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Sample records for fluconazole plasma concentration

  1. Fluconazole treatment hyperpolarizes the plasma membrane of Candida cells.

    PubMed

    Elicharova, Hana; Sychrova, Hana

    2013-11-01

    Five pathogenic Candida species were compared in terms of their osmotolerance, tolerance to toxic sodium and lithium cations, and resistance to fluconazole. The species not only differed, in general, in their tolerance to high osmotic pressure (C. albicans and C. parapsilosis being the most osmotolerant) but exhibited distinct sensitivities to toxic sodium and lithium cations, with C. parapsilosis and C. tropicalis being very tolerant but C. krusei and C. dubliniensis sensitive to LiCl. The treatment of both fluconazole-susceptible (C. albicans and C. parapsilosis) and fluconazole-resistant (C. dubliniensis, C. krusei and C. tropicalis) growing cells with subinhibitory concentrations of fluconazole resulted in substantially elevated intracellular Na(+) levels. Using a diS-C3(3) assay, for the first time, to monitor the relative membrane potential (ΔΨ) of Candida cells, we show that the fluconazole treatment of growing cells of all five species results in a substantial hyperpolarization of their plasma membranes, which is responsible for an increased non-specific transport of toxic alkali metal cations and other cationic drugs (e.g., hygromycin B). Thus, the combination of relatively low doses of fluconazole and drugs, whose import into the tested Candida strains is driven by the cell membrane potential, might be especially potent in terms of its ability to inhibit the growth of or even kill various Candida species. PMID:23547882

  2. Fluconazole

    MedlinePlus

    Fluconazole is used to treat fungal infections, including yeast infections of the vagina, mouth, throat, esophagus (tube leading ... by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become infected ...

  3. Influence of sustained low-efficiency diafiltration (SLED-f) on interstitial fluid concentrations of fluconazole in a critically ill patient: Use of microdialysis.

    PubMed

    Sinnollareddy, Mahipal G; Roberts, Michael S; Lipman, Jeffrey; Peake, Sandra L; Roberts, Jason A

    2015-07-01

    Acute kidney injury is a common complication in critically ill patients, and hybrid techniques including sustained low-efficiency dialysis/diafiltration (SLED-f) are being increasingly utilised in intensive care units. Most fungal infections occur in the interstitial fluid (ISF) of tissues and successful treatment of a fungal infection relies on the ability of an antifungal agent to achieve adequate concentrations at the site of infection. Tissue distribution of antimicrobials is impaired in critically ill patients owing to a variety of disease-related physiological changes, e.g. sepsis. Fluconazole is a widely used antifungal agent used to treat Candida spp. infections in critically ill patients. The implications for ISF concentrations of enhanced elimination during renal replacement therapy have not yet been reported for fluconazole. The aim of this single-patient case report was to describe the influence of SLED-f on subcutaneous (SC) ISF concentrations of fluconazole and the implications for achieving pharmacokinetic/pharmacodynamic targets. Serial blood and ISF samples were collected at pre- and post-filter ports within the SLED-f circuit and subcutaneously inserted microdialysis probe, respectively. Fluconazole concentrations were measured using a validated chromatography method. The SC ISF-to-plasma partition coefficient of fluconazole in this patient was 0.91, indicating rapid equilibrium. SC ISF fluconazole concentrations consistently decreased after initiating SLED-f. The majority of the fluconazole was eliminated from the SC ISF as a result of redistribution. Considering the extensive tissue re-distribution of fluconazole and observed elimination from tissue compartments, higher doses may be required to treat deep-seated fungal infections. PMID:25888463

  4. Retrospective Study of Cryptococcal Meningitis With Elevated Minimum Inhibitory Concentration to Fluconazole in Immunocompromised Patients

    PubMed Central

    Nasri, Hashem; Kabbani, Sarah; Bou Alwan, Melhim; Wang, Yun F.; Rebolledo, Paulina A.; Kraft, Colleen S.; Nguyen, Minh L.; Anderson, Albert M.; Rouphael, Nadine

    2016-01-01

    Background. Mortality for cryptococcal meningitis remains significant, in spite of available treatment. Resistance to first-line maintenance therapy, particularly fluconazole, has been reported. Methods. A retrospective chart review was performed on immunocompromised patients with cryptococcal meningitis, who had susceptibility testing performed between January 2001 and December 2011, at 3 hospitals in Atlanta, Georgia. Results. A total of 35 immunocompromised patients with cryptococcal meningitis were identified, 13 (37.1%) of whom had an elevated minimum inhibitory concentration (MIC) to fluconazole (MIC ≥16 µg/mL). Eighty percent of patients were males with African American predominance, the median age was 37 years, and 80% of the patients were human immunodeficiency virus (HIV) positive. Subsequent recurrence of cryptococcal meningitis was more likely in HIV patients compared with solid organ transplant patients (P = .0366). Overall, there was a statistically significant increase in an elevated MIC to fluconazole in patients who had a history of prior azole use (odds ratio, 10.12; 95% confidence interval, 2.04–50.16). Patients with an elevated MIC to fluconazole and those with a high cerebrospinal fluid cryptococcal antigen load (≥1:512) were more likely to have central nervous system complications (P = .0358 and P = .023, respectively). Although no association was observed between an elevated MIC to fluconazole and mortality, those who received voriconazole or high-dose fluconazole (≥800 mg) for maintenance therapy were more likely to survive (P = .0288). Conclusions. Additional studies are required to further investigate the morbidity and mortality associated with an elevated MIC to fluconazole in cryptococcal meningitis, to determine when it is appropriate to perform susceptibility testing, and to evaluate its cost effectiveness. PMID:27419153

  5. Human subcutaneous tissue distribution of fluconazole: comparison of microdialysis and suction blister techniques

    PubMed Central

    Sasongko, Lucy; Williams, Kenneth M; Day, Richard O; McLachlan, Andrew J

    2003-01-01

    Aims To investigate uptake of fluconazole into the interstitial fluid of human subcutaneous tissue using the microdialysis and suction blister techniques. Methods A sterile microdialysis probe (CMA/60) was inserted subcutaneously into the upper arm of five healthy volunteers following an overnight fast. Blisters were induced on the lower arm using gentle suction prior to ingestion of a single oral dose of fluconazole (200 mg). Microdialysate, blister fluid and blood were sampled over 8 h. Fluconazole concentrations were determined in each sample using a validated HPLC assay. In vivo recovery of fluconazole from the microdialysis probe was determined in each subject by perfusing the probe with fluconazole solution at the end of the 8 h sampling period. Individual in vivo recovery was used to calculate fluconazole concentrations in subcutaneous interstitial fluid. A physiologically based pharmacokinetic (PBPK) model was used to predict fluconazole concentrations in human subcutaneous interstitial fluid. Results There was a lag-time (approximately 0.5 h) between detection of fluconazole in microdialysate compared with plasma in each subject. The in vivo recovery of fluconazole from the microdialysis probe ranged from 57.0 to 67.2%. The subcutaneous interstitial fluid concentrations obtained by microdialysis were very similar to the unbound concentrations of fluconazole in plasma with maximum concentration of 4.29 ± 1.19 µg ml−1 in subcutaneous interstitial fluid and 3.58 ± 0.14 µg ml−1 in plasma. Subcutaneous interstitial fluid-to-plasma partition coefficient (Kp) of fluconazole was 1.16 ± 0.22 (95% CI 0.96, 1.35). By contrast, fluconazole concentrations in blister fluid were significantly lower (P < 0.05, paired t-test) than unbound plasma concentrations over the first 3 h and maximum concentrations in blister fluid had not been achieved at the end of the sampling period. There was good agreement between fluconazole concentrations derived from microdialysis

  6. Correlation between in vitro and in vivo antifungal activities in experimental fluconazole-resistant oropharyngeal and esophageal candidiasis.

    PubMed

    Walsh, T J; Gonzalez, C E; Piscitelli, S; Bacher, J D; Peter, J; Torres, R; Shetti, D; Katsov, V; Kligys, K; Lyman, C A

    2000-06-01

    Oropharyngeal and esophageal candidiasis (OPEC) is a frequent opportunistic mycosis in immunocompromised patients. Azole-resistant OPEC is a refractory form of this infection occurring particularly in human immunodeficiency virus (HIV)-infected patients. The procedures developed by the Antifungal Subcommittee of the National Committee for Clinical Laboratory Standards (NCCLS) are an important advance in standardization of in vitro antifungal susceptibility methodology. In order to further understand the relationship between NCCLS methodology and antifungal therapeutic response, we studied the potential correlation between in vitro susceptibility to fluconazole and in vivo response in a rabbit model of fluconazole-resistant OPEC. MICs of fluconazole were determined by NCCLS methods. Three fluconazole-susceptible (FS) (MIC, fluconazole-resistant (FR) (MIC, >/=64 microgram/ml) isolates of Candida albicans from prospectively monitored HIV-infected children with OPEC were studied. FR isolates were recovered from children with severe OPEC refractory to fluconazole, and FS isolates were recovered from those with mucosal candidiasis responsive to fluconazole. Fluconazole at 2 mg/kg of body weight/day was administered to infected animals for 7 days. The concentrations of fluconazole in plasma were maintained above the MICs for FS isolates throughout the dosing interval. Fluconazole concentrations in the esophagus were greater than or equal to those in plasma. Rabbits infected with FS isolates and treated with fluconazole had significant reductions in oral mucosal quantitative cultures (P < 0.001) and tissue burden of C. albicans in tongue, soft palate, and esophagus (P < 0.001). In comparison, rabbits infected with FR isolates were unresponsive to fluconazole and had no reduction in oral mucosal quantitative cultures or tissue burden of C. albicans versus untreated controls. We conclude that there is a strong correlation between in vitro

  7. Fluconazole Injection

    MedlinePlus

    ... injection is used to treat fungal infections, including yeast infections of the mouth, throat, esophagus (tube leading from ... by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become infected ...

  8. Synergistic Effect of the Flavonoid Catechin, Quercetin, or Epigallocatechin Gallate with Fluconazole Induces Apoptosis in Candida tropicalis Resistant to Fluconazole

    PubMed Central

    da Silva, Cecília Rocha; de Andrade Neto, João Batista; de Sousa Campos, Rosana; Figueiredo, Narjara Silvestre; Sampaio, Letícia Serpa; Magalhães, Hemerson Iury Ferreira; Cavalcanti, Bruno Coêlho; Gaspar, Danielle Macêdo; de Andrade, Geanne Matos; Lima, Iri Sandro Pampolha; de Barros Viana, Glauce Socorro; de Moraes, Manoel Odorico; Lobo, Marina Duarte Pinto; Grangeiro, Thalles Barbosa

    2014-01-01

    Flavonoids are a class of phenolic compounds commonly found in fruits, vegetables, grains, flowers, tea, and wine. They differ in their chemical structures and characteristics. Such compounds show various biological functions and have antioxidant, antimicrobial, anti-inflammatory, and antiapoptotic properties. The aim of this study was to evaluate the in vitro interactions of flavonoids with fluconazole against Candida tropicalis strains resistant to fluconazole, investigating the mechanism of synergism. Three combinations formed by the flavonoids (+)-catechin hydrated, hydrated quercetin, and (−)-epigallocatechin gallate at a fixed concentration with fluconazole were tested. Flavonoids alone had no antifungal activity within the concentration range tested, but when they were used as a cotreatment with fluconazole, there was significant synergistic activity. From this result, we set out to evaluate the possible mechanisms of cell death involved in this synergism. Isolated flavonoids did not induce morphological changes or changes in membrane integrity in the strains tested, but when they were used as a cotreatment with fluconazole, these changes were quite significant. When evaluating mitochondrial damage and the production of reactive oxygen species (ROS) only in the cotreatment, changes were observed. Flavonoids combined with fluconazole were shown to cause a significant increase in the rate of damage and the frequency of DNA damage in the tested strains. The cotreatment also induced an increase in the externalization of phosphatidylserine, an important marker of early apoptosis. It is concluded that flavonoids, when combined with fluconazole, show activity against strains of C. tropicalis resistant to fluconazole, promoting apoptosis by exposure of phosphatidylserine in the plasma membrane and morphological changes, mitochondrial depolarization, intracellular accumulation of ROS, condensation, and DNA fragmentation. PMID:24366745

  9. Some pharmacokinetic indices of oral fluconazole administration to koalas (Phascolarctos cinereus) infected with cryptococcosis.

    PubMed

    Govendir, M; Black, L A; Jobbins, S E; Kimble, B; Malik, R; Krockenberger, M B

    2016-08-01

    Three asymptomatic koalas serologically positive for cryptococcosis and two symptomatic koalas were treated with 10 mg/kg fluconazole orally, twice daily for at least 2 weeks. The median plasma Cmax and AUC0-8 h for asymptomatic animals were 0.9 μg/mL and 4.9 μg/mL·h, respectively; and for symptomatic animals 3.2 μg/mL and 17.3 μg/mL·h, respectively. An additional symptomatic koala was treated with fluconazole (10 mg/kg twice daily) and a subcutaneous amphotericin B infusion twice weekly. After 2 weeks the fluconazole Cmax was 3.7 μg/mL and the AUC0-8 h was 25.8 μg/mL*h. An additional three koalas were treated with fluconazole 15 mg/kg twice daily for at least 2 weeks, with the same subcutaneous amphotericin protocol co-administered to two of these koalas (Cmax : 5.0 μg/mL; mean AUC0-8 h : 18.1 μg/mL*h). For all koalas, the fluconazole plasma Cmax failed to reach the MIC90 (16 μg/mL) to inhibit C. gattii. Fluconazole administered orally at either 10 or 15 mg/kg twice daily in conjunction with amphotericin is unlikely to attain therapeutic plasma concentrations. Suggestions to improve treatment of systemic cryptococcosis include testing pathogen susceptibility to fluconazole, monitoring plasma fluconazole concentrations, and administration of 20-25 mg/kg fluconazole orally, twice daily, with an amphotericin subcutaneous infusion twice weekly. PMID:26667113

  10. Influence of different susceptibility testing methods and media on determination of the relevant fluconazole minimum inhibitory concentrations for heavy trailing Candida isolates with low-high phenotype.

    PubMed

    Alp, Sehnaz; Sancak, Banu; Hascelik, Gulsen; Arikan, Sevtap

    2010-11-01

    We investigated the incidence of trailing growth with fluconazole in 101 clinical Candida isolates (49 C. albicans and 52 C. tropicalis) and tried to establish the convenient susceptibility testing method and medium for fluconazole minimum inhibitory concentration (MIC) determination. MICs were determined by CLSI M27-A2 broth microdilution (BMD) and Etest methods on RPMI-1640 agar supplemented with 2% glucose (RPG) and on Mueller-Hinton agar supplemented with 2% glucose and 0.5 μg ml(-1) methylene blue (GMB). BMD and Etest MICs were read at 24 and 48 h, and susceptibility categories were compared. All isolates were determined as susceptible with BMD, Etest-RPG and Etest-GMB at 24 h. While all isolates were interpreted as susceptible at 48 h on Etest-RPG and Etest-GMB, one C. albicans isolate was interpreted as susceptible-dose dependent (S-DD) and two C. tropicalis isolates were interpreted as resistant with BMD. On Etest-RPG, trailing growth caused widespread microcolonies within the inhibition zone and resulted in confusion in MIC determination. On Etest-GMB, because of the nearly absence of microcolonies within the zone of inhibition, MICs were evaluated more easily. We conclude that, for the determination of fluconazole MICs of trailing Candida isolates, the Etest method has an advantage over BMD and can be used along with this reference method. Moreover, GMB appears more beneficial than RPG for the fluconazole Etest. PMID:19563491

  11. [Severe neurotoxicological reaction by combined treatment with vincristine and fluconazole].

    PubMed

    Hellfritzsch, Maja; Lassen, Pernille; Nielsen, Lars Peter

    2013-04-01

    We describe the case of a woman, aged 41 years, who received a combination chemotherapy including vincristine, doxorubicine, ifosfamide and etoposide due to Ewings sarcoma. She was treated prophylactic with fluconazole to prevent oral candidosis. Unexpectedly, she developed severe neurotoxic side effects. Treatment with multiple substrates of cytochrome P450 3A4 combined with inhibition of the enzyme by fluconazole impairs metabolism and thereby increase plasma concentrations of vincristine, which is considered to be the main reason for the neurotoxic side effects. PMID:23582127

  12. Plasma concentrations of benzodiazepines.

    PubMed Central

    Bond, A J; Hailey, D M; Lader, M H

    1977-01-01

    1. Twenty anxious patients were treated with medazepam, diazepam, chlordiazepoxide, amylobarbitone and placebo, each given in flexible dosage for 2-4 weeks. 2. At the end of each treatment, a series of clinical, physiological and behavioural variables were measured and plasma samples were taken for estimation of the appropriate drug and metabolite concentrations. 3. Nordiazepam was shown to be an important metabolite of both medazepam and diazepam: the ratio of medazepam to noradiazepam was 0.14 and the ratio of diazepam to nordiazepam following diazepam administration was 0.72. 4. No significant correlations were found between the plasma concentrations of any of the treatments and the clinical ratings or behavioural measures. 5. Some relationship was shown between levels of medazepam and its physiological effects. PMID:14659

  13. In Vivo Microdialysis To Determine Subcutaneous Interstitial Fluid Penetration and Pharmacokinetics of Fluconazole in Intensive Care Unit Patients with Sepsis.

