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Sample records for plasma efavirenz concentrations

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-01-01

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

  3. Inhibition of Efavirenz Metabolism by Sertraline and Nortriptyline and Their Effect on Efavirenz Plasma Concentrations

    PubMed Central

    Melis, Virginia; Usach, Iris; Gandía, Patricia

    2015-01-01

    Between 22 and 45% of HIV-positive subjects are likely to report symptoms of depression. Considering this background, a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor efavirenz (EFV) and two antidepressants, sertraline (SRT) and nortriptyline (NT), was studied. Rats were administered EFV alone or together with the antidepressants, and changes in the plasma levels and pharmacokinetic parameters of EFV were analyzed. Additional in vitro experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effect of SRT and NT on EFV metabolism by determining the formation rate of the major EFV metabolite (8-OH-EFV). In vivo studies showed similar increases in the plasma levels of EFV when it was coadministered with SRT or NT. However, the studies using rat hepatic microsomes showed a more potent inhibitory effect of NT than of SRT on the metabolism of EFV, with values for the 50% inhibition constant (IC50) and inhibitory constant (Ki) for NT about 9-fold lower than those for SRT. An equation was deduced that explains the similar in vivo effects of SRT and NT in spite of the different in vitro performance data. Using human hepatic microsomes, the strongest inhibitory effect was observed with SRT. In summary, pharmacokinetic interactions between EFV, SRT, and NT, associated with the inhibition of hepatic metabolism of EFV, have been detected in rats. Both antidepressants also inhibit EFV metabolism in human hepatic microsomes, but additional in vivo studies in humans are required to evaluate the clinical implication of this interaction. PMID:26643342

  4. Haplotype structure of CYP2B6 and association with plasma efavirenz concentrations in a Chilean HIV cohort

    PubMed Central

    Carr, Daniel F.; la Porte, Charles J. L.; Pirmohamed, Munir; Owen, Andrew; Cortes, Claudia P.

    2010-01-01

    Objectives Efavirenz is extensively metabolized by CYP2B6, and associations between CYP2B6 polymorphisms and plasma efavirenz exposure have been reported. The objective of this study was to investigate CYP2B6 haplotype structure and functional consequences in a Latin American population. Patients and methods Two hundred and nineteen patients were recruited at Fundación Arriarán, Chile, between September and December 2008. Plasma efavirenz concentrations were determined using liquid chromatography with mass spectrometry. Genotyping for 30 single nucleotide polymorphisms (SNPs) with a minor allele frequency of >0.05 in the HapMap CEU population at intervals of ∼1 kb across the CYP2B6 locus was conducted using Sequenom iPLEX MALDI-TOF. Results Thirteen SNPs passed quality control and, of these, statistically significant associations (P < 0.001) with plasma efavirenz concentrations were observed for 11. Pairwise tagging SNP analysis (R2 > 0.8) identified 3 SNPs (rs10403955, rs2279345 and rs8192719) representative of the 11 associated SNPs. A composite genetic model of these three alleles was constructed, and an association between carriers of four to six of these alleles and the risk of efavirenz plasma concentrations >4 µg/mL was identified with an odds ratio of 48.1 (95% confidence interval: 13.5–207.7). This represents a positive predictive value of 80.9% and a negative predictive value of 91.8%, with sensitivity of 57.9% and specificity of 97.2%. Conclusions A composite genetic model of CYP2B6 SNPs in a Chilean HIV-positive cohort may have value in predicting concentrations of efavirenz associated with a higher likelihood of CNS toxicity. Further investigation of the functional basis of these associations is now required. PMID:20639527

  5. Plasma Concentrations, Efficacy and Safety of Efavirenz in HIV-Infected Adults Treated for Tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA Trial)

    PubMed Central

    Borand, Laurence; Madec, Yoann; Laureillard, Didier; Chou, Monidarin; Marcy, Olivier; Pheng, Phearavin; Prak, Narom; Kim, Chindamony; Lak, Khemarin Kim; Hak, Chanroeun; Dim, Bunnet; Nerrienet, Eric; Fontanet, Arnaud; Sok, Thim; Goldfeld, Anne E.; Blanc, François-Xavier; Taburet, Anne-Marie

    2014-01-01

    Objective To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients. Methods HIV-infected adults with CD4+ T cell count ≤200/mm3 received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week +6 after antiretroviral therapy initiation, and week 22 of follow-up) and off tuberculosis treatment (week 50 of follow-up). Considered therapeutic range was 1,000 to 4,000 ng/mL. Multivariate analysis was performed to evaluate the association between efavirenz concentration below 1,000 ng/mL and virological failure. Linear regression was used to test the association between efavirenz exposure and CD4+ T cell gain. Severe side effects potentially related to efavirenz were described and their association with efavirenz exposure was tested by multivariate analysis. Results Efavirenz plasma concentrations were available in 540 patients. Median [interquartile range] efavirenz concentrations were 2,674 ng/mL [1,690–4,533], 2,667 ng/mL [1,753–4,494] and 2,799 ng/mL [1,804–4,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,941–3,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (p<0.001). Late attendance to study visit and low hemoglobinemia were the only factors associated with an increased risk of efavirenz concentration below 1,000 ng/mL. Efavirenz concentration below 1,000 ng/mL was not associated with treatment failure. Efavirenz concentration above 4,000 ng/mL was associated with higher risk of central nervous system side effects (p<0.001) and of hepatotoxicity (p<0.001). Conclusion Body weight and tuberculosis treatment were not associated with low efavirenz concentrations or treatment failure

  6. Plasma Concentrations of Efavirenz and Nevirapine among HIV-Infected Patients with Immunological Failure Attending a Tertiary Hospital in North-Western Tanzania

    PubMed Central

    Kidenya, Benson R.; Kabangila, Rodrick; Mshana, Stephen E.; Kidola, Jeremiah; Kalluvya, Samuel E.; Kongola, Gilbert W.; Klinker, Hartwig

    2013-01-01

    Background Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania. Materials and Methods A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12. Results Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3%), 76/152 (50.0%) and 33/152 (21.7%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value<0.001), NRTI backbone (p-value = 0.039), HIV stage (p-value = 0.026) and viral load (p-value = 0.007) within sub-therapeutic, therapeutic and supra-therapeutic ARV plasma drug concentrations. Conclusion There is a wide inter-individual variability of plasma ARV concentrations among HIV patients with immunological failure, with a large proportion of patients being outside therapeutic window. This variability is significant based on ARV adherence, NRTI backbone, viral load and HIV stage. Routine

  7. Efavirenz

    MedlinePlus

    ... Although efavirenz does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) ... sex and making other life-style changes may decrease the risk of transmitting (spreading) the HIV virus ...

  8. Efavirenz concentrations in CSF exceed IC50 for wild-type HIV

    PubMed Central

    Best, Brookie M.; Koopmans, Peter P.; Letendre, Scott L.; Capparelli, Edmund V.; Rossi, Steven S.; Clifford, David B.; Collier, Ann C.; Gelman, Benjamin B.; Mbeo, Gilbert; McCutchan, J. Allen; Simpson, David M.; Haubrich, Richard; Ellis, Ronald; Grant, Igor; Grant, Igor; McCutchan, J. Allen; Ellis, Ronald J.; Marcotte, Thomas D.; Franklin, Donald; Ellis, Ronald J.; McCutchan, J. Allen; Alexander, Terry; Letendre, Scott; Capparelli, Edmund; Heaton, Robert K.; Atkinson, J. Hampton; Woods, Steven Paul; Dawson, Matthew; Wong, Joseph K.; Fennema-Notestine, Christine; Taylor, Michael J.; Theilmann, Rebecca; Gamst, Anthony C.; Cushman, Clint; Abramson, Ian; Vaida, Florin; Marcotte, Thomas D.; von Jaeger, Rodney; McArthur, Justin; Smith, Mary; Morgello, Susan; Simpson, David; Mintz, Letty; McCutchan, J. Allen; Toperoff, Will; Collier, Ann; Marra, Christina; Jones, Trudy; Gelman, Benjamin; Head, Eleanor; Clifford, David; Al-Lozi, Muhammad; Teshome, Mengesha

    2011-01-01

    Objectives HIV-associated neurocognitive disorders remain common despite use of potent antiretroviral therapy (ART). Ongoing viral replication due to poor distribution of antivirals into the CNS may increase risk for HIV-associated neurocognitive disorders. This study's objective was to determine penetration of a commonly prescribed antiretroviral drug, efavirenz, into CSF. Methods CHARTER is an ongoing, North American, multicentre, observational study to determine the effects of ART on HIV-associated neurological disease. Single random plasma and CSF samples were drawn within 1 h of each other from subjects taking efavirenz between September 2003 and July 2007. Samples were assayed by HPLC or HPLC/mass spectrometry with detection limits of 39 ng/mL (plasma) and <0.1 ng/mL (CSF). Results Eighty participants (age 44 ± 8 years; 79 ± 15 kg; 20 females) had samples drawn 12.5 ± 5.4 h post-dose. The median efavirenz concentrations after a median of 7 months [interquartile range (IQR) 2–17] of therapy were 2145 ng/mL in plasma (IQR 1384–4423) and 13.9 ng/mL in CSF (IQR 4.1–21.2). The CSF/plasma concentration ratio from paired samples drawn within 1 h of each other was 0.005 (IQR 0.0026–0.0076; n = 69). The CSF/IC50 ratio was 26 (IQR 8–41) using the published IC50 for wild-type HIV (0.51 ng/mL). Two CSF samples had concentrations below the efavirenz IC50 for wild-type HIV. Conclusions Efavirenz concentrations in the CSF are only 0.5% of plasma concentrations but exceed the wild-type IC50 in nearly all individuals. Since CSF drug concentrations reflect those in brain interstitial fluids, efavirenz reaches therapeutic concentrations in brain tissue. PMID:21098541

  9. CYP2B6*6 genotype and high efavirenz plasma concentration but not nevirapine are associated with low lumefantrine plasma exposure and poor treatment response in HIV-malaria-coinfected patients.

    PubMed

    Maganda, B A; Minzi, O M S; Ngaimisi, E; Kamuhabwa, A A R; Aklillu, E

    2016-02-01

    We investigated the influence of efavirenz (EFV)- or nevirapine (NVP)-based antiretroviral therapy (ART) on lumefantrine plasma exposure in HIV-malaria-coinfected patients and implication of pharmacogenetic variations. A total of 269 HIV patients with uncomplicated falciparum malaria on NVP-based ART (NVP-arm), EFV-based ART (EFV-arm) or not receiving ART (control-arm) were enrolled and treated with artemether-lumefantrine. Day-7 lumefantrine, baseline EFV and NVP plasma concentrations, and CYP2B6*6,*18, CYP3A4*1B, CYP3A5*3,*6,*7, ABCB1 c.3435C>T and ABCB1 c.4036A>G genotypes were determined. The median day-7 lumefantrine plasma concentration was significantly lower in the EFV-arm compared with that in NVP- and control-arm. High EFV plasma concentrations and CYP2B6*6/*6 genotype significantly correlated with low lumefantrine plasma concentrations and high rate of recurrent parasitemia. No significant effect of NVP-based ART on lumefantrine exposure was observed. In conclusion, owing to long-term CYP3A induction, EFV-based ART cotreatment significantly reduces lumefantrine plasma exposure leading to poor malaria treatment response, which is more pronounced in CYP2B6 slow metabolizers.

  10. Pharmacogenetics of plasma efavirenz exposure in HIV-infected adults and children in South Africa

    PubMed Central

    Sinxadi, Phumla Z; Leger, Paul D; McIlleron, Helen M; Smith, Peter J; Dave, Joel A; Levitt, Naomi S; Maartens, Gary; Haas, David W

    2015-01-01

    Aims Genetic factors, notably CYP2B6 516G→T [rs3745274] and 983T→C [rs28399499], explain much of the interindividual variability in efavirenz pharmacokinetics, but data from Africa are limited. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations in HIV-infected Black South African adults and children. Methods Steady-state mid-dosing interval efavirenz concentrations were measured. We genotyped 241 polymorphisms in genes potentially relevant to efavirenz metabolism and transport, including ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3. Results Among 113 participants (59 adults and 54 children), minor allele frequencies for CYP2B6 516G→T, 983T→C, and 15582C→T [rs4803419] were 0.36, 0.07, and 0.09, respectively. Based on composite CYP2B6 15582/516/983 genotype, there were 33 extensive metabolizer, 62 intermediate metabolizer and 18 slow metabolizer genotypes. Median (IQR) mid-dose efavirenz concentrations were 1.44 (1.21–1.93) µg ml–1, 2.08 (1.68–2.94) µg ml–1 and 7.26 (4.82–8.34) µg ml–1 for extensive, intermediate and slow metabolizers, respectively. In univariate analyses, a model that included composite genotype best predicted efavirenz concentrations (β = 0.28, 95% CI 0.21, 0.35, P = 2.4 × 10–11). Among individual CYP2B6 polymorphisms, 516G→T best predicted efavirenz concentrations (β = 0.22, 95% CI 0.13, 0.30, P = 1.27 × 10−6). There was also associations with 983T→C (β = 0.27, 95% CI 0.10, 0.44, P = 0.002) and 15582C→T (β = 0.11, 95% CI 0.01, 0.22, P = 0.04). Associations were consistent in adults and children. No other polymorphisms were independently associated with efavirenz concentrations. Conclusions Composite CYP2B6 genotype based on CYP2B6 516G→T, 983T→C, and 15582C→T best described efavirenz exposure in HIV-infected Black South African adults and children. PMID:25611810

  11. Effect of Efavirenz on Endogenous Progesterone Concentrations and Contraceptive Outcomes among Ugandan HIV Infected Women Coadministering Ethinylestradiol/Levonorgestrel.

    PubMed

    Munkwase, Grant; Bisaso, Kuteesa R; Kakaire, Othman; Nanzigu, Sarah

    2017-01-01

    This study assessed the effect of efavirenz mid-dose plasma concentrations on mid-luteal endogenous progesterone concentrations and contraceptive outcomes among 49 HIV infected women coadministering ethinylestradiol/levonorgestrel, including 34 HIV positive women on Highly Active Antiretroviral Therapy (HAART) and 15 HAART naïve HIV infected women, purposively selected from Mulago Hospital, Uganda. A blood sample was collected once between days 20 and 22 of each woman's menstrual cycle for measuring endogenous progesterone and efavirenz concentrations by electrochemiluminescence technology and High Performance Liquid Chromatography (HPLC), respectively. Descriptive statistical analysis and correlation and logistic regression analysis were done using SPSS v.21 and R3.1. Efavirenz showed a weak positive linear relationship with endogenous progesterone at efavirenz concentrations below 12 μg/ml. Based on serum endogenous progesterone, the observed hormonal contraceptives failure rate (24.5%) was higher than expected (maximum 8%). A higher proportion of HIV positive women on efavirenz based HAART (26.5%) was at risk of contraceptive failure than their HIV infected HAART naïve counterparts (20%) though it was not statistically significant (p = 0.63). Efavirenz mid-dose plasma concentrations seem to have no significant effect on mid-luteal endogenous progesterone concentrations and contraceptive outcomes among HIV infected Ugandan women coadministering ethinylestradiol/levonorgestrel oral pills.

  12. Effect of Efavirenz on Endogenous Progesterone Concentrations and Contraceptive Outcomes among Ugandan HIV Infected Women Coadministering Ethinylestradiol/Levonorgestrel

    PubMed Central

    Bisaso, Kuteesa R.; Kakaire, Othman; Nanzigu, Sarah

    2017-01-01

    This study assessed the effect of efavirenz mid-dose plasma concentrations on mid-luteal endogenous progesterone concentrations and contraceptive outcomes among 49 HIV infected women coadministering ethinylestradiol/levonorgestrel, including 34 HIV positive women on Highly Active Antiretroviral Therapy (HAART) and 15 HAART naïve HIV infected women, purposively selected from Mulago Hospital, Uganda. A blood sample was collected once between days 20 and 22 of each woman's menstrual cycle for measuring endogenous progesterone and efavirenz concentrations by electrochemiluminescence technology and High Performance Liquid Chromatography (HPLC), respectively. Descriptive statistical analysis and correlation and logistic regression analysis were done using SPSS v.21 and R3.1. Efavirenz showed a weak positive linear relationship with endogenous progesterone at efavirenz concentrations below 12 μg/ml. Based on serum endogenous progesterone, the observed hormonal contraceptives failure rate (24.5%) was higher than expected (maximum 8%). A higher proportion of HIV positive women on efavirenz based HAART (26.5%) was at risk of contraceptive failure than their HIV infected HAART naïve counterparts (20%) though it was not statistically significant (p = 0.63). Efavirenz mid-dose plasma concentrations seem to have no significant effect on mid-luteal endogenous progesterone concentrations and contraceptive outcomes among HIV infected Ugandan women coadministering ethinylestradiol/levonorgestrel oral pills. PMID:28831309

  13. [Efavirenz and nevirapine plasma levels in HIV-infected patients with hemophilia].

    PubMed

    Martorell, Marta; López, Rosa M; Ribera, Esteban; Ruiz, Isabel; Tural, Cristina; Puig, Lluís; Monterde, Josep

    2005-01-01

    The aim of this study was to evaluate efavirenz and nevirapine plasma levels in HIV-infected hemophilic patients seen in two hospitals in Barcelona. Plasma levels of these drugs were determined by high-performance liquid chromatography (HPLC) at four-month intervals, together with viral load and CD4 cell count. Nineteen patients treated with efavirenz and 8 with nevirapine were included, and 68 efavirenz and 31 nevirapine determinations were performed. Mean study time was 12 months. Median efavirenz plasma concentration was 2.95 .g/ml (interval: 1.54-5.26 .g/ml) in patients with favorable virological response and 1.86 .g/ml (0.82-4.88 .g/ml) in patients with detectable viral load (p = 0.32). Nevirapine plasma concentrations were 4.41 .g/ml (3.50-6.72 .g/ml) and 3.12 .g/ml (2.44-3.80 .g/ml) respectively (p = 0.18).

  14. Simultaneous plasma and genital pharmacokinetics and pharmacodynamics of atazanavir and efavirenz in HIV-infected women starting therapy

    PubMed Central

    Neely, Michael; Louie, Stan; Xu, Jiaao; Anthony, Patricia; Thuvamontolrat, Kasalyn; Mordwinkin, Nicholas; Kovacs, Andrea

    2015-01-01

    Few studies characterize longitudinal female plasma and genital antiretroviral pharmacokinetics and pharmacodynamics. Among 20 regimen-naïve HIV-infected adult women initiating atazanavir- (n=9) or efavirenz-based therapy (n=11), we measured blood CD4+ T-lymphocytes, and paired plasma and genital HIV RNA and atazanavir or efavirenz 2 days before starting therapy, and 2, 4, 7, 10, 21, 28, 60, 120, and 180 days after. The mean (range) log10 baseline plasma viral load was 4.89 (2.64 – 6.09) copies/mL and genital was 3.30 (1.60 – 5.00). In the atazanavir and efavirenz groups, mean (SD) days to 50% decrease in plasma viral load was 8.2 (4.9) vs. 9.3 (7.4), P=0.7, and in the genital tract was 7.3 (3.5) vs. 9.3 (7.7), P=0.5. The median (interquartile range) plasma:genital concentration ratio for atazanavir was 0.11 (0.001 to 0.46), vs. 0.34 (0.05 to 1.30) for efavirenz, P=0.5. Average plasma efavirenz or atazanavir concentrations over time did not affect virologic response. Blood CD4+ percentages increased by +2.3 (P=0.06) and +3.0 (P=0.003) for every 1 mg/L increase in average plasma and genital drug concentration, respectively. Plasma and genital viral pharmacodynamics were similar between the groups and independent of average concentrations, but blood CD4+ response was related in particular to genital extravascular drug concentrations. PMID:25683232

  15. Hair and Plasma Data Show that Lopinavir, Ritonavir and Efavirenz All Transfer from Mother to Infant in Utero, but only Efavirenz Transfers via Breastfeeding

    PubMed Central

    Gandhi, Monica; Mwesigwa, Julia; Aweeka, Francesca; Plenty, Albert; Charlebois, Edwin; Ruel, Theodore D.; Huang, Yong; Clark, Tamara; Ades, Veronica; Natureeba, Paul; Luwedde, Flavia A.; Achan, Jane; Kamya, Moses R.; Havlir, Diane V.; Cohan, Deborah

    2013-01-01

    Background As efforts intensify to eliminate perinatal HIV transmission, understanding kinetics of maternal-to-child transfer of antiretrovirals during pregnancy and breastfeeding is critical. Antiretroviral levels in plasma, cord blood and breastmilk reflect exposure over short intervals. Hair concentrations reflect cumulative exposure and can uniquely quantify in-utero transfer of maternal medications to infants. We measured plasma and hair antiretroviral levels in HIV-infected Ugandan mothers and their infants at delivery and during breastfeeding to assess transfer. Methods HIV-infected pregnant women were randomized to lopinavir/ritonavir- or efavirenz-based therapy in a larger trial (PROMOTE). At 0, 8 and 12 weeks postpartum, plasma antiretroviral levels were measured in 117 mother-infant pairs; hair levels were assayed at 12 weeks. Ratios and correlations of infant:maternal concentrations were calculated. Results By 12 weeks, 90.4% of mothers reported exclusive breastfeeding. Hair and plasma levels over time suggest moderate (47%) to extensive (87%) in-utero transfer of lopinavir and ritonavir, respectively, but negligible transfer of either via breastfeeding. Moderate transfer of efavirenz occurs during pregnancy and breastfeeding (40% cumulative; 15% during breastfeeding). Despite differences in exposure, no infant seroconversions or correlations between infant hair/plasma antiretroviral levels and adverse effects were observed. Conclusions Using a unique approach combining hair and plasma data, we found that different antiretrovirals had distinct kinetics of mother-to-infant transfer. Efavirenz transfers during both pregnancy and breastfeeding, whereas lopinavir and ritonavir transfer only in-utero. Further study of the degree and timing of maternal-to-child transfer by antiretroviral will help optimize strategies that protect infants and minimize toxicities during periods of risk. PMID:24135775

  16. Compartmentalization and antiviral effect of efavirenz metabolites in blood plasma, seminal plasma, and cerebrospinal fluid.

    PubMed

    Avery, Lindsay B; VanAusdall, Jennifer L; Hendrix, Craig W; Bumpus, Namandjé N

    2013-02-01

    Efavirenz (EFV) is one of the most commonly prescribed antiretrovirals for use in the treatment of human immunodeficiency virus (HIV) infection. EFV is extensively metabolized by cytochrome P450 to a number of oxygenated products; however, the pharmacologic activity and distribution of these metabolites in anatomic compartments have yet to be explored. The systemic distribution of EFV oxidative metabolites was examined in blood plasma, seminal plasma, and cerebrospinal fluid from subjects on an EFV-based regimen. The 8-hydroxy EFV metabolite was detected in blood plasma, seminal plasma, and cerebrospinal fluid, with median concentrations of 314.5 ng/ml, 358.5 ng/ml, and 3.37 ng/ml, respectively. In contrast, 7-hydroxy and 8,14-hydroxy EFV were only detected in blood plasma and seminal plasma with median concentrations of 8.84 ng/ml and 10.23 ng/ml, and 5.63 ng/ml and 5.43 ng/ml, respectively. Interestingly, protein-free concentrations of metabolites were only detectable in seminal plasma, where a novel dihdyroxylated metabolite of EFV was also detected. This accumulation of protein-free EFV metabolites was demonstrated to be the result of differential protein binding in seminal plasma compared with that of blood plasma. In addition, the oxidative metabolites of EFV did not present with any significant pharmacologic activity toward HIV-1 as measured using an HIV green fluorescent protein single-round infectivity assay. This study is the first to report the physiologic distribution of metabolites of an antiretroviral into biologic compartments that the virus is known to distribute and to examine their anti-HIV activity. These data suggest that the male genital tract may be a novel compartment that should be considered in the evaluation of drug metabolite exposure.

  17. Determination of efavirenz in human plasma by high-performance liquid chromatography with ultraviolet detection.

    PubMed

    Saras-Nacenta, M; López-Púa, Y; Lípez-Cortés, L F; Mallolas, J; Gatell, J M; Carné, X

    2001-11-05

    Efavirenz is a non-nucleoside reverse transcriptase inhibitor for the treatment of the HIV infection. A simple, high-performance liquid chromatographic method has been developed and validated for the quantitative determination of efavirenz in human plasma. The method involved solid-phase extraction of the drug and the internal standard (L-737,354) from 300 microl of human plasma. The analysis was via UV detection at 250 nm using a reversed-phase C8 analytical column and a isocratic mobile phase consisting of phosphate buffer (pH 5.75)-acetonitrile that resolved the drug and internal standard from endogenous matrix components and potential coadministered drugs. Within- and between-day precisions were less than 8.6% for all quality control samples. The lower limit of quantification was 0.1 microg/ml. Recovery of efavirenz from human plasma was greater than 83%. This validated assay is being used in pharmacokinetic studies with efavirenz.

  18. Plasma Efavirenz Exposure, Sex, and Age Predict Virological Response in HIV-Infected African Children

    PubMed Central

    Bienczak, Andrzej; Denti, Paolo; Cook, Adrian; Wiesner, Lubbe; Mulenga, Veronica; Kityo, Cissy; Kekitiinwa, Addy; Gibb, Diana M.; Burger, David; Walker, A. Sarah

    2016-01-01

    Background: Owing to insufficient evidence in children, target plasma concentrations of efavirenz are based on studies in adults. Our analysis aimed to evaluate the pediatric therapeutic thresholds and characterize the determinants of virological suppression in African children. Methods: We analyzed data from 128 African children (aged 1.7–13.5 years) treated with efavirenz, lamivudine, and one among abacavir, stavudine, or zidovudine, and followed up to 36 months. Individual pharmacokinetic (PK) measures [plasma concentration 12 hours after dose (C12h), plasma concentration 24 hours after dose (C24h), and area under the curve (AUC0-24)] were estimated using population PK modeling. Cox multiple failure regression and multivariable fractional polynomials were used to investigate the risks of unsuppressed viral load associated with efavirenz exposure and other factors among 106 initially treatment-naive children, and likelihood profiling was used to identify the most predictive PK thresholds. Results: The risk of viral load >100 copies per milliliter decreased by 42% for every 2-fold increase in efavirenz mid-dose concentration [95% confidence interval (CI): 23% to 57%; P < 0.001]. The most predictive PK thresholds for increased risk of unsuppressed viral load were C12h 1.12 mg/L [hazard ratio (HR): 6.14; 95% CI: 2.64 to 14.27], C24h 0.65 mg/L (HR: 6.57; 95% CI: 2.86 to 15.10), and AUC0-24 28 mg·h/L (HR: 5.77; 95% CI: 2.28 to 14.58). Children older than 8 years had a more than 10-fold increased risk of virological nonsuppression (P = 0.005); among children younger than 8 years, boys had a 5.31 times higher risk than girls (P = 0.007). Central nervous system adverse events were infrequently reported. Conclusions: Our analysis suggests that the minimum target C24h and AUC0-24 could be lowered in children. Our findings should be confirmed in a prospective pediatric trial. PMID:27116047

  19. Plasma Efavirenz Exposure, Sex, and Age Predict Virological Response in HIV-Infected African Children.

    PubMed

    Bienczak, Andrzej; Denti, Paolo; Cook, Adrian; Wiesner, Lubbe; Mulenga, Veronica; Kityo, Cissy; Kekitiinwa, Addy; Gibb, Diana M; Burger, David; Walker, A Sarah; McIlleron, Helen

    2016-10-01

    Owing to insufficient evidence in children, target plasma concentrations of efavirenz are based on studies in adults. Our analysis aimed to evaluate the pediatric therapeutic thresholds and characterize the determinants of virological suppression in African children. We analyzed data from 128 African children (aged 1.7-13.5 years) treated with efavirenz, lamivudine, and one among abacavir, stavudine, or zidovudine, and followed up to 36 months. Individual pharmacokinetic (PK) measures [plasma concentration 12 hours after dose (C12h), plasma concentration 24 hours after dose (C24h), and area under the curve (AUC0-24)] were estimated using population PK modeling. Cox multiple failure regression and multivariable fractional polynomials were used to investigate the risks of unsuppressed viral load associated with efavirenz exposure and other factors among 106 initially treatment-naive children, and likelihood profiling was used to identify the most predictive PK thresholds. The risk of viral load >100 copies per milliliter decreased by 42% for every 2-fold increase in efavirenz mid-dose concentration [95% confidence interval (CI): 23% to 57%; P < 0.001]. The most predictive PK thresholds for increased risk of unsuppressed viral load were C12h 1.12 mg/L [hazard ratio (HR): 6.14; 95% CI: 2.64 to 14.27], C24h 0.65 mg/L (HR: 6.57; 95% CI: 2.86 to 15.10), and AUC0-24 28 mg·h/L (HR: 5.77; 95% CI: 2.28 to 14.58). Children older than 8 years had a more than 10-fold increased risk of virological nonsuppression (P = 0.005); among children younger than 8 years, boys had a 5.31 times higher risk than girls (P = 0.007). Central nervous system adverse events were infrequently reported. Our analysis suggests that the minimum target C24h and AUC0-24 could be lowered in children. Our findings should be confirmed in a prospective pediatric trial.

  20. Effect of mid-dose efavirenz concentrations and CYP2B6 genotype on viral suppression in patients on first-line antiretroviral therapy.

    PubMed

    Orrell, Catherine; Bienczak, Andrzej; Cohen, Karen; Bangsberg, David; Wood, Robin; Maartens, Gary; Denti, Paolo

    2016-06-01

    The therapeutic range for efavirenz plasma concentrations is unclear and some studies found no correlation with viral non-suppression. Efavirenz concentrations are variable, driven in part by polymorphisms in CYP2B6. We hypothesised that efavirenz mid-dosing concentrations, together with CYP2B6 metaboliser genotype, could predict viral non-suppression. Participants starting first-line efavirenz-based antiretroviral therapy were monitored for 48 weeks. HIV-RNA and efavirenz mid-dose interval concentrations were determined at Weeks 16 and 48. CYP2B6 metaboliser genotype status was determined by 516G→T and 983T→C polymorphisms. Cox proportional hazards modelling was used to predict viral non-suppression and to determine the most predictive efavirenz mid-dosing concentration threshold. In total, 180 participants were included. Median efavirenz concentrations were 2.3 mg/L (IQR 1.6-4.6 mg/L) and 2.2 mg/L (IQR 1.5-3.9 mg/L) at Weeks 16 and 48, respectively. Moreover, 49 (27.2%), 84 (46.7%) and 39 (21.7%) participants had extensive, intermediate or slow CYP2B6 metaboliser genotype, respectively. Log2 efavirenz concentrations [adjusted hazard ratio (aHR) = 0.77, 95% CI 0.67-0.89] and baseline CD4 cell count (aHR = 0.994, 95% CI 0.989-0.998), but not CYP2B6 genotype, were predictive of viral non-suppression. For every doubling of efavirenz concentration there was a 23% decrease in the hazard of non-suppression. A threshold of 0.7 mg/L was found to be the efavirenz mid-dosing concentration that was most predictive of non-suppression. Mid-dosing efavirenz concentrations are predictive of viral non-suppression, but the currently recommended lower therapeutic limit (1 mg/L) is higher than our finding. Knowledge of CYP2B6 metaboliser genotype is not required for prediction of virological outcomes.

  1. Combined effect of CYP2B6 and NAT2 genotype on plasma efavirenz exposure during rifampin-based antituberculosis therapy in the STRIDE study.

    PubMed

    Luetkemeyer, Anne F; Rosenkranz, Susan L; Lu, Darlene; Grinsztejn, Beatriz; Sanchez, Jorge; Ssemmanda, Michael; Sanne, Ian; McIlleron, Helen; Havlir, Diane V; Haas, David W

    2015-06-15

    In STRIDE, slow metabolizer CYP2B6 and NAT2 genotypes were each associated with increased plasma efavirenz concentrations during antituberculosis therapy. Concentrations were greater on therapy than off therapy in 58% with CYP2B6 and 93% with NAT2 slow metabolizer genotypes. Individuals with slow metabolizer genotypes in both genes had markedly elevated concentrations.

  2. PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients.

    PubMed

    Swart, Marelize; Whitehorn, Heather; Ren, Yuan; Smith, Peter; Ramesar, Rajkumar S; Dandara, Collet

    2012-11-22

    This study investigated variation in NR1I2 and NR1I3 and its effect on plasma efavirenz levels in HIV/AIDS patients. Variability in plasma drug levels has largely led research on identifying causative variants in drug metabolising enzyme (DME) genes, with little focus on the nuclear receptor genes NR1I2 and NR1I3, coding for PXR and CAR, respectively, that are involved in regulating DMEs. 464 Bantu-speaking South Africans comprising of HIV/AIDS patients on efavirenz-based treatment (n=301) and 163 healthy subjects were genotyped for 6 SNPs in NR1I2 and NR1I3. 32 of the 301 patients had their DNA binding domains (DBDs) in NR1I2 and NR1I3 sequenced. Significantly decreased efavirenz plasma concentrations were observed in patients carrying the NR1I3 rs3003596C/C and T/C genotypes (P=0.015 and P=0.010, respectively). Sequencing resulted in the discovery of a further 13 SNPs, 3 of which are novel variants in the DBD of NR1I2. There were significant differences in the distribution of NR1I2 and NR1I3 SNPs between South Africans when compared to Caucasian, Asian and Yoruba population groups. For the realisation of personalised medicine, PXR and CAR genetic variation should be taken into consideration because of their involvement in the regulation of DMEs.

  3. Mechanism of efavirenz influence on methadone pharmacokinetics and pharmacodynamics.

    PubMed

    Kharasch, E D; Whittington, D; Ensign, D; Hoffer, C; Bedynek, P S; Campbell, S; Stubbert, K; Crafford, A; London, A; Kim, T

    2012-04-01

    Mechanisms by which efavirenz diminishes methadone plasma concentrations are unknown. This investigation determined efavirenz influence on clinical methadone disposition and miosis, intravenous and oral alfentanil clearance (hepatic and intestinal cytochrome P450 3A4/5 (CYP3A4/5) activity), fexofenadine disposition (intestinal transporters activity), and efavirenz clearance and 8-hydroxylation (CYP2B6 activity), and human hepatocyte effects. Efavirenz induced systemic and oral alfentanil clearances two- to fivefold and induced efavirenz 8-hydroxylation. Efavirenz stereoselectively decreased methadone plasma concentrations 50-70%. Methadone systemic and oral clearances, hepatic clearance and extraction ratio, N-demethylation, and metabolite formation clearance were stereoselectively increased two- to threefold. Bioavailability decreased. Efavirenz shifted methadone concentration-miosis curves leftward and upward. Efavirenz induced hepatocyte CYP2B6 and CYP3A4 expression, activity, and methadone N-demethylation. Results show that efavirenz coinduced hepatic CYP2B6 and CYP3A4/5, coinduced hepatic and intestinal CYP3A4/5, and coinduced gastrointestinal CYP3A4/5 and efflux transporters. Methadone disposition was most consistent with efavirenz induction of hepatic CYP2B6-mediated methadone N-demethylation. Efavirenz may alter methadone pharmacodynamics.

  4. CYP2B6 18492T->C polymorphism compromises efavirenz concentration in coinfected HIV and tuberculosis patients carrying CYP2B6 haplotype *1/*1.

    PubMed

    Manosuthi, Weerawat; Sukasem, Chonlaphat; Thongyen, Supeda; Nilkamhang, Samruay; Manosuthi, Sukanya; Sungkanuparph, Somnuek

    2014-01-01

    Data regarding the effect of the CYP2B6 18492T→C polymorphism on plasma efavirenz concentrations and 96-week virologic responses in patients coinfected with HIV and tuberculosis (TB) are still unavailable. A total of 139 antiretroviral-naive HIV-infected adults with active TB were prospectively enrolled to receive efavirenz 600 mg-tenofovir 300 mg-lamivudine 300 mg. Eight single nucleotide polymorphisms (SNPs) within CYP2B6 were genotyped. Seven SNPs, including 64C→T, 499C→G, 516G→T, 785A→G, 1375A→G, 1459C→T, and 21563C→T, were included for CYP2B6 haplotype determination. The CYP2B6 18492T→C polymorphism was studied in 48 patients who carried haplotype *1/*1. At 12 and 24 weeks after antiretroviral therapy, plasma efavirenz concentrations at 12 h after dosing were measured. Plasma HIV RNA was monitored every 12 weeks for 96 weeks. Of 48 patients {body weight [mean±standard deviation (SD)], 56±10 kg}, 77% received a rifampin-containing anti-TB regimen. No drug resistance-associated mutation was detected at baseline. The frequencies of the wild type (18492TT) and the heterozygous (18492TC) and homozygous (18492CC) mutants of the CYP2B6 18492T→C polymorphism were 39%, 42%, and 19%, respectively. At 12 weeks, mean (±SD) efavirenz concentrations of patients who carried the 18492TT, 18492TC, and 18492CC mutants were 2.8±1.6, 1.7±0.9, and 1.4±0.5 mg/liter, respectively (P=0.005). At 24 weeks, the efavirenz concentrations of the corresponding groups were 2.4±0.8, 1.7±0.8, and 1.2±0.4 mg/liter, respectively (P=0.003). A low efavirenz concentration was independently associated with 18492T→C (β=-0.937, P=0.004) and high body weight (β=-0.032, P=0.046). At 96 weeks, 19%, 17%, and 28% of patients carrying the 18492TT, 18492TC, and 18492CC mutants, respectively, had plasma HIV RNA levels of >40 copies/ml and developed efavirenz-associated mutations (P=0.254). In summary, the CYP2B6 18492T→C polymorphism compromises efavirenz concentrations in

  5. [Evidence-based therapeutic drug monitoring for efavirenz].

    PubMed

    Solas, Caroline; Gagnieu, Marie-Claude

    2011-01-01

    The efavirenz, a non nucleoside reverse transcriptase inhibitor of HIV-1, presents a marked pharmacokinetics variability related to an intense hepatic metabolism. Efavirenz is also a potent inducer. Central nervous system (CNS) toxicity associated with efavirenz therapy is a major cause of non adherence and therefore treatment failure. The literature has been analyzed to evaluate the level of evidence of the interest of a therapeutic drug monitoring for efavirenz. Several studies have reported that an efavirenz plasma concentration >1 000 ng/mL is a predictive factor of the viral response. Efavirenz plasma concentrations >4 000 ng/mL were associated to an increase frequency of CNS side effects. CNS toxicity was also more frequent in patients carrying the 516G > T mutation (CYP2B6*6 allele), associated with a significantly greater efavirenz plasma exposure. Non-randomized studies have reported the interest of efavirenz therapeutic drug monitoring to optimize viral response and prevent CNS toxicity, allowing to suggest a level of evidence "recommended" for efavirenz.

  6. Efavirenz enhances HIV-1 gag processing at the plasma membrane through Gag-Pol dimerization.

    PubMed

    Sudo, Sho; Haraguchi, Hiyori; Hirai, Yoko; Gatanaga, Hiroyuki; Sakuragi, Jun-ichi; Momose, Fumitaka; Morikawa, Yuko

    2013-03-01

    Efavirenz (EFV), a nonnucleoside reverse transcriptase (RT) inhibitor, also inhibits HIV-1 particle release through enhanced Gag/Gag-Pol processing by protease (PR). To better understand the mechanisms of the EFV-mediated enhancement of Gag processing, we examined the intracellular localization of Gag/Gag-Pol processing products and their precursors. Confocal microscopy revealed that in the presence of EFV, the N-terminal p17 matrix (p17MA) fragment was uniformly distributed at the plasma membrane (PM) but the central p24 capsid (p24CA) and the Pol-encoded RT antigens were diffusely distributed in the cytoplasm, and all of the above were observed in puncta at the PM in the absence of EFV. EFV did not impair PM targeting of Gag/Gag-Pol precursors. Membrane flotation analysis confirmed these findings. Such uniform distribution of p17MA at the PM was not seen by overexpression of Gag-Pol and was suppressed when EFV-resistant HIV-1 was used. Forster's fluorescence resonance energy transfer assay revealed that Gag-Pol precursor dimerization occurred mainly at the PM and that EFV induced a significant increase of the Gag-Pol dimerization at the PM. Gag-Pol dimerization was not enhanced when HIV-1 contained the EFV resistance mutation in RT. Bacterial two-hybrid assay showed that EFV enhanced the dimerization of PR-RT fragments and restored the dimerization impaired by the dimerization-defective mutation in the RT tryptophan repeat motif but not that impaired by the mutation at the PR dimer interface. Collectively, our data indicate that EFV enhances Gag-Pol precursor dimerization, likely after PM targeting but before complete particle assembly, resulting in uniform distribution of p17MA to and dissociation of p24CA and RT from the PM.

  7. Factors influencing lopinavir and atazanavir plasma concentration

    PubMed Central

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

    2010-01-01

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

  8. Factors influencing lopinavir and atazanavir plasma concentration.

    PubMed

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

    2010-01-01

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

  9. High plasma efavirenz level and CYP2B6*6 are associated with efavirenz-based HAART-induced liver injury in the treatment of naïve HIV patients from Ethiopia: a prospective cohort study.

    PubMed

    Yimer, G; Amogne, W; Habtewold, A; Makonnen, E; Ueda, N; Suda, A; Worku, A; Haefeli, W E; Burhenne, J; Aderaye, G; Lindquist, L; Aklillu, E

    2012-12-01

    The objective of this study was to assess the incidence, timing and identify pharmacogenetic, efavirenz (EFV) pharmacokinetic and biochemical predictors of EFV-based antiretroviral therapy (ART) drug-induced liver injury (DILI). ART-naïve HIV patients (n = 285) were prospectively enrolled. Pretreatment laboratory evaluations included hepatitis B surface antigen and C antibody, CD4 count and viral load. Liver tests were done at baseline, 1st, 2nd, 4th, 8th, 12th, 24th and 48th weeks during ART. Plasma EFV and 8-hydroxyefvairenz concentration was determined at week 4 using liquid chromatography-mass spectrometry. CYP2B6, CYP3A5, ABCB1 3435C/T and UGT2B7*2 genotyping was done using Taqman genotyping assay. Data were analyzed using survival analysis and Cox proportional hazards model. The incidence of DILI was 15.7% or 27.9 per 100 person-years and that of severe injury was 3.4% or 6.13 per 100 person-years. The median time for the development of DILI and severe injury was 2 and 4 weeks after initiation of ART, respectively. There was significant association of DILI with lower baseline platelet, albumin, log plasma viral load and CD4 count (P = 0.031, 0.037, 0.06 and 0.019, respectively). Elevated baseline alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, plasma EFV level and CYP2B6*6 were good predictors for the development of DILI (P = 0.03, 0.01, 0.016, 0.017 and 0.04, respectively). We report for the first time CYP2B6*6 as a putative genetic marker and high plasma EFV concentration as intermediate biomarker for vulnerability to EFV-induced liver injury in HIV patients. CYP2B6 genotyping and/or regular monitoring of EFV and lever enzymes level during early therapy is advised for early diagnosis and management of DILI.

  10. Dream changes following initiation of efavirenz treatment.

    PubMed

    Velasco, María; Pareja, Juan Antonio; Losa, Juan Emilio; Valverde, José Francisco; Espinosa, Alfredo; Gujarro, Carlos

    2011-02-12

    The objective was to evaluate abnormalities in the quality of dreams after the use of efavirenz. Ten HIV patients without neuropsychiatric diseases underwent a polisomnography (PSG) study before and after efavirenz treatment, [after 10.4 (SD 5.4) days]. Patients were awoke after REM phases to record their dreams. All patients had therapeutic efavirenz plasma levels. Dreams were recalled in 84% before efavirenz and 43% after efavirenz (p=0.024). There were no differences in the mean number of words per dream before and after efavirenz treatment (61.9 versus 47.5, p=0.115). The proportion of dreams with no neutral emotional content (either pleasant or unpleasant) was 37.5% in the first night and 66.7% in the second night (p=0.046). There were a higher proportion of dreams with no neutral emotional content after efavirenz treatment in this group of patients. However, no longer dreams and no more dreams with negative emotional content were noted. Dream recall was lower after efavirenz treatment. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  11. Efavirenz, Emtricitabine, and Tenofovir

    MedlinePlus

    Atripla® (as a combination product containing Efavirenz, Emtricitabine, Tenofovir) ... years of age or older. Efavirenz is in a class of medications non-nucleoside reverse transcriptase inhibitors ( ...

  12. Serum Nevirapine and Efavirenz concentrations and effect of concomitant rifampicin in HIV infected children on antiretroviral therapy.

    PubMed

    Shah, Ira; Swaminathan, Soumya; Ramachandran, Geetha; Kumar, A K Hemanth; Goray, Apurva; Chaddha, Udit; Tayal, Swati; Lala, Mamatha

    2011-12-01

    To determine factors affecting serum levels of Efavirenz and Nevirapine and analyze the effect of Rifampicin on Nevirapine drug levels. A cross-sectional study was conducted on 30 HIV infected children on Antiretroviral therapy (ART) with Nevirapine or Efavirenz. Patients on simultaneous Rifampicin and Nevirapine were given higher doses of Nevirapine with regular monitoring of liver function tests. Trough levels (before morning dose of Nevirapine) and levels after 2 hours of administration of Nevirapine and levels of Efavirenz were assessed using HPLC and were checked to see if they fall within the therapeutic range. Thirty patients (14 males) were enrolled in the study with 20 on Nevirapine and 10 (33.3%) on Efavirenz. Seven (23.3%) patients were simultaneously taking rifampicin. The mean Nevirapine dose given to the patients was 350.9±59.8 mg/m2/day (on simultaneous rifampicin) and 309.2±54.6 mg/m2/day (not on concurrent rifampicin). Thirteen (81.3%) of the 16 patients with trough Nevirapine had values in the normal range, 1 (6.3%) had low Nevirapine trough levels and 2 (12.5%) had high Nevirapine trough levels. Of the post 2 hours Nevirapine levels, 1 (5%) had low levels and 3 (15%) had high Nevirapine blood levels. Factors like age (P=0.4, P=0.4087), nourishment (P=0.2679, P=0.4132), ART combination (P=0.4199, P=0.4132), form of the drug (tablet/syrup) (P=0.1964, P=0.4696) or if it was being given as single or in a fixed dose combination (P=0.4179, P=0.4696) and even concurrent rifampicin administration (P=0.284, P=0.472) did not significantly affect the trough and post 2 hours Nevirapine values, respectively. All the five patients being given concurrent rifampicin had normal trough and post 2 hours levels of Nevirapine. The Efavirenz drug levels were 1.9±1.1 g/mL. Of the 10 patients on Efavirenz, 2 (20%) had high and 1 (10%) had low blood levels. Concurrent Rifampicin administration does not alter blood levels of Nevirapine; provided the dose of Nevirapine

  13. Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1.

