse-phase capture and analytical HPLC column-switch method was used to detect (R)-[{sup 11}C]rolipram, (S)-[{sup 11}C]rolipram and their radiolabeled metabolites in rat plasma and tissue extracts. The relative proportion of PDE4-specific binding of the radiotracers and their labeled metabolites was analyzed following co-injections with a saturating dose of unlabeled (R)-rolipram at 45 min post-tracer injection in tissue extracts. Results: Radiolabeled metabolites were found in the plasma (72-75% of total radioactive signal), and in the heart, skeletal muscle, pancreas and brown adipose tissue (44-52%), but not in the brain. In comparison to polar labeled metabolites, the proportion of unchanged (R)-[{sup 11}C]rolipram was reduced in PDE4-rich organs by co-injection of unlabeled (R)-rolipram. Conversely, no changes were obtained in brown adipose tissue, or with (S)-[{sup 11}C]rolipram, suggesting that radiolabeled metabolites of (R)-[{sup 11}C]rolipram display no specific binding to PDE4. Conclusions: Radiolabeled hydrophilic metabolites are unlikely to compete with (R)-[{sup 11}C]rolipram for PDE4-specific retention. However, due to the high proportion of the radioactive metabolites in the total radioactive signal, any kinetic modeling calculations in the peripheral tissues will need to take into account the presence of labeled metabolites.

  8. Identification and comparison of marbofloxacin metabolites from the plasma of ball pythons (Python regius) and blue and gold macaws (Ara ararauna).

    Science.gov (United States)

    Hunter, R P; Koch, D E; Coke, R L; Carpenter, J W; Isaza, R

    2007-06-01

    Marbofloxacin is a veterinary only, synthetic, broad spectrum fluoroquinolone antimicrobial agent. In mammals, approximately 40% of the oral dose of marbofloxacin is excreted unchanged in the urine; the remaining is excreted via the bile as unchanged drug in the feces. The Vd ranges from 1.1 (cattle) to 1.3 (dog, goat, swine) L/kg. Because of extra-label use of marbofloxacin in birds and reptiles, this study was designed to determine the profile of metabolites in plasma and compare the circulating metabolite profile between a reptile and an avian species. Six adult ball pythons (Python regius) and 10 blue and gold macaws (Ara ararauna) were used in this study. The macaws were dosed both i.v. and p.o. with a single 2.5 mg/kg administration where as the pythons received a single 10 mg/kg dose both i.v. and p.o. The metabolite profiles of marbofloxacin in the plasma of these species were determined using a high performance liquid chromatography system with a mass spectrometer for detection (LC/MS/MS). Mass spectra data generated from the snake and bird plasma samples were compared with previously reported LC/MS/MS mass spectral data. Evidence does not suggest differences due to route of administration (i.v. vs. p.o.) in either species. Four chromatographic peaks with resulting daughter spectrum were identified and represent 12 possible metabolite structures. All of the proposed metabolites, except for the N-oxide, appear to be unique to macaws. The potential metabolites identified in macaws appear to be very different than those reported for chickens.

  9. Associations of plasma uric acid and purine metabolites with blood pressure in children: the KOALA Birth Cohort Study.

    Science.gov (United States)

    Scheepers, Lieke E J M; Boonen, Annelies; Pijnenburg, Wieke; Bierau, Jörgen; Staessen, Jan A; Stehouwer, Coen D A; Thijs, Carel; Arts, Ilja C W

    2017-05-01

    Elevated serum uric acid concentration has been associated with high blood pressure (BP) and hypertension. A putative underlying mechanism is the accumulation of reactive oxygen species when uric acid is generated by an increased enzyme activity of xanthine oxidase (XO). The aims of the present study were to investigate the associations between plasma uric acid concentration, purine metabolite ratios, as proxies for increased XO activity, and SBP and DBP in school-age children. Cross-sectional analyses were performed in 246 children (46% boys; mean age 7.1 years) from the Dutch KOALA Birth Cohort Study. Purine metabolites were determined with ultra-performance liquid chromatography-tandem mass spectrometry. During a home visit, a nurse collected a blood sample and measured BP three times; in addition, parents measured their child's BP on three consecutive days, in the morning and evening. Generalized estimating equations were used for analyses while controlling for variables such as sex, age, BMI, physical activity, and dietary intake. In multivariable analysis, uric acid (per SD of 38 μmol/l) was associated with DBP z-scores [sβ 0.07; confidence interval (CI), 0.01-1.14], but not with SBP z-scores. Higher ratios of uric acid/xanthine (per SD of 138) (sβ 0.09; CI, 0.01-0.17) and xanthine/hypoxanthine (per SD of 321) (sβ 0.08; CI, 0.02-0.17) were associated with higher DBP z-scores, but not with SBP z-scores. In school-age children, uric acid and the ratios of uric acid/xanthine and xanthine/hypoxanthine were significantly associated with DBP z-scores. Suggesting that, both uric acid concentration and increased XO activity are associated with BP.

  10. Quantification of phenolic acids and their methylates, glucuronides, sulfates and lactones metabolites in human plasma by LC-MS/MS after oral ingestion of soluble coffee.

    Science.gov (United States)

    Marmet, Cynthia; Actis-Goretta, Lucas; Renouf, Mathieu; Giuffrida, Francesca

    2014-01-01

    Chlorogenic acids and derivatives like phenolic acids are potentially bioactive phenolics, which are commonly found in many foods. Once absorbed, chlorogenic and phenolic acids are highly metabolized by the intestine and the liver, producing glucuronidated and/or sulphated compounds. These metabolites were analyzed in human plasma using a validated liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method. After protein precipitation, phenolic acids and their metabolites were extracted by using ethanol and chromatographic separation was achieved by reversed-phase using an Acquity UPLC BEH C18 column combined with a gradient elution system using 1% acetic acid aqueous solution and 1% acetic acid with 100% acetonitrile. The method was able to quantify 56 different compounds including 24 phenolic acids, 4 lactones, 15 sulfates and 13 glucuronides metabolites between 5 and 1000nM in plasma for most of them, except for m-dihydrocoumaric acid, 5-ferulloylquinic-glucuronide, 4-methoxycinnamic acid, 3-phenylpropionic acid, 3-(4-methoxyphenyl)propionic acid (25 to 1000nM) and p-dihydrocoumaric acid (50-1000nM). Values of repeatability and intermediate reproducibility were below 15% of deviation in general, and maximum 20% for the lowest concentrations. The validated method was successfully applied to quantify phenolic acids and their metabolites in plasma obtained after oral ingestion of soluble coffee. In conclusion, the developed and validated method is proved to be very sensitive, accurate and precise for the quantification of these possible dietary phenols.

  11. Plasma protein carbonyl levels and breast cancer risk.

    Science.gov (United States)

    Rossner, Pavel; Terry, Mary Beth; Gammon, Marilie D; Agrawal, Meenakshi; Zhang, Fang Fang; Ferris, Jennifer S; Teitelbaum, Susan L; Eng, Sybil M; Gaudet, Mia M; Neugut, Alfred I; Santella, Regina M

    2007-01-01

    To study the role of oxidative stress in breast cancer risk, we analysed plasma levels of protein carbonyls in 1050 cases and 1107 controls. We found a statistically significant trend in breast cancer risk in relation to increasing quartiles of plasma protein carbonyl levels (OR = 1.2, 95% CI = 0.9-1.5; OR = 1.5, 95% CI = 1.2-2.0; OR = 1.6, 95% CI = 1.2-2.1, for the 2(nd), 3(rd) and 4(th) quartile relative to the lowest quartile, respectively, P for trend = 0.0001). The increase in risk was similar for younger ( or = 15 grams/day for 4(th) quartile versus lowest quartile OR = 2.3, 95% CI = 1.1-4.7), and hormone replacement therapy use (HRT, OR = 2.6, 95% CI = 1.6-4.4 for 4(th) quartile versus lowest quartile). The multiplicative interaction terms were statistically significant only for physical activity and HRT. The positive association between plasma protein carbonyl levels and breast cancer risk was also observed when the analysis was restricted to women who had not received chemotherapy or radiation therapy prior to blood collection. Among controls, oxidized protein levels significantly increased with cigarette smoking and higher fruit and vegetable consumption, and decreased with alcohol consumption >30 grams per day. Women with higher levels of plasma protein carbonyl and urinary 15F(2t)-isoprostane had an 80% increase in breast cancer risk (OR = 1.8, 95% CI = 1.2-2.6) compared to women with levels below the median for both markers of oxidative stress. In summary, our results suggest that increased plasma protein carbonyl levels may be associated with breast cancer risk.

  12. Plasma separation: physical separation at the molecular level

    Science.gov (United States)

    Gueroult, Renaud; Rax, Jean-Marcel; Fisch, Nathaniel J.

    2016-09-01

    Separation techniques are usually divided in two categories depending on the nature of the discriminating property: chemical or physical. Further to this difference, physical and chemical techniques differ in that chemical separation typically occurs at the molecular level, while physical separation techniques commonly operate at the macroscopic scale. Separation based on physical properties can in principle be realized at the molecular or even atomic scale by ionizing the mixture. This is in essence plasma based separation. Due to this fundamental difference, plasma based separation stands out from other separation techniques, and features unique properties. In particular, plasma separation allows separating different elements or chemical compounds based on physical properties. This could prove extremely valuable to separate macroscopically homogeneous mixtures made of substances of similar chemical formulation. Yet, the realization of plasma separation techniques' full potential requires identifying and controlling basic mechanisms in complex plasmas which exhibit suitable separation properties. In this paper, we uncover the potential of plasma separation for various applications, and identify the key physics mechanisms upon which hinges the development of these techniques.

  13. Plasma transport of ergocalciferol and cholecalciferol and their 25-hydroxylated metabolites in dairy cows

    DEFF Research Database (Denmark)

    Hymøller, Lone; Jensen, Søren Krogh

    2017-01-01

    . About 70% to 90% of 25ERG was found in the protein fraction and the remaining 25ERG was found in HLP, whereas ERG was found in both HLP and LLP fractions. In liver tissue, the expression of vitamin D-25-hydroxylase was lower in D2+D3 (P ≤ 0.05) and SUN (P ≤ 0.05) than that in the remaining groups......, and the vitamin D receptor was expressed in the liver to a larger extent in D2+SUN than that in D2+D3 (P ≤ 0.05) and SUN (P ≤ 0.05). In conclusion, different plasma transport mechanisms may explain the lower physiological efficiency of ERG compared to CHO in securing the vitamin D status in plasma but do...... treatments: D2, housed indoor and fed 625-μg/d (25.000 IU) ERG; D3, housed indoor and fed 625-μg/d CHO; D2+D3, housed indoor and fed 625-μg/d ERG and 625-μg/d CHO; SUN, let out for daily pasture to facilitate CHO synthesis from sunlight; and D2+SUN, fed 625-μg/d ERG and let out for daily pasture. Blood...

  14. Supplemental dietary protein for grazing dairy cows: reproduction, condition loss, plasma metabolites, and insulin.

    Science.gov (United States)

    Chapa, A M; McCormick, M E; Fernandez, J M; French, D D; Ward, J D; Beatty, J F

    2001-04-01

    An experiment was conducted over a 2-yr period to investigate the influence of grain crude protein (CP) and rumen undegradable protein (RUP) concentration on reproduction and energy status of dairy cows grazing annual ryegrass (Lolium multiflorum) and oats (Avena sativa). Holstein cows (n = 122) were blocked by calving group [partum (0 d postpartum) vs. postpartum (41 +/- 19 d postpartum at study initiation)] and assigned to grain supplements containing high CP [22.8% of dry matter (DM)], moderate CP (16.6%), or moderate CP (16.2%)] supplemented with RUP from blood meal and corn gluten meal. Postpartum condition loss was greater and first-service pregnancy rate was lower for partum-group cows receiving high CP grain supplements compared with control cows receiving moderate CP supplements. The RUP supplements reduced grain consumption, increased days to first estrus, and reduced first-service pregnancy rate of partum-group cows. The reproduction of postpartum group cows was unaffected by protein supplements. Plasma urea nitrogen was higher for cows fed high CP diets, but plasma ammonia nitrogen, glycated hemoglobin, nonesterified fatty acids, beta-hydoxybutyrate, glucose, and insulin concentrations were similar to cows fed moderate CP. Excess postpartum condition loss, coupled with inconsistent protein supplement effects on days to first service and first-service pregnancy rate, suggest that energy deprivation may have contributed to the low fertility experienced by grazing cows in this study.

  15. Identification of metabolites in plasma and urine of Uruguayan propolis-treated rats.

    Science.gov (United States)

    Kumazawa, Shigenori; Shimoi, Kayoko; Hayashi, Katsumi; Ishii, Takeshi; Hamasaka, Tomoko; Nakayama, Tsutomu

    2004-05-19

    Propolis is a resinous substance collected by honeybees from various plant sources. It is extensively used in food and beverages to improve health and prevent diseases such as heart disease, diabetes, and cancer. To investigate the absorption and metabolism of the components in propolis, in the present study, we administered ethanol extracts of Uruguayan propolis (poplar type propolis) orally to rats and analyzed their plasma and urine by high-performance liquid chromatography with photodiode array and mass spectrometric detection. After deconjugation of the components by beta-glucuronidase/sulfatase treatment of the specimen, pinobanksin 5-methyl ether, pinobanksin, kaempferol, chrysin, pinocembrin, and galangin were detected in plasma of rats orally administered propolis. These compounds were detected also in urine after beta-glucuronidase/sulfatase treatment. Furthermore, pinobanksin 5-methyl ether, pinobanksin, chrysin, pinocembrin, and galangin were present in the urine also in free form. These results suggest that flavonoids in propolis are metabolized and circulate in the body after oral administration of propolis.

  16. Simultaneous Determination of 6-Mercaptopurine and its Oxidative Metabolites in Synthetic Solutions and Human Plasma using Spectrophotometric Multivariate Calibration Methods

    Directory of Open Access Journals (Sweden)

    Mohammad-Reza Rashidi

    2011-06-01

    Full Text Available Introduction: 6-Mercaptopurine (6MP is an important chemotherapeutic drug in the conventional treatment of childhood acute lymphoblastic leukemia (ALL. It is catabolized to 6-thiouric acid (6TUA through 8-hydroxo-6-mercaptopurine (8OH6MP or 6-thioxanthine (6TX intermediates. Methods: High-performance liquid chromatography (HPLC is usually used to determine the contents of therapeutic drugs, metabolites and other important biomedical analytes in biological samples. In the present study, the multivariate calibration methods, partial least squares (PLS-1 and principle component regression (PCR have been developed and validated for the simultaneous determination of 6MP and its oxidative metabolites (6TUA, 8OH6MP and 6TX without analyte separation in spiked human plasma. Mixtures of 6MP, 8-8OH6MP, 6TX and 6TUA have been resolved by PLS-1 and PCR to their UV spectra. Results: Recoveries (% obtained for 6MP, 8-8OH6MP, 6TX and 6TUA were 94.5-97.5, 96.6-103.3, 95.1-96.9 and 93.4-95.8, respectively, using PLS-1 and 96.7-101.3, 96.2-98.8, 95.8-103.3 and 94.3-106.1, respectively, using PCR. The NAS (Net analyte signal concept was used to calculate multivariate analytical figures of merit such as limit of detection (LOD, selectivity and sensitivity. The limit of detections for 6MP, 8-8OH6MP, 6TX and 6TUA were calculated to be 0.734, 0.439, 0.797 and 0.482 µmol L-1, respectively, using PLS and 0.724, 0.418, 0783 and 0.535 µmol L-1, respectively, using PCR. HPLC was also applied as a validation method for simultaneous determination of these thiopurines in the synthetic solutions and human plasma. Conclusion: Combination of spectroscopic techniques and chemometric methods (PLS and PCR has provided a simple but powerful method for simultaneous analysis of multicomponent mixtures.

  17. Fat oxidation, hormonal and plasma metabolite kinetics during a submaximal incremental test in lean and obese adults.

    Science.gov (United States)

    Lanzi, Stefano; Codecasa, Franco; Cornacchia, Mauro; Maestrini, Sabrina; Salvadori, Alberto; Brunani, Amelia; Malatesta, Davide

    2014-01-01

    This study aimed to compare fat oxidation, hormonal and plasma metabolite kinetics during exercise in lean (L) and obese (O) men. Sixteen L and 16 O men [Body Mass Index (BMI): 22.9 ± 0.3 and 39.0 ± 1.4 kg · m(-2)] performed a submaximal incremental test (Incr) on a cycle-ergometer. Fat oxidation rates (FORs) were determined using indirect calorimetry. A sinusoidal model, including 3 independent variables (dilatation, symmetry, translation), was used to describe fat oxidation kinetics and determine the intensity (Fat(max)) eliciting maximal fat oxidation. Blood samples were drawn for the hormonal and plasma metabolite determination at each step of Incr. FORs (mg · FFM(-1) · min(-1)) were significantly higher from 20 to 30% of peak oxygen uptake (VO2peak) in O than in L and from 65 to 85% VO2peak in L than in O (p ≤ 0.05). FORs were similar in O and in L from 35 to 60% VO2peak. Fat max was 17% significantly lower in O than in L (p<0.01). Fat oxidation kinetics were characterized by similar translation, significantly lower dilatation and left-shift symmetry in O compared with L (p<0.05). During whole exercise, a blunted lipolysis was found in O [lower glycerol/fat mass (FM) in O than in L (p ≤ 0.001)], likely associated with higher insulin concentrations in O than in L (p<0.01). Non-esterified fatty acids (NEFA) were significantly higher in O compared with L (p<0.05). Despite the blunted lipolysis, O presented higher NEFA availability, likely due to larger amounts of FM. Therefore, a lower Fat(max), a left-shifted and less dilated curve and a lower reliance on fat oxidation at high exercise intensities suggest that the difference in the fat oxidation kinetics is likely linked to impaired muscular capacity to oxidize NEFA in O. These results may have important implications for the appropriate exercise intensity prescription in training programs designed to optimize fat oxidation in O.

  18. Measurement of concentrations of whole blood levels of choline, betaine, and dimethylglycine and their relations to plasma levels.

    Science.gov (United States)

    Awwad, Hussain Mohamad; Kirsch, Susanne H; Geisel, Juergen; Obeid, Rima

    2014-04-15

    We aimed at developing a method for the measurement of choline and its metabolites in whole blood (WB). After an extraction step, quantification of choline, betaine, and dimethylglycine (DMG) was performed using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Plasma and WB metabolites were evaluated in a group of 61 elderly people. The calibration curves were linear (r(2)>0.997) for all compounds. The inter- and intra-assay coefficients of variation for all analytes were 90% and the relative matrix effect were ≤4.0%. The median concentrations of choline, betaine, and DMG were 11.3, 27.8, and 5.9μmol/L in plasma and 66.6, 165, and 13.7μmol/L in WB, respectively. There were positive correlations between WB and plasma markers; for choline (r=0.42), betaine (r=0.61), and DMG (r=0.56) (all p≤0.001). The concentrations of betaine in WB and plasma were significantly higher in men than in women. The concentrations of WB choline and DMG did not differ significantly according to sex. In conclusion, we have established a reliable method for measuring choline metabolites in WB. The concentrations of WB choline, betaine, and DMG seem to reflect intracellular concentrations of these metabolites.

  19. Plasma brain natriuretic peptide levels in COPD without pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Ahmed G. El Gazzar

    2017-01-01

    Conclusion: Plasma BNP can be used as a useful prognostic biomarker of COPD and a good predictor of exacerbation, As BNP level was significantly higher in COPD patients than in control groups, (p < 0.005 and also significantly higher in grade (IV, III than grade (II and was significantly higher in grade (II than grade (I COPD patients, BNP level significantly higher (p < 0.005 during exacerbation than during remission of COPD patients.

  20. Plasma and platelet serotonin levels in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To analyze the relationship between plasmaand platelet serotonin levels and the degree of liverinsufficiency.METHODS: The prospective study included 30 patients with liver cirrhosis and 30 healthy controls. The degree of liver failure was assessed according to the Child-Pugh classification. Platelet and platelet poor plasma serotonin levels were determined.RESULTS: The mean plasma serotonin level was higher in liver cirrhosis patients than in healthy subjects (215.0± 26.1 vs 63.1 ± 18.1 nmol/L; P < 0.0001). The mean platelet serotonin content was not significantly different in patients with liver cirrhosis compared with healthy individuals (4.8 ± 0.6; 4.2 ± 0.3 nmol/platelet; P > 0.05).Plasma serotonin levels were significantly higher in ChildPugh grade A/B than in grade C patients (246.8 ± 35.0vs132.3 ± 30.7 nmol/L; P < 0.05). However, platelet serotonin content was not significantly different between Child-Pugh grade C and grade A/B (4.6 ± 0.7 vs 5.2 ± 0.8nmol/platelet; P > 0.05).CONCLUSION: Plasma serotonin levels are significantly higher in patients with cirrhosis than in the controls and represent the degree of liver insufficiency. In addition,platelet poor plasma serotonin estimation is a better marker for liver insufficiency than platelet serotonin content.

  1. Effects of lactation upon circulating plasma metabolites in cafeteria-fed rats

    OpenAIRE

    Salvadó, J.; Segués Piqué, Teresa; Alemany, Marià; Arola i Ferrer, Lluís

    1986-01-01

    1. The effects of "cafeteria feeding" on primiparous Wistar rats during lactation have been studied by measuring circulating levels of glucose, amino acids, lactate, urea and ammonia as well as glycogen levels in liver and muscle. 2. No significant changes in glucose levels were observed despite alterations in blood glucose compartmentation. 3. Compared with controls, the dams given the cafeteria diet had higher liver glycogen stores which were more easily mobilized at the peak of lactation. ...

  2. Investigation of the selective androgen receptor modulators S1, S4 and S22 and their metabolites in equine plasma using high-resolution mass spectrometry.

    Science.gov (United States)

    Hansson, Annelie; Knych, Heather; Stanley, Scott; Thevis, Mario; Bondesson, Ulf; Hedeland, Mikael

    2016-04-15

    Selective androgen receptor modulators (SARMs) are prohibited in sports due to their performance enhancing ability. It is important to investigate the metabolism to determine appropriate targets for doping control. This is the first study where the equine metabolites of SARMs S1, S4 (Andarine) and S22 (Ostarine) have been studied in plasma. Each SARM was administered to three horses as an intravenous bolus dose and plasma samples were collected. The samples were pretreated with protein precipitation using cold acetonitrile before separation by liquid chromatography. The mass spectrometric analysis was performed using negative electrospray, quadrupole time-of-flight mass spectrometry operated in MS(E) mode and triple-quadrupole mass spectrometry operated in selected reaction monitoring mode. For the quantification of SARM S1, a deuterated analogue was used as internal standard. The numbers of observed metabolites were eight, nine and four for the SARMs S1, S4 and S22, respectively. The major metabolite was formed by the same metabolic reactions for all three SARMs, namely amide hydrolysis, hydroxylation and sulfonation. The values of the determined maximum plasma concentrations were in the range of 97-170 ng/mL for SARM S1, 95-115 ng/mL for SARM S4 and 92-147 ng/mL for SARM S22 and the compounds could be detected for 96 h, 12 h and 18 h, respectively. The maximum plasma concentration of SARMs S1, S4 and S22 was measured in the first sample (5 min) after administration and they were eliminated fast from plasma. The proposed targets to be used in equine doping control are the parent compounds for all three SARMs, but with the metabolite yielding the highest response as a complementary target. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. In matrix derivatization of trichloroethylene metabolites in human plasma with methyl chloroformate and their determination by solid-phase microextraction-gas chromatography-electron capture detector.

    Science.gov (United States)

    Mudiam, Mohana Krishna Reddy; Jain, Rajeev; Varshney, Meenu; Ch, Ratnasekhar; Chauhan, Abhishek; Goyal, Sudhir Kumar; Khan, Haider A; Murthy, R C

    2013-04-15

    Trichloroethylene (TCE) is a common industrial chemical that has been widely used as metal degreaser and for many industrial purposes. In humans, TCE is metabolized into dichloroacetic acid (DCA), trichloroacetic acid (TCA) and trichloroethanol (TCOH). A simple and rapid method has been developed for the quantitative determination of TCE metabolites. The procedure involves the in situ derivatization of TCE metabolites with methyl chloroformate (MCF) directly in diluted plasma samples followed by extraction and analysis with solid-phase microextraction (SPME) coupled to gas chromatography-electron capture detector (GC-ECD). Factors which can influence the efficiency of derivatization such as amount of MCF and pyridine (PYR), ratio of water/methanol were optimized. The factors which can affect the extraction efficiencies of SPME were screened using 2(7-4) Placket-Burman Design (PBD). A central composite design (CCD) was then applied to further optimize the most significant factors for optimum SPME extraction. The optimum factors for the SPME extraction were found to be 562.5mg of NaCl, pH at 1 and an extraction time of 22 min. Recoveries and detection limits of all three analytes in plasma were found to be in the range of 92.69-97.55% and 0.036-0.068 μg mL(-1) of plasma, respectively. The correlation coefficients were found to be in the range of 0.990-0.995. The intra- and inter-day precisions for TCE metabolites were found to be in the range of 2.37-4.81% and 5.13-7.61%, respectively. The major advantage of this method is that MCF derivatization allows conversion of TCE metabolites into their methyl esters in very short time (≤30 s) at room temperature directly in the plasma samples, thus makes it a solventless analysis. The method developed was successfully applied to the plasma samples of humans exposed to TCE.

  4. Change of plasma visfatin level in the population with different glucose tolerances

    Institute of Scientific and Technical Information of China (English)

    杨媚

    2006-01-01

    Objective To investigate the change of plasma visfatin level and the relationship of plasma visfatin level to body mass index (BMI) , waist hip ratio (WHR) , blood glucose, plasma insulin levels as well as other factors in the subjects with different glucose tolerances. Methods Fasting and glucose loading 2 h plasma visfatin levels were assayed by ELISA in patients with type 2 diabetes

  5. Levels of compounds and metabolites in wheat ears and grains in organic and conventional agriculture.

    Science.gov (United States)

    Zörb, Christian; Niehaus, Karsten; Barsch, Aiko; Betsche, Thomas; Langenkämper, Georg

    2009-10-28

    In this work, wheat from two farming systems, organic and conventional, was analyzed. Organic agriculture is one of the fastest growing sectors in the food industry of Europe and the United States. It is an open question, whether organic or conventional agricultural management influences variables such as metabolism, nutrient supply, seed loading and metabolite composition of wheat. Our aim was to detect if organic or conventional farming systems would affect concentrations of metabolites and substances in developing ears and in corresponding matured grain. Therefore, broadband metabolite profiles together with lipids, cations, starch and protein concentrations of wheat ears in the last phase of grain development and of matured grain from organic and conventional agriculture of a rigorously controlled field trial with two organic and two conventional systems were examined. It appears that seed metabolism and supply of developing ears differ in organic and conventional agriculture. However, the differences in 62 metabolite concentrations become marginal or disappear in the matured grains, indicating an adjustment of nutrients in the matured grain from organic agriculture. This result suggests a high degree of homeostasis in the final seed set independent of the growing regime.

  6. Changes in plasma taurine levels after different endurance events.

    Science.gov (United States)

    Ward, R J; Francaux, M; Cuisinier, C; Sturbois, X; De Witte, P

    1999-01-01

    The sulphonated amino acid taurine increased significantly in the plasma of trained athletes after three endurance exercises of different duration and intensity, a 90 min run on a treadmill at 75% of an individual's VO2 peak, a Marathon, 42.2 km and a 100 km run, by 19%, 77% and 36%, respectively. Such results indicated that the speed at which the exercise is performed, referred to as the intensity, rather than the duration of the exercise, correlated with the elevated taurine levels possibly indicating its release from muscle fibres. The plasma amino acid pool decreased significantly in relationship with the duration of the exercise, caused by their utilisation for glucogenesis. The possible sources of the increased plasma taurine are discussed.

  7. Phthalate metabolites in obese individuals undergoing weight loss: Urinary levels and estimation of the phthalates daily intake.

    Science.gov (United States)

    Dirtu, Alin C; Geens, Tinne; Dirinck, Eveline; Malarvannan, Govindan; Neels, Hugo; Van Gaal, Luc; Jorens, Philippe G; Covaci, Adrian

    2013-09-01

    Human exposure to chemicals commonly encountered in our environment, like phthalates, is routinely assessed through urinary measurement of their metabolites. A particular attention is given to the specific population groups, such as obese, for which the dietary intake of environmental chemicals is higher. To evaluate the exposure to phthalates, nine phthalate metabolites (PMs) were analyzed in urine collected from obese individuals and a control population. Obese individuals lost weight through either bariatric surgery or a conservative weight loss program with dietary and lifestyle counseling. Urine samples were also collected from the obese individuals after 3, 6 and 12months of weight loss. Individual daily intakes of the corresponding phthalate diesters were estimated based on the urinary PM concentrations. A high variability was recorded for the levels of each PM in both obese and control urine samples showing the exposure to high levels of PMs in specific subgroups. The most important PM metabolite as percentage contribution to the total PM levels was mono-ethyl phthalate followed by the metabolites of di-butyl phthalate and di 2-ethyl-hexyl phthalate (DEHP). No differences in the PM levels and profiles between obese entering the program and controls were observed. Although paralleled by a significant decrease of their weight, an increase in the urinary PM levels after 3 to 6months loss was seen. Constant figures for the estimated phthalates daily intake were observed over the studied period, suggesting that besides food consumption, other human exposure sources to phthalates (e.g. air, dust) might be also important. The weight loss treatment method followed by obese individuals influenced the correlations between PM levels, suggesting a change of the intake sources with time. Except for few gender differences recorded between the urinary DEHP metabolites correlations, no other differences were observed for the urinary PM levels as a function of age, body

  8. A highly sensitive method for the simultaneous UHPLC-MS/MS analysis of clonidine, morphine, midazolam and their metabolites in blood plasma using HFIP as the eluent additive.

    Science.gov (United States)

    Veigure, Rūta; Aro, Rudolf; Metsvaht, Tuuli; Standing, Joseph F; Lutsar, Irja; Herodes, Koit; Kipper, Karin

    2017-05-01

    In intensive care units, the precise administration of sedatives and analgesics is crucial in order to avoid under- or over sedation and for appropriate pain control. Both can be harmful to the patient, causing side effects or pain and suffering. This is especially important in the case of pediatric patients, and dose-response relationships require studies using pharmacokinetic-pharmacodynamic modeling. The aim of this work was to develop and validate a rapid ultra-high performance liquid chromatographic-tandem mass spectrometric method for the analysis of three common sedative and analgesic agents: morphine, clonidine and midazolam, and their metabolites (morphine-3-glucuronide, morphine-6-glucuronide and 1'-hydroxymidazolam) in blood plasma at trace level concentrations. Low concentrations and low sampling volumes may be expected in pediatric patients; we report the lowest limit of quantification for all analytes as 0.05ng/mL using only 100μL of blood plasma. The analytes were separated chromatographically using the C18 column with the weak ion-pairing additive 1,1,1,3,3,3-hexafluoro-2-propanol and methanol. The method was fully validated and a matrix matched calibration range of 0.05-250ng/mL was attained for all analytes In addition, between-day accuracy for all analytes remained within 93-108%, and precision remained within 1.5-9.6% for all analytes at all concentration levels over the calibration range. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  9. Abnormal plasma prothrombin (PIVKA-II) levels in hepatocellular carcinoma.

    Science.gov (United States)

    Kawaguchi, Y

    1989-05-01

    The concentration of abnormal prothrombin, or the protein induced by vitamin K absence or antagonist II (PIVKA-II) in 102 patients with hepatic disorders was measured by an enzyme immunoassay method. The concentration of PIVKA-II in the plasma was elevated in 11 out of 18 patients with hepatocellular carcinoma and also in a patient with hepatoblastoma. There was no correlation between serum alpha-fetoprotein and plasma PIVKA-II levels. The PIVKA-II level was normal in 11 patients who had metastatic carcinoma or cholangiocellular carcinoma. Moreover, benign diseases of the liver did not cause an elevation in PIVKA-II. PIVKA-II might be an useful marker of hepatocellular carcinoma because, like alpha-fetoprotein, its level changes in close relation to the effects of treatment.

  10. Determination of piroxicam and its major metabolite 5-hydroxypiroxicam in human plasma by zero-crossing first-derivative spectrophotometry.

    Science.gov (United States)

    Klopas, A; Panderi, I; Parissi-Poulou, M

    1998-07-01

    A zero-crossing first-derivative spectrophotometric method for the determination of piroxicam and its major metabolite 5-hydroxypiroxicam (5-HP) in human plasma is described. This technique permits the quantification of compounds with closely overlapping spectral bands without any separation step. The method consists of direct extraction of the less-ionised forms of piroxicam and 5-hydroxypiroxicam with pure diethyl ether. First derivative values at 343.5 and 332.5 nm for piroxicam and 5-HP, respectively, were obtained. The absolute recovery of the method was found to be 89.4% for piroxicam and 90.3% for 5-HP. Calibration graphs are linear (r better than 0.9998), with zero-intercept, in the concentration range 0.5-12.0 micrograms ml-1 for both compounds. The limits of quantification attained according to the IUPAC definition were 0.29 and 0.27 micrograms ml-1 for piroxicam and 5-HP, respectively. The results obtained by the proposed method were in good agreement with those found by the high-performance liquid chromatographic method (HPLC).

  11. An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma

    Directory of Open Access Journals (Sweden)

    Snežana Uskoković-Marković

    2013-02-01

    Full Text Available The aim of the present study was to optimize a chromatographic method for the analysis of atorvastatin (acid and lactone forms, ortho- and para-hydroxyatorvastatin by using an experimental design approach. Optimization experiments were conducted through a process of screening and optimization. The purpose of a screening design is to identify the factors that have significant effects on the selected chromatographic responses, and for this purpose a full 23 factorial design was used. The location of the true optimum was established by applying Derringer’s desirability function, which provides simultaneously optimization of all seven responses. The ranges of the independent variables used for the optimization were content of acetonitrile in mobile phase (60–70%, temperature of column (30–40 °C and flow rate (0.8–1.2 mL min−1. The influences of these independent variables were evaluated for the output responses: retention time of first peak (p-hydroxyatorvastatin and of last peak (atorvastatin, lactone form, symmetries of all four peaks and relative retention time of p-hydroxyatorvastatin. The primary goal of this investigation was establishing a new simple and sensitive method that could be used in analysis of biological samples. The method was validated and successfully applied for determination of atorvastatin (acid and lactone forms and its metabolites in plasma.

  12. Simultaneous quantitation of atorvastatin and its two active metabolites in human plasma by liquid chromatography/(-) electrospray tandem mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Pankaj Partani; S. Manaswita Verma; Sanjay Gurule; Arshad Khuroo; Tausif Monif

    2014-01-01

    A sensitive, accurate and selective liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed and validated for the simultaneous quantitation of atorvastatin (AT) and its equipotent hydroxyl metabolites, 2-hydroxy atorvastatin (2-AT) and 4-hydroxy atorvastatin (4-AT), in human plasma. Electrospray ionization (ESI) interface in negative ion mode was selected to improve the selectivity and the sensitivity required for this application. Additionally, a solid phase extraction (SPE) step was performed to reduce any ion-suppression and/or enhancement effects. The separation of all compounds was achieved in less than 6 min using a C18 reverse-phase fused-cores column and a mobile phase, composed of a mixture of 0.005%formic acid in water:acetonitrile:methanol (35:25:40, v/v/v), in isocratic mode at a flow rate of 0.6 mL/min. The method has lower limit of quantitation (LLOQ) of 0.050 ng/mL for all analytes. The method has shown tremendous reproducibility, with intra-and inter-day precision less than 6.6%, and intra- and inter-day accuracy within 74.3% of nominal values, for all analytes, and has proved to be highly reliable for the analysis of clinical samples.