    PubMed

    Sinnollareddy, Mahipal G; Roberts, Michael S; Lipman, Jeffrey; Lassig-Smith, Melissa; Starr, Therese; Robertson, Thomas; Peake, Sandra L; Roberts, Jason A

    2016-02-01

    The objective of the study was to describe the subcutaneous interstitial fluid (ISF) pharmacokinetics of fluconazole in critically ill patients with sepsis. This prospective observational study was conducted at two tertiary intensive care units in Australia. Serial fluconazole concentrations were measured over 24 h in plasma and subcutaneous ISF using microdialysis. The concentrations in plasma and microdialysate were measured using a validated high-performance liquid chromatography system with electrospray mass spectrometer detector method. Noncompartmental pharmacokinetic analysis was performed. Twelve critically ill patients with sepsis were enrolled. The mean in vivo fluconazole recovery rates ± standard deviation (SD) for microdialysis were 51.4% ± 16.1% with a mean (±SD) fluconazole ISF penetration ratio of 0.52 ± 0.30 (coefficient of variation, 58%). The median free plasma area under the concentration-time curve from 0 to 24 h (AUC0-24) was significantly higher than the median ISF AUC0-24 (340.4 versus 141.1 mg · h/liter; P = 0.004). There was no statistical difference in median fluconazole ISF penetration between patients receiving and not receiving vasopressors (median, 0.28 versus 0.78; P = 0.106). Both minimum and the maximum concentrations of drug in serum (Cmax and Cmin) showed a significant correlation with the fluconazole plasma exposure (Cmax, R(2) = 0.86, P < 0.0001; Cmin, R(2) = 0.75, P < 0.001). Our data suggest that fluconazole was distributed variably, but incompletely, from plasma into subcutaneous interstitial fluid in this cohort of critically ill patients with sepsis. Given the variability of fluconazole interstitial fluid exposures and lack of clinically identifiable factors by which to recognize patients with reduced distribution/exposure, we suggest higher than standard doses to ensure that drug exposure is adequate at the site of infection. PMID:26596947

  14. Population Pharmacokinetics of Fluconazole in Premature Infants with Birth Weights Less than 750 Grams.

    PubMed

    Momper, Jeremiah D; Capparelli, Edmund V; Wade, Kelly C; Kantak, Anand; Dhanireddy, Ramasubbareddy; Cummings, James J; Nedrelow, Jonathan H; Hudak, Mark L; Mundakel, Gratias T; Natarajan, Girija; Gao, Jamie; Laughon, Matt; Smith, P Brian; Benjamin, Daniel K

    2016-09-01

    Fluconazole is an effective agent for prophylaxis of invasive candidiasis in premature infants. The objective of this study was to characterize the population pharmacokinetics (PK) and dosing requirements of fluconazole in infants with birth weights of <750 g. As part of a randomized clinical trial, infants born at <750 g birth weight received intravenous (i.v.) or oral fluconazole at 6 mg/kg of body weight twice weekly. Fluconazole plasma concentrations from samples obtained by either scheduled or scavenged sampling were measured using a liquid chromatography-tandem mass spectrometry assay. Population PK analysis was conducted using NONMEM 7.2. Population PK parameters were allometrically scaled by body weight. Covariates were evaluated by univariable screening followed by multivariable assessment. Fluconazole exposures were simulated in premature infants using the final PK model. A population PK model was developed from 141 infants using 604 plasma samples. Plasma fluconazole PK were best described by a one-compartment model with first-order elimination. Only serum creatinine was an independent predictor for clearance in the final model. The typical population parameter estimate for oral bioavailability in the final model was 99.5%. Scavenged samples did not bias the parameter estimates and were as informative as scheduled samples. Simulations indicated that the study dose maintained fluconazole troughs of >2,000 ng/ml in 80% of simulated infants at week 1 and 59% at week 4 of treatment. Developmental changes in fluconazole clearance are best predicted by serum creatinine in this population. A twice-weekly dose of 6 mg/kg achieves appropriate levels for prevention of invasive candidiasis in extremely premature infants. PMID:27401564

  15. Fluconazole resistance in Candida glabrata.

    PubMed Central

    Hitchcock, C A; Pye, G W; Troke, P F; Johnson, E M; Warnock, D W

    1993-01-01

    We report a case of infection with Candida glabrata in which the organism became resistant to fluconazole and in which pre- and posttreatment isolates were available for comparison. The organism was cross-resistant to ketoconazole and itraconazole, in common with other azole-resistant yeasts. Fluconazole was a potent inhibitor of cytochrome P-450-dependent 14 alpha-sterol demethylase (P-450DM) in lysates of cells from both susceptible and resistant cultures (50% inhibitory concentration, 0.2 microM), indicating that resistance was unrelated to changes in P-450DM. Instead, it appeared to arise from a permeability barrier to fluconazole, since resistant cells were unable to take up radiolabelled drug. PMID:8239613

  16. The Influence of Tea Tree Oil (Melaleuca alternifolia) on Fluconazole Activity against Fluconazole-Resistant Candida albicans Strains

    PubMed Central

    Garbusińska, Aleksandra; Kowalska, Magdalena; Król, Wojciech

    2015-01-01

    The aim of this study was to evaluate the activity of fluconazole against 32 clinical strains of fluconazole-resistant Candida albicans, and C. albicans ATCC 10231 reference strain, after their exposure to sublethal concentrations of tea tree oil (TTO) or its main bioactive component terpinen-4-ol. For all tested fluconazole-resistant C. albicans strains TTO and terpinen-4-ol minimal inhibitory concentrations (MICs) were low, ranging from 0.06% to 0.5%. The 24-hour exposure of fluconazole-resistant C. albicans strains to fluconazole with sublethal dose of TTO enhanced fluconazole activity against these strains. Overall, 62.5% of isolates were classified as susceptible, 25.0% exhibited intermediate susceptibility, and 12.5% were resistant. For all of the tested clinical strains the fluconazole MIC decreased from an average of 244.0 μg/mL to an average of 38.46 μg/mL, and the fluconazole minimal fungicidal concentrations (MFC) decreased from an average of 254.67 μg/mL to an average of 66.62 μg/mL. Terpinen-4-ol was found to be more active than TTO, and strongly enhanced fluconazole activity against fluconazole-resistant C. albicans strains. The results of this study demonstrate that combining natural substances such as TTO and conventional drug such as fluconazole, may help treat difficult yeast infections. PMID:25722982

  17. Fluconazole dosing predictions in critically-ill patients receiving prolonged intermittent renal replacement therapy: a Monte Carlo simulation approach.

    PubMed

    Gharibian, Katherine N; Mueller, Bruce A

    2016-07-01

    Fluconazole is a renally-eliminated antifungal commonly used to treat Candida species infections. In critically-ill patients receiving prolonged intermittent renal replacement therapy (PIRRT), limited pharmacokinetic (PK) data are available to guide fluconazole dosing. We used previously-published fluconazole clearance data and PK data of critically-ill patients with acute kidney injury to develop a PK model with the goal of determining a therapeutic dosing regimen for critically-ill patients receiving PIRRT. Monte Carlo simulations were performed to create a virtual cohort of patients receiving different fluconazole dosing regimens. Plasma drug concentration-time profiles were evaluated on the probability of attaining a mean 24-hour area under the drug concentration-time curve to minimum inhibitory concentration ratio (AUC24h : MIC) of 100 during the initial 48 hours of antifungal therapy. At the susceptibility breakpoint of Candida albicans (2 mg/L), 93 - 96% of simulated subjects receiving PIRRT attained the pharmacodynamic target with a fluconazole 800-mg loading dose plus 400 mg twice daily (q12h or pre and post PIRRT) regimen. Monte Carlo simulations of a PK model of PIRRT provided a basis for the development of an informed fluconazole dosing recommendation when PK data was limited. This finding should be validated in the clinical setting. PMID:27251341

  18. Fluconazole use during breastfeeding

    PubMed Central

    Kaplan, Yusuf Cem; Koren, Gideon; Ito, Shinya; Bozzo, Pina

    2015-01-01

    Abstract Question I have a patient with persistent breast and nipple thrush. Other therapies have failed, so I have decided to treat her with a loading dose of 400 mg of oral fluconazole followed by 100 mg twice daily for at least 2 weeks. Is there any need for her to interrupt breastfeeding during this treatment? Answer Available data regarding fluconazole use during breastfeeding are reassuring. Fluconazole is also used in the treatment of fungal diseases in infants and has a good safety profile. Therefore, there is no need to interrupt breastfeeding when a mother is treated with fluconazole. PMID:26759844

  19. Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes.

    PubMed Central

    Back, D J; Tjia, J F

    1991-01-01

    Four antimycotic drugs, the azoles ketoconazole, itraconazole and fluconazole, and the allylamine terbinafine have been studied for their effect on the metabolism of cyclosporin by human liver microsomes (n = 3) in vitro. Ketoconazole caused marked inhibition of cyclosporin hydroxylase (to metabolites M17 and M1) with IC50 and Ki values of 0.24 +/- 0.01 and 0.022 +/- 0.004 microM, respectively. Based on IC50 values, itraconazole was ten times less potent (IC50 value of 2.2 +/- 0.2 microM) and both fluconazole and terbinafine had values above 100 microM. Ki values for itraconazole and fluconazole were 0.7 +/- 0.2 and 40 +/- 5.6 microM, respectively. No kinetic parameters were calculated for terbinafine because of the lack of inhibitory effects. Based on these data, ketoconazole is confirmed as being a potent inhibitor of cyclosporin metabolism and this has clinical relevance. Although inhibition by fluconazole was much less than that by itraconazole at equimolar concentrations, it should be noted that in patients plasma concentrations of fluconazole are much greater than those of itraconazole. Clinical interactions of cyclosporin with both fluconazole and itraconazole have been reported. In contrast to the azoles, terbinafine does not have the same potential for interaction. PMID:1659439

  20. Development and Validation of Simple RP-HPLC Method for Intracellular Determination of Fluconazole Concentration and Its Application to the Study of Candida albicans Azole Resistance

    PubMed Central

    Davtyan, Tigran K.; Melikyan, Levon A.; Nikoyan, Nune A.; Aleksanyan, Hripsime P.; Grigoryan, Nairi G.

    2015-01-01

    Candida albicans (strains NCTC-885-653 and ATCC-10231) long-term cultivated in the presence of antifungal agent fluconazole (FLC) and classical microbiological methods for determination of minimal inhibitory concentration (MIC) were used in this study. A simple and sensitive method based on reverse-phase high-performance liquid chromatography (RP-HPLC) has been developed for the determination of FLC intracellular concentration in C. albicans using tinidazole as an internal standard. Following extraction with dichloromethane, the chromatographic separation was achieved on a Machery-Nagel EC250/2 Nucleodur-100-3 C18 column by gradient elution using the mobile phase consisting of (A) 0.01 M ammonium acetate buffer, pH = 5.00, and (B) acetonitrile. Different analytical performance parameters such as linearity, precision, accuracy, limit of quantification (LOQ), and robustness were determined according to US DHHS FDA and EMEA guidelines. The method was linear for FLC (r = 0.9999) ranging from 100 to 10000 ng/mL. The intraday and interday precisions (relative standard deviation) were within 2.79 and 2.64%, respectively, and the accuracy (relative error) was less than 2.82%. The extraction recovery ranged from 79.3 to 85.5%. The reliable method was successfully applied to C. albicans azole-resistance study and it was shown that intracellular concentration of FLC correlated with a yeast drug susceptibility profile and MIC values. PMID:26783393

  1. Fluconazole and Pregnancy

    MedlinePlus

    ... It is used in the treatment of vaginal yeast infections when topical creams are not effective. It ... the most commonly used dose to treat vaginal yeast infections. I would like to stop taking fluconazole ...

  2. Fluconazole exposure during pregnancy

    PubMed Central

    Kaplan, Yusuf Cem; Koren, Gideon; Bozzo, Pina

    2015-01-01

    Abstract Question One of my patients has just learned that she is 8 weeks pregnant. She took a 150-mg dose of fluconazole 2 weeks ago for the treatment of vaginal candidiasis and she is worried about the effect on her child and pregnancy. Can I reassure her? Answer Short-term and low-dose fluconazole exposure, such as that indicated in the treatment of vaginal candidiasis, is not expected to increase the overall risk of major congenital malformations. PMID:26505064

  3. Effects of the Antifungals Voriconazole and Fluconazole on the Pharmacokinetics of S-(+)- and R-(−)-Ibuprofen

    PubMed Central

    Hynninen, Ville-Veikko; Olkkola, Klaus T.; Leino, Kari; Lundgren, Stefan; Neuvonen, Pertti J.; Rane, Anders; Valtonen, Mika; Vyyryläinen, Hanna; Laine, Kari

    2006-01-01

    Our objective was to study the effects of the antifungals voriconazole and fluconazole on the pharmacokinetics of S-(+)- and R-(−)-ibuprofen. Twelve healthy male volunteers took a single oral dose of 400 mg racemic ibuprofen in a randomized order either alone, after ingestion of voriconazole at 400 mg twice daily on the first day and 200 mg twice daily on the second day, or after ingestion of fluconazole at 400 mg on the first day and 200 mg on the second day. Ibuprofen was ingested 1 h after administration of the last dose of voriconazole or fluconazole. Plasma concentrations of S-(+)- and R-(−)-ibuprofen were measured for up to 24 h. In the voriconazole phase, the mean area under the plasma concentration-time curve (AUC) of S-(+)-ibuprofen was 205% (P < 0.001) of the respective control value and the mean peak plasma concentration (Cmax) was 122% (P < 0.01) of the respective control value. The mean elimination half-life (t1/2) was prolonged from 2.4 to 3.2 h (P < 0.01) by voriconazole. In the fluconazole phase, the mean AUC of S-(+)-ibuprofen was 183% of the control value (P < 0.001) and its mean Cmax was 116% of the control value (P < 0.05). The mean t1/2 of S-(+)-ibuprofen was prolonged from 2.4 to 3.1 h (P < 0.05) by fluconazole. The geometric mean S-(+)-ibuprofen AUC ratios in the voriconazole and fluconazole phases were 2.01 (90% confidence interval [CI], 1.80 to 2.22) and 1.82 (90% CI, 1.72 to 1.91), respectively, i.e., above the bioequivalence acceptance upper limit of 1.25. Voriconazole and fluconazole had only weak effects on the pharmacokinetics of R-(−)-ibuprofen. In conclusion, voriconazole and fluconazole increased the levels of exposure to S-(+)-ibuprofen 2- and 1.8-fold, respectively. This was likely caused by inhibition of the cytochrome P450 2C9-mediated metabolism of S-(+)-ibuprofen. A reduction of the ibuprofen dosage should be considered when ibuprofen is coadministered with voriconazole or fluconazole, especially when the initial

  4. Correlation of Fluconazole MICs with Clinical Outcome in Cryptococcal Infection

    PubMed Central

    Aller, A. I.; Martin-Mazuelos, E.; Lozano, F.; Gomez-Mateos, J.; Steele-Moore, L.; Holloway, W. J.; Gutiérrez, M. J.; Recio, F. J.; Espinel-Ingroff, A.

    2000-01-01

    We have correlated the in vitro results of testing the susceptibility of Cryptococcus neoformans to fluconazole with the clinical outcome after fluconazole maintenance therapy in patients with AIDS-associated cryptococcal disease. A total of 28 isolates of C. neoformans from 25 patients (24 AIDS patients) were tested. The MICs were determined by the broth microdilution technique by following the modified guidelines described in National Committee for Clinical Standards (NCCLS) document M27-A, e.g., use of yeast nitrogen base medium and a final inoculum of 104 CFU/ml. The fluconazole MIC at which 50% of isolates are inhibited (MIC50) and MIC90, obtained spectrophotometrically after 48 h of incubation, were 4 and 16 μg/ml, respectively. Of the 25 patients studied, 4 died of active cryptococcal disease and 2 died of other causes. Therapeutic failure was observed in five patients who were infected with isolates for which fluconazole MICs were ≥16 μg/ml. Four of these patients had previously had oropharyngeal candidiasis (OPC); three had previously had episodes of cryptococcal infection, and all five treatment failure patients had high cryptococcal antigen titers in either serum or cerebrospinal fluid (titers, >1:4,000). Although 14 of the 18 patients who responded to fluconazole therapy had previously had OPC infections, they each had only a single episode of cryptococcal infection. It appears that the clinical outcome after fluconazole maintenance therapy may be better when the infecting C. neoformans strain is inhibited by lower concentrations of fluconazole for eradication (MICs, <16 μg/ml) than when the patients are infected with strains that require higher fluconazole concentrations (MICs, ≥16 μg/ml). These findings also suggest that the MICs determined by the modified NCCLS microdilution method can be potential predictors of the clinical response to fluconazole therapy and may aid in the identification of patients who will not respond to fluconazole

  5. Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives.

    PubMed

    Devenport, M H; Crook, D; Wynn, V; Lees, L J

    1989-06-01

    1. Azole antifungal agents such as ketoconazole act by inhibiting cytochrome P-450 mediated sterol synthesis in the fungal cell membrane and thus have the potential to interfere with mammalian steroidogenesis. Fluconazole is a novel orally-effective antifungal triazole which has been reported to have more specific effects on the cytochrome P-450 enzymes involved in fungal sterol synthesis. 2. Due to the potential value of systemic antifungal agents in the treatment of infections commonly occurring in women, we assessed the effect of oral fluconazole on the metabolic profile of 18 healthy premenopausal women, 10 of whom were taking combined oral contraceptives (OC). Each woman acted as her own control, being studied both before and 21-28 days after fluconazole therapy (50 mg daily), in the luteal phase of consecutive menstrual cycles. 3. The endocrinological profile included measurement of serum oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) concentrations, short tetracosactrin adrenal stimulation test and thyroid function tests. Carbohydrate metabolism was investigated by means of an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations. Serum lipids, lipoproteins and apolipoproteins were analysed on samples taken after an overnight fast. 4. Minor biochemical changes associated with fluconazole treatment included increases in serum thyroxine and testosterone concentrations (but not in women taking OC as well as fluconazole) and in insulin and apolipoprotein B levels (but only in women taking OC as well as fluconazole). In general, these changes were small and of no clinical significance with the values remaining within the laboratory normal range. There were no adverse side-effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2547410

  6. 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. PMID:17720963

  7. Sensitization of Candida albicans biofilms to fluconazole by terpenoids of plant origin.

    PubMed

    Doke, Sonali Kashinath; Raut, Jayant Shankar; Dhawale, Shashikant; Karuppayil, Sankunny Mohan

    2014-01-01

    Infections associated with the biofilms of Candida albicans are a challenge to antifungal treatment. Combinatorial therapy involving plant molecules with antifungal drugs would be an effective complementary approach against drug-resistant Candida biofilms. The aim of this study was to evaluate the efficacy of three bioactive terpenoids (carvacrol, eugenol and thymol) in combination with fluconazole against planktonic cells, biofilm development and mature biofilms of C. albicans. Activities of the selected molecules were tested using a microplate-based methodology, while their combinations with fluconazole were performed in a checkerboard format. Biofilms were quantitated by XTT-metabolic assay and confirmed by microscopic observations. Combinations of carvacrol and eugenol with fluconazole were found synergistic against planktonic growth of C. albicans, while that of thymol with fluconazole did not have any interaction. Biofilm development and mature biofilms were highly resistant to fluconazole, but susceptible to three terpenoids. Sensitization of cells by sub-inhibitory concentrations of carvacrol and eugenol resulted in prevention of biofilm formation at low fluconazole concentrations, i.e. 0.032 and 0.002 mg ml(-1), respectively. Addition of thymol could not potentiate activity of fluconazole against biofilm formation by C. albicans. Fractional inhibitory concentration indices (FICI) for carvacrol-fluconazole and eugenol-fluconazole combinations for biofilm formation were 0.311 and 0.25, respectively. The FICI value of 1.003 indicated a status of indifference for the combination of thymol and fluconazole against biofilm formation. Eugenol and thymol combinations with fluconazole did not have useful interaction against mature biofilms of C. albicans, but the presence of 0.5 mg ml(-1) of carvacrol caused inhibition of mature biofilms at a significantly low concentration (i.e. 0.032 mg ml(-1)) of fluconazole. The study indicated that carvacrol and eugenol

  8. Plasma lipid concentrations during episodic occupational stress.

    PubMed

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

    1999-01-01

    The possibility that stress affects plasma lipid concentrations has been the subject of recent investigation, but the findings are equivocal in nonlaboratory settings. To determine whether psychological stress contributes to variability in plasma lipid concentrations and concomitant changes in health behaviors, the effect of increased work load on plasma lipids and apolipoproteins was examined in 173 lawyers. Plasma cholesterol, triglyceride, and apolipoprotein concentrations were studied during periods of high work load (corresponding to impending tax deadlines) and during periods of usual work load. Self-reports of stress, work load, and time pressure, and cortisol, blood pressure, and heart rate were measured to verify that impending deadlines were associated with increased stress levels. Health behaviors which may affect plasma lipoprotein concentrations, including dietary intake and exercise, were also examined. High work load was accompanied by increases in self-reported work load among lawyers most directly affected by the impending deadlines. Plasma apolipoprotein B and triglycerides increased during periods of high work load (M = 1.9 mg/dL, SD = 10.1 and M = 5.3, SD = 34.4, respectively). No changes in dietary intake and exercise were observed. Psychological stress (high work load) is associated with potentially atherogenic changes in plasma lipid concentrations. While the lipoprotein effect of this short-term work stress is small, the effects of longer-term stress on multiple rise factors including triglycerides and apolipoprotein B could have significance for the development of coronary artery disease. PMID:10499130

  9. Efficacy of the clinical agent VT-1161 against fluconazole-sensitive and -resistant Candida albicans in a murine model of vaginal candidiasis.