    PubMed

    Hofman, Michael J; Higgins, Joanne; Matthews, Timothy B; Pedersen, Niels C; Tan, Chalet; Schinazi, Raymond F; North, Thomas W

    2004-09-01

    The specificity of nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for the RT of human immunodeficiency virus type 1 (HIV-1) has prevented the use of simian immunodeficiency virus (SIV) in the study of NNRTIs and NNRTI-based highly active antiretroviral therapy. However, a SIV-HIV-1 chimera (RT-SHIV), in which the RT from SIVmac239 was replaced with the RT-encoding region from HIV-1, is susceptible to NNRTIs and is infectious to rhesus macaques. We have evaluated the antiviral activity of efavirenz against RT-SHIV and the emergence of efavirenz-resistant mutants in vitro and in vivo. RT-SHIV was susceptible to efavirenz with a mean effective concentration of 5.9 +/- 4.5 nM, and RT-SHIV variants selected with efavirenz in cell culture displayed 600-fold-reduced susceptibility. The efavirenz-resistant mutants of RT-SHIV had mutations in RT similar to those of HIV-1 variants that were selected under similar conditions. Efavirenz monotherapy of RT-SHIV-infected macaques produced a 1.82-log-unit decrease in plasma viral-RNA levels after 1 week. The virus load rebounded within 3 weeks in one treated animal and more slowly in a second animal. Virus isolated from these two animals contained the K103N and Y188C or Y188L mutations. The RT-SHIV-rhesus macaque model may prove useful for studies of antiretroviral drug combinations that include efavirenz.

  14. Efavirenz Therapy in Rhesus Macaques Infected with a Chimera of Simian Immunodeficiency Virus Containing Reverse Transcriptase from Human Immunodeficiency Virus Type 1

    PubMed Central

    Hofman, Michael J.; Higgins, Joanne; Matthews, Timothy B.; Pedersen, Niels C.; Tan, Chalet; Schinazi, Raymond F.; North, Thomas W.

    2004-01-01

    The specificity of nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for the RT of human immunodeficiency virus type 1 (HIV-1) has prevented the use of simian immunodeficiency virus (SIV) in the study of NNRTIs and NNRTI-based highly active antiretroviral therapy. However, a SIV-HIV-1 chimera (RT-SHIV), in which the RT from SIVmac239 was replaced with the RT-encoding region from HIV-1, is susceptible to NNRTIs and is infectious to rhesus macaques. We have evaluated the antiviral activity of efavirenz against RT-SHIV and the emergence of efavirenz-resistant mutants in vitro and in vivo. RT-SHIV was susceptible to efavirenz with a mean effective concentration of 5.9 ± 4.5 nM, and RT-SHIV variants selected with efavirenz in cell culture displayed 600-fold-reduced susceptibility. The efavirenz-resistant mutants of RT-SHIV had mutations in RT similar to those of HIV-1 variants that were selected under similar conditions. Efavirenz monotherapy of RT-SHIV-infected macaques produced a 1.82-log-unit decrease in plasma viral-RNA levels after 1 week. The virus load rebounded within 3 weeks in one treated animal and more slowly in a second animal. Virus isolated from these two animals contained the K103N and Y188C or Y188L mutations. The RT-SHIV-rhesus macaque model may prove useful for studies of antiretroviral drug combinations that include efavirenz. PMID:15328115

  15. Antiretroviral dose optimization: the future of efavirenz 400 mg dosing.

    PubMed

    Boffito, Marta; Lamorde, Mohammed; Watkins, Melynda; Pozniak, Anton

    2017-07-01

    Antiretroviral (ARV) therapy costs in low-income and middle-income countries are major concerns, and lower doses of first-line treatment components, when possible, would save millions of dollars, which could be used to treat more people living with HIV. The Encore-1 study, followed by a detailed pharmacokinetic analysis of efavirenz 400 versus 600 mg once daily, produced enough information for the most recent ARV treatment WHO guidelines to include efavirenz 400 mg among agents used for first-line treatment. However, data on efavirenz 400 mg plasma concentrations during pregnancy and when coadministered with rifampicin-containing antituberculosis (TB) treatment are not yet available as formal pharmacokinetic studies under these circumstances are ongoing. Although efavirenz at a daily dose of 400 mg once daily in combination with tenofovir disoproxil fumarate and emtricitabine has shown noninferiority to the approved 600 mg once-daily dose, large global uptake has been delayed by the lack of data on drug exposure during pregnancy and anti-TB treatment. Knowledge on efavirenz 400 mg exposure in these scenarios will arise in mid-late 2017.

  16. In vivo individual variations in pharmacokinetics of efavirenz in cynomolgus monkeys genotyped for cytochrome P450 2C9.

    PubMed

    Iwasaki, Kazuhide; Kitsugi, Yusuke; Ikeda, Kanami; Yoshikawa, Takahiro; Hosaka, Shinya; Uehara, Shotaro; Uno, Yasuhiro; Utoh, Masahiro; Yamazaki, Hiroshi

    2016-09-01

    Cynomolgus monkeys are used frequently in preclinical studies for new drug development due to their evolutionary closeness to humans. An antiretroviral drug, efavirenz, is a typical probe substrate for human cytochrome P450 (P450) 2B6, but is mainly metabolized by cynomolgus monkey P450 2C9. In this study, plasma concentrations of efavirenz were assessed in six cynomolgus monkeys genotyped for P450 2C9 c.334 A > C (I112L) (three wild-type, one heterozygote and two homozygotes) by high performance liquid chromatography with tandem mass spectrometry. After intravenous administration at a dose of 1.0 mg/kg, biphasic plasma elimination curves of efavirenz were seen in these cynomolgus monkeys. The mean plasma concentration of the primary metabolite 8-hydroxyefavirenz (1 h after treatment, with hydrolysis by β-glucuronidase) in the wild-type group was significantly higher (4.0-fold) than the combined heterozygous and homozygous group mean. The area under the plasma concentration-time curve value of efavirenz in the homozygous group after oral administration at a dose of 2.0 mg/kg was significantly higher (2.0-fold) than the combined wild-type and heterozygous group. These results collectively indicated that P450 2C9 c.334 A > C (I112L) variation was associated with efavirenz metabolic clearance in vivo. Cynomolgus P450 2C9 polymorphism might account for interindividual variations of efavirenz metabolism in cynomolgus monkeys. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS Clinical Trials Group Study A5267.

    PubMed

    Dooley, Kelly E; Park, Jeong-Gun; Swindells, Susan; Allen, Reena; Haas, David W; Cramer, Yoninah; Aweeka, Francesca; Wiggins, Ilene; Gupta, Amita; Lizak, Patricia; Qasba, Sonia; van Heeswijk, Rolf; Flexner, Charles

    2012-04-15

    Drug-drug interactions complicate management of coinfection with HIV-1 and Mycobacterium tuberculosis. Bedaquiline (formerly TMC207), an investigational agent for the treatment of tuberculosis, is metabolized by cytochrome P450 (CYP) 3A which may be induced by the antiretroviral drug efavirenz. This was a phase 1 pharmacokinetic drug interaction trial. Each healthy volunteer received two 400 mg doses of bedaquiline, the first alone and the second with concomitant steady-state efavirenz. Plasma pharmacokinetic sampling for bedaquiline and its N-monodesmethyl metabolite was performed over 14 days after each bedaquiline dose. Steady-state efavirenz pharmacokinetics were also determined. Efavirenz metabolizer status was based on CYP2B6 composite 516/983 genotype. Thirty-three of 37 enrolled subjects completed the study. Geometric mean of ratios for bedaquiline with efavirenz versus bedaquiline alone were 0.82 [90% confidence interval (CI): 0.75 to 0.89] for the 14-day area under the concentration-time curve (AUC0-336 h) and 1.00 (90% CI: 0.88 to 1.13) for the maximum concentration (Cmax). For N-monodesmethyl metabolite, the geometric mean of ratios was 1.07 (90% CI: 0.97 to 1.19) for AUC0-336 h and 1.89 (90% CI: 1.66 to 2.15) for C(max). There were no grade 3 or 4 clinical adverse events. One subject developed asymptomatic grade 3 serum transaminase elevation, prompting study drug discontinuation. Efavirenz concentrations stratified by CYP2B6 genotype were similar to historical data. Single-dose bedaquiline was well tolerated alone and with steady-state efavirenz. The effect of efavirenz on bedaquiline concentrations is unlikely to be clinically significant.

  18. Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS Clinical Trials Group study A5267

    PubMed Central

    Dooley, Kelly E; Park, Jeong-Gun; Swindells, Susan; Allen, Reena; Haas, David W.; Cramer, Yoninah; Aweeka, Francesca; Wiggins, Ilene; Gupta, Amita; Lizak, Patricia; Qasba, Sonia; van Heeswijk, Rolf; Flexner, Charles

    2012-01-01

    Background Drug-drug interactions complicate management of co-infection with HIV-1 and Mycobacterium tuberculosis. Bedaquiline (formerly TMC207), an investigational agent for the treatment of tuberculosis, is metabolized by cytochrome P450 (CYP) 3A which may be induced by the antiretroviral drug efavirenz. Methods This was a Phase I pharmacokinetic drug interaction trial. Each healthy volunteer received two 400 mg doses of bedaquiline, the first alone, and the second with concomitant steady-state efavirenz. Plasma pharmacokinetic sampling for bedaquiline and its N-monodesmethyl metabolite (M2) was performed over 14 days after each bedaquiline dose. Steady-state efavirenz pharmacokinetics were also determined. Efavirenz metabolizer status was based on CYP2B6 composite 516/983 genotype. Results Thirty-three of 37 enrolled subjects completed the study. Geometric mean ratios (GMR) for bedaquiline with efavirenz versus bedaquiline alone were 0.82 (90% CI 0.75 to 0.89) for the 14-day area under the concentration-time curve (AUC0-336h) and 1.00 (90% CI 0.88 to 1.13) for the maximum concentration (Cmax). For M2, the GMR was 1.07 (90% CI 0.97 to 1.19) for AUC0-336h and 1.89 (90% CI 1.66 to 2.15) for Cmax. There were no Grade 3 or 4 clinical adverse events. One subject developed asymptomatic Grade 3 serum transaminase elevation, prompting study drug discontinuation. Efavirenz concentrations stratified by CYP2B6 genotype were similar to historical data. Conclusions Single-dose bedaquiline was well-tolerated alone and with steady-state efavirenz. The effect of efavirenz on bedaquiline concentrations is unlikely to be clinically significant. PMID:22126739

  19. Stepped-dose versus full-dose efavirenz for HIV infection and neuropsychiatric adverse events: a randomized trial.

    PubMed

    Gutiérrez-Valencia, Alicia; Viciana, Pompeyo; Palacios, Rosario; Ruiz-Valderas, Rosa; Lozano, Fernando; Terrón, Alberto; Rivero, Antonio; López-Cortés, Luis F

    2009-08-04

    More than 50% of patients who start efavirenz treatment develop limiting neuropsychiatric adverse events (NPAEs). To assess whether stepwise dosing of efavirenz decreases the incidence and severity of NPAEs while maintaining virologic efficacy. Randomized, double-blind, controlled trial. 7 HIV clinics in Spain. 114 HIV-infected patients eligible for efavirenz treatment plus 2 nucleoside or nucleotide reverse transcriptase inhibitors. Random assignment (by computer-generated sequence) to receive efavirenz, 200 mg/d on days 1 through 6, 400 mg/d on days 7 through 13, and 600 mg/d on day 14 and after, or efavirenz, 600 mg/d, from day 1. Both groups received 2 nucleoside or nucleotide reverse transcriptase inhibitors chosen by the patient's physician. Neuropsychiatric symptoms and sleep quality were assessed by questionnaires at 0, 7, 14, and 30 days. The primary outcome was efavirenz-related NPAEs during the first 2 weeks, and the secondary outcome was plasma HIV RNA level at 24 weeks. Compared with the stepped-dose group, the full-dose group had higher incidence and severity of dizziness (66.0% vs. 32.8%; P = 0.001), hangover (45.8% vs. 20.7%; P = 0.008), impaired concentration (22.9% vs. 8.9%; P = 0.038), and hallucinations (6.1% vs. 0%; P = 0.056) during the first week. From week 2, the incidence of efavirenz-related NPAEs was similar in both groups, although the severity was greater in the full-dose group. Virologic and immunologic efficacy seemed similar in both groups. The sample size was calculated on the basis of a high absolute difference in rates of efavirenz-related NPAEs between the groups. A lower absolute difference and a larger sample size could have made the differences between groups reach statistical significance beyond the first week. In addition, the sample size does not allow confirmation of similar efficacy between treatment groups. Stepwise dose escalation of efavirenz over 2 weeks reduces the incidence and intensity of efavirenz-related NPAEs

  20. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies

    PubMed Central

    Gaur, Praveen Kumar; Mishra, Shikha; Bajpai, Meenakshi; Mishra, Anushika

    2014-01-01

    Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5 ± 3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75 ± 5% relative humidity (RH) for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (Cmax⁡) and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES). PMID:24967360

  1. Plasma Drug Concentrations and Virologic Evaluations after Stopping Treatment with Nonnucleoside Reverse-Transcriptase Inhibitors in HIV Type 1–Infected Children

    PubMed Central

    Cressey, Tim R.; Green, Hannah; Khoo, Saye; Treluyer, Jean-Marc; Compagnucci, Alexandra; Saidi, Yacine; Lallemant, Marc; Gibb, Diana M.; Burger, David M.

    2013-01-01

    Background The optimum strategy for stopping treatment with drugs that have different half-lives in a combination regimen to minimize the risk of selecting drug-resistant viruses remains unknown. We evaluated drug concentrations in plasma, human immunodeficiency virus (HIV) load, and development of drug resistance after a planned treatment interruption of a nonnucleoside reverse-transcriptase inhibitor (NNRTI)–containing regimen in HIV type 1–infected children. Methods Children with viral loads <50 copies/mL and CD4 cell percentages ≥30% (for children aged 2–6 years) or CD4 cell percentages ≥25% and CD4 cell counts ≥500 cells/μL (for children aged 7–15 years) were randomized to either a planned treatment interruption or to continuous therapy. In the planned treatment interruption arm, either (1) treatment with nevirapine or efavirenz was stopped, and treatment with the remaining drugs was continued for 7–14 days, or (2) nevirapine or efavirenz were replaced by a protease inhibitor, and all drugs were stopped after 7–14 days. Sampling for determination of plasma drug concentrations, measurement of viral load, and drug resistance testing was scheduled at day 0, day 7 (drug concentrations only), day 14, and day 28 after interruption of treatment with an NNRTI. Results Treatment with an NNRTI was interrupted for 35 children (20 were receiving nevirapine, and 15 were receiving efavirenz). Median time from NNRTI cessation to stopping all drugs was 9 days (range, 6–15 days) for nevirapine and 14 days (range, 6–18 days) for efavirenz. At 7 days, 1 (5%) of 19 and 4 (50%) of 8 children had detectable nevirapine and efavirenz concentrations, respectively; efavirenz remained detectable in 3 (25%) of 12 children at 14 days. At 14 days, viral load was ≥50 copies/mL in 6 of 16 children interrupting treatment with nevirapine (range, 52–7000 copies/mL) and in 2 of 12 children interrupting treatment with efavirenz (range, 120–1600 copies/mL). No new

  2. Markov model for characterizing neuropsychologic impairment and Monte Carlo simulation for optimizing efavirenz therapy.

    PubMed

    Bisaso, Kuteesa R; Mukonzo, Jackson K; Ette, Ene I

    2015-11-01

    The study was undertaken to develop a pharmacokinetic-pharmacodynamic model to characterize efavirenz-induced neuropsychologic impairment, given preexistent impairment, which can be used for the optimization of efavirenz therapy via Monte Carlo simulations. The modeling was performed with NONMEM 7.2. A 1-compartment pharmacokinetic model was fitted to efavirenz concentration data from 196 Ugandan patients treated with a 600-mg daily efavirenz dose. Pharmacokinetic parameters and area under the curve (AUC) were derived. Neuropsychologic evaluation of the patients was done at baseline and in week 2 of antiretroviral therapy. A discrete-time 2-state first-order Markov model was developed to describe neuropsychologic impairment. Efavirenz AUC, day 3 efavirenz trough concentration, and female sex increased the probability (P01) of neuropsychologic impairment. Efavirenz oral clearance (CL/F) increased the probability (P10) of resolution of preexistent neuropsychologic impairment. The predictive performance of the reduced (final) model, given the data, incorporating AUC on P01and CL /F on P10, showed that the model adequately characterized the neuropsychologic impairment observed with efavirenz therapy. Simulations with the developed model predicted a 7% overall reduction in neuropsychologic impairment probability at 450 mg of efavirenz. We recommend a reduction in efavirenz dose from 600 to 450 mg, because the 450-mg dose has been shown to produce sustained antiretroviral efficacy.

  3. Efavirenz does not meaningfully affect the single dose pharmacokinetics of 1200 mg raltegravir.

    PubMed

    Krishna, Rajesh; East, Lilly; Larson, Patrick; Siringhaus, Tara; Herpok, Lisa; Bethel-Brown, Crystal; Manthos, Helen; Brejda, John; Gartner, Michael

    2016-12-01

    Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice daily (BID). Raltegravir for once daily regimen (QD) at a dose of 1200 mg (2 x 600 mg) is under development and offers a new treatment option for HIV-1 infected treatment-naive subjects. Since raltegravir is eliminated mainly by metabolism via an UDP-glucuronosyltransferase (UGT) 1 A1-mediated glucuronidation pathway, co-administration of UGT1A1 inducers may alter plasma levels of raltegravir. Efavirenz, an UGT1A1 inducer, was used to assess the impact of altered UGT activity on a 1200 mg QD dose of raltegravir. An open label, randomized, 2-period fixed-sequence Phase 1 study was performed in adult healthy male and female subjects (non-childbearing potential) ≥ 19 and ≤55 years of age, with a body mass index (BMI) ≥ 18.5 and ≤32.0 kg/m(2) . Subjects (n = 21) received a single oral dose of 1200 mg raltegravir at bedtime on an empty stomach on Day 1 in Period 1. After a washout period of at least 7 days, subjects received oral doses of 600 mg efavirenz QD at bedtime for 14 consecutive days in Period 2. Subjects received a single oral dose of 1200 mg raltegravir co-administered with 600 mg efavirenz on Day 12 of Period 2. Pharmacokinetic (PK) samples were collected for 72 hours following raltegravir dosing and analyzed using a validated bioanalytical method to quantify raltegravir plasma concentrations. PK parameters were estimated using non-compartmental analysis. Administration of single 1200 mg oral doses of raltegravir alone and co-administered with multiple oral doses of efavirenz were generally well tolerated in healthy subjects. Co-administration with efavirenz yielded geometric mean ratios (GMRs) and their associated 90% confidence intervals (90% CIs) for raltegravir AUC0-∞, Cmax , and C24 of 0.86 (0.73, 1.01), 0.91 (0.70, 1.17), and 0.94 (0.76, 1.17), respectively. The results show that efavirenz

  4. Efavirenz Causes Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Endothelial Cells.

    PubMed

    Weiß, Marlene; Kost, Bernd; Renner-Müller, Ingrid; Wolf, Eckhard; Mylonas, Ioannis; Brüning, Ansgar

    2016-01-01

    The non-nucleoside reverse transcriptase inhibitor efavirenz is a widely prescribed antiretroviral drug used in combined antiretroviral therapy. Despite being an essential and life-saving medication, the required lifelong use of HIV drugs has been associated with a variety of adverse effects, including disturbances in lipid metabolism and increased cardiovascular risk. Efavirenz belongs to those HIV drugs for which cardiovascular and endothelial dysfunctions have been reported. It is here shown that elevated concentrations of efavirenz can inhibit endothelial meshwork formation on extracellular matrix gels by normal and immortalized human umbilical vein cells. This inhibition was associated with an increase in oxidative stress markers, endoplasmic reticulum (ER) stress markers, and autophagy. Induction of ER stress occurred at pharmacologically relevant concentrations of efavirenz and resulted in reduced proliferation and cell viability of endothelial cells, which worsened in the presence of elevated efavirenz concentrations. In combination with the HIV protease inhibitor nelfinavir, both oxidative stress and ER stress became elevated in endothelial cells. These data indicate that pharmacologically relevant concentrations of efavirenz can impair cell viability of endothelial cells and that these effects may be aggravated by either elevated concentrations of efavirenz or by a combined use of efavirenz with other oxidative stress-inducing medications.

  5. Nevirapine versus efavirenz-based antiretroviral therapy regimens in antiretroviral-naive patients with HIV and tuberculosis infections in India: a pilot study

    PubMed Central

    2013-01-01

    Background Administration of rifampicin along with nevirapine reduces the plasma concentration of nevirapine in human immunodeficiency virus positive individuals with concomitant tuberculosis (HIV-TB patients). Nevirapine is a much cheaper drug than its alternative efavirenz, and might be beneficial in resource constrained settings. Methods A randomised open label trial was conducted at All India Institute of Medical Sciences, New Delhi, India. During the regimen of an antiretroviral therapy (ART), naive HIV-TB patients were randomly assigned to receive either nevirapine or efavirenz based ART with concomitant rifampicin based anti-tubercular therapy (ATT). Participants were followed for 24 months after starting ART. The end points were virological, immunological and clinical responses, and progression of HIV disease marked by failure of ART. Results Of the 135 HIV-TB patients, who were receiving rifampicin based ATT, 68 were selected randomly to receive efavirenz based ART and 67 to receive nevirapine based ART. The virological failure rates in the overall population, and the nevirapine and efavirenz groups were 14.1% (19/135); 14.9% (10/67) and 13.2% (9/68), respectively (p = 0.94). No significant difference was found between the groups in the rate of clinical, immunological or virological failures. The overall mortality was 17% with no significant difference between the two groups. Except for the lead in period on day 14, the mean nevirapine concentration remained above 3 mg/L. No association was found between plasma levels of nevirapine and incidence of unfavourable outcomes in this group. Conclusions Outcome of ART in HIV-TB patients on rifampicin based ATT showed no significant difference, irrespective of whether efavirenz or nevirapine was used. Therefore, nevirapine based ART could be an alternative in the resource limited settings in patients with HIV and tuberculosis co-infection. Trial registration NCT No. 01805258. PMID:24134449

  6. Plasma leptin concentration in donkeys.

    PubMed

    Díez, E; López, I; Pérez, C; Pineda, C; Aguilera-Tejero, E

    2012-01-01

    Donkeys appear to be more predisposed than large breed horses to suffer from hyperlipemia. The reason for that predisposition is unknown but anorexia is a consistent feature of the disease. Leptin, a protein synthesized in fat tissue, is one of the major inhibitors of appetite in mammals. We hypothesized that donkeys could have elevated plasma leptin concentrations compared to horses. Blood samples were obtained from 50 donkeys for measurement of leptin, triglycerides (TGs), glucose, and insulin. Glucose/insulin ratio, modified insulin to glucose ratio, and reciprocal of the square root of insulin were calculated. Based on their body condition score (BCS), donkeys were classified as lean (n = 18), normal (n = 16), or overweight (n = 16). The results were compared with reference values from our laboratory and with a group of horses (n = 25) used as an internal control. Values of both leptin and TGs in donkeys were above the horse reference range and also significantly higher than those of the control horses: leptin (11.2 ± 1.7 versus 5.8 ± 0.5 µg/L, p < 0.05) and TGs (0.93 ± 0.1 versus 0.54 ± 0.1 mmol/L, p < 0.01). Overweight donkeys had leptin (19.3 ± 2.9 µg/L) and TG (1.3 ± 0.2 mmol/L) concentrations that were significantly (p < 0.01) higher than normal (9.4 ± 3.3 µg/L and 0.85 ± 0.1 mmol/L, respectively) and lean (5.5 ± 1.0 µg/L and 0.66 ± 0.1 mmol/L, respectively) donkeys. A significant positive correlation (p < 0.01) was found between BCS and leptin (r = 0.43), TGs (r = 0.46), glucose (r = 0.41), and insulin (r = 0.40). Donkeys have higher plasma leptin concentrations than horses and leptin is correlated with BCS.

  7. Efavirenz-induced exfoliative dermatitis.

    PubMed

    Zhang, Jiu-Cong; Sun, Yong-Tao

    2013-01-01

    Individuals with a human immunodeficiency virus (HIV) infection are at higher risk of developing adverse drug reactions. Multiple drugs are usually prescribed to patients with HIV infection for preventing the replication of HIV and for the treatment of the associated opportunistic infections. We report here the first case of an HIV-1-infected patient who developed an exfoliative dermatitis induced by efavirenz, a non-nucleoside reverse transcriptase inhibitor. Physicians should be aware of the possible occurrence of efavirenz-induced skin eruptions from the start of antiviral treatment of HIV infection.

  8. Isoniazid mediates the CYP2B6*6 genotype-dependent interaction between efavirenz and antituberculosis drug therapy through mechanism-based inactivation of CYP2A6.

    PubMed

    Court, Michael H; Almutairi, Fawziah E; Greenblatt, David J; Hazarika, Suwagmani; Sheng, Hongyan; Klein, Kathrin; Zanger, Ulrich M; Bourgea, Joanne; Patten, Christopher J; Kwara, Awewura

    2014-07-01

    Efavirenz is commonly used to treat patients coinfected with human immunodeficiency virus and tuberculosis. Previous clinical studies have observed paradoxically elevated efavirenz plasma concentrations in patients with the CYP2B6*6/*6 genotype (but not the CYP2B6*1/*1 genotype) during coadministration with the commonly used four-drug antituberculosis therapy. This study sought to elucidate the mechanism underlying this genotype-dependent drug-drug interaction. In vitro studies were conducted to determine whether one or more of the antituberculosis drugs (rifampin, isoniazid, pyrazinamide, or ethambutol) potently inhibit efavirenz 8-hydroxylation by CYP2B6 or efavirenz 7-hydroxylation by CYP2A6, the main mechanisms of efavirenz clearance. Time- and concentration-dependent kinetics of inhibition by the antituberculosis drugs were determined using genotyped human liver microsomes (HLMs) and recombinant CYP2A6, CYP2B6.1, and CYP2B6.6 enzymes. Although none of the antituberculosis drugs evaluated at up to 10 times clinical plasma concentrations were found to inhibit efavirenz 8-hydroxylation by HLMs, both rifampin (apparent inhibition constant [Ki] = 368 μM) and pyrazinamide (Ki = 637 μM) showed relatively weak inhibition of efavirenz 7-hydroxylation. Importantly, isoniazid demonstrated potent time-dependent inhibition of efavirenz 7-hydroxylation in both HLMs (inhibitor concentration required for half-maximal inactivation [KI] = 30 μM; maximal rate constant of inactivation [kinact] = 0.023 min(-1)) and recombinant CYP2A6 (KI = 15 μM; kinact = 0.024 min(-1)) and also formed a metabolite intermediate complex consistent with mechanism-based inhibition. Selective inhibition of the CYP2B6.6 allozyme could not be demonstrated for any of the antituberculosis drugs using either recombinant enzymes or CYP2B6*6 genotype HLMs. In conclusion, the results of this study identify isoniazid as the most likely perpetrator of this clinically important drug-drug interaction through

  9. Isoniazid Mediates the CYP2B6*6 Genotype-Dependent Interaction between Efavirenz and Antituberculosis Drug Therapy through Mechanism-Based Inactivation of CYP2A6

    PubMed Central

    Almutairi, Fawziah E.; Greenblatt, David J.; Hazarika, Suwagmani; Sheng, Hongyan; Klein, Kathrin; Zanger, Ulrich M.; Bourgea, Joanne; Patten, Christopher J.; Kwara, Awewura

    2014-01-01

    Efavirenz is commonly used to treat patients coinfected with human immunodeficiency virus and tuberculosis. Previous clinical studies have observed paradoxically elevated efavirenz plasma concentrations in patients with the CYP2B6*6/*6 genotype (but not the CYP2B6*1/*1 genotype) during coadministration with the commonly used four-drug antituberculosis therapy. This study sought to elucidate the mechanism underlying this genotype-dependent drug-drug interaction. In vitro studies were conducted to determine whether one or more of the antituberculosis drugs (rifampin, isoniazid, pyrazinamide, or ethambutol) potently inhibit efavirenz 8-hydroxylation by CYP2B6 or efavirenz 7-hydroxylation by CYP2A6, the main mechanisms of efavirenz clearance. Time- and concentration-dependent kinetics of inhibition by the antituberculosis drugs were determined using genotyped human liver microsomes (HLMs) and recombinant CYP2A6, CYP2B6.1, and CYP2B6.6 enzymes. Although none of the antituberculosis drugs evaluated at up to 10 times clinical plasma concentrations were found to inhibit efavirenz 8-hydroxylation by HLMs, both rifampin (apparent inhibition constant [Ki] = 368 μM) and pyrazinamide (Ki = 637 μM) showed relatively weak inhibition of efavirenz 7-hydroxylation. Importantly, isoniazid demonstrated potent time-dependent inhibition of efavirenz 7-hydroxylation in both HLMs (inhibitor concentration required for half-maximal inactivation [KI] = 30 μM; maximal rate constant of inactivation [kinact] = 0.023 min−1) and recombinant CYP2A6 (KI = 15 μM; kinact = 0.024 min−1) and also formed a metabolite intermediate complex consistent with mechanism-based inhibition. Selective inhibition of the CYP2B6.6 allozyme could not be demonstrated for any of the antituberculosis drugs using either recombinant enzymes or CYP2B6*6 genotype HLMs. In conclusion, the results of this study identify isoniazid as the most likely perpetrator of this clinically important drug-drug interaction through

  10. Plasma fibrinogen concentration in a Chinese population.

    PubMed

    Ko, G T; Yeung, V T; Chan, J C; Chow, C C; Li, J K; So, W Y; Tsang, L W; Cockram, C S

    1997-06-01

    Plasma fibrinogen concentration has been shown to be a predictor of major cardiovascular events. Information on plasma fibrinogen amongst Chinese has been scanty. We examined the relationships between plasma fibrinogen concentration and cardiovascular risk factors in 988 chinese subjects who underwent 75 g oral glucose tolerance test for screening for glucose intolerance. The study involved a selected sample with subjects who had an history of gestational diabetes, delivery of big babies (birth weight > or = 4 kg), equivocal plasma glucose concentrations and subjects who were family members of diabetic patients. This was mainly a non-smoking (96.6%), non-drinking (98%) and non-exercising (99%) population of which 87% (n = 855) were female. Among the 988 subjects (age +/- S.D. 36.8 +/- 10.2, range 16-79 years), plasma fibrinogen concentration ranged from 1.40 to 9.90 g/l with a mean of 3.26 +/- 0.93 g/l. On stratification of the subjects into 4 quartiles based on plasma fibrinogen concentrations, we found that increased plasma fibrinogen was associated with older age, higher body mass index (BMI), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose (PG), prevalence of diabetes, glycated haemoglobin (HbA1c) and triglyceride (TG) level. After adjustment for age and sex, increased plasma fibrinogen concentration remained associated with higher BMI, systolic BP, 2 h PG and TG level. On multivariate analysis using age, BMI, BP, TG, HbA1c and PG as independent variables, plasma fibrinogen was independently related to plasma TG concentration and HbA1c. With 1 S.D. change in TG concentration and HbA1c, there were 3.7 and 5.2% changes in plasma fibrinogen concentration respectively. These findings emphasize the close relationships between plasma fibrinogen and cardiovascular risk factors, in particular abnormal lipid and glucose metabolism.

  11. High concentration plasma-reduced plateletapheresis concentrates.

    PubMed

    Perseghin, Paolo

    2011-06-01

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

  12. Pharmacokinetics of Efavirenz and Treatment of HIV-1 Among Pregnant Women With and Without Tuberculosis Coinfection

    PubMed Central

    Dooley, Kelly E.; Denti, Paolo; Martinson, Neil; Cohn, Silvia; Mashabela, Fildah; Hoffmann, Jennifer; Haas, David W.; Hull, Jennifer; Msandiwa, Regina; Castel, Sandra; Wiesner, Lubbe; Chaisson, Richard E.; McIlleron, Helen

    2015-01-01

    Background Pregnancy and tuberculosis treatment or prophylaxis can affect efavirenz pharmacokinetics, maternal human immunodeficiency virus type 1 (HIV-1) treatment outcomes, and mother-to-child transmission (MTCT) risk. Methods We evaluated a prospective cohort of pregnant, HIV-infected women with and without tuberculosis in Soweto, South Africa. Pharmacokinetic sampling was performed at gestation week 37 and during the postpartum period. Efavirenz trough concentrations (Cmin) were predicted using population pharmacokinetic models. HIV-viral load was measured at delivery for mothers and at 6 weeks of age for infants. Results Ninety-seven women participated; 44 had tuberculosis. Median efavirenz Cmin during pregnancy was 1.35 µg/mL (interquartile range [IQR], 0.90–2.07 µg/mL; 27% had an efavirenz Cmin of < 1 µg/mL), compared with a median postpartum value of 2.00 µg/mL (IQR, 1.40–3.59 µg/mL; 13% had an efavirenz Cmin of < 1 µg/mL). A total of 72% of pregnant women with extensive CYP2B6 genotypes had an efavirenz Cmin of <1 µg/mL. Rifampin did not reduce the efavirenz Cmin. Isoniazid (for prophylaxis or treatment), though, reduced the rate of efavirenz clearance. At delivery, median durations of ART were 13 weeks (IQR, 9–18 weeks) and 21 weeks (IQR, 13–64 weeks) for women with and those without tuberculosis, respectively; 55% and 83%, respectively, had a viral load of <20 copies/mL (P = .021). There was 1 case of MTCT. Conclusions Pregnancy increased the risk of low efavirenz concentrations, but MTCT was rare. A detectable HIV-viral load at delivery was more common among pregnant women with tuberculosis, in whom ART was generally initiated later. PMID:25081933

  13. Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis coinfection.

    PubMed

    Dooley, Kelly E; Denti, Paolo; Martinson, Neil; Cohn, Silvia; Mashabela, Fildah; Hoffmann, Jennifer; Haas, David W; Hull, Jennifer; Msandiwa, Regina; Castel, Sandra; Wiesner, Lubbe; Chaisson, Richard E; McIlleron, Helen

    2015-01-15

    Pregnancy and tuberculosis treatment or prophylaxis can affect efavirenz pharmacokinetics, maternal human immunodeficiency virus type 1 (HIV-1) treatment outcomes, and mother-to-child transmission (MTCT) risk. We evaluated a prospective cohort of pregnant, HIV-infected women with and without tuberculosis in Soweto, South Africa. Pharmacokinetic sampling was performed at gestation week 37 and during the postpartum period. Efavirenz trough concentrations (Cmin) were predicted using population pharmacokinetic models. HIV-viral load was measured at delivery for mothers and at 6 weeks of age for infants. Ninety-seven women participated; 44 had tuberculosis. Median efavirenz Cmin during pregnancy was 1.35 µg/mL (interquartile range [IQR], 0.90-2.07 µg/mL; 27% had an efavirenz Cmin of < 1 µg/mL), compared with a median postpartum value of 2.00 µg/mL (IQR, 1.40-3.59 µg/mL; 13% had an efavirenz Cmin of < 1 µg/mL). A total of 72% of pregnant women with extensive CYP2B6 genotypes had an efavirenz Cmin of <1 µg/mL. Rifampin did not reduce the efavirenz Cmin. Isoniazid (for prophylaxis or treatment), though, reduced the rate of efavirenz clearance. At delivery, median durations of ART were 13 weeks (IQR, 9-18 weeks) and 21 weeks (IQR, 13-64 weeks) for women with and those without tuberculosis, respectively; 55% and 83%, respectively, had a viral load of <20 copies/mL (P = .021). There was 1 case of MTCT. Pregnancy increased the risk of low efavirenz concentrations, but MTCT was rare. A detectable HIV-viral load at delivery was more common among pregnant women with tuberculosis, in whom ART was generally initiated later. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Plasma concentrations of voriconazole in falcons.

    PubMed

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

    2007-08-25

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

  15. Plasma lipid concentrations for some Brazilian lizards.

    PubMed

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

    1979-01-01

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

  16. Mitochondrial (dys)function – a factor underlying the variability of efavirenz-induced hepatotoxicity?

    PubMed Central

    Polo, M; Alegre, F; Funes, H A; Blas-Garcia, A; Victor, V M; Esplugues, J V; Apostolova, N

    2015-01-01

    Background and Purpose The non-nucleoside analogue reverse transcriptase inhibitor efavirenz is associated with hepatic toxicity and metabolic disturbances. Although the mechanisms involved are not clear, recent evidence has pinpointed a specific mitochondrial action of efavirenz accompanied by the induction of an endoplasmic reticulum (ER) stress/unfolded protein response in human hepatic cells. The aim of this study was to further investigate the involvement of this organelle by evaluating efavirenz's effects in cells lacking functional mitochondria (rho°) and comparing them with those of the typical mitotoxic agent rotenone, a standard complex I inhibitor, and the ER stress inducer thapsigargin. Experimental Approach Hep3B rho+ and rho° cells were treated with clinically relevant concentrations of efavirenz, then mitochondrial function and cytotoxicity were studied using standard cell biology techniques. Key Results Efavirenz-treated rho° cells exhibited a substantial reduction in parameters indicative of mitochondrial interference, such as increased superoxide production, mitochondrial mass/morphology alterations and enhanced expression of LONP, a highly conserved mitochondrial protease. In line with these results, the cytotoxic effect (cell number, chromatin condensation, cell cycle alterations and induction of apoptosis) of efavirenz was less pronounced in Hep3B respiration-depleted cells than in wild-type cells. The effect of efavirenz was both similar and different from those of two distinct mitochondrial stressors, thapsigargin and rotenone. Conclusions and Implications Cells lacking normal mitochondria (rho°) are less vulnerable to efavirenz. Our results provide further evidence that the hepatic damage induced by efavirenz involves acute interference with mitochondria and extend our knowledge of the response of mitochondria/ER to a stress stimulus. PMID:25411110

  17. Influence of Milling Process on Efavirenz Solubility.

    PubMed

    Zaini, Erizal; Wahyu, Deni; Octavia, Maria Dona; Fitriani, Lili

    2017-01-01

    The aim of this study was to investigate the influence of the milling process on the solubility of efavirenz. Milling process was done using Nanomilling for 30, 60, and 180 min. Intact and milled efavirenz were characterized by powder X-ray diffraction, scanning electron microscopy (SEM), spectroscopy infrared (IR), differential scanning calorimetry (DSC), and solubility test. The X-ray diffractogram showed a decline on peak intensity of milled efavirenz compared to intact efavirenz. The SEM graph depicted the change from crystalline to amorphous habit after milling process. The IR spectrum showed there was no difference between intact and milled efavirenz. Thermal analysis which performed by DSC showed a reduction on endothermic peak after milling process which related to decreasing of crystallinity. Solubility test of intact and milled efavirenz was conducted in distilled water free CO2 with 0.25% sodium lauryl sulfate media and measured using high-performance liquid chromatography method with acetonitrile: distilled water (80:20) as mobile phases. The solubility was significantly increased (P < 0.05) after milling processes, which the intact efavirenz was 27.12 ± 2.05, while the milled efavirenz for 30, 60, and 180 min were 75.53 ± 1.59, 82.34 ± 1.23, and 104.75 ± 0.96 μg/mL, respectively. Based on the results, the solubility of efavirenz improved after milling process.

  18. Plasma lipid concentrations during episodic occupational stress.

    PubMed

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

    1999-01-01

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

  19. Plasma catecholamine concentrations associated with cerebral vasospasm.

    PubMed

    Loach, A B; Benedict, C R

    1980-03-01

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

  20. Decreased plasma motilin concentrations in pregnancy.

    PubMed Central

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

    1982-01-01

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

  1. Plasma Glutamine Concentrations in Liver Failure.

    PubMed

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

    2016-01-01

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

  2. Plasma Glutamine Concentrations in Liver Failure

    PubMed Central

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

    2016-01-01

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

  3. Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir- vs. efavirenz-based antiretroviral therapy.

    PubMed

    Estrada, V; Monge, S; Gómez-Garre, M D; Sobrino, P; Masiá, M; Berenguer, J; Portilla, J; Viladés, C; Martínez, E; Blanco, J R

    2016-10-01

    Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels. © 2016 British HIV Association.

  4. A 33-year-old patient with human immunodeficiency virus on antiretroviral therapy with efavirenz-induced complex partial seizures: a case report.

    PubMed

    Shehu, Nathan Yakubu; Ojeh, Victor; Osaigbovo, Godwin; Agaba, Patricia; Agbaji, Oche

    2016-04-13

    Efavirenz is a commonly prescribed antiretroviral drug that is largely well tolerated. However, seizure disorder is a rare side effect. Prompt identification and immediate replacement of efavirenz with an alternative drug would effectively stop the seizures. To the best of our knowledge, we present the first reported case in the literature of complex partial seizures arising due to efavirenz. We report a case of a 33-year-old Nigerian man treated with an efavirenz-based antiretroviral regimen for human immunodeficiency virus infection. He presented with seizures soon after commencement of antiretroviral drugs. His magnetic resonance imaging results were unremarkable. His blood levels of sodium, glucose, urea, and creatinine were within normal limits. However, his electroencephalogram showed intermittent bursts of high-voltage sharp waves and spikes bilaterally over frontotemporoparietal regions, a finding consistent with complex partial seizures. His efavirenz plasma level was 209.55 μg/ml. His seizures stopped following a switch to a non-efavirenz-based regimen. This report brings to light the occurrence of complex partial seizures in patients on efavirenz. It also demonstrates the effective resolution of seizures when efavirenz treatment is replaced with a non-efavirenz-based regimen.

  5. Pathogen Inactivated Plasma Concentrated: Preparation and Uses

    DTIC Science & Technology

    2004-09-01

    ultrasound to cold plasma. The ultrasound generates pure ice crystals, which are then removed to leave concentrated plasma. Testing: Porcine parvovirus ...of decontamination, porcine parvovirus (PPV) was selected as a model virus; B19 is the form that infects humans. PPV is an interesting pathogen...that all of the plasma is treated quite uniformly. Porcine Parvovirus Inactivation with Ozone 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 1.0 1.5 2.0 2.5 3.0

  6. Doxepin concentrations in plasma and cerebrospinal fluid.

    PubMed

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

    2011-04-01

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

  7. Plasma ascorbic acid concentrations in healthy dogs.

    PubMed

    Wang, S; Berge, G E; Sund, R B

    2001-08-01

    Using a highly sensitive and selective analytical method and careful stability control, plasma concentrations of ascorbic acid were determined in German Shepherd Dogs, Labrador Retrievers and Siberian Huskies, a total 99 animals. Mean concentration was 35.9 micromol l(-1)(range 18.2-50.7), and no significant variation was observed neither between breeds nor between females and males. These and previous reported data on plasma ascorbic acid levels in dogs are discussed in the light of methodological aspects. Copyright 2001 Harcourt Publishers Ltd.

  8. Plasma carnitine concentrations after chronic alcohol intoxication.

    PubMed

    Kępka, Alina; Waszkiewicz, Napoleon; Zalewska-Szajda, Beata; Chojnowska, Sylwia; Płudowski, Paweł; Konarzewska, Emilia; Szulc, Agata; Ladny, Jerzy Robert; Zwierz, Krzysztof; Szajda, Sławomir Dariusz

    2013-05-31

    Carnitine transports fatty acids from the cytoplasm to the mitochondrial matrix, where the fatty acids are oxidized. Chronic alcohol consumption reduces the concentration of carnitine and interferes with oxidative processes occurring in the cell. The assessment of carnitine concentrations in plasma of chronically intoxicated alcohol dependent persons in a 49-day abstinence period. The study included 31 patients (5 women and 27 men) aged from 26 to 60 years (44.6 ± 8.9) and 32 healthy subjects (15 women and 17 men) aged 22-60 years (39.8 ± 9.4). The patients' alcohol dependence ranged from 2 to 30 years (13.6 ± 7.5). Examined subjects consumed 75-700 g of ethanol/day (226.9 ± 151.5). Plasma concentrations of free and total carnitine were measured three times: at the first (T0), 30th (T30) and 49th (T49) day of hospital detoxification. Free (FC) and total (TC) carnitine were determined by the spectrophotometric method. Plasma acylcarnitine (AC) concentration was calculated from the difference between TC and FC; then the AC/FC ratio was calculated. To determine statistically significant differences for related variables, Student's t-test was used. At T0, alcoholics had significantly lower concentration of FC and TC (p < 0.05) in plasma, as compared to the control group. In comparison to controls, at T30, plasma TC and FC (p < 0.01) as well as AC (p < 0.001) were reduced. The lowest concentration of TC, FC and AC (p < 0.001)was found at T49. The ratio of AC/FC at T0 had a tendency to be higher in alcoholics than in the control group (p = 0.05), whereas at T49 it was significantly lower in alcoholics as compared to the control subjects (p < 0.05). Chronic alcohol intoxication causes a plasma deficiency of carnitine. Forty-nine days of abstinence showed a significant decrease in the concentration of TC, FC and AC. Further research is necessary to clarify whether a low level of plasma carnitine after chronic alcohol intoxication is caused by the uptake of blood

  9. Pharmacokinetic and Pharmacodynamic Comparison of Once-Daily Efavirenz (400 mg vs. 600 mg) in Treatment-Naïve HIV-Infected Patients: Results of the ENCORE1 Study.

    PubMed

    Dickinson, L; Amin, J; Else, L; Boffito, M; Egan, D; Owen, A; Khoo, S; Back, D; Orrell, C; Clarke, A; Losso, M; Phanuphak, P; Carey, D; Cooper, D A; Emery, S; Puls, R

    2015-10-01

    Daily efavirenz 400 mg (EFV400) was virologically noninferior to 600 mg (EFV600) at 48 weeks in treatment-naïve patients. We evaluated EFV400 and EFV600 pharmacokinetics (NONMEM v. 7.2), assessing patient demographics and genetic polymorphisms (CYP2B6, CYP2A6, CYP3A4, NR1I3) as covariates and explored relationships with efficacy (plasma HIV-RNA (pVL) <200 copies/mL) and safety outcomes at 48 weeks in 606 randomized ENCORE1 patients (female = 32%, African = 37%, Asian = 33%; EFV400 = 311, EFV600 = 295). CYP2B6 516G>T/983T>C/CYP2A6*9B/*17 and weight were associated with efavirenz CL/F. Exposure was significantly lower for EFV400 (geometric mean ratio, GMR; 90% confidence interval, CI: 0.73 (0.68-0.78)) but 97% (EFV400) and 98% (EFV600) of evaluable pVL was <200 copies/mL at 48 weeks (P = 0.802). Four of 20 patients with mid-dose concentrations <1.0 mg/L had pVL ≥200 copies/mL (EFV400 = 1; EFV600 = 3). Efavirenz exposure was similar between those with and without efavirenz-related side effects (GMR; 90% CI: 0.95 (0.88-1.02)). HIV suppression was comparable between doses despite significantly lower EFV400 exposure. Comprehensive evaluation of efavirenz pharmacokinetics/pharmacodynamics revealed important limitations in the accepted threshold concentration.

  10. Decreased maternal plasma apelin concentrations in preeclampsia.

    PubMed

    Bortoff, Katherine D; Qiu, Chunfang; Runyon, Scott; Williams, Michelle A; Maitra, Rangan

    2012-01-01

    Preeclampsia is a hypertensive disorder that complicates 3-7% of pregnancies. The development of preeclampsia has not been completely elucidated and current therapies are not broadly efficacious. The apelinergic system appears to be involved in hypertensive disorders and experimental studies indicate a role of this system in preeclampsia. Thus, an epidemiological evaluation of apelin protein concentration in plasma was conducted in case-control study of pregnant women. Data and maternal plasma samples were collected from pregnant women with confirmed preeclampsia (n = 76) or normotensive controls (n = 79). Concentrations of apelin peptides were blindly measured using enzyme-linked immunosorbent assay. Data were subjected to statistical analyses. Plasma apelin concentrations, measured at delivery, were lower in preeclampsia cases compared with controls (mean ± standard deviation: 0.66 ± 0.29 vs. 0.78 ± 0.31 ng/mL, p = 0.02). After controlling for confounding by maternal age, smoking status, and pre-pregnancy body mass index, odds of preeclampsia were 48% lower for women with high versus low plasma apelin (≥0.73 vs. <0.73 ng/mL) concentrations. Reduced circulating apelin peptides may be associated with preeclampsia. The apelinergic system should be further investigated to elucidate its role in preclampsia and other hypertensive maternal disorders.