  13. Production performance and plasma metabolites of dairy ewes in early lactation as affected by chitosan

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Rodriguez, A.; Arranz, J.; Mandaluniz, N.; Beltrán-de-Heredia, I.; Ruiz, R.; Goiri, I.

    2015-07-01

    The objective of this study was to evaluate the effects of chitosan (CHI) supplementation on production performance and blood parameters in dairy ewes. Twenty-four multiparous Latxa dairy ewes at d 16 of lactation were divided into two groups of 12 ewes each. Ewes were fed one of two experimental concentrates (0.840 kg dry matter/d), control or supplemented with 1.2% CHI, on a dry matter basis. Ewes also had free access to tall fescue hay, water, and mineral salts. The experimental period lasted for 25 d, of which the first 14 d were for treatment adaptation and the last 11 d for measurements and samplings. Supplementation with CHI decreased total (p=0.043) and fescue (p=0.035) dry matter intake (DMI), but did not affect concentrate DMI. Supplementation with CHI, moreover, increased plasma glucose (p=0.013) and BUN concentrations (p=0.035), but did not affect those of non-esterified fatty acids. Dietary supplementation with CHI, however, did not affect milk yield, 6.5% FCM, milk composition, or BW, but it improved dietary apparent efficiency by increasing the milk yield-to-DMI (p=0.055) and 6.5% FCM-to-DMI (p=0.045) ratios. In conclusion, dietary supplementation of chitosan maintained ewe performance while reducing feed intake and improving dietary apparent efficiency. (Author)

  14. Analysis of clobazam and its active metabolite norclobazam in plasma and serum using HPLC/DAD.

    Science.gov (United States)

    Akerman, K K

    1996-11-01

    This report describes a simple reversed-phase high-performance liquid chromatographic (HPLC) method with automated solid-phase extraction (SPE) for analysing clobazam and norclobazam concentrations in human serum or plasma. For the HPLC analysis the samples and standards are prepared with an ASPEC automatic sample preparer using 100-mg Bond-Elut C-18 solid-phase extraction columns. The HPLC method is an isocratic method with a mobile phase of acetonitrile:methanol:10 mmol l-1 dipotassium hydrogen phosphate, pH 3.7 (30:2:100), at a flow rate of 1.5 ml min-1. The benzodiazepines are detected with a diode array detector (DAD) at 240 nm and the peak purity analyses are performed at 210-365 nm. The recovery is over 97% for both analytes, and it is independent of the drug concentration. The intra-assay CVs vary between 0.7 and 2.2% and inter-assay CVs between 3.8 and 4.6% at therapeutic drug concentrations. The detection limit is 15 nmol l-1. The assay is linear from 30 to 20,000 nmol l-1 (clobazam) and from 170 to 105,000 nmol l-1 (norclobazam). This method leads to a very good separation of norclobazam from carbamazepine and phenytoin. None of the anti-epileptic or antidepressant drugs tested interfere with the assay.

  15. Radioimmunological analysis of plasma cortisole levels and daily plasma cortisole variation following triamcinolone acetonide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, F.; Schuster, E.

    1980-08-01

    Plasma cortisol levels in a four-point daily profile were measured by radioimmunoassay before and during treatment with corticoid-containing ointments (triamcinolone acetonide) in 21 patients with psoriasis, who had no endocrine disorders. In the pretreatment phase there were typical circadian fluctuations of the plasma cortisol concentrations. Already after two days of treatment a significant suppression of adrenal function could be detected. This disfunction increased during continuous treatment. In comparison with a fluorimetric method, the radioimmunoassay allowed a better differentiation. This could be due to a lack of specificity and to susceptibility to erroneous measurement of the fluorimetric method. We could also confirm that the distribution of plasma cortisol levels is not a linear but a logarithmic one. Considering the log-normal distribution different mean values and variances are obtained.

  16. Analysis of amphetamine-type stimulants and their metabolites in plasma, urine and bile by liquid chromatography with a strong cation-exchange column-tandem mass spectrometry.

    Science.gov (United States)

    Kuwayama, Kenji; Inoue, Hiroyuki; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Miyaguchi, Hajime; Iwata, Yuko T; Miyauchi, Seiji; Kamo, Naoki

    2008-05-01

    The aim of this work was to develop and validate a method for analysing amphetamine-type stimulants (ATSs) and their metabolites in plasma, urine and bile by liquid chromatography with a strong cation-exchange column-tandem mass spectrometry, and to apply it to the pharmacokinetic study of ATSs. 3,4-Methylenedioxymethamphetamine, methamphetamine, ketamine and their main metabolites, 4-hydroxy-3-methoxymethamphetamine, 3,4-methylenedioxyamphetamine, p-hydroxymethamphetamine, amphetamine and norketamine, were simultaneously quantified by the new method (50-5000 ng/ml). The coefficients of variation and the percent deviations for the eight compounds were in the range of 0.2 to 5.3% and -9.4 to +12.8%, respectively. The recoveries were over 90% in all biological samples tested. This method was effective for the separation and the identification of ATSs and their main metabolites having amine moieties in plasma, urine and bile, and was applicable to pharmacokinetic analysis of methamphetamine, ketamine and their main metabolites in biological samples. This analytical method should be useful for the pharmacokinetic analysis of ATSs.

  17. Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas;

    2015-01-01

    to prevent toxicities, but myelosuppression can also be prevented by pre-HD-MTX 6MP dose reductions. Accordingly, we monitored pre-HD-MTX erythrocyte levels of methylated 6MP metabolites (Ery-MeMP) and of thioguanine nucleotides (Ery-6TGN) as well as DNA-incorporated thioguanine nucleotides (DNA......, the pre-HD-MTX DNA-TGN levels in neutrophils (P Ery-MeMP (P Ery-6TGN (P = 0.01) levels were significant predictors of post-HD-MTX neutrophil nadirs, whereas Ery-MeMP (P

  18. Plasma carnitine levels in patients receiving home parenteral nutrition.

    Science.gov (United States)

    Bowyer, B A; Fleming, C R; Ilstrup, D; Nelson, J; Reek, S; Burnes, J

    1986-01-01

    Patients on long-term home parenteral nutrition (HPN) are known to frequently develop hepatic steatosis or steatohepatitis. The etiology of this steatosis or steatohepatitis is unknown, but carnitine deficiency has been one of the postulated mechanisms. The importance of L-carnitine in hepatic fatty acid oxidation and the steatosis observed in primary and acquired carnitine deficiencies prompted us to determine plasma carnitine levels in 37 patients receiving long-term HPN. Thirteen patients (35%) had low total and free plasma carnitine levels. Fifteen of the 37 HPN patients were matched for age and sex with 15 patients with Crohn's disease who did not require HPN. Mean total and free plasma carnitine values were significantly lower (p less than 0.001) in these 15 HPN patients (32.2 +/- 11.9 and 28.4 +/- 10.8) when compared to Crohn's patients not requiring HPN (49.1 +/- 10.9 and 46.4 +/- 11.5). Associations were not detected between plasma carnitine and clinical or biochemical parameters that might have explained the low values.

  19. Identification of metabolites of Radix Paeoniae Alba extract in rat bile, plasma and urine by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Zheng-Wei Chen; Ling Tong; Shu-Ming Li; Dong-Xiang Li; Ying Zhang; Shui-Ping Zhou; Yong-Hong Zhu; He Sun

    2014-01-01

    Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract (RPAE). A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC-Q-TOF/MS combined with MetaboLynx™ software and mass defect filtering (MDF) could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.

  20. Plasma Leptin Levels in Children Hospitalized with Cholera in Bangladesh.

    Science.gov (United States)

    Falkard, Brie; Uddin, Taher; Rahman, M Arifur; Franke, Molly F; Aktar, Amena; Uddin, Muhammad Ikhtear; Bhuiyan, Taufiqur Rahman; Leung, Daniel T; Charles, Richelle C; Larocque, Regina C; Harris, Jason B; Calderwood, Stephen B; Qadri, Firdausi; Ryan, Edward T

    2015-08-01

    Vibrio cholerae, the cause of cholera, induces both innate and adaptive immune responses in infected humans. Leptin is a hormone that plays a role in both metabolism and mediating immune responses. We characterized leptin levels in 11 children with cholera in Bangladesh, assessing leptin levels on days 2, 7, 30, and 180 following cholera. We found that patients at the acute stage of cholera had significantly lower plasma leptin levels than matched controls, and compared with levels in late convalescence. We then assessed immune responses to V. cholerae antigens in 74 children with cholera, correlating these responses to plasma leptin levels on day 2 of illness. In multivariate analysis, we found an association between day 2 leptin levels and development of later anti-cholera toxin B subunit (CtxB) responses. This finding appeared to be limited to children with better nutritional status. Interestingly, we found no association between leptin levels and antibody responses to V. cholerae lipopolysaccharide, a T cell-independent antigen. Our results suggest that leptin levels may be associated with cholera, including the development of immune responses to T cell-dependent antigens. © The American Society of Tropical Medicine and Hygiene.

  1. Primary, Secondary Metabolites, H2O2, Malondialdehyde and Photosynthetic Responses of Orthosiphon stimaneus Benth. to Different Irradiance Levels

    Directory of Open Access Journals (Sweden)

    Mohd Hafiz Ibrahim

    2012-01-01

    Full Text Available The resource availability hypothesis predicts an increase in the allocation to secondary metabolites when carbon gain is improved relative to nutrient availability, which normally occurs during periods of low irradiance. The present work was carried out to confirm this hypothesis by investigating the effects of decreasing irradiance on the production of plant secondary metabolites (flavonoids and phenolics in the herbal plant Orthosiphon stamineus, and to characterize this production by carbohydrate, H2O2, and malondialdehyde (MDA levels, net photosynthesis, leaf chlorophyll content and carbon to nitrogen ratio (C/N. Four levels of irradiance (225, 500, 625 and 900 µmol/m2/s were imposed onto two-week old seedlings for 12 weeks in a randomized complete block design experiment. Peak production of total flavonoids, phenolics, soluble sugar, starch and total non-structural carbohydrate ocurred under low irradiance of 225 µmol/m2/s, and decreased with increasing irradiance. The up-regulation of secondary metabolites could be explained by the concomitant increases in H2O2 and MDA activities under low irradiance. This condition also resulted in enhanced C/N ratio signifying a reduction in nitrogen levels, which had established significant negative correlations with net photosynthesis, total biomass and total chlorophyll content, indicating the possible existence of a trade-off between growth and secondary metabolism under low irradiance with reduced nitrogen content. The competition between total chlorophyll and secondary metabolites production, as exhibited by the negative correlation coefficient under low irradiance, also suggests a sign of gradual switch of investment from chlorophyll to polyphenols production.

  2. Rapid and simultaneous quantification of levetiracetam and its carboxylic metabolite in human plasma by liquid chromatography tandem mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Li-Ling Yeap

    Full Text Available A simple liquid chromatography tandem mass spectrometry method was developed and validated according to the guidelines of the US Food and Drug Administration and the European Medicines Agency for a simultaneous quantification of levetiracetam (LEV and its metabolite, UCB L057 in the plasma of patients. A 0.050 mL plasma sample was prepared by a simple and direct protein precipitation with 0.450 mL acetonitrile (ACN containing 1 µg/mL of internal standard (IS, diphenhydramine, then vortex mixed and centrifuged. A 0.100 mL of the clear supernatant was diluted with 0.400 mL water and well mixed. A 0.010 mL of the resultant solution was injected into an Agilent Zorbax SB-C18 (2.1 mm×100 mm, 3.5 µm column with an isocratic elution at 0.5 mL/min using a mixture of 0.1% formic acid in water and ACN (40:60 v/v. Detection was performed using an AB Sciex API 3000 triple quadrupole mass spectrometer, equipped with a Turbo Ion Spray source, operating in a positive mode: LEV at transition 171.1>154.1, UCB L057 at 172.5>126.1, and IS at 256.3>167.3; with an assay run time of 2 minutes. The lower limit of quantification (LLOQ for both LEV and UCB L057 was validated at 0.5 µg/mL, while their lower limit of detection (LOD was 0.25 µg/mL. The calibration curves were linear between 0.5 and 100 µg/mL for both analytes. The inaccuracy and imprecision of both intra-assay and inter-assay were less than 10%. Matrix effects were consistent between sources of plasma and the recoveries of all compounds were between 100% and 110%. Stability was established under various storage and processing conditions. The carryovers from both LEV and UCB L057 were less than 6% of the LLOQ and 0.13% of the IS. This assay method has been successfully applied to a population pharmacokinetic study of LEV in patients with epilepsy.

  3. Rapid and simultaneous quantification of levetiracetam and its carboxylic metabolite in human plasma by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Yeap, Li-Ling; Lo, Yoke-Lin

    2014-01-01

    A simple liquid chromatography tandem mass spectrometry method was developed and validated according to the guidelines of the US Food and Drug Administration and the European Medicines Agency for a simultaneous quantification of levetiracetam (LEV) and its metabolite, UCB L057 in the plasma of patients. A 0.050 mL plasma sample was prepared by a simple and direct protein precipitation with 0.450 mL acetonitrile (ACN) containing 1 µg/mL of internal standard (IS, diphenhydramine), then vortex mixed and centrifuged. A 0.100 mL of the clear supernatant was diluted with 0.400 mL water and well mixed. A 0.010 mL of the resultant solution was injected into an Agilent Zorbax SB-C18 (2.1 mm×100 mm, 3.5 µm) column with an isocratic elution at 0.5 mL/min using a mixture of 0.1% formic acid in water and ACN (40:60 v/v). Detection was performed using an AB Sciex API 3000 triple quadrupole mass spectrometer, equipped with a Turbo Ion Spray source, operating in a positive mode: LEV at transition 171.1>154.1, UCB L057 at 172.5>126.1, and IS at 256.3>167.3; with an assay run time of 2 minutes. The lower limit of quantification (LLOQ) for both LEV and UCB L057 was validated at 0.5 µg/mL, while their lower limit of detection (LOD) was 0.25 µg/mL. The calibration curves were linear between 0.5 and 100 µg/mL for both analytes. The inaccuracy and imprecision of both intra-assay and inter-assay were less than 10%. Matrix effects were consistent between sources of plasma and the recoveries of all compounds were between 100% and 110%. Stability was established under various storage and processing conditions. The carryovers from both LEV and UCB L057 were less than 6% of the LLOQ and 0.13% of the IS. This assay method has been successfully applied to a population pharmacokinetic study of LEV in patients with epilepsy.

  4. Development and validation of an HPLC-MS/MS method to quantify clopidogrel acyl glucuronide, clopidogrel acid metabolite, and clopidogrel in plasma samples avoiding analyte back-conversion.

    Science.gov (United States)

    Silvestro, Luigi; Gheorghe, Mihaela; Iordachescu, Adriana; Ciuca, Valentin; Tudoroniu, Ariana; Rizea Savu, Simona; Tarcomnicu, Isabela

    2011-08-01

    A new sensitive and fast quantitative analytical method for the simultaneous determination of clopidogrel, its main metabolite clopidogrel carboxylic acid, and the newly described acyl glucuronide metabolite, in human plasma samples, is presented. The analytical procedures (plasma storage, handling, and extract storage in the autosampler) were optimized in order to avoid back-conversion; a known drawback in measurements of clopidogrel. Clopidogrel acyl glucuronide was confirmed as a major source of back-conversion to the parent drug in the presence of methanol, and thorough stability experiments were carried out to find the most appropriate conditions for an accurate analysis of clopidogrel and the two metabolites. The method was validated by assessing selectivity, sensitivity, linearity, accuracy, and precision for all three analytes, in accordance to Food and Drug Administration guidelines. Spiked quality controls in plasma as well as incurred samples were used to verify back-conversion in the selected conditions, with results meeting European Medicines Agency acceptance criteria (concentrations within 80-120% of the first reading). The method was then applied to a pharmacokinetic study, and for the first time, a pharmacokinetic curve of clopidogrel acyl glucuronide in human plasma is presented. The concentrations ranged up to 1,048.684 ng/mL, with a mean of 470.268 ng/mL, while clopidogrel had a mean C(max) of 1.348 ng/mL; these orders of magnitude show how much the back-conversion of this metabolite may influence clopidogrel quantification if it is not properly controlled.

  5. Effect of crude glycerin on feed manufacturing, growth performance, plasma metabolites, and nutrient digestibility of growing-finishing pigs.

    Science.gov (United States)

    Madrid, J; Villodre, C; Valera, L; Orengo, J; Martínez, S; López, M J; Megías, M D; Hernández, F

    2013-08-01

    Three experiments were conducted to determine the effects of dietary addition of crude glycerin on pellet production efficiency and to evaluate its effect on growth performance and digestibility in growing-finishing pigs. Three dietary treatments were created by addition of 0, 2.5, or 5% crude glycerin to barley-soybean meal-based diet, and 4 batches of each dietary treatment (2 each for grower and finisher diets) were prepared. In the manufacturing process, crude glycerin supplementation linearly increased the feeder speed and production rate (P feed production rate compared with the control. Production efficiency (kg/kWh) increased linearly (P feed increased. A growth experiment was performed with 240 barrows (30 ± 1 kg initial BW) using a 2-phase feeding program over a 12-wk period with 4 pens per treatment and 20 pigs per pen. On the last day of the growth experiment, blood samples were collected to determine circulating glucose, fructosamine, and IGF-1 concentrations. Overall growth performance was not affected (P > 0.05) by dietary treatment, and there was no effect (P > 0.05) of dietary treatment on any plasma metabolite measured. A digestibility experiment involving 9 male pigs housed in metabolic cages was used to determine the coefficients of apparent fecal digestibility and N and mineral balances. Pigs were assigned to 1 of the 3 diets in each feeding period using a 3 × 3 Latin square arrangement of treatments (43 ± 3 and 74 ± 3 kg initial BW in the growing and finishing periods, respectively). In both feeding periods, fecal digestibility of OM and ether extract were affected by dietary treatment, increasing linearly (P feeding period. In conclusion, adding crude glycerin to the diet before pelleting improved feed mill production efficiency. The addition of crude glycerin up to 5% in the diet of growing-finishing pigs had no effect on growth performance, blood metabolites, nutrient digestibility, and N balance, but more studies are needed to

  6. Periodontal treatment decreases plasma oxidized LDL level and oxidative stress.

    Science.gov (United States)

    Tamaki, Naofumi; Tomofuji, Takaaki; Ekuni, Daisuke; Yamanaka, Reiko; Morita, Manabu

    2011-12-01

    Periodontitis induces excessive production of reactive oxygen species in periodontal lesions. This may impair circulating pro-oxidant/anti-oxidant balance and induce the oxidation of low-density lipoprotein (LDL) in blood. The purpose of this study was to monitor circulating oxidized LDL and oxidative stress in subjects with chronic periodontitis following non-surgical periodontal treatment. Plasma levels of oxidized LDL and oxidative stress in 22 otherwise healthy non-smokers with chronic periodontitis (mean age 44.0 years) were measured at baseline and at 1 and 2 months after non-surgical periodontal treatment. At baseline, chronic periodontitis patients had higher plasma levels of oxidized LDL and oxidative stress than healthy subjects (p surgical periodontal treatment were effective in decreasing oxLDL, which was positively associated with a reduction in circulating oxidative stress.

  7. Monitoring of benzodiazepines (clobazam, diazepam and their main active metabolites) in human plasma by column-switching high-performance liquid chromatography.

    Science.gov (United States)

    Lacroix, C; Wojciechowski, F; Danger, P

    1993-08-11

    A column-switching high-performance liquid chromatographic method for the simultaneous determination of clobazam, diazepam and their main metabolites in human plasma is described. A 200-microliters plasma sample was directly injected into a precolumn filled with TSK-gel PW. After a washing step with potassium phosphate buffer, the retained substances were backflushed into a reversed-phase column with a mobile phase of acetonitrile-phosphate buffer-diethylamine. Various drugs frequently co-administered with clobazam or diazepam do not interfere with the determination.

  8. In vivo biochemistry: quantifying ion and metabolite levels in individual cells or cultures of yeast.

    Science.gov (United States)

    Bermejo, Clara; Ewald, Jennifer C; Lanquar, Viviane; Jones, Alexander M; Frommer, Wolf B

    2011-08-15

    Over the past decade, we have learned that cellular processes, including signalling and metabolism, are highly compartmentalized, and that relevant changes in metabolic state can occur at sub-second timescales. Moreover, we have learned that individual cells in populations, or as part of a tissue, exist in different states. If we want to understand metabolic processes and signalling better, it will be necessary to measure biochemical and biophysical responses of individual cells with high temporal and spatial resolution. Fluorescence imaging has revolutionized all aspects of biology since it has the potential to provide information on the cellular and subcellular distribution of ions and metabolites with sub-second time resolution. In the present review we summarize recent progress in quantifying ions and metabolites in populations of yeast cells as well as in individual yeast cells with the help of quantitative fluorescent indicators, namely FRET metabolite sensors. We discuss the opportunities and potential pitfalls and the controls that help preclude misinterpretation. © The Authors Journal compilation © 2011 Biochemical Society

  9. LC-MS/MS quantification of sulforaphane and indole-3-carbinol metabolites in human plasma and urine after dietary intake of selenium-fortified broccoli.

    Science.gov (United States)

    Hauder, Johanna; Winkler, Stefanie; Bub, Achim; Rüfer, Corinna E; Pignitter, Marc; Somoza, Veronika

    2011-08-10

    This study aimed at developing a sensitive LC-MS/MS method for the quantification of sulforaphane (SFN) and indole-3-carbinol metabolites in plasma and urine after dietary intake of regular and selenium-fertilized broccoli using stable isotope dilution analysis. In a three-armed, placebo-controlled, randomized human intervention study with 76 healthy volunteers, 200 g of regular (485 μg of total glucosinolates and <0.01 μg of selenium per gram fresh weight) or selenium-fertilized broccoli (589 μg of total glucosinolates and 0.25 μg of selenium per gram fresh weight) was administered daily for 4 weeks. Glucoraphanin and glucobrassicin metabolites quantified in plasma and urine were SFN-glutathione, SFN-cysteine, SFN-cysteinylglycine, SFN-acetylcysteine, and indole-3-carboxaldehyde, indole-3-carboxylic acid, and ascorbigen, respectively. Dietary intake of selenium-fertilized broccoli increased serum selenium concentration analyzed by means of atomic absorption spectroscopy by up to 25% (p < 0.001), but affected neither glucosinolate concentrations in broccoli nor their metabolite concentrations in plasma and urine compared to regular broccoli.

  10. Determination of metoprolol and its two metabolites in human plasma and urine by high performance liquid chromatography with fluorescence detection and its application in pharmacokinetics.

    Science.gov (United States)

    Xu, Tao; Bao, Shihui; Geng, Peiwu; Luo, Jun; Yu, Lei; Pan, Peipei; Chen, Yi; Hu, Guoxin

    2013-10-15

    A simple, specific and sensitive HPLC method has been developed for the determination of metoprolol and its two metabolites in human plasma and urine. Separation of metoprolol, α-hydroxymetoprolol, O-desmethylmetoprolol and esmolol (internal standard) was achieved on an Agilent XDB-C18 column (150mm×4.6mm, 5μm) using fluorescence detection with Ex 216nm and Em 312nm. The mobile phase consisted of ACN-H2O-0.1%TFA. The analysis was performed in less than 16min with a flow rate of 0.8mL/min. The assay was linear over the concentration range of 5-600ng/mL and 2.5-300ng/mL for metoprolol and its metabolites, respectively. The LOQ were 5.0 and 2.5ng/mL for plasma and urine, respectively. Good precision and accuracy for metoprolol and its two metabolites were obtained. The extraction recoveries were found to be more than 86.91% both in plasma and urine. At the same time, the method was successfully applied to nine healthy volunteers who had been given an oral tablet of 100mg metoprolol.

  11. Plasma Lactate Dehydrogenase Levels Predict Mortality in Acute Aortic Syndromes

    OpenAIRE

    Morello, Fulvio; Ravetti, Anna; Nazerian, Peiman; Liedl, Giovanni; Veglio, Maria Grazia; Battista, Stefania; Vanni, Simone; Pivetta, Emanuele; Montrucchio, Giuseppe; Mengozzi, Giulio; Rinaldi, Mauro; Moiraghi, Corrado; Lupia, Enrico

    2016-01-01

    Abstract In acute aortic syndromes (AAS), organ malperfusion represents a key event impacting both on diagnosis and outcome. Increased levels of plasma lactate dehydrogenase (LDH), a biomarker of malperfusion, have been reported in AAS, but the performance of LDH for the diagnosis of AAS and the relation of LDH with outcome in AAS have not been evaluated so far. This was a bi-centric prospective diagnostic accuracy study and a cohort outcome study. From 2008 to 2014, patients from 2 Emergency...

  12. Relationship between Plasma Leptin Level and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Anoop Shankar

    2012-01-01

    Full Text Available Background. Leptin is an adipose tissue-derived hormone shown to be related to several metabolic, inflammatory, and hemostatic factors related to chronic kidney disease. Recent animal studies have reported that infusion of recombinant leptin into normal rats for 3 weeks fosters the development of glomerulosclerosis. However, few studies have examined the association between leptin and CKD in humans. Therefore, we examined the association between plasma leptin levels and CKD in a representative sample of US adults. Methods. We examined the third National Health and Nutrition Examination Survey participants >20 years of age (n=5820, 53.6% women. Plasma leptin levels were categorized into quartiles (≤4.3 Fg/L, 4.4–8.7 Fg/L, 8.8–16.9 Fg/L, >16.9 Fg/L. CKD was defined as a glomerular filtration rate of <60 mL/min/1.73 m2 estimated from serum creatinine. Results. Higher plasma leptin levels were associated with CKD after adjusting for age, sex, race/ethnicity, education, smoking, alcohol intake, body mass index (BMI, diabetes, hypertension, and serum cholesterol. Compared to quartile 1 of leptin (referent, the odds ratio (95% confidence interval of CKD associated with quartile 4 was 3.31 (1.41 to 7.78; P-trend = 0.0135. Subgroup analyses examining the relation between leptin and CKD by gender, BMI categories, diabetes, and hypertension status also showed a consistent positive association. Conclusion. Higher plasma leptin levels are associated with CKD in a representative sample of US adults.

  13. [Preoperative digitalization. Measurement of digoxin plasma levels (author's transl)].

    Science.gov (United States)

    Geiger, H J; Rietbrock, N

    1976-09-01

    In a study of 233 patients from the department of surgery and anesthesiology taking digoxin preparations 64, per cent exhibit digoxin levels in the therapeutic range (0.6--1.5 ng/ml), 19 per cent had subtoxic concentrations ranged from 1.6--2.0 ng/ml and 7 per cent were in the toxic range (greater than 2 ng/ml). In patients treated with digoxin before admission to hospital subtherapeutic levels were most frequent. An average loading dose of digoxin 1 mg or more on one day may result in subtoxic and toxic digoxin levels on the second day, in patients receiving less than 1 mg digoxin daily an increasing frequency of plasma digoxin concentrations of 1.5 ng/ml or higher values was present on the third day. Averaged plasma digoxin concentrations were correlated with daily maintenance dose. There was, however, a wide individual variation in digoxin plasma concentrations. A low incidence of toxic digoxin plasma levels was observed in patients receiving a daily oral maintenance dose of 0.375 mg digoxin (Lanicor). For prophylactic digitalization of patients with normal renal and thyroid function the following schedules or statistical guidlines are proposed: Lanicor (bioavailability 60%): oral loading dose of 0.75 mg over two days, and then daily oral maintenance dose of 0.375 mg; Novodigal (bioavailability 80%): oral loading dose of 0.6 mg over two days and then daily oral maintenance dose of 0.3 mg; Digoxin i.v.: intravenous loading dose of 0.5 (0.4) mg over two days and then 0.25 (0.2) mg daily intravenous maintenance dose. For any patient needing treatment with digitalis glycosides therapy must be individual and dynamic. The reasons for toxic concentrations were frequently attributed to wrong dosage.

  14. Analysis of metabolites in plasma reveals distinct metabolic features between Dahl salt-sensitive rats and consomic SS.13(BN) rats.

    Science.gov (United States)

    Wang, Le; Hou, Entai; Wang, Zhengjun; Sun, Na; He, Liqing; Chen, Lan; Liang, Mingyu; Tian, Zhongmin

    2014-07-18

    Salt-sensitive hypertension is a major risk factor for cardiovascular disorders. Our previous proteomic study revealed substantial differences in several proteins between Dahl salt-sensitive (SS) rats and salt-insensitive consomic SS.13(BN) rats. Subsequent experiments indicated a role of fumarase insufficiency in the development of hypertension in SS rats. In the present study, a global metabolic profiling study was performed using gas chromatography/mass spectrometry (GC/MS) in plasma of SS rats (n=9) and SS.13(BN) rats (n=8) on 0.4% NaCl diet, designed to gain further insights into the relationship between alterations in cellular intermediary metabolism and predisposition to hypertension. Principal component analysis of the data sets revealed a clear clustering and separation of metabolic profiles between SS rats and SS.13(BN) rats. 23 differential metabolites were identified (PSS rats. Pyruvate, which connects TCA cycle and glycolysis, was also increased in SS rats. Moreover, lower activity levels of fumarase, aconitase, α-ketoglutarate dehydrogenase and succinyl-CoA synthetase were detected in the heart, liver or skeletal muscles of SS rats. The distinct metabolic features in SS and SS.13(BN) rats indicate abnormalities of TCA cycle in SS rats, which may play a role in predisposing SS rats to developing salt-sensitive hypertension.

  15. Simultaneous quantification of phencynonate and its active metabolite N-demethyl phencynonate in human plasma using liquid chromatography and isotope-dilution mass spectrometry.

    Science.gov (United States)

    Chen, Zhengang; Xie, Hui; Liu, Jinbo; Wang, Guangshun

    2015-09-01

    A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously quantify phencynonate (PCN) and its major metabolite N-demethyl phencynonate (DM-PCN) in human plasma. Following one-step liquid-liquid extraction, the analytes were separated on a reversed-phase C18 column. Methanol and 0.02% formic acid in 10 mM ammonium acetate (62:38, v/v) was used as isocratic mobile phase at a flow-rate of 0.3 mL/min. An API 5000 tandem mass spectrometer equipped with a Turbo IonSpray ionization source was used as the detector and was operated in the positive ion mode. Multiple reaction monitoring using the transition of m/z 358.4 → m/z 156.2, m/z 344.4 → m/z 142.2, and m/z 361.3 → m/z 159.2 was performed to quantify PCN, DM-PCN, and the internal standard (D3 -PCN), respectively. This approach showed a lower limit of quantification of 10 pg/mL and 25 pg/mL for PCN and DM-PCN in plasma, respectively. This sensitivity was at least 50-fold superior to previously reported ones and thus enabled the approach well applicable to low-dose pharmacokinetic studies. The intra- and inter-day precisions were less than 14.2 % at each QC level for both PCN and DM-PCN. The inter-day relative errors ranged from -1.9% to -4.9% for PCN, and from 0.6% to 6.4% for DM-PCN. As a proof of principle, the validated method was successfully applied to simultaneous quantification of circulating PCN and DM-PCN in healthy subjects after a single oral administration of 2 mg phencynonate hydrochloride pellet.

  16. Quantitation of donepezil and its active metabolite 6-O-desmethyl donepezil in human plasma by a selective and sensitive liquid chromatography-tandem mass spectrometric method

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Bhavin N. [Chemistry Department, School of Sciences, Gujarat University, Navrangpura, Ahmedabad 380 009, Gujarat (India); Analytical Laboratory, BA Research India Ltd., Bodakdev, Ahmedabad 380 054, Gujarat (India); Sharma, Naveen [Analytical Laboratory, BA Research India Ltd., Bodakdev, Ahmedabad 380 054, Gujarat (India); Sanyal, Mallika [Chemistry Department, St. Xaviers' College, Navrangpura, Ahmedabad 380 009, Gujarat (India); Shrivastav, Pranav S. [Chemistry Department, School of Sciences, Gujarat University, Navrangpura, Ahmedabad 380 009, Gujarat (India)], E-mail: pranav_shrivastav@yahoo.com

    2008-11-23

    A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the simultaneous determination of donepezil (D) and its pharmacologically active metabolite, 6-O-desmethyl donepezil (6-ODD) in human plasma is developed using galantamine as internal standard (IS). The analytes and IS were extracted from 500 {mu}L aliquots of human plasma via solid-phase extraction (SPE) on Waters Oasis HLB cartridges. Chromatographic separation was achieved in a run time of 6.0 min on a Waters Novapak C18 (150 mm x 3.9 mm, 4 {mu}m) column under isocratic conditions. Detection of analytes and IS was done by tandem mass spectrometry, operating in positive ion and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for D, 6-ODD and IS were at m/z 380.1 {yields} 91.2, 366.3 {yields} 91.3 and 288.2 {yields} 213.2, respectively. The method was fully validated for its selectivity, interference check, sensitivity, linearity, precision and accuracy, recovery, matrix effect, ion suppression/enhancement, cross-specificity, stability and dilution integrity. A linear dynamic range of 0.10-50.0 ng mL{sup -1} for D and 0.02-10.0 ng mL{sup -1} for 6-ODD was evaluated with mean correlation coefficient (r) of 0.9975 and 0.9985, respectively. The intra-batch and inter-batch precision (%CV, coefficient of variation) across five quality control levels was less than 7.5% for both the analytes. The method was successfully applied to a bioequivalence study of 10 mg donepezil tablet formulation in 24 healthy Indian male subjects under fasting condition.

  17. Highly sensitive and selective high-performance liquid chromatography method for bioequivalence study of cefpodoxime proxetil in rabbit plasma via fluorescence labeling of its active metabolite.

    Science.gov (United States)

    Ahmed, Sameh; Abdel-Wadood, Hanaa M; Mohamed, Niveen A

    2013-09-01

    Cefpodoxime proxetil (CFP), a broad-spectrum third-generation cephalosporin, has been used most widely in the treatment of respiratory and urinary tract infections. For bioequivalence study of CFP in rabbit plasma, it was necessary to develop a highly sensitive and selective high-performance liquid chromatographic (HPLC) method with fluorescence (FL) detection. The pre-column labeling of cefpodoxime acid (CFA) (active metabolite) with an efficient benzofurazan type fluorogenic reagent, 4-N,N-dimethyl aminosulfonyl-7-fluoro-2,1,3-benzoxadiazole (DBD-F) was carried out in the present study in 100mM borate buffer (pH=8.5) at 50°C for 15min. The obtained fluorescent products were separated on C18 column with an isocratic elution of the mobile phase, which consists of 10mM phosphate buffer (pH=3.5)/CH3CN (70:30, v/v). The fluorescent product (DBD-CFA) was detected fluorimetrically at 556nm with an excitation wavelength of 430nm. Cefotaxime sodium was used as internal standard. The method was validated according to the requirements of US-FDA guidelines. The correlation coefficient of 0.999 was obtained in the concentration ranges of 10-1000ngmL(-1). The limits of detection and quantification (S/N=3) were 3 and 10ngmL(-1), respectively. Plasma CFA levels were successfully determined in rabbit with satisfactory precision and accuracy. The proposed HPLC-FL method was successfully applied to study bioequivalence in rabbits for two formulations of different brands contained CFP (prodrug) in a randomized, two-way, single-dose, crossover study and all pharmacokinetic parameters for the two formulations were assessed.

  18. Kissing reduces allergic skin wheal responses and plasma neurotrophin levels.

    Science.gov (United States)

    Kimata, Hajime

    2003-11-01

    The effect of kissing on allergen-induced skin wheal responses and plasma neurotrophin levels were studied in 30 normal subjects, 30 patients with allergic rhinitis (AR), and 30 patients with atopic dermatitis (AD). All of the patients with AR or AD are allergic to house dust mite (HDM) and Japanese cedar pollen (JCP). They are all Japanese and they do not kiss habitually. The subject kissed freely during 30 min with their lover or spouse alone in a room with closed doors while listening to soft music. Before and after kissing, skin prick tests were performed using commercial HDM allergen, JCP allergen, as well as histamine and control solution, and wheal responses were measured. Simultaneously, plasma levels of neurotrophin, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and -4 (NT-4) were measured. Kissing significantly reduced wheal responses induced by HDM and JCP, but not by histamine, and decreased plasma levels of NGF, BDNF, NT-3, and NT-4 in patients with AR or AD, while it failed to do so in normal subjects. These finding indicate that kissing have some implication in the study of neuroimmunology in allergic patients.