    PubMed

    Garvey, E P; Hoekstra, W J; Schotzinger, R J; Sobel, J D; Lilly, E A; Fidel, P L

    2015-09-01

    Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive Candida albicans, retained its in vitro potency (MIC50 of ≤0.015 and MIC90 of 0.12 μg/ml) against 10 clinical isolates from VVC or RVVC patients resistant to fluconazole (MIC50 of 8 and MIC90 of 64 μg/ml). VT-1161 pharmacokinetics in mice displayed a high volume of distribution (1.4 liters/kg), high oral absorption (73%), and a long half-life (>48 h) and showed rapid penetration into vaginal tissue. In a murine model of vaginal candidiasis using fluconazole-sensitive yeast, oral doses as low as 4 mg/kg VT-1161 significantly reduced the fungal burden 1 and 4 days posttreatment (P < 0.0001). Similar VT-1161 efficacy was measured when an isolate highly resistant to fluconazole (MIC of 64 μg/ml) but fully sensitive in vitro to VT-1161 was used. When an isolate partially sensitive to VT-1161 (MIC of 0.12 μg/ml) and moderately resistant to fluconazole (MIC of 8 μg/ml) was used, VT-1161 remained efficacious, whereas fluconazole was efficacious on day 1 but did not sustain efficacy 4 days posttreatment. Both agents were inactive in treating an infection with an isolate that demonstrated weaker potency (MICs of 2 and 64 μg/ml for VT-1161 and fluconazole, respectively). Finally, the plasma concentrations of free VT-1161 were predictive of efficacy when in excess of the in vitro MIC values. These data support the clinical development of VT-1161 as a potentially more efficacious treatment for VVC and RVVC. PMID:26124165

  10. Efficacy of the Clinical Agent VT-1161 against Fluconazole-Sensitive and -Resistant Candida albicans in a Murine Model of Vaginal Candidiasis

    PubMed Central

    Hoekstra, W. J.; Schotzinger, R. J.; Sobel, J. D.; Lilly, E. A.; Fidel, P. L.

    2015-01-01

    Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive Candida albicans, retained its in vitro potency (MIC50 of ≤0.015 and MIC90 of 0.12 μg/ml) against 10 clinical isolates from VVC or RVVC patients resistant to fluconazole (MIC50 of 8 and MIC90 of 64 μg/ml). VT-1161 pharmacokinetics in mice displayed a high volume of distribution (1.4 liters/kg), high oral absorption (73%), and a long half-life (>48 h) and showed rapid penetration into vaginal tissue. In a murine model of vaginal candidiasis using fluconazole-sensitive yeast, oral doses as low as 4 mg/kg VT-1161 significantly reduced the fungal burden 1 and 4 days posttreatment (P < 0.0001). Similar VT-1161 efficacy was measured when an isolate highly resistant to fluconazole (MIC of 64 μg/ml) but fully sensitive in vitro to VT-1161 was used. When an isolate partially sensitive to VT-1161 (MIC of 0.12 μg/ml) and moderately resistant to fluconazole (MIC of 8 μg/ml) was used, VT-1161 remained efficacious, whereas fluconazole was efficacious on day 1 but did not sustain efficacy 4 days posttreatment. Both agents were inactive in treating an infection with an isolate that demonstrated weaker potency (MICs of 2 and 64 μg/ml for VT-1161 and fluconazole, respectively). Finally, the plasma concentrations of free VT-1161 were predictive of efficacy when in excess of the in vitro MIC values. These data support the clinical development of VT-1161 as a potentially more efficacious treatment for VVC and RVVC. PMID:26124165

  11. Decreased plasma motilin concentrations in pregnancy.

    PubMed Central

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

    1982-01-01

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

  12. Plasma Glutamine Concentrations in Liver Failure

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  15. Fluconazole Assists Berberine To Kill Fluconazole-Resistant Candida albicans

    PubMed Central

    Li, De-Dong; Xu, Yi; Zhang, Da-Zhi; Quan, Hua; Mylonakis, Eleftherios; Hu, Dan-Dan; Li, Ming-Bang; Zhao, Lan-Xue; Zhu, Liang-Hua

    2013-01-01

    It was found in our previous study that berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. The aim of the present study was to clarify how BBR and FLC worked synergistically and the underlying mechanism. Antifungal time-kill curves indicated that the synergistic effect of the two drugs was BBR dose dependent rather than FLC dose dependent. In addition, we found that BBR accumulated in C. albicans cells, especially in the nucleus, and resulted in cell cycle arrest and significant change in the transcription of cell cycle-related genes. Besides BBR, other DNA intercalators, including methylene blue, sanguinarine, and acridine orange, were all found to synergize with FLC against FLC-resistant C. albicans. Detection of intracellular BBR accumulation by fluorescence measurement showed that FLC played a role in increasing intracellular BBR concentration, probably due to its effect in disrupting the fungal cell membrane. Similar to the case with FLC, other antifungal agents acting on the cell membrane were able to synergize with BBR. Interestingly, we found that the efflux of intracellular BBR was FLC independent but strongly glucose dependent and associated with the drug efflux pump Cdr2p. These results suggest that BBR plays a major antifungal role in the synergism of FLC and BBR, while FLC plays a role in increasing the intracellular BBR concentration. PMID:24060867

  16. Plasma concentration of itraconazole in patients receiving chemotherapy for hematological malignancies: the effect of famotidine on the absorption of itraconazole.

    PubMed

    Kanda, Y; Kami, M; Matsuyama, T; Mitani, K; Chiba, S; Yazaki, Y; Hirai, H

    1998-03-01

    Fungal infection is a serious complication in immunocompromised patients, especially those with neutropenia. Itraconazole (ITZ) is expected to be an effective prophylactic agent for fungal infection because it has more activity against Aspergillus species than fluconazole and it is less toxic than amphotericin-B. However, ITZ is available only as an oral capsule, the absorption of which is thought to depend on the presence of acid in the stomach. In this study, the effect of famotidine, an H2-blocker, on the absorption of ITZ was investigated. Patients undergoing chemotherapy for hematological malignancies were enrolled. To minimize the effect of famotidine, the time of ITZ intake was different from that of famotidine intake. The plasma concentrations of ITZ with or without taking famotidine were determined just before and 4 h after ITZ intake. Mean trough and peak concentrations of ITZ without famotidine were 332 ng/ml and 476 ng/ml, respectively. When famotidine was co-administered, the concentrations decreased to 204 ng/ml and 315 ng/ml, respectively. Statistical analyses revealed significant differences between trough concentrations in the presence and absence of famotidine (p = 0.008). There was also a clear tendency toward higher peak concentrations in the plasma concentrations with famotidine (p = 0.06). These findings suggest that famotidine decreases the plasma concentration of ITZ in patients undergoing chemotherapy. Close monitoring of the plasma concentration of ITZ and dose adjustment are required for efficient prophylaxis. PMID:9821410

  17. Do plasma melatonin concentrations decline with age?

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  18. [Plasma amino acid concentrations in aggressive dogs].

    PubMed

    Juhr, Norbert-Christian; Brand, Ulrike; Riedel, Eberhard

    2005-01-01

    Following the hypothesis that metabolic screens may be useful tools in the diagnosis of canine aggression we have investigated the blood plasma amino acid levels of dogs which have been found aggressive (N = 10) against dogs or men in comparison to non-aggressive dogs (N = 10). In summary, the aggressive dogs showed elevated plasma concentrations of the neurophysiological active aromatic amino acids tryptophan (46/171 micromol/l, p < 0,001), tyrosine (38/67 micromol/l, p < 0.01) and histidine (74/91 micromol/l, p < 0.01) and lower lysine concentrations (175/151 micromol/l, p < 0.05), which seems to point to a stress situation of these dogs. The nitrogen metabolism is impaired in the urea-cycle in the conversion of ornithine (17/34 micromol/l, p < 0.01) to citrulline (64/47 micromol/l). Higher levels of branched chain amino acids, especially leucine (122/150 micromol/l, p < 0.01), mainly metabolized in muscles, and isoleucin (60/71 micromol/l, p < 0.05) show a high energy potential. The acidose-stimulator methionine (48/78 micromol/l, p < 0.01) proved elevated. The results show that the changed behavior in the aggressive dogs is also reflected in their free amino acid plasma concentrations, independent of the question whether these data are the cause or the result of the aggressivity. PMID:15803756

  19. Plasma prolactin concentrations in lead exposed workers.

    PubMed

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

    1987-01-01

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

  20. Potent synergistic effect of doxycycline with fluconazole against Candida albicans is mediated by interference with iron homeostasis.

    PubMed

    Fiori, Alessandro; Van Dijck, Patrick

    2012-07-01

    Doxycycline was found to act synergistically with the antifungal fluconazole against Candida albicans. Combination with doxycycline converts fluconazole from fungistatic to fungicidal, prevents the onset of drug resistance, and is also effective against a clinical isolate characterized by elevated resistance to fluconazole. Investigation of the interactions between the two drugs by way of checkerboard assays indicated that doxycycline had an influence on the MIC for fluconazole, as defined by CLSI standards, only at high concentrations (200 μg/ml). However, lower concentrations were effective at eliminating residual cell growth at supra-MICs of fluconazole. Using MIC-0, defined as a drug combination resulting in optically clear wells, as an endpoint, doxycycline was found to be synergistic with fluconazole at a concentration as low as 25 μg/ml, with a fractional inhibitory concentration index of <0.5. Doxycycline-mediated growth inhibition can be reversed by externally added iron, indicating that iron depletion may account for the synergism. Consistently, we confirmed old literature data about iron-chelating activity of doxycycline. Synergism of fluconazole with doxycycline does not appear to be mediated by calcineurin, since doxycycline further aggravates the susceptibility to fluconazole of mutants lacking the catalytic or the regulatory subunits of calcineurin. Growth in the presence of fluconazole and doxycycline is restored by an elevated dosage of ERG11 in Saccharomyces cerevisiae but not in C. albicans, despite the full competence of the pathogen's protein to act as a suppressor in baker's yeast. PMID:22564841

  1. Anti-Candida activity of fluoxetine alone and combined with fluconazole: a synergistic action against fluconazole-resistant strains.

    PubMed

    Oliveira, Ana S; Gaspar, Carlos A; Palmeira-de-Oliveira, Rita; Martinez-de-Oliveira, José; Palmeira-de-Oliveira, Ana

    2014-07-01

    The purpose of this work was to determine the antimicrobial activity of fluoxetine, alone and combined with fluconazole, against 29 Candida strains isolated from patients with vulvovaginal candidiasis. MIC and minimum lethal concentration values ranged from 9.8 to 625 μg/ml for all strains tested. The combination of fluconazole with fluoxetine resulted in synergistic activity against six Candida strains, with fractional inhibitory index (FIX) values between 0.15 and 0.31. An indifferent effect was found for the remaining strains, with FIX values between 0.63 and 1. PMID:24798281

  2. Anti-Candida Activity of Fluoxetine Alone and Combined with Fluconazole: a Synergistic Action against Fluconazole-Resistant Strains

    PubMed Central

    Oliveira, Ana S.; Gaspar, Carlos A.; Palmeira-de-Oliveira, Rita; Martinez-de-Oliveira, José

    2014-01-01

    The purpose of this work was to determine the antimicrobial activity of fluoxetine, alone and combined with fluconazole, against 29 Candida strains isolated from patients with vulvovaginal candidiasis. MIC and minimum lethal concentration values ranged from 9.8 to 625 μg/ml for all strains tested. The combination of fluconazole with fluoxetine resulted in synergistic activity against six Candida strains, with fractional inhibitory index (FIX) values between 0.15 and 0.31. An indifferent effect was found for the remaining strains, with FIX values between 0.63 and 1. PMID:24798281

  3. In vitro evaluation of combination of fluconazole and flucytosine against Cryptococcus neoformans var. neoformans.

    PubMed Central

    Nguyen, M H; Barchiesi, F; McGough, D A; Yu, V L; Rinaldi, M G

    1995-01-01

    Amphotericin B and fluconazole are current acceptable therapies for cryptococcal meningitis; however, their effect remains suboptimal. The combination of fluconazole and flucytosine has yielded encouraging clinical results in human immunodeficiency virus patients with cryptococcal meningitis. To investigate the biological basis of this finding, we performed in vitro combination testing of fluconazole and flucytosine against 50 clinical strains of Cryptococcus neoformans var. neoformans. Synergy (fractional inhibitory concentration index of < 1.0) was observed in 62% of cases, while antagonism (fractional inhibitory concentration index of > 2.0) was not observed. For cases in which synergy was not achieved (autonomous or additive effects), the beneficial effect of the combination was still seen (i.e., there was still a decrease, although not as dramatic, in the MIC of one or both drugs when used in combination). The in vitro inhibitory action of flucytosine was greatly enhanced by the addition of fluconazole; the flucytosine MICs for Cryptococcus isolates were markedly decreased to concentrations which were severalfold lower than the achievable cerebrospinal fluid flucytosine concentration. On the other hand, the addition of flucytosine did not greatly enhance the in vitro activity of fluconazole if the initial fluconazole MIC for the isolate was > or = 8 micrograms/ml. Controlled clinical studies are warranted to further elucidate the potential utility of fluconazole-flucytosine combination therapy. PMID:7486902

  4. Potent antifungal activity of extracts and pure compound isolated from pomegranate peels and synergism with fluconazole against Candida albicans.

    PubMed

    Endo, Eliana Harue; Cortez, Diógenes Aparício Garcia; Ueda-Nakamura, Tânia; Nakamura, Celso Vataru; Dias Filho, Benedito Prado

    2010-09-01

    Activity-guided repeated fractionation of crude hydro alcoholic extract prepared from the fruit peel of Punica granatum on a silica-gel column yielded a compound that exhibited strong antifungal activity against Candida spp. Based on spectral analyses, the compound was identified as punicalagin. Punicalagin showed strong activity against Candida albicans and Candida parapsilosis, with MICs of 3.9 and 1.9 microg/ml, respectively. The combination of punicalagin and fluconazole showed a synergistic interaction. MIC for fluconazole decreased twofold when combined with the extract. The FIC index was 0.25. The synergism observed in disk-diffusion and checkerboard assays was confirmed in time-kill curves. The effect of punicalagin on the morphology and ultrastructure in treated yeast cells was examined by scanning and transmission electron microscopy. An irregular budding pattern and pseudohyphae were seen in treated yeasts. By transmission electron microscopy, treated cells showed a thickened cell wall, changes in the space between cell wall and the plasma membrane, vacuoles, and a reduction in cytoplasmic content. Since the punicalagin concentration effective in vitro is achievable in vivo, the combination of this agent with fluconazole represents an attractive prospect for the development of new management strategies for candidiasis, and should be investigated further in in vivo models. PMID:20541606

  5. Prolonged haloperidol and reduced haloperidol plasma concentrations after decanoate withdrawal.

    PubMed

    Chang, W H; Lin, S K; Juang, D J; Chen, L C; Yang, C H; Hu, W H; Chien, C P; Lam, Y W; Jann, M W

    1993-03-01

    Haloperidol and reduced haloperidol plasma concentrations were measured in twelve schizophrenic patients upon cessation of haloperidol decanoate (HLD) treatment. Each patient received HLD 100 mg every 4 weeks for five injections. After the fifth injection, HLD was discontinued. Haloperidol and reduced haloperidol plasma concentrations were obtained prior to cessation and at weeks 1, 3, 4, 5, 7, 9, 11, and 13 post-injection. Haloperidol and reduced haloperidol plasma concentrations were assayed by HPLC. Both haloperidol and reduced haloperidol plasma concentrations were detectable 13 weeks post HLD discontinuation. Maximal haloperidol plasma concentrations were observed at one week post cessation and gradually declined. The mean elimination half-life for haloperidol was 27.4 +/- 8.6 days (range 19.0-47.0 days). Reduced haloperidol plasma concentrations declined very slowly. Our results show that both haloperidol and reduced haloperidol plasma concentrations can remain for extended time periods after HLD is discontinued. PMID:8461270

  6. Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man.

    PubMed Central

    Touchette, M A; Chandrasekar, P H; Milad, M A; Edwards, D J

    1992-01-01

    Nine healthy male subjects received oral fluconazole 400 mg daily, ketoconazole 200 mg twice daily or no treatment for 6 days according to a randomized, cross-over design. A single 250 mg oral dose of phenytoin suspension was administered on day 5 and serum phenytoin concentrations were measured over the following 48 h. Serum testosterone concentrations were measured for 10 h after each dose of phenytoin. Ketoconazole had no significant effect on phenytoin concentrations while the mean AUC(0,48) for phenytoin was significantly higher with fluconazole (195.2 +/- 47.8 micrograms ml-1 h) than control (146.3 +/- 49.6 micrograms ml-1 h). At 48 h, the serum phenytoin concentration averaged 1.72 micrograms ml-1 under control conditions and 3.99 micrograms ml-1 with fluconazole (132% increase). AUC(0,10) for testosterone was 42% lower than control after ketoconazole administration (P less than 0.05) but increased by 33% from 55.6 +/- 9.4 ng ml-1 h (control) to 73.8 +/- 12.6 ng ml-1 h with fluconazole. AUC(0,10) values for the testosterone precursors androstenedione and 17 alpha-hydroxyprogesterone were significantly higher in the fluconazole treatment phase as were concentrations of luteinizing hormone. The mechanism and clinical significance of the increase in testosterone concentration caused by fluconazole remains to be determined. PMID:1633070

  7. Synergistic Activity of Chloroquine with Fluconazole against Fluconazole-Resistant Isolates of Candida Species

    PubMed Central

    Li, Yali; Wan, Zhe; Li, Ruoyu

    2014-01-01

    The in vitro activity of chloroquine and the interactions of chloroquine combined with fluconazole against 37 Candida isolates were tested using the broth microdilution, disk diffusion, and Etest susceptibility tests. Synergistic effect was detected with 6 of 9 fluconazole-resistant Candida albicans isolates, with Candida krusei ATCC 6258, and with all 12 fluconazole-resistant Candida tropicalis isolates. PMID:25512426

  8. Design and synthesis of new fluconazole analogues.

    PubMed

    Pore, Vandana S; Agalave, Sandip G; Singh, Pratiksha; Shukla, Praveen K; Kumar, Vikash; Siddiqi, Mohammad I

    2015-06-21

    We have synthesized new fluconazole analogues containing two different 1,2,3-triazole units in the side chain. The synthesis of new amide analogues using a variety of acids is also described. All the compounds showed very good antifungal activity. A hemolysis study of the most active compounds 6e and 13j showed that both compounds did not cause any hemolysis at the dilutions tested. These compounds did not exhibit any toxicity to L929 cells at MIC and lower concentrations. In the docking study, the overall binding mode of 6e and 13j appeared to be reasonable and provided a good insight into the structural basis of inhibition of Candida albicans Cyp51 by these compounds. PMID:25975803

  9. 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...

  10. Synergistic Antifungal Effect of Glabridin and Fluconazole

    PubMed Central

    Liu, Wei; Li, Li Ping; Zhang, Jun Dong; Li, Qun; Shen, Hui; Chen, Si Min; He, Li Juan; Yan, Lan; Xu, Guo Tong; An, Mao Mao; Jiang, Yuan Ying

    2014-01-01

    The incidence of invasive fungal infections is increasing in recent years. The present study mainly investigated glabridin (Gla) alone and especially in combination with fluconazole (FLC) against Cryptococcus neoformans and Candida species (Candida albicans, Candida tropicalis, Candida krusei, Candida parapsilosis and Candida Glabratas) by different methods. The minimal inhibitory concentration (MIC) and the minimal fungicidal concentration (MFC) indicated that Gla possessed a broad-spectrum antifungal activity at relatively high concentrations. After combining with FLC, Gla exerted a potent synergistic effect against drug-resistant C. albicans and C. tropicalis at lower concentrations when interpreted by fractional inhibitory concentration index (FICI). Disk diffusion test and time-killing test confirming the synergistic fungicidal effect. Cell growth tests suggested that the synergistic effect of the two drugs depended more on the concentration of Gla. The cell envelop damage including a significant decrease of cell size and membrane permeability increasing were found after Gla treatment. Together, our results suggested that Gla possessed a synergistic effect with FLC and the cell envelope damage maybe contributed to the synergistic effect, which providing new information for developing novel antifungal agents. PMID:25058485

  11. Cross-resistance to fluconazole induced by exposure to the agricultural azole tetraconazole: an environmental resistance school?