  11. A concise flow synthesis of efavirenz.

    PubMed

    Correia, Camille A; Gilmore, Kerry; McQuade, D Tyler; Seeberger, Peter H

    2015-04-13

    Efavirenz is an essential medicine for the treatment of HIV, which is still inaccessible to millions of people worldwide. A novel, semi-continuous process provides rac-Efavirenz with an overall yield of 45%. This streamlined proof-of-principle synthesis relies on the efficient copper-catalyzed formation of an aryl isocyanate and a subsequent intramolecular cyclization to install the carbamate core of Efavirenz in one step. The three-step method represents the shortest synthesis of this life-saving drug to date. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Plasma aminotransferase concentrations in preterm infants.

    PubMed

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

    2011-03-01

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

  13. [Monitoring plasma antibiotic concentrations in Spanish hospitals].

    PubMed

    Alvarez-Lerma, Francisco; Grau, Santiago; Marín-Casino, Mónica; Olaechea, Pedro; Sánchez, Miguel; Martín, Estrella; Pujol, Miquel

    2006-01-01

    Monitoring of plasma aminoglycoside and vancomycin concentrations is a measure of good clinical practice in critically ill patients. However, the frequency and application of this practice in Spanish hospitals is unknown. Observational, multicenter study based on a survey designed by the Study Group for Infection in the Critically Ill Patient of the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC, Spanish Society of Infectious Diseases and Clinical Microbiology). The survey was sent to the 221 general hospitals with a more than 150-bed capacity included in the hospital directory. Questions regarding the antibiotics monitored, hospital services involved, systems used to report the results, and levels of intervention were included. Information was recorded from 56 (25.3%) hospitals with a total of 36,886 beds, among which 933 (2.5%) corresponded to critically ill patients. In 47 (83.9%) hospitals, plasma concentrations of one or two antibiotics were determined: vancomycin in 47 (83.9% of the total), amikacin in 41 (73.2%), and gentamicin in 40 (71.2%). Analyses were performed by the following services: Biochemistry in 34%, Pharmacy in 25.5% and Pharmacology in 8.5%. Only 57.4% of services recommended dose adjustments according to the results obtained, using eight different dose adjustment models. In 16% of the hospitals surveyed, monitoring of antibiotic concentrations was not performed in daily practice. There was considerable variation in all phases of the process, especially with regard to adjustment of plasma antibiotic concentrations. Consensus recommendations established by all the Services implicated are required to standardize monitoring of plasma antibiotic concentrations.

  14. Do plasma melatonin concentrations decline with age?

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  15. Do plasma melatonin concentrations decline with age?

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  16. Crystal structure determination of Efavirenz

    SciTech Connect

    Popeneciu, Horea Dumitru, Ristoiu; Tripon, Carmen Borodi, Gheorghe Pop, Mihaela Maria

    2015-12-23

    Needle-shaped single crystals of the title compound, C{sub 14}H{sub 9}ClF{sub 3}NO{sub 2}, were obtained from a co-crystallization experiment of Efavirenz with maleic acid in a (1:1) ratio, using methanol as solvent. Crystal structure determination at room temperature revealed a significant anisotropy of the lattice expansion compared to the previously reported low-temperature structure. In both low- and room temperature structures the cyclopropylethynyl fragment in one of the asymmetric unit molecules is disordered. While at low-temperature only one C atom exhibits positional disorder, at room temperature the disorder is present for two C atoms of the cyclopropane ring.

  17. CYP2B6 haplotype and biological factors responsible for hepatotoxicity in HIV-infected patients receiving efavirenz-based antiretroviral therapy.

    PubMed

    Manosuthi, Weerawat; Sukasem, Chonlaphat; Lueangniyomkul, Aroon; Mankatitham, Wiroj; Thongyen, Supeda; Nilkamhang, Samruay; Manosuthi, Sukanya; Sungkanuparph, Somnuek

    2014-03-01

    Data on the pharmacogenetic markers of CYP2B6 and biological factors associated with hepatotoxicity in HIV-infected patients receiving an efavirenz-based antiretroviral therapy (ART) regimen are very limited. A total of 134 HIV-infected Thai adults were prospectively enrolled to receive a once-daily regimen of efavirenz 600 mg/tenofovir/lamivudine. Seven single nucleotide polymorphisms (SNPs) within CYP2B6 were genotyped using real-time PCR. At 12 weeks after ART, plasma efavirenz concentrations at 12h after dosing were measured. The mean ± standard deviation patient age was 37 ± 8 years, and 77.6% were male. The median (IQR) CD4 count was 43 cells/mm(3) (17-105 cells/mm(3)). Eighteen patients (13.4%) had positive anti-HCV and 5 patients (3.7%) had positive HBsAg. The frequencies of heterozygous/homozygous mutants of each SNP were 64C>T (11%), 499C>G (0%), 516G>T (55%), 785A>G (63%), 1375A>G (0%), 1459C>T (3%) and 21563C>T (62%). The three most frequent haplotypes identified included *1/*6 (40.3%), *1/*1 (34.3%) and *6/*6 (8.2%). The median (IQR) plasma efavirenz concentration was 2.3mg/L (1.4-3.7 mg/L). At 24 weeks, median (IQR) serum ALP was 98 mg/dL (73-133 mg/dL) and direct bilirubin was 0.11 mg/dL (0.10-0.19 mg/dL). The proportion of grade 1 and grade 2 elevated serum ALP was 12.7% and 1.5%, respectively. By multivariate analysis, factors associated with high ALP, total bilirubin and direct bilirubin included CYP2B6 haplotype *6/*6, high serum ALP at Week 0 and positive anti-HCV (all P<0.05). In summary, HIV-infected patients with the pharmacogenetic marker 'CYP2B6 haplotype *6/*6' may have increased susceptibility to hepatotoxicity with efavirenz-based ART. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  18. CSF and plasma vasopressin concentrations in dementia.

    PubMed Central

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

    1983-01-01

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

  19. Acute clozapine overdose: plasma concentration and outcome.

    PubMed

    Broich, K; Heinrich, S; Marneros, A

    1998-07-01

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

  20. Plasma prolactin concentrations in lead exposed workers.

    PubMed

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

    1987-01-01

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

  1. THERAPEUTIC DRUG MONITORING OF PROTEASE INHIBITORS AND EFAVIRENZ IN HIV-INFECTED INDIVIDUALS WITH ACTIVE SUBSTANCE RELATED DISORDERS

    PubMed Central

    Ma, Qing; Zingman, Barry S.; Luque, Amneris; Fischl, Margaret A.; Gripshover, Barbara; Venuto, Charles; DiFrancesco, Robin; Forrest, Alan; Morse, Gene D.

    2011-01-01

    Background Achieving targeted antiretroviral (ART) plasma concentrations during long-term treatment in HIV-infected patients with substance related disorders (SRD) may be challenging due to a number of factors including medication adherence, co-infection with hepatitis B or C virus, medication intolerance and drug interactions. One approach to investigate these factors is to conduct therapeutic drug monitoring (TDM) to measure ART exposure during treatment. The objective of this study was to utilize TDM to compare efavirenz and protease inhibitor pharmacokinetics in patients with and without SRDs. Methods This was a multi-center, cross-sectional open-label study in patients with HIV-1 infection receiving ART, with active (n=129) or without (n=146) SRD according to National Institute on Drug Abuse criteria. 275 subjects who were receiving either protease inhibitor- or efavirenz-based ART regimens for more than 6 months were enrolled at four HIV treatment centers with an equal distribution of SRD and non-SRD at each site. Patients were instructed during enrollment visits with regard to the importance of adherence prior to and after study visits. Demographics and routine clinical laboratory tests were recorded. Results Among the 275 patients, 47% had SRD with at least one substance. There were no significant differences between SRD and non-SRD groups for race, gender, age, or CD4 count at entry. A significantly higher proportion of patients with SRD had an entry HIV RNA plasma concentration > 75 copies/ml compared to patients without SRD (40% vs. 28%, p=0.044). Logistic regression modeling revealed an association between HIV RNA plasma concentration and African-American race (p=0.017). A significantly higher proportion of SRDs also had an efavirenz or protease inhibitor trough concentration below the desired range (23% vs. 9%, p=0.048). Significantly lower trough concentrations were noted in patients with SRDs receiving atazanavir (0.290 vs. 0.976 µg/mL) or lopinavir

  2. Genotypic Correlates of Phenotypic Resistance to Efavirenz in Virus Isolates from Patients Failing Nonnucleoside Reverse Transcriptase Inhibitor Therapy

    PubMed Central

    Bacheler, Lee; Jeffrey, Susan; Hanna, George; D'Aquila, Richard; Wallace, Lany; Logue, Kelly; Cordova, Beverly; Hertogs, Kurt; Larder, Brendan; Buckery, Renay; Baker, David; Gallagher, Karen; Scarnati, Helen; Tritch, Radonna; Rizzo, Chris

    2001-01-01

    Efavirenz (also known as DMP 266 or SUSTIVA) is a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity and of HIV-1 replication in vitro and in vivo. Most patients on efavirenz-containing regimens have sustained antiviral responses; however, rebounds in plasma viral load have been observed in some patients in association with the emergence of mutant strains of HIV-1. Virus isolates from the peripheral blood mononuclear cells (PBMCs) of patients with such treatment failures, as well as recombinant viruses incorporating viral sequences derived from patient plasma, show reduced in vitro susceptibility to efavirenz in association with mutations in the RT gene encoding K103N, Y188L, or G190S/E substitutions. Patterns of RT gene mutations and in vitro susceptibility were similar in plasma virus and in viruses isolated from PBMCs. Variant strains of HIV-1 constructed by site-directed mutagenesis confirmed the role of K103N, G190S, and Y188L substitutions in reduced susceptibility to efavirenz. Further, certain secondary mutations (V106I, V108I, Y181C, Y188H, P225H, and F227L) conferred little resistance to efavirenz as single mutations but enhanced the level of resistance of viruses carrying these mutations in combination with K103N or Y188L. Viruses with K103N or Y188L mutations, regardless of the initial selecting nonnucleoside RT inhibitor (NNRTI), exhibited cross-resistance to all of the presently available NNRTIs (efavirenz, nevirapine, and delavirdine). Some virus isolates from nevirapine or delavirdine treatment failures that lacked K103N or Y188L mutations remained susceptible to efavirenz in vitro, although the clinical significance of this finding is presently unclear. PMID:11333879

  3. Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention

    PubMed Central

    Podany, Anthony T.; Bao, Yajing; Swindells, Susan; Chaisson, Richard E.; Andersen, Janet W.; Mwelase, Thando; Supparatpinyo, Khuanchai; Mohapi, Lerato; Gupta, Amita; Benson, Constance A.; Kim, Peter; Fletcher, Courtney V.

    2015-01-01

    Background. Concomitant use of rifamycins to treat or prevent tuberculosis can result in subtherapeutic concentrations of antiretroviral drugs. We studied the interaction of efavirenz with daily rifapentine and isoniazid in human immunodeficiency virus (HIV)–infected individuals receiving a 4-week regimen to prevent tuberculosis. Methods. Participants receiving daily rifapentine and isoniazid with efavirenz had pharmacokinetic evaluations at baseline and weeks 2 and 4 of concomitant therapy. Efavirenz apparent oral clearance was estimated and the geometric mean ratio (GMR) of values before and during rifapentine and isoniazid was calculated. HIV type 1 (HIV-1) RNA was measured at baseline and week 8. Results. Eighty-seven participants were evaluable: 54% were female, and the median age was 35 years (interquartile range [IQR], 29–44 years). Numbers of participants with efavirenz concentrations ≥1 mg/L were 85 (98%) at week 0; 81 (93%) at week 2; 78 (90%) at week 4; and 75 (86%) at weeks 2 and 4. Median efavirenz apparent oral clearance was 9.3 L/hour (IQR, 6.42–13.22 L/hour) at baseline and 9.8 L/hour (IQR, 7.04–15.59 L/hour) during rifapentine/isoniazid treatment (GMR, 1.04 [90% confidence interval, .97–1.13]). Seventy-nine of 85 (93%) participants had undetectable HIV-1 RNA (<40 copies/mL) at entry; 71 of 75 (95%) participants had undetectable HIV-1 RNA at week 8. Two participants with undetectable HIV-1 RNA at study entry were detectable (43 and 47 copies/mL) at week 8. Conclusions. The proportion of participants with midinterval efavirenz concentrations ≥1 mg/L did not cross below the prespecified threshold of >80%, and virologic suppression was maintained. Four weeks of daily rifapentine plus isoniazid can be coadministered with efavirenz without clinically meaningful reductions in efavirenz mid-dosing concentrations or virologic suppression. Clinical Trials Registration. NCT 01404312. PMID:26082504

  4. Plasma bupivacaine concentrations following psoas compartment block.

    PubMed

    Odoom, J A; Zuurmond, W W; Sih, I L; Bovill, J; Osterlöf, G; Oosting, H V

    1986-02-01

    Fourteen patients undergoing hip replacement surgery under psoas compartment block combined with general anaesthesia were studied. Group 1 (n = 7) received plain and Group 2 (n = 7) received 0.25% bupivacaine with adrenaline. The mean maximum peak concentrations were 1.93 (SEM 0.46) micrograms/ml and 1.04 (SEM 0.19) micrograms/ml at 10 minutes in groups 1 and 2 respectively. Bupivacaine concentrations were higher at all times in the group which received plain than the group receiving solution containing adrenaline. These differences were statistically significant at 10, 15 (p less than 0.05) and 30 minutes (p less than 0.025). The highest recorded plasma bupivacaine concentration was 4.54 micrograms/ml in one patient receiving plain bupivacaine. No patient developed any signs of toxic symptoms. The duration of analgesia was longer (p less than 0.005) in the group receiving bupivacaine with adrenaline. Bupivacaine 0.25% with adrenaline 1:200 000 is safe for psoas compartment block, and is recommended for hip surgery.

  5. Phase I safety, pharmacokinetics, and pharmacogenetics study of the antituberculosis drug PA-824 with concomitant lopinavir-ritonavir, efavirenz, or rifampin.

    PubMed

    Dooley, Kelly E; Luetkemeyer, Anne F; Park, Jeong-Gun; Allen, Reena; Cramer, Yoninah; Murray, Stephen; Sutherland, Deborah; Aweeka, Francesca; Koletar, Susan L; Marzan, Florence; Bao, Jing; Savic, Rada; Haas, David W

    2014-09-01

    There is an urgent need for new antituberculosis (anti-TB) drugs, including agents that are safe and effective with concomitant antiretrovirals (ARV) and first-line TB drugs. PA-824 is a novel antituberculosis nitroimidazole in late-phase clinical development. Cytochrome P450 (CYP) 3A, which can be induced or inhibited by ARV and antituberculosis drugs, is a minor (∼20%) metabolic pathway for PA-824. In a phase I clinical trial, we characterized interactions between PA-824 and efavirenz (arm 1), lopinavir/ritonavir (arm 2), and rifampin (arm 3) in healthy, HIV-uninfected volunteers without TB disease. Participants in arms 1 and 2 were randomized to receive drugs via sequence 1 (PA-824 alone, washout, ARV, and ARV plus PA-824) or sequence 2 (ARV, ARV with PA-824, washout, and PA-824 alone). In arm 3, participants received PA-824 and then rifampin and then both. Pharmacokinetic sampling occurred at the end of each dosing period. Fifty-two individuals participated. Compared to PA-824 alone, plasma PA-824 values (based on geometric mean ratios) for maximum concentration (Cmax), area under the concentration-time curve from 0 to 24 h (AUC0-24), and trough concentration (Cmin) were reduced 28%, 35%, and 46% with efavirenz, 13%, 17%, and 21% with lopinavir-ritonavir (lopinavir/r) and 53%, 66%, and 85% with rifampin, respectively. Medications were well tolerated. In conclusion, lopinavir/r had minimal effect on PA-824 exposures, supporting PA-824 use with lopinavir/r without dose adjustment. PA-824 exposures, though, were reduced more than expected when given with efavirenz or rifampin. The clinical implications of these reductions will depend upon data from current clinical trials defining PA-824 concentration-effect relationships. (This study has been registered at ClinicalTrials.gov under registration no. NCT01571414.). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Predictors of plasma zinc concentrations in children with acute diarrhea.

    PubMed

    Strand, Tor A; Adhikari, Ramesh K; Chandyo, Ram K; Sharma, Pushpa R; Sommerfelt, Halvor

    2004-03-01

    Plasma and serum zinc concentrations are the most widely used markers of zinc status in individual persons and populations. The objective was to identify factors that influence plasma zinc concentrations during acute childhood diarrhea. This was a cross-sectional study of 1757 cases of acute diarrhea in 6-35-mo-old Nepalese children. The association between plasma zinc concentration and several clinical, anthropometric, socioeconomic, and biochemical variables was estimated in simple and multiple linear regression analyses. We observed a reduction in the mean plasma zinc concentration of 0.59 (95% CI: 0.44, 0.74) micro mol/L per degree ( degrees C) increase in axillary temperature. Having dysentery and an elevated plasma C-reactive protein concentration was also independently associated with lower plasma zinc. Children with clinical features of dehydration had higher plasma zinc concentrations than did those who were not dehydrated. Furthermore, a decrease in plasma albumin of 1 g/L was associated with a decrease in plasma zinc of 0.25 (95% CI: 0.21, 0.29) micro mol/L. The plasma albumin concentration confounded the associations between some clinical variables and plasma zinc, but the association between axillary temperature and dehydration on one hand and plasma zinc on the other was not substantially influenced by the albumin concentration. Moreover, the plasma zinc concentration increased with an increase in observed hemolysis. Dehydration, clinical and biochemical indicators of inflammation and hemolysis, and, when possible, plasma albumin concentrations should be taken into account when the plasma zinc concentration is used to estimate zinc status during episodes of diarrhea in childhood.

  7. Pharmacokinetic and Pharmacodynamic Comparison of Once‐Daily Efavirenz (400 mg vs. 600 mg) in Treatment‐Naïve HIV‐Infected Patients: Results of the ENCORE1 Study

    PubMed Central

    Amin, J; Else, L; Boffito, M; Egan, D; Owen, A; Khoo, S; Back, D; Orrell, C; Clarke, A; Losso, M; Phanuphak, P; Carey, D; Cooper, DA; Emery, S

    2015-01-01

    Daily efavirenz 400 mg (EFV400) was virologically noninferior to 600 mg (EFV600) at 48 weeks in treatment‐naïve patients. We evaluated EFV400 and EFV600 pharmacokinetics (NONMEM v. 7.2), assessing patient demographics and genetic polymorphisms (CYP2B6, CYP2A6, CYP3A4, NR1I3) as covariates and explored relationships with efficacy (plasma HIV‐RNA (pVL) <200 copies/mL) and safety outcomes at 48 weeks in 606 randomized ENCORE1 patients (female = 32%, African = 37%, Asian = 33%; EFV400 = 311, EFV600 = 295). CYP2B6 516G>T/983T>C/CYP2A6*9B/*17 and weight were associated with efavirenz CL/F. Exposure was significantly lower for EFV400 (geometric mean ratio, GMR; 90% confidence interval, CI: 0.73 (0.68–0.78)) but 97% (EFV400) and 98% (EFV600) of evaluable pVL was <200 copies/mL at 48 weeks (P = 0.802). Four of 20 patients with mid‐dose concentrations <1.0 mg/L had pVL ≥200 copies/mL (EFV400 = 1; EFV600 = 3). Efavirenz exposure was similar between those with and without efavirenz‐related side effects (GMR; 90% CI: 0.95 (0.88–1.02)). HIV suppression was comparable between doses despite significantly lower EFV400 exposure. Comprehensive evaluation of efavirenz pharmacokinetics/pharmacodynamics revealed important limitations in the accepted threshold concentration. PMID:26044067

  8. Plasma tryptophan concentration in depressive illness and mania.

    PubMed

    Peet, M; Moody, J P; Worrall, E P; Walker, P; Naylor, G J

    1976-03-01

    Total and free plasma trytophan levels were measured in depressive and manic patients before and after recovery. No change was found in total or free plasma trytophan concentration on recovery from depressive illness. Free plasma tryptophan levels were higher in recovered manics than in active manics, and a group of four manic patients tested before and after recovery showed a significant increase in free plasma tryptophan concentration on recovery.

  9. Plasma magnesium concentration in patients undergoing coronary artery bypass grafting.

    PubMed

    Kotlinska-Hasiec, Edyta; Makara-Studzinska, Marta; Czajkowski, Marek; Rzecki, Ziemowit; Olszewski, Krzysztof; Stadnik, Adam; Pilat, Jacek; Rybojad, Beata; Dabrowski, Wojciech

    2017-05-11

    [b]Introduction[/b]. Magnesium (Mg) plays a crucial role in cell physiology and its deficiency may cause many disorders which often require intensive treatment. The aim of this study was to analyse some factors affecting preoperative plasma Mg concentration in patients undergoing coronary artery bypass grafting (CABG). [b]Materials and method[/b]. Adult patients scheduled for elective CABG with cardio-pulmonary bypass (CPB) under general anaesthesia were studied. Plasma Mg concentration was analysed before surgery in accordance with age, domicile, profession, tobacco smoking and preoperative Mg supplementation. Blood samples were obtained from the radial artery just before the administration of anaesthesia. [b]Results. [/b]150 patients were studied. Mean preoperative plasma Mg concentration was 0.93 ± 0.17 mmol/L; mean concentration in patients - 1.02 ± 0.16; preoperative Mg supplementation was significantly higher than in patients without such supplementation. Moreover, intellectual workers supplemented Mg more frequently and had higher plasma Mg concentration than physical workers. Plasma Mg concentration decreases in elderly patients. Patients living in cities, on average, had the highest plasma Mg concentration. Smokers had significantly lower plasma Mg concentration than non-smokers. [b]Conclusions. [/b]1. Preoperative magnesium supplementation increases its plasma concentration. 2. Intellectual workers frequently supplement magnesium. 3. Smoking cigarettes decreases plasma magnesium concentration.

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  12. Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks

    PubMed Central

    Scarsi, Kimberly K.; Darin, Kristin M.; Nakalema, Shadia; Back, David J.; Byakika-Kibwika, Pauline; Else, Laura J.; Dilly Penchala, Sujan; Buzibye, Allan; Cohn, Susan E.; Merry, Concepta; Lamorde, Mohammed

    2016-01-01

    Background. Levonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of <1% over 5 years. We assessed the effect of efavirenz- or nevirapine-based antiretroviral therapy (ART) coadministration on levonorgestrel pharmacokinetics. Methods. This nonrandomized, parallel group, pharmacokinetic evaluation was conducted in three groups of human immunodeficiency virus–infected Ugandan women: ART-naive (n = 17), efavirenz-based ART (n = 20), and nevirapine-based ART (n = 20). Levonorgestrel implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies. Results. Week 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29, 1.43). Week 48 levonorgestrel concentrations were 580, 247, and 664 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups. Conclusions. Within 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy. Clinical Trials Registration. NCT01789879. PMID:26646680

  13. Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks.

    PubMed

    Scarsi, Kimberly K; Darin, Kristin M; Nakalema, Shadia; Back, David J; Byakika-Kibwika, Pauline; Else, Laura J; Dilly Penchala, Sujan; Buzibye, Allan; Cohn, Susan E; Merry, Concepta; Lamorde, Mohammed

    2016-03-15

    Levonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of <1% over 5 years. We assessed the effect of efavirenz- or nevirapine-based antiretroviral therapy (ART) coadministration on levonorgestrel pharmacokinetics. This nonrandomized, parallel group, pharmacokinetic evaluation was conducted in three groups of human immunodeficiency virus-infected Ugandan women: ART-naive (n = 17), efavirenz-based ART (n = 20), and nevirapine-based ART (n = 20). Levonorgestrel implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies. Week 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29, 1.43). Week 48 levonorgestrel concentrations were 580, 247, and 664 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups. Within 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy. NCT01789879. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells.

    PubMed

    Hecht, Markus; Erber, Sonja; Harrer, Thomas; Klinker, Hartwig; Roth, Thomas; Parsch, Hans; Fiebig, Nora; Fietkau, Rainer; Distel, Luitpold V

    2015-01-01

    Cancer prevention and therapy in HIV-1-infected patients will play an important role in future. The non-nucleoside reverse transcriptase inhibitors (NNRTI) Efavirenz and Nevirapine are cytotoxic against cancer cells in vitro. As other NNRTIs have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo. Cytotoxicity was studied by Annexin-V-APC/7AAD staining and flow cytometry in the pancreatic cancer cell lines BxPC-3 and Panc-1 and confirmed by colony formation assays. The 50% effective cytotoxic concentrations (EC50) were calculated and compared to the blood levels in our patients and published data. The in vitro EC50 of the different drugs in the BxPC-3 pancreatic cancer cells were: Efavirenz 31.5 μmol/l (= 9944 ng/ml), Nevirapine 239 μmol/l (= 63,786 ng/ml), Etravirine 89.0 μmol/l (= 38,740 ng/ml), Lersivirine 543 μmol/l (= 168,523 ng/ml), Delavirdine 171 μmol/l (= 78,072 ng/ml), Rilpivirine 24.4 μmol/l (= 8941 ng/ml). As Efavirenz and Rilpivirine had the highest cytotoxic potential and Nevirapine is frequently used in HIV-1 positive patients, the results of these three drugs were further studied in Panc-1 pancreatic cancer cells and confirmed with colony formation assays. 205 patient blood levels of Efavirenz, 127 of Rilpivirine and 31 of Nevirapine were analyzed. The mean blood level of Efavirenz was 3587 ng/ml (range 162-15,363 ng/ml), of Rilpivirine 144 ng/ml (range 0-572 ng/ml) and of Nevirapine 4955 ng/ml (range 1856-8697 ng/ml). Blood levels from our patients and from published data had comparable Efavirenz levels to the in vitro toxic EC50 in about 1 to 5% of all patients. All studied NNRTIs were toxic against cancer cells. A low percentage of patients taking Efavirenz reached in vitro cytotoxic blood levels. It can be speculated that in HIV-1 positive patients having high Efavirenz blood levels pancreatic cancer

  15. Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells

    PubMed Central

    Hecht, Markus; Erber, Sonja; Harrer, Thomas; Klinker, Hartwig; Roth, Thomas; Parsch, Hans; Fiebig, Nora; Fietkau, Rainer; Distel, Luitpold V.

    2015-01-01

    Background Cancer prevention and therapy in HIV-1-infected patients will play an important role in future. The non-nucleoside reverse transcriptase inhibitors (NNRTI) Efavirenz and Nevirapine are cytotoxic against cancer cells in vitro. As other NNRTIs have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo. Methods Cytotoxicity was studied by Annexin-V-APC/7AAD staining and flow cytometry in the pancreatic cancer cell lines BxPC-3 and Panc-1 and confirmed by colony formation assays. The 50% effective cytotoxic concentrations (EC50) were calculated and compared to the blood levels in our patients and published data. Results The in vitro EC50 of the different drugs in the BxPC-3 pancreatic cancer cells were: Efavirenz 31.5μmol/l (= 9944ng/ml), Nevirapine 239μmol/l (= 63786ng/ml), Etravirine 89.0μmol/l (= 38740ng/ml), Lersivirine 543μmol/l (= 168523ng/ml), Delavirdine 171μmol/l (= 78072ng/ml), Rilpivirine 24.4μmol/l (= 8941ng/ml). As Efavirenz and Rilpivirine had the highest cytotoxic potential and Nevirapine is frequently used in HIV-1 positive patients, the results of these three drugs were further studied in Panc-1 pancreatic cancer cells and confirmed with colony formation assays. 205 patient blood levels of Efavirenz, 127 of Rilpivirine and 31 of Nevirapine were analyzed. The mean blood level of Efavirenz was 3587ng/ml (range 162–15363ng/ml), of Rilpivirine 144ng/ml (range 0-572ng/ml) and of Nevirapine 4955ng/ml (range 1856–8697ng/ml). Blood levels from our patients and from published data had comparable Efavirenz levels to the in vitro toxic EC50 in about 1 to 5% of all patients. Conclusion All studied NNRTIs were toxic against cancer cells. A low percentage of patients taking Efavirenz reached in vitro cytotoxic blood levels. It can be speculated that in HIV-1 positive patients having high Efavirenz blood levels

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

    PubMed

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

    1992-01-01

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

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

    PubMed

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

    2015-06-01

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

  18. Use of in vitro to in vivo extrapolation to predict the optimal strategy for patients switching from efavirenz to maraviroc or nevirapine.

    PubMed

    Schipani, Alessandro; Back, David; Owen, Andrew; Davies, Gerry; Khoo, Saye; Siccardi, Marco

    2015-01-01

    In clinical practice, antiretroviral regimens are often interrupted or modified for intolerance and toxicity. The objective of this study was to develop an in vitro to in vivo extrapolation (IVIVE) approach to describe the interaction when efavirenz is switched to either maraviroc or nevirapine and to test different switching scenarios to identify the best strategy. In vitro data describing the chemical and absorption, tissue distribution, metabolism and excretion (ADME) characteristics of efavirenz, maraviroc and nevirapine were obtained from the literature, and used to simulate plasma exposures of these drugs using the Simcyp Population-Based Simulator. The predicted maraviroc and nevirapine exposures were compared with data from clinical studies evaluating their exposures following a switch from efavirenz. Model predictions for maraviroc and nevirapine exposure were in agreement with observed data. The simulations suggest that the waning efavirenz induction effect following discontinuation necessitated increasing maraviroc to 600 mg twice daily for 1 week after efavirenz cessation. Alternatively, adequate exposure of maraviroc was shown with a dose of 450 mg for 2 weeks. Efavirenz waning induction did not affect nevirapine exposure. IVIVE modelling successfully predicted patient drug exposure. This modelling technique is able to inform the design of clinical studies, and allows assessment of pragmatic dosing strategies under complex therapeutic scenarios.

  19. Efavirenz dissolution enhancement III: Colloid milling, pharmacokinetics and electronic tongue evaluation.

    PubMed

    Hoffmeister, Cristiane R D; Fandaruff, Cinira; da Costa, Maíra A; Cabral, Lucio M; Pitta, Luciana R; Bilatto, Stanley E R; Prado, Livia D; Corrêa, Daniel S; Tasso, Leandro; Silva, Marcos Antônio S; Rocha, Helvécio V A

    2017-03-01

    Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is part of first-line therapy for the treatment of human immunodeficiency virus type 1 infection (HIV-1/AIDS). This drug shows relatively low oral absorption and bioavailability, as well as high intra- and inter-subject variability. Several studies have shown that treatment failure and adverse effects are associated with low and high EFV plasma concentrations, respectively. Some studies suggest different EFV formulations to minimize inter-patient variability and improve its solubility and dissolution; however, all of these formulations are complex, using for instance, cyclodextrins, dendrimers and polymeric nanoparticles, rendering them inviable industrially. The aim of this work was to prepare simple and low-cost suspensions of EFV for improvement of solubility and dissolution rate by using colloid mill, spray or freeze-drying, and characterization of the powders obtained. The results demonstrated an increase in the dissolution rate of EFV, using 0.2% of sodium lauryl sulfate (SLS) and 0.2% of hydroxypropylcellulose (HPC) or hydroxypropylmetilcellulose (HPMC) in both freeze and spray dried powders. The pharmacokinetic studies demonstrated improved pharmacokinetic parameters for the formulation containing SLS and HPC. The powders obtained, which present enhanced dissolution properties, can be incorporated in a solid dosage form for treatment of AIDS in paediatric patients with promising results.

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

    SciTech Connect

    Andre, P.

    1995-06-01

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

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

    PubMed

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

    2006-07-01

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

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

    PubMed Central

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

    2006-01-01

    Plasma imipenem concentrations were measured in 19 critically ill children (median age, 0.8 year; range, 0.02 to 12.9 years). Wide interindividual variations (2 to 4× at peak and >10× at trough concentrations) resulted in unpredictable plasma levels in several children. To avoid subtherapeutic drug levels, we recommend treatment with at least 100 mg/kg of body weight/day of imipenem-cilastatin for critically ill children requiring such therapy. PMID:16801447

  3. Sleep quality in efavirenz-treated Chinese HIV patients - comparing between GT and GG genotype of CYP2B6-516 G/T polymorphisms.

    PubMed

    Lee, Shui Shan; To, Kin Wang; Lee, Man Po; Wong, Ngai Sze; Chan, Denise P C; Li, Patrick C K; Cheung, Siu Wai; Chan, Raphael C Y

    2014-03-01

    Seventy-two adult Chinese HIV-positive treatment-naïve patients were recruited in a study to evaluate prospectively the associations between CYP2B6 516 G/T polymorphisms and sleep quality following treatment with an efavirenz-based regimen. Overall, the patients gave an allelic frequency of 0.3 for CYP2B6 516 T, and a genotype frequency of 9.4% for TT. Compared to GG, GT gave a higher median value of plasma efavirenz level at four weeks (3.77 mg/L vs 2.59 mg/L, p < 0.001) and 12 months (3.57 mg/L vs 2.97 mg/L, p = 0.026). Using generalised estimating equations analysis to track the variance over time, there was poorer Pittsburgh Sleep Quality Index in GT compared to GG, while GT was associated with a higher efavirenz level of >4 mg/L. There was however no difference in the component sleep scores nor was there direct association between sleep quality and plasma efavirenz levels. The results suggested that CYP2B6 genotype was associated with different patterns of sleep problems, further investigation of which is warranted with the objective of optimizing therapy with efavirenz-based regimens.

  4. Plasma concentration of topically applied betaxolol in elderly glaucoma patients.

    PubMed

    Vainio-Jylhä, E; Vuori, M L; Pyykkö, K; Huupponen, R

    2001-06-01

    Our aim was to study the concentration of betaxolol in plasma after its topical ocular use during the normal 12 hr dosing interval. Twenty microliters of betaxolol 0.5% solution were applied into both eyes of nine glaucoma patients, and the plasma concentrations of the drug were measured 12 hr thereafter using a radioreceptor assay. The same amount of betaxolol was then applied ocularly, and its concentration in plasma was measured at 5, 10, 15, 30 min and 1, 2, 4 and 8 hr thereafter. The mean (SD) concentration of betaxolol in plasma twelve hr after the first dose was 0.4 (0.2) ng/ml. After the second dose, the patients showed a biphasic concentration vs. time curve, the first peak occurring at 8 (4) min, and the second peak at 210 (132) min; the mean (SD) peak concentrations being 1.1 (0.3) and 2.0 (1.1) ng/ml, respectively. The area under the concentration vs. time curve showed a 4-fold variation among our patients. Topically applied betaxolol was rapidly absorbed into systemic circulation, and concentrations were detectable even at 12 hr. The interindividual variation in the systemic absorption of betaxolol was large.

  5. Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda.

    PubMed

    Bartelink, Imke H; Savic, Rada M; Mwesigwa, Julia; Achan, Jane; Clark, Tamara; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Young, Sera L; Gandhi, Monica; Havlir, Diane; Cohan, Deborah; Aweeka, Francesca

    2014-02-01

    Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot samples DBS and 43 post-partum hair samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and 53 post-partum hair samples for EFV from 105 women. Eighty percent of Ugandan participants were severely food insecure, 26% lost weight ante-partum, and median BMI post-partum was only 20.2 kg/m(2) . Rich PK-data of normally nourished (pregnant) women and healthy Ugandans established prior information. Overall, drug exposure was reduced (LPV -33%, EFV -15%, ritonavir -17%) compared to well-nourished controls (P < 0.001), attributable to decreased bioavailability. Pregnancy increased LPV/r clearance 68% (P < 0.001), whereas EFV clearance remained unchanged. Hair concentrations correlated with plasma-exposure (P < 0.001), explaining 29% PK-variability. In conclusion, pregnancy and food insecurity were associated with lower ART exposures in this cohort of predominantly underweight women, compared to well-nourished women. Much variability in plasma-exposure was quantified using hair concentrations. Addressing malnutrition as well as ART-PK in this setting should be a priority.

  6. Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda

    PubMed Central

    Bartelink, Imke H.; Savic, Rada M.; Mwesigwa, Julia; Achan, Jane; Clark, Tamara; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Young, Sera L.; Gandhi, Monica; Havlir, Diane; Cohan, Deborah; Aweeka, Francesca

    2013-01-01

    Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot samples DBS and 43 post-partum hair samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and 53 post-partum hair samples for EFV from 105 women. 80% of Ugandan participants were severely food insecure, 26% lost weight ante-partum, and median BMI post-partum was only 20.2 kg/m2. Rich PK-data of normally nourished (pregnant) women and healthy Ugandans established prior information. Overall, drug exposure was reduced (LPV −33%, EFV −15%, ritonavir −17%) compared to well-nourished controls [p < 0.001], attributable to decreased bioavailability. Pregnancy increased LPV/r clearance 68% [p < 0.001], whereas EFV clearance remained unchanged. Hair concentrations correlated with plasma-exposure [p < 0.001], explaining 29% PK-variability. In conclusion, pregnancy and food insecurity were associated with lower ART exposures in this cohort of predominantly underweight women, compared to well-nourished women. Much variability in plasma-exposure was quantified using hair concentrations. Addressing malnutrition as well as ART-PK in this setting should be a priority. PMID:24038035

  7. The HIV antiretroviral drug efavirenz has LSD-like properties.

    PubMed

    Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C; France, Charles P; Dillon, Glenn H; Forster, Michael J; Schetz, John A

    2013-11-01

    Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT(2A) receptors. In rodents, interaction with the 5-HT(2A) receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT(2A) receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT(2A)-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT(2A) receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication.

  8. Postprandial changes in plasma urea and creatinine concentrations in dogs.

    PubMed

    Watson, A D; Church, D B; Fairburn, A J

    1981-11-01

    Changes in plasma urea and creatinine concentrations were compared in 6 dogs fed 3 meals (cooked meat, raw meat, and a soft-moist preparation) in a crossover fashion. Each meal produced changes in urea and creatinine values. Although increased urea values were seen after all meals, the effects on creatinine were varied; concentrations increased after feeding cooked meat, but decreased after consumption of raw meat or soft-moist food. Although the creatinine changes were less pronounced, the variable effect of diet complicates the interpretation of plasma creatinine concentration in evaluating renal function.

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

    PubMed

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

    2000-04-01

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

  10. Control of exogenous factors affecting plasma homovanillic acid concentration.

    PubMed

    Davidson, M; Giordani, A B; Mohs, R C; Mykytyn, V V; Platt, S; Aryan, Z S; Davis, K L

    1987-04-01

    Measurements of plasma homovanillic acid (pHVA) concentrations appear to be a valid research strategy in psychiatric disorders in which a central dopamine (DA) abnormality has been implicated. This study provides guidance about the control of some of the exogenous factors affecting pHVA concentrations. Fasting for 14 hours eliminates the dietary effects on pHVA in healthy human subjects. Changing position, walking for 30 minutes, or smoking two cigarettes has no effect on pHVA concentrations.

  11. Regular physical activity influences plasma ghrelin concentration in adolescent girls.

    PubMed

    Jürimäe, Jaak; Cicchella, Antonio; Jürimäe, Toivo; Lätt, Evelin; Haljaste, Kaja; Purge, Pritt; Hamra, Jena; von Duvillard, Serge P

    2007-10-01

    We examined the effect of regular physical activity on plasma ghrelin concentration after onset of puberty in girls. In addition, we also examined the association of fasting plasma ghrelin concentration with various plasma biochemical, body composition, and aerobic capacity variables in healthy adolescent girls. Fifty healthy schoolgirls ages 11 to 16 yr were divided either into a physically active (N = 25) or a physically inactive (N = 25) group. The physically active group consisted of swimmers who had trained on an average of 6.2 +/- 2.0 h.wk(-1) for the last 2 yr, whereas the inclusion criterion for the physically inactive group was the participation in physical education classes only. The subjects were matched for age (+/- 1 yr) and body mass index (BMI; +/- 2 kg.m(-2)). Maturation I group (14 matched pairs) included pubertal stages 2 and 3, and maturation II group (11 matched pairs) included pubertal stages 4 and 5. Physically active girls had significantly higher (P < 0.05) mean plasma ghrelin levels than the physically inactive girls (maturation I: 1152.1 +/- 312.9 vs 877.7 +/- 114.8 pg.mL(-1); maturation II: 1084.0 +/- 252.5 vs 793.4 +/- 164.9 pg.mL(-1)). Plasma ghrelin concentration was negatively related to percent body fat, fat mass, peak oxygen consumption per kilogram of body mass, leptin, estradiol, insulin, and insulin-like growth factor-I (IGF-I) (r > -0.298; P < 0.05). Multivariate linear regression analysis to determine the predictors of ghrelin concentration using the variables that were significantly associated with ghrelin concentration demonstrated that plasma IGF-I was the most important predictor of plasma ghrelin concentration (beta = -0.396; P = 0.008). Regular physical activity influences plasma ghrelin concentrations in girls with different pubertal maturation levels. Plasma IGF-I concentration seems to be the main determinant of circulating ghrelin in healthy, normal-weight adolescent girls.

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

    PubMed

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

    1998-01-01

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

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

    PubMed

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

    2016-01-01

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

  14. Triple combination MPT vaginal microbicide using curcumin and efavirenz loaded lactoferrin nanoparticles

    PubMed Central

    Lakshmi, Yeruva Samrajya; Kumar, Prashant; Kishore, Golla; Bhaskar, C; Kondapi, Anand K

    2016-01-01

    We report that a combination of anti-HIV-1 drug efavirenz (EFV), anti-microbial-spermicidal curcumin (Cur) and lactoferrin nanoparticles (ECNPs) act as MPT formulation. These nanoparticles are of well dispersed spherical shape with 40–70 nm size, with encapsulation efficiency of 63 ± 1.9% of Cur & 61.5% ± 1.6 of EFV, significantly higher than that of single drug nanoparticles (Cur, 59 ± 1.34%; EFV: 58.4 ± 1.79). ECNPs were found to be sensitive at pH 5 and 6 and have not effected viability of vaginal micro-flora, Lactobacillus. Studies in rats showed that ECNPs delivers 88–124% more drugs in vaginal lavage as compared to its soluble form, either as single or combination of EFV and Cur. The ECNPs also shows 1.39–4.73 fold lower concentration of absorption in vaginal tissue and plasma compared to soluble EFV + Cur. Furthermore, ECNPs show significant reduction in inflammatory responses by 1.6–3.0 fold in terms of IL-6 and TNF-α in vaginal tissue and plasma compared to soluble EFV + Cur. ECNPs showed improved pharmacokinetics profiles in vaginal lavage with more than 50% of enhancement in AUC, AUMC, Cmax and t1/2 suggesting longer exposure of Cur and EFV in vaginal lavage compared to soluble EFV + Cur. Histopathological analysis of vaginal tissue shows remarkably lower toxicity of ECNPs compared to soluble EFV + Cur. In conclusion, ECNPs are significantly safe and exhibit higher bioavailability thus constitute an effective MPT against HIV. PMID:27151598

  15. The Effect of Gene Variants on Levonorgestrel Pharmacokinetics when Combined with Antiretroviral Therapy containing Efavirenz or Nevirapine.

    PubMed

    Neary, M; Lamorde, M; Olagunju, A; Darin, K M; Merry, C; Byakika-Kibwika, P; Back, D J; Siccardi, M; Owen, A; Scarsi, K K

    2017-02-10

    Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2 and NR1I3 were analysed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based ART, in comparison to ART-naïve women using multivariate linear regression. Efavirenz group: CYP2B6 516G>T was associated with lower levonorgestrel log10 Cmax and log10 AUC. CYP2B6 15582C>T was associated with lower log10 AUC. Nevirapine group: CYP2B6 516G>T was associated with higher log10 Cmax and lower log10 Cmin . Pharmacogenetic variations influenced subdermal levonorgestrel pharmacokinetics in HIV-positive women, indicating that the magnitude of the interaction with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is influenced by host genetics. This article is protected by copyright. All rights reserved.

  16. Lipaemic plasma induces haemolysis in resuspended red cell concentrate.

    PubMed

    Bashir, S; Wiltshire, M; Cardigan, R; Thomas, S

    2013-04-01

    We investigated whether haemolysis in red cells suspended in plasma was affected by the lipid content and/or methylene blue (MB) treatment of fresh-frozen plasma (FFP). We also investigated whether haemolysis was affected by the conditions under which lipaemic plasma was stored. Study 1: Visibly lipaemic (n = 22) or nonlipaemic FFP (n = 24) units were thawed, pooled and split into identical pairs, one of which was MB treated. These units were used to resuspend red cell concentrates (RCC) and tested for haemolysis immediately and after 24 and 48 h of storage at 2-6°C. Study 2: Fresh plasma was aliquoted into 15-ml tubes and stored in one of four ways as follows: room temperature; 2-6°C; frozen and thawed; or twice frozen and thawed. A sample of RCC was resuspended in each of these plasmas and haemolysis measured after 2 h. Study 3: Plasma was divided into 15-ml tubes and stored as in study 2 followed by storage left standing upright in a refrigerator (2-6°C) for 24 h (with the exception of the room temperature sample). Plasma was separated into top, middle and bottom fractions and used to resuspend RCC that were assessed for haemolysis after 2 h. The levels of haemolysis in RCC were immediately greater when suspended in lipaemic plasma (0·70 ± 0·53% v 0·05 ± 0·06% for nonlipaemic plasma), which increased further on subsequent storage for 48 h (1·22 ± 0·40% v 0·15 ± 0·14% for nonlipaemic plasma). This was irrespective of whether plasma was MB treated. Lipaemic plasma stored frozen and then thawed resulted in the greatest haemolysis. In lipaemic plasma stored at 2-6°C, the chylomicron-rich top fraction caused the highest level of haemolysis. Haemolysis in red cells is increased in those suspended in lipaemic plasma and is dependent upon the storage conditions of that plasma prior to suspension. These data are relevant to the choice of plasma used to suspend red cells for neonatal exchange transfusion. © 2012 The Author(s). Vox Sanguinis © 2012

  17. Population Pharmacokinetics Modeling of Unbound Efavirenz, Atazanavir, and Ritonavir in HIV‐Infected Subjects With Aging Biomarkers

    PubMed Central

    Chen, J; Cottrell, M; Trezza, CR; Prince, HMA; Sykes, C; Torrice, C; White, N; Malone, S; Wang, R; Patterson, KB; Sharpless, NE; Forrest, A

    2016-01-01

    Unbound drug is the pharmacodynamically relevant concentration. This study aimed to determine if chronologic age or markers of biologic aging, such as the frailty phenotype and p16INK4a gene expression, altered unbound pharmacokinetics (PKs) of efavirenz (EFV) and atazanavir/ritonavir (ATV/RTV). Sixty human immunodeficiency virus (HIV)‐infected participants receiving EFV and 31 receiving ATV/RTV provided 1 to 11 samples to quantify total and unbound plasma concentrations. Population PK models with total and unbound concentrations simultaneously described are developed for each drug. The unbound fractions for EFV, ATV, and RTV are 0.65%, 5.67%, and 0.63%, respectively. Covariate analysis suggests RTV unbound PK is sensitive to body size; unbound fraction of RTV is 34% lower with body mass index (BMI) above 30 kg/m2. No alterations in drug clearance or unbound fraction with age, frailty, or p16INK4a expression were observed. Assessing functional and physiologic aging markers to inform potential PK changes is necessary to determine if drug/dosing changes are warranted in the aging population. PMID:28032946

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

    PubMed

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

    2005-12-01

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

  19. Use of refractometry for determination of psittacine plasma protein concentration.

    PubMed

    Cray, Carolyn; Rodriguez, Marilyn; Arheart, Kristopher L

    2008-12-01

    Previous studies have demonstrated both poor and good correlation of total protein concentrations in various avian species using refractometry and biuret methodologies. The purpose of the current study was to compare these 2 techniques of total protein determination using plasma samples from several psittacine species and to determine the effect of cholesterol and other solutes on refractometry results. Total protein concentration in heparinized plasma samples without visible lipemia was analyzed by refractometry and an automated biuret method on a dry reagent analyzer (Ortho 250). Cholesterol, glucose, and uric acid concentrations were measured using the same analyzer. Results were compared using Deming regression analysis, Bland-Altman bias plots, and Spearman's rank correlation. Correlation coefficients (r) for total protein results by refractometry and biuret methods were 0.49 in African grey parrots (n=28), 0.77 in Amazon parrots (20), 0.57 in cockatiels (20), 0.73 in cockatoos (36), 0.86 in conures (20), and 0.93 in macaws (38) (P< or =.01). Cholesterol concentration, but not glucose or uric acid concentrations, was significantly correlated with total protein concentration obtained by refractometry in Amazon parrots, conures, and macaws (n=25 each, P<.05), and trended towards significance in African grey parrots and cockatoos (P=.06). Refractometry can be used to accurately measure total protein concentration in nonlipemic plasma samples from some psittacine species. Method and species-specific reference intervals should be used in the interpretation of total protein values.