  19. Plasma bupivacaine levels following single dose intraarticular instillation for arthroscopy.

    Science.gov (United States)

    Meinig, R P; Holtgrewe, J L; Wiedel, J D; Christie, D B; Kestin, K J

    1988-01-01

    Arthroscopy of the knee was performed using 30 ml single dose intraarticular instillations of 0.5% or 0.25% solutions of bupivacaine (Marcaine). A total of 18 patients (mean age, 34 years), divided into two groups, participated in this study. Venous plasma levels were measured at 0, 10, 20, 30, 45, 60, 90, 120, and 240 minute intervals following a single instillation into the knee joint. All patients had suspected traumatic internal derangement of the knee. Electrocardiogram tracings, blood pressure, and neurologic assessment were monitored at each venous sampling interval or more often if clinically indicated. The type and amount of supplemental anesthesia were also recorded. None of our 18 patients required a general anesthetic because of pain although the following procedures were performed: meniscectomy, plica release, abrasion chondroplasty, loose body retrieval, and limited meniscal repair. A new methodology for the measurement of plasma bupivacaine using the gas chromatograph mass spectrometer is described. Monitoring specific molecular mass fragments allows the measurement of picogram per milliliter levels of bupivacaine. The highest peak plasma concentration occurred 20 minutes after instillation of 30 ml of 0.5% bupivacaine. The 625 +/- 225 ng/ml level was well below the 2,500 to 4,000 ng/ml reported to elicit early subjective CNS symptoms of bupivacaine toxicity. Thus, a single dose intraarticular instillation of 30 ml 0.5% or 0.25% bupivacaine is convenient, efficacious, and pharmacologically safe for routine clinical arthroscopy.

  20. Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype.

    Science.gov (United States)

    Abu-Hayyeh, Shadi; Papacleovoulou, Georgia; Lövgren-Sandblom, Anita; Tahir, Mehreen; Oduwole, Olayiwola; Jamaludin, Nurul Akmal; Ravat, Sabiha; Nikolova, Vanya; Chambers, Jenny; Selden, Clare; Rees, Myrddin; Marschall, Hanns-Ulrich; Parker, Malcolm G; Williamson, Catherine

    2013-02-01

    Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy-specific liver disease and is associated with an increased risk of adverse fetal outcomes, including preterm labor and intrauterine death. The endocrine signals that cause cholestasis are not known but 3α-sulfated progesterone metabolites have been shown to be elevated in ICP, leading us to study the impact of sulfated progesterone metabolites on farnesoid X receptor (FXR)-mediated bile acid homeostasis pathways. Here we report that the 3β-sulfated progesterone metabolite epiallopregnanolone sulfate is supraphysiologically raised in the serum of ICP patients. Mice challenged with cholic acid developed hypercholanemia and a hepatic gene expression profile indicative of FXR activation. However, coadministration of epiallopregnanolone sulfate with cholic acid exacerbated the hypercholanemia and resulted in aberrant gene expression profiles for hepatic bile acid-responsive genes consistent with cholestasis. We demonstrate that levels of epiallopregnanolone sulfate found in ICP can function as a partial agonist for FXR, resulting in the aberrant expression of bile acid homeostasis genes in hepatoma cell lines and primary human hepatocytes. Furthermore, epiallopregnanolone sulfate inhibition of FXR results in reduced FXR-mediated bile acid efflux and secreted FGF19. Using cofactor recruitment assays, we show that epiallopregnanolone sulfate competitively inhibits bile acid-mediated recruitment of cofactor motifs to the FXR-ligand binding domain. Our results reveal a novel molecular interaction between ICP-associated levels of the 3β-sulfated progesterone metabolite epiallopregnanolone sulfate and FXR that couples the endocrine component of pregnancy in ICP to abnormal bile acid homeostasis. Copyright © 2012 American Association for the Study of Liver Diseases.

  1. Association of plasma lipid levels with atherosclerosis prevalence in psittaciformes.

    Science.gov (United States)

    Beaufrère, Hugues; Vet, Dr Med; Cray, Carolyn; Ammersbach, Mélanie; Tully, Thomas N

    2014-09-01

    The prevalence of atherosclerosis is high in the captive psittacine population and increases with age and female sex. The genera Psittacus, Amazona, and Nymphicus are predisposed to atherosclerosis, whereas the genera Cacatua and Ara are less susceptible. Plasma cholesterol and lipoprotein abnormalities have been suggested as risk factors in the development of atherosclerosis as observed in mammals. To investigate whether the psittacine genera susceptibility to atherosclerosis and the known risk factors of age and sex could be associated with differences in the lipid profile, a retrospective analysis was conducted on blood lipid values from 5625 birds. Prevalence values were obtained from a previously published, large, case-control study and were compared with identified trends in plasma lipid profiles. Genus-specific differences were identified in plasma total cholesterol values that corresponded to observed trends in the prevalence of clinically important atherosclerotic lesions, which were also highly correlated. The effect of age was significant but was mild and may not account for the dramatic increase in atherosclerosis prevalence observed with age. In addition, Quaker parrots ( Myiopsitta monachus ), which were used as experimental models for psittacine atherosclerosis and dyslipidemia, were found to have the highest values in all lipid profile parameters. The results of this study suggest that the differences observed in prevalence among species of the psittacine genera may partly be explained by differences in plasma total cholesterol levels. Results also support the use of Quaker parrots as models for studying atherosclerosis and dyslipidemia.

  2. FABP4 plasma levels are increased in familial combined hyperlipidemia

    Science.gov (United States)

    Cabré, Anna; Lázaro, Iolanda; Cofán, Montserrat; Jarauta, Estibaliz; Plana, Núria; Garcia-Otín, Angel L.; Ascaso, Juan F.; Ferré, Raimón; Civeira, Fernando; Ros, Emilio; Masana, Lluís

    2010-01-01

    The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) μg/l and 19.2 (9.2) μg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P< 0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia. PMID:20388924

  3. Hip Osteonecrosis Is Associated with Increased Plasma IL-33 Level

    Science.gov (United States)

    Ma, Jinhui; Guo, Wanshou; Li, Zirong; Li, Shirui; Wang, Peng

    2017-01-01

    The recently discovered IL-33 as an IL-1 cytokine family member has been proved to be specifically released from osteonecrotic bones. We aimed to investigate the potential role of IL-33 in the development of osteonecrosis of femoral head (ONFH). Forty patients diagnosed with ONFH and forty age-, sex-, and body mass index- (BMI-) matched healthy subjects were included in this prospective study between March 2016 and September 2016. A commercially available ELISA kit was used to test the level of plasma IL-33. The IL-33 levels were compared among different ARCO stages, CJFH types, and etiology groups. Plasma IL-33 levels were significantly higher in the ONFH patients than that in the control subjects. The levels of IL-33 did not differ significantly among the ONFH patients with different ARCO stages. The IL-33 levels of patients with CJFH type L3 were significantly higher than that of patients with types L1 and L2. No significant differences were observed in IL-33 levels between steroid-induced, alcohol-induced, and idiopathic patients. Our findings seem to indicate that IL-33 effects may be detrimental during ONFH, which appeared to be associated with the prognosis of ONFH. The IL-33 deserves particular attention in the pathogenesis of ONFH. PMID:28167850

  4. Plasma total antioxidant capacity is associated with dietary intake and plasma level of antioxidants in postmenopausal women.

    Science.gov (United States)

    Wang, Ying; Yang, Meng; Lee, Sang-Gil; Davis, Catherine G; Kenny, Anne; Koo, Sung I; Chun, Ock K

    2012-12-01

    Increased plasma total antioxidant capacity (TAC) has been associated with a high consumption of fruits and vegetables. However, limited information is available on whether plasma TAC reflects the dietary intake of antioxidants and the levels of individual antioxidants in plasma. By using three different assays, the study aimed to determine if plasma TAC can effectively predict dietary intake of antioxidants and plasma antioxidant status. Forty overweight and apparently healthy postmenopausal women were recruited. Seven-day food records and 12-h fasting blood samples were collected for dietary and plasma antioxidant assessments. Plasma TAC was determined by vitamin C equivalent antioxidant capacity (VCEAC), ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) assays. TAC values determined by VCEAC were highly correlated with FRAP (r=0.79, Pantioxidants and represents more closely the plasma antioxidant levels than ORAC and FRAP.

  5. Potential utility of soluble p3-alcadein α plasma levels as a biomarker for sporadic Alzheimer's disease.

    Science.gov (United States)

    Kamogawa, Kenji; Kohara, Katsuhiko; Tabara, Yasuharu; Takita, Rie; Miki, Tetsuro; Konno, Tomoko; Hata, Saori; Suzuki, Toshiharu

    2012-01-01

    Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins (α, β, γ) that share identical localization and function to the amyloid-β protein precursor (AβPP) in the brain. Alcs are proteolyzed in neurons through successive cleavages via secretases, resulting in non-aggregative p3-Alc, where p3 corresponds to the AβPP-fragment. We found p3-Alcα detected in human plasma reflected the pathological process of amyloid-β accumulation in Alzheimer's disease (AD) patients and therefore investigated the utility of p3-Alcα as a plasma biomarker in AD. We measured p3-Alcα plasma levels in 83 sporadic-AD, 18 mild cognitive impaired (MCI), and 24 control subjects using the sandwich-ELISA system. Pooled samples with previously published data (171 AD and 45 controls) were also analyzed. The plasma p3-Alcα concentrations in patients with AD and MCI were significantly higher compared with control subjects (224.7 ± 40.4, 223.3 ± 53.9, and 189.1 ± 32.9 pg/ml, respectively; p = 0.0012). In AD patients, the plasma p3-Alcα concentration significantly correlated with age (r = 0.23, p = 0.037) and serum creatinine levels (r = 0.23, p = 0.0012). Even after adjusting for confounding factors of age, gender, renal function, and ApoE-ε4, high plasma p3-Alcα levels were correlated with significant AD risk, with an odds ratio 1.47 (95% confidence interval: 1.18-1.93, p = 0.0019) for every 10 pg/ml increase. Pooled analysis further confirmed these findings. Increased plasma p3-Alcα, evident in the early stages of cognitive impairment, suggests that Alc metabolites are useful plasma biomarkers of AD.

  6. Metabolite profiling of plasma and urine from rats with TNBS-induced acute colitis using UPLC-ESI-QTOF-MS-based metabonomics--a pilot study.

    Science.gov (United States)

    Zhang, Xiaojun; Choi, Franky F K; Zhou, Yan; Leung, Feung P; Tan, Shun; Lin, Shuhai; Xu, Hongxi; Jia, Wei; Sung, Joseph J Y; Cai, Zongwei; Bian, Zhaoxiang

    2012-07-01

    The incidence of inflammatory bowel disease, a relapsing intestinal condition whose precise etiology is still unclear, has continually increased over recent years. Metabolic profiling is an effective method with high sample throughput that can detect and identify potential biomarkers, and thus may be useful in investigating the pathogenesis of inflammatory bowel disease. In this study, using a metabonomics approach, a pilot study based on ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) was performed to characterize the metabolic profile of plasma and urine samples of rats with experimental colitis induced by 2,4,6-trinitrobenzene sulfonic acid. Acquired metabolic profile data were processed by multivariate data analysis for differentiation and screening of potential biomarkers. Five metabolites were identified in urine: two tryptophan metabolites [4-(2-aminophenyl)-2,4-dioxobutanoic acid and 4,6-cihydroxyquinoline], two gut microbial metabolites (phenyl-acetylglycine and p-cresol glucuronide), and the bile acid 12α-hydroxy-3-oxocholadienic acid. Seven metabolites were identified in plasma: three members of the bile acid/alcohol group (cholic acid, 12α-hydroxy-3-oxocholadienic acid and cholestane-3,7,12,24,25-pentol) and four lysophosphatidylcholines [LysoPC(20:4), LysoPC(16:0), LysoPC(18:1) and LysoPC(18:0)]. These metabolites are associated with damage of the intestinal barrier function, microbiota homeostasis, immune modulation and the inflammatory response, and play important roles in the pathogenesis of inflammatory bowel disease. Our results positively support application of the metabonomic approach in study of the pathophysiological mechanism of inflammatory bowel disease.

  7. Plasma-cortisol levels in experimental heatstroke in dogs

    Science.gov (United States)

    Assia, Ehud; Epstein, Yoram; Magazanik, Avraham; Shapiro, Yair; Sohar, Ezra

    1989-06-01

    The effect of external heat-load, exercise and dehydration on dynamic changes in plasma cortisol during the development of heatstroke was investigated. Thirty-three unanesthetized dogs were tested under two sets of climatic conditions: comfort conditions and hot-dry climatic conditions, half of them while exercising. Half of the dogs in each group were rehydrated. None of the dogs that were investigated at room temperature suffered heatstroke. Of the dogs exposed to high ambient temperature, all of the exercising, as well as five out of six non-hydrated dogs and one rehydrated non-exercising dog suffered heatstroke. Significant dehydration (6% 7% of body weight), occurred only under hgh ambient temperature. Plasma cortisol levels of all dogs that suffered heatstroke rose conspicuously for at least 5 h and returned to normal levels 24 h later. Cortisol levels of dogs who did not experience heatstroke remained within the normal range. Cortisol levels correlated with the severity of the stress leading to heatstroke. High and rising levels of cortisol, several hours after body temperature returns to normal, may support the diagnosis of heatstroke.

  8. Effect of rooibos tea (Aspalathus linearis) on Japanese quail growth, egg production and plasma metabolites.

    Science.gov (United States)

    Juráni, M; Lamosová, D; Mácajová, M; Kostál, L; Joubert, E; Greksák, M

    2008-01-01

    1. Birds have been proposed as a suitable model for studies on ageing because of their long life in comparison with similar-sized mammals. However, some weak fliers, such as Galliformes, are the exception to this rule. The aim of the present study was to determine the effects of the treatment with rooibos tea (Aspalathus linearis), a natural source of flavonoid antioxidants and compounds with phyto-oestrogenic activity, on postnatal development and egg production of aged Japanese quail (Coturnix coturnix japonica). 2. Substitution of drinking water with traditional rooibos tea or diet supplementation with ground rooibos tea affected body weight of Japanese quail up to 100 d of age. The body weight of males drinking rooibos tea or eating rooibos-supplemented food decreased significantly. There was a trend toward increased body weight of tea drinking females and a significant increase in the body weight of hens fed the rooibos-supplemented diet. Although rooibos treatment did not significantly increase egg production in young hens, the decrease in egg production of rooibos-treated aged hens (360 d of age) was significantly reduced, regardless of the egg production levels (high - 80%; low - 20%) before the treatment. 3. The results suggest that treatment with rooibos tea positively affected body weight and egg production in quail hens and prolonged the productive period of aged animals. Further studies would be needed to address the question whether these effects are due to the antioxidant or phyto-oestrogenic activities of rooibos.

  9. Resveratrol and its metabolites inhibit pro-inflammatory effects of lipopolysaccharides in U-937 macrophages in plasma-representative concentrations.

    Science.gov (United States)

    Walker, Jessica; Schueller, Katharina; Schaefer, Lisa-Marie; Pignitter, Marc; Esefelder, Laura; Somoza, Veronika

    2014-01-01

    Resveratrol has been shown to exploit various biological activities, including an anti-inflammatory activity. However, resveratrol is metabolized by phase II enzymes post-absorption to predominantly form glucuronides and sulfates. To investigate the anti-inflammatory effects of resveratrol and its dominating sulfated and glucuronated metabolites formed in vivo, U-937 macrophages were chosen as an immune-competent model system, known to release cytokines upon lipopolysaccharide stimulation. U-937 cells were stimulated with lipopolysaccharides from Escherichia coli (E. coli-LPS) to evoke an inflammatory reaction, and pre- or co-incubated with 1 or 10 μM of resveratrol (RES), resveratrol-3-sulfate (R3S), resveratrol-disulfates (RDS), resveratrol-3-glucuronide or resveratrol-4'-glucuronide. Time dependent gene expression of IL-6, IL-1α/β and IL-1R by qPCR was studied at 1 h, 3 h, 6 h, 9 h, and 24 h of incubation, and the release of IL-6 and TNF-α, after 6 h was analysed by means of non-magnetic or magnetic bead analysis. As a result, 10 μM resveratrol completely inhibited the E. coli-LPS-induced release of IL-6, while resveratrol-3-sulfate and resveratrol-disulfates decreased it by respective 84.2 ± 29.4% and 52.3 ± 39.5%. Whereas TNF-α release was reduced by 48.1 ± 15.4%, 33.0 ± 10.0% and 46.7 ± 8.7% by RES, R3S and RDS, respectively. These results show that not only resveratrol but also resveratrol-3-sulfate and resveratrol-disulfates exhibit an anti-inflammatory potential by counteracting an inflammatory challenge in U-937 macrophages at plasma representative concentrations.

  10. Magnetic resonance spectroscopy study of proton metabolite level changes in sensorimotor cortex after upper limb replantation-revascularization.

    Science.gov (United States)

    Ertem, Kadir; Alkan, Alpay; Sarac, Kaya; Onal, Cagatay; Bostan, Haci; Yologlu, Saim; Bora, Arslan

    2005-01-01

    We aimed to investigate the changes in proton metabolite levels at the motor and somatosensory cortex by magnetic resonance spectroscopy (MRS) after upper extremity replantation or revascularization. Nine patients who referred to our clinic suffering from major total (two) and subtotal (seven) amputation of the upper extremity were enrolled in this study. Mean time value between the injury and operation was 5.1 h. Mean follow-up period or mean time between the injury and MRS analysis was 26.2 months (ranging from 7 to 41 months). Voxels (TR: 2000; TE: 136 ms) were placed onto locations in the bilateral precentral and postcentral cortex area of the cerebral hemispheres that represent the upper extremity. Contralateral sides of the brain hemisphere that represent the injured extremity were accounted as control groups. Metabolite ratios [NAA (N-acetyl aspartate)/Cr (creatine) and Cho (choline)/Cr] of the motor and somatosensory cortex were calculated. The NAA/Cr and Cho/Cr metabolite ratios between the two groups were found to be insignificant, and these results may indicate that there is no remarkable somatosensorial cortex disruption or demyelination in these patients. Fifty-six percent of patients were found as functional according to Chen's scale.

  11. Metabolite profiling reveals novel multi-level cold responses in the diploid model Fragaria vesca (woodland strawberry).

    Science.gov (United States)

    Rohloff, Jens; Kopka, Joachim; Erban, Alexander; Winge, Per; Wilson, Robert C; Bones, Atle M; Davik, Jahn; Randall, Stephen K; Alsheikh, Muath K

    2012-05-01

    Winter freezing damage is a crucial factor in overwintering crops such as the octoploid strawberry (Fragaria × ananassa Duch.) when grown in a perennial cultivation system. Our study aimed at assessing metabolic processes and regulatory mechanisms in the close-related diploid model woodland strawberry (Fragaria vescaL.) during a 10-days cold acclimation experiment. Based on gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) metabolite profiling of three F. vesca genotypes, clear distinctions could be made between leaves and non-photosynthesizing roots, underscoring the evolvement of organ-dependent cold acclimation strategies. Carbohydrate and amino acid metabolism, photosynthetic acclimation, and antioxidant and detoxification systems (ascorbate pathway) were strongly affected. Metabolic changes in F. vesca included the strong modulation of central metabolism, and induction of osmotically-active sugars (fructose, glucose), amino acids (aspartic acid), and amines (putrescine). In contrast, a distinct impact on the amino acid proline, known to be cold-induced in other plant systems, was conspicuously absent. Levels of galactinol and raffinose, key metabolites of the cold-inducible raffinose pathway, were drastically enhanced in both leaves and roots throughout the cold acclimation period of 10 days. Furthermore, initial freezing tests and multifaceted GC/TOF-MS data processing (Venn diagrams, independent component analysis, hierarchical clustering) showed that changes in metabolite pools of cold-acclimated F. vesca were clearly influenced by genotype.

  12. Ghrelin plasma levels and appetite in peritoneal dialysis patients.

    Science.gov (United States)

    Aguilera, Abelardo; Cirugeda, Antonio; Amair, Ruth; Sansone, Gabriela; Alegre, Laura; Codoceo, Rosa; Bajo, M Auxiliadora; del Peso, Gloria; Díez, Juan J; Sánchez-Tomero, José A; Selgas, Rafael

    2004-01-01

    Anorexia-associated malnutrition is a severe complication that increases mortality in peritoneal dialysis (PD) patients. Ghrelin is a recently-discovered orexigenic hormone with actions in brain and stomach. We analyzed, in 42 PD patients, the possible relationship between ghrelin and appetite regulation with regard to other orexigens [neuropeptide Y (NPY), NO3] and anorexigens [cholecystokinin (CCK), leptin, glucose-dependent insulinotropic peptide (GIP), tumor necrosis factor alpha (TNFalpha)]. All orexigens and anorexigens were determined in plasma. Eating motivation was evaluated using a visual analog scale (VAS). The patients were divided into three groups: those with anorexia (n = 12), those with obesity associated with high intake (n = 12), and those with no eating behavior disorders (n = 18). A control group of 10 healthy volunteers was also evaluated. Mean plasma levels of ghrelin were high (3618.6 +/- 1533 mg/mL), with 36 patients showing values above the normal range (anorexia had lower ghrelin and NPY levels and higher peptide-C, CCK, interleukin-1 (IL-1), TNFalpha, and GIP levels than did the other patients. Patients with anorexia also had an early satiety score and low desire and pleasure in eating on the VAS and diet survey. We observed significant positive linear correlations between ghrelin and albumin (r = 0.43, p anorexia show relatively lower ghrelin plasma levels than the levels seen in obese patients or in patients with normal appetite. The role of ghrelin in appetite modulation is altered in uremic PD patients, and that alteration is possibly associated with disorders in insulin and growth hormone metabolism.

  13. Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ferenc Szalay; Mónika B Hantos; Andrea Horvath; Peter L. Lakatos; Aniko Folhoffer; Kinga Dunkel; Dalma Hegedus; Kornélia Tekes

    2004-01-01

    AIM: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist of opioid receptor-like1 receptor.It is involved in modulation of pain and cognition. High blood level was reported in patients with acute and chronic pain,and in Wilson disease. An accidental observation led us to investigate nociceptin in hepatocellular carcinoma.METHODS: Plasma nociceptin level was measured by radioimmunoassay, aprotinin was used as protease inhibitor.Hepatocellular carcinoma was diagnosed by laboratory,ultrasound, other imaging, and confirmed by fine needle biopsy. Results were compared to healthy controls and patients with other chronic liver diseases.RESULTS: Although nociceptin levels were elevated in patients with Wilson disease (14.0±2.7 pg/mL, n=26),primary biliary cirrhosis (12.1±3.2 pg/mL, n=21) and liver cirrhosis (12.8±4.0 pg/mL, n=15) compared to the healthy controls (9.2±1.8 pg/mL, n=29, P<0.001 for each), in patients with hepatocellular carcinoma a ten-fold increase was found (105.9±14.4 pg/mL, n=29, P<0.0001). High plasma levels were found in each hepatocellular carcinoma patient including those with normal alpha fetoprotein and those with pain (104.9±14.9 pg/mL, n=12) and without (107.7±14.5pg/mL, n=6).CONCLUSION: A very high nociceptin plasma level seems to be an indicator for hepatocellular carcinoma. Further research is needed to clarify the mechanism and clinical significance of this novel finding.

  14. Plasma profiling of intact isoflavone metabolites by high-performance liquid chromatography and mass spectrometric identification of flavone glycosides daidzin and genistin in human plasma after administration of kinako.

    Science.gov (United States)

    Hosoda, Kaori; Furuta, Takashi; Yokokawa, Akitomo; Ogura, Kenichiro; Hiratsuka, Akira; Ishii, Kazuo

    2008-08-01

    The roles of isoflavones in the prevention of several hormone-dependent cancers and osteoporosis are of great interest. Despite many pharmacokinetics studies of the isoflavones, the actual types of conjugates circulating in the body and the position(s) of conjugation sites on the flavone skeleton are still uncertain because, in general, conjugated compounds in biological fluids have been evaluated by measuring the free aglycones obtained after selective enzymatic hydrolysis. Using an high-performance (HPLC)-UV-diode-array detector (DAD) method combined with solid-phase extraction, we have obtained HPLC profiles of isoflavone glycosides [daidzin (Din) and genistin (Gin)] and of intact isoflavone metabolites in human plasma: daidzein, genistein, daizein-7-glucuronide, daidzein-4'-glucuronide, genistein-7-glucuronide, genistein-4'-glucuronide, daidzein-7-sulfate, daidzein-4'-sulfate, genistein-7-sulfate, and genistein-4'-sulfate. We investigated the plasma profile of intact isoflavone metabolites in plasma obtained 1 to-7 h after orally administration of 50 g of kinako (baked soybean powder) to two healthy volunteers. The results of DAD analysis indicated that the main isoflavone metabolite peaks were identified on the HPLC chromatogram. Furthermore, the intact glycosides Din and Gin were detected in 1-h plasma samples by their positive electrospray ionization mass spectra, demonstrating that the glycosides Din and Gin can be absorbed from the gut.

  15. Ovariectomy lowers urine levels of unconjugated (+)-catechin, (-)-epicatechin, and their methylated metabolites in rats fed grape seed extract.

    Science.gov (United States)

    Cutts, John K; Peavy, Thomas R; Moore, Doyle R; Prasain, Jeevan; Barnes, Stephen; Kim, Helen

    2013-12-01

    Abstract Steroid hormones modulate expression of enzymes that metabolize xenobiotics, including dietary supplements. Half of the human population undergoes menopause, yet the effect of this age-related loss of ovarian steroid hormones on the metabolism of dietary supplements has yet to be determined. Grape seed extract (GSE) is a dietary supplement comprised of monomeric and oligomeric catechins and has health benefits in models of age-related diseases. We hypothesized that surgically-induced loss of ovarian hormones would increase methylation, glucuronidation, and/or sulfation of the grape seed polyphenols (+)-catechin and (-)-epicatechin. Fourteen-week-old spontaneously hypertensive rats (SHRs) were ovariectomized (OVX) or sham-OVX. At 17 weeks of age, SHRs were gavaged with vehicle (water) or GSE (300 mg/kg body weight) once daily for 6 days. Urinary excretion of (+)-catechin, (-)-epicatechin, and their metabolites was analyzed by liquid chromatography-mass spectrometry. Although total urinary output of (+)-catechin, (-)-epicatechin, and their methylated metabolites was unaffected by OVX, the amounts of (+)-catechin, (-)-epicatechin and their methylated metabolites that were not conjugated with glucuronic acid or sulfate were lowered by OVX. Specifically, urine from OVX SHRs administered GSE contained 30% higher proportions (91.8% vs. 62.3%) of glucuronidated (+)-catechin and (-)-epicatechin and glucuronidated methyl (+)-catechin and methyl (-)-epicatechin than urine from sham-OVX SHRs. However, there were no differences in urinary levels of total methylated or sulfated catechins in OVX SHRs. This is the first quantitative characterization of metabolites of grape seed polyphenols in a model of menopause; it indicates that ovariectomy causes either an increase in expression and/or activity of select uridine 5'-diphospho-glucuronosyltransferase(s).

  16. Plasma levels of catecholamines and asymmetric dimethylarginine levels as predictive values of mortality among hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Dziedzic Marcin

    2014-06-01

    Full Text Available The aim of the study was to assess plasma concentration of catecholamines and asymmetric dimethyl arginine levels and a possible relationship to predict the mortality rates among hemodialysis patients. The study population comprised 27 subjects, aged 65-70 years. Each patient underwent dialysis thrice a week. Furthermore, the median duration of hemodialysis was 3.5 years. Based on the conducted research, it can be concluded that the concentrations of adrenaline and the level of asymmetric dimethylarginine have predictive value of mortality among hemodialysis patients. Of note, lowering plasma asymmetric dimethylarginine concentration may represent therapeutic target for prevention of progressive renal damage.

  17. Analysis of Plasma Homocysteine Levels in Patients with Unstable Angina

    Directory of Open Access Journals (Sweden)

    José Roberto Tavares

    2002-08-01

    Full Text Available OBJECTIVE - To determine the prevalence of hyperhomocystinemia in patients with acute ischemic syndrome of the unstable angina type. METHODS - We prospectively studied 46 patients (24 females with unstable angina and 46 control patients (19 males, paired by sex and age, blinded to the laboratory data. Details of diets, smoking habits, medication used, body mass index, and the presence of hypertension and diabetes were recorded, as were plasma lipid and glucose levels, C-reactive protein, and lipoperoxidation in all participants. Patients with renal disease were excluded. Plasma homocysteine was estimated using high-pressure liquid chromatography. RESULTS - Plasma homocysteine levels were significantly higher in the group of patients with unstable angina (12.7±6.7 µmol/L than in the control group (8.7±4.4 µmol/L (p<0.05. Among males, homocystinemia was higher in the group with unstable angina than in the control group, but this difference was not statistically significant (14.1±5.9 µmol/L versus 11.9±4.2 µmol/L. Among females, however, a statistically significant difference was observed between the 2 groups: 11.0±7.4 µmol/L versus 6.4±2.9 µmol/L (p<0.05 in the unstable angina and control groups, respectively. Approximately 24% of the patients had unstable angina at homocysteine levels above 15 µmol/L. CONCLUSION - High homocysteine levels seem to be a relevant prevalent factor in the population with unstable angina, particularly among females.

  18. Nanostructure imaging mass spectrometry: the role of fluorocarbons in metabolite analysis and yoctomole level sensitivity.

    Science.gov (United States)

    Kurczy, Michael E; Northen, Trent R; Trauger, Sunia A; Siuzdak, Gary

    2015-01-01

    Nanostructure imaging mass spectrometry (NIMS) has become an effective technology for generating ions in the gas phase, providing high sensitivity and imaging capabilities for small molecules, metabolites, drugs, and drug metabolites. Specifically, laser desorption from the nanostructure surfaces results in efficient energy transfer, low background chemical noise, and the nondestructive release of analyte ions into the gas phase. The modification of nanostructured surfaces with fluorous compounds, either covalent or non-covalent, has played an important role in gaining high efficiency/sensitivity by facilitating analyte desorption from the nonadhesive surfaces, and minimizing the amount of laser energy required. In addition, the hydrophobic fluorinated nanostructure surfaces have aided in concentrating deposited samples into fine micrometer-sized spots, a feature that further facilitates efficient desorption/ionization. These fluorous nanostructured surfaces have opened up NIMS to very broad applications including enzyme activity assays and imaging, providing low background, efficient energy transfer, nondestructive analyte ion generation, super-hydrophobic surfaces, and ultra-high detection sensitivity.

  19. Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage

    NARCIS (Netherlands)

    Michels, M.; Japtok, L.; Alisjahbana, B.; Wisaksana, R.; Sumardi, U.; Puspita, M.; Kleuser, B.; Mast, Q. de; Ven, A.J.A.M. van der

    2015-01-01

    BACKGROUND: A transient endothelial hyperpermeability is a hallmark of severe dengue infections. Sphingosine-1-phosphate (S1P) maintains vascular integrity and protects against plasma leakage. We related plasma S1P levels to dengue-induced plasma leakage and studied mechanisms that may underlie the

  20. Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy.

    Science.gov (United States)

    Cintron, Dahima; Beckman, John P; Bailey, Kent R; Lahr, Brian D; Jayachandran, Muthuvel; Miller, Virginia M

    2017-05-01

    Alterations in sleep quality and metabolism during menopause are improved by menopausal hormone therapy (MHT). The mechanisms mediating these effects remain unclear. Orexin A (OxA) is a neuro-peptide that regulates sleep/wakefulness, food intake and metabolism. This study examined changes in plasma OxA levels during and after treatment in women from the Kronos Early Estrogen Prevention Study (KEEPS). KEEPS randomized women within three years of menopause to: oral conjugated equine estrogen (o-CEE, 0.45mg/day), transdermal 17β estradiol (t-E2, 50μg/day), or placebo pills and patches for four years. Plasma OxA levels were measured by enzyme immunoassays in fasting blood samples collected annually from KEEPS participants at Mayo Clinic during and three years after MHT. Changes in menopausal symptoms and plasma OxA levels were assessed for treatment differences. During treatment, OxA levels increased more in women randomized to o-CEE compared with the other groups. Women randomized to either form of MHT demonstrated smaller increases in BMI than those on placebo. Insomnia severity decreased similarly among treatment groups. However, neither changes in sleep nor changes in BMI correlated with changes in plasma OxA levels. Changes in waist circumference correlated positively with changes in plasma OxA levels three years after discontinuation of study treatments. Although OxA levels increased only in women randomized to o-CEE, these changes did not correlate with changes in sleep quality or BMI. The modest correlation of OxA levels with waist circumference once study treatments were discontinued suggests that OxA may be modulated through multiple intermediary pathways affected by metabolites of 17β-estradiol. Clinical Trial Registration for KEEPS: NCT00154180. Copyright © 2017. Published by Elsevier B.V.

  1. Multi-level molecular modelling for plasma medicine

    Science.gov (United States)

    Bogaerts, Annemie; Khosravian, Narjes; Van der Paal, Jonas; Verlackt, Christof C. W.; Yusupov, Maksudbek; Kamaraj, Balu; Neyts, Erik C.

    2016-02-01

    Modelling at the molecular or atomic scale can be very useful for obtaining a better insight in plasma medicine. This paper gives an overview of different atomic/molecular scale modelling approaches that can be used to study the direct interaction of plasma species with biomolecules or the consequences of these interactions for the biomolecules on a somewhat longer time-scale. These approaches include density functional theory (DFT), density functional based tight binding (DFTB), classical reactive and non-reactive molecular dynamics (MD) and united-atom or coarse-grained MD, as well as hybrid quantum mechanics/molecular mechanics (QM/MM) methods. Specific examples will be given for three important types of biomolecules, present in human cells, i.e. proteins, DNA and phospholipids found in the cell membrane. The results show that each of these modelling approaches has its specific strengths and limitations, and is particularly useful for certain applications. A multi-level approach is therefore most suitable for obtaining a global picture of the plasma-biomolecule interactions.

  2. Plasmodium falciparum spermidine synthase inhibition results in unique perturbation-specific effects observed on transcript, protein and metabolite levels

    CSIR Research Space (South Africa)

    Becker, JVW

    2010-01-01

    Full Text Available :235 http://www.biomedcentral.com/1471-2164/11/235 Open AccessR E S E A R C H A R T I C L E Research articlePlasmodium falciparum spermidine synthase inhibition results in unique perturbation-specific effects observed on transcript, protein... and metabolite levels John VW Becker†1, Linda Mtwisha†1, Bridget G Crampton1, Stoyan Stoychev1, Anna C van Brummelen1, Shaun Reeksting2, Abraham I Louw2, Lyn-Marie Birkholtz2 and Dalu T Mancama*1 Abstract Background: Plasmodium falciparum, the causative agent...

  3. Atomic properties in hot plasmas from levels to superconfigurations

    CERN Document Server

    Bauche, Jacques; Peyrusse, Olivier

    2015-01-01

    This book is devoted to the calculation of hot-plasma properties which generally requires a huge number of atomic data. It is the first book that combines information on the details of the basic atomic physics and its application to atomic spectroscopy with the use of the relevant statistical approaches. Information like energy levels, radiative rates, collisional and radiative cross-sections, etc., must be included in equilibrium or non-equilibrium models in order to describe both the atomic-population kinetics and the radiative properties. From the very large number of levels and transitions involved in complex ions, some statistical (global) properties emerge. The book presents a coherent set of concepts and compact formulas suitable for tractable and accurate calculations. The topics addressed are: radiative emission and absorption, and a dozen of other collisional and radiative processes; transition arrays between level ensembles (configurations, superconfigurations); effective temperatures of configurat...