    PubMed

    Rocha, Marcos Fábio Gadelha; Alencar, L P; Paiva, M A N; Melo, Luciana Magalhães; Bandeira, Silviane Praciano; Ponte, Y B; Sales, Jamille Alencar; Guedes, G M M; Castelo-Branco, D S C M; Bandeira, T J P G; Cordeiro, R A; Pereira-Neto, W A; Brandine, G S; Moreira, José Luciano Bezerra; Sidrim, José Júlio Costa; Brilhante, Raimunda Sâmia Nogueira

    2016-05-01

    This study aimed to investigate the influence of tetraconazole and malathion, both used in agricultural activities, on resistance to fluconazole, itraconazole and voriconazole in Candida parapsilosis ATCC 22019. The susceptibility to tetraconazole, malathion, fluconazole, itraconazole and voriconazole, through broth microdilution. Then, 12 independent replicates, were separated and exposed to four treatment groups, each one containing three replicates: G1: tetraconazole; G2: malathion; G3: fluconazole (positive control); G4: negative control. Replicates from G1, G2 and G3, were exposed to weekly increasing concentrations of tetraconazole, malathion and fluconazole, respectively, ranging from MIC/2 to 32 × MIC, throughout 7 weeks. The exposure to tetraconazole, but not malathion, decreased susceptibility to clinical azoles, especially fluconazole. The tetraconazole-induced fluconazole resistance is partially mediated by the increased activity of ATP-dependent efflux pumps, considering the increase in antifungal susceptibility after the addition of the efflux pump inhibitor, promethazine, and the increase in rhodamine 6G efflux and CDR gene expression in the G1 replicates. Moreover, MDR expression was only detected in G1 and G3 replicates, suggesting that MDR pumps are also involved in tetraconazole-induced fluconazole resistance. It is noteworthy that tetraconazole and fluconazole-treated replicates behaved similarly, therefore, resistance to azoles of clinical use may be a consequence of using azoles in farming activities. PMID:26864989

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

    PubMed

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

    1992-01-01

    A trial was conducted to determine the doxycycline plasma concentrations attained by feeding a medicated corn diet to large psittacine birds. Doxycycline is the preferred drug for the treatment of chlamydiosis in psittacine birds. Healthy macaws were fed a 0.1% doxycycline-medicated corn diet for 45 days, and plasma doxycycline concentrations were determined by microbiological assay on treatment days 3, 15, 30, and 45. Plasma doxycycline concentrations exceeded 1 microgram/ml in 87% of the samples assayed. As blood concentrations of 1 microgram/ml are considered therapeutic, a doxycycline-medicated corn diet may be efficacious in the treatment of chlamydiosis in large psittacine birds. PMID:1627120

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

    PubMed

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

    2015-06-01

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

  14. Fluconazole

    MedlinePlus

    ... extreme tiredness unusual bruising or bleeding lack of energy loss of appetite pain in the upper right part of the stomach yellowing of the skin or eyes flu-like symptoms dark urine pale stools seizures rash blistering or peeling ...

  15. Interactions between copy number and expression level of genes involved in fluconazole resistance in Candida glabrata

    PubMed Central

    Abbes, Salma; Mary, Charles; Sellami, Hayet; Michel-Nguyen, Annie; Ayadi, Ali; Ranque, Stéphane

    2013-01-01

    Objectives: This study aimed to elucidate the relative involvement of drug resistance gene copy number and overexpression in fluconazole resistance in clinical C. glabrata isolates using a population-based approach. Methods: Fluconazole resistance levels were quantified using the minimal inhibitory concentration (MIC) via Etest method. Both gene expression levels and gene copy number of CgCDR1, CgPDH1, CgERG11, and CgSNQ2 were assessed via quantitative real-time PCR. The influence of the main effects and first-level interactions of both the expression level and copy number of these genes on fluconazole resistance levels were analyzed using a multivariate statistical model. Results: Forty-three C. glabrata isolates were collected from 30 patients during in a hospital survey. In the multivariate analysis, C. glabrata fluconazole MICs were independently increased by CgSNQ2 overexpression (p < 10−4) and the interaction between CgPDH1 gene copy number and CgPDH1 expression level (p = 0.038). In contrast, both CgPDH1 overexpression (p = 0.049) and the interaction between CgSNQ2 and CgERG11 expression (p = 0.003) led to a significant decrease in fluconazole MICs. Conclusion: Fluconazole resistance in C. glabrata involves complex interactions between drug resistance gene expression and/or copy number. The population-based multivariate analysis highlighted the involvement of the CgSNQ2 gene in fluconazole resistance and the complex effect of the other genes such as PDH1 for which overexpression was associated with reduced fluconazole resistance levels, while the interaction between PDH1 overexpression and copy number was associated with increased resistance levels. PMID:24273749

  16. Fluconazole-Induced Type 1 Kounis Syndrome.

    PubMed

    Singh Mahal, Hardeep

    2016-01-01

    The administration of fluconazole is commonly used in both inpatient and outpatient settings for the management of candidiasis infection. Although it is associated with a relatively safe side effect profile, some patients experience adverse effects associated with increased morbidity. We describe 1 such patient, a 42-year-old woman with a history of severe eczema who developed fluconazole-induced type 1 Kounis syndrome. Review of literature indicates that this as the first case reported of fluconazole-induced type 1 Kounis syndrome. PMID:26938747

  17. Fluconazole Alters the Polysaccharide Capsule of Cryptococcus gattii and Leads to Distinct Behaviors in Murine Cryptococcosis

    PubMed Central

    Santos, Julliana Ribeiro Alves; Holanda, Rodrigo Assunção; Frases, Susana; Bravim, Mayara; Araujo, Glauber de S.; Santos, Patrícia Campi; Costa, Marliete Carvalho; Ribeiro, Maira Juliana Andrade; Ferreira, Gabriella Freitas; Baltazar, Ludmila Matos; Miranda, Aline Silva; Oliveira, Danilo Bretas; Santos, Carolina Maria Araújo; Fontes, Alide Caroline Lima; Gouveia, Ludmila Ferreira; Resende-Stoianoff, Maria Aparecida; Abrahão, Jonatas Santos; Teixeira, Antônio Lúcio; Paixão, Tatiane Alves; Souza, Danielle G.; Santos, Daniel Assis

    2014-01-01

    Cryptococcus gattii is an emergent human pathogen. Fluconazole is commonly used for treatment of cryptococcosis, but the emergence of less susceptible strains to this azole is a global problem and also the data regarding fluconazole-resistant cryptococcosis are scarce. We evaluate the influence of fluconazole on murine cryptococcosis and whether this azole alters the polysaccharide (PS) from cryptococcal cells. L27/01 strain of C. gattii was cultivated in high fluconazole concentrations and developed decreased drug susceptibility. This phenotype was named L27/01F, that was less virulent than L27/01 in mice. The physical, structural and electrophoretic properties of the PS capsule of L27/01F were altered by fluconazole. L27/01F presented lower antiphagocytic properties and reduced survival inside macrophages. The L27/01F did not affect the central nervous system, while the effect in brain caused by L27/01 strain began after only 12 hours. Mice infected with L27/01F presented lower production of the pro-inflammatory cytokines, with increased cellular recruitment in the lungs and severe pulmonary disease. The behavioral alterations were affected by L27/01, but no effects were detected after infection with L27/01F. Our results suggest that stress to fluconazole alters the capsule of C. gattii and influences the clinical manifestations of cryptococcosis. PMID:25392951

  18. 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.

  19. Plasma von Willebrand factor concentration and thyroid function in dogs.

    PubMed

    Avgeris, S; Lothrop, C D; McDonald, T P

    1990-03-15

    Plasma von Willebrand factor antigen concentration was determined in 15 dogs with suspected hypothyroidism, in 1 dog with hyperthyroidism, and in 14 euthyroid dogs. The mean +/- SEM von Willebrand factor:antigen concentration in hypothyroid dogs (47.1% +/- 12.6%) was significantly decreased (P less than 0.0005), compared with that in euthyroid dogs (94.7 +/- 5.6%). Four hypothyroid dogs were given thyroxine for 1 month and all 4 had an increase in von Willebrand factor:antigen concentration. The plasma von Willebrand factor:antigen concentration was 200% in the hyperthyroid dog. Seemingly, reduced concentrations of plasma von Willebrand factor:antigen can be found in dogs in association with congenital von Willebrand disease or with von Willebrand disease acquired through hypothyroidism. PMID:2107158

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

    SciTech Connect

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

    1990-01-01

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

  1. Low plasma triiodothyronine concentrations and outcome in preterm infants.

    PubMed Central

    Lucas, A; Rennie, J; Baker, B A; Morley, R

    1988-01-01

    A major association has been found between low plasma triiodothyronine concentrations in preterm neonates and their later developmental outcome. Plasma triiodothyronine concentration was measured longitudinally in 280 preterm infants below 1850 g birth weight. Babies whose lowest recorded concentration was less than 0.3 nmol/l had, at 18 months' corrected age, 8.3 and 7.4 point disadvantages in Bayley mental and motor scales and a 8.6 point disadvantage on the academic scale of Developmental Profile II, even after adjusting for a range of antenatal and neonatal factors known to influence later development. Low concentrations of triiodothyronine were strongly associated with infant mortality, but not after adjusting for the presence of respiratory illness. There was no association between plasma triiodothyronine concentrations and somatic growth up to 18 months, and no association with necrotising enterocolitis or later cerebral palsy. Data on postnatal changes in plasma triiodothyronine concentrations are presented for reference purposes. While cited reference ranges for plasma triiodothyronine concentration appear suitable for well infants above 1500 g birth weight, smaller or ill babies often have very low values for many weeks. Our data are relevant to the debate on endocrine 'replacement' treatment in premature babies. PMID:2461683

  2. Ethosuximide plasma concentrations: influence of age and associated concomitant therapy.

    PubMed

    Battino, D; Cusi, C; Franceschetti, S; Moise, A; Spina, S; Avanzini, G

    1982-01-01

    The relationship between oral dose and plasma concentration of ethosuximide was evaluated retrospectively in 198 epileptic patients aged 2.5 to 34 years. Age appears to be a major factor in determining the ethosuximide plasma level/dose (L/D) ratio. Children younger than 10 years had men L/D ratios significantly lower (p less than 0.0003) than adolescents (10 to 15 years of age) and adults (16 to 34 years of age). Associated antiepileptic therapy reduced the ethosuximide L/D ratio: mean ethosuximide L/D ratios were significantly lower in patients also taking primidone (p less than 0.0005) or valproic acid (p less than 0.02). The correlation between the dose of ethosuximide administered and the plasma concentration was significant in the 3 age groups considered (p less than 0.0004), but the wide scattering of individual plasma concentrations makes it impossible to predict what plasma concentration of ethosuximide will be obtained after a given dose. For this reason, routine monitoring of ethosuximide plasma concentrations still appears to be necessary, especially in children and patients on polytherapy. PMID:6802548

  3. Pharmacokinetics/pharmacodynamic correlations of fluconazole in murine model of cryptococcosis.

    PubMed

    Santos, Julliana Ribeiro Alves; César, Isabela Costa; Costa, Marliete Carvalho; Ribeiro, Noelly Queiroz; Holanda, Rodrigo Assunção; Ramos, Lais Hott; Freitas, Gustavo José Cota; Paixão, Tatiane Alves; Pianetti, Gerson Antônio; Santos, Daniel Assis

    2016-09-20

    The emergence of fluconazole-resistant Cryptococcus gattii is a global concern, since this azole is the main antifungal used worldwide to treat patients with cryptococcosis. Although pharmacokinetic (PK) and pharmacodynamic (PD) indices are useful predictive factors for therapeutic outcomes, there is a scarcity of data regarding PK/PD analysis of antifungals in cryptococcosis caused by resistant strains. In this study, PK/PD parameters were determined in a murine model of cryptococcosis caused by resistant C. gattii. We developed and validated a suitable liquid chromatography-electrospray ionization tandem mass spectrometry method for PK studies of fluconazole in the serum, lungs, and brain of uninfected mice. Mice were infected with susceptible or resistant C. gattii, and the effects of different doses of fluconazole on the pulmonary and central nervous system fungal burden were determined. The peak levels in the serum, lungs, and brain were achieved within 0.5h. The AUC/MIC index (area under the curve/minimum inhibitory concentration) was associated with the outcome of anti-cryptococcal therapy. Interestingly, the maximum concentration of fluconazole in the brain was lower than the MIC for both strains. In addition, the treatment of mice infected with the resistant strain was ineffective even when high doses of fluconazole were used or when amphotericin B was tested, confirming the cross-resistance between these drugs. Altogether, our novel data provide the correlation of PK/PD parameters with antifungal therapy during cryptococcosis caused by resistant C. gattii. PMID:27235581

  4. In vitro activity of essential oils extracted from plants used as spices against fluconazole-resistant and fluconazole-susceptible Candida spp.

    PubMed

    Pozzatti, Patrícia; Scheid, Liliane Alves; Spader, Tatiana Borba; Atayde, Margareth Linde; Santurio, Janio Morais; Alves, Sydney Hartz

    2008-11-01

    In the present study, the antifungal activity of selected essential oils obtained from plants used as spices was evaluated against both fluconazole-resistant and fluconazole-susceptible Candida spp. The Candida species studied were Candida albicans, Candida dubliniensis, Candida tropicalis, Candida glabrata, and Candida krusei. For comparison purposes, they were arranged in groups as C. albicans, C. dubliniensis, and Candida non-albicans. The essential oils were obtained from Cinnamomum zeylanicum Breyn, Lippia graveolens HBK, Ocimum basilicum L., Origanum vulgare L., Rosmarinus officinalis L., Salvia officinalis L., Thymus vulgaris L., and Zingiber officinale. The susceptibility tests were based on the M27-A2 methodology. The chemical composition of the essential oils was obtained by gas chromatography-mass spectroscopy and by retention indices. The results showed that cinnamon, Mexican oregano, oregano, thyme, and ginger essential oils have different levels of antifungal activity. Oregano and ginger essential oils were found to be the most and the least efficient, respectively. The main finding was that the susceptibilities of fluconazole-resistant C. albicans, C. dubliniensis, and Candida non-albicans to Mexican oregano, oregano, thyme, and ginger essential oils were higher than those of the fluconazole-susceptible yeasts (P<0.05). In contrast, fluconazole-resistant C. albicans and Candida non-albicans were less susceptible to cinnamon essential oil than their fluconazole-susceptible counterparts (P<0.05). A relationship between the yeasts' susceptibilities and the chemical composition of the essential oils studied was apparent when these 2 parameters were compared. Finally, basil, rosemary, and sage essential oils did not show antifungal activity against Candida isolates at the tested concentrations. PMID:18997851

  5. Plasma atropine concentrations via intravenous, endotracheal, and intraosseous administration.

    PubMed

    Prete, M R; Hannan, C J; Burkle, F M

    1987-03-01

    To date, there have been limited studies on the pharmacokinetics of intravenous atropine and no pharmacokinetic studies on the endotracheal or intraosseous administration of atropine. This study examines the time to peak plasma concentration of atropine following intravenous, endotracheal, and intraosseous administration in anesthetized monkeys using a triple crossover design. Plasma atropine was assayed by a radioreceptor method. The time to peak plasma concentration of atropine was shortest with intravenous administration; and longest with endotracheal administration. The mean plasma concentration of atropine was significantly higher in intravenous administrations than in endotracheal administrations at 0.75 and 2 minutes; compared to that noted in intraosseous administrations, the concentration was significantly higher only at 0.75 minutes. The mean plasma concentration of atropine administered intraosseously was significantly higher than that of endotracheal administrations at 5 minutes and was greater than that of intravenous and endotracheal administrations for the samples collected from 5 to 30 minutes. The endotracheal and intraosseous routes provide alternatives to the intravenous administration of atropine when intravenous access is limited or not available. PMID:3828010

  6. Supplemental silicon increases plasma and milk silicon concentrations in horses.

    PubMed

    Lang, K J; Nielsen, B D; Waite, K L; Hill, G M; Orth, M W

    2001-10-01

    The primary objective of this research was to determine the effect of supplemental dietary silicon (Si) on plasma and milk Si concentrations of lactating mares and the subsequent effect on plasma Si concentrations in nursing foals. Additionally, the role of Si on altering biochemical markers of bone turnover was investigated, because supplemental Si may be advantageous in enhancing bone health. Twelve Arabian mare/foal units were pair-matched by foaling date and randomly assigned to two groups, Si-supplemented (Supplemented) or control (Control). Blood and milk samples were taken on d 0, 15, 30, and 45, d 0 being the 1st d after parturition. Plasma and milk (or colostrum) Si concentrations were determined and serum was analyzed for osteocalcin, carboxy-terminal pyridinoline cross-linked telopeptide region of type I collagen, and pyridinoline and deoxypyridinoline crosslinks. All Supplemented mares had higher (P < 0.01) plasma Si concentrations than Control by d 30, and Supplemented mares' milk had higher (P < 0.01) Si concentrations on d 45 than Control mares' milk. By d 45, foals of Supplemented mares had higher (P < 0.01) plasma Si concentrations than foals of Control mares. Supplemental Si did not influence (P > 0.36) bone metabolism in foals; however, trends (P < 0.10) for altered bone metabolism were observed in postpartum mares. Results indicate that supplemental Si increases plasma and milk Si concentrations. Further research is required to determine whether Si has a role in altering serum biochemical markers of bone and collagen activity. PMID:11721842

  7. Plasma glutamine concentration in spinal cord injured patients.

    PubMed

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

    2005-09-23

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

  8. Time course of microbiologic outcome and gene expression in Candida albicans during and following in vitro and in vivo exposure to fluconazole.