  20. Association between efavirenz-based compared with nevirapine-based antiretroviral regimens and virological failure in HIV-infected children.

    PubMed

    Lowenthal, Elizabeth D; Ellenberg, Jonas H; Machine, Edwin; Sagdeo, Aditi; Boiditswe, Sefelani; Steenhoff, Andrew P; Rutstein, Richard; Anabwani, Gabriel; Gross, Robert

    2013-05-01

    Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited. To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment. Retrospective cohort study of children (aged 3-16 years) who initiated efavirenz-based (n = 421) or nevirapine-based (n = 383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis. With a median follow-up time of 69 months (range, 6-112 months; interquartile range, 23-87 months), 57 children (13.5%; 95% CI, 10.4%-17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%-31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%-4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%-7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4-2.7; log rank P < .001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses. Among children aged 3 to 16 years

  1. Association Between Efavirenz-Based Compared With Nevirapine-Based Antiretroviral Regimens and Virological Failure in HIV-Infected Children

    PubMed Central

    Lowenthal, Elizabeth D.; Ellenberg, Jonas H.; Machine, Edwin; Sagdeo, Aditi; Boiditswe, Sefelani; Steenhoff, Andrew P.; Rutstein, Richard; Anabwani, Gabriel; Gross, Robert

    2013-01-01

    Importance Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited. Objective To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment. Design, Setting, and Participants Retrospective cohort study of children (aged 3–16 years) who initiated efavirenz-based (n=421) or nevirapine-based (n=383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. Main Outcomes and Measures The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis. Results With a median follow-up time of 69 months (range, 6–112 months; interquartile range, 23–87 months), 57 children (13.5%; 95% CI, 10.4%–17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%–31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%–4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%–7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4–2.7; log rank P<.001, favoring efavirenz). None of the measured covariates

  2. Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.

    PubMed

    Cristofoletti, Rodrigo; Nair, Anita; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

    2013-02-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products.

  3. Variations in plasma phytoestrogen concentrations in European adults.

    PubMed

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

    2007-05-01

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

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

    PubMed

    Reaven, G M; Dall'Aglio, E

    1982-01-01

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

  5. Measurement of plasma homovanillic acid concentrations in schizophrenic patients.

    PubMed

    Kaminski, R; Powchick, P; Warne, P A; Goldstein, M; McQueeney, R T; Davidson, M

    1990-01-01

    1. Several lines of evidence suggest that abnormalities of central dopaminergic transmission may be involved in the expression of some schizophrenic symptoms. However, elucidation of the role of dopamine (DA) in schizophrenia has eluded investigative efforts partially because no accurate and easily repeatable measure of brain DA activity exists. 2. The development of a technique to measure homovanillic acid in plasma has offered the possibility of performing serial measurements of this major DA metabolite. 3. Assuming that plasma homovanillic acid (PHVA) concentrations is an index of brain DA activity, measurement of PHVA can play a role in elucidating the DA abnormality in schizophrenia. 4. Results to date suggest that plasma homovanillic acid concentrations are lower in chronic schizophrenic patients compared to normal controls, and that PHVA values correlate with schizophrenic symptom severity. 5. In addition, PHVA levels were shown to initially rise and subsequently decline during chronic neuroleptic administration in treatment responsive but not in treatment refractory schizophrenic patients.

  6. Plasma Concentrations of Fentanyl Achieved With Transdermal Application in Chickens.

    PubMed

    Delaski, Kristina M; Gehring, Ronette; Heffron, Brendan T; Negrusz, Adam; Gamble, Kathryn C

    2017-03-01

    Providing appropriate analgesia is an important concern in any species. Fentanyl, a μ-receptor specific opioid, use is common in mammalian species but has been incompletely evaluated for this purpose in avian species. Transdermal fentanyl patches were applied to domestic chickens (n = 10) of varying breeds for 72 hours. Repeated blood samples were collected from the birds to assess time-concentration of fentanyl and norfentanyl in plasma, as assayed by liquid chromatography-mass spectrometry, throughout patch application and for 48 hours after patch removal. Compartmental modeling was used to characterize the elimination profiles. Evaluation as a large bolus, followed by slower elimination rates over the remaining time, best fit the data as a one-compartment open model. Although maximum plasma fentanyl concentrations varied substantially by individual birds, chickens trended into 2 general groups of maximum plasma concentration, clearance, and volume of distribution, which was attributed to absorption variability. For all birds, harmonic mean of elimination half-life was 7.2 ± 3.7 hours and showed less individual variation than the other pharmacokinetic parameters. Because the application of transdermal fentanyl patches in the chickens achieved plasma fentanyl concentrations considered therapeutic in people, this approach could provide an additional analgesic option for avian patients.

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

    PubMed

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

    2006-02-01

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

  8. Environmentally relevant concentrations of nitrate increase plasma testosterone concentrations in female American alligators (Alligator mississippiensis).

    PubMed

    Hamlin, Heather J; Edwards, Thea M; McCoy, Jessica; Cruze, Lori; Guillette, Louis J

    2016-11-01

    Anthropogenic nitrogen is a ubiquitous environmental contaminant that is contributing to the degradation of freshwater, estuarine, and coastal ecosystems worldwide. The effects of environmental nitrate, a principal form of nitrogen, on the health of aquatic life is of increasing concern. We exposed female American alligators to three concentrations of nitrate (0.7, 10 and 100mg/L NO3-N) for a duration of five weeks and five months from hatch. We assessed growth, plasma sex steroid and thyroid hormone concentrations, and transcription levels of key genes involved in steroidogenesis (StAR, 3β-HSD, and P450scc) and hepatic clearance (Cyp1a, Cyp3a). Exposure to 100mg/L NO3-N for both five weeks and five months resulted in significantly increased plasma testosterone (T) concentrations compared with alligators in the reference treatment. No differences in 17β-estradiol, progesterone, or thyroid hormones were observed, nor were there differences in alligator weight or the mRNA abundance of steroidogenic or hepatic genes. Plasma and urinary nitrate concentrations increased with increasing nitrate treatment levels, although relative plasma concentrations of nitrate were significantly lower in five month, versus five week old animals, possibly due to improved kidney function in older animals. These results indicate that environmentally relevant concentrations of nitrate can increase circulating concentrations of T in young female alligators. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Plasma concentrations of transthyretin in older Sardinians including centenarians.

    PubMed

    Pasella, Sara; Pinna, Sara; Deiana, Marta; Baralla, Angela; Dore, Simone; Mannu, Andrea; Canu, Elisabetta; Sotgiu, Giovanni; Zinellu, Angelo; Mangoni, Arduino A; Sotgia, Salvatore; Carru, Ciriaco; Deiana, Luca

    2016-02-01

    Plasma concentrations of transthyretin (TTR), a negative acute-phase protein, can be influenced by many factors including aging. Under physiological circumstances, TTR concentrations are very low in the fetus, increase slowly after birth up to the fifth decade and, then, decrease slowly. Some studies have shown sex-related differences up to about 70 years, when the differences disappear. The aim of this study was to evaluate the change in TTR concentrations in healthy males and females aged more than sixty, including numerous centenarians living in Sardinia, a large Italian island located in the Mediterranean Sea. The study sample consisted of 211 healthy subjects grouped by age and sex (male/female ratio: 1:1). Plasma TTR was assessed using a non-competitive enzyme immunoassay (ELISA Assaypro LLC, prealbumin AssayMAX Human ELISA Kit). In subjects aged between 60 and 99 years, plasma TTR concentrations were higher compared to the reference ranges reported by CRM 470. Moreover, unlike other studies, sex-related differences in TTR concentrations were only observed in nonagenarians and centenarians. We hypothesize that there are TTR-related genetic differences between the Sardinian population and other Caucasian ethnic groups. Further studies and a larger sample are needed to confirm our hypothesis.

  10. Plasma mepivacaine concentrations in patients undergoing third molar surgery.

    PubMed

    Scarparo, H C; Maia, R N; Filho, Ea Dos Santos; Soares, Ecs; Costa, Fwg; Fonteles, Csr; Bezerra, T P; Ribeiro, T R; Romero, N R

    2016-12-01

    Local anaesthetic-related systemic toxicity mainly results from elevated plasma concentrations of these drugs. We hypothesized that intraoral injection of submaximal doses of mepivacaine does not lead to toxic levels of this drug in blood. This study evaluated the plasma levels of mepivacaine in third molars surgeries. Twenty-one patients were randomly assigned into two groups: group I (two unilateral third molars; submaximal dose of mepivacaine 108 mg with epinephrine 54 μg) and group II (four third molars; submaximal dose of mepivacaine 216 mg with epinephrine 108 μg). Blood samples were collected before anaesthesia, and 5, 10, 15, 20, 30, 40, 60, 90 and 120 min after anaesthesia. Individual peak plasma concentrations ranged 0.77-8.31 μg/mL (group I) and from 2.36-7.72 μg/mL (group II). An increase in the average dose of mepivacaine from 1.88 ± 0.12 mg/kg (group I) to 3.35 ± 0.17 mg/kg (group II) increased the mean mepivacaine peak plasma levels from 2.33 ± 0.58 to 4.01 ± 0.69 μg/mL, respectively. Four patients obtained plasma levels of mepivacaine above the threshold for toxicity (5 μg/mL). Toxic levels of mepivacaine are possible, even when a submaximal dose is used. A twofold increase in the dose of mepivacaine caused the mean peak plasma concentration to increase proportionally, indicating that they may be predicted based on the relation of dose per bodyweight. © 2016 Australian Dental Association.

  11. Laser system for measuring small changes in plasma tracer concentrations.

    PubMed

    Klaesner, J W; Pou, N A; Parker, R E; Galloway, R L; Roselli, R J

    1996-01-01

    The authors developed a laser-diode system that can be used for on-line optical concentration measurements in physiologic systems. Previous optical systems applied to whole blood have been hampered by artifacts introduced by red blood cells (RBCs). The system introduced here uses a commercially available filter cartridge to separate RBCs from plasma before plasma concentration measurements are made at a single wavelength. The filtering characteristics of the Cellco filter cartridge (#4007-10, German-town, MD) were adequate for use in the on-line measurement system. The response time of the filter cartridge was less than 40 seconds, and the sieving characteristics of the filter for macromolecules were excellent, with filtrate-to-plasma albumin ratios of 0.98 +/- 0.11 for studies in sheep and 0.94 +/- 0.15 for studies in dogs. The 635-nm laser diode system developed was shown to be more sensitive than the spectrophotometer used in previous studies (Klaesner et al., Annals of Biomedical Engineering, 1994; 22, 660-73). The new system was used to measure the product of filtration coefficient (Kfc) and reflection coefficient for albumin (delta f) in an isolated canine lung preparation. The delta fKfc values [mL/(cmH2O.min.100 g dry lung weight)] measured with the laser diode system (0.33 +/- 0.22) compared favorably with the delta fKfc obtained using a spectrophotometer (0.27 +/- 0.20) and with the Kfc obtained using the blood-corrected gravimetric method (0.32 +/- 0.23). Thus, this new optical system was shown to accurately measure plasma concentration changes in whole blood for physiologic levels of Kfc. The same system can be used with different optical tracers and different source wavelengths to make optical plasma concentration measurements for other physiologic applications.

  12. Gastrin concentrations in plasma of cats with chronic renal failure.

    PubMed

    Goldstein, R E; Marks, S L; Kass, P H; Cowgill, L D

    1998-09-15

    To determine the prevalence of hypergastrinemia in cats with naturally developing chronic renal failure (CRF) and the correlation between gastrin concentration in plasma and severity of CRF. Cohort study. 30 cats with naturally developing CRF and 12 clinically normal control cats. Gastrin concentrations in plasma were determined by double-antibody radioimmunoassay of blood samples obtained from cats after food was withheld 8 hours. Concentrations were compared, using a nonparametric Kruskal-Wallis ANOVA. 18 cats with CRF had high gastrin concentrations (median, 45 pg/ml; range, < 18 to > 1,333 pg/ml), compared with those for control cats (< 18 pg/ml). Prevalence of hypergastrinemia increased with severity of renal insufficiency. Three of 9 cats with mild CRF, 6 of 11 cats with moderate CRF, and 9 of 10 cats with severe CRF had high gastrin concentrations. Gastrin concentrations were significantly different between control cats and cats with CRF, regardless of disease severity. The potential role of high concentrations of gastrin on gastric hyperacidity, uremic gastritis, bleeding from the gastrointestinal tract, and associated clinical signs of hypergastrinemia (e.g., anorexia and vomiting) may justify use of histamine2-receptor antagonists or proton pump inhibitors to suppress gastric acid secretion in cats with CRF that have these clinical signs.

  13. 77 FR 35985 - Determination That PARAPLATIN (Carboplatin) Injection and SUSTIVA (Efavirenz) Capsules Were Not...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... SUSTIVA (Efavirenz) Capsules Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY... (efavirenz) Capsule, 100 Bristol Myers Squibb. milligrams (mg). NDA 20-452 PARAPLATIN (carboplatin) Do...

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

    PubMed

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

    1984-01-01

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

  15. Plasma concentrations of sucralose in children and adults.

    PubMed

    Sylvetsky, Allison C; Bauman, Viviana; Blau, Jenny E; Garraffo, H Martin; Walter, Peter J; Rother, Kristina I

    2017-01-01

    Sucralose is partially absorbed after oral ingestion, with the majority excreted in the feces. We aimed to measure plasma sucralose concentrations following ingestion of doses reflecting a range of consumption (from one can of diet soda up to multiple sodas over the course of a day) and to compare concentrations in children and adults. Eleven adults (7 females, 4 males) consumed 355 mL water containing 0 mg sucralose (control) or 68, 170, or 250 mg sucralose (equivalent to 1-4 diet sodas). A second group of adults (n=11, 6 females and 5 males) consumed 355 mL Diet Rite Cola™ (68 mg sucralose and 41 mg acesulfame-potassium (ace-K)) or 68 mg sucralose and 41 mg ace-K in seltzer. Beverages were provided at separate visits in randomized order, prior to an oral glucose tolerance test. Eleven children (7 females and 4 males) consumed 0 or 68 mg sucralose in 240 mL water, in an identical study design. Blood was collected before beverage ingestion and serially for 120 min. Sucralose doses (corrected for weight) resulted in similar plasma concentrations in children and adults. Children reached peak concentrations of 145-400 ng/mL after 68 mg (mean 262.3 ± 24.6 ng/mL). Most adults reached similar peak concentrations (200-400 ng/mL after 250 mg (365.6 ± 69.9 ng/mL)) with the exception of two adults (1520 ng/mL and 1557 ng/mL, respectively). Concentrations were comparable whether sucralose was administered in water, combined with ace-K, or in diet soda. Due to their lower body weight and blood volume, children have markedly higher plasma sucralose concentrations after consumption of a typical diet soda, emphasizing the need to determine the clinical implications of sucralose use in children.

  16. Drug concentrations in post-mortem femoral blood compared with therapeutic concentrations in plasma

    PubMed Central

    Launiainen, Terhi; Ojanperä, Ilkka

    2014-01-01

    Therapeutic drug concentrations measured in plasma are of limited value as reference intervals for interpretation in post-mortem (PM) toxicology. In this study, drug concentration distributions were studied in PM femoral venous blood from 57 903 Finnish autopsy cases representing all causes of death during an 11-year period. Cause-of-death information was obtained from death certificates issued by forensic pathologists. Median, mean, and upper percentile (90th, 95th, 97.5th) concentrations were calculated for 129 drugs. To illustrate how PM median concentrations relate to established therapeutic ranges in plasma, a PM blood/plasma relationship was calculated for each drug. Males represented 75% of the subjects and showed a lower median age (55 yrs) than females (59 yrs). In 43% of these cases, blood alcohol concentration was higher than 0.2‰, and the median was 1.8‰. Sixty-one (47%) of the 129 drugs showed a PM blood/plasma relationship of 1. For 22 drugs (17%), the relationship was <1, and for 46 drugs (35%), the relationship was >1. No marked correlation was found between the PM blood/plasma relationship and the volume of distribution (Vd). For 36 drugs, more than 10% of cases were fatal poisonings attributed to this drug as the main finding. These drug concentration distributions based on a large database provide a helpful reference not only to forensic toxicologists and pathologists but also to clinical pharmacologists in charge of interpreting drug concentrations in PM cases. © 2013 The Authors. Drug Testing and Analysis published by John Wiley & Sons, Ltd. PMID:23881890

  17. Daily concentrations of air pollution and plasma fibrinogen in London.

    PubMed

    Pekkanen, J; Brunner, E J; Anderson, H R; Tiittanen, P; Atkinson, R W

    2000-12-01

    The reason for the association between air pollution and risk of cardiovascular diseases is unknown. The hypothesis was examined that daily concentrations of air pollution are associated with daily concentrations of fibrinogen, a risk factor for cardiovascular disease. Data on concentrations of plasma fibrinogen for 4982 male and 2223 female office workers, collected in a cross sectional survey in London between September 1991 and May 1993, were combined with data on concentrations of air pollution during the day of blood sampling and during the 3 preceding days. After adjustment for weather and other confounding factors, an increase in the 24 hour mean NO(2) during the previous day from the 10th to the 90th percentile (61.7 microg/m(3)) was associated with a 1.5% (95% confidence interval (95% CI) 0.4% to 2.5%) higher fibrinogen concentration. The respective increase for CO (1.6 mg/m(3)) was 1.5% (95% CI 0.5%, 2.5%). These associations tended to be stronger in the warm season (April to September). Significant associations were found for black smoke and particulate matter of diameter 10 microm (PM(10)) only in the warm season. No association with fibrinogen was found for SO(2) or ozone. The short term association between air pollution, possibly from traffic, and risk of cardiovascular events may be at least partly mediated through increased concentrations of plasma fibrinogen, possibly due to an inflammatory reaction caused by air pollution.

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

    PubMed

    Lynch, Kathleen S; Wilczynski, Walter

    2006-06-01

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

  19. A study of plasma bicalutamide concentrations in hemodialysis patients.

    PubMed

    Ito, Fumio; Goya, Nobuyuki; Nakazawa, Hayakazu; Suzuki, Toshiaki; Suzuki, Keiko; Kubo, Kazuo; Kihara, Takeshi

    2012-01-01

    Bicalutamide is an anti-androgen that is used worldwide to treat prostate cancer (CaP). However, there are no data on blood bicalutamide concentrations in hemodialysis (HD) patients with CaP. Therefore, we investigated the plasma levels of bicalutamide during the peridialysis period in this population. The study group included 5 HD patients with CaP who had been treated with bicalutamide (80 mg/day) for at least 3 months. Blood samples were taken during and between HD sessions and the plasma concentrations of the active R enantiomer (R-bicalutamide) were assessed using an HPLC assay. The plasma R-bicalutamide levels on the non-dialysis day were measured in 2 patients (patients 1 and 2) immediately before dosing and 8 and 24 h after dosing. These levels were 18,730, 19,090 and 19,420 ng/ml (patient 1), and 4,522, 4,581, and 5,296 ng/ml (patient 2), respectively. The mean plasma levels of R-bicalutamide in all 5 subjects just before HD, and 2 and 4 h after the start of HD were 8,726, 9,354 and 10,068 ng/ml, respectively. These results show that bicalutamide does not accumulate and is not diluted in the blood circulation of HD patients when given at the normal dosage used in the general population. Copyright © 2012 S. Karger AG, Basel.

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

    PubMed

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

    1983-01-01

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

  1. Mass spectrometer for measurements of relative ion concentrations in plasmas

    NASA Technical Reports Server (NTRS)

    Suszcynsky, David M.; D'Angelo, Nicola; Merlino, Robert L.

    1988-01-01

    A mass spectrometer which can be used to measure relative ion concentrations in a multiion component plasma has been designed for use in a strong (1-4-kG) uniform magnetic field. The spectrometer features an acceleration region which accelerates thermal ions through a series of three tantalum electrodes at a 30 deg angle to the B field, and a collection region in which ions are selectively collected, depending on the size of their gyroradii, by a cylindrical collector. Relative ion concentrations are determined from measurements of the collector current as a function of accelerating voltage. Results obtained using this instrument in a Q-machine device operated with a two-ion (Cs+/K+) component plasma are presented.

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

    PubMed Central

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

    2014-01-01

    Background Polychlorinated biphenyl (PCB) exposure has been associated with non-Hodgkin lymphoma in several studies, and the immune system is a potential mediator. Objectives We analyzed associations of plasma PCBs with immune function measures. We hypothesized that higher plasma PCB concentrations are associated with lower immune function cross-sectionally, and that increases in PCB concentrations over a one year period are associated with decreases in immune function. Methods Plasma PCB concentrations and immune function [natural killer (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were measured at baseline and one year in 109 postmenopausal overweight women participating in an exercise intervention study in the Seattle, Washington (USA) area. Mixed models, with adjustment for body mass index and other potential confounders, were used to estimate associations of PCBs with immune function cross-sectionally and longitudinally. Results Associations of PCBs with immune function measures differed across groups of PCBs (e.g., medium- and high-chlorinated and dioxin-like [mono-ortho substituted]) and by the time frame for the comparison (cross-sectional vs. longitudinal). Higher concentrations of medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross-sectionally but not longitudinally. The mean decrease in 0.5 μg/mL PHA-TLP per 50.0 pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and NK cytotoxicity. Conclusions These results do not provide strong evidence of impaired cellular immunity from PCB exposure. Larger longitudinal studies with greater variability in PCB exposures are needed to further examine temporal associations of PCBs with immune function. PMID:24721136

  3. Plasma leptin concentrations and esophageal hypomotility in obese patients

    PubMed Central

    Côté-Daigneault, Justin; Poitras, Pierre; Rabasa-Lhoret, Rémi; Bouin, Mickael

    2015-01-01

    BACKGROUND: Although esophageal hypomotility is prevalent in obese patients, its cause remains unknown. Leptin, a hormone derived from adipose tissue, may be involved in this phenomenon because it has been shown to decrease gastric and intestinal motility in animals. It has been hypothesized that elevated plasma leptin concentration is a risk factor for esophageal dysmotility in obese patients. OBJECTIVE: To determine whether plasma leptin concentrations are higher in obese patients with esophageal hypomotility than in obese patients with a normal motility profile. METHOD: Fasting plasma leptin concentration (assessed by radioimmuoassay) was measured in all patients who were included in a study protocol investigating esophageal manometry before bariatric surgery. The patients completed standardized surveys regarding epidemiological data, upper gastrointestinal symptoms, medical history and medication(s). Basal levels of leptin, as well as corrected leptin scores adjusted for sex and body mass index, were compared in patients with and without esophageal dysmotility. RESULTS: Nine patients without dysmotility and eight with dysmotility were included. Both groups were comparable with regard to age (42±9 versus 38±9 years), sex (78% versus 75% women) and body mass index (49±10 kg/m2 versus 42±7 kg/m2). There were no significant differences regarding medication(s) and comorbidities between the two groups. When compared with normal predicted values, the corrected leptin scores were 30% higher in patients with dysmotility than in the control group with normal motility (P≤0.05). CONCLUSION: Obese patients with esophageal dysmotility exhibited elevated plasma leptin concentrations, suggesting a role for leptin in promoting esophageal hypomotility. PMID:25706575

  4. Five-year follow up of once-daily therapy with emtricitabine, didanosine and efavirenz (Montana ANRS 091 trial).

    PubMed

    Molina, Jean-Michel; Journot, Valérie; Furco, André; Palmer, Pierre; De Castro, Nathalie; Raffi, François; Morlat, Philippe; May, Thierry; Rancinan, Corinne; Chêne, Geneviève

    2007-01-01

    Once-daily combination therapy with emtricitabine, didanosine and efavirenz has been highly effective in clinical trials but its long-term efficacy and safety has not been previously reported. This multicentre, single-arm, open-label trial enrolled 40 antiretroviral-naive HIV-1-infected patients who received a once-daily regimen of emtricitabine, didanosine and efavirenz. The objective was to assess the long-term effects of this combination on plasma HIV RNA levels, CD4+ T-cell counts, safety and tolerability. After 5 years, 73% and 68% of patients had plasma HIV RNA levels < 400 and < 50 copies/ml, respectively, in an intent-to-treat, missing-equals-failure analysis. Genotypic resistance on treatment emerged in six patients. There was a significant increase in CD4+ T-cell count of 294 x 10(6) cells/l. Only six patients discontinued study treatment, because of non-severe adverse events. Lipodystrophy was infrequent, and lipid and glucose profiles were favourable with a significant increase in high-density lipoprotein cholesterol. A convenient once-daily regimen of emtricitabine, didanosine and efavirenz provided durable antiretroviral response and was well tolerated through 5 years of therapy.

  5. HPLC analysis of K-48 concentration in plasma.

    PubMed

    Kalász, H; Hasan, M Y; Sheen, R; Kuca, K; Petroianu, G; Ludányi, K; Gergely, A; Tekes, K

    2006-07-01

    K-48 is a new oxime-type compound to be used as an enzyme reactivator in the treatment of exposure to organophosphorous compounds. Plasma concentration of K-48 can be determined using reversed-phase HPLC. Analysis using octyl silica stationary phase and ultraviolet-absorbance detection is fast and simple. K-48 displays a relatively high dose-normalized area under the curve as compared to pralidoxime, which might be beneficial for an antidote. After i.m. administration of 50 mumol K-48, the time course of the concentration can be approximated by a straight line between 15 and 120 min meaning the elimination follows zero-order kinetics.

  6. Efavirenz Induces Neuronal Autophagy and Mitochondrial Alterations

    PubMed Central

    Purnell, Phillip R.

    2014-01-01

    Efavirenz (EFV) is a non-nucleoside reverse-transcriptase inhibitor in wide use for the treatment of human immunodeficiency virus infection. Although EFV is generally well tolerated, neuropsychiatric toxicity has been well documented. The toxic effects of EFV in hepatocytes and keratinocytes have been linked to mitochondrial perturbations and changes in autophagy. Here, we studied the effect of EFV on mitochondria and autophagy in neuronal cell lines and primary neurons. In SH-SY5Y cells, EFV induced a drop in ATP production, which coincided with increased autophagy, mitochondrial fragmentation, and mitochondrial depolarization. EFV-induced mitophagy was also detected by colocalization of mitochondria and autophagosomes and use of an outer mitochondrial membrane tandem fluorescent vector. Pharmacologic inhibition of autophagy with 3-methyladenine increased the cytotoxic effect of EFV, suggesting that autophagy promotes cell survival. EFV also reduces ATP production in primary neurons, induces autophagy, and changes mitochondrial morphology. Overall, EFV is able to acutely induce autophagy and mitochondrial changes in neurons. These changes may be involved in the mechanism leading to central nervous system toxicity observed in clinical EFV use. PMID:25161171

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

    SciTech Connect

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

    2014-05-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-06

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

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

    PubMed

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

    2011-12-01

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

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

    DOEpatents

    Hull, Donald E.; Bieniewski, Thomas M.

    1988-01-01

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

  12. Factors affecting plasma aluminum concentrations in nonexposed workers

    SciTech Connect

    House, R.A. )

    1992-10-01

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

  13. Factors affecting plasma aluminum concentrations in nonexposed workers.

    PubMed

    House, R A

    1992-10-01

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

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

    PubMed

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

    2004-02-01

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

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

    PubMed

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

    2014-08-01

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

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

    PubMed Central

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

    2014-01-01

    MDMA (±3,4-methylenedioxymethamphetamine, ‘ecstasy’) is reportedly used recreationally because it increases feelings of sociability and interpersonal closeness. Prior work suggests that the pro-social effects of MDMA may be mediated by release of oxytocin. A direct examination of plasma levels of oxytocin after acute doses of oxytocin and MDMA, in the same individuals, would provide further evidence for the idea that MDMA produces its prosocial effects by increasing oxytocin. Fourteen healthy MDMA users participated in a 4-session, double-blind study in which they received oral MDMA (0.75 and 1.5 mg/kg), intranasal oxytocin (20 IU or 40 IU), and placebo. Plasma oxytocin concentrations, as well as cardiovascular and subjective effects were assessed before and at several time points after drug administration. MDMA (1.5 mg/kg only) increased plasma oxytocin levels to a mean peak of 83.7 pg/ml at approximately 90–120 minutes, compared to 18.6 pg/ml after placebo. Intranasal oxytocin (40 IU, but not 20 IU) increased plasma oxytocin levels to 48.0 pg/ml, 30–60 min after nasal spray administration. MDMA dose-dependently increased heart rate, blood pressure, feelings of euphoria (e.g., ‘High’ and ‘Like Drug’), and feelings of sociability, whereas oxytocin had no cardiovascular or subjective effects. The subjective and cardiovascular responses to MDMA were not related to plasma oxytocin levels, although the N was small for this analysis. Future studies examining the effects of oxytocin antagonists on responses to MDMA will help to determine the mechanism by which MDMA produces pro-social effects. PMID:24882155

  17. Effects of administration of glucocorticoids and feeding status on plasma leptin concentrations in dogs.

    PubMed

    Nishii, Naohito; Takasu, Masaki; Ohba, Yasunori; Maeda, Sadatoshi; Kitoh, Katsuya; Ohtsuka, Yoshihiko; Honjo, Tsutomu; Saito, Masayuki; Kitagawa, Hitoshi

    2006-02-01

    To investigate effects of short- and long- term administration of glucocorticoids, feeding status, and serum concentrations of insulin and cortisol on plasma leptin concentrations in dogs. 20 nonobese dogs. For experiment 1, plasma leptin concentrations and serum concentrations of insulin and cortisol were monitored for 24 hours in 4 dogs administered dexamethasone (0.1 mg/kg, IV) or saline (0.9% NaCl) solution for fed and nonfed conditions. For experiment 2, 11 dogs were administered prednisolone (1 mg/kg, PO, q 24 h for 56 days [7 dogs] and 2 mg/kg, PO, q 24 h for 28 days [4 dogs]) and 5 dogs served as control dogs. Plasma leptin and serum insulin concentrations were monitored weekly. For experiment 1, dexamethasone injection with the fed condition drastically increased plasma leptin concentrations. Furthermore, injection of saline solution with the fed condition increased plasma leptin concentrations. These increases in plasma leptin concentrations correlated with increases in serum insulin concentrations. Dexamethasone injection with the nonfed condition increased plasma leptin concentrations slightly but continuously. Injection of saline solution with the nonfed condition did not alter plasma leptin concentrations. For experiment 2, prednisolone administration at either dosage and duration did not alter plasma leptin concentrations in any dogs. Dexamethasone injection and feeding increased plasma leptin concentrations in dogs. In addition, dexamethasone administration enhanced the effect of feeding on increases in plasma leptin concentrations. Daily oral administration of prednisolone (1 or 2 mg/kg) did not affect plasma leptin concentrations in dogs.

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

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

    PubMed

    Rose, Rajiv; Klemcke, Harold G

    2015-09-01

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

  1. Plasma digoxin concentrations and urinary excretion during a 'simpler' regimen of infant digitalization.

    PubMed Central

    Savage, M O; Hibble, A G; Pickering, D

    1975-01-01

    We have measured the plasma concentrations in sick neonates and infants being administered digoxin by a safer regimen. In the presence of normal renal function the plasma concentrations appear to be satisfactory. PMID:1103751

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

    NASA Astrophysics Data System (ADS)

    Tokar, Mikhail Z.

    2016-02-01

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

  3. Midazolam plasma concentration after anesthesia premedication in clinical routine - an observational study : Midazolam plasma concentration after anesthesia premedication.

    PubMed

    Steiner, C; Steurer, M P; Mueller, D; Zueger, M; Dullenkopf, A

    2016-10-24

    Midazolam is commonly used as a pre-anesthesia anxiolytic. It`s elimination may not be fast enough for short procedures. In orally premedicated patients we obtained midazolam plasma concentrations at the end of surgical procedures and compared those to concentrations at anesthesia induction. The study was conducted prospectively with consent of the local ethics committee (Ethikkomission Kanton Thurgau, Switzerland) and carried out with written informed consent of each patient. Female patients aged 20 to 60 years undergoing elective procedures with general anesthesia were included, and were divided in two groups according to the planned surgical time: group S (<30 min) and group L (90-120 min), respectively. All patients received 7.5 mg Midazolam po as premedication. Blood samples were drawn at anesthesia induction, and at the end of surgery. Data were compared with t-test (independent samples; significance level p <0.05). Twenty-five patients per group were included. Four patients were excluded from analysis, since midazolam was not detectable in any samples. Time of premedication to the 1st blood sample was not statistically different between groups, neither were Midazolam plasma levels at this time point (p = 0.94). None of the patients from group L (n = 24), but five patients in group S (n = 22) did have a higher plasma level of Midazolam at the end of the case compared to the beginning. The elimination half-life of oral Midazolam can lead to higher plasma levels at the end of a short procedure compared to those at induction of anesthesia. German Clinical Trials Register (Deutsches Register Klinischer Studien), DRKS00005429 ; date of registration 3(rd) January 2014.

  4. Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent mechanism in primary human hepatocytes

    SciTech Connect

    Bumpus, Namandje N.

    2011-12-15

    Chronic use of efavirenz (EFV) has been linked to incidences of hepatotoxicity in patients receiving EFV to treat HIV-1. While recent studies have demonstrated that EFV stimulates hepatic cell death a role for the metabolites of efavirenz in this process has yet to be examined. In the present study, incubation of primary human hepatocytes with synthetic 8-hydroxyEFV (8-OHEFV), which is the primary metabolite of EFV, resulted in cell death, caspase-3 activation and reactive oxygen species formation. The metabolite exerted these effects at earlier time points and using lower concentrations than were required for the parent compound. In addition, pharmacological inhibition of cytochrome P450-dependent metabolism of EFV using 1-aminobenzotriazole markedly decreased reactive oxygen species formation and cell death. Treatment of primary human hepatocytes with EFV and 8-OHEFV also stimulated phosphorylation of c-Jun N-terminal kinase (JNK) as well as phosphorylation of the JNK substrate c-Jun. Further, the mRNA and protein expression of an isoform of Bim (Bcl-2 interacting mediator of cell death) denoted as BimEL, which is proapoptotic and has been shown to be modulated by JNK, was increased. Inhibition of JNK using SP600125 prevented the EFV- and 8-OHEFV-mediated cell death. Silencing of Bim using siRNA transfected into hepatocytes also prevented cell death resulting from 8-OHEFV-treatment. These data suggest that the oxidative metabolite 8-OHEFV is a more potent inducer of hepatic cell death than the parent compound EFV. Further, activation of the JNK signaling pathway and BimEL mRNA expression appear to be required for EFV- and 8-OHEFV-mediated hepatocyte death. -- Highlights: Black-Right-Pointing-Pointer 8-Hydroxyefavirenz is a more potent stimulator of cell death than efavirenz. Black-Right-Pointing-Pointer Efavirenz and 8-hydroxyefavirenz increase JNK activity and BimEL mRNA expression. Black-Right-Pointing-Pointer JNK and Bim are required for efavirenz- and 8

  5. Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-09-01

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

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

    PubMed

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

    2007-10-01

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

  8. Technical pitfalls in measurement of venous plasma NH3 concentration.

    PubMed

    Gerron, G G; Ansley, J D; Isaacs, J W; Kutner, M H; Rudman, D

    1976-05-01

    Measurement of venous plasma NH3 in normal subjects by the ion-exchange method of Forman [Clin. Chem. 10, 497 (1964)] in a hospital clinical laboratory gave a mean value of 640 mug/liter (range, 300-1320 mug/liter; intraassay, intra-individual, and inter-individual coefficients of variation, 8, 47, and 47%, respectively). The following conditions adversely affect the reproducibility of the test: pollution of laboratory atmosphere and glassware by NH3-containing detergents; smoking by patient or analyst; delay, turbulence, or use of heparin lock in venipuncture; delay or warming of plasma above degrees C before mixing it with resin; and delay in colorimetric analysis of resin eluate. When these sources of error were eliminated, the mean value for normals was reduced to 330 mug/liter, the range was narrowed to 220-470 mug/liter, and the above-mentioned CV's were 5, 16, and 17%, respectively. With the precautions cited, furthermore, the intra-assay and intra-individual CV's for fasting NH3 concentration in cirrhotic patients were similarly reduced. An NH3 tolerance test was done by administering a standard dose of NH4Cl to patients and measuring venous plasma NH3 at 0, 15, 30, 60, and 90 min; the NH3 tolerance was quantified from the area under the curve relating concentration to time (mug - min/liter). As measured in the clinical laboratory, NH3 tolerance of cirrhotic patients showed intra-assay and intra-individual CV's of 50 to 90%. When the tolerance tests were repeated in the same subjects with the laboratory precautions listed above, these CV's were reduced to 8-15%.

  9. Engineered nanoparticles of Efavirenz using methacrylate co-polymer (Eudragit-E100) and its biological effects in-vivo.

    PubMed

    Hari, B N Vedha; Narayanan, N; Dhevendaran, K; Ramyadevi, D

    2016-10-01

    Nanotechnology in drug delivery is explored widely to improve therapeutic efficacy and minimize undesirable effects of several anti-HIV drugs. Efavirenz is a non-nucleoside reverse transcriptase inhibitor, prescribed as first-line drug of choice for treatment of AIDS. It is poorly soluble and exhibits variable bioavailability hence, a high oral dose is recommended for therapy. The present work focuses on improving the dissolution and bioavailability of Efavirenz through nano drug delivery approach. Polymeric nanoparticles were developed using Eudragit E100 and characterized for size, stability, morphology, cytotoxicity (MTT assay in T-lymphatic (C8166) cell lines) and in-vivo biodistribution in mice models. The optimized nanoparticles exhibited average particle size of 110nm, zeta potential of -33mV and entrapment efficiency 99%. The SEM images displayed the formation of nano-size particles. The cell viability was significantly improved in the nanoparticles (99%) compared to pure drug (15%) at the concentration of 8μg/mL. The in-vivo biodistribution profile of the nanoparticles showed considerably higher drug concentration in serum and major organs, especially in the brain compared to the free drug. The optimized Efavirenz loaded nanoparticles clearly demonstrated an increase in dissolution, drug distribution, and bioavailability, which implies better control over the therapeutic dosing.

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

    PubMed

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

    2011-12-01

    Thyroid hormones, essential for normal growth and health, are associated with changes in temperature, photoperiod, and reproduction. Iodide, a necessary element for thyroid hormone production, varies in diet, and is more abundant in estuarine environments, which could alter thyroid hormone variation. However, associations between thyroid hormone concentrations in animals from marine versus freshwater environments, which could become more pertinent with rising sea levels associated with global climate change, are not well studied. To determine the importance of dietary iodide in seasonal variation of plasma thyroid hormone concentrations, we analyzed seasonal variation of plasma thyroxine (T(4)) and triiodothyronine (T(3)) concentrations in juvenile alligators from an estuarine habitat (Merritt Island National Wildlife Refuge; MI) and a freshwater habitat (Lake Woodruff National Wildlife Refuge; LW) and compared these results to plasma inorganic iodide (PII) concentrations. Alligators from MI did not display seasonal variation in plasma T(4), but exhibited a seasonal pattern in plasma T(3) concentrations similar to alligators from LW. Plasma thyroid hormone concentrations were consistently higher at MI than at LW. PII concentrations were correlated with plasma T(4) and T(3) concentrations in juvenile alligators from LW but not MI. The data on plasma T(4) and T(3) concentrations suggest altered iodide metabolism in estuarine alligators. Differences in thyroid hormone concentrations between the populations could be due to differences in dietary iodide, which need to be further evaluated. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. EXTENDED STORAGE OF PLATELET-RICH PLASMA PREPARED PLATELET CONCENTRATES IN PLASMA OR PLASMALYTE

    PubMed Central

    Slichter, Sherrill J.; Bolgiano, Doug; Corson, Jill; Jones, Mary Kay; Christoffel, Todd

    2010-01-01

    Background Using bacterial detection or pathogen reduction, extended platelet storage may be licensed if platelet viability is maintained. FDA's post-storage platelet acceptance guidelines are that autologous stored platelet recoveries and survivals should be ≥66% and ≥58%, respectively, of each donor's fresh platelet data. Study Design And Methods Non-leukoreduced platelet concentrates were prepared from whole blood donations. Autologous platelet concentrates from 62 subjects were stored in 100% plasma (n=44) or 20% plasma/80% Plasmalyte (n=18), an acetate based, non-glucose containing crystalloid solution previously used for platelet storage.(1-3) Fresh platelets were obtained on the day the donor's stored platelets were to be transfused. The fresh and stored platelets were alternately radiolabeled with either 51Chromium or 111Indium, and in vitro measurements were performed on the stored platelets. Results FDA's platelet recovery criterion was met for 7 days of plasma storage, but platelet survivals maintained viability for only 6 days. Plasmalyte stored platelets did not meet either acceptance criteria after 6 days of storage. After 7 days of storage, platelet recoveries averaged 43 ± 4% and 30 ± 4% and survivals 4.1 ± 0.4 days and 2.0 ± 0.2 days for plasma and Plasmalyte-stored platelets, respectively (p=0.03 for recoveries and p<0.001 for survivals). Post-storage platelet recoveries correlated with the commonly-used in vitro platelet quality measurements of HSR and Annexin V binding, while survivals correlated with ESC, morphology score, and pH. Conclusion There is a progressive decrease in recoveries and survivals of plasma stored platelets over time. Platelet viability is better maintained in plasma than Plasmalyte. PMID:20456703

  12. In vitro suppression of the lipogenic pathway by the nonnucleoside reverse transcriptase inhibitor efavirenz in 3T3 and human preadipocytes or adipocytes.

    PubMed

    El Hadri, Khadija; Glorian, Martine; Monsempes, Christelle; Dieudonné, Marie-Noëlle; Pecquery, René; Giudicelli, Yves; Andreani, Marise; Dugail, Isabelle; Fève, Bruno

    2004-04-09

    A serious metabolic syndrome combining insulin-resistance, dyslipidemia, central adiposity, and peripheral lipoatrophy has arisen in HIV-infected patients receiving highly active antiretroviral therapy. The aim of this work was to examine the effects of the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz on adipocyte differentiation and metabolism. When induced to differentiate in the presence of efavirenz (5-50 microm), 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol droplets. This phenomenon was rapidly reversible and was also readily detectable in the 3T3-L1 preadipose cell line and in primary cultures of human preadipocytes. When applied to mature 3T3-F442A adipocytes, efavirenz induced a delayed and moderate reduction in cell triglyceride content. Measurement of [(3)H]deoxyglucose uptake, basal and agonist-stimulated lipolysis, and cell viability indicated that these pathways are not involved in efavirenz effects on triacylglycerol accumulation. By contrast, we found that the NNRTI induced a dramatic dose- and time-dependent decrease in gene and protein expression of the lipogenic transcription factor sterol regulatory element-binding protein-1c (SREBP-1c). Adipose conversion was only altered at the highest efavirenz concentrations, as suggested by the mild reduction in peroxisome proliferator-activated receptor-gamma and CCAAT/enhancer-binding protein-alpha. CCAAT/enhancer-binding protein-beta remained unchanged. The inhibition of SREBP-1c expression was accompanied by a sharp reduction in the expression of SREBP-1c target genes and in the adipocyte lipogenic activity in efavirenz-treated cells. Finally, the inhibitory effect of efavirenz on cell triglyceride accumulation was prevented by directly providing free fatty acids to the cells and was reversed by overexpression of a dominant positive form of SREBP-1c, reinforcing the implication of this transcription factor in the antilipogenic effect of the drug. When

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Elevated Plasma Homocysteine Concentration in Opium-Addicted Individuals

    PubMed Central

    Masoomi, Mohammad; Azdaki, Nahid; Shahouzehi, Beydolah

    2015-01-01

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

  16. Plasma Cannabinoid Concentrations during Dronabinol Pharmacotherapy for Cannabis Dependence

    PubMed Central

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

    2013-01-01

    Background Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic daily cannabis smokers who received high-dose oral THC pharmacotherapy and later, a smoked cannabis challenge. Methods 11 daily cannabis smokers received 0, 30, 60, or 120 mg/day THC for four 5-day medication sessions, each separated by 9-days of ad-libitum cannabis smoking. On the 5th day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the 1st and 5th days was quantified by GC-GC-MS for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5–100 for THC, 1–50 11-OH-THC, and 0.5–200 THCCOOH. Results During placebo dosing, THC, 11-OH-THC and THCCOOH concentrations consistently decreased, while all cannabinoids increased dose-dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during 60 and 120 mg/day doses, and THCCOOH increased significantly only during the 120 mg/day dose. THC and 11-OH-THC, and THCCOOH concentrations peaked within 0.25 h after cannabis smoking, except after 120 mg/day THC when THCCOOH peaked 0.5 h before smoking. Conclusions The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 h, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 h after overnight oral dronabinol abstinence, but cannot distinguish oral THC dosing from smoked cannabis intake. PMID:24067260

  17. Plasma IL-8 concentrations are increased in dogs with spirocercosis.

    PubMed

    Dvir, E; Mellanby, R J; Kjelgaard-Hansen, M; Schoeman, J P

    2012-11-23

    The nematode Spirocerca lupi (S. lupi) induces sarcoma in the dog oesophagus in about 25% of cases. The aim of this study was to compare the differences in the cytokine milieu between dogs with neoplastic (n=29) and non-neoplastic disease (n=49) and age- and gender-matched healthy controls (n=25). We measured IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, GM-CSF and MCP-1 in a specific canine multiplex immunoassay kit. Cytokine concentrations were compared between the different groups using the Kruskal-Wallis test followed by Dunn's test. Only IL-8 and IL-18 showed significant differences in their plasma concentration among the three groups. Kruskal-Wallis test revealed a significant (p=0.001) difference in IL-8 concentration between the neoplastic group (634pg/ml), the non-neoplastic (429 pg/ml) and the control groups (150 pg/ml). Post-test analysis revealed a significance difference between the two S. lupi groups and the control group (p<0.01). The highest IL-18 concentration was found in the non-neoplastic group (53 pg/ml), followed by the control group (46 pg/ml) and finally the neoplastic group (33 pg/ml). IL-18 concentrations were significantly higher in the non-neoplastic group than in the neoplastic group (p=0.05). The increased IL-8 in the spirocercosis groups is consistent with the neutrophilic infiltrate in spirocercosis lesions and in those of other inflammatory-induced neoplasias such as Barret's oesophagus and Helicobacter gastritis. IL-18 showed negative regulatory effect in several worm infections and it is possible that it plays the same role in spirocercosis, allowing the worm to evade the host response and to induce neoplastic transformation. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Therapeutic drug monitoring of protease inhibitors and efavirenz in HIV-infected individuals with active substance-related disorders.