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

    Science.gov (United States)

    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.

  5. Increased plasma concentrations of vitamin D metabolites and vitamin D binding protein in women using hormonal contraceptives: a cross-sectional study

    DEFF Research Database (Denmark)

    Liendgaard, Ulla Kristine Møller; við Streym, Susanna; Jensen, Lars Thorbjørn

    2013-01-01

    UNLABELLED: Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D...... winter season. Compared with non-users (n = 23), users of HC (n = 52) had significantly higher plasma concentrations of 25-hydroxyvitamin D (25OHD) (median 84 interquartile range: [67-111] vs. 70 [47-83] nmol/L, p = 0.01), 1,25-dihydroxyvitamin D (1,25(OH)2D) (198 [163-241] vs. 158 [123-183] pmol/L, p...... = 0.01) and VDBP (358 [260-432] vs. 271 [179-302] µg/mL, p OH)2D) were not significantly different between groups (p > 0.10). There were no significant differences in indices of calcium homeostasis (plasma concentrations of calcium...

  6. Quantitation of Cotinine and its Metabolites in Rat Plasma and Brain Tissue by Hydrophilic Interaction Chromatography Tandem Mass Spectrometry (HILIC-MS/MS)

    Science.gov (United States)

    Li, Pei; Beck, Wayne D.; Callahan, Patrick M.; Terry, Alvin V.; Bartlett, Michael G.

    2014-01-01

    In this work, we developed a sensitive method to quantify cotinine (COT), norcotinine (NCOT), trans-3′-hydroxycotinine (OHCOT) and cotinine-N-oxide (COTNO) in rat plasma and brain tissue, using solid phase extraction (SPE), hydrophilic interaction liquid chromatography (HILIC) and tandem mass spectrometry (MS/MS). The linear range was 1–100 ng/ml for each analyte in rat plasma and brain homogenate (3–300 ng/g brain tissue). The method was validated with precision within 15% relative standard deviation (RSD) and accuracy within 15% relative error (RE). Stable isotope-labeled internal standards (IS) were used for all the analytes to achieve good reproducibility, minimizing the influence of recovery and matrix effects. This method can be used in future studies to simultaneously determine the concentrations of COT and three major metabolites in rat plasma and brain tissue. PMID:23022114

  7. Plasma zinc antioxidant vitamins, glutathione levels and total antioxidant activity in oral leukoplakia

    Directory of Open Access Journals (Sweden)

    Subhash Chandra Bose

    2012-01-01

    Full Text Available Background: Leukoplakia is a common, potentially premalignant lesion with malignant transformation rate from 1 to 17% with highest transformation rate for the lesions on the floor of the mouth, soft palate and tongue. One of the main etiological factors is consuming areca nut and its commercial preparations which generate high levels of reactive oxygen species during their metabolism. So the aim of this present study is to evaluate the plasma levels of antioxidant vitamins, antioxidant mineral zinc, glutathione and total antioxidant status (TAS in leukoplakia patients. Materials and Methods: For this cross-sectional study, we selected 23 newly diagnosed oral leukoplakia patients of both sexes within the age group 28-40 years and the same number of age and sex matched healthy individuals without having history of any systemic illness were selected as control group. In both the groups, we measured plasma antioxidant vitamins A, C, E, antioxidant mineral zinc, GSH and TAS. Student′s t test was applied and the P value <0.001 was considered as statistically significant. Results: We observed very low levels of antioxidant vitamins A, C, E, antioxidant mineral zinc and antioxidant metabolite GSH (P<0.001 and at the same time we also observed very poor (TAS (P<0.001 in leukoplakia patients when compared to patients in control group. Conclusion: The consumption of tobacco or areca quid which contains high copper levels creates an oxidative stress like environment during their metabolism, might play a major role in causation and propagation of oral leukoplakia.

  8. Plasma lactoferrin level as a predictor to endothelial dysfunction in patients with obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Abir Zakaria

    2013-01-01

    Conclusion The present study showed that low circulating plasma lactoferrin levels in OSA patients independently predict endothelial dysfunction as assessed by FMD%. High BMI in OSA patients negatively influences plasma lactoferrin levels unrelated to other OSA severity predictors.

  9. Effects of Various Levels of Oxidized Oil on Performance, Egg Quality and Some Blood Metabolites in Laying Hens

    Directory of Open Access Journals (Sweden)

    AA Saki

    2016-06-01

    Full Text Available The influence of dietary oxidized oil was studied on laying hen performance, egg quality and blood metabolites.  Experiment was conducted on 160 laying hens (Hy-Line W-36, 54-61 wk of age in a completely randomized design with five treatments and four replicated cages containing eight birds per cage. Dietary treatments replaced fresh soybean oil in the control diet (3% fresh soybean oil, 15.25% crude protein, and 2858 Kcal/kg metabolizable energy with 0, 25, 50, 75 and 100% oxidized oil. Egg production and egg weight were recorded daily and feed intake, feed conversion ratio, and egg mass were calculated weekly. Egg quality traits were recorded on a biweekly basis. Hen’s body weight was measured individually at the beginning and end of the experiment. Serum metabolites were determined at the end of the experiment. There was a significant difference between diets with different oxidized oil levels in egg weight, egg mass, Egg production, and feed conversion ratio (P < 0.05. Feed intake was not affected by dietary treatments. There was no significant difference between oxidized oil levels on blood serum triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein and very low-density lipoprotein. Malondialdehyde of the liver was not affected by oxidized oils. The results of this study have clearly demonstrated that maximum 25% oxidized oil could be replaced by fresh oil in the diets without any adverse effect on the performance of laying hens.

  10. Quantitation of anacetrapib, stable-isotope labeled-anacetrapib (microdose), and four metabolites in human plasma using liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Chavez-Eng, C M; Lutz, R W; Li, H; Goykhman, D; Bateman, K P; Woolf, E

    2016-02-01

    An ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of (4S,5R)-5-[3,5-bis (trifluoromethyl)phenyl]-3-{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl] methyl}-4-methyl-1,3-oxazolidin-2-one (anacetrapib, I) and [(13)C5(15)N]-anacetrapib, II in human plasma has been developed to support a clinical study to determine the absolute bioavailability of I. The analytes and the stable-isotope labeled internal standard ([(13)C7(15)N(2)H7]-anacetrapib, III) were extracted from 100μL of human plasma by liquid-liquid extraction using 20/80 isopropyl alcohol/hexane (v/v). The chromatographic separation of the analytes was achieved using Waters BEH Shield RP 18 (50×2.1mm×1.7μm) column and mobile phase gradient of 0.1% formic acid in water (Solvent A) and 0.1% formic acid in acetonitrile (Solvent B) at 0.6mL/min flow rate. The MS/MS detection was performed on AB Sciex 5000 or AB 5500 in positive electrospray ionization mode, operated in selected reaction monitoring mode. The assay was validated in the concentration range 1-2000ng/mL for I; and a lower curve range, 0.025-50ng/mL for II. In addition to the absolute bioavailability determination, it was desired to better elucidate the pharmacokinetic behavior of several hydroxylated metabolites of I. Toward this end, two exploratory assays for the hydroxy metabolites of I were qualified in the concentration range 0.5-500ng/mL. All metabolites were separated on a Supelco Ascentis Express Phenyl-Hexyl (50×2.1mm, 2.7μm) column. Metabolite M4 was analyzed in the negative mode with a mobile phase consisting of a gradient mixture of water (A) and acetonitrile (B). The other three metabolites, M1-M3 were analyzed in the positive mode using a mobile phase gradient of water with 0.1% formic acid (A) and acetonitrile with 0.1% formic acid (B). The assays were utilized to support a clinical study in which a microdosing approach was used to

  11. Rapid determination of PEGylated liposomal doxorubicin and its major metabolite in human plasma by ultraviolet–visible high-performance liquid chromatography

    Science.gov (United States)

    Chin, David L.; Lum, Bert L.; Sikic, Branimir I.

    2014-01-01

    A high-performance liquid chromatographic method was developed for the quantification of doxorubicin derived from PEGylated liposomal doxorubicin (Doxil) and its major metabolite in human plasma. This method utilizes Triton X-100 to disperse the liposome, followed by a protein precipitation step with 5-sulfosalicylic acid. Analytes in the resultant supernatant are separated on a Discovery RP amide C16 column (250×3 mm I.D., 5 µm) using an isocratic elution with a mobile phase consisting of 0.05 M sodium acetate (pH 4.0) and acetonitrile (72:28). The retention times for doxorubicin and the internal standard daunorubicin were 4.8 and 10.1 min, respectively. The column eluate was monitored by UV-visible detection at 487 nm. The determination of doxorubicin was found to be linear in the range of 1.0 ng/mL to 25 µg/mL, with intra-day and inter-day coefficients of variation and percent error ≤10%. The recovery of doxorubicin from plasma was >69.3%, with a liposomal dispersion efficiency of >95.7%. Our analytical method for free and PEGylated doxorubicin in human plasma is rapid, avoids organic extractions, and maintains sensitivity for the parent compound and its major metabolite, doxorubicinol. PMID:12361740

  12. Effects of exercise on plasma adiponectin levels in athletes

    Directory of Open Access Journals (Sweden)

    Popović Mirjana

    2016-01-01

    Full Text Available Adipose tissue is an endocrine organ which releases biologically active adipokines. Adiponectin, an adipocyte-derived protein structurally similar to complement 1q, plays a significant role in metabolic disorders, due to its insulin sensitizing, anti-inflammatory and anti-atherogenic properties. AdipoR1 and AdipoR2, mediate the metabolic actions of adiponectin by activating adenosine monophosphate-activated protein kinase (AMPK and peroxisome proliferator-activated receptors- alpha (PPAR-α which leads to an increase in fatty acid combustion and energy consumption, fatty acid oxidation and glucose uptake in myocytes and reduces gluconeogenesis and thus leads to increased insulin sensitivity. Plasma adiponectin level is affected by multiple factors: gender (females have higher plasma adiponectin levels, obesity-linked diseases (metabolic syndrome, diabetes mellitus type 2 and atherosclerosis are associated with lower adiponectin levels, lifestyle -including exercise. Yet, to date, little is known about the response of adiponectin concentrations to exercise and, in particular, the response of this hormone to training in population of athletes. The aim of this review is to overview the published evidence for the effects of exercise on adiponectin levels in athletes. Adiponectin concentration presents a delayed increase (30 min after short-term intense performance, by athletes, both male and female. It seems that adiponectin concentrations do not change in response to long-term exercise. No significant difference was found in total adiponectin and/or high-molecular weight (HMW oligomers in long-term effects of high physical training in athletes. Adiponectin can serve to monitor training loads and the establishment of individual limit values of training loads. Further studies are needed to clarify possible mechanisms by which adiponectin might influence energy homeostasis during heavy training in elite athletes.

  13. Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

    National Research Council Canada - National Science Library

    Hagman, R; Kindahl, H; Lagerstedt, A-S

    2006-01-01

    .... Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α...

  14. Influence of parenting style on the offspring's behaviour and CSF monoamine metabolite levels in crossfostered and noncrossfostered female rhesus macaques.

    Science.gov (United States)

    Maestripieri, Dario; McCormack, Kai; Lindell, Stephen G; Higley, J Dee; Sanchez, Mar M

    2006-11-25

    We investigated the association between variation in parenting style and the offspring's behaviour and CSF monoamine metabolite (5-HIAA, HVA, and MHPG) levels in rhesus monkeys. Study subjects were 25 two-year-old females reared by their biological mothers and 15 same-aged females that were crossfostered at birth and reared by unrelated mothers. Subjects that were rejected more by their mothers in the first 6 months of life engaged in more solitary play and had lower CSF concentrations of 5-HIAA than subjects that were rejected less. The relation between these variables was generally similar in crossfostered and noncrossfostered females. CSF levels of 5-HIAA were negatively correlated with rates of scratching, a behavioural indicator of anxiety. These results suggest that that early exposure to high rates of maternal rejection can result in higher anxiety later in life, and that this effect may be mediated by serotonergic mechanisms. Variation in maternal protectiveness did not affect offspring behaviour and neither protectiveness nor rejection affected CSF levels of HVA and MHPG. CSF levels of MHPG, however, were negatively correlated with solitary play behaviour and avoidance of other individuals, suggesting that individuals with lower CSF MHPG were more fearful and socially phobic than those with higher CSF MHPG. Taken together, these findings suggest that individual differences in anxiety and fearfulness in young rhesus monkeys are accounted for, at least in part, by variation in CSF levels of monoamine metabolites, and that the development of brain monoamine systems, particularly serotonin, can be affected by early exposure to variable maternal behaviour.

  15. Simultaneous determination of ledipasvir, sofosbuvir and its metabolite in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Pan, Chenwei; Chen, Yongping; Chen, Weilai; Zhou, Guangyao; Jin, Lingxiang; Zheng, Yi; Lin, Wei; Pan, Zhenzhen

    2016-01-01

    In this work, a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of ledipasvir, sofosbuvir and its metabolite GS-331007 in rat plasma was developed. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 889.8→130.1 for ledipasvir, m/z 530.3→243.1 for sofosbuvir, m/z 261.5→113.1 for GS-331007 and m/z 285.2→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 2-500ng/mL for ledipasvir, 10-2000ng/mL for sofosbuvir and 10-2000ng/mL for GS-331007. Total time for each chromatography was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)sofosbuvir and GS-331007 in rats.

  16. Differences in intestinal microbial metabolites in laying hens with high and low levels of repetitive feather-pecking behavior.

    Science.gov (United States)

    Meyer, Beatrice; Zentek, Jürgen; Harlander-Matauschek, Alexandra

    2013-02-17

    Feather pecking in laying hens is a serious behavioral problem and is often associated with feather eating. There is some evidence that ingested feathers affect gut function. The aim of the present study was to explore whether differences in intestinal microbial metabolites in laying hens with high and low levels of repetitive feather-pecking behavior exist. Sixty high feather-pecking birds (H) and sixty low feather-pecking birds (L) of the White Leghorn breed were used for behavioral recordings of feather pecking. Feather pecking activity was observed for 5 weeks, after which 22 H birds with the highest and 22 L birds with the lowest feather pecking activity were chosen. The number of whole feathers and feather parts in the gizzard and intestinal microbial metabolites in the ileum and ceca of these laying hens was examined. Biogenic amines, short-chain fatty acids, ammonia and lactate were measured as microbial metabolites. A higher number of feather parts and particles were found in H than in L birds. Putrescine and cadaverine concentrations were higher in the ileum of the hens with low pecking activity (P<0.001 and P=0.012). In the cecum the amounts of l-lactate, d-lactate and total lactate and SCFA were higher in H birds (P=0.007, P=0.005, P=0.006, and P<0.001). Acetate, i-butyrate, i-valeriate and n-valeriate all displayed significantly higher molar ratios in the cecal contents of L birds (P=0.001, P=0.003, P=0.001, and P<0.001). Propionate and n-butyrate showed higher molar ratios in H birds (P<0.001 and P=0.034). Ammonia was higher in the ileum and cecum of the L birds (P<0.001 and P=0.004). For the first time, this study shows that birds with high and low numbers of repetitive pecking movements to the plumage of other birds differ in their intestinal microbial metabolism. Further experiments should be conducted to investigate whether these differences alter behavior in H and L feather pecking birds. The present results, however, open new avenues of research

  17. Lower Vitamin D Metabolites Levels Were Associated With Increased Coronary Artery Diseases in Type 2 Diabetes Patients in India

    Science.gov (United States)

    Adela, Ramu; Borkar, Roshan M; Bhandi, Murali Mohan; Vishwakarma, Gayatri; Reddy, P. Naveen Chander; Srinivas, R.; Banerjee, Sanjay K

    2016-01-01

    The purpose of the present study was to measure six vitamin D metabolites and to find the association between vitamin D deficiency and coronary artery diseases in diabetes (T2DM_CAD). Four groups [control (n = 50), type 2 diabetes (T2DM, n = 71), coronary artery diseases (CAD, n = 28), T2DM_CAD (n = 38)] of total 187 subjects were included in the study. Six vitamin D metabolites (D2, D3, 25(OH)D2, 25(OH)D3, 1,25(OH)2D2, 1,25(OH)2D3), total 25(OH)D and total 1,25(OH)2D were measured by UPLC/APCI/HRMS method in these subjects. Although all the vitamin D metabolites were significantly decreased in T2DM_CAD as compared to both control and T2DM subjects (p < 0.05), only two metabolites i.e., 25(OH)D3 and total 25(OH)D were significantly (p < 0.05) decreased in the T2DM subjects as compared with the control subjects (p < 0.05). Vitamin D3, 1,25(OH)2D2, 25(OH)D, and 1,25(OH)2D levels were significantly decreased in T2DM_CAD subjects as compared with CAD subjects (p < 0.05). Further, multiple logistic regression analysis revealed that total 25(OH)D and total 1,25(OH)2D can be used to predict T2DM (OR 0.82.95% CI 0.68–0.99; p = 0.0208) and T2DM with CAD (OR 0.460, 95% CI 0.242–0.874; p = 0.0177), respectively. Our data concludes that lower concentration of 1,25(OH)2D is associated with type 2 diabetes coexisting with coronary artery diseases in South Indian subjects. PMID:27883024

  18. Longitudinal relationships between fluid status, inflammation, urine volume and plasma metabolites of icodextrin in patients randomized to glucose or icodextrin for the long exchange.

    Science.gov (United States)

    Davies, Simon J; Garcia Lopez, Elvia; Woodrow, Graham; Donovan, Kieron; Plum, Jorg; Williams, Paul; Johansson, Ann Catherine; Bosselmann, Hans-Peter; Heimburger, Olof; Simonsen, Ole; Davenport, Andrew; Lindholm, Bengt; Tranaeus, Anders; Divino Filho, Jose C

    2008-09-01

    Randomized trials have shown that icodextrin reduces the volume of extra-cellular fluid (ECFv) with variable effects on residual renal function. To explore this fluid shift and its possible mechanisms in more detail, prospectively collected data from one such trial, including measures of inflammation (C-reactive protein, tumour necrosis factor-alpha, albumin and low and high molecular weight hyaluronan) ANP (atrial naturetic peptide), an indirect marker of intra-vascular volume, plasma concentrations of icodextrin metabolites and alpha-amylase activity were analysed. 50 patients were randomized to either 2.27% glucose or icodextrin (n = 28) for a long exchange following a month run in. Blood samples were obtained at -1, 0, 3 and 6 months, coincident with measurements of urine volume and fluid status. In both randomized groups, a significant correlation between the fall in ECFv and the decline in urine volume was observed (P = 0.001), although the relative drop in urine volume for patients randomized to icodextrin tended to be less. At baseline, ANP was higher in patients with proportionately more ECFv for a given body water or height. Icodextrin patients had non-significantly higher ANP levels at baseline, whereas by 3 (P = 0.026) and 6 months (P = 0.016) these differed between groups due to divergence. There was a correlation between increasing ANP and reduced ECF at 3 months, r = -0.46, P = 0.007, in patients randomized to icodextrin, but not glucose. There were no relationships between fluid status and any inflammatory markers at any point of the study, with the exception of albumin at baseline, r = -0.39, P = 0.007. Amylase activities at -1 month and baseline were highly correlated, r = 0.89, P volume, fluid or inflammatory status. This analysis supports observational data that changes in fluid status are associated with changes in urine volume. Icodextrin was not associated with a greater fall in urine output despite its larger effect on ECFv. Changes in fluid

  19. Development of a high throughput 96-well plate sample preparation method for the determination of trileptal (oxcarbazepine) and its metabolites in human plasma.

    Science.gov (United States)

    Souppart, C; Decherf, M; Humbert, H; Maurer, G

    2001-10-05

    A high throughput preparation method for the determination of trileptal (oxcarbazepine, OXC) and its mono (MHD) and dihydroxy (DHD) metabolites in human plasma, using 96-well plate technology, has been developed and validated according to international regulatory requirements. Preparation of plasma samples (50 microl) containing the compounds to be analysed involved solid-phase extraction (SPE) on Empore C18 96-well SPE plates. Eluates from the plate were injected onto a reversed-phase column (Hypersil C18,3 microm) with UV detection at 210 nm. Detector response was linear over the ranges 0.2-10, 0.1-200 and 0.1-20 micromol/l, for OXC, MHD and DHD, respectively, with relative standard deviations from 1 to 10% and mean accuracies within 4% of the nominal values (number of standard curves=3 in duplicate). The limits of quantitation were 0.2, 0.1 and 0.1 micromol/l, respectively. The overall mean accuracies ranged from 96 to 106% and precision was in the range 4 to 11%. Cross validation indicated no significant difference between plasma concentrations obtained using the 96-well method and the previous method using a traditional SPE method with a 50 mg C18 cartridge. About a threefold increase in sample throughput and a twofold decrease of plasma volume required for the assays, were the main advantages obtained from the previous method. The method was applied for the determination of 3000 plasma samples from clinical studies.

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

    Science.gov (United States)

    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.

  1. The role of cardiorespiratory fitness on plasma lipid levels.

    Science.gov (United States)

    Parto, Parham; Lavie, Carl J; Swift, Damon; Sui, Xuemei

    2015-11-01

    Dyslipidemia is a treatable risk factor for cardiovascular disease. Epidemiological studies have demonstrated the importance of treatment for abnormalities in total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. Aside from pharmacotherapy, exercise and cardio-respiratory fitness have been shown to have beneficial effects on decreasing cardiovascular disease risk. Even though previous data regarding the benefits of exercise on plasma lipids have been somewhat conflicting, numerous studies have demonstrated that exercise increases HDL-cholesterol and reduces the triglyceride levels. Also, smaller, more atherogenic LDL particles seem to decrease with increases in cardio-respiratory fitness and exercise, and favorable blood lipid profiles seem to persist longer through the adult life span.

  2. [Plasma taurine levels in patients with esophagus cancer].

    Science.gov (United States)

    Lamônica-Garcia, Vânia Cristina; Marin, Flávia Andréa; Lerco, Mauro Masson; Moreto, Fernando; Henry, Maria Aparecida Coelho Arruda; Burini, Roberto Carlos

    2008-01-01

    The esophagus cancer-host has a two way close relationship as seen in its sulphur-amino acid metabolism. Taurine one of these compounds has ubiquous role in host defense and other physiological mechanisms related to survival. To study the plasma levels of taurine and its precursors in patients with esophagus cancer. In a sectional design both groups, patients (n = 16, 43-73 yrs old) and healthy controls (n = 20, 27-65 yrs old) were assessed for anthropometry, body-weight lost, hematology (Hb, Ht, total leukocytes and lymphocyte counts), general biochemistry (albumin, glucose, lipids and aminotransferases) and chromatographic analysis for taurine, cysteine, and homocysteine. The survival time was registered there since from the clinical-histopathological diagnosis. All participants had a written ethical consent for the research. The cancer patients were predominantly, white males of low social economic class, with spinocellular carcinoma stage IV located at upper 3rd half of them presented hypoalbuminemia and 16% referred significant body-weight loss. The patients showed statistically lower values of Hb, Ht, total and HDL cholesterol and cysteine and significantly higher values of taurine, homocysteine and aminotransferases than healthy controls. A positive relationship was found between taurine and either TLC (r = 0.50) and survival (r = 0.81). Lower plasma cysteine along with higher levels of taurine and homocysteine and the positive direct association of taurine with indications of survival suggest an effective role of this compound and therefore a prospective special nutritional care in its precursors (cysteine, methionine and B vitamins) of these patients.

  3. Development and Validation of an HPLC Method for Simultaneous Quantification of Clopidogrel Bisulfate, Its Carboxylic Acid Metabolite, and Atorvastatin in Human Plasma: Application to a Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Octavian Croitoru

    2015-01-01

    Full Text Available A simple, sensitive, and specific reversed phase liquid chromatographic method was developed and validated for simultaneous quantification of clopidogrel, its carboxylic acid metabolite, and atorvastatin in human serum. Plasma samples were deproteinized with acetonitrile and ibuprofen was chosen as internal standard. Chromatographic separation was performed on an BDS Hypersil C18 column (250 × 4.6 mm; 5 μm via gradient elution with mobile phase consisting of 10 mM phosphoric acid (sodium buffer solution (pH = 2.6 adjusted with 85% orthophosphoric acid : acetonitrile : methanol with flow rate of 1 mL·min−1. Detection was achieved with PDA detector at 220 nm. The method was validated in terms of linearity, sensitivity, precision, accuracy, limit of quantification, and stability tests. Calibration curves of the analytes were found to be linear in the range of 0.008–2 μg·mL−1 for clopidogrel, 0.01–4 μg·mL−1 for its carboxylic acid metabolite, and 0.005–2.5 μg·mL−1 for atorvastatin. The results of accuracy (as recovery with ibuprofen as internal standard were in the range of 96–98% for clopidogrel, 94–98% for its carboxylic acid metabolite, and 90–99% for atorvastatin, respectively.

  4. HPLC-MS analysis of Schisandra lignans and their metabolites in Caco-2 cell monolayer and rat everted gut sac models and in rat plasma

    Directory of Open Access Journals (Sweden)

    Jia-ming Yang

    2011-06-01

    Full Text Available The absorption profiles of Schisandra chinensis were evaluated using the human Caco-2 cell monolayer and rat everted gut sac models, as well as in rat plasma. By analyzing the chromatographic and MSn characteristics of individual peak acquired by HPLC-DAD-APCI-MSn determination, thirteen lignans were identified as the major in vitro absorbable components of the Schisandra extract. Most of these compounds were also detected and identified in rat plasma after an oral administration of the Schisandra extract, except for angeloyl(tigloylgomisin H and angeloyl(tigloylgomisin Q, whose structures possess an ester group at the cyclooctadiene ring. In addition, four metabolites, corresponding to the hydroxylation and demethylation products of schisandrin and the hydrolysis derivative of angeloyl(tigloylgomisin Q, were tentatively identified. The results demonstrate that Schisandra lignans are the major absorbable components of this crude drug, and hydroxylation, demethylation and hydrolysis are important metabolic transformations of the absorbable lignans.

  5. Effects of physical exercise on serum levels of serotonin and its metabolite in fibromyalgia: a randomized pilot study.

    Science.gov (United States)

    Valim, Valéria; Natour, Jamil; Xiao, Yangming; Pereira, Abraão Ferraz Alves; Lopes, Beatriz Baptista da Cunha; Pollak, Daniel Feldman; Zandonade, Eliana; Russell, Irwin Jon

    2013-01-01

    To evaluate the effects of aerobic training and stretching on serum levels of serotonin (5HT) and its main metabolite 5-hydroxindolacetic acid (5HIAA). Twenty-two women with FM were randomized into one of two exercise modalities (aerobic walking exercise or stretching exercise) to be accomplished three times a week for 20 weeks. The serum levels of 5HT and 5HIAA were evaluated before and after the exercise program by high performance liquid chromatography (HPLC) with colorimetric detection. Within group analysis (pre-post) showed that serum levels of both 5HT and 5HIAA changed significantly in the aerobic group during the 20-week course of therapy (5HT: P = 0,03; 5HIAA: P = 0,003). In the stretching group, however, no statistically significant change was observed (5HT: P=0,491; 5HIAA: P=0,549). Between group statistical comparisons of laboratory measures disclosed that aerobic training was superior to stretching in that it significantly increased the levels of 5HIAA (F test = 6.61; P = 0.01), but the average difference between groups on the levels of 5HT did not meet significance criteria (F test = 3.42; P = 0.08). Aerobic training increases the 5HIAA and 5HT levels and it could explain why aerobic exercise can improve symptoms in fibromyalgia syndrome patient more than stretching exercise.

  6. Natural carbon isotope abundance of plasma metabolites and liver tissue differs between diabetic and non-diabetic Zucker diabetic fatty rats.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Godin

    Full Text Available BACKGROUND: 'You are what you eat' is an accurate summary for humans and animals when it comes to carbon isotope abundance. In biological material, natural(13C/(12C ratio is subject to minute variations due to diet composition (mainly from ingestion of C3 and C4 metabolism plants and to the discrimination between 'light' and 'heavy' isotopes during biochemical reactions (isotope effects and isotopic fractionation. METHODOLOGY/PRINCIPAL FINDINGS: Carbon isotopic abundance was measured in ZDF (fa/+ and ZDF (fa/fa, (lean and obese-diabetic rats respectively fed the same diet. By analysing plasma metabolites (glucose and non-esterified fatty acids, breath and liver tissue by high-precision isotope ratio mass spectrometry, we demonstrate for the first time statistically distinguishable metabolic carbon isotope abundance between ZDF (fa/+ and ZDF (fa/fa rats based on plasma glucose, palmitic, oleic, linoleic, arachidonic acids and bulk analysis of liver tissue (P<0.005 resulting into clear isotopic fingerprints using principal component analysis. We studied the variation of isotopic abundance between both groups for each metabolite and through the metabolic pathways using the precursor/product approach. We confirmed that lipids were depleted in (13C compared to glucose in both genotypes. We found that isotopic abundance of linoleic acid (C18: 2n-6, even though both groups had the same feed, differed significantly between both groups. The likely reason for these changes between ZDF (fa/+ and ZDF (fa/fa are metabolic dysregulation associated with various routing and fluxes of metabolites. CONCLUSION/SIGNIFICANCE: This work provides evidence that measurement of natural abundance isotope ratio of both bulk tissue and individual metabolites can provide meaningful information about metabolic changes either associated to phenotype or to genetic effects; irrespective of concentration. In the future measuring the natural abundance δ(13C of key metabolites

  7. Nonlinear associations between plasma cholesterol levels and neuropsychological function.

    Science.gov (United States)

    Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I; Rosenberger, William F; Plamadeala, Victoria V; Hosey, Megan M; Waldstein, Shari R

    2016-11-01

    Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as quadratic effect of Total Cholesterol² × Age was identified for Logical Memory II (b = -.0013, p = .039), such that the 70+ group performed best at high and low levels of total cholesterol than at midrange total cholesterol (U-shaped) and the Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  8. Changes in plasma TIMP-1 levels after resection for primary colorectal cancer

    DEFF Research Database (Denmark)

    Frederiksen, C.; Lomholt, A.F.; Davis, G.J.

    2009-01-01

    BACKGROUND: Increased plasma levels of tissue inhibitor of metalloproteinases (TIMP-1) are associated with poor outcome in colorectal cancer (CRC), however postoperative changes in plasma TIMP-1 levels after resections for CRC have not been thoroughly evaluated. MATERIALS AND METHODS: Plasma samp...

  9. Effects of Elevated Atmospheric CO2 on Primary Metabolite Levels in Arabidopsis thaliana Col-0 Leaves: An Examination of Metabolome Data.

    Science.gov (United States)

    Noguchi, Ko; Watanabe, Chihiro K; Terashima, Ichiro

    2015-11-01

    Elevated atmospheric CO(2) concentrations ([CO(2)]) affect primary metabolite levels because CO(2) is a direct substrate for photosynthesis. In several studies, the responses of primary metabolite levels have been examined using Arabidopsis thaliana leaves, but these results have not been comprehensively discussed. Here, we examined metabolome data for A. thaliana accession Col-0 leaves that were grown at elevated [CO(2)] with sufficient nitrogen (N) nutrition. At elevated [CO(2)], starch, monosaccharides and several major amino acids accumulated in leaves. The degree of accumulation depended on whether the rooting medium contained NH(4) (+) or only NO(3) (-). Because low N conditions induce an increase in carbohydrates similar to that of elevated [CO(2)], we compared the responses of primary metabolite levels between elevated [CO(2)] and low N conditions. Levels of the tricarboxylic acid (TCA) cycle-associated organic acids and major amino acids decreased with low N, but not with elevated [CO(2)]. Even at elevated [CO(2)], the low N induced the decreases in the levels of organic acids and major amino acids. A small sink size also affects the primary metabolite response patterns in leaves under elevated [CO(2)] conditions. Thus, care is necessary when interpreting primary metabolite changes in leaves of field-grown plants.

  10. High levels of PAH-metabolites in urine of e-waste recycling workers from Agbogbloshie, Ghana

    Energy Technology Data Exchange (ETDEWEB)

    Feldt, Torsten, E-mail: feldt@bni-hamburg.de [Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht Str. 74, 20359 Hamburg (Germany); Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Moorenstr. 5, 40225 Düsseldorf (Germany); Fobil, Julius N., E-mail: jfobil@ug.edu.gh [Department of Biological, Environmental and Occupational Health Sciences, School of Public Health, University of Ghana, P.O. Box LG13, Legon (Ghana); Wittsiepe, Jürgen [Department of Hygiene, Social and Environmental Medicine, Ruhr-University Bochum, Universitätsstr. 150, 44801 Bochum (Germany); Wilhelm, Michael, E-mail: wilhelm@hygiene.rub.de [Department of Hygiene, Social and Environmental Medicine, Ruhr-University Bochum, Universitätsstr. 150, 44801 Bochum (Germany); Till, Holger, E-mail: holger.till@giz.de [GIZ — Regional Coordination Unit for HIV and TB (GiZ-ReCHT), 32 Cantonment Crescent, Cantonments, Accra (Ghana); Zoufaly, Alexander [Department of Medicine, Section Infectious Diseases and Tropical Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Burchard, Gerd, E-mail: gerd.burchard@bni-hamburg.de [Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht Str. 74, 20359 Hamburg (Germany); Department of Medicine, Section Infectious Diseases and Tropical Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Göen, Thomas, E-mail: thomas.goeen@ipasum.med.uni-erlangen.de [Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Schillerstr. 25/29, 91054 Erlangen (Germany)

    2014-01-01

    The informal recycling of electronic waste (e-waste) is an emerging source of environmental pollution in Africa. Among other toxins, polycyclic aromatic hydrocarbons (PAHs) are a major health concern for exposed individuals. In a cross-sectional study, the levels of PAH metabolites in the urine of individuals working on one of the largest e-waste recycling sites of Africa, and in controls from a suburb of Accra without direct exposure to e-waste recycling activities, were investigated. Socioeconomic data, basic health data and urine samples were collected from 72 exposed individuals and 40 controls. In the urine samples, concentrations of the hydroxylate PAH metabolites (OH-PAH) 1-hydroxyphenanthrene (1-OH-phenanthrene), the sum of 2- and 9-hydroxyphenanthrene (2-/9-OH-phenanthrene), 3-hydroxyphenanthrene (3-OH-phenanthrene), 4-hydroxyphenanthrene (4-OH-phenanthrene) and 1-hydroxypyrene (1-OH-pyrene), as well as cotinine and creatinine, were determined. In the exposed group, median urinary concentrations were 0.85 μg/g creatinine for 1-OH-phenanthrene, 0.54 μg/g creatinine for 2-/9-OH-phenanthrene, 0.99 μg/g creatinine for 3-OH-phenanthrene, 0.22 μg/g creatinine for 4-OH-phenanthrene, and 1.33 μg/g creatinine for 1-OH-pyrene, all being significantly higher compared to the control group (0.55, 0.37, 0.63, 0.11 and 0.54 μg/g creatinine, respectively). Using a multivariate linear regression analysis including sex, cotinine and tobacco smoking as covariates, exposure to e-waste recycling activities was the most important determinant for PAH exposure. On physical examination, pathological findings were rare, but about two thirds of exposed individuals complained about cough, and one quarter about chest pain. In conclusion, we observed significantly higher urinary PAH metabolite concentrations in individuals who were exposed to e-waste recycling compared to controls who were not exposed to e-waste recycling activities. The impact of e-waste recycling on exposure to

  11. Effect of intake on fasting heat production, respiratory quotient and plasma metabolites measured using the washed rumen technique

    Science.gov (United States)

    The objective was to investigate the effect of intake prior to fasting on concentrations of metabolites and hormones, respiratory quotient (RQ) and fasting heat production (HP) using the washed rumen technique and to compare these values with those from the fed state. Six Holstein steers (360 ± 22 k...