    PubMed

    Lepak, A; Nett, J; Lincoln, L; Marchillo, K; Andes, D

    2006-04-01

    Pharmacodynamics (PD) considers the relationship between drug exposure and effect. The two factors that have been used to distinguish the PD behaviors of antimicrobials are the impact of concentration on the extent of organism killing and the duration of persistent microbiologic suppression (postantibiotic effect). The goals of these studies were (i) to examine the relationship between antimicrobial PD and gene expression and (ii) to gain insight into the mechanism of fluconazole effects persisting following exposure. Microarrays were used to estimate the transcriptional response of Candida albicans to a supra-MIC F exposure over time in vitro. Fluconazole at four times the MIC was added to a log-phase C. albicans culture, and cells were collected to determine viable growth and for microarray analyses. We identified differential expression of 18% of all genes for at least one of the time points. More genes were upregulated (n=1,053 [16%]) than downregulated (174 [3%]). Of genes with known function that were upregulated during exposure, most were related to plasma membrane/cell wall synthesis (18%), stress responses (7%), and metabolism (6%). The categories of downregulated genes during exposure included protein synthesis (15%), DNA synthesis/repair (7%), and transport (7%) genes. The majority of genes identified at the postexposure time points were from the protein (17%) and DNA (7%) synthesis categories. In subsequent studies, three genes (CDR1, CDR2, and ERG11) were examined in greater detail (more concentration and time points) following fluconazole exposure in vitro and in vivo. Expression levels from the in vitro and in vivo studies were congruent. CDR1 and CDR2 transcripts were reduced during in vitro fluconazole exposure and during supra-MIC exposure in vivo. However, in the postexposure period, the mRNA abundance of both pumps increased. ERG11 expression increased during exposure and fell in the postexposure period. The expression of the three genes

  9. Identification and properties of plasma membrane azole efflux pumps from the pathogenic fungi Cryptococcus gattii and Cryptococcus neoformans

    PubMed Central

    Basso, Luiz R.; Gast, Charles E.; Bruzual, Igor; Wong, Brian

    2015-01-01

    Objectives Cryptococcus gattii from the North American Northwest (NW) have higher azole MICs than do non-NW C. gattii or Cryptococcus neoformans. Since mechanisms of azole resistance in C. gattii are not known, we identified C. gattii and C. neoformans plasma membrane azole efflux pumps and characterized their properties. Methods The C. gattii R265 genome was searched for orthologues of known fungal azole efflux genes, expression of candidate genes was assessed by RT–PCR and the expressed genes' cDNAs were cloned and expressed in Saccharomyces cerevisiae. Azole MICs and intracellular [3H]fluconazole were measured in C. gattii and C. neoformans and in S. cerevisiae expressing each cDNA of interest, as was [3H]fluconazole uptake by post-Golgi vesicles (PGVs) isolated from S. cerevisiae sec6-4 mutants expressing each cDNA of interest. Results Intracellular [3H]fluconazole concentrations were inversely correlated with fluconazole MICs only in 25 NW C. gattii strains. S. cerevisiae expressing three C. gattii cDNAs (encoded by orthologues of C. neoformans AFR1 and MDR1 and the previously unstudied gene AFR2) and their C. neoformans counterparts had higher azole MICs and lower intracellular [3H]fluconazole concentrations than did empty-vector controls. PGVs from S. cerevisiae expressing all six Cryptococcus cDNAs also accumulated more [3H]fluconazole than did controls, and [3H]fluconazole transport by all six transporters of interest was ATP dependent and was inhibited by excess unlabelled fluconazole, voriconazole, itraconazole and posaconazole. Conclusions We conclude that C. gattii and C. neoformans AFR1, MDR1 and AFR2 encode ABC transporters that pump multiple azoles out of S. cerevisiae cells, thereby causing azole resistance. PMID:25630649

  10. Genetic and Clinical Factors Affecting Plasma Clozapine Concentration

    PubMed Central

    Edman, Gunnar; Bertilsson, Leif; Hukic, Dzana Sudic; Lavebratt, Catharina; Eriksson, Sven V.; Ösby, Urban

    2015-01-01

    Objective: To assess (1) the variance of plasma clozapine levels; (2) the relative importance of sex, smoking habits, weight, age, and specific genetic variants of cytochrome P450 1A2 (CYP1A2), uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4), and multidrug resistance protein 1 (MDR1) on plasma levels of clozapine; and (3) the relation between plasma clozapine levels, fasting glucose levels, and waist circumference. Method: There were 113 patients on clozapine treatment recruited from psychosis outpatient clinics in Stockholm County, Sweden. Patients had genotype testing for single nucleotide polymorphisms: 2 in MDR1, 3 in CYP1A2, and 1 in UGT1A4. Multiple and logistic regression were used to analyze the relations. Results: There was a wide variation in plasma concentrations of clozapine (mean = 1,615 nmol/L, SD = 1,354 nmol/L), with 37% of the samples within therapeutic range (1,100–2,100 nmol/L). Smokers had significantly lower plasma clozapine concentrations than nonsmokers (P ≤ .03). There was a significant association between the rs762551 A allele of CYP1A2 and lower plasma clozapine concentration (P ≤ .05). Increased fasting glucose level was 3.7-fold more frequent in CC and CA genotypes than AA genotype (odds ratio = 0.27; 95% confidence interval, 0.10–0.72). There was no significant relation between higher fasting glucose levels, larger waist circumference, and higher clozapine levels. Conclusions: It is difficult to predict plasma clozapine concentration, even when known individual and genetic factors are considered. Therefore, therapeutic drug monitoring is recommended in patients who are treated with clozapine. PMID:26137357

  11. Pharmacokinetics and Safety of Fluconazole in Young Infants Supported with Extracorporeal Membrane Oxygenation

    PubMed Central

    Watt, Kevin M.; Benjamin, Daniel K.; Cheifetz, Ira M.; Moorthy, Ganesh; Wade, Kelly C.; Smith, P. Brian; Brouwer, Kim L. R.; Capparelli, Edmund V.; Cohen-Wolkowiez, Michael

    2012-01-01

    Background Candida infections are a leading cause of infectious disease-related death in infants supported with extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK), thus standard fluconazole dosing in children on ECMO may result in suboptimal drug exposure. This study determined the PK of fluconazole in infants on ECMO. Methods Infants <120 days old received either intravenous fluconazole prophylaxis (25 mg/kg once a week) or treatment (12 mg/kg daily) while on ECMO. Paired plasma samples were collected pre- and post-oxygenator around doses 1 and 2 to calculate PK indices and describe oxygenator extraction. A 1-compartment model was fit to the data using non-linear regression. Surrogate pharmacodynamic targets for efficacy were evaluated. Results Ten infants were enrolled. After dose 1 (n=9), the median clearance was 17 mL/kg/h, the median volume of distribution was 1.5 L/kg, and the median exposure in the first 24 hours (AUC0–24) was 322 h*mg/L. After multiple doses (n=7), the median clearance was 22 mL/kg/h, the median volume of distribution was 1.9 L/kg, and the AUC0–24 was 352 h*mg/L. After dose 1, 78% of infants achieved the prophylaxis target, while only 11% achieved the therapeutic target. Oxygenator extraction of fluconazole was minimal (−2.0%, standard deviation 15.0), and extraction was not correlated with age of the ECMO circuit (rho= − 0.05). There were no adverse events related to fluconazole. Conclusions Infants on ECMO had higher volume of distribution but similar clearance when compared with historical controls not on ECMO. In infants on ECMO, a fluconazole dose of 25 mg/kg weekly provides adequate exposure for prophylaxis against Candida infections. However, higher doses may be needed for treatment. PMID:22627870

  12. Antifungal activity of Rubus chingii extract combined with fluconazole against fluconazole-resistant Candida albicans.

    PubMed

    Han, Bing; Chen, Jia; Yu, Yi-qun; Cao, Yong-bing; Jiang, Yuan-ying

    2016-02-01

    This study aimed to investigate the antifungal activity of Rubus chingii extract in combination with fluconazole (FLC) against FLC-resistant Candida albicans 100 in vitro. A R. chingii extract and FLC-resistant C. albicans fungus suspension were prepared. The minimum inhibitory concentration and fractional inhibitory concentration index of R. chingii extract combined with FLC against C. albicans were determined, after which growth curves for C. albicans treated with R. chingii extract, FLC alone and a combination of these preparations were constructed. Additionally, the mechanisms of drug combination against C. albicans were explored by flow cytometry, gas chromatographic mass spectrometry and drug efflux pump function detection. R. chingii extract combined with FLC showed significant synergy. Flow cytometry suggested that C. albicans cells mainly arrest in G1 and S phases when they have been treated with the drug combination. The drug combination resulted in a marked decrease in the ergosterol content of the cell membrane. Additionally, efflux of Rhodamine 6G decreased with increasing concentrations of R. chingii extract. R. chingii extract combined with FLC has antifungal activity against FLC-resistant C. albicans. PMID:26891940

  13. Disruption of the Transcriptional Regulator Cas5 Results in Enhanced Killing of Candida albicans by Fluconazole

    PubMed Central

    Vasicek, Erin M.; Berkow, Elizabeth L.; Bruno, Vincent M.; Mitchell, Aaron P.; Wiederhold, Nathan P.; Barker, Katherine S.

    2014-01-01

    Azole antifungal agents such as fluconazole exhibit fungistatic activity against Candida albicans. Strategies to enhance azole antifungal activity would be therapeutically appealing. In an effort to identify transcriptional pathways that influence the killing activity of fluconazole, we sought to identify transcription factors (TFs) involved in this process. From a collection of C. albicans strains disrupted for genes encoding TFs (O. R. Homann, J. Dea, S. M. Noble, and A. D. Johnson, PLoS Genet. 5:e1000783, 2009, http://dx.doi.org/10.1371/journal.pgen.1000783), four strains exhibited marked reductions in minimum fungicidal concentration (MFCs) in both RPMI and yeast extract-peptone-dextrose (YPD) media. One of these genes, UPC2, was previously characterized with regard to its role in azole susceptibility. Of mutants representing the three remaining TF genes of interest, one (CAS5) was unable to recover from fluconazole exposure at concentrations as low as 2 μg/ml after 72 h in YPD medium. This mutant also showed reduced susceptibility and a clear zone of inhibition by Etest, was unable to grow on solid medium containing 10 μg/ml fluconazole, and exhibited increased susceptibility by time-kill analysis. CAS5 disruption in highly azole-resistant clinical isolates exhibiting multiple resistance mechanisms did not alter susceptibility. However, CAS5 disruption in strains with specific resistance mutations resulted in moderate reductions in MICs and MFCs. Genome-wide transcriptional analysis was performed in the presence of fluconazole and was consistent with the suggested role of CAS5 in cell wall organization while also suggesting a role in iron transport and homeostasis. These findings suggest that Cas5 regulates a transcriptional network that influences the response of C. albicans to fluconazole. Further delineation of this transcriptional network may identify targets for potential cotherapeutic strategies to enhance the activity of the azole class of antifungals

  14. 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. PMID:16192986

  15. Safety and Tolerability of Fluconazole in Children

    PubMed Central

    Novelli, Vas; Holzel, Helen

    1999-01-01

    The safety profile of fluconazole was assessed for 562 children (ages, 0 to 17 years) comprising 323 males and 239 females. The data are derived from 12 clinical studies of fluconazole as prophylaxis or treatment for a variety of fungal infections in predominantly immunocompromised patients. Most children received multiple doses of fluconazole in the range of 1 to 12 mg/kg of body weight; a few received single doses. Administration was mainly by oral suspension or intravenous injection. Overall, 58 (10.3%) children reported 80 treatment-related side effects. The most common side effects were associated with the gastrointestinal tract (7.7%) or skin (1.2%). Self-limiting, treatment-related side effects affecting the liver and biliary system were reported in three patients (0.5%). Overall, 18 patients (3.2%) discontinued treatment due to side effects, mainly gastrointestinal symptoms. Dose and age did not appear to influence the incidence and pattern of side effects. Treatment-related laboratory abnormalities were uncommon, the most frequent being transient elevated alanine aminotransferase (4.9%), aspartate aminotransferase (2.7%), and alkaline phosphatase (2.3%) levels. Although 98.6% of patients were taking concomitant medications, no clinical or laboratory interactions were observed. The safety profile of fluconazole was compared with those of other antifungal agents, mostly oral polyenes, by using a subset of data from five controlled studies. Side effects were reported by more patients treated with fluconazole (45 of 382; 11.8%) than by those patients treated with comparable agents (25 of 381; 6.6%); vomiting and diarrhea were the most common events in both groups. The incidence and type of treatment-related laboratory abnormalities were similar for the two groups. In conclusion, fluconazole was well tolerated by the pediatric population, many of whom were suffering from severe underlying disease and were taking a variety of concurrent medications. The safety

  16. Plasma fibronectin concentrations in dogs with disseminated intravascular coagulation.

    PubMed

    Feldman, B F; Thomson, D B; O'Neill, S

    1985-05-01

    Plasma fibronectin concentrations were significantly (P less than 0.001) below the reference range in dogs with disseminated intravascular coagulation (DIC) secondary to nonlymphomatous neoplasia, acute necrotizing pancreatitis, sepsis, chronic active hepatitis, and heat stroke. There was no statistical evidence of a group effect. Decrease in fibronectin concentration was associated with severe DIC, although no attempt was made to correlate fibronectin concentration with prognosis. These findings parallel those reported for severely ill human beings with diseases associated with DIC. They exemplify the potential of spontaneous diseases in animals as models for the study of human disease. PMID:4003893

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

    PubMed

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

    2002-07-01

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

  18. 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

  19. Intracutaneous Distributions of Fluconazole, Itraconazole, and Griseofulvin in Guinea Pigs and Binding to Human Stratum Corneum

    PubMed Central

    Sobue, Satoshi; Sekiguchi, Kaneo; Nabeshima, Toshitaka

    2004-01-01

    We have compared the distribution of fluconazole (FLC) with that of itraconazole (ITC) and griseofulvin (GRF) in the abdominal skin tissues after a single oral dose was administered to guinea pigs. The FLC concentrations in the stratum corneum reached a peak at 2 h after administration and were similar to those of ITC and higher than those of GRF in spite of the administration of a lower dose. GRF was eliminated from the stratum corneum faster than FLC and ITC. The FLC concentrations were also remarkably higher than those of ITC and GRF in the epidermis-cutis but lower in the subcutaneous fatty tissue. The distribution characteristics of each drug result from differences in their physicochemical properties. Following the administration of multiple doses, the FLC concentrations in the stratum corneum were highest in the abdominal skin tissues; those at 24 h after each administration increased gradually and were maintained at a level more than 10 times higher than that of the plasma concentrations. The FLC concentrations in the planta pedis stratum corneum and in the nail showed good dose proportionality and obvious accumulation and were 60 and 40 times as high as that in plasma on day 14. The extent of binding of FLC to human corneous keratin in vitro was about 10%, which is lower than those of ITC (94 to 97%) and GRF (36 to 38%). FLC, unlike ITC, therefore, is presumed to exist in the stratum corneum at high concentrations in an active nonbinding form. These excellent intracutaneous pharmacokinetic properties of FLC probably account in large part for the in vivo efficacy of FLC. PMID:14693542

  20. Evaluation of cerebrospinal fluid concentration and plasma free concentration as a surrogate measurement for brain free concentration.

    PubMed

    Liu, Xingrong; Smith, Bill J; Chen, Cuiping; Callegari, Ernesto; Becker, Stacey L; Chen, Xi; Cianfrogna, Julie; Doran, Angela C; Doran, Shawn D; Gibbs, John P; Hosea, Natilie; Liu, Jianhua; Nelson, Frederick R; Szewc, Mark A; Van Deusen, Jeffrey

    2006-09-01

    This study was designed to evaluate the use of cerebrospinal fluid (CSF) drug concentration and plasma unbound concentration (C(u,plasma)) to predict brain unbound concentration (C(u,brain)). The concentration-time profiles in CSF, plasma, and brain of seven model compounds were determined after subcutaneous administration in rats. The C(u,brain) was estimated from the product of total brain concentrations and unbound fractions, which were determined using brain tissue slice and brain homogenate methods. For theobromine, theophylline, caffeine, fluoxetine, and propranolol, which represent rapid brain penetration compounds with a simple diffusion mechanism, the ratios of the area under the curve of C(u,brain)/C(CSF) and C(u,brain)/C(u,plasma) were 0.27 to 1.5 and 0.29 to 2.1, respectively, using the brain slice method, and were 0.27 to 2.9 and 0.36 to 3.9, respectively, using the brain homogenate method. A P-glycoprotein substrate, CP-141938 (methoxy-3-[(2-phenyl-piperadinyl-3-amino)-methyl]-phenyl-N-methyl-methane-sulfonamide), had C(u,brain)/C(CSF) and C(u,brain)/C(u,plasma) ratios of 0.57 and 0.066, using the brain slice method, and 1.1 and 0.13, using the brain homogenate method, respectively. The slow brain-penetrating compound, N[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl-]sarcosine, had C(u,brain)/C(CSF) and C(u,brain)/C(u,plasma) ratios of 0.94 and 0.12 using the brain slice method and 0.15 and 0.018 using the brain homogenate method, respectively. Therefore, for quick brain penetration with simple diffusion mechanism compounds, C(CSF) and C(u,plasma) represent C(u,brain) equally well; for efflux substrates or slow brain penetration compounds, C(CSF) appears to be equivalent to or more accurate than C(u,plasma) to represent C(u,brain). Thus, we hypothesize that C(CSF) is equivalent to or better than C(u,plasma) to predict C(u,brain). This hypothesis is supported by the literature data. PMID:16760229

  1. Modulation of plasma melatonin concentrations by changes in posture.

    PubMed

    Nathan, P J; Jeyaseelan, A S; Burrows, G D; Norman, T R

    1998-05-01

    Posture change from a lying position to a standing position results in a decrease in plasma volume, which leads to an increase in plasma constituents, especially that of proteins and blood constituents bound to them. The aim of the present study was to investigate the physiological effects of postural changes on plasma nocturnal melatonin concentrations in healthy human volunteers. The study was divided into four stages. During stage one, subjects were seated from 21.00 hr to 01.00 hr. In stage two, subjects were lying at ground level from 21.00 hr to 01.00 hr. In stage three, subjects were is a sitting position from 2100 hr to 2300 hr and then in a standing position from 23.00 hr to 24.00 hr, and back to the sitting position from 24.00 hr to 01.00 hr. In the final stage, subjects were in a lying position from 21.00 hr to 23.00 hr and then in a standing position from 23.00 hr to 24.00 hr and back to the lying position from 24.00 hr to 01.00 hr. AUC analysis showed significant differences between sitting and lying positions (t=2.84; P<0.05; df=5), with higher melatonin levels associated with the sitting position (mean difference in peak concentration of 17.1 pg/ml). Furthermore a change in posture from the lying to the standing position produced a statistically significant increase in melatonin concentrations (final stage) (t=-3.37; P<0.05; df=5) (mean difference in peak concentration of 28.5 pg/ml). No differences were found with a change in posture from a sitting to a standing position. The hemoconcentration and hemodilution associated with posture changes may play a role in altering plasma protein bound hormones such as melatonin. PMID:9572531

  2. Fluconazole in the treatment of Cushing's disease

    PubMed Central

    Christie-David, Darshika; Gunton, Jenny E

    2016-01-01

    Summary Ketoconazole was a first-line agent for suppressing steroidogenesis in Cushing's disease. It now has limited availability. Fluconazole, another azole antifungal, is an alternative, although its in vivo efficacy is unclear. A 61-year-old female presented with weight gain, abdominal striae and worsening depression. HbA1c increased to 76 mmol/mol despite increasing insulin. Investigations confirmed cortisol excess; afternoon serum cortisol was 552 nmol/l with an inappropriate ACTH of 9.3 pmol/l. In total, 24-h urinary free cortisol (UFC):creatinine ratio was 150 nmol/mmol with failure to suppress after 48 h of low-dose dexamethasone. Pituitary MRI revealed a 4-mm microadenoma. Inferior petrosal sinus sampling confirmed Cushing's disease. Transsphenoidal resection was performed and symptoms improved. However, disease recurred 6 months later with elevated 24-h UFC >2200 nmol/day. Metyrapone was commenced at 750 mg tds. Ketoconazole was later added at 400 mg daily, with dose reduction in metyrapone. When ketoconazole became unavailable, fluconazole 200 mg daily was substituted. Urine cortisol:creatinine ratio rose, and the dose was increased to 400 mg daily with normalisation of urine hormone levels. Serum cortisol and urine cortisol:creatinine ratios remain normal on this regimen at 6 months. In conclusion, to our knowledge, this is the first case demonstrating prolonged in vivo efficacy of fluconazole in combination with low-dose metyrapone for the treatment of Cushing's disease. Fluconazole has a more favourable toxicity profile, and we suggest that it is a potential alternative for medical management of Cushing's disease. Learning points Surgery remains first line for the management of Cushing's disease with pharmacotherapy used where surgery is unsuccessful or there is persistence of cortisol excess.Ketoconazole has previously been used to treat cortisol excess through inhibition of CYP450 enzymes 11-β-hydroxylase and 17-

  3. In vitro activity of essential oils extracted from condiments against fluconazole-resistant and -sensitive Candida glabrata.