    PubMed

    Ma, Qing; Zingman, Barry S; Luque, Amneris E; Fischl, Margaret A; Gripshover, Barbara M; Venuto, Charles S; DiFrancesco, Robin; Forrest, Alan; Morse, Gene D

    2011-06-01

    Achieving targeted antiretroviral (ARV) plasma concentrations during long-term treatment in human immunodeficiency virus (HIV)-infected patients with substance-related disorders (SRDs) may be challenging due to a number of factors, including medication adherence, coinfection with hepatitis B or C virus, medication intolerance, and drug interactions. One approach to investigate these factors is to conduct therapeutic drug monitoring to measure ARV exposure during treatment. The objective of this study was to utilize therapeutic drug monitoring to compare efavirenz (EFV) and protease inhibitor pharmacokinetics in patients with and without SRDs. This was a multicenter, cross-sectional open-label study in patients with HIV-1 infection receiving antiretroviral therapy (ART), with active (n=129) or without (n=146) SRD according to National Institute on Drug Abuse criteria. Two hundred seventy-five subjects who were receiving either protease inhibitor-based or EFV-based ART regimens for >6 months were enrolled at 4 HIV treatment centers with an equal distribution of SRD and non-SRD at each site. The patients were instructed during enrollment visits with regard to the importance of adherence before and after study visits. Demographics and routine clinical laboratory tests were recorded. Among the 275 patients, 47% had SRD with at least 1 substance. There were no significant differences between SRD and non-SRD groups for race, gender, age, or CD4 count at entry. A significantly higher proportion of patients with SRD had an entry HIV RNA plasma concentration>75 copies per milliliter compared with patients without SRD (40% vs 28%, P=0.044). Logistic regression modeling revealed an association between HIV RNA plasma concentration and African American race (P=0.017). A significantly higher proportion of SRDs also had an EFV or protease inhibitor trough concentration below the desired range (23% vs 9%, P=0.048). Significantly lower trough concentrations were noted in patients

  19. Antibiotic aerosolization: tissue and plasma oxytetracycline concentrations in turkey poults.

    PubMed

    Van Alstine, W G; Dyer, D C

    1985-01-01

    Oxytetracycline hydrochloride (OTC) was delivered by aerosol to healthy 3-week-old turkeys. Trachea, lung, and plasma were evaluated for OTC levels at 1, 4, 8, 12, 24, and 48 hours after aerosol exposure. In Expt. 1, 15 poults in a modified Horsfall unit were exposed to 1 g OTC/m3 of air using a DeVilbiss ultrasonic nebulizer. In Expt. 2, 25,000 poults in a commercial confinement unit were exposed to 0.075 g of OTC/m3 of air using a Fogmaster fogger. In each case, initially high tracheal and lung OTC concentrations were obtained. OTC levels in the trachea fell to less than 1 microgram/g between 4 and 8 hours postexposure. Plasma OTC levels remained low throughout both experiments. Oxytetracycline was still detectable in room air 60 min after aerosol exposure and before ventilation was restored. This method of administration may have promise for use in respiratory infections, but additional studies are needed to further define the use of aerosol therapy in poultry production units.

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

    PubMed

    Goch, Aleksander

    2005-10-01

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

  1. Pharmacokinetics of Rifampin and Isoniazid in Tuberculosis-HIV-Coinfected Patients Receiving Nevirapine- or Efavirenz-Based Antiretroviral Treatment

    PubMed Central

    Bhatt, N. B.; Barau, C.; Amin, A.; Baudin, E.; Meggi, B.; Silva, C.; Furlan, V.; Grinsztejn, B.; Barrail-Tran, A.; Bonnet, M.

    2014-01-01

    This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4+ T cell count, 104 cells/μl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of

  2. Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment.

    PubMed

    Bhatt, N B; Barau, C; Amin, A; Baudin, E; Meggi, B; Silva, C; Furlan, V; Grinsztejn, B; Barrail-Tran, A; Bonnet, M; Taburet, A M

    2014-06-01

    This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4(+) T cell count, 104 cells/μl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of

  3. Decrease in pyridoxal-5'-phosphate concentration and increase in pyridoxal concentration in rat plasma by 4'-O-methylpyridoxine administration.

    PubMed

    Kobayashi, Daisuke; Yoshimura, Teruki; Johno, Atsushi; Ishikawa, Mika; Sasaki, Keiko; Wada, Keiji

    2015-07-01

    Food poisoning from Ginkgo biloba seeds can cause epilepsy because of a decrease in γ-aminobutyric acid (GABA) concentrations in the brain. We previously demonstrated that 4'-O-methylpyridoxine (MPN) is responsible for this observed toxicity of G biloba seeds; however, the mechanism for the decrease in GABA and plasma concentration profile of MPN has not been clarified. Our hypothesis is that MPN induces a decrease in vitamin B6 concentrations, resulting in a decrease in GABA concentration. This study aimed to characterize the plasma concentration profile of MPN and intrinsic vitamin B6 concentrations (pyridoxal [PL], PL-5'-phosphate [PLP], and 4-pyridoxic acid) using a rat model. Plasma concentrations of B6 vitamers after intravenous MPN administration (5 mg/kg) were determined using high-performance liquid chromatography with a fluorescence detector. The half-life of MPN (0.91 ± 0.05 hours) was shorter in rats than the previously reported value in humans. We found a significant decrease in the plasma concentration of PLP, an active form of vitamin B6, after MPN administration. We also observed an increase in plasma PL and 4-pyridoxic acid concentrations; the increase in PL concentration may be caused by either metabolism of MPN to PL or by MPN-mediated inhibition of PL kinase. The present study is the first in vivo study showing relatively rapid elimination of MPN in rats and a decrease in plasma PLP concentration caused by MPN. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    1988-01-01

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

  5. Dolutegravir and elvitegravir plasma concentrations following cessation of drug intake.

    PubMed

    Elliot, Emilie; Amara, Alieu; Jackson, Akil; Moyle, Graeme; Else, Laura; Khoo, Saye; Back, David; Owen, Andrew; Boffito, Marta

    2016-04-01

    To evaluate dolutegravir and elvitegravir/cobicistat pharmacokinetics in HIV-negative volunteers up to 10 days after drug cessation. Healthy volunteers received 50 mg of dolutegravir once-daily for 10 days, then underwent a 9 day wash-out period, and then received elvitegravir/cobicistat as part of Stribild(®) (245 mg of tenofovir, 200 mg of emtricitabine, 150 mg of elvitegravir and 150 mg of cobicistat) for 10 days. Serial pharmacokinetic (PK) sampling occurred prior to the final dose of each course and at regular intervals for up to 216 h (10 days) after drug cessation. Concentrations were determined by LC-MS/MS, and PK parameters were illustrated as geometric mean and 90% CI. Seventeen volunteers completed the study. For dolutegravir, plasma terminal elimination t1/2 to the last measurable concentration (within 216 h) was longer than its t1/2 within the dosing interval (0-24 h): 14.3 h (12.9-15.7 h) versus 23.1 h (19.7-26.6 h); conversely, the terminal elimination t1/2 for elvitegravir was lower than its t1/2 within the dosing interval (0-24 h): 10.8 h (9.7-13.0 h) versus 5.2 h (4.7-6.1 h). Dolutegravir concentrations were above the protein-adjusted (PA) IC90 (64 ng/mL) in 100% of subjects after 36 and 48 h and in 94% after 60 and 72 h. All subjects had detectable dolutegravir concentrations at 96 h, a mean of 23.5% above the IC90. Elvitegravir concentrations were above the PA IC95 (45 ng/mL) in 100% of subjects at 24 h, 65% at 36 h but 0% after 48 h. Our data show marked differences in the elimination rates of dolutegravir and elvitegravir following treatment interruption, which is likely to impact the extent to which drug doses can be delayed or missed. They suggest that clinical differences may emerge in patients who have suboptimal adherence. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed

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

    2005-05-01

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

  7. Copper deficiency in sheep: an assessment of relationship between concentrations of copper in serum and plasma.

    PubMed

    Laven, Ra; Smith, Sl

    2008-12-01

    To assess the relationship between concentrations of copper in serum and plasma in sheep. Concentrations of Cu were measured in paired serum and heparinised plasma samples collected from 110 sheep in nine flocks. Linear regression was used to evaluate whether flock or gender had a significant effect on the association between concentrations of Cu in serum and plasma. The individual results for concentrations of Cu in serum were then compared with those from plasma, using correlation and limits of agreement plotting. Concentrations of Cu in serum ranged from 7.3 to 22 (mean 14.0) micromol/L, while concentrations in plasma ranged from 9 to 27 (mean 16.3) micromol/L. On average, concentrations of Cu in serum were 2.3 micromol/L lower than in plasma. Over the range of values seen in this study, concentrations of Cu in plasma and serum were significantly correlated (r=0.89), and mean concentrations in serum were 87% of those in plasma. There was no effect of flock or gender on the relationship between concentrations of Cu in serum and plasma. Despite the significant correlation, there was marked variability between individual samples in the proportion of Cu that was lost during clotting, with the 95% limits of agreement for serum Cu ranging from 70 to 104% of the plasma concentration. As in cattle, the individual variability in the loss of Cu during clotting in sheep is too great for concentration of Cu in serum to be used as a substitute for that in plasma. When assessing the blood Cu pool as part of the diagnosis of Cu-responsive disease in sheep, the concentration of Cu in plasma should be measured in preference to that of serum. We suggest that a range of 4.5 to 9 micromol/L in plasma be used to define marginal Cu status in sheep.

  8. Influence of the Efavirenz Micronization on Tableting and Dissolution

    PubMed Central

    Pinto, Eduardo Costa; do Carmo, Flávia Almada; da Silva Honório, Thiago; da Silva Ascenção Barros, Rita de Cássia; Castro, Helena Carla Rangel; Rodrigues, Carlos Rangel; Esteves, Valéria Sant'Anna Dantas; Rocha, Helvécio Vinícius Antunes; de Sousa, Valeria Pereira; Cabral, Lucio Mendes

    2012-01-01

    The purpose of this study was to propose an analytical procedure that provides the effects of particle size and surface area on dissolution of efavirenz. Five different batches obtained by different micronization processes and with different particle size distribution and surface area were studied. The preformulation studies and dissolution curves were used to confirm the particle size distribution effect on drug solubility. No polymorphic variety or amorphization was observed in the tested batches and the particle size distribution was determined as directly responsible for the improvement of drug dissolution. The influence of the preparation process on the tablets derived from efavirenz was observed in the final dissolution result in which agglomeration, usually seen in non-lipophilic micronized material, was avoided through the use of an appropriate wet granulation method. For these reasons, micronization may represent one viable alternative for the formulation of brick dust drugs. PMID:24300301

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

    PubMed

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

    2014-01-01

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

  10. Bayesian network analyses of resistance pathways against efavirenz and nevirapine.

    PubMed

    Deforche, Koen; Camacho, Ricardo J; Grossman, Zehave; Soares, Marcelo A; Van Laethem, Kristel; Katzenstein, David A; Harrigan, P Richard; Kantor, Rami; Shafer, Robert; Vandamme, Anne-Mieke

    2008-10-18

    To clarify the role of novel mutations selected by treatment with efavirenz or nevirapine, and investigate the influence of HIV-1 subtype on nonnucleoside reverse transcriptase inhibitor (nNRTI) resistance pathways. By finding direct dependencies between treatment-selected mutations, the involvement of these mutations as minor or major resistance mutations against efavirenz, nevirapine, or coadministrated nucleoside analogue reverse transcriptase inhibitors (NRTIs) is hypothesized. In addition, direct dependencies were investigated between treatment-selected mutations and polymorphisms, some of which are linked with subtype, and between NRTI and nNRTI resistance pathways. Sequences from a large collaborative database of various subtypes were jointly analyzed to detect mutations selected by treatment. Using Bayesian network learning, direct dependencies were investigated between treatment-selected mutations, NRTI and nNRTI treatment history, and known NRTI resistance mutations. Several novel minor resistance mutations were found: 28K and 196R (for resistance against efavirenz), 101H and 138Q (nevirapine), and 31L (lamivudine). Robust interactions between NRTI mutations (65R, 74V, 75I/M, and 184V) and nNRTI resistance mutations (100I, 181C, 190E and 230L) may affect resistance development to particular treatment combinations. For example, an interaction between 65R and 181C predicts that the nevirapine and tenofovir and lamivudine/emtricitabine combination should be more prone to failure than efavirenz and tenofovir and lamivudine/emtricitabine. Bayesian networks were helpful in untangling the selection of mutations by NRTI versus nNRTI treatment, and in discovering interactions between resistance mutations within and between these two classes of inhibitors.

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

    NASA Astrophysics Data System (ADS)

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

    2004-01-01

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

  12. AIDS Diarrhea and Antiretroviral Drug Concentrations: A Matched-Pair Cohort Study in Port au Prince, Haiti

    PubMed Central

    Dillingham, Rebecca; Leger, Paul; Beauharnais, Carole-Anne; Miller, Erica; Kashuba, Angela; Jennings, Steven; Dupnik, Kathryn; Samie, Amidou; Eyma, Etna; Guerrant, Richard; Pape, Jean; Fitzgerald, Daniel

    2011-01-01

    Diarrhea in patients with acquired immunodeficiency syndrome (AIDS) may cause malabsorption of medications and failure of antiretroviral therapy (ART). We prospectively evaluated human immunodeficiency virus-1 (HIV-1)-infected patients with and without chronic diarrhea initiating ART in Haiti. We report mean plasma antiretroviral concentrations at 2 and 4 weeks. We measured plasma HIV-1 RNA levels at four points. Fifty-two HIV-1-infected patients (26 matched pairs) were enrolled. No differences in antiretroviral concentrations were detected. At week 24, 18/25 (72%) cases and 16/24 (68%) controls had undetectable plasma HIV-1 RNA levels (P = 0.69). Patients with plasma HIV-1 RNA levels > 50 copies/mL at week 24 had lower early efavirenz concentrations than patients with undetectable HIV-1 RNA (2,621 ng/mL versus 5,278 ng/mL; P = 0.02). Diarrhea at ART initiation does not influence plasma concentrations of the medications evaluated. Virologic outcome at Week 24 does correlate with efavirenz concentrations early in therapy but not with the presence of chronic diarrhea. PMID:21633022

  13. Efficacy and safety of efavirenz 400 mg daily versus 600 mg daily: 96-week data from the randomised, double-blind, placebo-controlled, non-inferiority ENCORE1 study.

    PubMed

    Carey, Dianne; Puls, Rebekah; Amin, Janaki; Losso, Marcelo; Phanupak, Praphan; Foulkes, Sharne; Mohapi, Lerato; Crabtree-Ramirez, Brenda; Jessen, Heiko; Kumar, Suresh; Winston, Alan; Lee, Man-Po; Belloso, Waldo; Cooper, David A; Emery, Sean

    2015-07-01

    The week 48 primary analysis of the ENCORE1 trial established the virological non-inferiority and safety of efavirenz 400 mg compared with the standard 600 mg dose, combined with tenofovir and emtricitabine, as first-line HIV therapy. This 96-week follow-up of the trial assesses the durability of efficacy and safety of this treatment over 96 weeks. ENCORE1 was a double-blind, placebo-controlled, non-inferiority trial done at 38 clinical sites in 13 countries. HIV-infected adult patients (≥16 years of age) with no previous antiretroviral therapy, a CD4 cell count of 50-500 cells per μL, and plasma HIV-1 viral load of at least 1000 copies per mL were randomly assigned (1:1) by an electronic case report form to receive fixed-dose daily tenofovir 300 mg and emtricitabine 200 mg plus efavirenz either 400 mg daily or 600 mg daily. Participants, physicians, and all other trial staff were masked to treatment assignment. Randomisation was stratified by HIV-1 viral load at baseline (≤ or >100 000 copies per mL). The primary endpoint was the difference in the proportions of patients in the two treatment groups with a plasma HIV-1 viral load below 200 copies per mL at week 96. Treatment groups were deemed to be non-inferior if the lower limit of the 95% CI for the difference in viral load was above -10% by modified intention-to-treat analysis. Non-inferiority was assessed in the modified intention-to-treat, per-protocol, and non-completer=failure (NC=F) populations. Adverse events and serious adverse events were summarised by treatment group. This study is registered with ClinicalTrials.gov, number NCT01011413. Between Aug 24, 2011, and March 19, 2012, 636 eligible participants were enrolled and randomly assigned to the two treatment groups (324 to efavirenz 400 mg and 312 to efavirenz 600 mg). The intention-to-treat population who received at least one dose of study drug comprised 630 patients: 321 in the efavirenz 400 mg group and 309 in the efavirenz 600 mg group

  14. Modeling transportation of efavirenz: inference on possibility of mixed modes of transportation and kinetic solubility.

    PubMed

    Nemaura, Tafireyi

    2015-01-01

    Understanding drug transportation mechanisms in the human body is of paramount importance in modeling Pharmacokinetic-Pharmacodynamic relationships. This work gives a novel general model of efavirenz transportation projections based on concentrations simulated from patients on a dose of 600 mg. The work puts forward a proposition that transportation can wholly be modeled by concentration and time in a uniform volumetric space. Furthermore, movement entities are used to inform the state of "kinetic solubility" of a solution. There is use of Ricker's model, and forms of the Hill's equation in modeling transportation. Characterization on the movement rates of solution particle are suggested in relation to advection rate of solution particle. At turning points on the transportation rate of solution particle vs. concentration curve, a suggestion of possibly change of dominance in the mode of transportation and saturation is made. There are four movement rates postulated at primary micro-level transportation, that are attributed to convection, diffusion [passive transportation (EI )] and energy dependent system transportation (ED ) in relation to advection. Furthermore, a new parameter is introduced which is defined as an advection rate constant of solution particle. It is postulated to be dependent on two rate constants of solution particle, that is a convection rate constant of solution particle and a saturable transportation rate constant of solution particle. At secondary micro-level transportation, the results show convection as sum of advection and saturable transportation. The kinetics of dissolution of efavirenz in the solution space is postulated. Relatively, a good level of kinetics of dissolution is projected in the concentration region 0 - 32.82 μg/ml.

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

    PubMed

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

    2016-12-01

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

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

    PubMed

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

    2014-08-01

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

  17. Lutein Supplementation Increases Breast Milk and Plasma Lutein Concentrations in Lactating Women and Infant Plasma Concentrations but Does Not Affect Other Carotenoids123

    PubMed Central

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

    2014-01-01

    Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2–3 mo postpartum. Lutein is the dominant carotenoid in the infant brain and the major carotenoid found in the retina of the eye. Eighty-nine lactating women 4–6 wk postpartum were randomly assigned to be administered either 0 mg/d of lutein (placebo), 6 mg/d of lutein (low-dose), or 12 mg/d of lutein (high-dose). The supplements were consumed for 6 wk while mothers followed their usual diets. Breast milk carotenoids were measured weekly by HPLC, and maternal plasma carotenoid concentrations were measured at the beginning and end of the study. Infant plasma carotenoid concentrations were assessed at the end of the study. No significant differences were found between dietary lutein + zeaxanthin intake and carotenoid concentrations in breast milk and plasma or body mass index at baseline. Total lutein + zeaxanthin concentrations were greater in the low- and high-dose–supplemented groups than in the placebo group in breast milk (140% and 250%, respectively; P < 0.0001), maternal plasma (170% and 250%, respectively; P < 0.0001), and infant plasma (180% and 330%, respectively; P < 0.05). Lutein supplementation did not affect other carotenoids in lactating women or their infants. Lactating women are highly responsive to lutein supplementation, which affects plasma lutein concentrations in the infant. This trial was registered at clinicaltrials.gov as NCT01747668. PMID:24899160

  18. Plasma noradrenaline concentration and blood pressure in essential hypertension, phaeochromocytoma and depression.

    PubMed

    Louis, W J; Doyle, A E; Anavekar, S N

    1975-06-01

    1. Mean plasma noradrenaline concentration was elevated in forty-four patients with established essential hypertension. Eighteen of the hypertensive patients had resting plasma noradrenaline concentrations in the normal range. 2. Patients with endogenous depression had higher mean plasma noradrenaline concentrations but significantly lower blood pressure than patients with essential hypertension. 3. Patients with phaeochromocytoma had plasma noradrenaline concentrations twenty-eight times greater than those found in essential hypertension, but blood pressures were less than 20% higher. 4. It is concluded that excess of sympathetic drive only partly explains the level of the blood pressure in essential hypertension.

  19. Efavirenz and Metabolites in Cerebrospinal Fluid: Relationship with CYP2B6 c.516G→T Genotype and Perturbed Blood-Brain Barrier Due to Tuberculous Meningitis

    PubMed Central

    Chau, Tran Thi Hong; Fisher, Martin; Nelson, Mark; Winston, Alan; Else, Laura; Carr, Daniel F.; Taylor, Steven; Ustianowski, Andrew; Back, David; Pirmohamed, Munir; Solomon, Tom; Farrar, Jeremy; Törok, M. Estée; Khoo, Saye

    2016-01-01

    Efavirenz (EFZ) has been associated with neuropsychiatric side effects. Recently, the 8-hydroxy-EFZ (8OH-EFZ) metabolite has been shown to be a potent neurotoxin in vitro, inducing neuronal damage at concentrations of 3.3 ng/ml. EFZ induced similar neuronal damage at concentrations of 31.6 ng/ml. We investigated the effect of genotype and blood-brain barrier integrity on EFZ metabolite concentrations in cerebrospinal fluid (CSF). We measured CSF drug concentrations in subjects from two separate study populations: 47 subjects with tuberculous meningitis (TBM) coinfection in Vietnam receiving 800 mg EFZ with standard antituberculous treatment and 25 subjects from the PARTITION study in the United Kingdom without central nervous system infection receiving 600 mg EFZ. EFZ and metabolite concentrations in CSF and plasma were measured and compared with estimates of effectiveness and neurotoxicity from available published in vitro and in vivo data. The effect of the CYP2B6 c.516G→T genotype (GG genotype, fast EFV metabolizer status; GT genotype, intermediate EFV metabolizer status; TT genotype, slow EFV metabolizer status) was examined. The mean CSF concentrations of EFZ and 8OH-EFZ in the TBM group were 60.3 and 39.3 ng/ml, respectively, and those in the no-TBM group were 15.0 and 5.9 ng/ml, respectively. Plasma EFZ and 8OH-EFZ concentrations were similar between the two groups. CSF EFZ concentrations were above the in vitro toxic concentration in 76% of samples (GG genotype, 61%; GT genotype, 90%; TT genotype, 100%) in the TBM group and 13% of samples (GG genotype, 0%; GT genotype, 18%; TT genotype, 50%) in the no-TBM group. CSF 8OH-EFZ concentrations were above the in vitro toxic concentration in 98% of the TBM group and 87% of the no-TBM group; levels were independent of genotype but correlated with the CSF/plasma albumin ratio. Potentially neurotoxic concentrations of 8OH-EFZ are frequently observed in CSF independently of the CYP2B6 genotype, particularly in those

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

    PubMed

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

    2014-01-01

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

  1. Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase.

    PubMed

    Brehm, Jessica H; Lalama, Christina M; Hughes, Michael D; Haubrich, Richard; Riddler, Sharon A; Sluis-Cremer, Nicolas; Mellors, John W

    2011-04-01

    It is uncertain how often mutations in the connection or RNase H domains of HIV-1 reverse transcriptase (RT) emerge with failure of first-line antiretroviral therapy. Full-length RT sequences in plasma obtained pretherapy and at virologic failure were compared in 53 patients on first-line efavirenz-containing regimens from AIDS Clinical Trials Group study A5142. HIV-1 was mostly subtype B (48 of 53). Mutations in the polymerase but not in connection or RNase H domains of RT increased in frequency between pretherapy and failure (K103N, P = 0.001; M184I/V, P = 0.016). Selection of mutations in C-terminal domains of RT is not common with early failure of efavirenz-containing regimens.

  2. Intracellular CD3+ T Lymphocyte Teriflunomide Concentration Is Poorly Correlated with and Has Greater Variability Than Unbound Plasma Teriflunomide Concentration.

    PubMed

    Hopkins, Ashley M; Moghaddami, Mahin; Foster, David J R; Proudman, Susanna M; Upton, Richard N; Wiese, Michael D

    2017-01-01

    Leflunomide's active metabolite teriflunomide inhibits dihydro-oroate dehydrogenase, an enzyme essential to proliferation of T lymphocytes. As teriflunomide must reach the target site to have this effect, this study assessed the distribution of teriflunomide into T lymphocytes, as intracellular concentrations may be a superior response biomarker to plasma concentrations. CD3 MicroBeads (Miltenyi Biotec, Bergisch Gladbach, Germany) were used to extract CD3(+) T cells from the peripheral blood of patients with rheumatoid arthritis who were taking a stable dose of leflunomide. Unbound plasma and intra-CD3(+) T cell teriflunomide concentrations were quantified using liquid chromatography-mass spectrometry. Concentration (log transformed) and partition differences were assessed through paired Student t tests. Sixteen patients provided plasma steady-state teriflunomide samples, and eight provided a sample 6-12 weeks later. At time-point one, the geometric mean teriflunomide concentration (range) in CD3(+) T cells was 18.12 μg/L (6.15-42.26 μg/L) compared with 69.75 μg/L (32.89-263.1 μg/L) unbound in plasma (P < 0.001). The mean partition coefficient (range) for unbound plasma teriflunomide into CD3(+) T cells was 0.295 (0.092-0.632), which was significantly different from unity (P < 0.001). The median (range) change in teriflunomide concentration between the two time points was 14% (-10% to 40%) in unbound plasma and -29% (-69 to 138%) for CD3(+) T cells. Because teriflunomide concentrations in CD3(+) T cells were lower and displayed a higher intraindividual variability than the unbound plasma concentrations, its applicability as a therapeutic drug-monitoring marker may be limited. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Improvement of Depression and Anxiety After Discontinuation of Long- Term Efavirenz Treatment.

    PubMed

    Mothapo, Khutso M; Schellekens, Arnt; van Crevel, Reinout; Keuter, Monique; Grintjes-Huisman, K; Koopmans, Peter; van der Ven, Andre

    2015-01-01

    Neuropsychiatric symptoms in human immunodeficiency virus (HIV)-infected patients may be a late complication of efavirenz treatment. This study: 1) assessed the level of neuropsychiatric symptoms in HIV-infected patients on long-term efavirenz therapy; 2) explored the effect of a switch to non-efavirenz containing anti-retroviral treatment on neuropsychiatric symptoms. A consecutive series of 47 HIV-infected participants on long-term efavirenz treatment were included in an observational clinical trial. Participants completed three self-report questionnaires on neuropsychiatric symptoms. Patients switching to a non-efavirenz regimen were retested 2 weeks and 3 months after switching. Data were analyzed using repeated measures ANOVA to assess the effect of switching over time. A change in the percentage of patients scoring above norm scores after switching was analyzed using Chi square. Neuropsychiatric symptoms were common among HIV-infected patients on long-term efavirenz therapy, mainly depression, anxiety, stress, insufficiency in thinking and paranoia. After switching, these symptoms improved significantly to (near) normal levels. Our results show that neuropsychiatric symptoms are common among HIV-infected subjects and may be caused by long-term efavirenz use. Neuropsychiatric assessment, such as the Depression, Anxiety and Stress scale and Symptom Checklist 90, can identify those that may benefit from the discontinuation of efavirenz.

  4. Urinary strong ion difference is a major determinant of plasma chloride concentration changes in postoperative patients

    PubMed Central

    Masevicius, Fabio Daniel; Vazquez, Alejandro Risso; Enrico, Carolina; Dubin, Arnaldo

    2013-01-01

    Objective To show that alterations in the plasma chloride concentration ([Cl-]plasma) during the postoperative period are largely dependent on the urinary strong ion difference ([SID]urine=[Na+]urine+[K+]urine-[Cl-]urine) and not on differences in fluid therapy. Methods Measurements were performed at intensive care unit admission and 24 hours later in a total of 148 postoperative patients. Patients were assigned into one of three groups according to the change in [Cl-]plasma at the 24 hours time point: increased [Cl-]plasma (n=39), decreased [Cl-]plasma (n=56) or unchanged [Cl-]plasma (n=53). Results On admission, the increased [Cl-]plasma group had a lower [Cl-]plasma (105±5 versus 109±4 and 106±3mmol/L, p<0.05), a higher plasma anion gap concentration ([AG]plasma) and a higher strong ion gap concentration ([SIG]). After 24 hours, the increased [Cl-]plasma group showed a higher [Cl-]plasma (111±4 versus 104±4 and 107±3mmol/L, p<0.05) and lower [AG]plasma and [SIG]. The volume and [SID] of administered fluids were similar between groups except that the [SID]urine was higher (38±37 versus 18±22 and 23±18mmol/L, p<0.05) in the increased [Cl-]plasma group at the 24 hours time point. A multiple linear regression analysis showed that the [Cl-]plasma on admission and [SID]urine were independent predictors of the variation in [Cl-]plasma 24 hours later. Conclusions Changes in [Cl-]plasma during the first postoperative day were largely related to [SID]urine and [Cl-]plasma on admission and not to the characteristics of the infused fluids. Therefore, decreasing [SID]urine could be a major mechanism for preventing the development of saline-induced hyperchloremia. PMID:24213082

  5. Seasonal variation in plasma free normetanephrine concentrations: implications for biochemical diagnosis of pheochromocytoma.

    PubMed

    Pamporaki, Christina; Bursztyn, Michael; Reimann, Manja; Ziemssen, Tjalf; Bornstein, Stefan R; Sweep, Fred C G J; Timmers, Henri; Lenders, Jacques W M; Eisenhofer, Graeme

    2014-03-01

    Higher plasma concentrations of catecholamines in winter than in summer have been established, but whether this impacts the plasma concentrations of metanephrines used for the diagnosis of pheochromocytoma is unknown. In this study, we examined seasonal variations in the plasma concentrations of metanephrines, the impact of this on diagnostic test performance and the influences of forearm warming ('arterialization' of venous blood) on blood flow and measured concentrations. The measurements of the plasma concentrations of metanephrines were recorded from 4052 patients tested for pheochromocytoma at two clinical centers. Among these patients, 107 had tumors. An additional 26 volunteers were enrolled for the measurements of plasma metanephrines and forearm blood flow before and after forearm warming. There was no seasonal variation in the plasma concentrations of metanephrines among patients with pheochromocytoma, whereas among those without tumors, the plasma concentrations of normetanephrine were higher (P<0.0001) in winter than in summer. Lowest concentrations of normetanephrine were measured in July, with those recorded from December to April being more than 21% higher (P<0.0001). These differences resulted in a twofold higher (P=0.0012) prevalence of false-positive elevations of normetanephrine concentrations in winter than in summer, associated with a drop in overall diagnostic specificity from 96% in summer to 92% in winter (P=0.0010). Forearm warming increased blood flow and lowered (P=0.0020) plasma normetanephrine concentrations. The plasma concentrations of normetanephrine are subject to seasonal variation with a resulting higher prevalence of false-positive results in winter than in summer. Lowered plasma concentrations of normetanephrine with forearm warming suggest an effect of temperature. These results have implications for considerations of temperature to minimize false-positive results.

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

    PubMed

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

    1979-11-01

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

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

    NASA Technical Reports Server (NTRS)

    Tacker, M. M.

    1975-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Tacker, M. M.

    1975-01-01

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

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

    PubMed Central

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

    1988-01-01

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

  10. Efavirenz-induced gynecomastia in a prepubertal girl with human immunodeficiency virus infection: a case report

    PubMed Central

    2013-01-01

    Background Prepubertal gynecomastia is a rare condition and most frequently classified as idiopathic. In HIV-infected adults gynecomastia is a recognised but infrequent side-effect of antiretroviral treatment (ART) and mostly attributed to efavirenz use. Gynecomastia should be distinguished from pseudogynecomastia as part of the lipodystrophy syndrome caused by Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to avoid incorrect substitution of drugs. In the medical literature only five cases of prepubertal gynecomastia in children taking ART are described and underlying pathogenesis was unknown. The occurrence of adverse effects of ART may interfere with therapy adherence and long-term prognosis and for that reason requires attention. We report the first case of prepubertal gynecomastia in a young girl attributed to efavirenz use. Case presentation A seven-year-old African girl presented with true gynecomastia four months after initiation on ART (abacavir, lamivudine, efavirenz). History, physical examination and laboratory tests excluded known causes of gynecomastia and efavirenz was considered as the most likely cause. Six weeks after withdrawal of efavirenz the breast enlargement had completely resolved. Conclusions Efavirenz-induced gynecomastia may occur in children as well as in adults. With the increasing access to ART, the possibility of efavirenz-exposure and the potential occurrence of its associated side-effects may be high. In resource-poor settings, empirical change from efavirenz to nevirapine may be considered, providing no other known or alarming cause is identified, as efavirenz-induced gynecomastia can resolve quickly after withdrawal of the drug. Timely recognition of gynecomastia as a side-effect of efavirenz is important in order to intervene while the condition may still be reversible, to sustain adherence to ART and to maintain the sociopsychological health of the child. PMID:23941256

  11. An Expanded Analysis of Pharmacogenetics Determinants of Efavirenz Response that Includes 3′-UTR Single Nucleotide Polymorphisms among Black South African HIV/AIDS Patients

    PubMed Central

    Swart, Marelize; Evans, Jonathan; Skelton, Michelle; Castel, Sandra; Wiesner, Lubbe; Smith, Peter J.; Dandara, Collet

    2016-01-01

    Introduction: Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor prescribed as part of first-line highly active antiretroviral therapy (HAART) in South Africa. Despite administration of fixed doses of EFV, inter-individual variability in plasma concentrations has been reported. Poor treatment outcomes such as development of adverse drug reactions or treatment failure have been linked to EFV plasma concentrations outside the therapeutic range (1–4 μg/mL) in some studies. The drug metabolizing enzyme (DME), CYP2B6, is primarily responsible for EFV metabolism with minor contributions by CYP1A2, CYP2A6, CYP3A4, CYP3A5, and UGT2B7. DME coding genes are also regulated by microRNAs through targeting the 3′-untranslated region. Expanded analysis of 30 single nucleotide polymorphisms (SNPs), including those in the 3′-UTR, was performed to identify pharmacogenetics determinants of EFV plasma concentrations in addition to CYP2B6 c.516G>T and c.983T>C SNPs. Methods: SNPs in CYP1A2, CYP2B6, UGT2B7, and NR1I2 (PXR) were selected for genotyping among 222 Bantu-speaking South African HIV-infected patients receiving EFV-containing HAART. This study is a continuation of earlier pharmacogenetics studies emphasizing the role of genetic variation in the 3′-UTR of genes which products are either pharmacokinetic or pharmacodynamic targets of EFV. Results: Despite evaluating thirty SNPs, CYP2B6 c.516G>T and c.983T>C SNPs remain the most prominent predictors of EFV plasma concentration. Conclusion: We have shown that CYP2B6 c.516G>T and c.983T>C SNPs are the most important predictors of EFV plasma concentration after taking into account all other SNPs, including genetic variation in the 3′-UTR, and variables affecting EFV metabolism. PMID:26779253

  12. Venlafaxine and O-desmethylvenlafaxine concentrations in plasma and cerebrospinal fluid.

    PubMed

    Paulzen, Michael; Groppe, Sarah; Tauber, Simone C; Veselinovic, Tanja; Hiemke, Christoph; Gründer, Gerhard

    2015-01-01

    To investigate whether drug concentrations of venlafaxine and its metabolite O-desmethylvenlafaxine in plasma can be considered as a surrogate marker of concentrations in brain/cerebrospinal fluid (CSF). For therapeutic drug monitoring purposes, plasma and CSF concentrations of venlafaxine and O-desmethylvenlafaxine were measured between November 2011 and August 2013 in 16 depressive inpatients (ICD-10 diagnoses) who were treated with daily doses of venlafaxine extended release (dose range, 75-225 mg). Daily doses were correlated with plasma and CSF levels. The correlation between venlafaxine, O-desmethylvenlafaxine, and the active moiety (AM) in plasma and CSF was calculated. Venlafaxine in plasma (P = .005) and CSF (P = .023) correlated significantly with the daily dose, while O-desmethylvenlafaxine and the active moiety (AM = venlafaxine + O-desmethylvenlafaxine) did not. The correlation between venlafaxine, O-desmethylvenlafaxine, and the AM in plasma and CSF was highly significant (P < .001). The calculated CSF/plasma ratio was 0.74 for venlafaxine, 0.88 for O-desmethylvenlafaxine, and 0.84 for the AM. Venlafaxine and O-desmethylvenlafaxine were found to penetrate well into CSF in patients, which indicated good availability of the drug in the brain, although the findings on CSF concentrations do not allow calculation of concentrations at the target structure within the brain. CSF/plasma ratios for venlafaxine and its metabolite were high probably due to low plasma protein binding. The poor correlation of dose to concentrations in body fluids and the highly significant correlation of plasma to CSF concentrations indicate that plasma concentration is a much better marker of drug concentration in brain than the dose. © Copyright 2015 Physicians Postgraduate Press, Inc.

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

    PubMed

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

    2015-10-05

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

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

    PubMed

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

    2016-03-01

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

  15. Seminal plasma hormone concentration after oral application of progesterone.

    PubMed

    Feuring, M; Bertsch, T; Tran, B M; Rossol-Haseroth, K; Losel, R; Tillmann, H C; Schultz, A; Weigel, M; Wehling, M

    2002-02-01

    Previous studies have revealed beneficial in vitro effects of progesterone on sperm function. The aim of this pilot study was to prove if orally given micronized progesterone leads to elevations in progesterone and/or 17alpha-hydroxyprogesterone levels in seminal plasma, since higher seminal plasma levels of these hormones could possibly have a beneficial effect on sperm function as seen in in vitro investigations. Multiple application of micronized progesterone given over 4 days (daily dose 400 mg) to 6 healthy subjects resulted in elevated seminal plasma levels of progesterone (10.90 +/- 9.02 nmol/l vs. 1.43 +/- 0.56 nmol/l, p = 0.04) and 17alpha-hydroxyprogesterone (3.09 +/- 1.72 nmol/l vs. 1.62 +/- 1.26 nmol/l, p = 0.04) whereas no significant difference could be found in testosterone levels (34.82 +/- 13.00 vs. 30.91 +/- 8.56 nmol/l, p = 0.43). In contrast, androstendione levels in seminal plasma were reduced (2.68 1.28 nmol/l vs. 3.65 +/- 1.36 nmol/l, p = 0.01). Although micronized progesterone is rapidly metabolized, oral application resulted in pronounced elevations of progesterone and 17alpha-hydroxyprogesterone in seminal plasma. Further studies will show if oral application of micronized progesterone can induce beneficial effects on sperm function such as those seen in in vitro investigations.

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

    PubMed

    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.

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

    PubMed

    Sigg, C; Brüngger, A; Rakosi, T

    1994-01-01

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

  18. Dietary salt influences postprandial plasma sodium concentration and systolic blood pressure.

    PubMed

    Suckling, Rebecca J; He, Feng J; Markandu, Nirmala D; MacGregor, Graham A

    2012-02-01

    The plasma sodium concentration has a direct effect on blood pressure in addition to its effects on extracellular volume regulated through changes in the endothelium. The mechanism for elevated blood pressure seen with habitually increased salt intake is unclear, especially the effect of salt in a single meal on plasma sodium concentration and blood pressure. To resolve this we compared the effect of soup with or without 6 g of salt (an amount similar to that in a single meal) on the plasma sodium concentration and blood pressure in 10 normotensive volunteers using a randomized, crossover design. The plasma sodium concentration was significantly increased by 3.13±0.75 mmol/l with salted compared with unsalted soup. Blood pressure increased in volunteers ingesting soup with added salt, and there was a significant positive correlation between plasma sodium concentration and systolic blood pressure. A 1-mmol/l increase in plasma sodium was associated with a 1.91-mm Hg increase in systolic blood pressure by linear regression. Thus, changes in plasma sodium concentration occur each time a meal containing salt is consumed. A potential mechanism for the changes in blood pressure seen with salt intake may be through its effects on plasma sodium concentration.

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

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

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

    PubMed

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

    2006-01-01

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

  1. The effect of interval versus continuous exercise on plasma leptin and ghrelin concentration in young trotters.

    PubMed

    Kowalik, S; Kedzierski, W

    2011-01-01

    The effect of interval vs. continuous exercise on plasma leptin and ghrelin concentration in young Standardbred horses was studied. The experiment was conducted on 27 trotters, in the age between 2 and 3 years. They were divided into two groups according to the type of exercise. Blood samples were collected through jugular venipuncture in the following experimental conditions: at rest, immediately after exercise and 30 minutes after the end of the effort. Plasma leptin and ghrelin concentrations were determined using RIA tests. The continuous exercise induced an increase in plasma leptin concentration whereas the interval type of exercise did not influence the level of this hormone (3.47 +/- 0.78 vs. 4.07 +/- 0.94 and 2.31 +/- 0.15 vs. 2.36 +/- 0.21 ng/mL, respectively). The plasma ghrelin concentration measured after the continuous exercise, significantly increased (720 +/- 27.4 vs. 814 +/- 13.8; p < or = 0.05) whereas concentration of this hormone assessed after the interval exercise, significantly dropped (982 +/- 56.5 vs. 842 +/- 35.6 pg/mL; p < or = 0.05). The changes in plasma ghrelin concentration measured after the end of the effort correlated inversely with blood lactic acid concentration. In conclusion, the obtained results showed that medium-intensive type of exercise, such as trot, interval or continuous, slightly affected plasma leptin level but significantly affected plasma ghrelin concentration in young Standardbred trotters.

  2. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans.

    PubMed

    Stefan, Norbert; Vozarova, Barbora; Funahashi, Tohru; Matsuzawa, Yuji; Weyer, Christian; Lindsay, Robert S; Youngren, Jack F; Havel, Peter J; Pratley, Richard E; Bogardus, Clifton; Tataranni, P Antonio

    2002-06-01

    Adiponectin, the most abundant adipose-specific protein, has been found to be negatively associated with degree of adiposity and positively associated with insulin sensitivity in Pima Indians and other populations. Moreover, adiponectin administration to rodents has been shown to increase insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and also increase whole-body insulin sensitivity. To further characterize the relationship between plasma adiponectin concentration and insulin sensitivity in humans, we examined 1) the cross-sectional association between plasma adiponectin concentration and skeletal muscle IR tyrosine phosphorylation and 2) the prospective effect of plasma adiponectin concentration at baseline on change in insulin sensitivity. Fasting plasma adiponectin concentration, body composition (hydrodensitometry or dual energy X-ray absorptiometry), insulin sensitivity (insulin-stimulated glucose disposal, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) were measured in 55 Pima Indians (47 men and 8 women, aged 31 +/- 8 years, body fat 29 +/- 8% [mean +/- SD]; 50 with normal glucose tolerance, 3 with impaired glucose tolerance, and 2 with diabetes). Group 1 (19 subjects) underwent skeletal muscle biopsies for the measurement of basal and insulin-stimulated tyrosine phosphorylation of the IR (stimulated by 100 nmol/l insulin). The fold increase after insulin stimulation was calculated as the ratio between maximal and basal phosphorylation. Group 2 (38 subjects) had follow-up measurements of insulin-stimulated glucose disposal. Cross-sectionally, plasma adiponectin concentration was positively associated with insulin-stimulated glucose disposal (r = 0.58, P < 0.0001) and negatively associated with percent body fat (r = -0.62, P < 0.0001) in the whole group. In group 1 plasma adiponectin was negatively associated with the basal (r = -0.65, P = 0.003) and positively associated with the fold increase in IR

  3. Plasma prion protein concentration and progression of Alzheimer disease

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-04-01

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

  5. The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda.

    PubMed

    Bartelink, Imke H; Savic, Rada M; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J; Capparelli, Edmund; Jullien, Vincent; Young, Sera L; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

    2015-03-01

    Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Sparse dried blood spot samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from 3 resource-rich countries (RRC) were utilized to develop the PK models. Concentrations in 330 dried blood spot from 163 Ugandan children aged 0.7-7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5-12 years. Among Ugandan children, 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008), respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (P<0.001) with a trend toward greater bioavailability when malnourished. Children receiving LPV, EFV or NVP had comparable risk of virologic failure. Among children on NVP, low height and weight for age Z scores were associated with reduced risk of virologic failure (P=0.034, P=0.068, respectively). Ugandan children demonstrated lower EFV and LPV and higher NVP exposure compared to children in RRC, perhaps reflecting the consequence of malnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessments, to further assess causes of virologic failure in Ugandan children.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed

    Hammarlund-Udenaes, Margareta

    2010-03-01

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

  9. Variable aromatase inhibitor plasma concentrations do not correlate with circulating estrogen concentrations in post-menopausal breast cancer patients.

    PubMed

    Hertz, Daniel L; Speth, Kelly A; Kidwell, Kelley M; Gersch, Christina L; Desta, Zeruesenay; Storniolo, Anna Maria; Stearns, Vered; Skaar, Todd C; Hayes, Daniel F; Henry, N Lynn; Rae, James M

    2017-06-22

    The aromatase inhibitors (AI) exemestane (EXE), letrozole (LET), and anastrozole suppress estrogen biosynthesis, and are effective treatments for estrogen receptor (ER)-positive breast cancer. Prior work suggests that anastrozole blood concentrations are associated with the magnitude of estrogen suppression. The objective of this study was to determine whether the magnitude of estrogen suppression, as determined by plasma estradiol (E2) concentrations, in EXE or LET treated patients is associated with plasma AI concentrations. Five hundred post-menopausal women with ER-positive breast cancer were enrolled in the prospective Exemestane and Letrozole Pharmacogenetic (ELPh) Study conducted by the COnsortium on BReast cancer phArmacogomics (COBRA) and randomly assigned to either drug. Estrogen concentrations were measured at baseline and after 3 months of AI treatment and drug concentrations were measured after 1 or 3 months. EXE or LET concentrations were compared with 3-month E2 concentration or the change from baseline to 3 months using several complementary statistical procedures. Four-hundred patients with on-treatment E2 and AI concentrations were evaluable (EXE n = 200, LET n = 200). Thirty (7.6%) patients (EXE n = 13, LET n = 17) had 3-month E2 concentrations above the lower limit of quantification (LLOQ) (median: 4.75; range: 1.42-63.8 pg/mL). EXE and LET concentrations were not associated with on-treatment E2 concentrations or changes in E2 concentrations from baseline (all p > 0.05). Steady-state plasma AI concentrations do not explain variability in E2 suppression in post-menopausal women receiving EXE or LET therapy, in contrast with prior evidence in anastrozole treated patients.