  12. Disturbed flow induces systemic changes in metabolites in mouse plasma: a metabolomics study using ApoE⁻/⁻ mice with partial carotid ligation.

    Science.gov (United States)

    Go, Young-Mi; Kim, Chan Woo; Walker, Douglas I; Kang, Dong Won; Kumar, Sandeep; Orr, Michael; Uppal, Karan; Quyyumi, Arshed A; Jo, Hanjoong; Jones, Dean P

    2015-01-01

    Disturbed blood flow (d-flow) occurring in branched and curved arteries promotes endothelial dysfunction and atherosclerosis, in part, by altering gene expression and epigenomic profiles in endothelial cells. While a systemic metabolic change is known to play a role in atherosclerosis, it is unclear whether it can be regulated by local d-flow. Here, we tested this hypothesis by carrying out a metabolomics study using blood plasma samples obtained from ApoE(-/-) mice that underwent a partial carotid ligation surgery to induce d-flow. Mice receiving sham ligation were used as a control. To study early metabolic changes, samples collected from 1 wk after partial ligation when endothelial dysfunction occurs, but before atheroma develops, were analyzed by high-resolution mass spectrometry. A metabolome-wide association study showed that 128 metabolites were significantly altered in the ligated mice compared with the sham group. Of these, sphingomyelin (SM; m/z 703.5747), a common mammalian cell membrane sphingolipid, was most significantly increased in the ligated mice. Of the 128 discriminatory metabolites, 18 and 41 were positively and negatively correlated with SM, respectively. The amino acids methionine and phenylalanine were increased by d-flow, while phosphatidylcholine and phosphatidylethanolamine were decreased by d-flow, and these metabolites were correlated with SM. Other significantly affected metabolites included dietary and environmental agents. Pathway analysis showed that the metabolic changes of d-flow impacted broad functional networks. These results suggest that signaling from d-flow occurring in focal regions induces systemic metabolic changes associated with atherosclerosis.

  13. Determination of cilostazol and its active metabolite 3,4-dehydro cilostazol from small plasma volume by UPLC-MS/MS

    Institute of Scientific and Technical Information of China (English)

    Nejal M. Bhatt; Vijay D. Chavada; Daxesh P. Patel; Primal Sharma; Mallika Sanyal; Pranav S. Shrivastav

    2015-01-01

    A simple, rapid and sensitive ultra performance liquid chromatography-tandem mass cilostazol and its pharmacologically active metabolite 3,4-dehydro cilostazol in human plasma using deuterated analogs as internal standards (ISs). Plasma samples were prepared using solid phase extraction 18 (50 mm ? 2.1 mm, 1.7 mm) column. The method was established over a concentration range of 0.5–1000 ng/mL for cilostazol and 0.5–mL for 3,4-dehydro cilostazol. Intra-and inter-batch precision (%CV) and accuracy for the analytes were found within 0.93–1.88 and 98.8–101.7% for cilostazol and 0.91–2.79 and 98.0–102.7% for the metabolite respectively. The assay recovery was within 95–97% for both the analytes and internal standards. The method was successfully applied to support a bioequivalence study of 100 mg cilostazol in 30 healthy subjects.

  14. Determination of cilostazol and its active metabolite 3,4-dehydro cilostazol from small plasma volume by UPLC−MS/MS

    Directory of Open Access Journals (Sweden)

    Nejal M. Bhatt

    2015-02-01

    Full Text Available A simple, rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC−MS/MS method has been developed for the simultaneous determination of cilostazol and its pharmacologically active metabolite 3,4-dehydro cilostazol in human plasma using deuterated analogs as internal standards (ISs. Plasma samples were prepared using solid phase extraction and chromatographic separation was performed on UPLC BEH C18 (50 mm×2.1 mm, 1.7 µm column. The method was established over a concentration range of 0.5–1000 ng/mL for cilostazol and 0.5–500 ng/mL for 3,4-dehydro cilostazol. Intra- and inter-batch precision (% CV and accuracy for the analytes were found within 0.93–1.88 and 98.8–101.7% for cilostazol and 0.91–2.79 and 98.0–102.7% for the metabolite respectively. The assay recovery was within 95–97% for both the analytes and internal standards. The method was successfully applied to support a bioequivalence study of 100 mg cilostazol in 30 healthy subjects.

  15. Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene

    Directory of Open Access Journals (Sweden)

    Rongli Sun

    2014-03-01

    Full Text Available Benzene is identified as a carcinogen. Continued exposure of benzene may eventually lead to damage to the bone marrow, accompanied by pancytopenia, aplastic anemia or leukemia. This paper explores the variations of endogenous metabolites to provide possible clues for the molecular mechanism of benzene-induced hematotoxicity. Liquid chromatography coupled with time of flight-mass spectrometry (LC-TOF-MS and principal component analysis (PCA was applied to investigate the variation of endogenous metabolites in bone marrow cells and plasma of male C3H/He mice. The mice were injected subcutaneously with benzene (0, 300, 600 mg/day once daily for seven days. The body weights, relative organ weights, blood parameters and bone marrow smears were also analyzed. The results indicated that benzene caused disturbances in the metabolism of oxidation of fatty acids and essential amino acids (lysine, phenylalanine and tyrosine in bone marrow cells. Moreover, fatty acid oxidation was also disturbed in plasma and thus might be a common disturbed metabolic pathway induced by benzene in multiple organs. This study aims to investigate the underlying molecular mechanisms involved in benzene hematotoxicity, especially in bone marrow cells.

  16. Simultaneous quantification of VX and its toxic metabolite in blood and plasma samples and its application for in vivo and in vitro toxicological studies.

    Science.gov (United States)

    Reiter, Georg; Mikler, John; Hill, Ira; Weatherby, Kendal; Thiermann, Horst; Worek, Franz

    2011-09-15

    The present study was initiated to develop a sensitive and highly selective method for the simultaneous quantification of the nerve agent VX (O-ethyl S-[2(diisopropylamino)ethyl] methylphosphonothioate) and its toxic metabolite (EA-2192) in blood and plasma samples in vivo and in vitro. For the quantitative detection of VX and EA-2192 the resolution was realized on a HYPERCARB HPLC phase. A specific procedure was developed to isolate both toxic analytes from blood and plasma samples. The limit of detection was 0.1 pg/ml and the absolute recovery of the overall sample preparation procedure was 74% for VX and 69% for EA-2192. After intravenous and percutaneous administration of a supralethal doses of VX in anaesthetised swine both VX and EA-2192 could be quantified over 540 min following exposure. This study is the first to verify the in vivo formation of the toxic metabolite EA-2192 after poisoning with the nerve agent VX. Further toxicokinetic and therapeutic studies are required in order to determine the impact of EA-2192 on the treatment of acute VX poisoning.

  17. Plasma YKL-40 levels in healthy subjects from the general population

    DEFF Research Database (Denmark)

    Bojesen, Stig E; Johansen, Julia S; Nordestgaard, Børge G

    2011-01-01

    Plasma YKL-40 is a new biomarker in patients with cancer and inflammatory diseases. High plasma YKL-40 is associated with poor prognosis. Our aim was to determine reference levels in healthy subjects....

  18. A PHARMACOKINETIC STUDY ON RU 486 AND ITS METABOLITES AFTER ORAL ADMINISTRATION AT VARIOUS DOSES

    Institute of Scientific and Technical Information of China (English)

    SHIYong-En; YEZhi-Hou; HEChang-Hai; ZHANGGuo-Qin; XUJian-Qiu; BAJXiu-Mei

    1989-01-01

    The purpose of the present study is to obtain pharmacokinetic parameters of RU486 and its metabolites and then to find out an optimal regimen of the compound for termination of human early pregnancy. Plasma levels of RU486 and its metabolites,

  19. Development and validation of a high performance liquid chromatography quantification method of levo-tetrahydropalmatine and its metabolites in plasma and brain tissues: application to a pharmacokinetic study.

    Science.gov (United States)

    Abdallah, Inas A; Huang, Peng; Liu, Jing; Lee, David Y; Liu-Chen, Lee-Yuan; Hassan, Hazem E

    2017-04-01

    Levo-tetrahydropalmatine (l-THP) is an alkaloid isolated from Chinese medicinal herbs of the Corydalis and Stephania genera. It has been used in China for more than 40 years mainly as an analgesic with sedative/hypnotic effects. Despite its extensive use, its metabolism has not been quantitatively studied, nor there a sensitive reliable bioanalytical method for its quantification simultaneously with its metabolites. As such, the objective of this study was to develop and validate a sensitive and selective HPLC method for simultaneous quantification of l-THP and its desmethyl metabolites l-corydalmine (l-CD) and l-corypalmine (l-CP) in rat plasma and brain tissues. Rat plasma and brain samples were processed by liquid-liquid extraction using ethyl acetate. Chromatographic separation was achieved on a reversed-phase Symmetry® C18 column (4.6 × 150 mm, 5 μm) at 25°C. The mobile phase consisted of acetonitrile-methanol-10 mm ammonium phosphate (pH 3) (10:30:60, v/v) and was used at a flow rate of 0.8 mL/min. The column eluent was monitored at excitation and emission wavelengths of 230 and 315 nm, respectively. The calibration curves were linear over the concentration range of 1-10,000 ng/mL. The intra- and interday reproducibility studies demonstrated accuracy and precision within the acceptance criteria of bioanalytical guidelines. The validated HPLC method was successfully applied to analyze samples from a pharmacokinetic study of l-THP in rats. Taken together, the developed method can be applied for bioanalysis of l-THP and its metabolites in rodents and potentially can be transferred for bioanalysis of human samples.

  20. Plasma Cytokine Levels in Astronauts Before and after Spaceflight

    Science.gov (United States)

    Mehta, Satish K.; Aggarwal, Barat B.; Feiveson, Alan H.; Hammond, Dinne K.; Castro, Victoria A.; Stowe, Raymond; Pierson Duane L.

    2008-01-01

    Space flight is a unique experience and results in adverse effects on human physiology. Changes have been reported in various physiological systems, including musculoskeletal, neurovestibular, cardiovascular, endocrine, immunity and increased latent viral reactivation as well as others. The potential mechanisms behind these changes are not fully understood. Various cytokines such as IL-1, IL-6, TNF and chemokines have been linked to several of these changes, like muscle loss, bone loss, fatigue, sleep deprivation and viral reactivation. Eighteen astronauts (15 M and 3 F) from 8 spaceflights and 10 healthy age-matched adults (6 M, 4 F) were included in the present study. A panel of 21 plasma cytokines was analyzed with the Luminex 100 to measure the cytokines in these subjects 10 days before the flight (L-10), 2-3 hour after landing (R+0), 3 days after landing (R+3), and at their annual medical exam (AME). IL-10, IL-1, IFN-alpha, MCP-1 and IP-10 increased significantly at L-10 as compared with AME levels. IL-6 and IFN-alpha showed significant increases at R + 0 (P less than .05) over their baseline levels (AME). Cytokine levels at R+3 were not significantly different from R+0. IL-10 and IL-6 have been reported to increase in during viral reactivation. These data show that there was a shift from TH1 to TH2 cytokines L-10 and R+0. We also studied viral reactivation in 10 of the 18 subjects included in the present study before, during, and after space flight. Increased salivary varicella zoster virus (VZV) shedding in these subjects was found either during or after the mission. VZV shedding correlated with the increased levels of cytokines especially IL-10 and IL-6. Overall, our data suggests that cytokines may play an important role in regulating adverse changes in astronauts, and further studies are needed to fully understand the mechanism.

  1. Effect of intake on fasting heat production, respiratory quotient and plasma metabolites measured using the washed rumen technique.

    Science.gov (United States)

    Kim, D H; McLeod, K R; Koontz, A F; Foote, A P; Klotz, J L; Harmon, D L

    2015-01-01

    The objective was to investigate the effect of intake before fasting on concentrations of metabolites and hormones, respiratory quotient (RQ) and fasting heat production (HP) using the washed rumen technique and to compare these values with those from the fed state. Six Holstein steers (360±22 kg) were maintained at 21°C and fed three different energy intakes within a replicated 3×3 Latin square design with 21-day periods. Steers were fed alfalfa cubes to provide 1.0, 1.5 and 2.0×NEm during 19 days of each experimental period. Steers were placed in individual metabolism stalls fitted with indirect calorimetry head-boxes on day 20 of each experimental period (FED steers) and fed their normal meal. On day 21 of each period the reticulorumen was emptied, washed and refilled with ruminal buffer (NaCl=96; NaHCO3=24; KHCO3=30; K2HPO4=2; CaCl2=1.5; MgCl2=1.5 mmol/kg of buffer) aerated with 75% N2 and 25% CO2 before introduction to the rumen (steers were not fed; WASHED steers). Each gas exchange was measured over 24 h. HP for 1.0, 1.5 and 2.0×NEm were 479, 597 and 714 kJ/daykg0.75 (s.e.m. =16), respectively. The plateau RQ was 0.756, 0.824 and 0.860 for the 1.0, 1.5 and 2.0×NEm intakes for the FED steers, respectively. After rumen washing, fasting HP was 331, 359 and 400 kJ/daykg0.75 (s.e.m.=13) for 1.0, 1.5, and 2.0×NEm intakes before fasting, respectively. The RQ for WASHED rumen steers was 0.717, 0.710 and 0.719, respectively. Cortisol and β-hydroxybutyrate concentrations in WASHED rumen steers did not exceed threshold levels for severe energy deficit and stress as can be induced from prolonged fasting. This study demonstrates that a fasting state can be emulated using the washed rumen technique, minimizing the time required as opposed to traditional fasting methodologies, without causing a severe energy deficit and stress.

  2. Concentrations of Monoamines and Their Metabolites in Blood Plasma and Some Brain Structures of Mice, Participated in a Space Flight on the Aircraft BION-M1

    Science.gov (United States)

    Shtemberg, Andrey; Kudrin, Vladimir

    The purpose of this work was to study the possible disturbances of monoamines concentration and their metabolites in some structures of mouse brain and blood plasma caused by the influence of space flight. The forty eight C57BL/6 mice were divided into the following groups : basal control - animals , which together with a group of space flight arrived at Baykonur and then were returned to Moscow; the first space flight group - animals who spent 30 days in space, BION-M1 - board and decapitated 12 hours after the landing; animal house control to the first space flight group; second space flight group - animals who spent 30 days in space, aboard the BION-M1, and then recovered at ground conditions for 7 days; animal house control to the second space flight group; space flight imitation group - spent 30 days on board at ground model of BION-M1; animal house control to the imitation group. In all animals concentration of HA, DA, 5 -HT and their metabolites DOPAC, HVA, 3 -MT, 5 - HIAA in plasma and in the prefrontal cortex, hypothalamus, striatum and hippocampus were studied. In the blood plasma of first space flight group the concentrations of DOPAC were significantly higher compared to animal house control. The most significant changes were observed in the second space flight group, in those animals which recovered after the flight. There was a significant increase in the concentration of HA and A in blood plasma relative to the basal control and increased concentration of HA and the DOPAC/DA ratio relative to the first space flight group. No significant changes were observed in the hippocampus. In the first space flight group there was observed an increase in concentration of HA and DOPAC in the hypothalamus relative to controls. Seven days after rest concentrations of monoamines and their metabolites were significantly enhanced relative to the control and the first space flight groups. In physiology and pharmacology there is a process called as withdrawal effect

  3. Improved analysis of vitamin D metabolites in plasma using liquid chromatography tandem mass spectrometry, and its application to cardiovascular research.

    Science.gov (United States)

    Sandhu, Jatinderpal K; Auluck, Janica; Ng, Leong L; Jones, Donald J L

    2014-06-01

    The accurate and specific measurement of vitamin D is increasingly important for determining the role of vitamin D in the pathogenesis of disease. Liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) has increasingly become the analytical modality of choice for the analysis of vitamin D. There are many advantages to using LC/MS/MS, such as high specificity and sensitivity to help distinguish the isomers of vitamin D. This rapid method, modified from a Waters Corporation application note, consists of minimal sample manipulation using liquid-liquid extraction and incorporates an internal standard. The supernatant is dried down and injected onto an ultra-high-performance liquid chromatography/electrospray ionization tandem mass spectrometer. The total analysis time is 10 min per injection, enabling high throughput of samples. This method also incorporates two commercial quality control standards to provide a robust system with acceptable coefficient of variation. The analysis of control and heart failure plasma samples showed significant differences in the levels of vitamin D3 between these two groups; however, in the control group, there were individuals who were vitamin D deficient. Overall, the vitamin D3 levels were higher in control samples than in heart failure individuals. As expected, vitamin D2 levels were not observed in many of the samples analysed. This modified method is quick and incorporates an internal standard to allow for any loss in the extraction procedure. The method also includes quality control samples to enable assay standardization. The assay involves inexpensive pre-sample clean-up, aiding high throughput, which is important in many laboratories.

  4. Age and Gender Differences in Urinary Levels of Eleven Phthalate Metabolites in General Taiwanese Population after a DEHP Episode.

    Directory of Open Access Journals (Sweden)

    Po-Chin Huang

    Full Text Available In 2011, the Taiwan FDA disclosed illegal di(2-ethylhexyl phthalate (DEHP and dibutyl phthalate (DBP use in beverage and nutrition supplements. We aim to determine phthalate exposure and other relevant factors in a sample of the general Taiwanese population in order to evaluate actual phthalate exposure levels after this disclosure of DEHP use.We selected subjects aged 7 years old and older in 2013 from the general Taiwanese population. First morning urine samples from each participant were collected to analyze 11 phthalate metabolites representing 7 parent phthalates using on-line liquid chromatography/ tandem mass spectrometry. An interview questionnaire was applied to obtain participant demographic characteristics, lifestyle, and other relevant factors.The median levels of metabolites of DEHP, including mono-ethylhexyl phthalate (MEHP, mono-(2-ethyl-5-oxohexyl phthalate (MEOHP, mono-(2-ethyl-5-hydroxyhexyl phthalate (MEHHP, mono-(2-ethyl-5-carboxypentyl phthalate (MECPP, DBP (DnBP and DiBP, including mono-n-butyl phthalate (MnBP and mono-iso-butyl phthalate (MiBP, and mono-ethyl phthalate (MEP in urine samples of 290 adults/ 97 minors (<18 years were 7.9/ 6.1, 12.6/ 17.8, 22.0/ 25.8, 25.4/ 30.8, 18.1/ 23.6, 9.4/ 13.6 and 14.5/ 12.4 μg/g creatinine, respectively. Women (≧18 years were exposed to significantly higher levels of MEHHP (P=0.011, MECPP (P=0.01, MnBP (P=0.001 and MEP (P<0.001 than men (≧18 years, whereas no gender difference was observed in minors. We found significant higher level of MEP (creatinine-unadjusted in subject aged between 18 to 40 years old (P<0.001, especially for women. Exposure levels of MEOHP (P<0.001, MECPP (P=0.002 and MnBP (P=0.044 in minors were significantly higher than those of adults. High frequency usage of food preservation film and bags, and personal care products are potential sources of phthalates exposure in general Taiwanese.Our findings indicated that DEHP and DBP exposure in a sample of the

  5. Sequential plasma angiogenic factors levels in women with suspected preeclampsia.

    Science.gov (United States)

    Baltajian, Kedak; Bajracharya, Surichhya; Salahuddin, Saira; Berg, Anders H; Geahchan, Carl; Wenger, Julia B; Thadhani, Ravi; Karumanchi, S Ananth; Rana, Sarosh

    2016-07-01

    Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate. During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine

  6. Associations between dietary acrylamide intake and plasma sex hormone levels

    Science.gov (United States)

    Hogervorst, Janneke G.; Fortner, Renee T.; Mucci, Lorelei A.; Tworoger, Shelley S.; Eliassen, A. Heather; Hankinson, Susan E.; Wilson, Kathryn M.

    2013-01-01

    Background The rodent carcinogen acrylamide was discovered in 2002 in commonly consumed foods. Epidemiological studies have observed positive associations between acrylamide intake and endometrial, ovarian and breast cancer risks, which suggests that acrylamide may have sex-hormonal effects. Methods We cross-sectionally investigated the relationship between acrylamide intake and plasma levels of sex hormones and SHBG among 687 postmenopausal and 1300 premenopausal controls from nested case-control studies within the Nurses’ Health Studies. Results There were no associations between acrylamide and sex hormones or SHBG among premenopausal women overall or among never-smokers. Among normal-weight premenopausal women, acrylamide intake was statistically significantly positively associated with luteal total and free estradiol levels. Among postmenopausal women overall and among never-smokers, acrylamide was borderline statistically significantly associated with lower estrone sulfate levels but not with other estrogens, androgens, prolactin or SHBG. Among normal weight women, (borderline) statistically significant inverse associations were noted for estrone, free estradiol, estrone sulfate, DHEA, and prolactin, while statistically significant positive associations for testosterone and androstenedione were observed among overweight women. Conclusions Overall, this study did not show conclusive associations between acrylamide intake and sex hormones that would lend unequivocal biological plausibility to the observed increased risks of endometrial, ovarian and breast cancer. The association between acrylamide and sex hormones may differ by menopausal and overweight status. We recommend other studies investigate the relationship between acrylamide and sex hormones in women, specifically using acrylamide biomarkers. Impact The present study showed some interesting associations between acrylamide intake and sex hormones that urgently need confirmation. PMID:23983241

  7. Plasma IGFBP-2 levels after postoperative combined radiotherapy and chemotherapy predict prognosis in elderly glioblastoma patients.

    Directory of Open Access Journals (Sweden)

    Sheng Han

    Full Text Available It has been found that preoperative plasma IGFBP-2 levels correlate with prognosis in glioma patients. The prognostic value of plasma IGFBP-2 after postoperative combined radiotherapy and chemotherapy in glioma patients is unknown. Plasma IGFBP-2 levels in 83 glioblastoma patients after postoperative radiotherapy plus chemotherapy were analyzed using an IGFBP-2 ELISA kit. We found that after standard therapy plasma IGFBP-2 levels significantly correlated with the patient's age (R = 0.738, P<0.001 and Karnofsky performance status (KPS, R =  -0.633, P<0.05. Cox proportional hazards models were used to calculate hazard ratios (HRs of death according to plasma IGFBP-2 levels adjusted for patient clinical characteristics. Plasma IGFBP-2 levels significantly correlated with overall survival in glioblastoma patients (multivariate HR = 1.035; 95% CI, 1.024-1.047; P<0.001. The effect of plasma IGFBP-2 levels on survival seemed to differ according to patients' age. Among patients older than 60, high plasma IGFBP-2 levels were associated with a significant increase in overall mortality (HR = 1.097; 95% CI, 1.055-1.140; P<0.001. In contrast, plasma IGFBP-2 levels conferred no significant effect on mortality among patients younger than 60. Elevated plasma IGFBP-2 levels after combined postoperative radiotherapy and chemotherapy in elderly glioblastoma patients correlate with poor KPS score and predicts poor prognosis.

  8. A liquid chromatography with tandem mass spectrometry method for simultaneous determination of UTL-5g and its metabolites in human plasma.

    Science.gov (United States)

    Shaw, Jiajiu; Wiegand, Richard; Wu, Jianmei; Bao, Xun; Valeriote, Frederick; Li, Jing

    2015-06-01

    UTL-5g is a novel small-molecule TNF-α inhibitor under investigation as both a chemoprotective and radioprotective agent. Animal studies showed that pretreatment of UTL-5g protected kidney, liver, and platelets from cisplatin-induced toxicity. In addition, UTL-5g reduced liver and lung injuries induced by radiation in vivo. Although a number of preclinical studies have been conducted, a validated bioanalytical method for UTL-5g in human plasma has not been published. In this work, a sensitive and reproducible reverse-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assay was developed and validated for the determination of UTL-5g and its metabolites, 5-methylisoxazole-3-carboxylic acid (ISOX) and 2,4-dichloroaniline (DCA), in human plasma. The method involves a simple methanol precipitation step followed by injection of the supernatant onto a Waters 2695 HPLC system coupled with a Waters Quattro Micro™ triple quadrupole mass spectrometer. Chromatographic separation was accomplished using a Waters Nova-Pak C18 column maintained at 30°C, running at gradient mode with mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in methanol at a flow rate of 0.2mL/min. The analytes were monitored under positive electrospray ionization (ESI). Quantitation of these compounds in plasma was linear from 0.05 to 10μM. The lower limit of quantitation (LLOQ) was 0.05, 0.1, and 0.2μM for UTL-5g, ISOX and DCA, respectively. The accuracy and intra-and inter-day precisions were within the generally accepted criteria for bioanalytical method (5g and its metabolites, ISOX and DCA. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Liquid chromatography-tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma$

    Institute of Scientific and Technical Information of China (English)

    Huan Lu; Chong Su; Lei Yin; Liqiang Gu; Jingkai Gu; Xiaohui Chen

    2016-01-01

    A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasma using liquid chromatography–tandem mass spectrometry. Probenecid was used as in-ternal standard and solid-phase extraction was selected for sample preparation. A chromatographic separation was performed on an Agilent Poroshell SB-C18 column (50 mm ? 4.6 mm i.d., 2.7μm) by an optimized gradient elution at a flow rate of 0.9 mL/min. The total run time was 7 min. Electrospray ionization was used in negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 143.0-143.0 for valproic acid, m/z 140.9-140.9 for 2-enevalproic acid and 4-enevalproic acid for their poor fragments, and m/z 283.9-239.9 for probenecid. The results showed good linearity of valproic acid, 2-enevalproic acid and 4-enevalproic acid in their respective linear ranges. The correlation coefficients were more than 0.998. The intra- and inter-day precision of the assay was less than 11.0%and the accuracy ranged from 2%to 12%. This analytical method was successfully applied to assay plasma concentrations of valproic acid and its two ene-metabolites in epilepsy patient plasma and used for therapeutic drug monitoring.

  10. A restricted access material for rapid analysis of [(11)C]-labeled radiopharmaceuticals and their metabolites in plasma

    DEFF Research Database (Denmark)

    Gillings, N.

    2009-01-01

    , sensitive and robust method for the measurement of plasma samples from PET studies using [(11)C]-labeled radiopharmaceuticals. METHODS: Unadulterated plasma samples were analyzed directly, following a simple filtration, by the use of a small extraction column, containing a restricted access material...

  11. Effect of fasting on hormones and metabolites in plasma of fast-growing, lean and slow-growing obese pigs.

    Science.gov (United States)

    Wangsness, P J; Acker, W A; Burdette, J H; Krabill, L F; Vasilatos, R

    1981-01-01

    Plasma concentrations of glucose, free fatty acids (FFA), insulin and growth hormone (GH) were determined immediately after food removal and then hourly for 24 hours. Blood was sampled from six lean and six obese pigs at 10 weeks of age via indwelling catheters. Plasma glucose decreased but was similar in both pig strains shortly after feed removal; at the end of the 24-hr fast, plasma glucose was higher (P less than .01) in lean pigs. Plasma FFA concentrations were similar in lean and obese pigs and increased five-fold within 24 hr of fasting. Plasma insulin was higher (P less than .05) in obese pigs than in lean pigs immediately after food removal only (21.4 +/- 3.0 vs 9.8 +/- 2.4 microU/ml). Pattern of GH secretion over 24 hr was episodic; average plasma GH was lower in obese pigs than in lean pigs (2.8 +/- .7 vs 9.4 +/- 1.9 ng/ml). In summary, FFA mobilization was similar in lean and obese pigs, GH concentrations were lower in plasma of obese pigs and relative differences in plasma glucose and insulin between pig strains were influenced by time after feed removal.

  12. Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer's disease transgenic mice.

    Science.gov (United States)

    Cao, Chuanhai; Cirrito, John R; Lin, Xiaoyang; Wang, Li; Wang, Lilly; Verges, Deborah K; Dickson, Alexander; Mamcarz, Malgorzata; Zhang, Chi; Mori, Takashi; Arendash, Gary W; Holtzman, David M; Potter, Huntington

    2009-01-01

    Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer's disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain amyloid-beta (Abeta) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Abeta levels in both brain interstitial fluid and plasma without affecting Abeta elimination. Long-term oral caffeine treatment to aged AD mice provided not only sustained reductions in plasma Abeta, but also decreases in both soluble and deposited Abeta in hippocampus and cortex. Irrespective of caffeine treatment, plasma Abeta levels did not correlate with brain Abeta levels or with cognitive performance in individual aged AD mice. Although higher plasma caffeine levels were strongly associated with lower plasma Abeta1-40 levels in aged AD mice, plasma caffeine levels were also not linked to cognitive performance. Plasma caffeine and theophylline levels were tightly correlated, both being associated with reduced inflammatory cytokine levels in hippocampus. Our conclusion is two-fold: first, that both plasma and brain Abeta levels are reduced by acute or chronic caffeine administration in several AD transgenic lines and ages, indicating a therapeutic value of caffeine against AD; and second, that plasma Abeta levels are not an accurate index of brain Abeta levels/deposition or cognitive performance in aged AD mice.

  13. Plasma levels of immunosuppressive mediators during cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    E. Borrelli

    1996-01-01

    Full Text Available The aim of this study was to evaluate plasma levels of two mediators with immunosuppressive properties, complement fraction C3a (C3a and transforming growth factor-β1 (TGF-β1, during extracorporeal circulation. The proliferation index after phytohaemagglutinin (PHA stimulation of isolated peripheral blood mononuclear cells was also investigated. Sixteen patients undergoing hypothermic (n = 8, group 1 and normothermic (n = 8, group 2 cardiopulmormry bypass (CPB were enrolled in this study. As a control, we evaluated four patients undergoing thoracovascular operations without CPB. Blood samples were collected before CPB but after anaesthesia, every 30 min during CPB, at the end of CPB and 10 min after protamine administration. Both C3a and TGF-β1 increased significantly during CPB and after protamine administration in the hypothermic as well as the normothermic group. In the latter case the increase of C3a and TGF-β1, although more prominent, was not significantl higher than in the former group. Conversely, the proliferation, index of peripheral mononuclear cells had already decreased 30 min after CPB was started and remained depressed throughout the CPB time. These results suggest a possible role of C3a and TGF-β1 in the immunological changes occurring during extracorporeal circulation.

  14. Elevated levels of procoagulant plasma microvesicles in dialysis patients.

    Science.gov (United States)

    Burton, James O; Hamali, Hassan A; Singh, Ruchir; Abbasian, Nima; Parsons, Ruth; Patel, Amit K; Goodall, Alison H; Brunskill, Nigel J

    2013-01-01

    Cardiovascular (CV) death remains the largest cause of mortality in dialysis patients, unexplained by traditional risk factors. Endothelial microvesicles (EMVs) are elevated in patients with traditional CV risk factors and acute coronary syndromes while platelet MVs (PMVs) are associated with atherosclerotic disease states. This study compared relative concentrations of circulating MVs from endothelial cells and platelets in two groups of dialysis patients and matched controls and investigated their relative thromboembolic risk. MVs were isolated from the blood of 20 haemodialysis (HD), 17 peritoneal dialysis (PD) patients and 20 matched controls. Relative concentrations of EMVs (CD144(+ ve)) and PMVs (CD42b(+ ve)) were measured by Western blotting and total MV concentrations were measured using nanoparticle-tracking analysis. The ability to support thrombin generation was measured by reconstituting the MVs in normal plasma, using the Continuous Automated Thrombogram assay triggered with 1µM tissue factor. The total concentration of MVs as well as the measured sub-types was higher in both patient groups compared to controls (p0.3). Dialysis patients have higher levels of circulating procoagulant MVs than healthy controls. This may represent a novel and potentially modifiable mediator or predictor of occlusive cardiovascular events in these patients.

  15. Elevated levels of procoagulant plasma microvesicles in dialysis patients.

    Directory of Open Access Journals (Sweden)

    James O Burton

    Full Text Available Cardiovascular (CV death remains the largest cause of mortality in dialysis patients, unexplained by traditional risk factors. Endothelial microvesicles (EMVs are elevated in patients with traditional CV risk factors and acute coronary syndromes while platelet MVs (PMVs are associated with atherosclerotic disease states. This study compared relative concentrations of circulating MVs from endothelial cells and platelets in two groups of dialysis patients and matched controls and investigated their relative thromboembolic risk. MVs were isolated from the blood of 20 haemodialysis (HD, 17 peritoneal dialysis (PD patients and 20 matched controls. Relative concentrations of EMVs (CD144(+ ve and PMVs (CD42b(+ ve were measured by Western blotting and total MV concentrations were measured using nanoparticle-tracking analysis. The ability to support thrombin generation was measured by reconstituting the MVs in normal plasma, using the Continuous Automated Thrombogram assay triggered with 1µM tissue factor. The total concentration of MVs as well as the measured sub-types was higher in both patient groups compared to controls (p0.3. Dialysis patients have higher levels of circulating procoagulant MVs than healthy controls. This may represent a novel and potentially modifiable mediator or predictor of occlusive cardiovascular events in these patients.

  16. Plasma Cytokine Levels During Long-Duration Spaceflight

    Science.gov (United States)

    Crucian, Brian E.; Zwart, Sara R.; Quiriarte, Heather A.; Smith, Scott M.; Sams, Clarence F.

    2012-01-01

    Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation. Specific measurements include leukocyte distribution, T cell function, cytokine production profiles (mRNA, intracellular, secreted, plasma), virus-specific T cell number/function, latent herpesvirus reactivation, stress hormone levels. Determine the clinical risk related to immune dysregulation for exploration class spaceflight, as well as an appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures. Specific Study Objectives: Determine the nutritional status of astronauts before, during, and after spaceflight ensure adequate intake of energy, protein, and vitamins during missions. The Clinical Nutritional Status Assessment measures dietary intake, body composition, protein, bone, iron, mineral, vitamin, and antioxidant status (60 total analytes). Currently, it is a medical requirement for U.S. crewmembers on-board the ISS. The results of data analysis are used both to understand the connections between nutrition and human health during space flight, and to develop effective dietary strategies to reduce adverse health impacts (including bone loss, loss of important vitamins and minerals, and increased genetic damage from radiation).