    PubMed

    Soares, I H; Loreto, É S; Rossato, L; Mario, D N; Venturini, T P; Baldissera, F; Santurio, J M; Alves, S H

    2015-09-01

    In the present study, the antifungal activity of essential oils obtained from Origanum vulgare (oregano), Cinnamomum zeylanicum (cinnamon), Lippia graveolens (Mexican oregano), Thymus vulgaris (thyme), Salvia officinalis (sage), Rosmarinus officinalis (rosemary), Ocimum basilicum (basil) and Zingiber officinale (ginger) were assessed against Candida glabrata isolates. One group contained 30 fluconazole-susceptible C. glabrata isolates, and the second group contained fluconazole-resistant isolates derived from the first group after the in vitro induction of fluconazole-resistance, for a total of 60 tested isolates. The broth microdilution methodology was used. Concentrations of 50μg/mL, 100μg/mL, 200μg/mL, 400μg/mL, 800μg/mL, 1600μg/mL and 3200μg/mL of the essential oils were used, and the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined. Thyme, sage, rosemary, basil and ginger essential oils showed no antifungal activity at the tested concentrations. Antimicrobial activity less than or equal to 3200μg/mL was observed for oregano, Mexican oregano and cinnamon essential oils. Both the oregano and Mexican oregano essential oils showed high levels of antifungal activity against the fluconazole-susceptible C. glabrata group, whereas the cinnamon essential oil showed the best antifungal activity against the fluconazole-resistant C. glabrata isolates. PMID:26281965

  4. Fluconazole-Induced Acute Generalized Exanthematous Pustulosis

    PubMed Central

    Di Lernia, Vito; Ricci, Cinzia

    2015-01-01

    Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction and is usually caused by drugs. It is characterized by fever and acute, extensive occurrence of disseminated sterile pustules, accompanied by fever, malaise and peripheral blood leucocytosis. There have been several reports to date of AGEP following exposure to antifungals. In particular, terbinafine is included in the list of the agents conferring the highest risk of AGEP. The authors report the case of a 70-year-old male patient who developed AGEP shortly after commencing treatment with fluconazole, which has been reported in association with AGEP in a single case report. To our knowledge, this is the first reported case of AGEP associated with positive fluconazole patch test. PMID:25814733

  5. Bioadhesive Films Containing Fluconazole for Mucocutaneous Candidiasis

    PubMed Central

    Patel, S. K.; Shah, D. R.; Tiwari, S.

    2015-01-01

    Fluconazole is a broad spectrum antifungal agent that has been extensively applied for the management of oral, pharyngeal and cutaneous candidiasis. Fluconazole has a high volume of distribution (0.55–0.65 l/kg) and has systemic toxicity due to high drug-drug interaction. The present study focuses on the formulation of bioadhesive film as a controlled release carrier for fluconazole. The formulation was intended to provide localized delivery of fluconazole exclusively at the site of infection, thereby reducing its total dose and hence, dose-related toxicities. Bioadhesive films were prepared by solvent casting method using sodium alginate and polyvinyl alcohol alone as well as in various combinations. Prepared films were evaluated for physical characteristics like, weight and content uniformity, film thickness, swelling index, microenvironment pH and folding endurance. In vitro drug release, in vitro and ex vivo residence time, bioadhesive strength and skin irritation were also studied. Accelerated stability study was conducted on the optimized formulation as per ICH guidelines. Weight of all the films were not more than 20 mg. Thickness of the films ranged between 0.09 to 0.15 mm whereas swelling indices showed a high extent of variation. Films composed of polyvinyl alcohol alone provided a swelling index of 6%. Bioadhesive strength was found to be more than 18 g. Microenvironment pH was near to 7.0 for most of the formulations. Ex vivo residence time of optimized batch was more than 5 h and it provided controlled drug release up to 8 h. As revealed in FT-IR and DSC studies, drug was found to be compatible with the excipients used in this study. PMID:25767319

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

    PubMed Central

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

    2006-01-01

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

  7. Fluconazole use and safety in the nursery.

    PubMed

    Castagnola, E; Jacqz-Aigrain, E; Kaguelidou, F; Maragliano, R; Stronati, M; Rizzollo, S; Farina, D; Manzoni, P

    2012-05-01

    Fluconazole is a triazole antifungal agent that is widely used in the nursery. It is available in both intravenous and oral formulation, and is active against most of the fungal pathogens that require treatment when retrieved from culture samples in neonatal intensive care units. Although clinical use has been wide for over 15 years, there have been small safety and efficacy studies completed in young infants. Randomised clinical trials assessing effectiveness of this agent in prevention of systemic fungal infections in neonates have been published in the last decade, and one large additional randomised study has been recently completed. Nevertheless, a certain degree of uncertainty still exists regarding the kinetics and appropriate dosing of this agent in premature and term infants, as well as regarding safety. Areas of poignant debate include the feasibility of loading dose strategies, appropriate dosages in the early days of life in the different subgroups of preterm infants, and long-term safety of fluconazole administered in prophylaxis during the first weeks of life in extremely premature infants. This paper reviews the most recent evidence on fluconazole and its role in the NICU settings. PMID:22633503

  8. 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

  9. 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.

  10. Anti-Trichophyton Activity of Protocatechuates and Their Synergism with Fluconazole

    PubMed Central

    Gullo, Fernanda Patrícia; Sardi, Janaina de Cássia Orlandi; Costa-Orlandi, Caroline Barcelos; Sangalli-Leite, Fernanda; Scorzoni, Liliana; Regasini, Luis Octávio; Petrônio, Maicon Segalla; Souza, Patrícia Fernanda; Silva, Dulce Helena Siqueira; Mendes-Giannini, Maria José Soares

    2014-01-01

    Dermatophytosis and superficial mycosis are a major global public health problem that affects 20–25% of the world's population. The increase in fungal resistance to the commercially available antifungal agents, in conjunction with the limited spectrum of action of such drugs, emphasises the need to develop new antifungal agents. Natural products are attractive prototypes for antifungal agents due to their broad spectrum of biological activities. This study aimed to verify the antifungal activity of protocatechuic acid, 3,4-diacetoxybenzoic, and fourteen alkyl protocatechuates (3,4-dihydroxybenzoates) against Trichophyton rubrum and Trichophyton mentagrophytes and to further assess their activities when combined with fluconazole. Susceptibility and synergism assays were conducted as described in M38-A2 (CLSI), with modifications. Three strains of Trichophyton rubrum and three strains of Trichophyton mentagrophytes were used in this work. The pentyl, hexyl, heptyl, octyl, nonyl, and decyl protocatechuates showed great fungicidal effects, with minimum inhibitory concentration (MIC) values ranging from 0.97 to 7.8 mg/L. Heptyl showed a synergistic activity (FIC index = 0.49), reducing the MIC of fluconazole by fourfold. All substances tested were safe, especially the hexyl, heptyl, octyl, and nonyl compounds, all of which showed a high selectivity index, particularly in combination with fluconazole. These ester associations with fluconazole may represent a promising source of prototypes in the search for anti-Trichophyton therapeutic agents. PMID:25136374

  11. Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering

    PubMed Central

    2010-01-01

    Background Fungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure. Results Conserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither, leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity. Conclusions We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways. PMID:20653936

  12. Antimicrobial photodynamic therapy on Candida albicans pre-treated by fluconazole delayed yeast inactivation.

    PubMed

    Ferreira, Luis Rodolfo; Sousa, Aline Silva; Alvarenga, Letícia Heineck; Deana, Alessandro Melo; de Santi, Maria Eugênia Onofre Simões; Kato, Ilka Tiemy; Leal, Cintia Raquel Lima; Ribeiro, Martha Simões; Prates, Renato Araujo

    2016-09-01

    Antimicrobial photodynamic therapy (APDI) has been used to treat localized infection and the aim of this study was to evaluate the effect of APDI combined with fluconazole in suspension of Candida albicans. C. albicans ATCC90028 was subcultured onto Sabouraud agar and inocula were prepared at yeast density of 1×10(6)CFU/mL. Methylene blue (MB) was used with concentration of 100mM. Yeast cells were incubated for 30min in 24-well plate and then irradiated by LED (660nm; 690mW; A=2.7cm(2); I=250mW/cm(2)) with radiant exposure of 30, 60, and 120J/cm(2). The same APDI setup was used with 2h fluconazole (0.5μg/mL) incubation. A UV-vis optical absorption spectroscopy was achieved following fractionated irradiation up to 960s. There were substantial differences in the killing effect following MB-mediated APDI and C. albicans was eradicated in the both APDI groups. The fluconazole combined to APDI delayed the complete inactivation of the yeast (p<0.05). Spectroscopy showed a decrease in absorption following irradiation for all absorption peaks. APDI presented an antagonist effect in the presence of fluconazole. PMID:27179711

  13. 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

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

    PubMed Central

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

    2016-01-01

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

  15. 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.

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

    PubMed

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

    2001-10-01

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

  17. 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.

  18. 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

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

    PubMed Central

    Rose, Rajiv; Klemcke, Harold G

    2015-01-01

    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. PMID:26424242

  20. The effect of acute haemorrhage in the dog and man on plasma-renin concentration

    PubMed Central

    Brown, J. J.; Davies, D. L.; Lever, A. F.; Robertson, J. I. S.; Verniory, A.

    1966-01-01

    1. The effect of acute haemorrhage on the plasma renin concentration was studied in the dog and man. 2. Plasma-renin concentration was regularly increased after the larger bleeds; after the smaller haemorrhages plasma-renin concentration remained unchanged. 3. The results are discussed in relation to current hypotheses concerning the control of renin and aldosterone secretion. PMID:4287431

  1. Plasma phylloquinone concentrations increase following acupoint injection for primary dysmenorrhea

    PubMed Central

    Chao, Maria T.; Wade, Christine M.; Booth, Sarah L.

    2014-01-01

    Therapeutic benefits of acupoint injection of vitamin K in Spleen-6 for the treatment of primary dysmenorrhea have been observed in limited clinical settings. However, menadione, the form of vitamin K most studied for treating dysmenorrhea, is not routinely used in clinical practice in North America. As part of a larger clinical trial among women with primary dysmenorrhea aged 18 to 25 years old, we conducted a sub-study to test the plasma concentration of phylloquinone (vitamin K1). We collected blood samples of four women prior to and 24-48 hours following acupoint injection of phylloquinone in Spleen-6. Despite rapid turnover of phylloquinone observed in prior studies, we found that plasma phylloquinone concentrations significantly increased from pre-injection to one to two days after injection. Interestingly, higher phylloquinone was correlated with less pain intensity among women with dysmenorrhea. Additional research is needed on the association between vitamin K and menstrual pain, including the role of vitamin K deficiency in inflammation and pain, and the possible mechanisms of acupoint injection of vitamin K for the treatment of primary dysmenorrhea. PMID:24929459

  2. 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. PMID:26663920

  3. Dynamic and Heterogeneous Mutations to Fluconazole Resistance in Cryptococcus neoformans

    PubMed Central

    Xu, Jianping; Onyewu, Chiatogu; Yoell, Heather J.; Ali, Rabia Y.; Vilgalys, Rytas J.; Mitchell, Thomas G.

    2001-01-01

    Infections with the human pathogenic basidiomycetous yeast Cryptococcus neoformans are often treated with fluconazole. Resistance to this antifungal agent has been reported. This study investigated the patterns of mutation to fluconazole resistance in C. neoformans in vitro. The MIC of fluconazole was measured for 21 strains of C. neoformans. The MICs for these 21 strains differed (0.25 to 4.0 μg/ml), but the strains were selected for this study because they exhibited no growth on plates of yeast morphology agar (YMA) containing 8 μg of fluconazole per ml. To determine their mutation rates, six independent cultures from a single original colony were established for each of the 21 strains. Each culture was then spread densely on a YMA plate with 8 μg of fluconazole per ml. A random set of putative mutants was subcultured, and the MIC of fluconazole was determined for each mutant. The 21 strains evinced significant heterogeneity in their mutation rates. The MICs of the putative mutants ranged widely, from their original MIC to 64 μg of fluconazole per ml. However, for this set of 21 strains, there was no significant correlation between the original MIC for a strain and the mutation rate of that strain; the MIC for the mutant could not be predicted from the original MIC. These results suggest that dynamic and heterogeneous mutational processes are involved in generating fluconazole resistance in C. neoformans. PMID:11158735

  4. Efficacy of PLD-118, a Novel Inhibitor of Candida Isoleucyl-tRNA Synthetase, against Experimental Oropharyngeal and Esophageal Candidiasis Caused by Fluconazole-Resistant C. albicans

    PubMed Central

    Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M.; Sarafandi, Alia A.; Sein, Tin; Mickiene, Diana; Bacher, John; Groll, Andreas H.; Walsh, Thomas J.

    2004-01-01

    PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring β-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 μg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P ≤ 0.05, P ≤ 0.01, P ≤ 0.001, respectively), while FLC had no significant activity. PLD-118 demonstrated nonlinear plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve. The biochemical safety profile was similar to that of FLC. In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and esophageal candidiasis. PMID:15388459

  5. Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans.

    PubMed

    Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M; Sarafandi, Alia A; Sein, Tin; Mickiene, Diana; Bacher, John; Groll, Andreas H; Walsh, Thomas J

    2004-10-01

    PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve. The biochemical safety profile was similar to that of FLC. In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and esophageal candidiasis. PMID:15388459

  6. Fabrication and design of transdermal fluconazole spray.

    PubMed

    Gohel, Mukesh C; Nagori, Stavan A

    2009-01-01

    The objective of the present study was to formulate fluconazole transdermal spray for obtaining modified drug transport using eutectic mixture, ethyl cellulose, polyethylene oxide and alcohol. The formulated products were characterized. The selection of the optimized batch was done considering the results of drug transport in the first hour, the time required for 90% drug transport, viscosity and spray angle of the formulations. The inclusion of eutectic mixture, consisting of equal parts of camphor and menthol, showed improved drug transport through rat skin. The optimized batch exhibited larger mean zone of inhibition (antifungal activity), efficient in vivo activity and short term stability. PMID:19519193

  7. 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. PMID:26092494

  8. Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects.

    PubMed

    Nieminen, T; Lehtimäki, T; Mäenpää, J; Ropo, A; Uusitalo, H; Kähönen, M

    2007-01-01

    Timolol maleate is a non-selective beta-adrenoceptor antagonist currently used mainly as an ocular preparation for the treatment of glaucoma and ocular hypertension. Despite the topical administration, ophthalmic timolol causes systemic adrenergic beta-blocking because of absorption from the eye into the systemic circulation. Gel formulations of ophthalmic timolol have been developed to reduce systemic absorption and adverse effects in comparison with conventional aqueous solution formulations. Timolol is metabolized by the polymorphic cytochrome P450 2D6 enzyme (CYP2D6). The changes in heart rate (HR) are the most striking effects of the systematically absorbed fraction of ophthalmic timolol, with 0.5 % aqueous formulations presenting larger effects than 0.1 % hydrogel formulations, especially during exercise. Plasma levels of ophthalmic timolol correlate with the changes in HR. Neither 0.5 % aqueous nor 0.1 % hydrogel formulations of timolol have exerted noteworthy effects on systolic (SAP) or diastolic (DAP) arterial pressures, probably because of a compensatory increase in systemic vascular resistance due to the attenuation of HR. Ophthalmic timolol does not exert remarkable effects on pulmonary parameter peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) in non-asthmatic patients. CYP2D6 activity is clearly associated with the pharmacokinetic parameters, particularly when 0.5 % aqueous solution of timolol is used: peak plasma concentration, elimination half-life and area-under-the-curve are highest in CYP2D6 poor metabolizers. Finally, since there is a correlation between the plasma level of timolol and several haemodynamic effects - especially HR in the state of elevated beta-adrenergic tonus - the CYP2D6 poor metabolizers may be more prone to bradycardia during treatment with (aqueous) ophthalmic timolol. PMID:17366003

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

    PubMed

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

    2011-03-01

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

  10. Fluconazole pharmacokinetics in a morbidly obese, critically ill patient receiving continuous venovenous hemofiltration.

    PubMed

    Lopez, Natasha D; Phillips, Kristy M

    2014-09-01

    Current fluconazole dosing strategies can be described using either standardized doses (800 or 400 mg) or as weight-based dosing recommendations (12 mg/kg loading dose followed by 6 mg/kg maintenance dose). The ideal method of fluconazole dosing is still unclear for certain patient populations, such as those receiving renal replacement therapy or the morbidly obese. We describe a 48-year-old man with a body mass index of 84 kg/m(2) who was receiving continuous venovenous hemofiltration (CVVH) and was treated with fluconazole by using a weight-based dose determined by lean body weight, infused at a rate of 200 mg/hour. Blood samples were collected at hour 0 (i.e., ~24 hrs after the loading dose was administered) and at 3.5, 6.8, and 11.3 hours after the start of the 600-mg maintenance dose, infused over 3 hours. Pharmacokinetic parameters calculated were maximum serum concentration 9.64 mg/L, minimum serum concentration 5.98 mg/L, area under the serum concentration-time curve from 0-24 hours (AUC0-24 ) 184.75 mg/L•hour, elimination rate constant 0.0199 hour(-1) , elimination half-life 34.8 hours, and total body clearance 3.25 L/hour. Our data, when combined with previously published literature, do not support using a linear dose-to-AUC approximation to estimate drug dosing needs in the critically ill patient population receiving CVVH. In addition, our results suggest that morbidly obese patients are able to achieve pharmacodynamic goals defined as an AUC:MIC ratio higher than 25 by using a lean body weight for fluconazole dosing calculations. PMID:25074285

  11. Release profiles and morphological characterization by atomic force microscopy and photon correlation spectroscopy of 99mTechnetium-fluconazole nanocapsules.

    PubMed

    de Assis, Danielle Nogueira; Mosqueira, Vanessa Carla Furtado; Vilela, José Mário Carneiro; Andrade, Margareth Spangler; Cardoso, Valbert Nascimento

    2008-02-12

    Several classes of antifungal have been employed in candidiasis treatment, but patients with advanced immunodeficiency can present unsatisfactory results after therapy. In these cases, high doses of drugs or the use of multiple agents are sometimes used, and hence increasing the risk of serious side effects. Considering theses difficulties, the encapsulation of antifungal agents in nanoparticulate carriers has been used with the objective of modifying the pharmacokinetic of drugs resulting in more efficient treatments with less side effects. The purpose of this work was the preparation, characterization and the investigation of the release profiles of radiolabeled fluconazole nanocapsules. The size, homogeneity and zeta potential of NC preparations were determined with a Zetasizer 3000HS. The morphology and the structural organization were evaluated by atomic force microscopy (AFM). The release study in vitro of NC was evaluated in physiologic solution with or without 70% mouse plasma. The labeling yield of fluconazole with 99mTc was 94% and the radiolabeled drug was stable within 24h period. The encapsulation percentage of 99mTc-fluconazole in PLA-POLOX NC and PLA-PEG NC was approximately of 30%. The average diameter calculated by photon correlation spectroscopy (PCS) varied from 236 to 356 nm, while the average diameter determined by AFM varied from 238 to 411 nm. The diameter/height relation decreased significantly when 25% glutaraldehyde was used for NC fixation on mica. The zeta potential varied from -55 to -69 nm and surface-modified NC showed lower absolute values than conventional NC. The in vitro release of 99mTc-fluconazole in plasma medium of the conventional and surface-modified NC was greater than in saline. The drug release in plasma medium from conventional NC was faster than for surface-modified NC. The results obtained in this work suggest that the nanocapsules containing fluconazole could be used to identify infectious foci, due to the properties

  12. Temporal variations in plasma vitamin K and lipid concentrations and clotting factor activity in humans.

    PubMed

    Kamali, F; Edwards, C; Wood, P; Wynne, H A; Kesteven, P

    2001-11-01

    There is no information available on temporal variability in plasma vitamin K concentrations and its relationship to coagulation processes. We investigated the possible existence of temporal changes in plasma vitamin K and lipid concentrations and activity of clotting factors II, VII, IX, and X and relationships between these variables. Plasma vitamin K and lipid concentrations and clotting factor activity were measured at four-hour intervals for 28 hours in a group of healthy volunteers. Temporal variations existed in plasma vitamin K concentrations, with a mean maximum at 22:00 hr and a mean minimum (32% of the maximum) at 10:00 hr. Plasma triglycerol concentrations mirrored the changes in vitamin K concentrations. Mean factor VII activity was positively correlated with mean total plasma cholesterol concentrations (r = 0.714; P < 0.0001) and with mean plasma low density lipoprotein (LDL) cholesterol concentrations (r = 0.461; P < 0.0001). No distinct correlations were found between plasma vitamin K concentrations and either high density lipoprotein (HDL) or LDL cholesterol concentrations, or between triglycerol, HDL, or LDL cholesterol concentrations and functional activity of factors II, IX, and X. Plasma vitamin K concentrations did not correlate with the functional activity of any of the clotting factors. The presence of a correlation between plasma cholesterol concentrations and factor VII activity for blood samples collected at four-hour intervals suggests that plasma cholesterol concentrations may have a more acute effect on factor VII activity. Temporal variations in plasma vitamin K concentrations indicate that a single time point measurement may be an inappropriate method of establishing vitamin K status in an individual. PMID:11754396

  13. Demonstration of Therapeutic Equivalence of Fluconazole Generic Products in the Neutropenic Mouse Model of Disseminated Candidiasis.