  10. Population Pharmacokinetics Analysis To Inform Efavirenz Dosing Recommendations in Pediatric HIV Patients Aged 3 Months to 3 Years

    PubMed Central

    Luo, Man; Chapel, Sunny; Sevinsky, Heather; Savant, Ishani; Cirincione, Brenda; Bertz, Richard

    2016-01-01

    Efavirenz (EFV) is a nonnucleoside reverse transcriptase inhibitor approved worldwide for the treatment of HIV in adults and children over 3 years of age or weighing over 10 kg. Only recently EFV was approved in children over 3 months and weighing at least 3.5 kg in the United States and the European Union. The objective of this analysis was to support the selection of an appropriate dose for this younger pediatric population and to explore the impact of CYP2B6 genetic polymorphisms on EFV systemic exposures. A population pharmacokinetic (PPK) model was developed using data from three studies in HIV-1-infected pediatric subjects (n = 168) and one study in healthy adults (n = 24). The EFV concentration-time profile was best described by a two-compartment model with first-order absorption and elimination. Body weight was identified as a significant predictor of efavirenz apparent clearance (CL), oral central volume of distribution (VC), and absorption rate constant (Ka). The typical values of efavirenz apparent CL, VC, oral peripheral volume of distribution (VP), and Ka for a reference pediatric patient were 4.8 liters/h (4.5 to 5.1 liters/h), 84.9 liters (76.8 to 93.0 liters), 287 liters (252.6 to 321.4 liters), and 0.414 h−1 (0.375 to 0.453 h−1), respectively. The final model was used to simulate steady-state efavirenz concentrations in pediatric patients weighing <10 kg to identify EFV doses that produce comparable exposure to adult and pediatric patients weighing ≥10 kg. Results suggest that administration of EFV doses of 100 mg once daily (QD) to children weighing ≥3.5 to <5 kg, 150 mg QD to children weighing ≥5 to <7.5 kg, and 200 mg QD to children weighing ≥7.5 to <10 kg produce exposures within the target range. Further evaluation of the impact of CYP2B6 polymorphisms on EFV PK showed that the identification of CYP2B6 genetic status is not predictive of EFV exposure and thus not informative to guide pediatric dosing regimens. PMID:27067333

  11. Plasma 8-iso-Prostaglandin F2α concentrations and outcomes after acute intracerebral hemorrhage.

    PubMed

    Du, Quan; Yu, Wen-Hua; Dong, Xiao-Qiao; Yang, Ding-Bo; Shen, Yong-Feng; Wang, Hao; Jiang, Li; Du, Yuan-Feng; Zhang, Zu-Yong; Zhu, Qiang; Che, Zhi-Hao; Liu, Qun-Jie

    2014-11-01

    Higher plasma 8-iso-Prostaglandin F2α concentrations have been associated with poor outcome of severe traumatic brain injury. We further investigated the relationships between plasma 8-iso-Prostaglandin F2α concentrations and clinical outcomes in patients with acute intracerebral hemorrhage. Plasma 8-iso-Prostaglandin F2α concentrations of 128 consecutive patients and 128 sex- and gender-matched healthy subjects were measured by enzyme-linked immunosorbent assay. We assessed their relationships with disease severity and clinical outcomes including 1-week mortality, 6-month mortality and unfavorable outcome (modified Rankin Scale score>2). Plasma 8-iso-Prostaglandin F2α concentrations were substantially higher in patients than in healthy controls. Plasma 8-iso-Prostaglandin F2α concentrations were positively associated with National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume using a multivariate linear regression. It emerged as an independent predictor for clinical outcomes of patients using a forward stepwise logistic regression. ROC curves identified the predictive values of plasma 8-iso-Prostaglandin F2α concentrations, and found its predictive value was similar to NIHSS scores and hematoma volumes. However, it just numerically added the predictive values of NIHSS score and hematoma volume. Increased plasma 8-iso-Prostaglandin F2α concentrations are associated with disease severity and clinical outcome after acute intracerebral hemorrhage. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Thermosensitive Gel Containing Cellulose Acetate Phthalate-Efavirenz Combination Nanoparticles for Prevention of HIV-1 Infection.

    PubMed

    Date, Abhijit A; Shibata, Annemaria; McMullen, Emily; La Bruzzo, Krista; Bruck, Patrick; Belshan, Michael; Zhou, You; Destache, Christopher J

    2015-03-01

    The objective of this investigation was to develop and evaluate a nano-microbicide containing a combination of cellulose acetate phthalate (HIV-1 entry inhibitor) and efavirenz (anti-HIV agent) for HIV prophylaxis. Cellulose acetate phthalate-efavirenz combination nanoparticles (CAP-EFV-NPs) were fabricated by the nanoprecipitation method and were characterized for particle size, zeta potential and encapsulation efficiency of efavirenz. CAP-EFV-NPs were incorporated into a thermosensitive gel (CAP-EFV-NP-Gel). CAP-EFV-NPs, CAP-EFV-NP-Gel and efavirenz solution were evaluated for cytotoxicity to HeLa cells and for in vitro short-term (1-day) and long-term (3-day) prophylaxis against HIV-1 infection in TZM-bl cells. CAP-EFV-NPs had size < 100 nm, negative surface charge and encapsulation efficiency of efavirenz was > 98%. CAP-EFV-NPs and CAP-EFV-NP-Gel were significantly less toxic (P < 0.01) to HeLa cells as compared to efavirenz solution. CAP-EFV-NPs showed significantly higher prophylactic activity (P < 0.01) against HIV-1 infection to TZM-bl cells as compared to efavirenz solution and blank CAP nanoparticles. CAP-EFV-NP-Gel can be a promising nano-microbicide for long-term HIV prophylaxis.

  13. Pharmacogenetics of pregnancy-induced changes in efavirenz pharmacokinetics.

    PubMed

    Olagunju, A; Bolaji, O; Amara, A; Else, L; Okafor, O; Adejuyigbe, E; Oyigboja, J; Back, D; Khoo, S; Owen, A

    2015-03-01

    Pregnancy-induced physiological changes alter many drugs' pharmacokinetics. We investigated pregnancy-induced changes in efavirenz pharmacokinetics in 25 pregnant and 19 different postpartum women stratified from 211 HIV-positive women in whom a preliminary pharmacogenetic study had been undertaken. Despite significant changes in CL/F during pregnancy (42.6% increase; P = 0.023), median (range) Cmin was 1,000 ng/mL (429-5,190) with no significant change in Cmax (P = 0.072). However, when stratified for CYP2B6 516G>T (rs3745274) genotype, efavirenz AUC0-24 , Cmax and Cmin were 50.6% (P = 0.0013), 17.2% (P = 0.14), and 61.6% (P = 0.0027) lower during pregnancy (n = 8) compared with postpartum (n = 6) in 516G homozygotes, with values of 25,900 ng.h/mL (21,700-32,600), 2,640 ng/mL (1,260-3,490), and 592 ng/mL (429-917), respectively, and CL/F was 100% higher (P = 0.0013). No changes were apparent in CYP2B6 516 heterozygotes (14 pregnant vs. 7 postpartum). The clinical implications of these findings warrant further investigation.

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

    PubMed Central

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

    1996-01-01

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

  15. Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

    PubMed

    Suzuki, E; Kanba, S; Koshikawa, H; Nibuya, M; Yagi, G; Asai, M

    1996-05-01

    Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were measured, and psychiatric symptoms were scored. In the NDS patients, both positive and negative symptoms improved. However, only the positive symptom scores changed in the DS patients. On day 4, pHVA concentrations of the NDS patients alone were significantly elevated. Plasma bromperidol concentrations did not differ between the groups. These results suggest that bromperidol exerts different effects on negative symptoms and pHVA concentrations between NDS and DS patients, effects that are unrelated to plasma bromperidol concentrations.

  16. Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

    PubMed Central

    Suzuki, E; Kanba, S; Koshikawa, H; Nibuya, M; Yagi, G; Asai, M

    1996-01-01

    Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were measured, and psychiatric symptoms were scored. In the NDS patients, both positive and negative symptoms improved. However, only the positive symptom scores changed in the DS patients. On day 4, pHVA concentrations of the NDS patients alone were significantly elevated. Plasma bromperidol concentrations did not differ between the groups. These results suggest that bromperidol exerts different effects on negative symptoms and pHVA concentrations between NDS and DS patients, effects that are unrelated to plasma bromperidol concentrations. PMID:8935328

  17. Plasma lactate concentrations in free-ranging moose (Alces alces) immobilized with etorphine.

    PubMed

    Haga, Henning A; Wenger, Sandra; Hvarnes, Silje; Os, Oystein; Rolandsen, Christer M; Solberg, Erling J

    2009-11-01

    To investigate plasma lactate concentrations of etorphine-immobilized moose in relation to environmental, temporal and physiological parameters. Prospective clinical study. Fourteen female and five male moose (Alces alces), estimated age range 1-7 years. The moose were darted from a helicopter with 7.5 mg etorphine per animal using projectile syringes and a dart gun. Once immobilized, the moose were approached, a venous blood sample was obtained and vital signs including pulse oximetry were recorded. Diprenorphine was administered to reverse the effects of etorphine. Timing of events, ambient temperature and snow depth were recorded. Blood samples were cooled and centrifuged before plasma was harvested and frozen. The plasma was thawed later and lactate analysed. Data were analysed using descriptive statistics and regression analysis. All animals recovered uneventfully and were alive 12 weeks after immobilization. Mean +/- SD plasma lactate was found to be 9.2 +/- 2.1 mmol L(-1). Plasma lactate concentrations were related positively to snow depth and negatively to time from induction of immobilization to blood sampling. The model that best described the variability in plasma lactate concentrations used induction time (time from firing the dart to the moose being immobilized). The second best model included induction time and snow depth. Plasma lactate concentrations in these etorphine-immobilized moose were in the range reported for other immobilized wild ruminants. Decreasing induction time, which may be related to a more profound etorphine effect, and increasing snow depth possibly may increase plasma lactate concentrations in etorphine-immobilized moose.

  18. Tacrolimus-induced elevation in plasma triglyceride concentrations after administration to renal transplant patients is partially due to a decrease in lipoprotein lipase activity and plasma concentrations.

    PubMed

    Tory, Rita; Sachs-Barrable, Kristina; Goshko, Caylee-Britt; Hill, John S; Wasan, Kishor M

    2009-07-15

    Hyperlipidemia is a frequent and persistent complication in solid organ transplant recipients, leading to the high occurrence of cardiovascular disease in this patient population. Lipid abnormalities including increased total cholesterol, triglycerides (TG), and low-density lipoprotein-cholesterol have been reported frequently in transplantation patients and a variety of immunosuppressive therapies seem to be one of the main factors that influence posttransplant lipidemic profiles. For many years, tacrolimus (TAC) has been used as an immunosuppressive drug in transplantation. The aim of our investigation was to determine the effect of TAC administration on the plasma lipid profile and some key regulatory proteins of plasma lipid metabolism including cholesterol ester transfer protein, hepatic lipase and lipoprotein lipase (LPL) within renal transplant patients. Twenty-five renal transplant patients were recruited and received TAC therapy, of which nine of these patients were treated with statin therapy for dyslipidemia. The effects of TAC on plasma total cholesterol, TG, HDL-C, low-density lipoprotein-cholesterol, cholesterol ester transfer protein, hepatic lipase and LPL concentration and activity were determined from patients plasma samples collected before the transplant surgery (baseline), and weekly for four consecutive weeks after surgery and TAC administration. We observed that TAC significantly increases plasma TG concentrations and reduces LPL plasma concentration and activity in renal transplant patients, independent of any lipid lowering drug treatment patients received. Taken together, these findings suggest that the reduction in LPL activity, partly due to the decrease of plasma LPL concentration after TAC administration may be an explanation for hypertriglyceridemia observed in patients administered TAC.

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

    PubMed

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

    2008-02-01

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

  20. Glycine and ammonia plasma concentrations during sedation with remifentanil in critically ill patients.

    PubMed

    Bonnet, Marie-Pierre; Minville, Vincent; Asehnoune, Karim; Bridoux, Delphine; Poggi-Bach, Joséphine; Duranteau, Jacques; Benhamou, Dan

    2007-07-01

    To investigate glycine and ammonia plasma concentrations during a 72-h remifentanil infusion and the relationship between glycine concentration and remifentanil infusion rate. A prospective open-label observational clinical trial in a trauma and a neurosurgical intensive care unit in a university teaching hospital. Nine consecutive patients requiring sedation and ventilatory support for at least 72 h. One was excluded due to acute cardiac failure. Patients were sedated with remifentanil and propofol. Glycine and ammonia plasma concentrations were measured every 12 h during an intravenous remifentanil infusion performed over 72 h, and 24 h after the end of the infusion. Cumulative remifentanil dose and rate of infusion were recorded for each patient. Clinical and biological signs of glycine toxicity were evaluated. Glycine and ammonia plasma concentrations did not exceed the toxic threshold at any time. Plasma glycine concentration measured at the end of remifentanil infusion was significantly correlated with the mean weighted rate of remifentanil infusion and with the cumulative remifentanil dose. A correlation between plasma glycine concentration and creatinine clearance at the end of remifentanil infusion was also documented. Plasma glycine concentration was correlated with the remifentanil cumulative dose and the infusion rate and did not reach the toxic threshold. As glycine concentration was also correlated with creatinine clearance and because remifentanil was the only source of exogenous glycine, additional data are necessary to ascertain the safety of remifentanil infusion in ICU patients.

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2005-11-01

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

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

    PubMed Central

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

    1984-01-01

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

  4. High plasma uric acid concentration: causes and consequences

    PubMed Central

    2012-01-01

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

  5. The effect of estrogens on plasma ghrelin concentrations in women.

    PubMed

    Dafopoulos, K; Chalvatzas, N; Kosmas, G; Kallitsaris, A; Pournaras, S; Messinis, I E

    2010-02-01

    Data regarding the possible effects of estrogen on ghrelin secretion in humans are limited and contradictory. To investigate the effect of estradiol (E2) on ghrelin levels in normal pre- and post-menopausal women. A total of 21 women divided into 3 groups, i.e.13 normally cycling women (no.=7, group 1 and no.=6, group 2) and 8 post-menopausal women (group 3). Women of group 1 received increasing doses of E2 through skin patches from cycle days 3 to 5. Women of group 2, underwent total abdominal hysterectomy plus bilateral salpingo-oophorectomy (TAH+BSO) on cycle day 3. Women of group 3 received po increasing doses of E2 valerate for 15 days. Acylated ghrelin and E2 were measured in all blood samples. In group 1, plasma ghrelin levels did not show any significant changes for the week following cycle day 3. In group 2, ghrelin levels were similar before and after TAH+BSO and remained stable during the first 7 post-operative days. In group 3, no significant changes in plasma ghrelin levels were seen during the 15 days of E2 administration. The present study demonstrates for the first time that ghrelin values were not affected either by exogenous short-term estrogen administration to pre- and post-menopausal women or following ovariectomy in pre-menopausal women. It is suggested that ovarian hormones are not involved in the regulation of ghrelin secretion in women.

  6. Plasma IL-5 concentration and subclinical carotid atherosclerosis

    PubMed Central

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

    2015-01-01

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

  7. MEASURING NICOTINE INTAKE AMONG HIGHLY DEPENDENT ADOLESCENT SMOKERS: COMPARABILITY OF SALIVA AND PLASMA COTININE CONCENTRATIONS

    PubMed Central

    Parzynski, Craig S.; Jaszyna-Gasior, Maria; Franken, Frederick H.; Moolchan, Eric T.

    2008-01-01

    Cotinine is the most common biomarker used to assess nicotine exposure and abstinence. It can be measured in various matrices including saliva, plasma, and urine. Previous research with adults has shown high correlations between saliva and plasma cotinine concentrations. However, research has not examined this relationship in adolescents. Additionally, variability in saliva flow and metabolism across gender, ethnicity, and age may impact the relationship between saliva and plasma cotinine concentration. Our aim was to examine the relationship between saliva and plasma cotinine concentration in a group of nicotine-dependent adolescent smokers. Additionally, we examined these correlations across gender, ethnicity and age. The sample consisted of 66 adolescent smokers (age 15.1 ± 1.3, 63.6% girls, 66.7% European American, CPD 18.3 ± 8.5, FTND 7.1 ± 1.3). Saliva and plasma specimens were collected before the treatment phase of a nicotine replacement therapy trial and analyzed. The relationship between saliva and plasma cotinine concentration was analyzed using Pearson’s correlation coefficients. We performed a secondary analysis using multiple regression to compare correlations across race, gender and age. Results indicated a positive correlation between saliva cotinine and plasma cotinine concentration (r = .84, p < .001). Differences in correlations across age were significant (t = 3.03, p < .01). Differences across ethnicity approached significance (t = −1.93, p = .058). Future research should seek to further validate saliva-to-plasma cotinine concentration ratios in adolescents as well as characterize saliva-to-plasma concentration differences and their underlying mechanisms. PMID:18199474

  8. On the relationship between plasma concentrations of drugs and outcome of stroke studies in laboratory animals.

    PubMed

    Curry, S H

    2001-06-01

    In assessing plasma concentrations of drugs in relation to neuroprotective effect, emphasis should be placed on measured or calculated concentrations during the window of opportunity for effect, rather than at the end of the experiment. Unbound (plasma free) concentrations should be especially considered as should brain penetration to the stroked area. Problem-solving exercises should include post hoc assessment of dosing residues and proof of exposure. The shape of the graph of response versus concentration in plasma is very steep, giving the impression of an all-or-none effect. Although higher doses lead to greater effects, attempts to statistically correlate plasma level and infarct size are likely to be unsuccessful. There is strong evidence that the pharmacokinetic properties of drugs are affected by the physiological consequences of ischemia.

  9. Plasma adiponectin concentration is strongly associated with VLDL-TG catabolism in postmenopausal women.

    PubMed

    Lapointe, A; Tchernof, A; Lamarche, B; Piché, M E; Weisnagel, J; Bergeron, J; Lemieux, S

    2011-04-01

    To investigate associations between plasma adiponectin concentration and very-low density lipoprotein-triglyceride (VLDL-TG) secretion and catabolism in postmenopausal women. This cross-sectional study included 30 postmenopausal women. Plasma adiponectin concentration was measured by ELISA. Insulin sensitivity was assessed by a 2-h euglycemic-hyperinsulinemic clamp. Fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) were measured during an oral glucose tolerance test. The calculation of VLDL-TG fractional catabolic rate (FCR) and VLDL-TG total secretion rate (TSR) were based on the monoexponential decrease of TG-[²H₅] glycerol values obtained following the administration of a ²H₅-glycerol bolus. Plasma adiponectin concentration was negatively associated with VLDL-TG TSR (r=-0.50; p=0.005) and positively associated with VLDL-TG FCR (r=0.54; p<0.002). This latter association remained significant after further adjustments for insulin sensitivity, visceral adipose tissue, HDL-C, FPG and 2hPG concentrations. In a multivariate model including adiponectin, insulin sensitivity and 2hPG, plasma adiponectin level was the strongest correlate of VLDL-TG FCR. Elevated plasma adiponectin concentration is associated with a favourable VLDL-TG metabolism. Copyright © 2009 Elsevier B.V. All rights reserved.

  10. Evaluation of factors important in modeling plasma concentrations of tetracycline hydrochloride administered in water in swine.

    PubMed

    Mason, Sharon E; Almond, Glen W; Riviere, Jim E; Baynes, Ronald E

    2012-10-01

    To model the plasma tetracycline concentrations in swine (Sus scrofa domestica) treated with medication administered in water and determine the factors that contribute to the most accurate predictions of measured plasma drug concentrations. Plasma tetracycline concentrations measured in blood samples from 3 populations of swine. Data from previous studies provided plasma tetracycline concentrations that were measured in blood samples collected from 1 swine population at 0, 4, 8, 12, 24, 32, 48, 56, 72, 80, 96, and 104 hours and from 2 swine populations at 0, 12, 24, 48, and 72 hours hours during administration of tetracycline hydrochloride dissolved in water. A 1-compartment pharmacostatistical model was used to analyze 5 potential covariate schemes and determine factors most important in predicting the plasma concentrations of tetracycline in swine. 2 models most accurately predicted the tetracycline plasma concentrations in the 3 populations of swine. Factors of importance were body weight or age of pig, ambient temperature, concentration of tetracycline in water, and water use per unit of time. The factors found to be of importance, combined with knowledge of the individual pharmacokinetic and chemical properties of medications currently approved for administration in water, may be useful in more prudent administration of approved medications administered to swine. Factors found to be important in pharmacostatistical models may allow prediction of plasma concentrations of tetracycline or other commonly used medications administered in water. The ability to predict in vivo concentrations of medication in a population of food animals can be combined with bacterial minimum inhibitory concentrations to decrease the risk of developing antimicrobial resistance.

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

    PubMed

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

    1986-03-01

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

  12. Monitoring imatinib plasma concentrations in chronic myeloid leukemia

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Goldsmith, J C

    2000-03-01

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

  14. Plasma and gingival crevicular fluid phenytoin concentrations as risk factors for gingival overgrowth.

    PubMed

    Güncü, Güliz N; Caglayan, Feriha; Dinçel, Aysun; Bozkurt, Atilla; Saygi, Serap; Karabulut, Erdem

    2006-12-01

    Gingival enlargement is one of the side effects associated with the administration of phenytoin. The mechanism by which phenytoin induces gingival enlargement is not well understood. This study was conducted to investigate the relationship between plasma and gingival crevicular fluid (GCF) phenytoin concentrations and the degree of gingival overgrowth in patients with similar gingival and plaque indices and also to determine the risk factors for gingival enlargement. Eighteen patients taking phenytoin in regular doses > or =6 months prior to the investigation participated in the study. Gingival enlargement was evaluated with two indices to score vertical and horizontal overgrowth. The gingival index (GI), plaque index (PI), gingival bleeding time index (GBTI), probing depth (PD), and clinical attachment level (CAL) were also evaluated. GCF and plasma phenytoin concentrations were determined by using high-performance liquid chromatography (HPLC). There was no significant difference between responders and non-responders for PD, CAL, PI, GI, and GBTI. Phenytoin was detected in all of the GCF and plasma samples using the HPLC analysis method. The mean concentration of phenytoin in GCF was significantly greater than the concentration of phenytoin in plasma. No significant difference was observed for the concentration of GCF phenytoin between responders and non-responders. However, the concentration of plasma phenytoin was significantly higher in responders than non-responders. This study showed that plasma phenytoin level appeared to be a risk factor for phenytoin-induced gingival overgrowth.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  20. Plasma concentration of vitamin C in dogs with a portosystemic shunt.

    PubMed

    Hishiyama, Nobuya; Kayanuma, Hideki; Matsui, Tohru; Yano, Hideo; Suganuma, Tsunenori; Funaba, Masayuki; Fujise, Hiroshi

    2006-10-01

    Most mammals, including dogs, synthesize vitamin C in the liver. We measured the plasma concentration of vitamin C to assess the body vitamin C status in 15 dogs with a portosystemic shunt (PSS). The plasma biochemical parameters indicated liver abnormalities in all the dogs. In contrast, the plasma concentration of vitamin C ranged from 2.21 to 9.03 mg/L in the 15 dogs and was below the reference range (3.2 to 8.9 mg/L) in only 2 dogs. These findings suggest that vitamin C status is not impaired in dogs with PSS.

  1. The effect of plasma antithrombin concentration on thrombin generation and fibrin gel structure.

    PubMed

    Elgue, G; Sanchez, J; Fatah, K; Olsson, P; Blombäck, B

    1994-07-15

    Congenital deficiency of antithrombin (AT) is associated with thrombotic events and AT consumption occurs in some severe disorders and after treatment with heparin. The aim of this study was to investigate whether variations in the level of plasma AT modify thrombin generation and the fibrin formation process after the intrinsic coagulation mechanism is triggered. Normal plasma was depleted of AT by immunoadsorption on CNBr-Sepharose coupled with the anti-AT-IgG fraction of antiserum. The AT-depleted plasma was reconstituted with AT (between 0.3 and 1.5 AT units per ml). Thrombin generation was measured as the development of thrombin-antithrombin complexes (TAT). The lag phase preceding fibrin formation depended on the concentration of AT. The short lag phase was seen in completely AT-depleted plasma and the long in plasma with 1.5 AT units per ml. TAT generation, determined in parallel consecutive samples, showed that the rate at which thrombin was generated was inverse to the AT concentration in plasma. The network structure of hydrated fibrin gels in the clotted plasma was studied by measuring the wavelength dependence of gel turbidity. The mass/length ratio value, -i.e. the thickness of fiber strands and porosity of the gel increased with increasing AT concentrations. It is concluded that plasma AT regulates the rate of prothrombin-thrombin conversion, the clotting time and the consequently network structure of the fibrin gel.

  2. Sensitive analysis of anti-HIV drugs, efavirenz, lopinavir and ritonavir, in human hair by liquid chromatography coupled with tandem mass spectrometry.

    PubMed

    Huang, Yong; Gandhi, Monica; Greenblatt, Ruth M; Gee, Winnie; Lin, Emil T; Messenkoff, Nicholas

    2008-11-01

    A highly sensitive and selective method using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) was developed and validated for the measurement of three antiretroviral agents, efavirenz, lopinavir and ritonavir, in human hair. Hair samples from adherent HIV-infected patients on antiretroviral therapies were cut into about 1 mm length segments and drugs were extracted by first shaking the samples with methanol in a 37 degrees C water bath overnight (>14 h), followed by methyl tert-butyl ether/ethyl acetate (1:1) extraction under weak alkaline conditions. The extracted lopinavir and ritonavir were separated by reversed-phase chromatography and detected by tandem mass spectrometry in electrospray positive ionization mode with multiple reaction monitoring (MRM), while efavirenz was monitored in negative ionization MRM mode. This method was validated from 0.01 to 4.0 ng/mg hair for ritonavir and 0.05-20 ng/mg hair for lopinavir and efavirenz by using 2 mg of a human hair sample. The interday and intraday assay precision (coefficients of variation, CV) for spiked quality control (QC) samples at low, medium and high concentrations were within 15% and accuracy ranged from 89% to 110%. Assay reproducibility was also demonstrated by analysis of incurred hair QC samples (CV <14%). No significant matrix ionization suppression was observed. This developed method allowed for the monitoring of these target medications in the hair samples of HIV-infected women on antiretroviral therapy in an observational study using small amounts of hair.

  3. Plasma lactate concentrations in septic peritonitis: A retrospective study of 83 dogs (2007-2012).

    PubMed

    Cortellini, Stefano; Seth, Mayank; Kellett-Gregory, Lindsay M

    2015-01-01

    To determine if absolute plasma lactate concentration or lactate clearance in dogs with septic peritonitis is associated with morbidity or mortality. Retrospective cohort study from 2007 to 2012. University teaching hospital. Eighty-three dogs with septic peritonitis were included. Patients had at least 1 plasma lactate measurement during the course of the hospitalization. Sixty-four percent of the patients survived to discharge, 22% were euthanized, and 14% died during hospitalization. Plasma lactate concentration >2.5 mmol/L on admission (29% of the patients) was associated with mortality (P = 0.001). Median admission plasma lactate concentration (n = 81) was significantly different between nonsurvivors (2.5 mmol/L, range 0.5-8.4) and survivors (1.4 mmol/L, range 0.5-9.7; P = 0.007). Admission plasma lactate concentration >4 mmol/L yielded a sensitivity of 36% and a specificity of 92% for nonsurvival. The inability to normalize plasma lactate concentration within 6 hours of admission (n = 10/24) yielded a sensitivity of 76% and specificity of 100% for nonsurvival. Postoperative hyperlactatemia (plasma lactate concentration >2 mmol/L; n = 18/76) had a sensitivity of 46% and specificity of 88% for nonsurvival. Persistent postoperative hyperlactatemia (n = 11/18) had a sensitivity of 92% and a specificity of 100% for nonsurvival. Lactate clearance less than 21% at 6 hours (n = 20) had a sensitivity of 54% and specificity of 91% for nonsurvival. Lactate clearance less than 42% at 12 hours (n = 18) had a sensitivity of 82% and a specificity of 100% for nonsurvival. Admission plasma lactate concentration and lactate clearance were good prognostic indicators in dogs with septic peritonitis. © Veterinary Emergency and Critical Care Society 2014.

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

    SciTech Connect

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

    2003-08-15

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

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

    PubMed Central

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

    1973-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

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

  7. Design and formulation of nano-sized spray dried efavirenz-part I: influence of formulation parameters

    NASA Astrophysics Data System (ADS)

    Katata, Lebogang; Tshweu, Lesego; Naidoo, Saloshnee; Kalombo, Lonji; Swai, Hulda

    2012-11-01

    Efavirenz (EFV) is one of the first-line antiretroviral drugs recommended by the World Health Organisation for treating HIV. It is a hydrophobic drug that suffers from low aqueous solubility (4 μg/mL), which leads to a limited oral absorption and low bioavailability. In order to improve its oral bioavailability, nano-sized polymeric delivery systems are suggested. Spray dried polycaprolactone-efavirenz (PCL-EFV) nanoparticles were prepared by the double emulsion method. The Taguchi method, a statistical design with an L8 orthogonal array, was implemented to optimise the formulation parameters of PCL-EFV nanoparticles. The types of sugar (lactose or trehalose), surfactant concentration and solvent (dichloromethane and ethyl acetate) were chosen as significant parameters affecting the particle size and polydispersity index (PDI). Small nanoparticles with an average particle size of less than 254 ± 0.95 nm in the case of ethyl acetate as organic solvent were obtained as compared to more than 360 ± 19.96 nm for dichloromethane. In this study, the type of solvent and sugar were the most influencing parameters of the particle size and PDI. Taguchi method proved to be a quick, valuable tool in optimising the particle size and PDI of PCL-EFV nanoparticles. The optimised experimental values for the nanoparticle size and PDI were 217 ± 2.48 nm and 0.093 ± 0.02.

  8. Age-related increases in plasma phosphatidylcholine hydroperoxide concentrations in control subjects and patients with hyperlipidemia.

    PubMed

    Kinoshita, M; Oikawa, S; Hayasaka, K; Sekikawa, A; Nagashima, T; Toyota, T; Miyazawa, T

    2000-06-01

    The basal lipid peroxide concentration in the plasma of patients with hyperlipidemia may be related to atherosclerosis. Quantitative determination of lipid peroxides in the plasma is an important step in the overall evaluation of the biochemical processes leading to oxidative injury. Unfortunately, the currently available methods for lipid peroxidation lack specificity and sensitivity. Hyperlipidemic patients (44 males and 50 females), ages 12-82 years (mean +/- SE, 53 +/- 2.3 years for males, 58 +/- 2.0 years for females, and 56 +/- 14 years for total cases), and normolipidemic volunteers (controls, 32 males and 15 females), ages 13-90 years (49 +/- 4 years for males, 65 +/- 4 years for females, and 55 +/- 24 years for total cases), were recruited in the present study. Plasma phosphatidylcholine hydroperoxide (PCOOH) was determined by chemiluminescence-HPLC (CL-HPLC). Plasma PCOOH concentrations increased with age in both controls and hyperlipidemic patients. However, the mean plasma PCOOH concentration in patients with hyperlipidemia (331 +/- 19 nmol/L; n = 94) was significantly (P <0.001) higher than in the controls (160 +/- 65 nmol/L; n = 47). Plasma PCOOH concentrations were similar in three hyperlipidemic phenotypes: hypercholesterolemia (IIa), hypertriglyceridemia (IV), and combined hyperlipidemia (IIb). The mean plasma PCOOH in patients with treatment-induced normalized plasma lipids was 202 +/- 17 nmol/L. There was no significant correlation between plasma PCOOH concentration and total cholesterol, triglycerides, or phospholipids in hyperlipidemic patients. For all subjects, there was a significantly positive correlation between plasma PCOOH and each lipid (total cholesterol, P = 0.0002; triglycerides, P = 0.0137; and phospholipids, P <0.0001). Analysis of fatty acids composition of plasma phosphatidylcholine showed significantly low concentrations of n-6 fatty acids moieties (linoleic acid and arachidonic acid) in patients compared with controls. Our

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

    USGS Publications Warehouse

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

    1986-01-01

    1. To examine the effects of parathion on basal plasma luteinizing hormone (LH) concentration, male Japanese quail (Coturnix japonica) were orally intubated with 0, 5 or 10 mg/kg parathion and sacrificed after 4, 8 and 24 hr.2. At the 5 mg/kg dose, plasma LH levels were reduced at 4 and 8 hr, but returned to control values by 24 hr. Brain acetylcholinesterase activity was substantially reduced by 10 mg/kg parathion (52, 75 and 37% inhibition at 4, 8 and 24 hr, respectively) and plasma LH concentration remained depressed through the 24-hr period.3. These findings suggest that the organophosphorus insecticide parathion may alter plasma LH concentration in a manner which might impair reproductive activity, and provide indirect evidence for a cholinergic component in the regulation of LH secretion in quail.

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

    USGS Publications Warehouse

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

    1986-01-01

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

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

    PubMed

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

    2007-06-01

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

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

    PubMed Central

    Klinker, H; Langmann, P; Richter, E

    1996-01-01

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

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

    PubMed

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

    2012-04-01

    Pennsylvania (PA) State Racing Commissions regulate the endogenous androgenic steroid, testosterone (TES), in racing intact males (RIM) by quantification of TES in post-race samples. Post-race plasma samples (2209) collected between March 2008 and November 2010 were analyzed for TES, nandrolone (NAN), and other anabolic steroids (ABS). Of the 2209 plasma samples, 2098 had quantifiable TES ≥ 25 pg/mL. Plasma (mean ± SD) concentrations of TES and NAN in RIM were 329.2 ± 266.4 and 96.0 ± 67.8 pg/mL, respectively. Only 64.6% of RIM had quantifiable concentration of NAN, and there was no relationship between TES and NAN. Plasma TES concentrations were significantly (P < 0.0001) higher during the months of April, May, June, July, and August. A significantly higher (P < 0.006) plasma TES was observed in Thoroughbred (TB) (347.6 ± 288.5 pg/mL) vs. that in Standardbred (STB) (315.4 ± 247.7 pg/mL). Plasma concentrations of TES from breeding stallions (BS) were 601.6 ± 356.5 pg/mL. Statistically significant (P < 0.0001) lower plasma concentrations of the two steroids were observed in RIM horses. Based on quantile distribution of TES in the RIM and BS populations, 99.5% were at or below 1546.1 and 1778.0 pg/mL, respectively. Based on this population of RIM, the suggested upper threshold plasma concentration of endogenous TES in horses competing in PA should remain at 2000 pg/mL. © 2011 Blackwell Publishing Ltd.

  14. Retinol, carotenoids, and tocopherols in the milk of lactating adolescents and relationships with plasma concentrations.

    PubMed

    de Azeredo, Vilma B; Trugo, Nadia M F

    2008-02-01

    We determined the concentrations of retinol, carotenoids, and tocopherols in breast milk of adolescents and evaluated their associations with plasma levels and with maternal characteristics (period of lactation, body mass index, age of menarche, and years postmenarche). This was a single cross-sectional survey of retinol, carotenoid, and tocopherol composition of milk and plasma of lactating adolescent mothers (n = 72; 30-120 d postpartum) attending public daycare clinics in Rio de Janeiro, Brazil. Milk and plasma components were analyzed by high-performance liquid chromatography. Nutrient concentrations (micromoles per liter, mean +/- SE) in plasma and milk were, respectively, retinol 2.1 +/- 0.5 and 0.62 +/- 0.44, beta-carotene 0.18 +/- 0.19 and 0.016 +/- 0.017, alpha-carotene 0.05 +/- 0.04 and 0.0035 +/- 0.002, lutein plus zeaxanthin 0.15 +/- 0.11 and 0.025 +/- 0.024, lycopene 0.1 +/- 0.11 and 0.016 +/- 0.025, alpha-tocopherol 10.8 +/- 5.3 and 2.7 +/- 1.8, gamma-tocopherol 2.6 +/- 2.3 and 0.37 +/- 0.15. The milk/plasma molar ratios of retinol and tocopherols were two times higher than those of carotenoids. Significant correlations (P < 0.001) between milk and plasma nutrient levels were observed for beta-carotene (r = 0.41), alpha-carotene (r = 0.60), and lutein plus zeaxanthin (r = 0.57), but not for lycopene, retinol, and tocopherols. Nutrient concentrations in plasma and in milk were not associated with the maternal characteristics investigated. Concentrations of the nutrients studied, especially retinol and alpha-tocopherol, in mature milk of lactating adolescents were, in general, lower than in milk of adult lactating women. Milk concentrations were associated with plasma concentrations only for beta-carotene, alpha-carotene, and lutein plus zeaxanthin.

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

    PubMed

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

    2015-11-01

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

  16. Measurement of plasma cell-free DNA concentrations in dogs with sepsis, trauma, and neoplasia.

    PubMed

    Letendre, Jo-Annie; Goggs, Robert

    2017-05-01

    To determine if cell-free DNA (cfDNA) was identifiable in canine plasma, to evaluate 3 techniques for the measurement of plasma cfDNA concentrations in dogs presented to an emergency service, and to compare the plasma cfDNA concentrations of healthy dogs to those with sepsis, trauma, and neoplasia. Retrospective study of banked canine plasma samples collected between May 2014 and December 2014. Dogs presented to the emergency service of a university veterinary teaching hospital. Plasma cfDNA was measured on residual plasma samples obtained from 15 dogs with sepsis, 15 dogs with moderate-severe trauma, 15 dogs diagnosed with a sarcoma. Plasma cfDNA was also measured in 15 healthy dogs. None. Assay linearity, repeatability, and reproducibility were evaluated. Quantification of cfDNA was performed in duplicate on diluted citrated plasma and following DNA purification using 2 fluorescence assays (SYBR-Gold; Quant-iT) and by ultraviolet absorbance spectroscopy. Fluorescence intensities (FIs) were converted to cfDNA concentrations using standard curves. Median FI values and cfDNA concentrations were compared to healthy controls using the Kruskal-Wallis test, with adjustment for multiple comparisons. Alpha was set at 0.05. Both assays had excellent linearity, and acceptable repeatability and reproducibility. Compared to controls, plasma cfDNA concentrations were significantly increased in dogs with sepsis or moderate-severe trauma with both assays (P ≤ 0.003). Dogs with neoplasia had significantly increased cfDNA concentrations with the Quant-iT assay only (P = 0.003). When measurements were performed on purified DNA, only dogs with moderate-severe trauma had significantly increased cfDNA concentrations (P < 0.001; SYBR-Gold assay). cfDNA can be readily identified in canine plasma using 2 fluorescence assays. DNA extraction offers no advantage over direct measurement. Compared to healthy controls, dogs with sepsis or moderate-severe trauma have significantly increased

  17. Dysregulation of Endoplasmic Reticulum Stress and Autophagic Responses by the Antiretroviral Drug Efavirenz

    PubMed Central

    Bertrand, Luc

    2015-01-01

    Increasing evidence demonstrates that the antiretroviral drugs (ARVds) used for human immunodeficiency virus (HIV) treatment have toxic effects that result in various cellular and tissue pathologies; however, their impact on the cells composing the blood-brain barrier is poorly understood. The current study focused on ARVds, used either in combination or alone, on the induction of endoplasmic reticulum (ER) stress responses in human brain endothelial cells. Among studied drugs (efavirenz, tenofovir, emtricitabine, lamivudine, and indinavir), only efavirenz increased ER stress via upregulation and activation of protein kinase-like ER kinase PERK and inositol requiring kinase 1α (IRE1α). At the same time, efavirenz diminished autophagic activity, a surprising result because typically the induction of ER stress is linked to enhanced autophagy. These results were confirmed in microvessels of HIV transgenic mice chronically administered with efavirenz. In a series of further experiments, we identified that efavirenz dysregulated ER stress and autophagy by blocking the activity of the Beclin-1/Atg14/PI3KIII complex in regard to synthesis of phosphatidylinositol 3-phosphate, a process that is linked to the formation of autophagosomes. Because autophagy is a protective mechanism involved in the removal of dysfunctional proteins and organelles, its inhibition can contribute to the toxicity of efavirenz or the development of neurodegenerative disease in HIV patients treated with this drug. PMID:25987489

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

    NASA Astrophysics Data System (ADS)

    Hong, Wanshu

    1992-03-01

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

  19. Moringa Oleifera leaf extract increases plasma antioxidant status associated with reduced plasma malondialdehyde concentration without hypoglycemia in fasting healthy volunteers.

    PubMed

    Ngamukote, Sathaporn; Khannongpho, Teerawat; Siriwatanapaiboon, Marent; Sirikwanpong, Sukrit; Dahlan, Winai; Adisakwattana, Sirichai

    2016-12-29

    To investigate the effect of Moringa Oleifera leaf extract (MOLE) on plasma glucose concentration and antioxidant status in healthy volunteers. A randomized crossover design was used in this study. Healthy volunteers were randomly assigned to receive either 200 mL of warm water (10 cases) or 200 mL of MOLE (500 mg dried extract, 10 cases). Blood samples were drawn at 0, 30, 60, 90, and 120 min for measuring fasting plasma glucose (FPG), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC) and malondialdehyde (MDA). FPG concentration was not signifificantly different between warm water and MOLE. The consumption of MOLE acutely improved both FRAP and TEAC, with increases after 30 min of 30 μmol/L FeSO4 equivalents and 0.18 μmol/L Trolox equivalents, respectively. The change in MDA level from baseline was signifificantly lowered after the ingestion of MOLE at 30, 60, and 90 min. In addition, FRAP level was negatively correlated with plasma MDA level after an intake of MOLE. MOLE increased plasma antioxidant capacity without hypoglycemia in human. The consumption of MOLE may reduce the risk factors associated with chronic degenerative diseases.

  20. Impact of hemolysis during sample collection: how different is drug concentration in hemolyzed plasma from that of normal plasma?

    PubMed

    Tan, Aimin; Gagné, Sébastien; Lévesque, Isabelle A; Lachance, Sylvain; Boudreau, Nadine; Lévesque, Ann

    2012-07-15

    Hemolysis is a common phenomenon in clinical studies. Despite the growing interest in hemolysis matrix effect, how hemolysis impacts the representability of hemolyzed plasma samples was rarely evaluated. The purpose of this research is to perform such an evaluation by theoretical consideration and experiment. A formula for estimating the impact is proposed, which includes the degree of hemolysis and the drug's red blood cell (RBC): plasma concentration ratio. The impact of hemolysis on the representability of hemolyzed plasma samples is compound-dependant. Given the same degree of hemolysis, the stronger a drug binds to RBCs, the more significant the impact of hemolysis. For a drug with high affinity to RBCs, the results of hemolyzed plasma samples may not be useful even though they are accurate. There is an overall agreement between theoretical predication and experimental results. Among the ten different drug compounds tested, only methazolamide, which binds strongly to RBCs, showed significant change in plasma concentration due to hemolysis. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2013-10-01

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

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

    PubMed

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

    2006-01-01

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

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

    PubMed

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

    1975-10-01

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

  4. The prognostic value of plasma nesfatin-1 concentrations in patients with traumatic brain injury.

    PubMed

    Wu, Gang-Qun; Chou, Xiao-Min; Ji, Wen-Jian; Yang, Xiao-Gang; Lan, Luo-Xin; Sheng, Yan-Jun; Shen, Yang-Fang; Li, Jian-Rong; Huang, Guo-Zhong; Yu, Wen-Hua; Dong, Xiao-Qiao; Du, Quan; Yang, Ding-Bo; Zhang, Zu-Yong; Wang, Hao; Shen, Yong-Feng; Jiang, Li

    2016-07-01

    Nesfatin-1 is related to inflammation. Its increased circulating concentrations are associated with the severity and prognosis of subarachnoid hemorrhage. In-hospital major adverse events (IMAEs), including acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction, are correlated with mortality after traumatic brain injury (TBI). The present study was designed to investigate the changes of plasma nesfatin-1 concentrations and further assess its association with inflammation, trauma severity, in-hospital mortality and IMAEs following TBI. We measured plasma nesfatin-1 concentrations of 100 severe TBI patients and 100 controls. Progressive hemorrhagic injury and posttraumatic cerebral infarction were diagnosed based on a follow-up computerized tomography scan. Acute traumatic coagulopathy was identified according to a coagulation test. Plasma nesfatin-1 concentrations were significantly higher in patients than in controls and associated highly with Glasgow coma scale (GCS) scores and plasma C-reactive protein concentrations. Nesfatin-1 was indicated as an independent predictor for in-hospital mortality and IMAEs. In accordance with area under receiver operating characteristic curve, its predictive value was similar to GCS scores. Increased plasma nesfatin-1 concentrations are associated closely with inflammation, trauma severity and clinical outcomes, indicating that nesfatin-1 might be involved in inflammation and become a good prognostic biomarker following TBI. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Circadian and postprandial variation in plasma citrulline concentration in healthy dogs.

    PubMed

    Dahan, Julien M; Giron, Celine; Concordet, Didier; Dossin, Olivier

    2016-03-01

    To evaluate circadian and postprandial variations in plasma citrulline concentration in healthy dogs. 8 healthy Beagles. Blood samples were collected from dogs after 12 hours of food withholding (0 hours; 8:00 am) and then every 2 hours for 12 hours (until 8:00 pm) and again at 24 hours (8:00 am the next day). The same protocol was repeated, with the only difference being that a meal was given immediately after the 0-hour sample collection point. Plasma citrulline concentration was measured by ion exchange chromatography. No significant difference in plasma citrulline concentration was identified among measurement points when food was withheld. Mean ± SD plasma citrulline concentration at 4 hours (72.2 ± 12.7 μmol/L) and 24 hours (56.1 ± 12.5 μmol/L) after dogs were fed was significantly different from that at 0 hours (64.4 ± 12.7 μmol/L). Plasma citrulline concentration had no circadian variation in unfed dogs but increased significantly in fed dogs 4 hours after a meal. Therefore, food should be withheld from dogs for 8 to 12 hours before blood sample collection for measurement of citrulline concentration.