  17. Urinary Level of Prostaglandin E2 Metabolite and Risk of Incident Breast Cancer

    Science.gov (United States)

    2012-01-01

    p=0.08) [Table 3]. On the other hand, women with rheumatoid arthritis had lower levels of PGE-M compared to those who didn’t report having the...8.07) 0.012 6.33 (5.27-7.6) 0.078 Rheumatoid arthritis Yes 569 5.47 (5.19-5.77) Ref 5.47 (5.2-5.77) Ref No 35 4.44 (3.59-5.51) 0.064 4.44 (3.59...through various venues, incorporating new understanding of breast cancer etiology in the analyses of epidemiologic data. These experiences have

  18. Plasma Lactate Dehydrogenase Levels Predict Mortality in Acute Aortic Syndromes

    Science.gov (United States)

    Morello, Fulvio; Ravetti, Anna; Nazerian, Peiman; Liedl, Giovanni; Veglio, Maria Grazia; Battista, Stefania; Vanni, Simone; Pivetta, Emanuele; Montrucchio, Giuseppe; Mengozzi, Giulio; Rinaldi, Mauro; Moiraghi, Corrado; Lupia, Enrico

    2016-01-01

    Abstract In acute aortic syndromes (AAS), organ malperfusion represents a key event impacting both on diagnosis and outcome. Increased levels of plasma lactate dehydrogenase (LDH), a biomarker of malperfusion, have been reported in AAS, but the performance of LDH for the diagnosis of AAS and the relation of LDH with outcome in AAS have not been evaluated so far. This was a bi-centric prospective diagnostic accuracy study and a cohort outcome study. From 2008 to 2014, patients from 2 Emergency Departments suspected of having AAS underwent LDH assay at presentation. A final diagnosis was obtained by aortic imaging. Patients diagnosed with AAS were followed-up for in-hospital mortality. One thousand five hundred seventy-eight consecutive patients were clinically eligible, and 999 patients were included in the study. The final diagnosis was AAS in 201 (20.1%) patients. Median LDH was 424 U/L (interquartile range [IQR] 367–557) in patients with AAS and 383 U/L (IQR 331–460) in patients with alternative diagnoses (P < 0.001). Using a cutoff of 450 U/L, the sensitivity of LDH for AAS was 44% (95% confidence interval [CI] 37–51) and the specificity was 73% (95% CI 69–76). Overall in-hospital mortality for AAS was 23.8%. Mortality was 32.6% in patients with LDH ≥ 450 U/L and 16.8% in patients with LDH < 450 U/L (P = 0.006). Following stratification according to LDH quartiles, in-hospital mortality was 12% in the first (lowest) quartile, 18.4% in the second quartile, 23.5% in the third quartile, and 38% in the fourth (highest) quartile (P = 0.01). LDH ≥ 450 U/L was further identified as an independent predictor of death in AAS both in univariate and in stepwise logistic regression analyses (odds ratio 2.28, 95% CI 1.11–4.66; P = 0.025), in addition to well-established risk markers such as advanced age and hypotension. Subgroup analysis showed excess mortality in association with LDH ≥ 450 U/L in elderly, hemodynamically stable

  19. Plasma Potassium Levels in Healthy Prehypertension Subjects and the Role of A High Potassium Drink.

    Science.gov (United States)

    Farapti, Farapti; Sayogo, Savitri; Siregar, Parlindungan

    2017-02-24

    Most populations around the world consume less than the recommended levels of potassium. Long term low potassium intake could lead to decreased plasma potassium levels and induce hypokalemia. The increasing of plasma potassium levels 0,2-0,4 mmol/L by improving potassium intake decreased significantly blood pressure (BP). Assessing plasma potassium levels in healthy people related to potassium intake have not been studied. In this study, we analysed plasma potassium levels in prehypertension (PHT) subjects and to evaluate the effect of tender coconut water (TCW) as a high potassium drink on plasma potassium levels in PHT adults. Thirthy-two female aged 25-44 years were randomly allocated to 14 days on TCW or water in a parallel randomized clinical trial . The treatment (T) group received TCW 300 ml twice daily and the control (C) group received water 300 ml twice daily too. At baseline, plasma potassium levels was 3.71±0.41 mmol/L, and 22.58% were categorized as hypokalemia. After 14 days treatment, potassium plasma level between T and C groups were not significantly different (p=0,247). The change of plasma potassium levels in both groups showed tendency to increase but not statistically significant (p=0.166). In healthy prehypertension women, the low levels of potassium plasma may be caused by low potassium intake for long time and intervension with TCW 300 ml twice daily for 14 consecutive days has not proven yet to increase plasma potassium levels. It is necessary to give higher dose and longer time to increase potassium plasma in low potassium plasma level subjects.

  20. Plasma levels of OLFM4 in normals and patients with gastrointestinal cancer

    DEFF Research Database (Denmark)

    Clemmensen, Stine N; Glenthøj, Anders J; Heebøll, Sara;

    2015-01-01

    levels in plasma, the majority with OLFM4 in plasma between 0 and 0.1 μg/ml, mean 0.028 μg/ml while 10% of both normals and patients with cancers had OLFM4 between 4 and 60 μg/ml, mean 15 μg/ml. The levels were constant over time. The background for this high plasma level is not known, but must be taken...

  1. Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows.

    Science.gov (United States)

    Krogh, U; Bruun, T S; Poulsen, J; Theil, P K

    2017-06-01

    Sow lactation diets often include fat sources without considering the impact on digestion, metabolism and performance. Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. Litter gain and milk yield during late lactation were greater in sows fed C8TG or SOYO than in sows fed PFAD (P=0.05), whereas loss of BW (P=0.60) and backfat (P=0.70) was unaffected by fat source. Milk protein on days 3 and 10 of lactation were lower in C8TG and SOYO sows, than in PFAD sows (Psows. Milk yield was unaffected by fiber treatment (P=0.43), whereas milk protein concentration was lowest in ALF sows (Psows. In conclusion, performance was enhanced in SOYO and C8TG compared with PFAD sows, possibly associated with reduced energy intake in PFAD-fed sows. Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential

  2. Simultaneous determination of imperatorin and its metabolite xanthotoxol in rat plasma and urine by LC-MS/MS and its application to pharmacokinetic studies.

    Science.gov (United States)

    Ngo, Lien; Tran, Phuong; Ham, Seong-Ho; Cho, Jung-Hee; Cho, Hea-Young; Lee, Yong-Bok

    2017-02-15

    An accurate, precise, selective, and sensitive liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of imperatorin (IMP) and its metabolite, xanthotoxol (XAN), in rat plasma and urine samples. The analytes, along with psoralen as an internal standard, were determined by multiple reaction monitoring (MRM) operated in the positive electrospray ionization (ESI) mode. Chromatographic separation was performed on an Acquity UPLC BEH C18 column (50mm×2.1mm, 1.7μm) with a mobile phase consisting of 0.1% formic acid solution and 0.1% formic acid in methanol at a flow rate of 0.3mL/min. The run time was 6min per sample and the injection volume was 5μL. The method had a lower limit of quantification (LLOQ) of 0.25ng/mL for IMP in plasma and urine, and 1ng/mL for XAN in urine. The linear calibration curves were fitted over the range of 0.25-1000ng/mL for IMP in plasma, 0.25-1000ng/mL for IMP in urine, and 1-1000ng/mL for XAN in urine, with correlation coefficients greater than 0.995. The inter- and intra-day accuracies (relative error, RE%) were between -8.5% and 3.5%, and the precisions (relative standard deviation, RSD%) were less than 10.0% for all quality control samples (QCs). The analytes were extracted from rat plasma and urine samples using a liquid-liquid extraction method with the extraction recovery in the range of 60.3-79.1%. A good stability of the analytes was observed in all the analysis procedures. The method was successfully validated and applied to determine the pharmacokinetics of IMP in rat plasma and, for the first time, the metabolite kinetics of IMP to XAN in rat urine after IMP administration.

  3. Plasma GLP-2 levels and intestinal markers in the juvenile pig during intestinal adaptation

    DEFF Research Database (Denmark)

    Paris, Monique C; Fuller, Peter J; Carstensen, Bendix

    2004-01-01

    , villus height, lactase, sucrase, maltase, crypt depth, or villus/crypt ratio. Plasma GLP-2 levels increase in the first weeks following massive small intestinal resection. The increase in plasma GLP-2 levels was enhanced by supplementation of the diet with CPC. The changes in GLP-2 levels observed...

  4. Plasma levels of soluble endothelial cell protein C receptor in patients with Wegener's granulomatosis

    NARCIS (Netherlands)

    Boomsma, MM; Stearns-Kurosawa, DJ; Stegeman, CA; Raschi, E; Meroni, PL; Kurosawa, S; Tervaert, JWC

    Elevated soluble thrombomodulin (sTM) levels are an accepted marker of endothelial damage. The physiological significance of plasma endothelial protein C receptor (sEPCR) levels is not known. To assess the relevance of this plasma protein in Wegener's granulomatosis (WG), sEPCR levels were measured

  5. Liquid chromatography-tandem mass spectrometry (LC/APCI-MS/MS) methods for the quantification of captan and folpet phthalimide metabolites in human plasma and urine.

    Science.gov (United States)

    Berthet, Aurélie; Bouchard, Michèle; Schüpfer, Patrick; Vernez, David; Danuser, Brigitta; Huynh, Cong Khanh

    2011-02-01

    Captan and folpet are fungicides largely used in agriculture. They have similar chemical structures, except that folpet has an aromatic ring unlike captan. Their half-lives in blood are very short, given that they are readily broken down to tetrahydrophthalimide (THPI) and phthalimide (PI), respectively. Few authors measured these biomarkers in plasma or urine, and analysis was conducted either by gas chromatography coupled to mass spectrometry or liquid chromatography with UV detection. The objective of this study was thus to develop simple, sensitive and specific liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) methods to quantify both THPI and PI in human plasma and urine. Briefly, deuterated THPI was added as an internal standard and purification was performed by solid-phase extraction followed by LC/APCI-MS/MS analysis in negative ion mode for both compounds. Validation of the methods was conducted using spiked blank plasma and urine samples at concentrations ranging from 1 to 250 μg/L and 1 to 50 μg/L, respectively, along with samples of volunteers and workers exposed to captan or folpet. The methods showed a good linearity (R (2) > 0.99), recovery (on average 90% for THPI and 75% for PI), intra- and inter-day precision (RSD, <15%) and accuracy (<20%), and stability. The limit of detection was 0.58 μg/L in urine and 1.47 μg/L in plasma for THPI and 1.14 and 2.17 μg/L, respectively, for PI. The described methods proved to be accurate and suitable to determine the toxicokinetics of both metabolites in human plasma and urine.

  6. Levels of DDT and its metabolites in placenta, maternal and cord blood and their potential influence on neonatal anthropometric measures

    Energy Technology Data Exchange (ETDEWEB)

    Al-Saleh, Iman, E-mail: iman@kfshrc.edu.sa [Environmental Health Section, Biological and Medical Research Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh (Saudi Arabia); Al-Doush, Inaam; Alsabbaheen, Ammar [Environmental Health Section, Biological and Medical Research Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh (Saudi Arabia); Mohamed, Gamal El Din [Biostatistics, Epidemiology and Scientific Computing Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh (Saudi Arabia); Rabbah, Abdullah [Department of Pediatrics, King Khalid Hospital, Al-Kharj (Saudi Arabia)

    2012-02-01

    Previous studies of in utero exposure to dichlorodiphenyltrichloroethane (DDT) have shown mixed results for the harmful effects on fetal growth and development. This cross-sectional study was designed to: (1) examine the extent of DDT exposure in 1578 women, aged 28.5 {+-} 6.0 who delivered between June 2005 and 2006 in the area of Al-Kharj, Saudi Arabia; and (2) assess its influence on neonatal anthropometric measurement of newly born babies. DDT and its metabolites, namely 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p Prime -DDE), 1,1-dichloro-2,2-bis (p-chlorophenyl) ethane (p,p Prime -DDD) and 1,1,1-trichloro-2,2 Prime bis (p-chlorophenyl) ethane (p,p Prime -DDT) were measured in cord and maternal serum as well as placenta by Gas Chromatography coupled with an Electron Capture Detector (GC/ECD). p,p Prime -DDE was detected in 28.3% of cord and 54.4% of maternal serum, reflecting past exposure, whereas the p,p Prime -DDT was only found in 0.46% cord and 1.2% maternal samples. As expected the p,p Prime -DDE cord levels (0.197 {+-} 0.961 {mu}g/L) were 2.8 times lower than the maternal levels (0.551 {+-} 1.778 {mu}g/L), and both were significantly correlated (r = 0.517) suggesting its transplacental transfer. The picture was different in placental tissues. p,p Prime -DDE and p,p Prime -DDT were detected in 84% and 99% of placental tissues, with the highest p,p Prime -DDT in placental tissues (29.62 {+-} 158.282 Micro-Sign g/kg dry wt.) compare to p,p Prime -DDE (10.167 {+-} 18.851 {mu}g/kg dry wt.). In general, the presence of DDT metabolites in our participants indicates that these chemicals are still relevant despite the fact that they have been banned or restricted in the study area for many years. Our results support the view for an association between low in utero exposure to DDT and the anthropometric development of the fetus leading to a reduction in its head circumference, crown-heel length, birth weight and birth height. Since the reduction in these

  7. Pharmacokinetics of Tyrosol Metabolites in Rats

    OpenAIRE

    Da-Hye Lee; Yang-Ji Kim; Min Jung Kim; Jiyun Ahn; Tae-Youl Ha; Sang Hee Lee; Young Jin Jang; Chang Hwa Jung

    2016-01-01

    Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol-derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Two tyrosol metabolites (M1 and M2) were detected in the plasma. M1 was identified as...

  8. Development and validation of bioanalytical UHPLC-UV method for simultaneous analysis of unchanged fenofibrate and its metabolite fenofibric acid in rat plasma: Application to pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Rayan G. Alamri

    2017-01-01

    Full Text Available A simple, precise, selective and fast ultra-high performance liquid chromatography (UHPLC-UV method has been developed and validated for the simultaneous determination of a lipid regulating agent fenofibrate and its metabolite fenofibric acid in rat plasma. The chromatographic separation was carried out on a reversed-phase Acquity® BEH C18 column using methanol–water (65:35, v/v as the mobile phase. The isocratic flow was 0.3 ml/min with rapid run time of 2.5 min and UV detection was at 284 nm. The method was validated over a concentration range of 100–10000 ng/ml (r2 ⩾ 0.9993. The selectivity, specificity, recovery, accuracy and precision were validated for determination of fenofibrate/fenofibric acid in rat plasma. The lower limits of detection and quantitation of the method were 30 and 90 ng/ml for fenofibrate and 40 and 100 ng/ml for fenofibric acid, respectively. The within and between-day coefficients of variation were less than 5%. The validated method has been successfully applied to measure the plasma concentrations in pharmacokinetics study of fenofibrate in an animal model to illustrate the scope and application of the method.

  9. Quantitative analyses of schizophrenia-associated metabolites in serum: serum D-lactate levels are negatively correlated with gamma-glutamylcysteine in medicated schizophrenia patients.

    Directory of Open Access Journals (Sweden)

    Takeshi Fukushima

    Full Text Available The serum levels of several metabolites are significantly altered in schizophrenia patients. In this study, we performed a targeted analysis of 34 candidate metabolites in schizophrenia patients (n = 25 and compared them with those in age- and gender-matched healthy subjects (n = 27. Orthogonal partial least square-discriminant analysis revealed that complete separation between controls and patients was achieved based on these metabolites. We found that the levels of γ-glutamylcysteine (γ-GluCys, linoleic acid, arachidonic acid, D-serine, 3-hydroxybutyrate, glutathione (GSH, 5-hydroxytryptamine, threonine, and tyrosine were significantly lower, while D-lactate, tryptophan, kynurenine, and glutamate levels were significantly higher in schizophrenia patients compared to controls. Using receiver operating characteristics (ROC curve analysis, the sensitivity, specificity, and the area under curve of γ-GluCys, a precursor of GSH, and D-lactate, a terminal metabolite of methylglyoxal, were 88.00%, 81.48%, and 0.8874, and 88.00%, 77.78%, and 0.8415, respectively. In addition, serum levels of D-lactate were negatively correlated with γ-GluCys levels in patients, but not in controls. The present results suggest that oxidative stress-induced damage may be involved in the pathogenesis of schizophrenia.

  10. Increased plasma levels of soluble IL-2R are associated with severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; Morris-Jones, S; Theander, T G;

    1994-01-01

    Plasma samples from children with mild and severe Plasmodium falciparum malaria and from children with unrelated diseases were collected to investigate whether the clinical outcome of infection was associated with plasma factors which reflected the activity of different cells of the immune system....... Children with severe P. falciparum malaria had significantly higher plasma levels of soluble IL-2R than children with mild malaria. Plasma levels of IL-2R and levels of parasitaemia were significantly correlated. Neither parasitaemia nor plasma levels of tumour necrosis factor-alpha (TNF-alpha), IL-6......, lymphotoxin (LT), interferon-gamma (IFN-gamma), IL-4, soluble IL-4R or soluble CD8 differed significantly between the two groups of children with malaria. High plasma levels of soluble CD8 were associated with failure of lymphocytes to produce IFN-gamma in vitro following stimulation with P. falciparum...

  11. Simultaneous stereoselective analysis of tramadol and its primary phase I metabolites in plasma by liquid chromatography. Application to a pharmacokinetic study in humans.

    Science.gov (United States)

    Campanero, Miguel Angel; García-Quetglas, Emilio; Sádaba, Belén; Azanza, Jose Ramón

    2004-03-26

    This paper describes a bioanalytical method involving a simple liquid-liquid extraction for the simultaneous HPLC determination of the enantiomers of tramadol, the active metabolite O-desmethyltramadol (M1), and the other main metabolite N-desmethyltramadol (M2) in biological samples. Chromatography was performed at 5 degrees C on a Chiracel OD-R column containing cellulose tris(3,5-dimethylphenylcarbamate) as chiral selector, preceded by a achiral end-capped C8 column (LiChrospher 60-RP-selected B 5 microm, 250 mm x 4 mm). The mobile phase was a mixture of phosphate buffer containing sodium perchlorate (1 M) adjusted to pH 2.5-acetonitrile-N,N-dimethyloctylamine (74.8:25:0.2). The flow rate was 0.5 ml/min. Fluorescence detection (lambda(ex) 200 nm/lambda(em) 301 nm) was used. Fluconazol was selected as internal standard. The limit of quantitation of each enantiomer of tramadol and their metabolites was 0.5 ng/ml (sample size = 0.5 ml). The chiral conditions and the LC optimisation were investigated in order to select the most appropriate operating conditions. The method developed has also been validated. Mean recoveries above of 95% for each enantiomer were obtained. Calibration curves for tramadol enantiomers (range 1-500 ng/ml), M1 enantiomers (range 0.5-100 ng/ml), and M2 enantiomers (range 0.5-250 ng/ml) were linear with coefficients of correlation better than 0.996. Within-day variation determined on four different concentrations showed acceptable values. The relative standard deviation (R.S.D.) was determined to be less than 10%. This method was successfully used to investigate plasma concentration of enantiomers of tramadol, O-desmethyltramadol and N-desmethyltramadol in a pharmacokinetic study.

  12. Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3-methoxy-4-hydroxyphenylglycol and homovanillic acid in Japanese patients with major depressive disorder

    Science.gov (United States)

    Atake, Kiyokazu; Yoshimura, Reiji; Hori, Hikaru; Katsuki, Asuka; Nakamura, Jun

    2015-01-01

    Purpose This study investigated the relationships among the plasma levels of catecholamine metabolites, the clinical response to duloxetine treatment, and Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene. Subjects and methods Sixty-four patients and 30 healthy control subjects were recruited. Major depressive episodes were diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. The severity of depression was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD17). Patients whose HAMD17 scores were 15 or greater were enrolled in the study. Blood sampling and clinical evaluation were performed at week 0 and week 8. The levels of plasma catecholamine metabolites were measured using high-performance liquid chromatography with electrochemical detection. Genotyping was performed using direct sequencing. Results Thirty of 45 patients (67%) responded to duloxetine treatment during the 8 weeks of treatment. The baseline plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), but not homovanillic acid (HVA), were lower in patients with major depressive disorder (MDD) who had the Val/Val genotype than in patients who were Met-carriers. Patients with MDD and the Val/Val genotype, but not Met carriers, had increased plasma levels of MHPG after 8 weeks of duloxetine treatment. The baseline plasma MHPG levels in healthy control subjects with the Val/Val genotype were significantly higher than those in patients with MDD. Among the subjects in the MDD group with the Val/Val genotype, the plasma MHPG levels increased to the same degree as in the healthy control subjects with the Val/Val genotype after 8 weeks of duloxetine treatment. Conclusion The relationship among the COMT Val158Met polymorphism, plasma levels of catecholamine metabolites, and responses to duloxetine is complex. Nevertheless, our results suggest that patients with MDD and the

  13. Blood levels of polychlorinated biphenyls and their hydroxylated metabolites in Baikal seals (Pusa sibirica): emphasis on interspecies comparison, gender difference and association with blood thyroid hormone levels.

    Science.gov (United States)

    Imaeda, Daisuke; Nomiyama, Kei; Kunisue, Tatsuya; Iwata, Hisato; Tsydenova, Oyuna; Amano, Masao; Petrov, Evgeny A; Batoev, Valeriy B; Tanabe, Shinsuke

    2014-11-01

    We have previously demonstrated that Baikal seals (Pusa sibirica) are still being exposed to polychlorinated biphenyls (PCBs), and the population is at risk. In the present study, we measured the residue levels of PCBs and their hydroxylated metabolites (OH-PCBs) in the blood of Baikal seals and assessed the impact of OH-PCBs on the thyroid function. Blood concentrations of PCBs and OH-PCBs were in the range of 2.8-130 ng g(-1)wet wt. and 0.71-4.6 ng g(-1)wetwt., respectively. Concentrations of higher-chlorinated OH-PCBs (hexa- to octa-PCBs) were more than 70% to total OH-PCB concentrations, indicating Baikal seals are mostly risked by higher-chlorinated OH-PCBs. High levels of 4OH-CB146 and 4OH-CB187 and low levels of 4OH-CB107/4'OH-CB108 found in Baikal seals were different from those in other phocidae species, suggesting the unique drug-metabolizing enzyme activities and/or contamination sources in this species. Concentrations of some OH-PCBs in males were significantly higher than those in females. These results suggest that these isomers may be preferentially transferred from mother to pup via cord blood. However, concentrations of almost all the isomers were not significantly correlated with the levels of blood total T3 and T4, implying less impact of PCB-related compounds on the thyroid hormone circulation.

  14. Simultaneous determination of morniflumate and its major active metabolite, niflumic acid, in human plasma by high-performance liquid chromatography in stability and pharmacokinetic studies.

    Science.gov (United States)

    Cho, Hea-Young; Park, Geun-Kyeong; Lee, Yong-Bok

    2013-11-01

    A rapid, sensitive and stable high-performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of morniflumate and its major active metabolite, niflumic acid, in human plasma. HPLC analysis was carried out using a 5 µm particle size, C18 -bonded silica column with a mixture of acetonitrile and 0.005 m potassium phosphate monobasic in water (60:40, v/v) as the mobile phase and UV detection at 287 nm. The method involved the treatment with 50 μL of 0.4 m hydrochloric acid for the stability of morniflumate, extraction with diethylether and evaporation to dryness under a nitrogen stream. The lower limit of quantitation for morniflumate and niflumic acid was 50 and 500 ng/mL, respectively. The calibration curves for morniflumate and niflumic acid were linear over the concentration range of 50-20,000 ng/mL and 500-50,000 ng/mL, respectively, with correlation coefficients greater than 0.9995 and inter- or intra-batch coefficients of variation not exceeding 13.79%. The variability (percentage difference) of incurred sample re-analysis did not exceed 11.72% and all of the repeat samples fell within 20% of the mean value. This assay procedure was applied successfully to an examination of the pharmacokinetics of morniflumate and its metabolite, niflumic acid, in human subjects.

  15. The Measurement of Meloxicam and Meloxicam Metabolites in Rat Plasma Using a High-Performance Liquid Chromatography-Ultraviolet Spectrophotometry Method.

    Science.gov (United States)

    Miyamoto, Aoi; Aoyama, Takahiko; Matsumoto, Yoshiaki

    2017-02-01

    A high-performance liquid chromatography-ultraviolet spectrophotometry (HPLC-UV) method for the determination of meloxicam (MEL) and meloxicam metabolites (5'-hydroxy meloxicam (5-HMEL) and 5'-carboxy meloxicam (5-CMEL)) has been developed. After extraction of MEL, 5-HMEL, and 5-CMEL from rat plasma using Oasis HLB cartridges, the extracts were separated with a Luna C18 (2) 100 A column (5 µm, 4.6×150 mm, Phenomenex) using a mobile phase of 50 mM phosphate buffer (pH 2.15, solvent A) and acetonitrile (solvent B) at a flow rate of 0.8 mL/min in a linear gradient. The detection wavelength was 360 nm, and the internal standard (IS) was piroxicam. Each calibration curve was linear in the range of 40 to 1000 ng/mL (r(2)>0.999). The extraction rates of MEL, 5-HMEL, and 5-CMEL were greater than 86.9%. The intra- and inter-day accuracies were in the range of 95.0 to 119.0%, and the precision was 0.2 to 17.0%. To the best of our knowledge, this is the first report of the quantitative and qualitative measurement of meloxicam and each metabolite using an HPLC-UV method.

  16. Simultaneous determination of quetiapine and three metabolites in human plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Kun-yanLI; Ze-nengCHENG; XinLI; Xue-lianBAI; Bi-kuiZHANG; FengWANG; Huan-deLI

    2004-01-01

    AIM:To develop a high performance liquid chromatography-electrospray mass spectrometry (HPLC-MS/ESI)method for simultaneous determination of quetiapine and its sulfoxide-, 7-hydroxy-, 7-hydroxy-N-dealkyl-metabolites in human plasma. METHODS: The HPLC separation of the compounds was performed on a Kromasil C18, (5μm, 4.6 mm×150 mm) column, using water (formic acid: 1.70 mmol/L, ammonium acetate: 5.8 mmol/L)-acetoni-trile (65:35) as mobile phase, with a flow-rate of 0.95 mL/min. The compounds were ionized in the electrospray ionization (ESI) ion source of the mass spectrometer and detected in the selected ion recording (SIR) mode. The samples were extracted using solid-phase extraction columns. RESULTS: The calibration curves were linear in theranges of 10-2000 μg/L for quetiapine, 1-200 μg/L for its metabolites, respectively. The average extraction recoveries for all the four samples were above 85 %. The methodology recoveries were much higher than 95 %. Theintra-day and inter-day RSD are less than 15 %. CONCLUSION: The method is accurate, sensitive, and simple for study of pharmacokinetics and metabolic mechanism of quetiapine in patients at therapeutic dose.

  17. Development of a sensitive UPLC-ESI-MS/MS method for quantification of sofosbuvir and its metabolite, GS-331007, in human plasma: Application to a bioequivalence study.

    Science.gov (United States)

    Rezk, Mamdouh R; Basalious, Emad B; Karim, Iman A

    2015-10-10

    A rapid and simple LC-MS/MS method was developed and validated for the simultaneous estimation of sofosbuvir (SF) and its metabolite GS-331007 (GS) using famotidine as an internal standard (IS). The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Extraction with ethyl acetate was used in sample preparation. The prepared samples were chromatographed on Acquity UPLC HSS C₁₈ (50 mm × 2.1 mm, 1.8 μm) column by pumping 0.1% formic acid and acetonitrile (50:50, v/v) in an isocratic mode at a flow rate of 0.3 ml/min. Method validation was performed as per the FDA guidelines and the standard curves were found to be linear in the range of 10-2500 ng/ml for both SF and its metabolite. The intra-day and inter-day precision and accuracy results were within the acceptable limits. A very short run time of 1.2 min made it possible to analyze more than 300 human plasma samples per day. The developed assay method was successfully applied to a bioequivalence study in human volunteers.

  18. Temporal variability of pyrethroid metabolite levels in bedtime, morning, and 24-h urine samples for 50 adults in North Carolina.

    Science.gov (United States)

    Morgan, Marsha K; Sobus, Jon R; Barr, Dana Boyd; Croghan, Carry W; Chen, Fu-Lin; Walker, Richard; Alston, Lillian; Andersen, Erik; Clifton, Matthew S

    2016-01-01

    Pyrethroid insecticides are widely used to control insects in both agricultural and residential settings worldwide. Few data are available on the temporal variability of pyrethroid metabolites in the urine of non-occupationally exposed adults. In this work, we describe the study design and sampling methodology for the Pilot Study to Estimate Human Exposures to Pyrethroids using an Exposure Reconstruction Approach (Ex-R study). Two major objectives were to quantify the concentrations of several pyrethroid metabolites in bedtime, first morning void (FMV), and 24-h urine samples as concentration (wet weight), specific-gravity (SG) corrected, creatinine (CR) corrected, and excretion rate values for 50 Ex-R adults over a six-week monitoring period and to determine if these correction approaches for urine dilution reduced the variability of the biomarker levels. The Ex-R study was conducted at the United States Environmental Protection Agency's Human Studies Facility in Chapel Hill, North Carolina USA and at participants' homes within a 40-mile radius of this facility. Recruitment of participants and field activities occurred between October 2009 and May 2011. Participants, ages 19-50 years old, provided daily food, activity, and pesticide-use diaries and collected their own urine samples (bedtime, FMV, and 24-h) during weeks 1, 2, and 6 of a six-week monitoring period. A total of 2503 urine samples were collected from the study participants. These samples were analyzed for the pyrethroid metabolites 3-phenoxybenzoic acid (3-PBA), cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid (cis/trans-DCCA), and 2-methyl-3-phenylbenzoic acid (MPA) using high performance liquid chromatography/tandem mass spectrometry. Only 3-PBA was frequently detected (>50%) in the adult urine samples. Median urinary 3-PBA levels were 0.88 ng/mL, 0.96 ng/mL-SG, 1.04 ng/mg, and 1.04 ng/min for concentration, SG-corrected, CR-corrected, and excretion rate values, respectively

  19. Levels of Pesticides and Their Metabolites in Wistar Rat Amniotic Fluids and Maternal Urine upon Gestational Exposure

    DEFF Research Database (Denmark)

    Bossi, Rossana; Vinggaard, Anne Marie; Taxvig, Camilla;

    2013-01-01

    Concentrations of pesticides and selected metabolites in rat urine and amniotic fluid were determined as biomarker upon oral administration of Wistar rats to two pesticide mixtures consisting of three to five pesticides (bitertanol, propiconazole, cypermethrin, malathion, and terbuthylazine......). The pesticides and their metabolites were found in rat amniotic fluid and urine, generally in dose-response concentrations in relation to dosage. The measurement of the substances in the amniotic fluid indicated that the fetus was exposed to the pesticides as well as their metabolites. Moreover, the pesticides...

  20. Levels of Pesticides and Their Metabolites in Wistar Rat Amniotic Fluids and Maternal Urine upon Gestational Exposure

    Science.gov (United States)

    Bossi, Rossana; Vinggaard, Anne Marie; Taxvig, Camilla; Boberg, Julie; Bonefeld-Jørgensen, Eva Cecilie

    2013-01-01

    Concentrations of pesticides and selected metabolites in rat urine and amniotic fluid were determined as biomarker upon oral administration of Wistar rats to two pesticide mixtures consisting of three to five pesticides (bitertanol, propiconazole, cypermethrin, malathion, and terbuthylazine). The pesticides and their metabolites were found in rat amniotic fluid and urine, generally in dose-response concentrations in relation to dosage. The measurement of the substances in the amniotic fluid indicated that the fetus was exposed to the pesticides as well as their metabolites. Moreover, the pesticides detected in urine demonstrated the exposure as well as the ability of the rat to excrete these compounds. PMID:23736656

  1. Physical activity affects plasma coenzyme Q10 levels differently in young and old humans.

    Science.gov (United States)

    Del Pozo-Cruz, Jesús; Rodríguez-Bies, Elisabet; Ballesteros-Simarro, Manuel; Navas-Enamorado, Ignacio; Tung, Bui Thanh; Navas, Plácido; López-Lluch, Guillermo

    2014-04-01

    Coenzyme Q (Q) is a key lipidic compound for cell bioenergetics and membrane antioxidant activities. It has been shown that also has a central role in the prevention of oxidation of plasma lipoproteins. Q has been associated with the prevention of cholesterol oxidation and several aging-related diseases. However, to date no clear data on the levels of plasma Q during aging are available. We have measured the levels of plasmatic Q10 and cholesterol in young and old individuals showing different degrees of physical activity. Our results indicate that plasma Q10 levels in old people are higher that the levels found in young people. Our analysis also indicates that there is no a relationship between the degree of physical activity and Q10 levels when the general population is studied. However, very interestingly, we have found a different tendency between Q10 levels and physical activity depending on the age of individuals. In young people, higher activity correlates with lower Q10 levels in plasma whereas in older adults this ratio changes and higher activity is related to higher plasma Q10 levels and higher Q10/Chol ratios. Higher Q10 levels in plasma are related to lower lipoperoxidation and oxidized LDL levels in elderly people. Our results highlight the importance of life habits in the analysis of Q10 in plasma and indicate that the practice of physical activity at old age can improve antioxidant capacity in plasma and help to prevent cardiovascular diseases.

  2. Metabolite identification of seven active components of Huan-Nao-Yi-Cong-Fang in rat plasma using high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry.

    Science.gov (United States)

    Wang, Minchao; Lu, Yanzhen; Liu, Jiangang; Li, Hao; Wei, Yun

    2016-02-01

    Huan-Nao-Yi-Cong-Fang (HNYCF) is a potential prescription in treating Alzheimer's disease. Seven constituents [ferulic acid (FA), 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG), berberine hydrochloride (BHCl), emodin, ginsenoside Rg1 (Rg1), ginsenoside Re (Re) and ginsenoside Rb1 (Rb1)] have been used as quality chemical markers of HNYCF owing to their biological significance and high contents in crude plant materials. This study explored the metabolites of the seven bioactive components in rat plasma to give useful data for further study of the action mechanism of HNYCF. LC/MS-IT-TOF was used to simultaneously characterize the metabolites of the seven components. Using the combination of MetID Solution 1.0 software and accurate mass measurements, the metabolites of HNYCF were reliably characterized. Their structures were elucidated based on the accurate MS(2) spectra and comparisons of their changes in accurate molecular masses and fragment ions with those of parent compounds. A total of five parent active compounds (BHCl, emodin, Rg1, Rb1 and Re) and 10 metabolites were found from the rat plasma 2 h after oral administration of HNYCF dosage, of which two metabolites of emodin were observed for the first time. The proposed metabolic pathways of the bioactive components in the rat plasma are helpful for further studies on the pharmacokinetics and real active compound forms of this drug.

  3. Disulfiram Metabolite S-Methyl-N, N-Diethylthiocarbamate Quantitation in Human Plasma with Reverse Phase Ultra Performance Liquid Chromatography and Mass Spectrometry

    Science.gov (United States)

    Hochreiter, Jill; McCance-Katz, Elinore F.; Lapham, Jill; Ma, Qing; Morse, Gene D.

    2012-01-01

    Disulfiram has been used extensively for alcohol abuse and may have a role in treatment for cocaine addiction. Recent data suggest that disulfiram may also reactivate latent HIV in reservoirs. Disulfiram has complex pharmacokinetics with rapid metabolism to active metabolites, including S-Methyl-N, N-Diethylthiocarbamate (DET-Me) which is formed from cytochrome P450 (CYP450). Assessing disulfiram in HIV-infected individuals with a CYP450 inducing drug (e.g., efavirenz) or a CYP450 inhibiting drug (e.g., HIV-1 protease inhibitors) requires an assay that can measure a metabolite that is formed directly via CYP450 oxidation. Therefore, an assay to measure concentrations of DET-Me in human plasma was validated. DET-Me and the internal standard, S-ethyldipropylthiocarbamate (EPTC) were separated by isocratic ultra performance liquid chromatography using a Waters Acquity HSS T3 column (2.1×100mm, 1.8μm) and detection via electrospray coupled to a triple quadrupole mass spectrometer. Multiple reaction monitoring in positive mode was used with DET-Me at 148/100 and the internal standard at 190/128 with a linear range of 0.500 to 50.0 ng/mL with a five minute run time. Human plasma (500 μL) was extracted using a solid phase procedure. The interassay variation ranged from 1.86 to 7.74% while the intra assay variation ranged from 3.38 to 5.94% over three days. Representative results are provided from samples collected from subjects receiving daily doses of disulfiram 62.5 mg or 250 mg. PMID:22534656

  4. Measurement of 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid and its metabolite 12-oxo-5Z,8E,10E-heptadecatrienoic acid in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, U.; Seefried, S.; Meese, C.O.; Mettang, T.; Huebel, E.K.; Kuhlmann, U. (Dr. Margarete Fischer-Bosch-Institut fuer Klinische Pharmakologie, Stuttgart (Germany, F.R.))

    1990-09-01

    Thromboxane A2, the predominant product of arachidonic acid metabolism in the blood platelet, is a potent vasoconstrictor and platelet agonist. During its biosynthesis from cyclic endoperoxide, 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) is formed in equal amounts. The further metabolism of HHT, catalyzed by 15-hydroxyprostaglandin dehydrogenase, leads to 12-oxo-5Z,8E,10E-heptadecatrienoic acid (Oxo-HT). Sample workup procedures are described which allow for the sensitive and reproducible determination of these two arachidonic acid metabolites in human plasma by gas chromatography-mass spectrometry in the presence of deuterated analogues as internal standards. HHT is derivatized to the pentafluorobenzyl ester tert-butyldimethylsilyl ether. In order to enable quantification of low concentrations of about 10 pg/ml in nonstimulated human plasma, the samples have to be purified by HPLC. Oxo-HT is derivatized to the pentafluorobenzyl ester, which is purified by HPLC, and then derivatized to the trimethylsilyloxime. The method allows quantification of Oxo-HT in concentrations down to 10 pg/ml plasma. The reported methods have been used to measure HHT and Oxo-HT in stimulated platelet rich plasma and to quantify HHT in nonstimulated plasma. Determination of endogenous levels of these two arachidonic acid metabolites may give new insights into the overall biosynthesis of thromboxane A2 in man.