    PubMed

    Gonzalez, Javier M; Rodriguez, Carlos A; Zuluaga, Andres F; Agudelo, Maria; Vesga, Omar

    2015-01-01

    Some generics of antibacterials fail therapeutic equivalence despite being pharmaceutical equivalents of their innovators, but data are scarce with antifungals. We used the neutropenic mice model of disseminated candidiasis to challenge the therapeutic equivalence of three generic products of fluconazole compared with the innovator in terms of concentration of the active pharmaceutical ingredient, analytical chemistry (liquid chromatography/mass spectrometry), in vitro susceptibility testing, single-dose serum pharmacokinetics in infected mice, and in vivo pharmacodynamics. Neutropenic, five week-old, murine pathogen free male mice of the strain Udea:ICR(CD-2) were injected in the tail vein with Candida albicans GRP-0144 (MIC = 0.25 mg/L) or Candida albicans CIB-19177 (MIC = 4 mg/L). Subcutaneous therapy with fluconazole (generics or innovator) and sterile saline (untreated controls) started 2 h after infection and ended 24 h later, with doses ranging from no effect to maximal effect (1 to 128 mg/kg per day) divided every 3 or 6 hours. The Hill's model was fitted to the data by nonlinear regression, and results from each group compared by curve fitting analysis. All products were identical in terms of concentration, chromatographic and spectrographic profiles, MICs, mouse pharmacokinetics, and in vivo pharmacodynamic parameters. In conclusion, the generic products studied were pharmaceutically and therapeutically equivalent to the innovator of fluconazole. PMID:26536105

  14. Demonstration of Therapeutic Equivalence of Fluconazole Generic Products in the Neutropenic Mouse Model of Disseminated Candidiasis

    PubMed Central

    Gonzalez, Javier M.; Rodriguez, Carlos A.; Zuluaga, Andres F.; Agudelo, Maria; Vesga, Omar

    2015-01-01

    Some generics of antibacterials fail therapeutic equivalence despite being pharmaceutical equivalents of their innovators, but data are scarce with antifungals. We used the neutropenic mice model of disseminated candidiasis to challenge the therapeutic equivalence of three generic products of fluconazole compared with the innovator in terms of concentration of the active pharmaceutical ingredient, analytical chemistry (liquid chromatography/mass spectrometry), in vitro susceptibility testing, single-dose serum pharmacokinetics in infected mice, and in vivo pharmacodynamics. Neutropenic, five week-old, murine pathogen free male mice of the strain Udea:ICR(CD-2) were injected in the tail vein with Candida albicans GRP-0144 (MIC = 0.25 mg/L) or Candida albicans CIB-19177 (MIC = 4 mg/L). Subcutaneous therapy with fluconazole (generics or innovator) and sterile saline (untreated controls) started 2 h after infection and ended 24 h later, with doses ranging from no effect to maximal effect (1 to 128 mg/kg per day) divided every 3 or 6 hours. The Hill’s model was fitted to the data by nonlinear regression, and results from each group compared by curve fitting analysis. All products were identical in terms of concentration, chromatographic and spectrographic profiles, MICs, mouse pharmacokinetics, and in vivo pharmacodynamic parameters. In conclusion, the generic products studied were pharmaceutically and therapeutically equivalent to the innovator of fluconazole. PMID:26536105

  15. Antioxidant plasma concentration and supplementation in carotid intima media thickness.

    PubMed

    Riccioni, Graziano; Bazzano, Lydia A

    2008-06-01

    Cerebrovascular diseases represent a major problem in Western countries. Oxidative stress, an important condition of increased amounts of reactive oxygen species, is now recognized to be a prominent feature of many acute and chronic diseases, and even of the normal aging process. Carotid intima media thickness is an important marker of atherosclerosis that correlates with established coronary heart disease. Changes in carotid intima media thickness, measured by B-mode high-resolution carotid ultrasonography, represent an important and early step in carotid plaque formation and progression and are the most common currently used marker to evaluate the progression of atherosclerotic processes. Several therapeutic strategies have been adopted to slow the early atherosclerotic process in asymptomatic subjects in order to reduce the risk of cardiovascular events. An additional step to slow the atherosclerotic process may include interventions to decrease newly emerging coronary risk factors, such as oxidative stress and inflammation. Consuming a diet rich in fruits and vegetables will provide antioxidant vitamins, and carotenoids, which are believed to inhibit tissue damage derived from oxidative processes and may slow the progression of early atherosclerosis, modify the increase in carotid intima media thickness and, consequently, reduce cardiovascular events. This review synthesizes the published literature regarding antioxidant vitamins plasma concentration and supplementation and carotid intima media thickness. PMID:18510488

  16. 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. PMID:23817382

  17. Plasma, urinary, and erythrocyte concentrations of guanidino compounds in patients with chronic renal failure.

    PubMed

    Tanaka, A; Takahashi, Y; Mizokuchi, M; Shimada, N; Koide, H

    1999-09-01

    Guanidino compounds are among the most likely candidates for uremic toxins. We determined the plasma, erythrocyte, and urinary concentration of guanidino compounds in 30 hemodialysis patients and 15 patients with chronic renal failure who had not undergone hemodialysis. Guanidino compounds were measured by high-performance liquid chromatography. Plasma levels of taurocyamine, guanidinosuccinic acid, alpha-N-acetyl-L-arginine, creatine, guanidinobutyric acid, guanidine, and methylguanidine were significantly increased in patients with chronic renal failure with or without hemodialysis. In contrast, plasma guanidinoacetic acid concentrations were significantly decreased. Erythrocyte concentrations of creatinine, guanidinosuccinic acid, guanidine and methylguanidine were also markedly elevated. No correlation was observed between plasma creatinine concentration and erythrocyte concentration of guanidinosuccinic acid or methylguanidine. However, there was a significant correlation between plasma and erythrocyte methylguanidine, and between plasma and erythrocyte guanidinosuccinic acid. PMID:10516995

  18. Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans

    PubMed Central

    Liu, Shuyuan; Yue, Longtao; Gu, Wenrui; Li, Xiuyun; Zhang, Liuping; Sun, Shujuan

    2016-01-01

    Candidiasis has increased significantly recently that threatens patients with low immunity. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of fungal resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapy is one of the most widely used and effective strategy to alleviate this problem. In this paper, we were aimed to evaluate the combined antifungal effects of four CCBs (calcium channel blockers), amlodipine (AML), nifedipine (NIF), benidipine (BEN) and flunarizine (FNZ) with fluconazole against C. albicans by checkerboard and time-killing method. In addition, we determined gene (CCH1, MID1, CNA1, CNB1, YVC1, CDR1, CDR2 and MDR1) expression by quantitative PCR and investigated the efflux pump activity of resistant candida albicans by rhodamine 6G assay to reveal the potential mechanisms. Finally, we concluded that there was a synergy when fluconazole combined with the four tested CCBs against resistant strains, with fractional inhibitory concentration index (FICI) <0.5, but no interaction against sensitive strains (FICI = 0.56 ~ 2). The mechanism studies revealed that fluconazole plus amlodipine caused down-regulating of CNA1, CNB1 (encoding calcineurin) and YVC1 (encoding calcium channel protein in vacuole membrane). PMID:26986478

  19. Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans.

    PubMed

    Liu, Shuyuan; Yue, Longtao; Gu, Wenrui; Li, Xiuyun; Zhang, Liuping; Sun, Shujuan

    2016-01-01

    Candidiasis has increased significantly recently that threatens patients with low immunity. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of fungal resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapy is one of the most widely used and effective strategy to alleviate this problem. In this paper, we were aimed to evaluate the combined antifungal effects of four CCBs (calcium channel blockers), amlodipine (AML), nifedipine (NIF), benidipine (BEN) and flunarizine (FNZ) with fluconazole against C. albicans by checkerboard and time-killing method. In addition, we determined gene (CCH1, MID1, CNA1, CNB1, YVC1, CDR1, CDR2 and MDR1) expression by quantitative PCR and investigated the efflux pump activity of resistant candida albicans by rhodamine 6G assay to reveal the potential mechanisms. Finally, we concluded that there was a synergy when fluconazole combined with the four tested CCBs against resistant strains, with fractional inhibitory concentration index (FICI) <0.5, but no interaction against sensitive strains (FICI = 0.56 ~ 2). The mechanism studies revealed that fluconazole plus amlodipine caused down-regulating of CNA1, CNB1 (encoding calcineurin) and YVC1 (encoding calcium channel protein in vacuole membrane). PMID:26986478

  20. Variability of plasma phenobarbitone concentration in Asian children in Singapore.

    PubMed

    Lee, H S

    1984-01-01

    In a study with 113 Asian children in which phenobarbitone was used as the sole antiepileptic drug in 75 children, including Chinese, Malays, and Indians, the mean phenobarbitone dosage required to produce a plasma level of 15 micrograms/ml was 5.2 mg/kg/day. While the mean plasma level/dose ratio varied, the differences between the three ethnic groups were not statistically significant. Also of little difference were the ratios between the male and female groups. For those patients with poor seizure control, however, the mean plasma level/dose ratio was significantly lower than in those whose seizures were controlled. Using additional anticonvulsant drugs concurrently with phenobarbitone in 40 children raised the mean plasma level/dose ratios significantly in each ethnic group. Further, the greater age level in those given additional antiepileptic drugs might have contributed slightly to a higher mean plasma level/dose ratio. PMID:6740737

  1. Plasma Copper and Zinc Concentration in Individuals with Autism Correlate with Selected Symptom Severity

    PubMed Central

    Russo, Anthony J.; Bazin, Andrea P.; Bigega, Richard; Carlson, Robert S.; Cole, Martin G.; Contreras, Dilenia C.; Galvin, Matthew B.; Gaydorus, Sayde S.; Holik, Sierra D.; Jenkins, Gavin P.; Jones, Brandon M.; Languell, Penelope A.; Lyman, Padraic J.; March, Kareem P.; Meuer, Katie A.; Peterson, Serena R.; Piedmonte, Matthew T.; Quinn, Michael G.; Smaranda, Nicole C.; Steves, Patrick L.; Taylor, Heather P.; Waddingham, Teagan E.; Warren, Janine S.

    2012-01-01

    Aim: To assess plasma zinc and copper concentration in individuals with autism and correlate these levels with symptom severity. Subjects and methods: Plasma from 102 autistic individuals, and 18 neurotypical controls, were tested for plasma zinc and copper using inductively-coupled plasma-mass spectrometry. Copper and zinc levels and Cu/Zn were analyzed for possible correlation with severity of 19 symptoms. Results: Autistic individuals had elevated plasma levels of copper and Cu/Zn and lower, but not significantly lower, plasma Zn compared to neurotypical controls. There was a correlation between Cu/Zn and expressive language, receptive language, focus attention, hyperactivity, fine motor skills, gross motor skills and Tip Toeing. There was a negative correlation between plasma zinc concentration and hyperactivity, and fine motor skills severity. Discussion: These results suggest an association between plasma Cu/Zn and severity of symptoms associated with autism. PMID:23882147

  2. Feto-maternal plasma phenylalanine concentration gradient from 19 weeks gestation to term.

    PubMed

    Schoonheyt, W E; Clarke, J T; Hanley, W B; Johnson, J M; Lehotay, D C

    1994-03-01

    Plasma phenylalanine concentrations in fetal blood, obtained by cordocentesis, were compared with simultaneous peripheral venous plasma phenylalanine levels in mothers. The feto-maternal phenylalanine concentration ratio showed a gradual decrease from 19 weeks of gestation to term with an overall ratio of 1.35 +/- 0.42 (mean +/- S.D., n = 14). PMID:8088005

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

    PubMed

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

    2015-01-01

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

  4. Mutation of G234 amino acid residue in Candida albicans drug-resistance-related protein Rta2p is associated with fluconazole resistance and dihydrosphingosine transport

    PubMed Central

    Zhang, Shi-Qun; Miao, Qi; Li, Li-Ping; Zhang, Lu-lu; Yan, Lan; Jia, Yu; Cao, Yong-Bing; Jiang, Yuan-Ying

    2015-01-01

    Widespread and repeated use of azoles has led to the rapid development of drug resistance in Candida albicans. Our previous study found Rta2p, a membrane protein with 7 transmembrane domains, was involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans. Conserved amino acids in the transmembrane domain of Rta2p were subjected to site-directed mutagenesis. The sensitivity of C. albicans to fluconazole in vitro was examined by minimum inhibitory concentration and killing assay, and the therapeutic efficacy of fluconazole in vivo was performed by systemic mice candidiasis model. Furthermore, dihydrosphingosine transport activity was detected by NBD labeled D-erythro-dihydrosphingosine uptake and release assay, and the sensitivity to sphingolipid biosynthesis inhibitors. We successfully constructed 14 mutant strains of Rta2p, screened them by minimum inhibitory concentration and found Ca2+ did not completely induce fluconazole resistance with G158E and G234S mutations. Furthermore, we confirmed that G234S mutant enhanced the therapeutic efficacy of fluconazole against systemic candidiasis and significantly increased the accumulation of dihydrosphingosine by decreasing its release. However, G158E mutant didn't affect drug therapeutic efficacy in vivo and dihydrosphingosine transport in C. albicans. G234 of Rta2p in C. albicans is crucial in calcineurin-mediated fluconazole resistance and dihydrosphingosine transport. PMID:26220356

  5. Mutation of G234 amino acid residue in candida albicans drug-resistance-related protein Rta2p is associated with fluconazole resistance and dihydrosphingosine transport.

    PubMed

    Zhang, Shi-Qun; Miao, Qi; Li, Li-Ping; Zhang, Lu-Lu; Yan, Lan; Jia, Yu; Cao, Yong-Bing; Jiang, Yuan-Ying

    2015-01-01

    Widespread and repeated use of azoles has led to the rapid development of drug resistance in Candida albicans. Our previous study found Rta2p, a membrane protein with 7 transmembrane domains, was involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans. Conserved amino acids in the transmembrane domain of Rta2p were subjected to site-directed mutagenesis. The sensitivity of C. albicans to fluconazole in vitro was examined by minimum inhibitory concentration and killing assay, and the therapeutic efficacy of fluconazole in vivo was performed by systemic mice candidiasis model. Furthermore, dihydrosphingosine transport activity was detected by NBD labeled D-erythro-dihydrosphingosine uptake and release assay, and the sensitivity to sphingolipid biosynthesis inhibitors. We successfully constructed 14 mutant strains of Rta2p, screened them by minimum inhibitory concentration and found Ca(2+) did not completely induce fluconazole resistance with G158E and G234S mutations. Furthermore, we confirmed that G234S mutant enhanced the therapeutic efficacy of fluconazole against systemic candidiasis and significantly increased the accumulation of dihydrosphingosine by decreasing its release. However, G158E mutant didn't affect drug therapeutic efficacy in vivo and dihydrosphingosine transport in C. albicans. G234 of Rta2p in C. albicans is crucial in calcineurin-mediated fluconazole resistance and dihydrosphingosine transport. PMID:26220356

  6. 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

  7. Plasma lactate concentration as a prognostic biomarker in dogs with gastric dilation and volvulus.

    PubMed

    Mooney, Erin; Raw, Cameron; Hughes, Dez

    2014-09-01

    Initial and serial plasma lactate concentrations can be used to guide decision making in individual dogs with GDV but care is necessary in phrasing conversations with owners. Published data suggests that survival is more likely and the chance of complications less in dogs with an initial plasma lactate of <4 mmol/L. An initial lactate >6 mmol/L makes gastric necrosis and greater expense more likely. However, because of the overlap between groups and the good overall survival rates, exploratory laparotomy should always be recommended irrespective of the plasma lactate concentration. Falls in plasma lactate of greater than ~40% after fluid resuscitation are likely to indicate better survival. If the initial plasma lactate concentration is moderately to severely increased (5->10 mmol/L) and a sustained increase in plasma lactate occurs after fluid resuscitation, the cause should be aggressively pursued. Many dogs with persistent hyperlactatemia over 24-48 hours do not survive. PMID:25496924

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

    PubMed

    Orchinik, M; Licht, P; Crews, D

    1988-09-01

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

  9. Candida albicans biofilm inhibition by synergistic action of terpenes and fluconazole.

    PubMed

    Pemmaraju, Suma C; Pruthi, Parul A; Prasad, R; Pruthi, Vikas

    2013-11-01

    The current treatment options for Candida albicans biofilm-device related infections are very scarce due to their intrinsic increased tolerance to antimycotics. The aim of this work was to study synergistic action of terpenes (eugenol, menthol and thymol) with fluconazole (FLA) on C. albicans biofilm inhibition. The minimum inhibitory concentration (MIC) assayed using CLSI M27-A3 broth micro-dilution method showed antifungal activity against C. albicans MTCC 227 at a concentration of 0.12 % (v/v) for both thymol and eugenol as compared to 0.25 % (v/v) for menthol. FLA was taken as positive control. The effect of these terpenes on metabolic activity of preformed C. albicans biofilm cells was evaluated using 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay in 96-well polystyrene microtiter plate. Thymol and eugenol were more effective at lower concentrations of > or = 1.0 % (v/v) than menthol. Synergistic studies using checkerboard micro-dilution assay showed fractional inhibitory concentration index (sigma FIC = 0.31) between thymol/FLA followed by eugenol/FLA (sigma FIC = 0.37) and menthol/FLA (sigma FIC < 0.5) against pre-formed C. albicans biofilms. Thymol with fluconazole showed highest synergy in reduction of biofilm formation than eugenol and menthol which was not observed when their activities were observed independently. Adherence assay showed 30% viability of C. albicans cells after 2 h of treatment with 0.05 % (v/v) thymol/FLA. Effect of thymol/FLA on C. albicans adhesion visualized by SEM micrographs showed disruption in number of candidal cells and alteration in structural design of C. albicans. Thus, the study demonstrated synergistic effect of terpenes with fluconazole on C. albicans biofilm, which could be future medications for biofilm infections. PMID:24416942

  10. Kinetics of plasma potassium concentrations during exhausting exercise in trained and untrained men.

    PubMed

    Marcos, E; Ribas, J

    1995-01-01

    The purpose of this study was to examine the time course of changes in plasma potassium concentration during high intensity exercise and recovery in trained and untrained men. The subjects performed two exercise protocols, an incremental test and a sprint, on a cycle ergometer. A polyethylene catheter was inserted into the antecubital vein to obtain blood samples for the analysis of plasma electrolyte concentrations and acid-base parameters, during and after exercise. During both tests, venous plasma sodium, potassium and chloride concentrations increased in all the subjects, although the largest relative increase was detected in potassium concentration--35% and 31% over rest in the progressive test and 61% and 37.7% in the sprint test, for cyclists and controls, respectively. After exercise plasma potassium concentration decreased exponentially to below resting values. There was a linear correlation between the amount of potassium accumulated in plasma during exercise and the amount eliminated from plasma when the exercise ceased. We found that, although plasma potassium accumulation occurred in both forms of exercise in the trained and nontrained subjects, the time constant of potassium decrease following exercise was shorter in the trained subjects. Thus, the trained subjects exhibited a better capacity to recover to resting concentrations of plasma potassium. We propose that the extracellular potassium accumulation acts as a negative feedback signal for sarcolemma excitability depending on the muscle metabolic rate. PMID:7588690

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

    PubMed Central

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

    2015-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. Watermelon consumption increases plasma arginine concentrations in adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Watermelon is a good source of citrulline, an amino acid that can be converted to arginine in the human body. Arginine helps in cardiovascular and immune health. No studies have been conducted to evaluate plasma arginine response in humans following consumption of citrulline from natural plant so...