  6. Plasma concentrations of fluticasone propionate and budesonide following inhalation: effect of induced bronchoconstriction

    PubMed Central

    Mortimer, Kevin J; Tattersfield, Anne E; Tang, Yufei; Wu, Kai; Lewis, Sarah; Hochhaus, Gunther; Harrison, Tim W

    2007-01-01

    What is already known about this subject All inhaled corticosteroids are absorbed into the systemic circulation and hence have the potential to cause adverse systemic effects. Plasma drug concentrations following inhalation of 1000 µg fluticasone are considerably lower in people with airflow obstruction than in healthy volunteers but this is not the case for budesonide. What this study adds This is the first study to determine whether changes in airflow obstruction within an individual affect the systemic absorption of inhaled fluticasone and budesonide; Plasma concentrations of fluticasone and, to a lesser extent, those of budesonide were lower when the drugs were inhaled following induced bronchoconstriction; The lower plasma concentrations of corticosteroids seen when the drugs were inhaled following induced bronchoconstriction is likely to reflect variations that will occur with fluctuations in airway caliber in asthma. Aims To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation. Methods Twenty people with mild asthma inhaled 1000 µg fluticasone (Accuhaler®) plus 800 µg budesonide (Turbohaler®) on two visits. On one occasion, prior to drug inhalation, FEV1 was decreased by at least 25% using inhaled methacholine. Plasma drug concentrations were measured for each drug over 5 h and area under the plasma concentration-time curve (AUC(0,5 h)) compared between visits. Results The mean difference in FEV1 prior to drug inhalation on the 2 days was 33%. AUC(0,5 h) values for fluticasone and budesonide were lower by a median of 60% (IQR 36–75) and 29% (IQR 2–44), respectively, when administered following bronchoconstriction; the reduction was greater for fluticasone than for budesonide, P = 0.007. Conclusions The lower plasma concentrations of fluticasone and, to a lesser extent, budesonide seen when the drugs were inhaled following induced bronchoconstriction, is likely to

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

    USGS Publications Warehouse

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

    1999-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    SciTech Connect

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

    1981-06-01

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

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

    USGS Publications Warehouse

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

    1981-01-01

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

  11. Rolling out Efavirenz for HIV Precision Medicine in Africa: Are We Ready for Pharmacovigilance and Tackling Neuropsychiatric Adverse Effects?

    PubMed

    Masimirembwa, Collen; Dandara, Collet; Leutscher, Peter Derek Christian

    2016-10-01

    The introduction of antiretroviral therapy (ART) led to huge reductions in human immunodeficiency virus (HIV)-related deaths, turning HIV-infection into a chronic condition. Attention is now turning to quality of life for patients on lifelong ART treatment, reflecting on the safety of antiretroviral drugs. In sub-Saharan Africa, efavirenz (EFV) forms the preferred first-line ART but adverse drug events have also been reported. We express our concern on EFV-based regimens being part of mass rollout programs without full attention to toxicities. EFV is associated with various neuropsychiatric adverse events (AEs). If EFV use is not monitored, a huge burden of neuropsychiatric AEs and elevated risk of drug resistance due to nonadherence are likely to follow. A monumental EFV-based ART regimen rollout program, through the UNAIDS 90-90-90 and option B plus programs/approaches, is planned, which will more than double the number of patients on EFV-containing ART. According to this ambitious treatment target, by 2020, 90% of all people living with HIV will know their HIV status; 90% of all people with diagnosed HIV infection will receive sustained ART; and 90% of all people receiving ART will have viral suppression. On the other hand, HIV patients of African origin are predisposed to developing EFV-induced neuropsychiatric AEs due to specific CYP2B6 genetic variants causing impaired metabolism of EFV. It is our considered opinion that the potential quantitative and qualitative burden of EFV-induced neuropsychiatric AEs, which can vary from person-to-person and between populations, deserve special attention and action during the ART rollout program. We here make a case for Africa in particular where we project the burden of neuropsychiatric AEs to be greatest. We advocate for surveillance of neuropsychiatric AEs due to EFV therapy, incorporation of pharmacogenetics testing for CYP2B6 to assist in EFV dosing, and measurement of plasma EFV concentration, as a three

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

    PubMed

    Schwertner, Harvey A; Weld, Kyle J

    2015-10-01

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

  13. Plasma Retinol Concentration Is Mainly Driven by Transthyretin in Hemodialysis Patients.

    PubMed

    Bataille, Stanislas; Landrier, Jean-François; Astier, Julien; Cado, Sylvie; Sallette, Jérôme; Serveaux, Marianne; Burtey, Stéphane; Cohen, Julien; Tournier, Charlène; Tourniaire, Franck; Darmon, Patrice

    2017-07-06

    Micronutrients deficiencies in hemodialysis patients are due to low dietary intakes and intradialytic losses for hydrophilic micronutrients. Conversely, lipophilic nondialyzable compounds might accumulate because of a lack of elimination through renal metabolism or dialysis. Other compounds have complex metabolism: their concentration is not explained by these phenomenons. The aim of this study was to report plasma concentrations of lipophilic micronutrients in hemodialysis patients and to analyze if these concentrations were predictive of mortality. The design was monocentric observational longitudinal study. A total of 123 hemodialysis patients included in this observational study. Plasma concentration of lipophilic micronutrients retinol and its two co-transporters transthyretin and retinol-binding protein 4, tocopherol, and carotenoids (α-carotene and β-carotene, β-cryptoxanthin, lycopene, lutein, and zeaxanthin), and all factors associated with 1-year mortality. Within the 123 patients of the study, median age (interquartile range) was 77.5 (69.5-84.5) years and 58.5% were male. Median retinol plasma concentration was 4.07 (2.65-5.51) μmol/L, and 91.9% of patient had high plasma retinol concentrations. In monovariate analysis, retinol levels were inversely correlated with mortality (hazard ratio = 0.57 [0.45-0.72]; P < .001). This effect remained significant after adjustment with several parameters. Nevertheless, the correlation between retinol and mortality disappeared as soon as transthyretin was added in the statistical model, suggesting an effect of transthyretin as confusing bias. Median tocopherol plasma concentration was 34.8 (28.3-42.9) μmol/L and 72.4% of patients had high plasma tocopherol concentration. Neither tocopherol plasma levels nor carotenoids concentrations were correlated with death in multivariate analysis. In hemodialysis patients, the correlation between retinol plasma concentration and mortality represents the nutritional

  14. Role of ouabain-like compound in the regulation of plasma aldosterone concentration in rats.

    PubMed

    Yamada, K; Goto, A; Hui, C; Omata, M

    1996-01-01

    A major biologically active Na,K-ATPase inhibitor in the mammalian circulation may be ouabain-like compound(OLC). We developed a population of immunized rats against ouabain to block the actions of circulating OLC. To investigate the roles of OLC in the regulation of aldosterone secretion and/or production, we measured plasma aldosterone concentration after a week of low salt diet. No significant changes in serum Na and K concentrations were observed in immune rats. The plasma aldosterone concentration was significantly decreased by 30% in 17 immune rats as compared with 11 control rats(control: 455 +/- 53, immune: 315 +/- 21 pg/mL, p < 0.05). These data indicate that chronic blockade of the circulating OLC significantly decreases plasma aldosterone concentration during salt depletion and suggest that endogenous OLC may play an important role in the regulation of aldosterone secretion and/or production.

  15. Plasma cortisol concentrations following cortisone infusion in dogs before and after treatment with cortisone acetate.

    PubMed

    Church, D B; Emslie, D R; Watson, A D

    1999-10-01

    To evaluate effects of iatrogenic hyperadrenocorticism on plasma cortisol concentrations produced by an infusion of hydrocortisone in dogs. Plasma cortisol concentrations were measured regularly during a 6 h infusion of hydrocortisone sodium succinate at two dose rates. The infusions were performed before and after treatment for 30 d with oral cortisone acetate at 10 mg/kg/24 h, divided thrice daily. Adrenal activity during the experimental period was assessed by weekly ACTH stimulation tests. Both infusion rates produced lower plasma cortisol concentrations after treatment for 30 d with cortisone. Prior exposure to high concentrations of glucocorticoids may result in accelerated metabolism of glucocorticoids administered subsequently. This may necessitate increased dosages when using glucocorticoids to support inadequate adrenal function.

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

    PubMed

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

    2014-03-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed

    Kędzierski, W

    2014-09-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2005-03-01

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

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

    PubMed

    Benamou, A E; Harris, R C

    1993-01-01

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

  4. A mixed fruit and vegetable concentrate increases plasma antioxidant vitamins and folate and lowers plasma homocysteine in men.

    PubMed

    Samman, Samir; Sivarajah, Gayathri; Man, June C; Ahmad, Ziaul I; Petocz, Peter; Caterson, Ian D

    2003-07-01

    Fruit and vegetable consumption is inversely associated with coronary heart disease (CHD) risk. The aim of the present study was to determine the effect of supplementation with dehydrated juice concentrates from mixed fruit and vegetables on selected plasma vitamins and antioxidant status. We assessed CHD risk by measuring the concentrations of homocysteine, lipids, lipoproteins, glucose and insulin. Men were recruited to participate in a randomized double-blind, crossover trial with 2 periods of 6 wk, separated by a 3-wk wash-out period. Supplementation with the encapsulated mixed extract (Juice Plus) was compared with physically similar placebo capsules. Thirty-two men (13 smokers, 19 nonsmokers) completed the study with a mean compliance of 88%. Compared with placebo, supplementation increased the concentrations of plasma beta-carotene (0.24 +/- 0.15 vs. 1.12 +/- 0.70 micro mol/L; mean +/- SD; P < 0.0001), retinol (1.87 +/- 0.33 vs. 2.00 +/- 0.43 micro mol/L; P < 0.05), alpha-tocopherol (16.8 +/- 7.3 vs. 19.3 +/- 6.8 micro mol/L; P < 0.01), ascorbic acid (72.1 +/- 19.4 vs. 84.1 +/- 13.5 micro mol/L; P < 0.002) and folic acid (24.5 +/- 10.0 vs. 44.9 +/- 16.9 nmol/L; P < 0.0001). Plasma homocysteine was reduced (8.2 +/- 1.5 vs. 7.6 +/- 1.1; P < 0.05) and inversely related (r = -0.40, P < 0.001) with serum folate concentrations. Plasma vitamin C was positively correlated with the resistance of LDL to oxidation (r = 0.26, P < 0.05) and the plasma ferric reducing/antioxidant power (FRAP) tended to be greater after supplementation than after the placebo period (1125.5 +/- 144.1 vs. 1180.3 +/- 158.1 micro mol/L; P < 0.065). Plasma glucose, insulin and lipid concentrations were unaffected. Responses of smokers and nonsmokers did not differ. In the absence of dietary modification, supplementation with a fruit and vegetable concentrate produced responses consistent with a reduction in CHD risk.

  5. Increased plasma proline concentrations are associated with sarcopenia in the elderly.

    PubMed

    Toyoshima, Kenji; Nakamura, Marie; Adachi, Yusuke; Imaizumi, Akira; Hakamada, Tomomi; Abe, Yasuko; Kaneko, Eiji; Takahashi, Soiciro; Shimokado, Kentaro

    2017-01-01

    Metabolome analyses have shown that plasma amino acid profiles reflect various pathological conditions, such as cancer and diabetes mellitus. It remains unclear, however, whether plasma amino acid profiles change in patients with sarcopenia. This study therefore aimed to investigate whether sarcopenia-specific changes occur in plasma amino acid profiles. A total of 153 community-dwelling and seven institutionalized elderly individuals (56 men, 104 women; mean age, 77.7±7.0 years) were recruited for this cross-sectional analysis. We performed a comprehensive geriatric assessment, which included an evaluation of hand grip strength, gait speed, muscle mass and blood chemistry, including the concentration of 18 amino acids. Twenty-eight of the 160 participants met the criteria for sarcopenia established by the Asian Working Group on Sarcopenia in Older People. Univariate analysis revealed associations between the presence of sarcopenia and a higher plasma concentration of proline and glutamine, lower concentrations of histidine and tryptophan. Multivariable analysis revealed that a higher concentration of proline was the only variable independently associated with sarcopenia. The plasma concentration of proline may be useful for understanding the underlying pathophysiology of sarcopenia.

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

    PubMed

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

    2014-01-01

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

  7. Antibiotic treatment of acute salpingitis. A study of plasma concentrations of two tetracyclines (doxycycline and lymecycline).

    PubMed

    Forslin, L; Danielson, D; Kjellander, J; Falk, V

    1982-01-01

    A group of 782 patients with a diagnosis of acute salpingitis (a few of the patients because of other infection in the pelvis) were treated with the recommended oral dose of doxycycline (200 mg the first day and 100 mg once daily for at least the following 9-12 days) in combination with 1 g benzyl penicillin and 0.6 g procaine penicillin twice daily intramuscularly for 5-7 days. The plasma concentrations of doxycycline were determined on the third day of treatment before the next dose was given. In 26.5% of the patients the concentrations were below 1 microgram/ml plasma, considered as the minimum therapeutic level. The dose of doxycycline was increased to 200 mg a day in these patients and the plasma concentrations increased accordingly. In another group of 80 patients, 40 were treated with the standard doxycycline dose, and the other 40 patients with the standard lymecycline dose (300 mg twice a day). The plasma concentrations, determined before the dose on the third day, were below 1 microgram/ml in 35% of the patients treated with doxycycline, and in 5% of those treated with lymecycline. Since acute salpingitis in most cases is a serious complication to a lower genital tract infection, often a sexually transmitted disease caused by tetracycline-sensitive organisms, the importance of achieving and determining the therapeutic plasma concentrations of tetracyclines is stressed.

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

    PubMed

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

    1999-01-01

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

  9. Pharmacokinetic Interactions between the Hormonal Emergency Contraception, Levonorgestrel (Plan B), and Efavirenz

    PubMed Central

    Carten, Monica L.; Kiser, Jennifer J.; Kwara, Awewura; Mawhinney, Samantha; Cu-Uvin, Susan

    2012-01-01

    Objectives. Compare the Plan B levonorgestrel (LNG) area under the concentration- time curve (AUC12) prior to and with efavirenz (EFV). Design. Prospective, open-label, single-arm, equivalence study. Methods. Healthy HIV-negative subjects underwent 12 hr intensive pharmacokinetic (PK) sampling following single dose LNG alone and after 14 days of EFV. Geometric means, Geometric Mean Ratios, and 90% confidence intervals (CI) are reported for PK Parameters. T-tests were utilized. Clinical parameters and liver function tests (LFTs) were assessed. Results. 24 women enrolled and 21 completed the study. With EFV, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) from 42.9 to 17.8 ng∗hr/mL, and maximum concentration (Cmax⁡) was reduced 41% (95% CI: 33%, 50%) from 8.4 to 4.6 ng/mL. LNG was well tolerated with no grade 3 or 4 treatment-related toxicities. Conclusions. EFV significantly reduced LNG exposures. Higher LNG doses may be required with EFV. These results reinforce the importance of effective contraception in women taking EFV. PMID:22536010

  10. Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity

    PubMed Central

    Ramos-Roman, Maria A.; Sweetman, Lawrence; Valdez, Maressa J.; Parks, Elizabeth J.

    2011-01-01

    Objective This study determined whether reductions in postprandial plasma FFA flux would lead to reductions in plasma acylcarnitine (AC) concentrations. Materials/Methods Plasma AC were measured by LC-MS/MS in the fasting state and over 6h after a high-fat (50% energy) meal was fed to 16 overweight and obese subjects with a wide range of insulin sensitivities. Body composition was measured by DEXA, insulin sensitivity by FSIVGTT, substrate oxidation by indirect calorimetry, blood metabolite and hormone concentrations biochemically, and fatty acid flux by using stable isotope tracers. Results Lean body mass (LBM) and fasting fat oxidation correlated positively (r > 0.522, P<0.05), while glucose oxidation correlated negatively (r < −0.551, P <0.04) with fasting AC. Postprandially, plasma glucose, insulin, and TG concentrations increased, and FFA concentrations decreased significantly. The responses of plasma AC species depended on chain length and saturation, with C14:0, C16:0, and C18:0 remaining unchanged, and unsaturated species (e.g., C14:1, C14:2) falling significantly (21–46%, P < 0.03). Post-meal nadir AC concentrations were positively associated with LBM, postprandial fatty acid flux and FFA concentrations (r > 0.515, P < 0.05). By contrast, nadir AC correlated negatively with insulin sensitivity and spillover of meal-derived fatty acids (r < −0.528, P < 0.04). Conclusions Conditions that impact fatty acid flux contribute to the control of postprandial plasma AC concentrations. These data underscore the need for a better understanding of postprandial fatty acid oxidation and dietary fat delivery in the setting of adipose insulin resistance to determine how postprandial lipemia contributes to chronic disease risk. PMID:21820684

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

    DTIC Science & Technology

    2012-09-25

    decreased morning awakening salivary cortisol . Psychoneuroendo- crinology 29: 1184–1191, 2004. 2. Balbo M, Leproult R, Van Cauter E. Impact of sleep and...A phenomenological model for circadian and sleep allostatic modulation of plasma cortisol concentration David Thorsley,1 Rachel Leproult,2,3 Karine...2012 Thorsley D, Leproult R, Spiegel K, Reifman J. A phenomenological model for circadian and sleep allostatic modulation of plasma cortisol

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

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

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

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

    PubMed

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

    2012-03-01

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

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

    PubMed Central

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

    2012-01-01

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

  15. Assessment of plasma ammonia and glutamine concentrations in urea cycle disorders.

    PubMed

    Serrano, M; Ormazábal, A; Vilaseca, M A; Lambruschini, N; Garcia-Romero, R; Meavilla, S; Perez-Dueñas, B; Pineda, M; Garcia-Cazorla, A; Campistol, J; Artuch, R

    2011-06-01

    To analyze the association between ammonia and glutamine used for metabolic control in inherited urea cycle disorders (UCD) in a large series of patients. Paired plasma amino acid-ammonia data from 26 UCD patients were analyzed (n=921). Increased plasma glutamine values were consistently observed in UCD patients, despite normal plasma ammonia concentrations, especially for mitochondrial UCD. Further therapeutic efforts are probably needed to control increased glutamine values, considering their potentially neurotoxic effect. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    PubMed

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

    1990-10-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2014-05-01

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

  20. Correlation of paired toxic plasma and saliva paracetamol concentrations following deliberate self-poisoning with paracetamol.

    PubMed

    Soderstrom, Jessamine H; Fatovich, Daniel M; Mandelt, Christine; Vasikaran, Sam; McCoubrie, David L; Daly, Frank F; Burrows, Sally A

    2012-07-01

    • Paracetamol is commonly used in deliberate self poisoning (DSP) and this requires blood sampling to refine risk assessment. If saliva concentrations agreed with plasma concentrations, then this could support the development of non-invasive testing. Our pilot work supports this hypothesis, but was largely confined to nontoxic concentrations. • We found agreement between the indications for treatment of paracetamol DSP based on plasma and saliva paracetamol concentrations. Saliva may hold promise as a non-invasive method to risk stratify paracetamol poisoning. Paracetamol is commonly used in deliberate self poisoning (DSP) and requires blood sampling to refine risk assessment. We aimed to test the agreement between plasma and saliva paracetamol concentrations in the toxic range in DSP. Contemporaneous paired plasma and saliva paracetamol concentrations were measured. Saliva was collected using a Sarstedt Salivette® device and the concentration was measured using a colorimetric method. Fifty-six patients (44, 78% female) median age 26 years (IQR 20-41) were enrolled. The median reported paracetamol ingestion was 10 g (IQR 6-14). Specimens were collected at a median of 4 h (IQR 4-5.3) post ingestion. The median plasma and saliva paracetamol concentrations were 29 mg l(-1) (IQR 8-110) and 38 mg l(-1) (IQR 10-105) respectively [mean difference 8 mg l(-1) , 95% confidence interval (CI) 2, 14]. Lin's concordance correlation was 0.97 (95% CI 0.96, 0.98). There were 15 patients who were treated with N-acetylcysteine. Their median reported paracetamol ingestion was 14 g (IQR 10-23) and samples were collected at a median of 4 h post ingestion. The median plasma and saliva paracetamol concentrations were 167 mg l(-1) (IQR 110-200) and 170 mg l(-1) (IQR 103-210) respectively (mean difference 15 mg l(-1) , 95% CI -4, 35). Lin's concordance correlation was 0.94 (95% CI 0.88, 0.99). No patient needing treatment would have been missed using saliva concentrations only. The

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

    PubMed

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

    2017-03-01

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

  2. Increased plasma concentrations of tumour markers in the absence of neoplasia.

    PubMed

    Trapé, Jaume; Filella, Xavier; Alsina-Donadeu, Montse; Juan-Pereira, Lluïsa; Bosch-Ferrer, Ángels; Rigo-Bonnin, Raül

    2011-10-01

    Tumour markers are a very heterogeneous group of molecules that are generally found in very small concentrations in the plasma and serum of healthy individuals. In the process of neoplastic differentiation the cell can synthesize, release, or induce synthesis of other cells, thus increasing their concentration in plasma and serum. These substances may also increase their plasma concentration in patients without cancer due to processes that increase the release or reduce catabolism, and so give rise to false positives. An understanding of the main physiopathological processes that increase the concentrations of these substances could improve our interpretation of tumour markers and their clinical application. In this study we review the physiopathological processes that may increase the plasma concentrations of tumour markers. We performed a bibliography review in PubMed, searching for causes of false positives for the following tumour markers: α-Fetoprotein, CA 125, CA 15-3, CA 19-9, CA 72-4, carcinoembryonic antigen, CYFRA 21-1, squamous cell carcinoma, prostatic specific antigen, β(2)-microglobulin, choriogonadotropin (β chain), chromogranin A, neuron specific enolase, HER2-neu, progastrin releasing peptide, S-100, and thyroglobulin. The results favour the use of tests which can identify pathological processes that may increase tumour marker concentrations.

  3. Effects of cholestyramine and colestipol on the plasma concentrations of propranolol.

    PubMed Central

    Hibbard, D M; Peters, J R; Hunninghake, D B

    1984-01-01

    The effect of equivalent hypolipidaemic doses of cholestyramine (8 g) or colestipol (10 g) on the plasma concentrations of propranolol and 4'-hydroxypropranolol was studied in 12 normal volunteers following the oral administration of 120 mg of normal release propranolol tablets. When two doses of either cholestyramine or colestipol were administered prior to the propranolol, the peak plasma concentrations and area under the curve for both propranolol and the metabolite 4'-hydroxypropranolol were reduced significantly (P less than 0.05). We conclude that the drug interaction between cholestyramine or colestipol and propranolol leads to significant reductions in plasma concentrations of propranolol and 4'-hydroxypropranolol which may cause a clinically diminished effect for a given dosage. Therefore, patients should be observed when either of these resins are added to or deleted from a therapeutic regimen. PMID:6487473

  4. Plasma Concentrations of Digoxin after Oral Administration in the Fasting and Postprandial State

    PubMed Central

    White, R. J.; Chamberlain, D. A.; Howard, M.; Smith, T. W.

    1971-01-01

    After the oral administration of 0·5 mg of digoxin in tablet form to fasting subjects peak plasma levels were reached in 30 to 60 minutes. Levels then fell to reach a plateau at six to eight hours. When the same dose was given after food the peak plasma concentrations were significantly lower, but the concentrations reached in samples obtained from two to eight hours after the dose did not differ appreciably from corresponding samples obtained in the fasting experiments. In a four-week cross-over study of 21 patients on maintenance therapy, digoxin taken regularly in the fasting state produced plasma concentrations similar to those obtained when the drug was taken after meals. The rapid appearance of digoxin in the blood suggests that the oral route of administration is adequate for most patients who require rapid digitalization, and the timing of maintenance dosage in relation to meals is unimportant. PMID:5100372

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

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

    PubMed

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

    2015-11-01

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

  7. Antifungal use and therapeutic monitoring of plasma concentrations of itraconazole in heart and lung transplantation patients.

    PubMed

    Brett, Jonathan; Chong, OiFong; Graham, Garry G; Ray, John E; Marriott, Deborah; Williams, Kenneth M; Day, Richard O

    2013-02-01

    The prophylactic use of itraconazole has dramatically reduced the incidence of fungal infections in patients after solid-organ transplantation. To further reduce this incidence, it has been suggested that plasma concentrations of itraconazole be monitored and maintained above a putative minimum target concentration of 500 ng/mL. A retrospective audit was undertaken of patients who had had a heart or lung transplant over a 14-month period (between January 1, 2010 and March 31, 2011). The itraconazole prophylaxis regimen (dose, time of last dose, time of blood collection) and plasma concentrations were recorded together with the use of concomitant antacid medication. Details of breakthrough fungal infections were documented. Eighty-four heart or lung organ transplantations were undertaken in the study period; 57 were treated prophylactically with itraconazole. Plasma concentrations of itraconazole were monitored in 56% (n = 32) of these cases. Considerable interpatient (range, 50-2000 ng/mL) and intrapatient variability in plasma concentrations was observed. The putative target was not achieved consistently in the majority of cases. All patients were taking a proton pump inhibitor. Six of the cohort developed an invasive fungal infection. None of the 3 patients for whom plasma concentrations were monitored was above the target concentration. Further clinical studies, involving monitoring of the active metabolite and attention to the importance of the stereoisomers of itraconazole, may give better insight into the appropriateness of the currently suggested minimum target concentration, whose validity remains uncertain. Formulations with improved absorption characteristics could reduce the variability of absorption with the goal of further reducing the incidence of infrequent, but life-threatening, invasive fungal infections.

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

    PubMed

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

    2016-12-01

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

  9. Plasma and skin blister fluid concentrations of trimethoprim following its oral administration.

    PubMed

    Klimowicz, A; Nowak, A; Kadyków, M

    1988-01-01

    Plasma and skin blister fluid concentration-time curves following a single oral dose of trimethoprim have been evaluated. Skin blisters were produced by the cantharides technique, using patches with cantharidin ointment. Trimethoprim concentrations in plasma following multiple doses of 200 mg were also determined. The maximal concentration in plasma after a single oral dose of 400 mg trimethoprim was 3.95 +/- 1.08 mg/l, and it was observed after 2 h, whereas in skin blister fluid the level was 2.21 +/- 0.62 mg/l, and it was delayed for up to 6 h. This means that a certain time is required for drug transfer from the capillaries via the basal membrane into blister fluid. Penetration of the drug into blister fluid, defined as the ratio of the areas under the trimethoprim level time curve in skin blister fluid to that of plasma, was 0.826 +/- 0.096. The steady-state concentration of trimethoprim in plasma during routine treatment with 200-mg doses ranged between 2 and 3.5 mg/l.

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

    PubMed

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

    1985-12-01

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

  11. Concentrations of danofloxacin 18% solution in plasma, milk and tissues after subcutaneous injection in dairy cows.

    PubMed

    Mestorino, N; Marchetti, M L; Turic, E; Pesoa, J; Errecalde, J

    2009-04-01

    Danofloxacin is a fluoroquinolone developed for use in veterinary medicine. Its concentrations and pharmacokinetic profile in plasma, milk and tissues of lactating dairy cows were determined, and its milk withdrawal time (WT) calculated. Twenty-one dairy cows received a single subcutaneous administration of 18% mesylate danofloxacin salt (6 mgkg(-1)). Plasma and milk samples were obtained at different times until 48 h. Groups of three animals were sacrificed at different post-administration times and tissue samples (mammary gland, uterus, duodenum, jejunum, ileum, colon and mesenteric lymph nodes) obtained. Danofloxacin concentrations were determined by liquid chromatography with fluorescence detection. The milk WT was calculated by the Time to Safe Concentration method (Software WTM 1.4, EMEA). Danofloxacin was rapidly absorbed and its distribution from plasma to all sampled tissues and milk was extensive. Milk and tissues concentrations were several times above those found in plasma. Plasma area under the curve (AUCp) was 9.69 microghmL(-1) and its elimination half life (T(beta)(1/2)) was 12.53 h. AUC values for the various tissues and milk greatly exceeded AUCp. T(beta)(1/2) from milk and tissues ranged between 4.57 and 21.91 h and the milk withdrawal time was 73.48 h. The reported results support the potential use of danofloxacin in the treatment of mastitis and other infections in milk cows with 3 days of withdrawal.

  12. Urine measurement indicates the plasma brain natriuretic peptide concentration during optimization of heart failure treatment.

    PubMed

    Hahn, Robert G; Jaarsma, Tiny; Waldréus, Nana; Linssen, Gerard C M

    2016-01-01

    To assess the correlation between the amino-terminal pro-hormone brain natriuretic peptide (NT-proBNP) concentration in blood and urine during a period when actively adjusting the treatment of heart failure (HF). Plasma and urine analyses of NT-proBNP were compared in 51 patients on admission to and discharge from a nurse-led outpatient clinic where HF treatment was optimized. The median time between the two measurements was 42 days. Correlations were analyzed using linear regression, where R(2) is the degree of variability in the plasma NT-proBNP concentration that can be accounted for by the urinary NT-proBNP. There was a statistically significant linear relationship between the urine and plasma concentrations of NT-proBNP on both occasions, but R(2) varied greatly depending on how the data were presented. The correlation between the raw data showed an R(2) of only 30%, and it almost doubled upon logarithm transformation, which shows that the variability (error) was concentration-dependent. Correction of the urinary NT-proBNP for urinary creatinine further increased R(2) for the logarithm-transformed correlation to 68% on admission and 76% on discharge. The highest R(2) (77%) was obtained when the relative changes in urinary NT-proBNP/creatinine between admission and discharge were compared with the corresponding relative changes in the plasma concentration. The sensitivity and specificity of the urine in indicating plasma concentration changes > 10% were 82% and 86%, respectively. Relative changes in plasma NT-proBNP could be reliably estimated from urine samples during a period of optimization of HF treatment.

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

    PubMed

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

    2015-05-01

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

  14. Relationship between craving and plasma leptin concentrations in patients with cocaine addiction.

    PubMed

    Martinotti, Giovanni; Montemitro, Chiara; Baroni, Gaia; Andreoli, Sara; Alimonti, Flaminia; Di Nicola, Marco; Tonioni, Federico; Leggio, Lorenzo; di Giannantonio, Massimo; Janiri, Luigi

    2017-08-05

    There is robust evidence indicating an overlap between neurobiological circuitry and pathways that regulate addictions and those that regulate appetite and food intake. Rodent work suggests a role of the appetitive peptide leptin in cocaine-seeking behaviours. The goal of this study was to investigate the possible relationship between plasma leptin concentrations and cocaine craving and use in patients seeking treatment for cocaine dependence. Patients (N=43) with a DSM-IV diagnosis of cocaine dependence were studied before starting detoxification (baseline; T0) and then again 14days after (T1; only those patients who abstained from cocaine during the study). Blood samples for plasma leptin concentrations were collected and cocaine craving was assessed using the Brief Cocaine Craving Questionnaire (Brief-CCQ). Food craving was also assessed using a food Visual Analogue Scale (f-VAS). Barratt Impulsiveness Scale (BIS) was used to evaluate impulsivity. Plasma leptin concentrations at T0 significantly correlated with baseline Brief-CCQ scores (r=0.34, p<0.05). Furthermore, plasma leptin concentrations at T1 significantly correlated with the baseline amount of cocaine used (r=0.5, p<0.05). There were no significant correlations between plasma leptin concentrations and f-VAS scores either at T0 or T1 (p's>0.05). The present study suggests a potential relationship between plasma leptin concentrations and cocaine craving and use. Future mechanistic studies are needed to determine whether manipulations of leptin signalling may lead to novel pharmacological approaches to treat cocaine addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-04-01

    Brassica vegetables are common components of the diet and have beneficial as well as potentially adverse health effects. Following enzymatic breakdown, some glucosinolates in brassica vegetables produce sulforaphane, phenethyl, and indolylic isothiocyanates that possess anticarcinogenic activity. In contrast, progoitrin and indolylic glucosinolates degrade to goitrin and thiocyanate, respectively, and may decrease thyroid hormone production. Radioiodine uptake to the thyroid is inhibited by 194 μmol of goitrin, but not by 77 μmol of goitrin. Collards, Brussels sprouts, and some Russian kale (Brassica napus) contain sufficient goitrin to potentially decrease iodine uptake by the thyroid. However, turnip tops, commercial broccoli, broccoli rabe, and kale belonging to Brassica oleracae contain less than 10 μmol of goitrin per 100-g serving and can be considered of minimal risk. Using sulforaphane plasma levels following glucoraphanin ingestion as a surrogate for thiocyanate plasma concentrations after indole glucosinolate ingestion, the maximum thiocyanate contribution from indole glucosinolate degradation is estimated to be 10 μM, which is significantly lower than background plasma thiocyanate concentrations (40-69 μM). Thiocyanate generated from consumption of indole glucosinolate can be assumed to have minimal adverse risks for thyroid health. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed Central

    Bunch, Ronald; Leung, Angela M.

    2016-01-01

    Brassica vegetables are common components of the diet and have beneficial as well as potentially adverse health effects. Following enzymatic breakdown, some glucosinolates in brassica vegetables produce sulforaphane, phenethyl, and indolylic isothiocyanates that possess anticarcinogenic activity. In contrast, progoitrin and indolylic glucosinolates degrade to goitrin and thiocyanate, respectively, and may decrease thyroid hormone production. Radioiodine uptake to the thyroid is inhibited by 194 μmol of goitrin, but not by 77 μmol of goitrin. Collards, Brussels sprouts, and some Russian kale (Brassica napus) contain sufficient goitrin to potentially decrease iodine uptake by the thyroid. However, turnip tops, commercial broccoli, broccoli rabe, and kale belonging to Brassica oleracae contain less than 10 μmol of goitrin per 100-g serving and can be considered of minimal risk. Using sulforaphane plasma levels following glucoraphanin ingestion as a surrogate for thiocyanate plasma concentrations after indole glucosinolate ingestion, the maximum thiocyanate contribution from indole glucosinolate degradation is estimated to be 10 μM, which is significantly lower than background plasma thiocyanate concentrations (40–69 μM). Thiocyanate generated from consumption of indole glucosinolate can be assumed to have minimal adverse risks for thyroid health. PMID:26946249

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

  19. Investigation of critical factors for the resolution of SR695, a key impurity, from efavirenz in the reversed-phase assay of efavirenz dosage forms.

    PubMed

    Weissburg, Robert P; Montgomery, Eda Ross; Junnier, Lisa A; Segretario, Jim; Cook, Stacy; Hovsepian, Paul K

    2002-04-01

    An investigation of the critical factors effecting the resolution of SR695 from efavirenz in the assay of efavirenz by reversed-phase HPLC was performed. This study was implemented to address the inability of a subset of the Zorbax SB-CN columns used in this method to adequately perform this separation, which were otherwise indistinguishable from columns of this type that could. In this study, column temperature, detector time-constant, pre-gradient isocratic hold-time, pre-column mixing volume, column, and HPLC type were considered. Experimental Design methods were employed to find the relative importance of these factors and to find parameters that would optimize the resolution of SR695 and efavirenz on any HPLC, with any column of this type, for both efavirenz oral liquid and capsule samples. It was also desired that this method change be minimal, so that extensive revalidation would not be required. The most important factors were the column temperature, with lower temperatures giving better resolution, and pre-column mixing volume of sample with mobile phase, with higher mixing volumes giving better resolution up to an asymptote reached at around 150 microl. Added pre-gradient isocratic hold time was found to result in a small improvement in resolution, but was insignificant compared with the other factors mentioned above. A possible explanation is given for the mechanism by which temperature and pre-column mixing have this effect on the resolution obtained in this assay.

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

    PubMed

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

    1994-01-01

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

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

    PubMed

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

    2007-01-01

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

  2. Depression and IL-6 blood plasma concentrations in advanced cancer patients.

    PubMed

    Jacobson, Colleen M; Rosenfeld, Barry; Pessin, Hayley; Breitbart, William

    2008-01-01

    The authors explored the relationship between depression and interleukin-6 (IL-6) blood plasma concentrations among advanced-stage cancer patients. Seventy-three patients with advanced cancer were rated on depression with the Hamilton Rating Scale for Depression and gave blood to be assayed for blood plasma concentration of IL-6. Initial results found no correlation between depression and IL-6. Subsequent analyses found that among those whose blood was drawn within 48 hours of interview completion, depression and IL-6 were highly correlated. Future studies focusing on the relationship between immune functioning and depression must be particularly vigilant regarding methodological issues.

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

    PubMed Central

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

    2003-01-01

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

  4. Pathogen inactivation treatment of plasma and platelet concentrates and their predicted functionality in massive transfusion protocols.

    PubMed

    Arbaeen, Ahmad F; Schubert, Peter; Serrano, Katherine; Carter, Cedric J; Culibrk, Brankica; Devine, Dana V

    2017-05-01

    Trauma transfusion packages for hemorrhage control consist of red blood cells, plasma, and platelets at a set ratio. Although pathogen reduction improves the transfusion safety of platelet and plasma units, there is an associated reduction in quality. This study aimed to investigate the impact of riboflavin/ultraviolet light-treated plasma or platelets in transfusion trauma packages composed of red blood cell, plasma, and platelet units in a ratio of 1:1:1 in vitro by modeling transfusion scenarios for trauma patients and assessing function by rotational thromboelastometry. Pathogen-reduced or untreated plasma and buffy coat platelet concentrate units produced in plasma were used in different combinations with red blood cells in trauma transfusion packages. After reconstitution of these packages with hemodiluted blood, the hemostatic functionality was analyzed by rotational thromboelastometry. Hemostatic profiles of pathogen-inactivated buffy coat platelet concentrate and plasma indicated decreased activity compared with their respective controls. Reconstitution of hemodiluted blood (hematocrit = 20%) with packages that contained treated or nontreated components resulted in increased alpha and maximum clot firmness and enhanced clot-formation time. Simulating transfusion scenarios based on 30% blood replacement with a transfusion trauma package resulted in a nonsignificant difference in rotational thromboelastometry parameters between packages containing treated and nontreated blood components (p ≥ 0.05). Effects of pathogen inactivation treatment were evident when the trauma package percentage was 50% or greater and contained both pathogen inactivation-treated plasma and buffy coat platelet concentrate. Rotational thromboelastometry investigations suggest that there is relatively little impact of pathogen inactivation treatment on whole blood clot formation unless large amounts of treated components are used. © 2017 AABB.

  5. Fatigue and plasma cytokine concentrations at rest and during exercise in patients with sarcoidosis.

    PubMed

    Baydur, Ahmet; Alavy, Bahram; Nawathe, Amar; Liu, Shanshan; Louie, Stan; Sharma, Om Prakash

    2011-07-01

    Patients with sarcoidosis exhibit exercise intolerance-related fatigue and increased levels of circulating proinflammatory cytokines at rest. Exercise may result in increased plasma cytokine levels (PCLs) in healthy adults, but such a relationship has not been studied in sarcoidosis patients. To assess relationship of fatigue in sarcoidosis with PCLs at rest and with cardiopulmonary exercise testing (CPET). We assessed lung function, CPET data, multidimensional fatigue inventory, plasma tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations before, immediately after, and 4-6 h following CPET in 22 sarcoidosis patients (13 receiving immunomodulatory drugs) and 22 controls. Patients exhibited greater fatigue, reduced cardiorespiratory function, higher Medical Research Council (MRC) scores and higher plasma TNF-α concentrations than controls at all times. Plasma IL-1β levels did not differ between cohorts. Patients exhibited a 28% increase (statistically not significant) in TNF-α level immediately post exercise. Plasma IL-β concentrations did not change among cohorts. Treated patients exhibited higher MRC and physical fatigue scores and lower breathing reserve, but no differences in cardiorespiratory function or PCLs compared to untreated patients. In treated patients, pre-exercise plasma IL-1β correlated with physical fatigue, reduced motivation and total fatigue; TNF-α levels only correlated with general fatigue score. Treated sarcoidosis patients exhibit a relation between physical fatigue, reduced motivation and total fatigue and pre-exercise plasma IL-1β concentrations. Acute exercise does not increase PCLs. Whether the reduced MRC score and physical fatigue in treated patients is related to the therapy or to the underlying inflammatory process is difficult to determine. © 2010 Blackwell Publishing Ltd.

  6. Intake of whole grains and vegetables determines the plasma enterolactone concentration of Danish women.

    PubMed

    Johnsen, Nina F; Hausner, Helene; Olsen, Anja; Tetens, Inge; Christensen, Jane; Knudsen, Knud Erik Bach; Overvad, Kim; Tjønneland, Anne

    2004-10-01

    The mammalian lignan enterolactone (ENL), which is produced from dietary plant-lignan precursors by the intestinal microflora, may protect against breast cancer and other hormone-dependent cancers. This cross-sectional study examined which variables related to diet and lifestyle were associated with high plasma concentrations of ENL in Danish postmenopausal women. Plasma ENL was measured by time-resolved fluoroimmunoassay in 857 Danish women aged 50-64 y who participated in a prospective cohort study. Diet was assessed using a semiquantitative FFQ, and background information on lifestyle was collected using a self-administered questionnaire. Multiple analyses of covariance were completed in two steps. The median plasma ENL concentration was 27 nmol/L (range 0-455 nmol/L). In covariance analyses, positive associations were found between consumption of cereals, vegetables, and beverages and plasma ENL concentration. When analyzing subgroups of these food groups, the associations were confined to whole-grain products, cabbage, leafy vegetables, and coffee. For fat and the nondietary variables, negative associations between BMI, smoking, and frequency of bowel movements and plasma ENL concentration were observed. These data show that foods high in ENL precursors are associated with high concentrations of ENL. Furthermore, smoking, frequent bowel movements, and consumption of fat seems to have a negative affect on the ENL concentration. In conclusion, whole grains and vegetables are the most important dietary providers of plant lignans for the concentration of ENL in Danish postmenopausal women, and if ENL is found to protect against cancer or heart disease, the intake of whole grains and vegetables should be increased.

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

    PubMed

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

    2008-06-01

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed

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

    2004-10-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2013-01-01

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

  13. High plasma concentrations of dolutegravir in patients with ABCG2 genetic variants.

    PubMed

    Tsuchiya, Kiyoto; Hayashida, Tsunefusa; Hamada, Akinobu; Oki, Sakurako; Oka, Shinichi; Gatanaga, Hiroyuki

    2017-08-29

    The ATP-binding cassette transporters B1 (ABCB1) and G2 (ABCG2) are both expressed in the intestine and known as efflux transporters of drugs. Dolutegravir was identified recently as a substrate of both ABCB1 and ABCG2. This study aimed to determine the relations between single-nucleotide polymorphisms of ABCB1 and ABCG2 genes and plasma dolutegravir concentrations. Plasma samples were obtained from 42 HIV-1-infected patients treated with dolutegravir-containing regimens 0.5-4 h after dolutegravir dosing. Plasma dolutegravir concentrations were measured by liquid chromatography-mass spectrometry. Genomic DNA was isolated from peripheral blood mononuclear cells. Genotyping of allelic variants of ABCB1 1236 C>T (rs1128503), 2677 G>T/A (rs2032582), 3435 C>T (rs1045642), 4036 A>G (rs3842), and ABCG2 421 C>A (rs2231142) was performed using the TaqMan drug metabolism assays. None of the genotypes in ABCB1 1236 C>T, 2677 G>T/A, 3435 C>T, and 4036 A>G correlated with plasma dolutegravir concentration. In contrast, the mean peak plasma concentration of dolutegravir was significantly higher in the genotypes of ABCG2 421 AA (5002 ng/ml, n=3) compared with the genotypes of ABCG2 421 CC (2569 ng/ml, n=22) and ABCG2 421 CA (2479 ng/ml, n=17) (P=0.0005). The speculated peak level of plasma dolutegravir concentration was significantly higher in ABCG2 genetic variant holders, probably, at least in part, because of low expression levels of efflux transporters in the intestines associated with these genetic variants.

  14. Differential alterations in plasma colony-stimulating factor concentrations in meningococcaemia.

    PubMed Central

    Waring, P M; Presneill, J; Maher, D W; Layton, J E; Cebon, J; Waring, L J; Metcalf, D

    1995-01-01

    To determine whether circulating levels of any of the colony-stimulating factors (CSF) might contribute to the host response in severe sepsis, plasma concentrations of granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF), and macrophage CSF (M-CSF) were measured by immunoassays in 20 subjects with meningococcaemia, a bloodstream infection caused by Neisseria meningitidis, that has proven to be a valuable model to study the responses of other inflammatory mediators during sepsis and septic shock in humans. Plasma G-CSF concentrations were transiently elevated in most subjects during the early phase of meningococcaemia, and were higher in subjects with septic shock (mean +/- s.d. = 165 +/- 142 ng/ml, n = 9) compared with those who remained normotensive (mean +/- s.d. = 7 +/- 2 ng/ml, n = 10) (P < 0.05). Peak plasma G-CSF concentrations > 10 ng/ml were associated with the development of septic shock (P < 0.01), disseminated intravascular coagulation (P < 0.01), fulminant infection (P < 0.05), and a fatal outcome (P < 0.01). Plasma GM-CSF concentrations > 1 ng/ml were briefly present in subjects with life-threatening septic shock (1-15 ng/ml, n = 5), and were strongly associated with fulminant meningococcaemia (P < 0.01). Plasma M-CSF concentrations were marginally elevated in all subjects, but were not associated with complications related to or arising from sepsis-induced organ injury. This study demonstrates that plasma levels of G-CSF, GM-CSF and M-CSF show very different responses during meningococcaemia, changes which presumably reflect the different roles played by these mediators in sepsis and, potentially, in septic shock. PMID:8536364

  15. Plasma concentration of ketorolac after local infiltration analgesia in hip arthroplasty.

    PubMed

    Affas, F; Eksborg, S; Wretenberg, P; Olofsson, C; Stephanson, N; Stiller, C-O

    2014-10-01

    Local infiltration analgesia (LIA) with local anaesthetic (ropivacaine), a nonsteroidal anti-inflammatory drug (ketorolac) and epinephrine after lower extremity arthroplasty has gained increasing popularity during the last decade. This method has certain advantages, which include minimal systemic side effects, faster post-operative mobilization, earlier post-operative discharge from hospital and less opioid consumption. However, information regarding plasma concentrations of ketorolac after LIA mixture is insufficient to predict the risk of renal impairment in patients subjected to arthroplasty. To determine the maximal plasma concentration and the exposure of ketorolac during the first 30 h following LIA in hip arthroplasty. Thirteen patients scheduled for primary total hip arthroplasty with LIA (ropivacaine 200 mg, ketorolac 30 mg and epinephrine 0.5 mg in a volume of 106 ml) were included. Plasma concentration of ketorolac was quantified by liquid chromatography-mass spectrometry. In addition, we assessed the effect of increasing age and decreasing glomerular filtration rate on the maximal plasma concentration and the total exposure to ketorolac during 30 h. The range of the maximal plasma concentration, 0.3-2.2 mg/l, was detected 30 min-4 h after completing the infiltration. Similar plasma levels have been reported after intramuscular injection of the same dose of ketorolac to healthy elderly volunteers. Exposure to ketorolac after LIA may be comparable to an intramuscular injection of the same dose. Decision of dose reduction should be based on clinical assessment of risk factors. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  16. Multicomponent systems with cyclodextrins and hydrophilic polymers for the delivery of Efavirenz.

    PubMed

    Vieira, Alexandre Couto Carneiro; Ferreira Fontes, Danilo Augusto; Chaves, Luise Lopes; Alves, Lariza Darlene Santos; de Freitas Neto, José Lourenço; de La Roca Soares, Monica Felts; Soares-Sobrinho, Jose L; Rolim, Larissa Araújo; Rolim-Neto, Pedro José

    2015-10-05

    Efavirenz (EFZ) is one of the most used drugs in the treatment of AIDS and is the first antiretroviral choice. However, since it has low solubility, it does not exhibit suitable bioavailability, which interferes with its therapeutic action and is classified as a class II drug according Biopharmaceutical Classification System (low solubility and high permeability). Among several drug delivery systems, the multicomponent systems with cyclodextrins and hydrophilic polymers are a promising alternative for increasing the aqueous solubility of the drug. The present study aimed to develop and characterize in a ternary system of EFZ, MβCD and PVP K30. The results showed that the solid ternary system provided a large increase in the dissolution rate which was greater than 80% and was characterized by DSC, TG, XRD, FT-IR and SEM. The use of the ternary system (EFZ, MβCD and PVP K30 1%) proved to be a viable, effective and safe delivery of the drug. The addition of the hydrophilic polymer appeared to be suitable for the development of a solid oral pharmaceutical product, with possible industrial scale-up and with low concentration of CDs (cyclodextrins).