  5. Zinc and copper levels in plasma, erythrocytes, and whole blood in cancer patients.

    Science.gov (United States)

    Aldor, Y; Walach, N; Modai, D; Horn, Y

    1982-04-01

    Zinc and copper levels in erythrocytes, plasma, and whole blood were determined in 35 cancer patients and compared with 24 normal individuals. A decrease in zinc was found in all three blood constituents of the cancer patients. The decrease was significant in plasma and whole blood and nonsignificant in erythrocytes. Copper levels in the cancer group showed a slight and nonsignificant increase in erythrocytes, plasma, and whole blood. The copper to zinc ratio revealed a significant increase only for plasma levels. Further investigations are indicated to determine whether these two elements could serve as indicators for diagnosis or prognosis in cancer patients.

  6. Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Gert T. Verhoeven

    2001-01-01

    Full Text Available Background: In smoking COPD patients the bronchoalveolar lavage (BAL fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA metabolites, which contribute to inflammation and an increased bronchomotor tone.

  7. Determination of intracellular levels of 6-mercaptopurine metabolites in erythrocytes utilizing capillary electrophoresis with laser-induced fluorescence detection.

    Science.gov (United States)

    Rabel, S R; Stobaugh, J F; Trueworthy, R

    1995-01-01

    Capillary electrophoresis proved to be a useful technique for the analysis of intracellular levels of 6-thioguanosine mono-, di-, and triphosphate with analysis times of 20 min. Conditions required for baseline separation of the thioguanine nucleotides consisted of a 25 mM KH2PO4 (pH 8.0) buffer and a separation voltage of +28 kV. Laser-induced fluorescence detection (lambda ex = 325 nm, lambda em = 410 nm) of the thioguanine nucleotide metabolites of 6-mercaptopurine (6-MP) was possible following oxidation of the thiol functionality. Tedious extraction procedures involving mercury cellulose resins or phenyl mercury adduct formation, which had been required previously for the selective extraction of thiopurines from erythrocytes, were unnecessary due to the overall specificity of the approach. However, the inclusion of 50 mM EDTA in the sample preparation was required to inhibit the anabolic/catabolic enzymatic activity, which was responsible for the degradation of the analytes. The method demonstrated linearity from 5 to 1700 pmol/100 microliters red blood cells for the three analytes (RSDs < or = 8%). The feasibility of the method was demonstrated for the quantitation of 6-thioguanine nucleotides in patients receiving either oral or intravenous 6-MP therapy.

  8. A validated enantioselective LC-MS/MS assay for quantification of a major chiral metabolite of an achiral 11-β-hydroxysteroid-dehydrogenase 1 inhibitor in human plasma: Application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Furlong, Michael T; Ji, Qin C; Iacono, Lisa; Dang, Oanh; Noren, Marzena; Bruce, John; Aubry, Anne-Françoise; Arnold, Mark E

    2016-06-01

    BMS-823778 is a potent 11-β-hydroxysteroid-dehydrogenase 1 (11βHSD-1) inhibitor and a potential therapeutic agent for type 2 diabetes mellitus (T2DM). A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed and validated to enable reliable separation and quantification of both enantiomers of a chiral hydroxy metabolite (BMT-094817) in human plasma. Following liquid-liquid extraction in a 96-well plate format, chromatographic separation of the metabolite enantiomers was achieved by isocratic elution on a Chiralpak IA-3 column. Chromatographic conditions were optimized to ensure separation of both metabolite enantiomers. Metabolite enantiomers and stable isotope-labeled (SIL) internal standards were detected by positive ion electrospray tandem mass spectrometry. The LC-MS/MS assay was validated over a concentration range of 0.200-200ng/mL. Intra- and inter-assay precision values for replicate quality control samples were less than 9.9% for both enantiomers during the assay validation. Mean quality control accuracy values were within ±7.3%. Assay recoveries were high (>75%) and consistent across the assay range. The metabolite enantiomers were stable in human blood for 2h on ice. The analytes were also stable in human plasma for 25h at room temperature, 34days at -20°C and -70°C, and following five freeze-thaw cycles. No interconversion of the metabolite enantiomers was detected under any bioanalytical stress conditions, from blood collection/processing through extracted sample storage. The validated assay was successfully applied to the quantification of both metabolite enantiomers in human plasma in support of a human pharmacokinetic study.

  9. Unbiased Scanning Method and Data Banking Approach Using Ultra-High Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry for Quantitative Comparison of Metabolite Exposure in Plasma across Species Analyzed at Different Dates.

    Science.gov (United States)

    Gao, Hongying; Deng, Shibing; Obach, R Scott

    2015-12-01

    An unbiased scanning methodology using ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry was used to bank data and plasma samples for comparing the data generated at different dates. This method was applied to bank the data generated earlier in animal samples and then to compare the exposure to metabolites in animal versus human for safety assessment. With neither authentic standards nor prior knowledge of the identities and structures of metabolites, full scans for precursor ions and all ion fragments (AIF) were employed with a generic gradient LC method to analyze plasma samples at positive and negative polarity, respectively. In a total of 22 tested drugs and metabolites, 21 analytes were detected using this unbiased scanning method except that naproxen was not detected due to low sensitivity at negative polarity and interference at positive polarity; and 4'- or 5-hydroxy diclofenac was not separated by a generic UPLC method. Statistical analysis of the peak area ratios of the analytes versus the internal standard in five repetitive analyses over approximately 1 year demonstrated that the analysis variation was significantly different from sample instability. The confidence limits for comparing the exposure using peak area ratio of metabolites in animal plasma versus human plasma measured over approximately 1 year apart were comparable to the analysis undertaken side by side on the same days. These statistical analysis results showed it was feasible to compare data generated at different dates with neither authentic standards nor prior knowledge of the analytes.

  10. Comparative evaluation of plasma ROM levels in chronic periodontitis patients before and after non-surgical and surgical periodontal therapy: A clinical trial

    Science.gov (United States)

    Chaudhary, Sohini; Gowda, Triveni M.; Mehta, Dhoom S.; Kumar, Tarun A. B.

    2014-01-01

    Objective: Chronic periodontitis (CP) is associated with increased levels of blood reactive oxygen species (ROS). So, treatment of CP may lead to decrease in blood ROS. However, not much literature is available comparing the effect of surgical and non-surgical periodontal treatment on blood ROS levels. Reactive oxygen metabolites (ROMs) are a useful measure of blood ROS. The aim of this study was to investigate the effect of periodontal treatment on plasma ROM levels in CP patients. Materials and Methods: Thirty CP patients and 15 controls were monitored. Plasma samples were collected at baseline and the clinical parameters were recorded. The CP patients were randomly divided into two groups: Scaling and root planing (Group II) and periodontal flap surgery (Group III). Both groups were re-evaluated 1 and 2 months after therapy. Clinical parameters were reviewed, plasma samples collected, and ROM levels were determined using a spectrophotometric technique. Results: At baseline, the ROM levels for Group II and Group III were 519.8 ± 62.4 and 513.4 ± 74.7 CARR U, respectively, which were higher than Group I value (282.9 ± 23.9, P surgical periodontal treatment was more effective in lowering the plasma ROM levels than when non-surgical periodontal treatment was performed alone and, therefore, may be more beneficial in reducing systemic oxidative stress. PMID:24872618

  11. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine frompatients with bladder cancer

    DEFF Research Database (Denmark)

    Holten Andersen, MN; Brunner, N; Nielsen, HJ;

    2006-01-01

    Aim: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. Methods: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...

  12. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine from patients with cancer

    DEFF Research Database (Denmark)

    Holten-Andersen, Mads Nikolaj; Brünner, Nils; Nielsen, Hans Jørgen;

    2006-01-01

    AIM: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. METHODS: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...

  13. Plasma levels of apolipoprotein E and risk of stroke in old age

    NARCIS (Netherlands)

    Vliet, P. van; Mooijaart, S.P.; Craen, A.J.M. de; Rensen, P.C.N.; Heemst, D. van; Westendorp, R.G.J.

    2007-01-01

    Recently, high plasma apoE levels have been shown to be related to increased cardiovascular mortality, independent of APOE genotype. Here we studied the association of plasma apoE levels with risk of stroke. Within the Leiden 85-plus Study, a prospective population-based study of 561 subjects aged

  14. Plasma levels of apolipoprotein E and cognitive function in old age

    NARCIS (Netherlands)

    Mooijaart, S.P.; Vliet, P. van; Heemst, D. van; Rensen, P.C.N.; Berbée, J.F.P.; Jolles, J.; Craen, A.J.M. de; Westendorp, R.G.J.

    2007-01-01

    The relationship between structural variants of the apolipoprotein E gene, APOE ε2/ε3/ε4, and dementia is well established, whereas the relationship of plasma apoE levels with dementia is less clear. Plasma apoE levels are under tight genetic control but vary widely within the various genotypes

  15. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine from patients with cancer

    DEFF Research Database (Denmark)

    Holten-Andersen, Mads Nikolaj; Brünner, Nils; Nielsen, Hans Jørgen

    2006-01-01

    AIM: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. METHODS: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...

  16. Caloric restriction and exercise increase plasma ANGPTL4 levels in humans via elevated free fatty acids

    NARCIS (Netherlands)

    Kersten, S.; Lichtenstein, L.; Steenbergen, E.; Mudde, K.; Hendriks, H.F.J.; Hesselink, M.K.; Schrauwen, P.; Müller, M.

    2009-01-01

    OBJECTIVE-: Plasma lipoprotein levels are determined by the balance between lipoprotein production and clearance. Recently, angiopoietin-like protein 4 (ANGPTL4) was uncovered as a novel endocrine factor that potently raises plasma triglyceride levels by inhibiting triglyceride clearance. However, v

  17. Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris

    NARCIS (Netherlands)

    Maat, M.P.M. de; Arnold, A.E.R.; Buuren, S. van; Paul Wilson, J.H.; Kluft, C.

    1996-01-01

    Elevated plasma fibrinogen levels represent an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The

  18. Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris

    NARCIS (Netherlands)

    Maat, M.P.M. de; Arnold, A.E.R.; Buuren, S. van; Wilson, J.H.P.; Kluft, C.

    1996-01-01

    Elevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases.

  19. Plasma S100 beta and NSE levels and progression in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus; Mostert, Jop; Heersema, Dorothea; Teelken, Albert; De Keyser, Jacques

    2007-01-01

    Plasma levels of the glial cell marker S100 beta and the neuronal marker neuron-specific enolase (NSE) are elevated in various conditions of central nervous system damage. In this study we investigated whether plasma levels of S 1000 and NSE are related to disease progression in multiple sclerosis (

  20. Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris

    NARCIS (Netherlands)

    Maat, M.P.M. de; Arnold, A.E.R.; Buuren, S. van; Paul Wilson, J.H.; Kluft, C.

    1996-01-01

    Elevated plasma fibrinogen levels represent an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechan

  1. Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris

    NARCIS (Netherlands)

    Maat, M.P.M. de; Arnold, A.E.R.; Buuren, S. van; Wilson, J.H.P.; Kluft, C.

    1996-01-01

    Elevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases.

  2. Plasma S100 beta and NSE levels and progression in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus; Mostert, Jop; Heersema, Dorothea; Teelken, Albert; De Keyser, Jacques

    2007-01-01

    Plasma levels of the glial cell marker S100 beta and the neuronal marker neuron-specific enolase (NSE) are elevated in various conditions of central nervous system damage. In this study we investigated whether plasma levels of S 1000 and NSE are related to disease progression in multiple sclerosis (

  3. Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model

    Science.gov (United States)

    Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasm...

  4. Whey Protein Delays Gastric Emptying and Suppresses Plasma Fatty Acids and Their Metabolites Compared to Casein, Gluten, and Fish Protein

    DEFF Research Database (Denmark)

    Stanstrup, Jan; Schou, Simon S; Holmer-Jensen, Jens

    2014-01-01

    Whey protein has been demonstrated to improve fasting lipid and insulin response in overweight and obese individuals. To establish new hypotheses for this effect and to investigate the impact of stomach emptying, we compared plasma profiles after intake of whey isolate (WI), casein, gluten (GLU...

  5. Population plasma and urine pharmacokinetics of ivabradine and its active metabolite S18982 in healthy Korean volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Bae, Kyun-Seop; Cho, Sang-Heon; Ghim, Jong-Lyul; Choe, Sangmin; Jung, Jin Ah; Lim, Hyeong-Seok

    2016-04-01

    Ivabradine, a selective inhibitor of the pacemaker current (If ), is used for heart failure and coronary heart disease and is mainly metabolized to S18982. The purpose of this study was to explore the pharmacokinetics (PK) of ivabradine and S18982 in healthy Korean volunteers. Subjects in a phase I study were randomized to receive 2.5, 5, or 10 mg of ivabradine administered every 12 hours for 4.5 days, and serial plasma and urine concentrations of ivabradine and S18982 were measured. The plasma PK of ivabradine was best described by a 2-compartment model with mixed 0- and first-order absorption, linked to a 2-compartment model for S18982. The introduction of interoccasional variabilities and period as covariate into absorption-related parameters improved the model fit. Urine data have been applied to estimate renal and nonrenal clearance, enabling a more detailed description of the elimination process. We developed a population PK model describing the plasma and urine PK of ivabradine and S18982 in healthy Korean adult males. This model might be useful for predicting the plasma and urine PK of ivabradine, potentially helping to identify the optimal dosing regimens in various clinical situations.

  6. Plasma Histamine And Serotonin Levels In Children With Nephrotic Syndrome And Acute Poststreptococcal Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Nagwa Mohamed and Talaat El sayed

    2005-12-01

    Full Text Available Plasma histamine and serotonin concentrations were measured using fluorimeteric assay in 40 children with renal diseases. Minimal change nephrotic syndrome (15 focal segmental glomerulosclerosis(10 and acute poststreptococcal glomerulonephritis(15 to determine the relation between plasma levels of histamine and serotonin and these various types of renal diseases in children. Plasma histamine level was significantly increased in group of children with acute poststreptococcal glomerulonephritis. Plasma serotonin levels were significantly increased in all 3 groups of patient, when compared with those of controls. Raised plasma histamine in acute poststreptococcal glomerulonephritis group may be evidence of the acute immunological inflammation and defective renal excretion due to mild renal impairment in these children. Raised plasma serotonin in all 3 groups of patients may be due to diminished uptake and release of serotonin from platelets in children with minimal change nephrotic syndrome and focal segmental glomerulosclerosis and due to defective renal execretion in children with acute poststreptococcal glomerulo-nephritis.

  7. Plasma levels of oestriol-17 beta, oestriol and human placental lactogen during bed rest.

    Science.gov (United States)

    Chew, P C; Mok, H; Ratnam, S S

    1976-11-01

    Plasma unconjugated oestradiol-17 beta, total oestriol and human placental lactogen levels were measured in twelve healthy volunteers admitted for bed rest in the last trimester of pregnancy. No significant alteration in levels was observed.

  8. Study of plasma amino acid levels in children with autism: An Egyptian sample

    Directory of Open Access Journals (Sweden)

    Farida M. ElBaz

    2014-04-01

    Conclusions: Autistic children had lower levels of some plasma amino acids except for glycine and glutamic acids and phosphoserine were increased with normal serum levels of urea, ammonia, total proteins, albumin and globulins (alpha 1, alpha 2, beta and gamma.

  9. Plasma ion levels of freshwater and marine/estuarine teleosts from Southern Brazil

    Directory of Open Access Journals (Sweden)

    Alexssandro Geferson Becker

    Full Text Available The purpose of this study was to investigate Na+, Cl-, K+, Ca2+, and Mg2+ levels in the plasma of freshwater and marine/estuarine teleosts collected at different salinities (0 to 34 from the estuarine and freshwater portions of the São Gonçalo channel in Southern Brazil. Any relationship between plasma ion levels and salinity and the capacity of ionic regulation of teleosts found at three or more different salinities (Genidens barbus and Micropogonias furnieri was also investigated. Results showed no relationship between plasma ion levels and salinity when considering all species together, but the two species collected from three or more different salinities showed a significant positive relationship between plasma ion levels and salinity, indicating that G. barbus and M. furnieri have a high capacity to regulate plasma ion levels at both low and high salinities.

  10. The contribution of different adipose tissue depots to plasma plasminogen activator inhibitor-1 (PAI-1) levels.

    Science.gov (United States)

    Barnard, Sunelle A; Pieters, Marlien; De Lange, Zelda

    2016-11-01

    Increased plasma plasminogen activator inhibitor-1 (PAI-1) level is considered a mechanistic pathway through which obesity contributes to increased cardiovascular disease risk. Abdominal adipose tissue specifically, is a major PAI-1 source with visceral adipose tissue (VAT), an ectopic fat depot, generally considered to produce more PAI-1 than subcutaneous adipose tissue. However, this does not necessarily lead to increased plasma PAI-1 levels. This review provides an overview of studies investigating the association between body fat distribution and plasma PAI-1 levels. It discusses factors that influence this relationship and also considers the contribution of other tissue to plasma PAI-1 levels, placing the relative contribution of adipose tissue into perspective. In conclusion, the relationship between VAT and plasma PAI-1 levels is not fixed but can be modulated by a number of factors such as the size of the subcutaneous adipose tissue depot, ethnicity, possibly genetics and other obesity-related metabolic abnormalities.

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

    Science.gov (United States)

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

    1999-02-01

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

  12. Comparative evaluation of plasma ROM levels in chronic periodontitis patients before and after non-surgical and surgical periodontal therapy: A clinical trial

    Directory of Open Access Journals (Sweden)

    Sohini Chaudhary

    2014-01-01

    Full Text Available Objective: Chronic periodontitis (CP is associated with increased levels of blood reactive oxygen species (ROS. So, treatment of CP may lead to decrease in blood ROS. However, not much literature is available comparing the effect of surgical and non-surgical periodontal treatment on blood ROS levels. Reactive oxygen metabolites (ROMs are a useful measure of blood ROS. The aim of this study was to investigate the effect of periodontal treatment on plasma ROM levels in CP patients. Materials and Methods: Thirty CP patients and 15 controls were monitored. Plasma samples were collected at baseline and the clinical parameters were recorded. The CP patients were randomly divided into two groups: Scaling and root planing (Group II and periodontal flap surgery (Group III. Both groups were re-evaluated 1 and 2 months after therapy. Clinical parameters were reviewed, plasma samples collected, and ROM levels were determined using a spectrophotometric technique. Results: At baseline, the ROM levels for Group II and Group III were 519.8 ± 62.4 and 513.4 ± 74.7 CARR U, respectively, which were higher than Group I value (282.9 ± 23.9, P < 0.001. Periodontal treatment in CP patients resulted in improvement of clinical parameters and a highly significant reduction in plasma ROM level (P < 0.001 after 2 months. Also, there was a more significant reduction in plasma ROM levels in Group III as compared to Group II (P < 0.05. Conclusions: In CP patients, surgical periodontal treatment was more effective in lowering the plasma ROM levels than when non-surgical periodontal treatment was performed alone and, therefore, may be more beneficial in reducing systemic oxidative stress.

  13. Plasma cathepsin S and cystatin C levels and risk of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Lv, Bing-Jie; Lindholt, Jes Sanddal; Cheng, Xiang

    2012-01-01

    Human abdominal aortic aneurysm (AAA) lesions contain high levels of cathepsin S (CatS), but are deficient in its inhibitor, cystatin C. Whether plasma CatS and cystatin C levels are also altered in AAA patients remains unknown.......Human abdominal aortic aneurysm (AAA) lesions contain high levels of cathepsin S (CatS), but are deficient in its inhibitor, cystatin C. Whether plasma CatS and cystatin C levels are also altered in AAA patients remains unknown....

  14. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Hellsten, Ylva

    2013-01-01

    AIMS: Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension...... performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. CONCLUSION: Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes...... plasma endothelin-1 levels in individuals with essential hypertension. This effect may explain some of the beneficial effects of training on the cardiovascular system in older and hypertensive subjects....

  15. Simultaneous determination of praziquantel, pyrantel embonate, febantel and its active metabolites, oxfendazole and fenbendazole, in dog plasma by liquid chromatography/mass spectrometry.

    Science.gov (United States)

    Klausz, Gabriella; Keller, Éva; Sára, Zoltán; Székely-Körmöczy, Péter; Laczay, Péter; Ary, Kornélia; Sótonyi, Péter; Róna, Kálmán

    2015-12-01

    A liquid chromatography-electrospray-mass spectrometry method (LC/MS) has been developed and validated for determination of praziquantel (PZQ), pyrantel (PYR), febantel (FBT), and the active metabolites fenbendazole (FEN) and oxfendazole (OXF), in dog plasma, using mebendazole as internal standard (IS). The method consists of solid-phase extractions on Strata-X polymeric cartridges. Chromatographic separation was carried out on a Phenomenex Gemini C6 -Phenyl column using binary gradient elution containing methanol and 50 mm ammonium-formate (pH 3). The method was linear (r(2)  ≥ 0.990) over concentration ranges of 3-250 ng/mL for PYR andFEB, 5-250 ng/mL for OXF and FEN, and 24-1000 ng/mL for PZQ. The mean precisions were 1.3-10.6% (within-run) and 2.5-9.1% (between-run), and mean accuracies were 90.7-109.4% (within-run) and 91.6-108.2% (between-run). The relative standard deviations (RSD) were <9.1%. The mean recoveries of five targeted compounds from dog plasma ranged from 77 to 94%.The new LC/MS method described herein was fully validated and successfully applied to the bioequivalence studies of different anthelmintic formulations such as tablets containing PZQ, PYR embonate and FBT in dogs after oral administration.

  16. Simultaneous quantification of methylene blue and its major metabolite, azure B, in plasma by LC-MS/MS and its application for a pharmacokinetic study.

    Science.gov (United States)

    Kim, Soo-Jin; Ha, Dong-Jin; Koo, Tae-Sung

    2014-04-01

    A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of methylene blue (MB) and its major metabolite, azure B (AZB), in rat plasma. A simple protein precipitation using acetonitrile was followed by injection of the supernatant on to a Zorbax HILIC Plus column (3.5 µm, 2.1 × 100 mm) with isocratic mobile phase consisting of 5 mM ammonium acetate in 10:90 (v/v) water:methanol at a flow rate of 0.3 mL/min and detection in positive ionization mode. The standard curve was linear over the concentration range from 1 to 1000 ng/mL for MB and AZB with coefficient of determination above 0.9930. The lower limit of quantification was 1 ng/mL using 20 μL of rat plasma sample. The intra- and inter-assay precision and accuracy were <12%. The developed analytical method was successfully applied to the pharmacokinetic study of MB and AZB in rats.

  17. Liquid Chromatography/Tandem Mass Spectrometry for the Simultaneous Determination of Alverine and its Metabolite, Monohydroxy Alverine, in Human Plasma: Application to a Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Rahul C. Gavhane

    2011-01-01

    Full Text Available A rapid and sensitive LC-MS-MS method for the determination of alverine (ALV and its major metabolite, monohydroxy alverine (MHA, in human plasma using imipramine as an internal standard was developed and validated. The analytes were extracted from 0.5 mL aliquots of human plasma by solid phase extraction, using oasis cartridge. Chromatographic separation was carried on Thermo Gold C18 column (50 × 4.6 mm, 5 μ at 30 °C, with isocratic mobile phase, a flow rate of 0.4 mL/min and a total run time of 3.5 min. Detection and quantification were performed using a mass spectrometer in the selected reaction-monitoring mode with positive electrospray ionization at m/z 282.3 → 91.11 for alverine, m/z 298.3 → 106.9 for mono-hydroxy-alverine, and m/z 281.0 → 86.0 for internal standard (IS respectively. This assay was linear over a concentration range of 0.060-10 ng/mL with a lower limit of quantification of 0.060 ng/mL for both alverine and monohydroxy alverine. The coefficient of variation for the assay precision were 104.66% and >100.38% for alverine and monohydroxy alverine respectively. This method was successfully applied to a pharmacokinetic study after oral administration of alverine citrate 60 mg capsule in healthy male subjects.

  18. Optimizing high-performance liquid chromatography method with fluorescence detection for quantification of tamoxifen and two metabolites in human plasma: application to a clinical study.

    Science.gov (United States)

    Zhu, Yu-Bing; Zhang, Qian; Zou, Jian-Jun; Yu, Cui-Xia; Xiao, Da-Wei

    2008-01-22

    We set an improved high-performance liquid chromatography method with fluorescence detection HPLC-FLU assay with more sensitivity and precision for the quantification of tamoxifen and two metabolites: 4-hydroxytamoxifen and N-desmethyltamoxifen. The compounds and internal standard, mexiletine, were separated with an Agilent Extend C18 column set at 65 degrees C and a mobile phase of methanol-1% triethylamine aqueous solution (pH 11; 82:18, v/v). The detection system utilized offline ultraviolet irradiation to convert the analytes to their respective photocyclisation products, followed by fluorescence detection (lambda ex=260 nm and lambda em=375 nm). The limits of quantification for tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen in plasma were improved to 0.5, 0.5 and 0.1 ng/ml, respectively. And the retention times for tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen were minimized to 11, 10 and 3.9 min, respectively. A single stage liquid-liquid extraction method for determination of these triphenylethylene drugs in plasma was developed, with high extraction efficiency and rapid sample treatment for target compounds. The method has been validated for use in a clinical bioavailability research of tamoxifen.

  19. Effects of the percentage of concentrate on rumen fermentation, nutrient digestibility, plasma metabolites, and milk composition in mid-lactation goats.

    Science.gov (United States)

    Serment, A; Schmidely, P; Giger-Reverdin, S; Chapoutot, P; Sauvant, D

    2011-08-01

    The aim of this work was to study the effects of the dietary percentage of concentrate on patterns of intake, the evolution of rumen fermentation characteristics and plasma metabolites after a meal, nutrient digestibility, and milk production and composition in a medium-term trial in dairy goats. These effects have been well studied in dairy cattle but seldom in goats. Thirteen ruminally and duodenally cannulated dairy goats (95±4 d in milk) fed ad libitum were used in this study. Goats were assigned to 1 of 2 dietary treatments: high-concentrate (70% concentrate on dry matter basis) or a low-concentrate (35%) total mixed rations. The experiment was conducted over a period of 10 wk, including 3 wk of adaption to the diets. Patterns of intake, rumen fermentation characteristics, and plasma metabolites after a meal and fatty acids profile of milk fat were compared at the onset and at the end of the experiment. The increase in dietary percentage of concentrate decreased rumen pH, acetate to propionate ratio, ammonia-N concentration, and plasma urea concentration. The percentage of concentrate did not affect total volatile fatty acid concentrations. The high-concentrate diet increased the rate of intake during the morning meal at the onset of the experiment, whereas it decreased total dry matter intake and the rate of intake during the morning meal at the end of the experiment. The high-concentrate diet resulted in greater organic matter digestibility. Raw milk yield and protein yield were greater in goats fed the high-concentrate diet, whereas fat yield was not affected by dietary treatments. The milk fat content was lower in goats fed the high-concentrate diet. Proportions of the trans-C18:1 isomer relative to total fatty acids in milk were higher with the high-concentrate diet, but no modification of the proportion of total trans-C18:1 was detected, in particular no shift from trans-11 C18:1 to trans-10 C18:1 was observed. Further, the isomer trans-10,cis-12 C18

  20. Plasma brain natriuretic peptide levels are elevated in patients with cancer.

    Science.gov (United States)

    Bando, Sachiko; Soeki, Takeshi; Matsuura, Tomomi; Tobiume, Takeshi; Ise, Takayuki; Kusunose, Kenya; Yamaguchi, Koji; Yagi, Shusuke; Fukuda, Daiju; Iwase, Takashi; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Muguruma, Naoki; Takayama, Tetsuji; Kishimoto, Ichiro; Kangawa, Kenji; Sata, Masataka

    2017-01-01

    Natriuretic peptides have been proposed as biomarkers of cardiovascular disease, especially heart failure. Brain natriuretic peptide (BNP) has also been shown to be upregulated at the transcriptional and translational levels by pro-inflammatory cytokines in cardiac myocytes. Although we often measure plasma BNP levels in cancer patients, it remains unknown whether cancer-related inflammation affects the plasma BNP levels. We investigated the relationship between the BNP and human cancers. We retrospectively studied 2,923 patients in whom the plasma BNP levels and serum C-reactive protein (CRP) were measured and echocardiography was performed. Patients with clinically evident heart failure (NYHA II or higher), heart disease requiring medical treatment or surgery, renal dysfunction, and inflammatory disease were excluded. There were 234 patients in the final analysis. Blood sampling was performed before surgery and chemotherapy. In addition, we evaluated the relationship between the inflammation and plasma BNP levels in mouse models of colon cancer. Of the 234 patients, 80 were diagnosed with cancer. Both the plasma BNP and serum CRP levels were significantly higher in cancer patients than those without. There were no significant differences in the echocardiographic parameters. There was a significant positive correlation between the plasma BNP and serum CRP levels in cancer patients (r = 0.360, P<0.01) but not in those without. In cancer patients, only the CRP correlated with the BNP independent of the age, creatinine level, hypertension, and body mass index. In addition, in nude mice with subcutaneous colon cancer, the plasma BNP level was elevated compared with that in non-cancer mice, and there was a significant relationship between the plasma BNP and serum levels of the inflammatory markers. In cancer patients, as well as colon cancer model mice, the plasma BNP levels were elevated, possibly due to cancer-related inflammation. The effect of cancer on the BNP

  1. Post-prandial decrease in plasma growth hormone levels is not related to the increase in plasma insulin levels in goats.

    Science.gov (United States)

    Nishihara, Koki; Kobayashi, Ryoko; Suzuki, Yutaka; Sato, Katsuyoshi; Katoh, Kazuo; Roh, Sang-Gun

    2017-06-26

    In the present study, we examined whether the post-prandial reduction in plasma growth hormone (GH) levels is related to the increase in plasma insulin levels in ruminants. We performed two experiments: intravenous bolus injection of insulin (0.2 IU/kg body weight) or glucose (1.0 mmol/kg body weight) was administered to increase the plasma insulin levels in male Shiba goats. In the insulin injection experiment, significant (pincrease in GH concentrations was observed, 15-20 min after the injection; it was accompanied with a significant (pincrease in cortisol concentrations at 45-90 min, when compared to the concentrations in the saline-injected controls. The glucose injection significantly (pincreased the plasma GH concentration at 20-45 min; this was not accompanied by significantly higher cortisol concentrations than were observed for the saline-injected control. Hypoglycemia induced by the insulin injection, which causes the excitation of the adrenal cortex, might be involved in the increase in insulin levels. Based on these results, we conclude that post-prandial increases in plasma insulin or glucose levels do not induce a decrease in GH concentration after feeding in the ruminants.

  2. Assessment of levels of organochlorine pesticides and their metabolites in the hair of a Greek rural human population.

    Science.gov (United States)

    Tsatsakis, A M; Tzatzarakis, M N; Tutudaki, M; Babatsikou, F; Alegakis, A K; Koutis, C

    2008-12-01

    We present the assessment of chronic exposure of the rural population of Helia Peloponnesus, Greece to banned organochlorine pesticides, hexachlorocyclohexane (HCH), and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), using hair analysis. A total of 222 head hair samples were collected and analyzed for the presence of those organochlorine pesticides and their metabolites or isomers. Gas chromatography coupled to mass spectrometry was used to measure the levels of the pollutants. The median concentrations of alpha-HCH, hexachlorobenzene, lindane, ortho para 1,1-dichloro-2,2-bis-(4-chlorophenyl)ethylene (opDDE), para para 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (ppDDE), ortho para 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (opDDD), para para 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (ppDDD) + ortho para 1,1,1-trichloro-2,2-bis(4-chlorophenyl)-ethane, and para para 1,1,1-trichloro-2,2-bis(4-chlorophenyl)-ethane were determined at 40.4, 19.7, 124.2, 6.2, 7.8, 73.1, 8.0, and 5.7 pg/mg. The median concentration of total HCHs and DDTs were 117.8 pg/mg and 9.4 pg/mg, respectively. The levels of total HCHs were much higher than the levels of DDTs in the hair samples of the studied population. This may be attributed to the presence of lindane, a pesticide officially banned in 2002. It is interesting to see that DDTs are still traced in samples despite their use being banned for more than three decades. There was no difference in the levels of the detected pesticides in hair sampled from men or women. The concentration of HCHs remains high and relatively stable across the age groups, suggesting constant exposure until very recently. The concentration of the total DDTs and the parent compound, pp-DDT presents a statistically significant decreasing trend across the age groups.

  3. LacaScore: a novel plasma sample quality control tool based on ascorbic acid and lactic acid levels.

    Science.gov (United States)

    Trezzi, Jean-Pierre; Bulla, Alexandre; Bellora, Camille; Rose, Michael; Lescuyer, Pierre; Kiehntopf, Michael; Hiller, Karsten; Betsou, Fay

    Metabolome analysis is complicated by the continuous dynamic changes of metabolites in vivo and ex vivo. One of the main challenges in metabolomics is the robustness and reproducibility of results, partially driven by pre-analytical variations. The objective of this study was to analyse the impact of pre-centrifugation time and temperature, and to determine a quality control marker in plasma samples. Plasma metabolites were measured by gas chromatography-mass spectrometry (GC-MS) and analysed with the MetaboliteDetector software. The metabolites, which were the most labile to pre-analytical variations, were further measured by enzymatic assays. A score was calculated for their use as quality control markers. The pre-centrifugation temperature was shown to be critical in the stability of plasma samples and had a significant impact on metabolite concentration profiles. In contrast, pre-centrifugation delay had only a minor impact. Based on the results of this study, whole blood should be kept on wet ice and centrifuged within maximum 3 h as a prerequisite for preparing EDTA plasma samples fit for the purpose of metabolome analysis. We have established a novel blood sample quality control marker, the LacaScore, based on the ascorbic acid to lactic acid ratio in plasma, which can be used as an indicator of the blood pre-centrifugation conditions, and hence the suitability of the sample for metabolome analyses. This method can be applied in research institutes and biobanks, enabling assessment of the quality of their plasma sample collections.

  4. Phenylalanine and tyrosine levels are rate-limiting factors in production of health promoting metabolites in Vitis vinifera cv. Gamay Red cell suspension.

    Science.gov (United States)

    Manela, Neta; Oliva, Moran; Ovadia, Rinat; Sikron-Persi, Noga; Ayenew, Biruk; Fait, Aaron; Galili, Gad; Perl, Avichai; Weiss, David; Oren-Shamir, Michal

    2015-01-01

    Environmental stresses such as high light intensity and temperature cause induction of the shikimate pathway, aromatic amino acids (AAA) pathways, and of pathways downstream from AAAs. The induction leads to production of specialized metabolites that protect the cells from oxidative damage. The regulation of the diverse AAA derived pathways is still not well understood. To gain insight on that regulation, we increased AAA production in red grape Vitis vinifera cv. Gamay Red cell suspension, without inducing external stress on the cells, and characterized the metabolic effect of this induction. Increased AAA production was achieved by expressing a feedback-insensitive bacterial form of 3-deoxy- D-arabino-heptulosonate 7-phosphate synthase enzyme (AroG (*)) of the shikimate pathway under a constitutive promoter. The presence of AroG(*) protein led to elevated levels of primary metabolites in the shikimate and AAA pathways including phenylalanine and tyrosine, and to a dramatic increase in phenylpropanoids. The AroG (*) transformed lines accumulated up to 20 and 150 fold higher levels of resveratrol and dihydroquercetin, respectively. Quercetin, formed from dihydroquercetin, and resveratrol, are health promoting metabolites that are induced due to environmental stresses. Testing the expression level of key genes along the stilbenoids, benzenoids, and phenylpropanoid pathways showed that transcription was not affected by AroG (*). This suggests that concentrations of AAAs, and of phenylalanine in particular, are rate-limiting in production of these metabolites. In contrast, increased phenylalanine production did not lead to elevated concentrations of anthocyanins, even though they are also phenylpropanoid metabolites. This suggests a control mechanism of this pathway that is independent of AAA concentration. Interestingly, total anthocyanin concentrations were slightly lower in AroG(*) cells, and the relative frequencies of the different anthocyanins changed as well.

  5. Phenylalanine and tyrosine levels are rate-limiting factors in production of health promoting metabolites in Vitis vinifera cv. Gamay Red cell suspension

    Directory of Open Access Journals (Sweden)

    Neta eManela

    2015-07-01

    Full Text Available Environmental stresses such as high light intensity and temperature cause induction of the shikimate pathway, aromatic amino acids (AAA pathways, and of pathways downstream from AAAs. The induction leads to production of specialized metabolites that protect the cells from oxidative damage. The regulation of the diverse AAA derived pathways is still not well understood. To gain insight on that regulation, we increased AAA production in red grape Vitis vinifera cv. Gamay Red cell suspension, without inducing external stress on the cells, and characterized the metabolic effect of this induction. Increased AAA production was achieved by expressing a feedback-insensitive bacterial form of 3-deoxy- D-arabino-heptulosonate 7-phosphate synthase enzyme (AroG* of the shikimate pathway under a constitutive promoter. The presence of AroG* protein led to elevated levels of primary metabolites in the shikimate and AAA pathways including phenylalanine and tyrosine, and to a dramatic increase in phenylpropanoids. The AroG* transformed lines accumulated up to 20 and 150 fold higher levels of resveratrol and dihydroquercetin, respectively. Quercetin, formed from dihydroquercetin, and resveratrol, are health promoting metabolites that are induced due to environmental stresses. Testing the expression level of key genes along the stilbenoids, benzenoids and phenylpropanoid pathways showed that transcription was not affected by AroG*. This suggests that concentrations of AAAs, and of phenylalanine in particular, are rate-limiting in production of these metabolites. In contrast, increased phenylalanine production did not lead to elevated concentrations of anthocyanins, even though they are also phenylpropanoid metabolites. This suggests a control mechanism of this pathway that is independent of AAA concentration. Interestingly, total anthocyanin concentrations were slightly lower in AroG* cells, and the relative frequencies of the different anthocyanins changed as

  6. Relationship between the plasma levels of neurodegenerative proteins and motor subtypes of Parkinson's disease.

    Science.gov (United States)

    Ding, Jian; Zhang, Jiejin; Wang, Xixi; Zhang, Li; Jiang, Siming; Yuan, Yongsheng; Li, Junyi; Zhu, Lin; Zhang, Kezhong

    2017-03-01

    The aim of our study is to examine the plasma levels of the four kinds of neurodegenerative proteins in plasma: α-syn, T-tau, P-tau181, and Aβ-42 in Parkinson's disease (PD) and to evaluate the relationship between their plasma levels and PD motor subtypes. 84 patients with PD were enrolled in our study, and finally, 73 of them were classified into the tremor-dominant subtype (TD) and the postural instability gait difficulty subtype (PIGD). Their motor performance was evaluated by a series of clinical assessments: Freezing of Gait Questionnaire (FOGQ), Timed Up and Go (TUGs), Tinetti balance, and Tinetti gait. Plasma levels of these proteins were measured by enzyme-linked immunosorbent assay (ELISA). The plasma level of α-syn was significantly higher in PD patients when compared to controls (p = 0.004), and significantly higher in the PIGD group when compared to the TD group (p = 0.03). While the plasma level of Aβ-42 was significantly lower in PD patients than in controls (p = 0.002), and significantly lower in the PIGD group than in the TD group (p = 0.05). In PD patients, the plasma level of α-syn (r = -0.355, p score, even after performing multiple linear regression (p = 0.002). While the plasma level of Aβ-42 (r = -0.261, p score and remained correlate when performed multiple linear regression (p = 0.005). The patients with PIGD subtype are characterized with a lower level of plasma Aβ-42 and a higher plasma level of α-syn, which may be used as biomarkers for diagnosis and progression of the subtypes of PD.

  7. Krill protein hydrolysate reduces plasma triacylglycerol level with concurrent increase in plasma bile acid level and hepatic fatty acid catabolism in high-fat fed mice

    Directory of Open Access Journals (Sweden)

    Marie S. Ramsvik

    2013-11-01

    Full Text Available Background: Krill powder, consisting of both lipids and proteins, has been reported to modulate hepatic lipid catabolism in animals. Fish protein hydrolysate diets have also been reported to affect lipid metabolism and to elevate bile acid (BA level in plasma. BA interacts with a number of nuclear receptors and thus affects a variety of signaling pathways, including very low density lipoprotein (VLDL secretion. The aim of the present study was to investigate whether a krill protein hydrolysate (KPH could affect lipid and BA metabolism in mice. Method: C57BL/6 mice were fed a high-fat (21%, w/w diet containing 20% crude protein (w/w as casein (control group or KPH for 6 weeks. Lipids and fatty acid composition were measured from plasma, enzyme activity and gene expression were analyzed from liver samples, and BA was measured from plasma. Results: The effect of dietary treatment with KPH resulted in reduced levels of plasma triacylglycerols (TAG and non-esterified fatty acids (NEFAs. The KPH treated mice had also a marked increased plasma BA concentration. The increased plasma BA level was associated with induction of genes related to membrane canalicular exporter proteins (Abcc2, Abcb4 and to BA exporters to blood (Abcc3 and Abcc4. Of note, we observed a 2-fold increased nuclear farnesoid X receptor (Fxr mRNA levels in the liver of mice fed KPH. We also observed increased activity of the nuclear peroxiosme proliferator-activated receptor alpha (PPARα target gene carnitine plamitoyltransferase 2 (CPT-2. Conclusion: The KPH diet showed to influence lipid and BA metabolism in high-fat fed mice. Moreover, increased mitochondrial fatty acid oxidation and elevation of BA concentration may regulate the plasma level of TAGs and NEFAs.

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

    Science.gov (United States)

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

    1993-10-01

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

  9. Dehydrin, alcohol dehydrogenase, and central metabolite levels are associated with cold tolerance in diploid strawberry (Fragaria spp.).

    Science.gov (United States)

    Davik, Jahn; Koehler, Gage; From, Britta; Torp, Torfinn; Rohloff, Jens; Eidem, Petter; Wilson, Robert C; Sønsteby, Anita; Randall, Stephen K; Alsheikh, Muath

    2013-01-01

    The use of artificial freezing tests, identification of biomarkers linked to or directly involved in the low-temperature tolerance processes, could prove useful in applied strawberry breeding. This study was conducted to identify genotypes of diploid strawberry that differ in their tolerance to low-temperature stress and to investigate whether a set of candidate proteins and metabolites correlate with the level of tolerance. 17 Fragaria vesca, 2 F. nilgerrensis, 2 F. nubicola, and 1 F. pentaphylla genotypes were evaluated for low-temperature tolerance. Estimates of temperatures where 50 % of the plants survived (LT₅₀) ranged from -4.7 to -12.0 °C between the genotypes. Among the F. vesca genotypes, the LT₅₀ varied from -7.7 °C to -12.0 °C. Among the most tolerant were three F. vesca ssp. bracteata genotypes (FDP821, NCGR424, and NCGR502), while a F. vesca ssp. californica genotype (FDP817) was the least tolerant (LT₅₀) -7.7 °C). Alcohol dehydrogenase (ADH), total dehydrin expression, and content of central metabolism constituents were assayed in select plants acclimated at 2 °C. The LT₅₀ estimates and the expression of ADH and total dehydrins were highly correlated (r(adh) = -0.87, r (dehyd) = -0.82). Compounds related to the citric acid cycle were quantified in the leaves during acclimation. While several sugars and acids were significantly correlated to the LT₅₀ estimates early in the acclimation period, only galactinol proved to be a good LT₅₀ predictor after 28 days of acclimation (r(galact) = 0.79). It is concluded that ADH, dehydrins, and galactinol show great potential to serve as biomarkers for cold tolerance in diploid strawberry.

  10. Correlation analysis between plasma D-dimer levels and orthopedic trauma severity

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-dan; LIU Hong-bo; LI Yu-neng; MA Hai-mei; LIU Ya-bo; WANG Man-yi

    2012-01-01

    Background The correlation between the plasma D-dimer level and deep vein thrombosis has not been conclusive in various studies.The aim of this research was to study the relationship between plasma D-dimer levels and the severity of orthopedic trauma by retrospective examination of orthopedic trauma cases.Methods Clinically acute trauma and non-acute trauma patients were selected and their plasma D-dimer levels were measured.Plasma D-dimer levels in patients of these two groups were compared.The relationship between the plasma D-dimer level and the severity of the trauma was also studied.Results There were 548 cases in the acute trauma group and 501 cases in the non-acute trauma group.The levels of plasma D-dimer were significantly higher in the acute trauma group than in the non-acute trauma group (P <0.01).In the acute trauma group,the correlation between the D-dimer level and the number of fractures was a positive linear correlation (r=0.9532).Conclusions Elevated plasma D-dimer is common in trauma patients.The D-dimer level and the number of fractures in the trauma patients are closely correlated.D-dimer is not only an indicator for the diagnosis of deep vein thrombosis and pulmonary embolus,but also an indicator of the severity of trauma in acute trauma patients.

  11. Effect of post-exercise protein-leucine feeding on neutrophil function, immunomodulatory plasma metabolites and cortisol during a 6-day block of intense cycling.

    Science.gov (United States)

    Nelson, Andre R; Jackson, Lara; Clarke, Jim; Stellingwerff, Trent; Broadbent, Suzanne; Rowlands, David S

    2013-09-01

    Whey protein and leucine ingestion following exercise increases muscle protein synthesis and could influence neutrophil function during recovery from prolonged intense exercise. We examined the effects of whey protein and leucine ingestion post-exercise on neutrophil function and immunomodulators during a period of intense cycling. In a randomized double-blind crossover, 12 male cyclists ingested protein/leucine/carbohydrate/fat (LEUPRO 20/7.5/89/22 g h(-1), respectively) or isocaloric carbohydrate/fat control (CON 119/22 g h(-1)) beverages for 1-3 h post-exercise during 6 days of high-intensity training. Blood was taken pre- and post-exercise on days 1, 2, 4 and 6 for phorbol myristate acetate (PMA)-stimulated neutrophil superoxide (O2 (-)) production, immune cell counts, amino acid and lipid metabolism via metabolomics, hormones (cortisol, testosterone) and cytokines (interleukin-6, interleukin-10). During recovery on day 1, LEUPRO ingestion increased mean concentrations of plasma amino acids (glycine, arginine, glutamine, leucine) and myristic acid metabolites (acylcarnitines C14, myristoylcarnitine; and C14:1-OH, hydroxymyristoleylcarnitine) with neutrophil priming capacity, and reduced neutrophil O2 production (15-17 mmol O2 (-) cell(-1) ± 90 % confidence limits 20 mmol O2 (-) cell(-1)). On day 2, LEUPRO increased pre-exercise plasma volume (6.6 ± 3.8 %) but haematological effects were trivial. LEUPRO supplementation did not substantially alter neutrophil elastase, testosterone, or cytokine concentrations. By day 6, however, LEUPRO reduced pre-exercise cortisol 21 % (±15 %) and acylcarnitine C16 (palmitoylcarnitine) during exercise, and increased post-exercise neutrophil O2 (-) (33 ± 20 mmol O2 (-) cell(-1)), relative to control. Altered plasma amino acid and acylcarnitine concentrations with protein-leucine feeding might partly explain the acute post-exercise reduction in neutrophil function and increased exercise-stimulated neutrophil oxidative burst on

  12. Clinical Implication of Plasma Hydrogen Sulfide Levels in Japanese Patients with Type 2 Diabetes

    Science.gov (United States)

    Suzuki, Kunihiro; Sagara, Masaaki; Aoki, Chie; Tanaka, Seiichi; Aso, Yoshimasa

    2017-01-01

    Objective The goal of the present study was to investigate the plasma hydrogen sulfide (H2S) levels in patients with type 2 diabetes, as the plasma H2S levels in Japanese patients with type 2 diabetes remain unclear. Methods The plasma H2S levels were measured in 154 outpatients with type 2 diabetes and 66 outpatients without diabetes. All blood samples were collected in the outpatient department from 09:00 to 10:00. The patients had fasted from 21:00 the previous evening and had not consumed alcohol or caffeine or smoked until sample collection. The plasma H2S levels were measured using the methylene blue assay. The plasma H2S levels were determined in triplicate, and the average concentrations were calculated against a calibration curve of sodium sulfide. Results The patients with type 2 diabetes showed a progressive reduction in the plasma H2S levels (45.1±15.5 μM versus 54.0±26.4 μM, p<0.05), which paralleled poor glycemic control. There was a significant correlation between a reduction in the plasma H2S levels and the HbA1c levels (β=-0.505, p<0.01), Furthermore, a reduction in the plasma H2S levels was found to be related to a history of cardiovascular diseases in patients with type 2 diabetes (39.9±13.8 μM versus 47.5±15.9 μM, p<0.01). Conclusion Collectively, the plasma H2S levels were reduced in patients with type 2 diabetes, which may have implications in the pathophysiology of cardiovascular disease in diabetic patients. The trial was registered with the University Hospital Medical Information Network (UMIN no. #000020549). PMID:28049995

  13. The determination of phenazone in blood plasma for obtained sistem suitable test of monitoring drug level

    OpenAIRE

    Mochamad Lazuardi

    2007-01-01

    The determining of Phenazone to human blood plasma from healthy man after separated by solid phase extraction (SPE) and spectroscopic measurements has been investigated. The objective of that research was to obtain system suitable test for determine the Phenazone level in biological fluids (human blood plasma), for new performed dosage regimented in clinical dentistry. The method can be divided into the following four steps. 1. Centrifugation the blood sample, 2. Extraction from blood plasma ...

  14. The effect of different alcoholic beverages on blood alcohol levels, plasma insulin and plasma glucose in humans.

    Science.gov (United States)

    Nogueira, L C; Couri, S; Trugo, N F; Lollo, P C B

    2014-09-01

    In the present work we studied the effects of four alcoholic beverages on blood alcohol levels, plasma insulin concentrations and plasma glucose concentrations in men and women. The volunteers were healthy non-smokers and they were divided according to sex into two groups of ten individuals. The alcoholic beverages used in the study were beer, red wine, whisky and "cachaça". In men, ingestion of the distilled drinks promoted a spike in blood alcohol levels more quickly than ingestion of the fermented drinks. In women, beer promoted the lowest blood alcohol levels over the 6h of the experiment. Whisky promoted highest blood alcohol levels in both sexes. The ingestion of wine promoted a significant difference in relation to the blood alcohol concentration (BAC) as a function of gender. The ingestion of cachaça by women produced BAC levels significantly smaller than those obtained for wine.

  15. Correlation between plasma component levels of cultured fish and resistance to bacterial infection

    Science.gov (United States)

    Maita, M.; Satoh, K.-I.; Fukuda, Y.; Lee, H.-K.; Winton, J.R.; Okamoto, N.

    1998-01-01

    Mortalities of yellowtail Seriola quinqueradiata artificially infected with Lactococcus garvieae and of rainbow trout Oncorhynchus mykiss artificially infected with Vibrio anguillarum were compared with the levels of plasma components measured prior to challenge. The levels of plasma total cholesterol, free cholesterol and phospholipid of fish surviving infection were significantly higher in both yellowtail and rainbow trout than those of fish which died during the challenge test. Mortality of yellowtail with plasma total cholesterol levels lower than 250 mg/100 ml was significantly higher than that of fish which had cholesterol levels higher than 275 mg/100 ml (p < 0.05). Rainbow trout whose cholesterol was lower than 520 mg/100 ml suffered a significantly higher mortality due to vibriosis than fish having cholesterol levels higher than 560 mg/100 ml (p < 0.005). These results indicate that low levels of plasma lipid components may be an indicator of lowered disease resistance in cultured fish.

  16. Plasma Antimicrobial Peptide LL-37 Level Is Inversely Associated with HDL Cholesterol Level in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Shu Meguro

    2014-01-01

    Full Text Available Introduction. Relation between atherosclerosis and innate immunity has attracted attention. As the antimicrobial peptide, LL-37, could have an important role in atherosclerosis, we supposed that there could be a meaningful association of plasma LL-37 level with risk factors for cardiovascular disease in subjects with type 2 diabetes mellitus. Materials and Methods. We evaluated plasma LL-37 level and other clinical markers in Japanese subjects with type 2 diabetes mellitus (n=133, 115 men and 18 women; age 64.7±11.5 years; HbA1c 8.1±1.6%. Plasma level of LL-37 was measured by ELISA. Results. Mean plasma LL-37 level was 71.2±22.3 ng/mL. Plasma LL-37 level showed significant correlations with HDL cholesterol (r=−0.450, P<0.01, triglyceride (r=0.445, P<0.01, and high sensitive C-reactive protein (r=0.316, P<0.01 but no significant correlation with age, body mass index, HbA1c, estimated glomerular filtration rate, 25-hydroxyvitamin D, or vitamin D binding protein. Multiple linear regression analysis showed significant correlations of plasma LL-37 level with HDL cholesterol (β=−0.411, P<0.01 and high sensitive C-reactive protein (β=0.193, P<0.05. Conclusion. Plasma LL-37 level was positively correlated with inflammatory markers and negatively correlated with HDL cholesterol in patients with type 2 diabetes mellitus.

  17. Plasma cortisol levels in malnourished children with and without superimposed acute stress

    Science.gov (United States)

    Paisey, R. B.; Angers, Marielena; Frenk, S.

    1973-01-01

    Plasma cortisol levels were measured in 13 children with marasmus, in 7 with kwashiorkor, and in 24 normal children. Cortisol levels in the malnourished children did not differ from those of the normal group, either before or after 15 or 30 days of treatment, unless there was superimposed acute stress. Stress caused by complications such as hypoglycaemia, infection, hypothermia, or acidosis led to raised plasma cortisol levels. PMID:4733640

  18. A systems-level "misunderstanding": the plasma metabolome in Huntington's disease.

    Science.gov (United States)

    Rosas, Herminia D; Doros, Gheorghe; Bhasin, Swati; Thomas, Beena; Gevorkian, Sona; Malarick, Keith; Matson, Wayne; Hersch, Steven M

    2015-07-01

    Huntington's disease (HD) is a rare neurodegenerative disease caused by the expansion of an N-terminal repeat in the huntingtin protein. The protein is expressed in all cells in the body; hence, peripheral tissues, such as blood, may recapitulate processes in the brain. The plasma metabolome may provide a window into active processes that influence brain health and a unique opportunity to noninvasively identify processes that may contribute to neurodegeneration. Alterations in metabolic pathways in brain have been shown to profoundly impact HD. Therefore, identification and quantification of critical metabolomic perturbations could provide novel biomarkers for disease onset and disease progression. We analyzed the plasma metabolomic profiles from 52 premanifest (PHD), 102 early symptomatic HD, and 140 healthy controls (NC) using liquid chromatography coupled with a highly sensitive electrochemical detection platform. Alterations in tryptophan, tyrosine, purine, and antioxidant pathways were identified, including many related to energetic and oxidative stress and derived from the gut microbiome. Multivariate statistical modeling demonstrated mutually distinct metabolomic profiles, suggesting that the processes that determine onset were likely distinct from those that determine progression. Gut microbiome-derived metabolites particularly differentiated the PHD metabolome, while the symptomatic HD metabolome was increasingly influenced by metabolites that may reflect mutant huntingtin toxicity and neurodegeneration. Understanding the complex changes in the delicate balance of the metabolome and the gut microbiome in HD, and how they relate to disease onset, progression, and phenotypic variability in HD are critical questions for future research.

  19. Investigation of ex vivo stability of fesoterodine in human plasma and its simultaneous determination together with its active metabolite 5-HMT by LC-ESI-MS/MS: Application to a bioequivalence study.

    Science.gov (United States)

    Parekh, Jignesh M; Sanyal, Mallika; Yadav, Manish; Shrivastav, Pranav S

    2013-01-15

    Fesoterodine is a non-selective muscarinic-receptor antagonist, used in the treatment of overactive bladder syndrome. A highly sensitive, selective and rapid method has been developed for the simultaneous determination of fesoterodine and its active metabolite, 5-hydroxymethyl tolterodine (5-HMT) in human plasma by liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS). Due to rapid conversion of parent drug to 5-HMT, ex vivo stability of fesoterodine in human plasma was extensively studied to optimize the extraction protocol. The analytes and their deuterated analogs were quantitatively extracted from 100μL human plasma by liquid-liquid extraction in methyl tert-butyl ether: n-hexane. The chromatographic separation of analytes was achieved on a Kromasil C18 (100mm×4.6mm, 5μm) column under isocratic conditions. The method was validated over a dynamic concentration range of 0.01-10ng/mL for both the analytes. Ion-suppression effects were investigated by post-column infusion of analytes. The precision (% CV) values for the calculated slopes of calibration curves, which would reflect the relative matrix effect, were less than 1.5% for both the analytes. The intra-batch and inter-batch precision (% CV) across quality control levels varied from 1.82 to 3.73% and the mean extraction recovery was >96% for both the analytes. The method was successfully applied to a bioequivalence study of 8mg fesoterodine tablet formulation (test and reference) in 12 healthy Indian subjects under fasted and fed condition. The assay reproducibility estimated by reanalysis of incurred samples showed a change of ±12.0%. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Lower Serum Vitamin D Metabolite Levels in Relation to Circulating Cytokines/Chemokines and Metabolic Hormones in Pregnant Women with Hypertensive Disorders

    Science.gov (United States)

    Adela, Ramu; Borkar, Roshan M.; Mishra, Navneeta; Bhandi, Murali Mohan; Vishwakarma, Gayatri; Varma, B. Aparna; Ragampeta, Srinivas; Banerjee, Sanjay K.

    2017-01-01

    The aim of this study was to investigate whether lower serum vitamin D metabolite levels were associated with altered cytokine/chemokine and metabolic hormone levels in three different hypertensive disorders in pregnancy (HDP). Healthy pregnancy (n = 30) and hypertensive disorders in pregnancy (HDP) (n = 30), i.e., gestational hypertension (GH), preeclampsia (PE), and eclampsia (EC) subjects were enrolled. Vitamin D metabolites were measured by UPLC/APCI/HRMS method. Circulatory 27 cytokines/chemokines and 10 metabolic hormones were measured. Significantly decreased 25(OH)D and 1,25(OH)2D levels were observed in HDP. The levels of 25(OH)D were significantly lower in PE and EC, whereas the serum levels of 1,25(OH)2D significantly decreased only in EC subjects. Serum 25(OH)D and 1,25(OH)2D levels were negatively correlated with systolic- and diastolic blood pressure, creatinine, and uric acid levels. Serum interleukin (IL)-6 and IL-13 decreased, and GIP levels were increased in gestational hypertensive subjects. Platelet-derived growth factor-BB and IL-8 levels were increased and macrophage inflammatory protein-1beta levels were decreased in EC subjects. IL-8 and IL-10 increased, and rantes and GIP levels decreased in the EC group as compared with the GH group. Multivariate logistic regression analysis showed that eotaxin, monocyte chemotactic protein-1, 25(OH)D, and 1,25(OH)2D were predictors of HDP. Our analyses suggest that lower vitamin D metabolites are associated with altered cytokines/chemokines and metabolic hormones in HDP.

  1. Effect of Pioglitazone on Plasma Levels of Phenytoin in Rats

    Directory of Open Access Journals (Sweden)

    Abolghasem Jouyban

    2013-10-01

    Full Text Available Introduction: Interaction between drugs represents a major clinical concern for health care professionals and their patients. Patients affected by both type 2 diabetes and epilepsy may be prescribed pioglitazone and an anti-epileptic drug such as phenytoin  concurrently. The aim of this study was to consider the interaction of pioglitazone with phenytoin in an experimental model. According to the result of this study, concurrent use of phenytoin and pioglitazone in clinic may cause therapeutic failure of phenytoin which may cause seizures and during seizures the cardiac function may be affected. Material and Methods: Two groups of rats were treated for 30 days. In group 1 (control group saline (10 ml/kg and phenytoin   (30 mg/kg were administered daily by intragastric gavage. In group 2 (test group , pioglitazone (10 mg/kg was administered daily 60 minutes before phenytoin  (30 mg/kg. Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 ml of blood was drawn from the heart into a syringe containing Ethylenediaminetetraacetic (EDTA, and phenytoin  concentration in rat plasma was determined by High performance liquid chromatography (HPLC.The study consisted of 2 groups of 10 male adult Wistar rats. Results: Compared with control group, concurrent use of pioglitazone and phenytoin   was associated with significantly lower mean plasma concentrations of phenytoin : 2.08 ± 0.03  µg/ml VS 1.2 ± 0.02  µg/ml. Conclusion: Concurrent use of pioglitazone and phenytoin was associated with a significant decrease in plasma concentration of phenytoin in this experimental model. In clinic, this interaction may cause seizures and it has been shown that both cardiac and respiratory functions may affected by seizures.

  2. Elevated plasma levels of chemerin in newly diagnosed type 2 diabetes mellitus with hypertension.

    Science.gov (United States)

    Yang, Mengliu; Yang, Gangyi; Dong, Jing; Liu, Ying; Zong, Haihong; Liu, Hua; Boden, Guenther; Li, Ling

    2010-10-01

    Chemerin is a recently discovered metabolic regulator hormone. The pathophysiologic role of this hormone in humans remains unknown. In this study, we have compared plasma chemerin levels in patients with type 2 diabetes mellitus with or without hypertension and in control subjects. We also assessed the association of plasma chemerin with body composition and metabolic parameters in these subjects. Plasma chemerin levels were found to be markedly increased in patients with type 2 diabetes mellitus with hypertension as compared with patients with type 2 diabetes mellitus and normal controls (P < 0.01). Multiple regression analysis showed that waist circumference, diastolic blood pressure, 2-hour plasma insulin after glucose overload, and HbA1c were independently related factors influencing plasma chemerin levels. The present work indicates the potential link of chemerin with the pathogenesis of insulin resistance, obesity, and metabolic syndrome.

  3. Effects of AT1 Receptor Blockade on Plasma Thromboxane A2 (TXA2 Level and Skin Microcirculation in Young Healthy Women on Low Salt Diet

    Directory of Open Access Journals (Sweden)

    Ana Cavka

    2013-10-01

    Full Text Available Objective: To determine the effect of AT1 receptor antagonism on skin microcirculation and plasma level of thromboxane A2 (TXA2. Methods: Healthy women (n=20 maintained 7 days low salt (LS diet (intake 2 metabolite thromboxane B2 (TXB2 and plasma renin activity (PRA aldosterone concentration, electrolytes (Na+, K+, as well as blood pressure and heart rate were determined before and after study protocols. Results: PRA and aldosterone increased significantly after 7 days of both LS diet and LS diet+losartan. LS diet or LS diet+losartan administrations had no significant effect on post-occlusion hyperemia While there was no change in TXB2 after LS diet TXB2 significantly increased after one week of LS+losartan compared to control levels (cTXB2 pg/mL control 101±80 vs. LS diet+losartan 190±116, pConclusion: These data suggest that inhibition of AT1 receptors could lead to activation of AT2 receptors, which maintain hyperemia, despite the increased level of vasoconstrictor TXA2. These findings also suggest an important role of crosstalk between renin-angiotensin system (RAS and arachidonic acid metabolites in the regulation of microcirculation under physiological conditions.

  4. Determination of tamoxifen and its main metabolites in plasma samples from breast cancer patients by micellar liquid chromatography.

    Science.gov (United States)

    Peris-Vicente, Juan; Ochoa-Aranda, Enrique; Bose, Devasish; Esteve-Romero, Josep

    2015-01-01

    A method was developed for the analysis of tamoxifen and its main derivatives (4-hydroxytamoxifen, N-desmethyl-tamoxifen, tamoxifen-N-oxide and endoxifen) in human plasma, using micellar liquid chromatography coupled with fluorescence detection. Analytes were off-line derivatized by sample UV-irradiation for 20 min to form the photocycled fluorescent derivatives. Then samples were diluted, filtered and directly injected, thus avoiding extraction steps. The analytes were resolved using a mobile phase containing 0.08 M SDS-4.5% butanol at pH 3 running at 1.5 mL/min through a C18 column at 40°C, without interferences from endogenous compounds in plasma. Excitation and emission wavelengths were 260 and 380 nm, respectively. The chromatographic analysis time was less than 40 min. The analytical methodology was validated following the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines in terms of: selectivity, linear range (0.3-15 μg/mL), linearity (r(2)>0.999), sensitivity (LOD, 65-80 ng/mL; LOQ, 165-200 ng/mL), intra- and interday accuracy (-12.2-11.5%) and precision (<9.2%) and robustness (<6.3%). The method was used to quantify the tamoxifen and tamoxifen derivatives in several breast cancer patients from a local hospital, in order to study the correlation between the genotype of the patient and the ability to metabolize tamoxifen.

  5. Decline of plasma 5alpha-dihydrotestosterone (DHT) levels upon testosterone administration to elderly men with subnormal plasma testosterone and high DHT levels.

    Science.gov (United States)

    Gooren, L J; Saad, F; Haide, A; Yassin, A

    2008-10-01

    The study was performed to measure the impact of testosterone (T) administration on circulating levels of 5alpha-dihydrotestosterone (DHT). Group 1 (32 men; mean age 61 years; mean T 6.9 +/- 1.9 nmol l(-1)) were treated for 15 months with long-acting T undecanoate. Group 2 (23 men, mean age 60 years, mean T 7.6 +/- 2.0 nmol l(-1)) were treated for 9 months with T gel. Plasma T and DHT were measured before and after 9 months T administration. In the men treated with T undecanoate plasma T and DHT were also measured after 12 and 15 months. Before T administration, plasma DHT ranged from 0.39 to 1.76 nmol l(-1) (0.30-1.90 nmol l(-1)). Mean DHT declined upon T administration from 0.95 +/- 0.50 to 0.55 +/- 0.30 nmol l(-1) (P DHT > 0.60 nmol l(-1) had fallen from 1.29 +/- 0.50 to 0.70 +/- 0.60 nmol l(-1) (P DHT levels declined upon T administration when they were in the higher range of normal (>0.6 nmol l(-1)), with a profound shift of DHT/T ratios presumed to be an indicator of a reduced 5alpha-reductase activity. Below plasma DHT levels of 0.6 nmol l(-1), responses of plasma DHT to T administration varied.

  6. Abnormal plasma levels of serine, methionine, and taurine in transient acute polymorphic psychosis

    NARCIS (Netherlands)

    D. Fekkes (Durk)

    1994-01-01

    textabstractThe present study explored the usefulness of plasma amino acid concentrations in discriminating a subgroup of patients with transient acute polymorphic psychoses characterized by psychosensory symptoms (APP+ patients). Levels of amino acids in the plasma of APP+ patients were compared

  7. Systematic construction of a conceptual minimal model of plasma cholesterol levels based on knockout mouse phenotypes

    NARCIS (Netherlands)

    Pas, N.C.A. van de; Soffers, A.E.M.F.; Freidig, A.P.; Ommen, B. van; Woutersen, R.A.; Rietjens, I.M.C.M.; Graaf, A.A. de

    2010-01-01

    Elevated plasma cholesterol, a well-known risk factor for cardiovascular diseases, is the result of the activity of many genes and their encoded proteins in a complex physiological network. We aim to develop a minimal kinetic computational model for predicting plasma cholesterol levels. To define th

  8. Elevated plasma vitamin B12 levels and cancer prognosis: A population-based cohort study

    DEFF Research Database (Denmark)

    Arendt, Johan Frederik Håkonsen; Farkas, Dora Kormendine; Pedersen, Lars;

    2015-01-01

    BACKGROUND: Elevated plasma vitamin B12 levels (cobalamin, Cbl) are associated with increased short-term cancer risk among patients referred for this laboratory measurement. We aimed to assess prognosis in cancer patients with elevated plasma Cbl. METHODS: We conducted a population-based cohort...

  9. Elevated Plasma Homocysteine Level in Vascular Dementia Reflects the Vascular Disease Process

    Directory of Open Access Journals (Sweden)

    Karin Nilsson

    2013-02-01

    Full Text Available Background: Patients with vascular dementia (VaD exhibit particularly elevated levels of plasma total homocysteine (tHcy compared to patients with other psychogeriatric diseases. Methods: We investigated the main determinants (age, renal impairment, cobalamin/folate status and presence of extracerebral vascular disease of plasma tHcy in 525 patients with VaD. Furthermore, 270 patients with depression were used as a reference group to reveal the potential specificity of elevated plasma tHcy in patients with VaD. Results: Elevated plasma tHcy levels in patients with VaD could only partly be attributed to cobalamin/folate deficiency or renal impairment. Plasma tHcy might also be related to the vascular disease process since patients with depression and vascular disease exhibited similar plasma tHcy levels to patients with VaD. Conclusion: Our findings suggest that elevated plasma tHcy might be a sensitive marker for the vascular disease process in patients with VaD and that the level also is a reflection of changes in the other main determinants of plasma tHcy.

  10. Effect of methadone on plasma arginine vasopressin level and urine production in conscious dogs

    NARCIS (Netherlands)

    Hellebrekers, L.J.; Mol, J.A.; Brom, W.E. van den; Wimersma Greidanus, T.B. van

    1987-01-01

    The aim of this study was to examine the effect of i.v. methadone on the plasma arginine-vasopressin (AVP) levels and urine production in 9 conscious dogs. A highly significant increase from the baseline plasma AVP values of below 3 pg/ml occurred within 5 min following methadone administration. Max

  11. The effect of the lunar cycle on fecal cortisol metabolite levels and foraging ecology of nocturnally and diurnally active spiny mice.

    Directory of Open Access Journals (Sweden)

    Roee Gutman

    Full Text Available We studied stress hormones and foraging of nocturnal Acomys cahirinus and diurnal A. russatus in field populations as well as in two field enclosures populated by both species and two field enclosures with individuals of A. russatus alone. When alone, A. russatus individuals become also nocturnally active. We asked whether nocturnally active A. russatus will respond to moon phase and whether this response will be obtained also in diurnally active individuals. We studied giving-up densities (GUDs in artificial foraging patches and fecal cortisol metabolite levels. Both species exhibited elevated fecal cortisol metabolite levels and foraged to higher GUDs in full moon nights; thus A. russatus retains physiological response and behavioral patterns that correlate with full moon conditions, as can be expected in nocturnal rodents, in spite of its diurnal activity. The endocrinological and behavioral response of this diurnal species to moon phase reflects its evolutionary heritage.

  12. The effect of the lunar cycle on fecal cortisol metabolite levels and foraging ecology of nocturnally and diurnally active spiny mice.

    Science.gov (United States)

    Gutman, Roee; Dayan, Tamar; Levy, Ofir; Schubert, Iris; Kronfeld-Schor, Noga

    2011-01-01

    We studied stress hormones and foraging of nocturnal Acomys cahirinus and diurnal A. russatus in field populations as well as in two field enclosures populated by both species and two field enclosures with individuals of A. russatus alone. When alone, A. russatus individuals become also nocturnally active. We asked whether nocturnally active A. russatus will respond to moon phase and whether this response will be obtained also in diurnally active individuals. We studied giving-up densities (GUDs) in artificial foraging patches and fecal cortisol metabolite levels. Both species exhibited elevated fecal cortisol metabolite levels and foraged to higher GUDs in full moon nights; thus A. russatus retains physiological response and behavioral patterns that correlate with full moon conditions, as can be expected in nocturnal rodents, in spite of its diurnal activity. The endocrinological and behavioral response of this diurnal species to moon phase reflects its evolutionary heritage.