  17. Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus.

    PubMed

    Lavra, Zênia Maria Maciel; Pereira de Santana, Davi; Ré, Maria Inês

    2017-01-01

    Efavirenz (EFV), a first-line anti-HIV drug largely used as part of antiretroviral therapies, is practically insoluble in water and belongs to BCS class II (low solubility/high permeability). The aim of this study was to improve the solubility and dissolution performances of EFV by formulating an amorphous solid dispersion of the drug in polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus(®)) using spray-drying technique. To this purpose, spray-dried dispersions of EFV in Soluplus(®) at different mass ratios (1:1.25, 1:7, 1:10) were prepared and characterized using particle size measurements, SEM, XRD, DSC, FTIR and Raman microscopy mapping. Solubility and dissolution were determined in different media. Stability was studied at accelerated conditions (40 °C/75% RH) and ambient conditions for 12 months. DSC and XRD analyses confirmed the EFV amorphous state. FTIR spectroscopy analyses revealed possible drug-polymer molecular interaction. Solubility and dissolution rate of EFV was enhanced remarkably in the developed spray-dried solid dispersions, as a function of the polymer concentration. Spray-drying was concluded to be a proper technique to formulate a physically stable dispersion of amorphous EFV in Soluplus(®), when protected from moisture.

  18. PLASMA THYROXINE (T4) CONCENTRATION IN ZOO-KEPT BLACK-TAILED PRAIRIE DOGS (CYNOMYS LUDOVICIANUS).

    PubMed

    Eshar, David; Nau, Melissa R; Pohlman, Lisa M

    2017-03-01

    This study was conducted to determine plasma thyroxine (T4) concentrations in zoo-kept black-tailed prairie dogs ( Cynomys ludovicianus ). Thirty-one healthy prairie dogs of both sexes were studied as part of their annual clinical health evaluation, performed under general isoflurane anesthesia. Each animal underwent a complete physical examination, complete blood count, plasma biochemistry, and venous blood gas analysis. Heparinized venous blood samples were collected individually and processed for plasma T4 analysis using a veterinary biochemistry analyzer. The median plasma T4 concentration for the prairie dogs in this study was 4.1 μg/dl (minimum = 0.6 μg/dl; maximum = 8.0 μg/dl). The mean ± standard deviation plasma T4 concentration was 4.49 ± 2.39 μg/dl. No significant differences were found for varying ages, sexes, weights, or housing systems. The data presented in this report can promote better physiologic understanding and improve clinical management of this rodent species.

  19. Interactions of orphenadrine and phenobarbitone with chlorpromazine: plasma concentrations and effects in man.

    PubMed Central

    Loga, S; Curry, S; Lader, M

    1975-01-01

    1 Two studies were carried out on acutely psychotic patients receiving chlorpromazine (100 mg) 8-hourly. 2 In the pilot study on five patients, plasma chlorpromazine concentrations fell over the course of 3 weeks of treatment and parallel changes were noted in the plasma half-life of antipyrine, salivation rate and handwriting length. 3 In the main study involving twelve patients treated for 15 weeks, the above findings were confirmed and were interpreted as indicating that chlorpromazine accelerated its own metabolism by inducing liver microsomal oxidising enzymes. No metabolites of chlorpromazine were detected in plasma. 4 The addition of phenobarbitone (50 mg) 8-hourly for 3 weeks, or orphenadrine (100 mg) 8-hourly for 3 weeks, resulted in a lowering of plasma chlorpromazine concentrations together with a further shortening of plasma antipyrine half-life. 5 Physiological effects of the additional treatments suggested that phenobarbitone lessens the effects of chlorpromazine by lowering body concentrations. However, orphenadrine acts more by virtue of its anticholinergic effects. 6 It was concluded that phenobarbitone and orphenadrine should not be prescribed routinely in patients receiving major tranquillisers. The need for the addition of orphenadrine should be assessed in each individual case. PMID:791320

  20. Low plasma selenium concentrations in critically ill children: the interaction effect between inflammation and selenium deficiency

    PubMed Central

    2014-01-01

    Introduction Low plasma selenium concentrations are frequent in critically ill patients. However, whether this is due to systemic inflammation, a deficient nutritional state or both is still not clear. We aimed to determine the factors associated with low plasma selenium in critically ill children while considering the inflammatory response and nutritional status. Method A prospective study was conducted in 173 children (median age 34 months) with systemic inflammatory response who had plasma selenium concentrations assessed 48 hours after admission and on the 5th day of ICU stay. The normal reference range was 0.58 μmol/L to 1.6 μmol/L. The outcome variable was ‘low plasma selenium’, which was defined as plasma selenium values below the distribution median during this period. The main explanatory variables were age, malnutrition, sepsis, C-reactive protein (CRP), and clinical severity scores. The data were analyzed using a Binomial Generalized Estimating Equations model, which includes the correlation between admission and 5th day responses. Results Malnutrition and CRP were associated with low plasma selenium. The interaction effect between these two variables was significant. When CRP values were less than or equal to 40 mg/L, malnutrition was associated with low plasma selenium levels (odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.39 to 7.63, P = 0.007; OR = 2.98, 95% CI 1.26 to 7.06, P = 0.013; OR = 2.49, 95% CI 1.01 to 6.17, P = 0.049, for CRP = 10, 20 and 40 mg/L, respectively). This effect decreased as CRP concentrations increased and there was loose significance when CRP values were >40 mg/L. Similarly, the effect of CRP on low plasma selenium was significant for well-nourished patients (OR = 1.13; 95% CI 1.06 to 1.22, P <0.001) but not for the malnourished (OR = 1.03; 95% CI 0.99 to 1.08, P = 0.16). Conclusions There is a significant interaction between the magnitude of the inflammatory

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

    PubMed Central

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

    1981-01-01

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

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

    PubMed

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

    1984-05-01

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

  3. Formulation Development and Dissolution Rate Enhancement of Efavirenz by Solid Dispersion Systems

    PubMed Central

    Koh, P. T.; Chuah, J. N.; Talekar, Meghna; Gorajana, A.; Garg, S.

    2013-01-01

    The aim of this study was to enhance the dissolution rate of efavirenz using solid dispersion systems (binary and ternary). A comparison between solvent and fusion method was also investigated. Solid dispersions of efavirenz were prepared using polyethylene glycol 8000, polyvinylpyrrolidone K30 alone and combination of both. Tween 80 was incorporated to obtain a ternary solid dispersion system. Dissolution tests were conducted and evaluated on the basis of cumulative percentage drug release and dissolution efficiency. Physicochemical characterizations of the solid dispersions were carried out using differential scanning calorimetric, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. Dissolution was remarkably improved in both systems compared to pure efavirenz (P<0.05). An optimum ratio was identified at a drug:polymer of 1:10. Incorporation of Tween 80 to 1:10 formulations formed using solvent method showed further improvement in the dissolution rate. Physicochemical characterization results suggested that efavirenz existed in the amorphous form in all the solid dispersion systems providing evidence of improvement in dissolution. No statistically significant difference (P>0.05) in dissolution was observed between the two methods. Binary and ternary solid dispersion systems both have showed a significant improvement in the dissolution rate of efavirenz. Formulations with only polyvinylpyrrolidone K30 showed best dissolution profile and 1:10 was identified as an optimum drug-polymer weight ratio. PMID:24082345

  4. [Budget impact analysis of efavirenz daily dose reduction at the Verona University Hospital].

    PubMed

    Costa, Enrico; Biasi, Valeria; Concia, Ercole; Jommi, Claudio; Lattuada, Emanuela; Manfre, Silvia; Venturini, Francesca; Lanzafame, Massimiliano

    2014-06-01

    Efavirenz is a non-nucleoside-reverse-transcriptase-inhibitor used as part of highly-active-antiretroviral-therapy for the treatment of the human immunodeficiency virus (HIV) type 1 infection. The present paper aims to describing the impact of efavirenz dose reduction on the pharmaceutical budget at the Verona University Hospital. A budget impact analysis comparing two prescribing scenarios was conducted: all patients treated with the efavirenz full dose (600 mg per day) vs. a proportion of patients treated with a reduced dose (200-400 mg per day). All outpatients referring to the Infectious Disease Clinic in the period November 2009-October 2011 were selected. Out of 132 patients treated with efavirenz, 25 were not considered, mainly due to a too short treatment period. Of the remaining 107 patients, 68 received the full dose, while 39 received a reduced dosage. The analysis included the cost of the drug and of diagnostic tests, from the National Health Service perspective. The daily dose reduction of efavirenz saved 54,664 euros (a 30% expenditure reduction). In sum, new strategies for pharmaceutical system sustainability are necessary; despite forthcoming expiring patents of several drugs, spending on antiretroviral drugs is expected to rise. This paper suggests a way of linking clinical benefits and cost reduction.

  5. Dose-adjusted plasma concentrations of sublingual buprenorphine are lower during than after pregnancy.

    PubMed

    Bastian, Jaime R; Chen, Huijun; Zhang, Hongfei; Rothenberger, Scott; Tarter, Ralph; English, Dennis; Venkataramanan, Raman; Caritis, Steve N

    2017-01-01

    Buprenorphine is a Food and Drug Administration-approved maintenance therapy for opioid use disorders and is increasingly being used in pregnant women with opioid use disorders as an alternative to methadone. Dosing of buprenorphine in pregnant women is based on the regimen recommended for nonpregnant females and males. Limited data are available defining the pharmacokinetic properties of sublingual buprenorphine administered during pregnancy. This study evaluated the impact of physiological changes associated with pregnancy on the pharmacokinetics of sublingual buprenorphine during and after pregnancy. Pregnant women (n = 13), between 18(0/7) and 37(6/7) weeks' singleton gestation, receiving sublingual buprenorphine twice daily for opioid use disorders were studied. Pharmacokinetic-2 studies were performed between 18 and 25 weeks (n = 7), pharmacokinetic-3 studies were performed between 31 and 37 weeks (n = 11), and pharmacokinetic-P was performed 4-18 weeks postpartum (n = 10). On the day of the study, blood was withdrawn prior to the daily morning dose of buprenorphine and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours after the dose. Buprenorphine plasma concentrations were analyzed by liquid chromatography tandem mass spectrometric detection. All pharmacokinetic parameters were observed or estimated using Microsoft Excel. Statistical analyses were performed to identify significant changes in study participants' buprenorphine pharmacokinetic parameter estimates over the duration of the study. Univariate linear and generalized linear mixed models were used to investigate changes in these measures over time, some of which were log transformed for normality. Dose-normalized (plasma concentration per dose) buprenorphine plasma concentrations were significantly lower during pregnancy (pharmacokinetic-2 plus pharmacokinetic-3) than during the postpartum period (pharmacokinetic-P). Specific pharmacokinetic parameters (and level of significance) were as follows

  6. Plasma Concentrations Following Application of Whole versus Cut Transdermal Clonidine Patches To Critically Ill Children

    PubMed Central

    Zuppa, Athena F.; Tejani, Shamim M.; Cullen, Edward J.; Nadkarni, Vinay M.

    2004-01-01

    Clonidine is used for hypertension and narcotic withdrawal prophylaxis in adults and children. This study described plasma absorption of clonidine from whole and cut transdermal clonidine patches. This was a retrospective descriptive study in an 18 bed multidisciplinary pediatric intensive care unit, evaluating 15 critically ill children with a median age of 1.1 years (range 0.3–11 years) treated with transdermal clonidine for narcotic withdrawal prophylaxis, and who had plasma clonidine concentrations measured. An assessment of the relationship between clonidine dose and patch integrity (whole vs. cut) with plasma concentrations was performed, with further analysis by Spearman Correlation Coefficient. Clonidine doses averaged 7.5±4.2 μg/kg/day (range 2.3–20 μg/kg/day) for 9.8±4.3 days (range 4–20 days). There were 9 cut patches and 6 whole patches. The average prescribed dose delivered by cut patches was 6.4±3 μg/kg/day, resulting in a mean plasma concentration of 1±1.1 ng/ mL (range <0.05–3.3 ng/mL). The average prescribed dose delivered by whole patches was 7±1.7 μg/kg/day, resulting in a mean plasma concentration of 0.55±0.3 ng/mL (range 0.13–1.5 ng/mL). The Spearman Correlation Coefficient was calculated to evaluate the correlation between dose and concentration. For whole and cut patches the correlation coefficient was 0.94 (P=0.005) and 0.72 (P=0.002), respectively. Doses ranging from 1.7 to 20 μg/kg/day using whole patches resulted in no plasma concentrations >2 ng/mL. However, a plasma concentration >2 ng/mL was achieved with a dose of 8.8 μg/kg/day delivered by a cut patch. In addition, the 2 samples that resulted in undetectable concentrations were taken from patients who were treated with cut patches. The results from this pilot study suggest that critically ill children absorb clonidine from transdermal patches, but the rate and extent of absorption appears to be more predictable with the use of whole patches compared to patches

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

    PubMed

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

    2002-04-01

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

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

    PubMed Central

    Pasloske, K; Burger, J; Conlon, P

    1998-01-01

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

  9. Elevated nonesterified fatty acid concentrations in severe preeclampsia shift the isoelectric characteristics of plasma albumin.

    PubMed

    Vigne, J L; Murai, J T; Arbogast, B W; Jia, W; Fisher, S J; Taylor, R N

    1997-11-01

    We previously hypothesized that the endothelial cell dysfunction observed in women with preeclampsia might be caused by an imbalance between circulating very low density lipoproteins and a cytoprotective pI 5.6 isoform of albumin, referred to as toxicity preventing albumin (TxPA). An accurate simplified method was developed to quantify TxPA in small volumes of pregnancy plasma by gel electrofocusing. This assay revealed that circulating TxPA concentrations in women with severe preeclampsia were significantly reduced compared to those in normal pregnant women and women with benign transient hypertension of pregnancy. Nonesterified fatty acids (NEFA) and triglycerides were elevated in plasma from women with severe preeclampsia compared to those in plasma from the two control groups. The inverse correlation between TxPA and NEFA values led us to analyze the NEFA bound to plasma albumin. Gas chromatography and mass spectrometry demonstrated no qualitative differences in the specific fatty acids bound to plasma albumin in severe preeclamptic and normal pregnant women. However, the quantity of NEFA bound to albumin was greater in preeclampsia plasma (2.5 mol NEFA/mol albumin) compared to that in normal pregnancy plasma (0.8 mol NEFA/mol albumin), accounting for the acidic pI shift observed in albumin from the former patients. Functional assays demonstrated that human very low density lipoprotein particles were toxic to human umbilical vein endothelial cells in vitro, but this toxicity was prevented by the addition of TxPA albumin to the culture medium.

  10. Kinetic and Related Determinants of Plasma Triglyceride Concentration in Abdominal Obesity: Multicenter Tracer Kinetic Study.

    PubMed

    Borén, Jan; Watts, Gerald F; Adiels, Martin; Söderlund, Sanni; Chan, Dick C; Hakkarainen, Antti; Lundbom, Nina; Matikainen, Niina; Kahri, Juhani; Vergès, Bruno; Barrett, P Hugh R; Taskinen, Marja-Riitta

    2015-10-01

    Patients with obesity and diabetes mellitus have increased risk of cardiovascular disease. A major cause is an atherogenic dyslipidemia related primarily to elevated plasma concentrations of triglyceride-rich lipoproteins. The aim of this study was to clarify determinants of plasma triglyceride concentration. We focused on factors that predict the kinetics of very-low density lipoprotein 1 (VLDL1) triglycerides. A multicenter study using dual stable isotopes (deuterated leucine and glycerol) and multicompartmental modeling was performed to elucidate the kinetics of triglycerides and apoB in VLDL1 in 46 subjects with abdominal obesity and additional cardiometabolic risk factors. Results showed that plasma triglyceride concentrations were dependent on both the secretion rate (r=0.44, P<0.01; r=0.45, P<0.01) and fractional catabolism (r=0.49, P<0.001; r=0.55, P<0.001) of VLDL1-triglycerides and VLDL1-apoB. Liver fat mass was independently and directly associated with secretion rates of VLDL1-triglycerides (r=0.56, P<0.001) and VLDL1-apoB (r=0.53, P<0.001). Plasma apoC-III concentration was independently and inversely associated with the fractional catabolisms of VLDL1-triglycerides (r=0.48, P<0.001) and VLDL1-apoB (r=0.51, P<0.001). Plasma triglyceride concentrations in abdominal obesity are determined by the kinetics of VLDL1 subspecies, catabolism being mainly dependent on apoC-III concentration and secretion on liver fat content. Reduction in liver fat and targeting apoC-III may be an effective approach for correcting triglyceride metabolism atherogenic dyslipidemia in obesity. © 2015 American Heart Association, Inc.

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

    PubMed

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

    2016-01-01

    The preferred sampling medium for measuring human exposures of persistent organic compounds (POPs) is blood, and relevant sample types include whole blood, plasma, and dried blood spots (DBS). Because information regarding the performance and comparability of measurements across these sample types is limited, it is difficult to compare across studies. This study evaluates the performance of POP measurements in plasma, whole blood and DBS, and presents the distribution coefficients needed to convert concentrations among the three sample types. Blood samples were collected from adult volunteers, along with demographic and smoking information, and analyzed by GC/MS for organochlorine pesticides (OCPs), chlorinated hydrocarbons (CHCs), polychlorinated biphenyls (PCBs), and brominated diphenyl ethers (PBDEs). Regression models were used to evaluate the relationships between the sample types and possible effects of personal covariates. Distribution coefficients also were calculated using physically-based models. Across all compounds, concentrations in plasma were consistently the highest; concentrations in whole blood and DBS samples were comparable. Distribution coefficients for plasma to whole blood concentrations ranged from 1.74 to 2.26 for pesticides/CHCs, averaged 1.69 ± 0.06 for the PCBs, and averaged 1.65 ± 0.03 for the PBDEs. Regression models closely fit most chemicals (R (2) > 0.80), and whole blood and DBS samples generally showed very good agreement. Distribution coefficients estimated using biologically-based models were near one and did not explain the observed distribution. Among the study population, median concentrations of several pesticides/CHCs and PBDEs exceeded levels reported in the 2007-2008 National Health and Nutrition Examination Survey, while levels of other OCPs and PBDEs were comparable or lower. Race and smoking status appeared to slightly affect plasma/blood concentration ratios for several POPs. The experimentally

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

    DTIC Science & Technology

    1993-01-01

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

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

    PubMed Central

    Phillips, W A

    1984-01-01

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

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

    SciTech Connect

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

    2004-03-11

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

  15. Dissociation between plasma concentrations of thyroxine and insulin-like growth factor-I.

    PubMed

    Dauncey, M J; Morovat, A; Rudd, B T; Shakespear, R A

    1990-09-01

    The relation between plasma concentrations of thyroxine (T4) and insulin-like growth factor-I (IGF-I) has been examined in young, growing pigs under controlled conditions of energy intake. Compared with euthyroid controls, plasma levels of IGF-I were significantly elevated (P less than 0.005) both in hypothyroid animals on the same food intake and in hyperthyroid animals on double the food intake. There was however no increase in IGF-I in a hyperthyroid group on the control level of intake. Contrary to previous reports in which energy intake was not controlled, it is concluded that there is no simple correlation between plasma concentrations of T4 and IGF-I.

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

    PubMed

    Kapuściński, A

    1991-01-01

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed

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

    1987-01-01

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

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

    PubMed

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

    2013-08-01

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

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

    PubMed Central

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

    2013-01-01

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

  1. Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease

    PubMed Central

    Thambisetty, Madhav; Simmons, Andrew; Velayudhan, Latha; Hye, Abdul; Campbell, James; Zhang, Yi; Wahlund, Lars-Olof; Westman, Eric; Kinsey, Anna; Güentert, Andreas; Proitsi, Petra; Powell, John; Causevic, Mirsada; Killick, Richard; Lunnon, Katie; Lynham, Steven; Broadstock, Martin; Choudhry, Fahd; Howlett, David R.; Williams, Robert J.; Sharp, Sally I.; Mitchelmore, Cathy; Tunnard, Catherine; Leung, Rufina; Foy, Catherine; O'Brien, Darragh; Breen, Gerome; Furney, Simon; Ward, Malcolm; Kloszewska, Iwona; Mecocci, Patrizia; Soininen, Hilkka; Tsolaki, Magda; Vellas, Bruno; Hodges, Angela; Murphy, Declan; Parkins, Sue; Richardson, Jill; Resnick, Susan M.; Ferrucci, Luigi; Wong, Dean F.; Zhou, Yun; Muehlboeck, Sebastian; Evans, Alan; Francis, Paul T.; Spenger, Christian; Lovestone, Simon

    2010-01-01

    Context Blood-based analytes as indicators of pathological processes in Alzheimer's disease (AD). Objective Combined proteomic and neuroimaging approach to identify plasma proteins associated with AD pathology. Design Discovery-phase proteomic experiments to identify plasma proteins associated with correlates of AD pathology including evidence of atrophy using neuroimaging and more rapid clinical progression, followed by replication using quantitative immunoassay. Extension studies in older non-demented humans using 11C-PiB amyloid imaging and transgenic mice with amyloid pathology. Setting Multi-center European study, AddNeuroMed, and the Baltimore Longitudinal Study of Aging (BLSA) in United States. Participants AD patients, mild cognitive impairment (MCI) subjects and healthy controls with standardized clinical assessments and structural neuroimaging. Plasma samples from non-demented older BLSA participants with brain amyloid imaging by PET. Main outcome measures Association of plasma proteins with brain atrophy, disease severity and rate of clinical progression. Extension studies in man and transgenic mice tested association between plasma proteins and brain amyloid. Results Clusterin/apolipoprotein-J was associated with atrophy of the entorhinal cortex, baseline disease severity and rapid clinical progression in AD. Increased plasma concentration of clusterin was predictive of greater beta amyloid (Aβ) burden in the medial temporal lobe. Subjects with AD had increased clusterin mRNA in blood but there was no effect of SNPs in the gene encoding clusterin (CLU) with gene or protein expression. Finally, APP/PS1 transgenic mice showed increased plasma clusterin, age-dependent increase in brain clusterin and amyloid and clusterin co-localisation in plaques. Conclusions Clusterin/apolipoprotein-J is a known amyloid chaperone associated with Alzheimer's disease severity, pathology and progression. Increased plasma concentration of clusterin is also associated with

  2. Effect of time exposure to high altitude on zinc and copper concentrations in human plasma.

    PubMed

    Rawal, S B; Singh, M V; Tyagi, A K; Roy, J; Dimri, G P; Selvamurthy, W

    1999-12-01

    Research has focused mainly on the relationship of zinc and copper contents and physical stresses like running, cycling, etc. It has also been reported that other forms of stresses change the concentration of these trace elements in humans. However,there are no reports on the effects of high altitude induced hypoxic stress on the plasma levels of these metals. Since hypoxia is one of the important stresses, we considered it appropriate to observe the changes in the levels of zinc and copper concentrations and in certain related zinc and copper enzymes and hormones in the plasma of human volunteers on acute induction to high altitude. From these findings, we intended to ascertain whether supplementation of these trace elements would be required for optimal health under such conditions. On acute induction to hypoxia, contents of these trace elements may change as the requirements of stressed organs and tissue may increase. Hence, further supplementation may be beneficial under hypoxic stress for better adaptability. Volunteers were divided into two groups: with and without zinc and copper salt supplementation. Blood samples were collected at sea level and on induction to acute hypoxia on days 3 and 10. Trace mineral contents and their related enzyme (alkaline phosphatase) and hormone (ceruloplasmin) levels were determined in plasma samples. Plasma zinc contents were significantly reduced upon induction to high altitude in the non-supplemented group, but not in the zinc-supplemented group. Alkaline phosphatase activity increased significantly upon induction to the high altitude stress. The enzyme activity remained elevated up to day 10 of the stress. Plasma copper contents and ceruloplasmin activity did not change upon induction to high altitude. Under hypoxic stress, circulating levels of zinc and alkaline phosphatase in plasma changed appreciably as plasma zinc was transported into the organs and tissues. However, circulating levels of copper and ceruloplasmin in

  3. Changes in sleep quality and brain wave patterns following initiation of an efavirenz-containing triple antiretroviral regimen.

    PubMed

    Moyle, G; Fletcher, C; Brown, H; Mandalia, S; Gazzard, B

    2006-05-01

    Initiation of efavirenz is commonly associated with sleep disturbances. Assessment of sleep using the electroencephalogram and electromyogram enables sleep staging to be performed and changes following the introduction of therapy to be evaluated. Using standardized sleep-staging methodology, we investigated sleep staging and sleep quality by patient self-report in an open-label cohort pilot study. Assessments were performed prior to the initiation of efavirenz, 2 weeks after the initiation of efavirenz and 3 months after the initiation of efavirenz. The study included HIV-positive individuals without central neurological disease who were naive to antiretroviral treatment. All patients initiated treatment with two nucleoside reverse transcriptase inhibitors in combination with efavirenz. Ten patients completed all three study visits. Patients reported an increase in recollection of dreams and morning sluggishness after the initiation of efavirenz which persisted for 3 months. Sleep-staging data indicated a modest reduction in stage 2 sleep with a corresponding increase in deep sleep stage 4 and a modest increase in rapid eye movement (REM) sleep. Overall sleep maintenance efficiency did not significantly change from baseline. Changes in sleep staging were most marked 2 weeks after the initiation of efavirenz but remained different from baseline patterns at 3 months. The data indicate that efavirenz has a modest but persistent impact on the time spent in several key sleep stages. Patients reported persistence of dream recollection but remained satisfied with sleep quality and overall quality of life.

  4. The role of competitive binding to human serum albumin on efavirenz-warfarin interaction: a nuclear magnetic resonance study.

    PubMed

    Wanke, Riccardo; Harjivan, Shrika G; Pereira, Sofia A; Marques, M Matilde; Antunes, Alexandra M M

    2013-11-01

    The potential for co-prescription of the anti-human immunodeficiency virus (anti-HIV) drug efavirenz (EFV) and the oral anticoagulant warfarin (WAR) is currently high as EFV is a drug of choice for HIV type 1 infection and because cardiovascular disease is increasing among HIV-infected individuals. However, clinical reports of EFV-WAR interaction, leading to WAR overdosing, call for elucidation of the mechanisms involved in this drug-drug interaction. Here we present the first report demonstrating competition of the two drugs for the same binding site of human serum albumin. Using ligand-based nuclear magnetic resonance experiments, this study proves that EFV has an effect on the concentration of free WAR. This previously unidentified EFV-WAR interaction represents a potential risk factor that should be taken into account when considering treatment options. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

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

    PubMed

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

    1998-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

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

  7. Inadequate plasma concentrations in some high-dose methadone maintenance patients.

    PubMed

    Tennant, F S

    1987-10-01

    The author studied 18 heroin addicts who had been maintained on 80 mg/day of methadone and who abused drugs or alcohol. His findings suggest that in some cases of aberrant methadone metabolism, the dose can be raised to achieve plasma concentrations adequate to eliminate drug and alcohol abuse.

  8. Plasma concentrations of disodium cromoglycate after various inhalation methods in healthy subjects

    PubMed Central

    Kato, Y; Muraki, K; Fujitaka, M; Sakura, N; Ueda, K

    1999-01-01

    Aims To compare the plasma concentrations of disodium cromoglycate (DSCG) following various inhalation procedures in healthy volunteers. Methods Nine healthy subjects inhaled 2 mg of aerosol, 20 mg of nebuliser solution only, 20 mg of nebuliser solution mixed with isotonic saline, or 20 mg of nebuliser solution mixed with saline and procaterol, a β2-adenoceptor agonist, on separate occasions 2–3 weeks apart. Plasma concentrations of DSCG were determined by high-performance liquid chromatography (h.p.l.c.). Results The peak plasma concentrations of DSCG were 1.5±0.7 (range 0.4–2.4) ng ml−1 in the aerosol group, 8.8±6.2 (range 5.3–19.9) ng ml−1 in the nebuliser solution only group, 17.2±16.3 (range 5.0–38.6) ng ml−1 in the nebuliser solution plus isotonic saline group, and 24.5±11.9 (range 10.2–44.9) ng ml−1 in the nebuliser solution plus saline and procaterol group. Thus subjects who used the nebuliser had markedly higher plasma concentrations of DSCG than subjects who used the aerosol inhaler. Conclusions These findings may have important implications for the evaluation of inhalation treatment with DSCG for bronchial asthma. PMID:10417491

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

    PubMed

    Pappu, A S; Illingworth, D R

    1994-10-01

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

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

    PubMed Central

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

    1987-01-01

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

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

    USDA-ARS?s Scientific Manuscript database

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

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

    PubMed

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

    2009-09-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2010-05-01

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

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

    PubMed

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

    1987-06-01

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

  16. Evaluation of the Lactate Plus monitor for plasma lactate concentration measurement in dogs.

    PubMed

    Nye, Carolyn J; Musulin, Sarah E; Hanel, Rita M; Mariani, Christopher L

    2017-01-01

    To compare the Lactate Plus handheld monitor to a reference blood gas analyzer for determining plasma lactate concentrations in canine whole blood. Prospective observational study. University teaching hospital. Ninety-four dogs hospitalized or admitted through the emergency service provided 125 blood samples. Only dogs that required a venous or arterial blood gas evaluation as a part of their diagnostic assessment or ongoing management were included. None. Canine whole blood samples were assayed for plasma lactate concentration with a reference blood gas analyzer and the Lactate Plus monitor. Correlation and Bland-Altman analyses were used to compare results between the 2 methods. A subset of blood samples was repeatedly analyzed with the Lactate Plus to assess monitor precision. Plasma lactate measurements from the Lactate Plus monitor showed excellent correlation with those from the reference analyzer (ρ = 0.98, P < 0.0001). Bland-Altman analysis revealed a small bias (0.1296). Agreement between the 2 methods was less consistent for lactate concentrations >5 mmol/L. The coefficient of variation ranged from 0-26.2% (median, 3.7%) and was <15% for 50/53 samples. The Lactate Plus provides a fast and affordable method to measure plasma lactate concentration in dogs. Results showed excellent agreement with the reference analyzer and precision of the instrument was acceptable. © Veterinary Emergency and Critical Care Society 2016.

  17. Plasma Progesterone Concentrations in Dairy Cows with Cystic Ovaries and Clinical Responses Following Treatment with Fenprostalene

    PubMed Central

    Leslie, K. E.; Bosu, W. T. K.

    1983-01-01

    Sixty-two dairy cows diagnosed as having cystic ovarian degeneration were used to study the correlation between rectal palpation findings and plasma progesterone concentrations and the response of cysts to treatment using fenprostalene, a luteolytic agent. Rectal palpation accurately determined the presence of luteal cysts as confirmed by plasma progesterone concentrations of 3 ng/mL or more. Treatment with fenprostalene was very effective for luteal cysts: a high percentage of treated cows exhibited estrus within seven days after treatment. The conception rate following artifical insemination during the induced estrus was 87.5% (21/24). Rectal palpation was much less accurate for the diagnosis of follicular cysts. Cows diagnosed as having follicular cysts had wide variations in plasma progesterone concentrations. Response to fenprostalene treatment was poor in cows with nonluteinized cystic follicles associated with low progesterone concentrations. However, cows diagnosed as having follicular cysts, but with progesterone concentrations of 1 ng/mL or more, responded better to fenprostalene treatment than cows with low progesterone concentrations. It was concluded that, if correctly diagnosed, luteal cysts can be successfully treated with fenprostalene, and conception rates following treatment can be expected to be normal. PMID:17422330

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

    PubMed

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

    2011-10-01

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

  19. COMPARISON OF THAI GOVERNMENT MANUFACTURED TENOFOVIR (TENOFOVIR GPO300) WITH PRIVATELY MANUFACTURED TENOFOVIR (VIREAD) USED ALONG WITH LAMIVUDINE AND EFAVIRENZ TO TREAT THAI HIV PATIENTS.

    PubMed

    Manosuthi, Weerawat; Thongyen, Supeda; Nilkamhang, Samruay; Manosuthi, Sukanya; Sungkanuparph, Somnuek

    2015-01-01

    The Thai Government Pharmaceutical Organization (GPO) has produced a nucleotide reverse transcriptase inhibitor, tenofovir disoproxil fumarate (Tenofovir GPO300). No clinical trial to date has compared plasma tenofovir concentrations, renal function, and treatment responses in HIV-infected patients who received Teno- fovir GPO300 versus Viread (original tenofovir) as part of an antiretroviral regimen. We studied 129 antiretroviral treatment (ART)-naive HIV-1 infected patients who received an antiretroviral regimen of lamivudine, efavirenz and Tenofovir GPO300 (n = 65) or Viread (n = 64). We examined plasma tenofovir concentrations (12 hours after dosing), serum creatinine, estimated glomerular filtration rate (eGFR) using the Modification in Diet in Renal Disease (MDRD) study formula, fractional excretion of phosphate (FEphos), CD4 and plasma HIV-1 RNA levels at 12 weeks, and CD4 and plasma HIV-1 RNA levels at 24 weeks after initiating the drugs. At baseline, the mean ± SD subject body weight was 54 ± 10 kilograms and the mean ± SD subject age was 37 ± 8 years. At baseline, the median (IQR) CD4 count was 44 (18-120) cells/ mm3 and the median (IQR) HIV-1 RNA level was 5.8 log copies/ml. At baseline, the mean ± SD eGFR was 134.8 ± 43.6 ml/min/1.73 m2. The baseline values for the two groups were not significantly different from each other (p > 0.05). At 12 weeks, the mean ± SD plasma tenofovir concentration was 106.9 ± 41.5 ng/ml among the patients who received Tenofovir GPO300 and 100.7 ± 49.4 ng/ml among those who received Viread (p = 0.437). At week 12, there were no differences between those who rceived Tenofovir GPO300 and Vilead in mean serum creatinine (0.78 vs 0.81 mg/dl, p = 0.283), mean eGFR (117.9 vs 109.1 ml/min/1.73 m2, p = 0.089), decline in eGFR from baseline (-21.8 vs -20.6 ml/min/1.73 m2, p = 0.860) or mean FEphos (11.4 vs 11.2, p = 0.923). The median CD4 cell counts and number of patients with undetectable plasma HIV-1 RNA at week 24 were

  20. Quantification of human plasma-busulfan concentration by liquid chromatography-tandem mass spectrometry.

    PubMed

    Moon, Soo Young; Lim, Min Kyoo; Hong, Susie; Jeon, Yongbum; Han, Minje; Song, Sang Hoon; Lim, Kyoung Soo; Yu, Kyung-Sang; Jang, In-Jin; Lee, Ji Won; Kang, Hyoung Jin; Song, Junghan

    2014-01-01

    Busulfan, an alkylating agent administered prior to hematopoietic stem cell transplantation, has a narrow therapeutic range and wide variability in metabolism. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for rapid and accurate quantification of plasma busulfan. Busulfan was separated and detected using an LC system containing a C18 column equipped with MS/MS. The sample was eluted with a mobile phase gradient for a total run time of 10 min. Plasma busulfan concentration was quantified against a 6-point standard curve in a multiple reaction monitoring mode at mass-to-charge (m/z) 264.1 > 151.1. Precision, recovery, matrix effect, linearity, detection capability, carryover, and stability were evaluated. The range of plasma busulfan concentration was obtained by analyzing samples from 9 children receiving busulfan. The coefficients of variation of within-run and within-laboratory precision were all below 5%. Recoveries were all within the range of 100-105%. Linearity was verified from 0 to 5,000 ng/mL. Limit of detection and limit of quantification were 1.56 and 25 ng/mL, respectively. Carryover rate was within allowable limits. Plasma busulfan concentration was stable for 2 weeks at -20℃ and -80℃, but decreased by 25% when the plasma was stored for 24 hr at room temperature, and by <5% in 24 hr at 4℃. The plasma busulfan concentrations were between 347 ng/mL and 5,076 ng/mL. Our method using LC-MS/MS enables highly accurate, reproducible, and rapid busulfan monitoring with minimal sample preparation. The method may also enable safe and proper dosage.

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

    PubMed

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

    2001-01-01

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

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

    SciTech Connect

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

    1991-03-11

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

  3. Weak acid-concentration Atot and dissociation constant Ka of plasma proteins in racehorses.

    PubMed

    Stampfli, H R; Misiaszek, S; Lumsden, J H; Carlson, G P; Heigenhauser, G J

    1999-07-01

    The plasma proteins are a significant contributor to the total weak acid concentration as a net anionic charge. Due to potential species difference, species-specific values must be confirmed for the weak acid anionic concentrations of proteins (Atot) and the effective dissociation constant for plasma weak acids (Ka). We studied the net anion load Atot of equine plasma protein in 10 clinically healthy mature Standardbred horses. A multi-step titration procedure, using a tonometer covering a titration range of PCO2 from 25 to 145 mmHg at 37 degrees C, was applied on the plasma of these 10 horses. Blood gases (pH, PCO2) and electrolytes required to calculate the strong ion difference ([SID] = [(Na(+) + K(+) + Ca(2+) + Mg(2+))-(Cl(-) + Lac(-) + PO4(2-))]) were simultaneously measured over a physiological pH range from 6.90-7.55. A nonlinear regression iteration to determine Atot and Ka was performed using polygonal regression curve fitting applied to the electrical neutrality equation of the physico-chemical system. The average anion-load Atot for plasma protein of 10 Standardbred horses was 14.89 +/- 0.8 mEq/l plasma and Ka was 2.11 +/- 0.50 x 10(-7) Eq/l (pKa = 6.67). The derived conversion factor (iterated Atot concentration/average plasma protein concentration) for calculation of Atot in plasma is 0.21 mEq/g protein (protein-unit: g/l). This value compares closely with the 0.24 mEq/g protein determined by titration of Van Slyke et al. (1928) and 0.22 mEq/g protein recently published by Constable (1997) for horse plasma. The Ka value compares closely with the value experimentally determined by Constable in 1997 (2.22 x 10(7) Eq/l). Linear regression of a set of experimental data from 5 Thoroughbred horses on a treadmill exercise test, showed excellent correlation with the regression lines not different from identity for the calculated and measured variables pH, HCO3 and SID. Knowledge of Atot and Ka for the horse is useful especially in exercise studies and in

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

    PubMed

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

    2009-11-01

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

  5. Plasma polychlorinated biphenyl and organochlorine pesticide concentrations in dementia: the Canadian Study of Health and Aging.

    PubMed

    Medehouenou, Thierry Comlan Marc; Ayotte, Pierre; Carmichael, Pierre-Hugues; Kröger, Edeltraut; Verreault, René; Lindsay, Joan; Dewailly, Éric; Tyas, Suzanne L; Bureau, Alexandre; Laurin, Danielle

    2014-08-01

    Even though polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides are recognized as neurotoxicants, few studies have investigated their associations with dementia. Here, we assess associations of plasma PCB and OC pesticide concentrations with all-cause dementia and Alzheimer's disease (AD). Analyses are based on data from the Canadian Study of Health and Aging, a population-based study of men and women aged 65+ years at baseline. PCB and OC pesticide concentrations were measured in 2023 participants who had complete clinical evaluations and blood samples; 574 had dementia, including 399 cases of AD. Concentrations were log-transformed and used as continuous variables in logistic regression models to assess their individual associations with dementia and AD. After adjustment for blood collection period, total plasma lipids, age, sex, education, apolipoprotein E e4 allele (ApoE4), tobacco and alcohol use, rural/urban residence, and comorbidities, elevated plasma PCB concentrations were not associated with increased prevalence of dementia and AD. Elevated concentrations of some OC pesticides and metabolites such as hexachlorobenzene, cis-nonachlor and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane were significantly associated with a reduced prevalence of dementia. A significant reduced prevalence of AD was also observed with elevated hexachlorobenzene concentrations. Other OC pesticides and metabolites were not associated with the prevalence of dementia or AD. No effect modification by sex and ApoE4 was observed for either dementia or AD. Elevated plasma PCB and OC pesticide concentrations were not associated with higher prevalence of all-cause dementia and AD. The possibility of modest reductions in prevalence with specific OC pesticides remains to be further investigated given the cross-sectional design of this study. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2003-01-01

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

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

    PubMed

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

    2013-11-01

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

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

    PubMed

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

    2011-02-01

    The aim of our study was twofold, firstly to examine the relationship between plasma concentrations of IL-6, hepcidin and iron following prolonged exercise and secondly, to assess the effect of carbohydrate ingestion on circulating hepcidin concentration post-exercise. The study was a randomised double-blind cross-over design, with participants consuming either a carbohydrate (CHO) or an isovolumetric placebo drink throughout the trial. Nine healthy, trained males completed a treadmill run at 60% vVO(2max) for 120 min followed by a 5 km time trial. Plasma concentrations of both IL-6 and hepcidin significantly increased post-exercise following both trials (p<.05) and returned to baseline by 24 h post (p>.05). A positive correlation between hepcidin and IL-6 was demonstrated immediately following exercise during PLA while there was a trend for a moderate correlation during CHO (PLA trial rho=0.81, p<0.001; CHO trial rho=0.36, p=0.07). Plasma iron was unaffected immediately post-exercise but significantly reduced by 24 h post-exercise compared to baseline. CHO ingestion significantly reduced post-exercise IL-6 (p<.05) but this had no effect on plasma hepcidin or iron concentration. Our data demonstrate CHO supplementation does not alter the rapid hepcidin response associated with exercise and does not prevent a subsequent fall in plasma iron concentration. This finding adds further support to the theory that an exercise-induced, up-regulation of hepcidin activity is a mechanism causing iron deficiency in endurance athletes. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    1983-05-01

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

  10. Oxytocin plasma concentrations in children and adolescents with autism spectrum disorder: correlation with autistic symptomatology.

    PubMed

    Taurines, Regina; Schwenck, Christina; Lyttwin, Benjamin; Schecklmann, Martin; Jans, Thomas; Reefschläger, Lennart; Geissler, Julia; Gerlach, Manfred; Romanos, Marcel

    2014-09-01

    Findings from research in animal models and humans have shown a clear role for the neuropeptide oxytocin (OT) on complex social behaviors. This is also true in the context of autism spectrum disorder (ASD). Previous studies on peripheral OT concentrations in children and young adults have reported conflicting results with the initial studies presenting mainly decreased OT plasma levels in ASD compared to healthy controls. Our study therefore aimed to further investigate changes in peripheral OT concentrations as a potential surrogate for the effects observed in the central nervous system (CNS) in ASD. OT plasma concentrations were assessed in 19 male children and adolescents with ASD, all with an IQ > 70 (age 10.7 ± 3.8 years), 17 healthy male children (age 13.6 ± 2.1 years) and 19 young male patients with attention deficit hyperactivity disorder (ADHD) as a clinical control group (age 10.4 ± 1.9 years) using a validated radioimmunoassay. Analysis of covariance revealed significant group differences in OT plasma concentrations (F(2, 48) = 9.574, p < 0.001, η2 = 0.285; plasma concentrations ASD 19.61 ± 7.12 pg/ml, ADHD 8.05 ± 5.49 pg/ml, healthy controls 14.43 ± 9.64 pg/ml). Post hoc analyses showed significantly higher concentrations in children with ASD compared to ADHD (p < 0.001). After Bonferroni correction, there was no significant difference in ASD in comparison with healthy controls (p = 0.132). A significant strong correlation between plasma OT and autistic symptomatology, assessed by the Autism Diagnostic Observation Schedule, was observed in the ASD group (p = 0.013, r = 0.603). Patients with ADHD differed from healthy control children by significantly decreased OT concentrations (p = 0.014). No significant influences of the covariates age, IQ, medication and comorbidity could be seen. Our preliminary results point to a correlation of OT plasma concentrations with autistic symptom load in children with ASD and a modulation of the OT system also in

  11. Complete dataset for 2-treatment, 2-sequence, 2-period efavirenz bioequivalence study conducted with nightly dosing

    PubMed Central

    Ibarra, Manuel; Magallanes, Laura; Lorier, Marianela; Vázquez, Marta; Fagiolino, Pietro

    2016-01-01

    The efavirenz pharmacokinetic raw data presented in this article was obtained in an average bioequivalence study between a local brand and Stocrin (Merck Sharp & Dohme, purchased from Australia, batch H009175, expiration date November 2013). Dose was administered at night (9:00 p.m.) two hours after food intake. Fourteen healthy subjects, 8 women and 6 men, completed the study. For each subject, 15 data points until 96 h post-administration are included. Subject demographic characteristics and sequences of administration are provided along with individual pharmacokinetic profiles of efavirenz obtained for both formulations after a single oral dose of 600 mg. This data provides information in support of the research article “Sex-by-formulation interaction assessed through a bioequivalence study of efavirenz tablets” [1]. PMID:27054190

  12. Antiretroviral Treatment with Efavirenz Disrupts the Blood-Brain Barrier Integrity and Increases Stroke Severity

    PubMed Central

    Bertrand, Luc; Dygert, Levi; Toborek, Michal

    2016-01-01

    The introduction of antiretroviral drugs (ARVd) changed the prognosis of HIV infection from a deadly disease to a chronic disease. However, even with undetectable viral loads, patients still develop a wide range of pathologies, including cerebrovascular complications and stroke. It is hypothesized that toxic side effects of ARVd may contribute to these effects. To address this notion, we evaluated the impact of several non-nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine) on the integrity of the blood-brain barrier, and their impact on severity of stroke. Among studied drugs, Efavirenz, but not other NNRTIs, altered claudin-5 expression, increased endothelial permeability, and disrupted the blood-brain barrier integrity. Importantly, Efavirenz exposure increased the severity of stroke in a model of middle cerebral artery occlusion in mice. Taken together, these results indicate that selected ARVd can exacerbate HIV-associated cerebrovascular pathology. Therefore, careful consideration should be taken when choosing an anti-retroviral therapy regimen. PMID:28008980

  13. Complete dataset for 2-treatment, 2-sequence, 2-period efavirenz bioequivalence study conducted with nightly dosing.

    PubMed

    Ibarra, Manuel; Magallanes, Laura; Lorier, Marianela; Vázquez, Marta; Fagiolino, Pietro

    2016-06-01

    The efavirenz pharmacokinetic raw data presented in this article was obtained in an average bioequivalence study between a local brand and Stocrin (Merck Sharp & Dohme, purchased from Australia, batch H009175, expiration date November 2013). Dose was administered at night (9:00 p.m.) two hours after food intake. Fourteen healthy subjects, 8 women and 6 men, completed the study. For each subject, 15 data points until 96 h post-administration are included. Subject demographic characteristics and sequences of administration are provided along with individual pharmacokinetic profiles of efavirenz obtained for both formulations after a single oral dose of 600 mg. This data provides information in support of the research article "Sex-by-formulation interaction assessed through a bioequivalence study of efavirenz tablets" [1].

  14. Polymorphisms in MTHFR and MTRR genes associated with blood plasma homocysteine concentration and sperm counts.

    PubMed

    Montjean, Debbie; Benkhalifa, Moncef; Dessolle, Lionel; Cohen-Bacrie, Paul; Belloc, Stéphanie; Siffroi, Jean-Pierre; Ravel, Célia; Bashamboo, Anu; McElreavey, Kenneth

    2011-02-01

    To investigate the relationship between MTHFR and MTRR genetic variants with respect to both blood plasma homocysteine concentration and sperm counts. Polymerase chain reaction followed by specific enzymatic digestion to determine the genotype of the indivi