  14. Fluconazole alters CYP26 gene expression in mouse embryos.

    PubMed

    Tiboni, Gian Mario; Marotta, Francesca; Carletti, Erminia

    2009-04-01

    Disruption of embryonal retinoic acid homeostasis has been postulated to represent an etiological factor involved in the onset of fluconazole-induced teratogenesis. In the present study the impact of a teratogenic pulse of fluconazole on the gene expression of cytochrome P450 (CYP) 26 isoforms, which plays a central role in maintaining proper retinoic acid levels by mediating its degradation, was investigated. ICR pregnant mice were orally administered with 0 (vehicle) or 700mg/kg of fluconazole on gestation day 8. Embryos were collected 12, 24 and 48h after treatment. Quantitative real-time reverse-transcription polymerase chain reaction (quantitative real-time RT-PCR) assay was used to quantify the mRNA expression of CYP26a1, CYP26b1 and CYP26c1 in embryos. As result, fluconazole exposure was associated to an up-regulation of CYP26a1, CYP26b1, whereas no significant change was identified for the CYP26c1 isoform. This study demonstrates the capacity of fluconazole to alter CYP26 gene expression in mouse embryos. PMID:19429397

  15. Topical fluconazole for experimental candida keratitis in rabbits.

    PubMed Central

    Behrens-Baumann, W; Klinge, B; Rüchel, R

    1990-01-01

    Using a reproducible model of Candida albicans keratitis in rabbits we studied the effect of topical fluconazole, a new triazole. Candida albicans DSM 70010 (2.5 X 10(5) cells) was injected into the corneal stroma of both eyes of 21 rabbits. All eyes developed a corneal ulcer. Forty-eight hours after inoculation the animals were divided into three groups: (1) 14 eyes, received fluconazole (2 mg/ml) and the epithelium subsequently removed; (2) 14 eyes, received only fluconazole drops; (3) 14 eyes, received 0.9% NaCl: half of this group was also debrided. We applied one drop of either substance 10 times a day for 24 days. A further six rabbits were used to judge if the drug penetrated into the cornea and aqueous humour. There was a highly significant difference between the fluconazole groups (1,2) and the control group (3) as to hypopyon and complications (descemetocele, corneal perforation) as well as recultivation of C. albicans from corneal tissue. The difference between the fluconazole groups with and without debridement was not significant. The drug penetrated into the cornea and aqueous humour of both uninflamed and inflamed eyes. Images PMID:2306443

  16. Molecularly imprinted solid phase extraction of fluconazole from pharmaceutical formulations.

    PubMed

    Manzoor, S; Buffon, R; Rossi, A V

    2015-03-01

    This work encompasses a direct and coherent strategy to synthesise a molecularly imprinted polymer (MIP) capable of extracting fluconazole from its sample. The MIP was successfully prepared from methacrylic acid (functional monomer), ethyleneglycoldimethacrylate (crosslinker) and acetonitrile (porogenic solvent) in the presence of fluconazole as the template molecule through a non-covalent approach. The non-imprinted polymer (NIP) was prepared following the same synthetic scheme, but in the absence of the template. The data obtained from scanning electronic microscopy, infrared spectroscopy, thermogravimetric and nitrogen Brunauer-Emmett-Teller plot helped to elucidate the structural as well as the morphological characteristics of the MIP and NIP. The application of MIP as a sorbent was demonstrated by packing it in solid phase extraction cartridges to extract fluconazole from commercial capsule samples through an offline analytical procedure. The quantification of fluconazole was accomplished through UPLC-MS, which resulted in LOD≤1.63×10(-10) mM. Furthermore, a high percentage recovery of 91±10% (n=9) was obtained. The ability of the MIP for selective recognition of fluconazole was evaluated by comparison with the structural analogues, miconazole, tioconazole and secnidazole, resulting in percentage recoveries of 51, 35 and 32%, respectively. PMID:25618633

  17. 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.

  18. Plasma concentrations of adrenomedullin and natriuretic peptides in patients with essential hypertension

    PubMed Central

    HU, WEI; ZHOU, PANG-HU; ZHANG, XIAO-BIN; XU, CHANG-GENG; WANG, WEI

    2015-01-01

    This study was designed to assess any changes in the plasma concentrations of adrenomedullin (ADM) and atrial and brain natriuretic peptide (ANP and BNP, respectively), and to investigate their pathophysiological roles in patients with essential hypertension (EH). The plasma ADM, ANP and BNP concentrations were measured in 64 patients with untreated EH and 35 normotensive control subjects. After 4 weeks of effective antihypertensive therapy with oral drugs for the hypertensive patients, the plasma concentrations of ADM, ANP and BNP in the hypertensive patients were measured again. The plasma concentrations of ADM, ANP and BNP were significantly higher in the hypertensive patients than those in the control subjects, and the concentrations increased with the clinical stage. Furthermore, the hypertensive patients exhibited increased mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr) and decreased glomerular filtration rates (GFRs) compared with the control subjects. The plasma ADM concentration was not only correlated with BUN, Scr and the GFR, but was also associated with the MAP and the plasma levels of ANP and BNP. Following effective antihypertensive therapy with oral medication for 4 weeks, the plasma concentrations of ADM, ANP and BNP were significantly, but not sharply, decreased. In conclusion, ADM, along with ANP and BNP, may be involved in the mechanisms acting against a further increase in blood pressure and may be useful biomarkers for the diagnosis and treatment of hypertensive patients. PMID:26136912

  19. Investigation of ERG11 gene expression among fluconazole-resistant Candida albicans: first report from an Iranian referral paediatric hospital.

    PubMed

    Teymuri, M; Mamishi, S; Pourakbari, B; Mahmoudi, S; Ashtiani, M T; Sadeghi, R H; Yadegari, M H

    2015-01-01

    The multiplicity of mechanisms of resistance to azole antifungal agents has been described. As fluconazole-resistant clinical Candida albicans isolates that constitutively over-express ERG11 have been identified in previous studies, the aim of this study is to investigate this molecular mechanism involved in fluconazole resistance of C. albicans clinical isolates. Fluconazole susceptibility testing was carried out on clinical isolates of Candida spp. obtained from hospitalised children in an Iranian referral children's hospital. A polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique was used to differentiate Candida spp. The resistant C. albicans isolates were subjected to RT-qPCR using primers that identify ERG11 gene expression. Of the 142 Candida spp. isolates studied, C. albicans was the most predominant isolate, occurring in 68.3% (97/142) of the patients. According to the CLSI method, the majority of the C. albicans isolates (91.7%, 89/97), categorised as susceptible (minimum inhibitory concentration [MIC] ≤8 μg/mL), five isolates were considered resistant (MIC ≤64 μg/mL) and three had dose-dependent susceptibility (MIC = 8.16-32 μg/mL). The ERG11 gene in the five fluconazole-resistant C. albicans isolates was upregulated 4.15-5.84-fold relative to the ATCC 10231 control strain. In this study, the expression of ERG11 was upregulated in all the fluconazole-resistant C. albicans isolates. There are limited data on the antifungal susceptibility of Candida spp. as well as the molecular mechanism of azole resistance in Iran, especially for isolates causing infections in children. Therefore, the surveillance of antifungal resistance patterns and investigation of other mechanisms of azole resistance in all Candida spp. isolates is recommended. PMID:25906488

  20. 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

  1. Plasma concentrations after high-dose (45 mg.kg-1) rectal acetaminophen in children.

    PubMed

    Montgomery, C J; McCormack, J P; Reichert, C C; Marsland, C P

    1995-11-01

    Although the recommended dose of rectal acetaminophen (25-30 mg.kg-1) is twice that for oral administration (10-15 mg.kg-1), the literature justifies the use of a higher dose when acetaminophen is administered via the rectal route. We measured venous plasma acetaminophen concentrations resulting from 45 mg.kg-1 of rectal acetaminophen in ten ASA 1, 15 kg paediatric patients undergoing minor surgery with a standardized anaesthetic. After induction of anaesthesia, a single 650 mg suppository (Abenol, SmithKline Beecham Pharma Inc.) was administered rectally. Plasma was sampled at t = 0, 15, 30, 45, 60, 90, 120, 180, 240 min in the first five patients and at t = 0, 30, 60, 90, 120, 180, 240, 300, 420 min in the subsequent five. Acetaminophen plasma concentrations were determined using a TDxFLx fluorescence polarization immunoassay (Abbott Laboratories, Toronto, Ontario). The maximum plasma concentration was 88 +/- 39 mumol.L-1 (13 +/- 6 micrograms.ml-1) and the time of peak plasma concentration was 198 +/- 70 min (mean +/- SD). At 420 min, the mean plasma concentration was 46 +/- 18 mumol.L-1 (7.0 +/- 0.9 micrograms.ml-1). No plasma concentrations associated with toxicity (> 800 mumol.L-1) were identified. A 45 mg.kg-1 rectal dose of acetaminophen resulted in peak plasma concentrations comparable with those resulting from 10-15 mg.kg-1 of oral acetaminophen at three hours after suppository insertion. It is concluded that the delayed and erratic absorption of acetaminophen after rectal administration leads to unpredictable plasma concentrations. Rectal acetaminophen will not be consistently effective for providing rapid onset of analgesia in children. PMID:8590508

  2. Changes in the plasma concentration of immunoreactive arginine vasotocin during oviposition in the domestic fowl.

    PubMed

    Tanaka, K; Goto, K; Yoshioka, T; Terao, T; Koga, O

    1984-10-01

    The plasma concentrations of immunoreactive arginine vasotocin (AVT) were measured during oviposition and shortly before ovulation of the first egg (Cl) of a clutch. Immunoreactive AVT was determined on bentonite extracts of 0.5 ml plasma samples using the method of Rosenbloom and Fisher (1974). The R-70 antiserum used to measure AVT cross reacted with arginine vasopressin (AVP), however the fowl pituitary does not synthesise AVP. Over a period of 10 to 90 min before oviposition the plasma AVT concentration was about 20 pg/ml; during oviposition it increased four-fold. Measurements made at frequent intervals showed that plasma AVT concentration increased 5 to 6 min before oviposition, reached a peak during oviposition itself and decreased rapidly in the following 5 to 6 min. The surge in plasma AVT occurred on average 48 min before Cl ovulation. PMID:6518411

  3. The Pressure-Induced Polymorphic Transformations in Fluconazole.

    PubMed

    Gorkovenko, Ekaterina A; Kichanov, Sergey E; Kozlenko, Denis P; Belushkin, Alexandr V; Wąsicki, Jan; Nawrocik, Wojciech; Mielcarek, Jadwiga; Dubrovinsky, Leonid S; Lathe, Christian; Savenko, Boris N

    2015-12-01

    The structural properties and Raman spectra of fluconazole have been studied by means of X-ray diffraction and Raman spectroscopy at pressures up to 2.5 and 5.5 GPa, respectively. At a pressure of 0.8 GPa, a polymorphic phase transition from the initial form I to a new triclinic form VIII has been observed. At higher pressure of P = 3.2 GPa, possible transformation into another new polymorphic form IX has been detected. The unit cell parameters and volumes, and vibration modes as functions of pressure have been obtained for the different forms of fluconazole. PMID:26367523

  4. Changes in plasma kynurenic acid concentration in septic shock patients undergoing continuous veno-venous haemofiltration.

    PubMed

    Dabrowski, Wojciech; Kocki, Tomasz; Pilat, Jacek; Parada-Turska, Jolanta; Malbrain, Manu L N G

    2014-02-01

    Kynurenic acid (KYNA) is one of the end products of tryptophan metabolism. The aim of this study was to analyse plasma KYNA concentration in septic shock patients (SSP) with acute kidney injury (AKI) undergoing continuous veno-venous haemofiltration (CVVH). Changes in KYNA content were compared to alterations in the levels of procalcitonin (PCT), C-reactive protein and lactate. Adult SSP with AKI were examined. Measurements were conducted at seven time points: before beginning CVVH and at 6, 12, 24, 48, 72 and 96 h after the beginning of CVVH. Based on clinical outcomes, the data were analysed separately for survivors and non-survivors. Twenty-seven patients were studied. CVVH was associated with reduced plasma KYNA concentration only in survivors. Plasma KYNA concentration correlated with the levels of lactate and PCT only in survivors. (1) CVVH reduced plasma KYNA concentration only in survivors; (2) lack of this reduction may predict fatal outcomes in SSP. PMID:24043287

  5. 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

  6. Biphasic response of plasma endothelin-1 concentration to exhausting submaximal exercise in man.

    PubMed

    Richter, E A; Emmeluth, C; Bie, P; Helge, J; Kiens, B

    1994-07-01

    The concentration of endothelin-1 in forearm venous plasma was measured in 10 healthy men at rest and during ergometer bicycling at 65% of maximal aerobic capacity until exhaustion (96 +/- 10 min, mean +/- SE). A control group of 10 comparable subjects rested for 2 h. Mean plasma endothelin-1 concentration at rest was 2.0 +/- 0.2 pg ml-1, n = 20. The concentration decreased significantly by 21% during the first 30 min of exercise, whereupon it increased so that the concentration after 60 min of exercise was no different from resting values. The change in endothelin concentration could not be explained by changes in plasma volume. Unspecific effects of catheterization or time could also not explain the change in endothelin-1, since in the 10 control subjects who did not exercise, plasma endothelin-1 did not change significantly over 120 min. It is concluded that the concentration of endothelin-1 in forearm venous plasma changes in a biphasic manner during prolonged exhaustive bicycle exercise in man. An initial decrease in concentration is followed by an increase restoring the concentration to resting values after 60 min exercise. PMID:7955935

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

    PubMed

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

    2005-01-01

    Kurz et al. conducted the first study of the intra-individual variability of clozapine plasma concentrations but did not take into account the effect of smoking and co-medication. As patients were receiving varying doses, Kurz et al. standardized plasma levels by using a plasma level/dose/kg ratio. In 15 patients, the mean coefficient of variation (CV) was 53% (S.D. = 21). In this new study, plasma clozapine and norclozapine concentrations were measured every 2 weeks in 47 patients randomized to 100, 300, or 600 mg/day for 16-week double-blind clozapine trials under controlled conditions (stable smoking, limited co-medication and absence of caffeinated beverages). For 100, 300 and 600 mg/day, the respective mean CVs for plasma clozapine concentrations were 23% (S.D. = 14), 19% (S.D.= 11) and 18% (S.D. = 8). For the combined concentrations of clozapine and norclozapine, the respective mean CVs were 20% (S.D. = 13), 16% (S.D. = 9) and 15% (S.D. = 7). Under 100 mg/day, the mean CV for clozapine concentrations was significantly higher for heavy smokers than non-heavy smokers (32%, S.D. = 3 vs. 19%, S.D. = 8) (p = 0.03). Studies of CVs in other environments are needed. Clozapine CVs may be important in order to understand the importance of variations around the therapeutic range and to interpret drug interactions above the usual noise of measuring plasma concentrations. PMID:15560958

  8. 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. PMID:26504722

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Respiratory alkalosis does not alter NOx concentrations in human plasma and erythrocytes.

    PubMed

    Ishibashi, T; Kubota, K; Himeno, M; Matsubara, T; Hori, T; Ozaki, K; Yamozoe, M; Aizawa, Y; Yoshida, J; Nishio, M

    2001-12-01

    To test the hypothesis that NOx (NO and NO, metabolites of NO) accumulates in red blood cells (RBC) in response to changes in PCO(2) and bicarbonate (HCO) concentration in blood, we examined the effect of changes in PCO(2) and HCO induced by hyperventilation in healthy adults on partitioning of NOx in whole blood. NOx in hemolysate was measured by a high-performance liquid chromatography-Griess system equipped with a C(18) reverse phase column to trap hemoglobin, which enables determination of whole blood NOx concentration and calculation of NOx concentration in RBC with high accuracy and reproducibility. NOx concentration in RBC was lower than that in plasma, and equilibrium between plasma and RBC was achieved rapidly after addition of NO. Changes in PCO(2) and HCO by hyperventilation failed to influence NOx concentrations in both plasma and RBC. Plasma NOx concentrations correlated with whole blood NOx and RBC NOx concentrations. Our results indicate that changes in PCO(2) or HCO induced by hyperventilation do not influence NOx compartmentalization in plasma and RBC. PMID:11709445

  14. Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor

    PubMed Central

    Bacus, Sarah; Blackwell, Kimberly; Smith, Deborah A.; Glenn, Kelli; Cartee, Leanne; Harris, Jennifer; Kimbrough, Carie L.; Gittelman, Mark; Avisar, Eli; Beitsch, Peter; Koch, Kevin M.

    2015-01-01

    Purpose The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER) in human tumors. Experimental Design Mice bearing BT474 HER2+ human breast cancer xenografts were dosed once or twice daily (BID) with lapatinib. Drug concentrations were measured in blood, tumor, liver, and kidney. In a randomized phase I clinical trial, 28 treatment-naïve female patients with early stage HER2+ breast cancer received lapatinib 1000 or 1500 mg once daily (QD) or 500 mg BID before evaluating steady-state lapatinib levels in plasma and tumor. Results In mice, lapatinib levels were 4-fold higher in tumor than blood with a 4-fold longer half-life. Tumor concentrations exceeded the in vitro IC90 (~ 900 nM or 500 ng/mL) for inhibition of HER2 phosphorylation throughout the 12-hour dosing interval. In patients, tumor levels were 6- and 10-fold higher with QD and BID dosing, respectively, compared to plasma trough levels. The relationship between tumor and plasma concentration was complex, indicating multiple determinants. HER receptor phosphorylation varied depending upon lapatinib tumor concentrations, suggestive of changes in the repertoire of HER homo- and heterodimers. Conclusion Plasma lapatinib concentrations underestimated tumor drug levels, suggesting that optimal dosing should be focused on the site of action to avoid to inappropriate dose escalation. Larger clinical trials are required to determine optimal dose and schedule to achieve tumor

  15. 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.

  16. Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine.

    PubMed Central

    Bridgeman, M. M.; Marsden, M.; MacNee, W.; Flenley, D. C.; Ryle, A. P.

    1991-01-01

    N-acetylcysteine (600 mg/day) was given to patients by mouth for five days before bronchoscopy and bronchoalveolar lavage to determine whether N-acetylcysteine could increase the concentrations of the antioxidant reduced glutathione in plasma and bronchoalveolar lavage fluid. Bronchoalveolar lavage was performed 1-3 hours (group 2, n = 9) and 16-20 hours (group 3, n = 10) after the last dose of N-acetylcysteine and the values were compared with those in a control group receiving no N-acetylcysteine (group 1, n = 8). N-acetylcysteine was not detected in plasma or lavage fluid. Plasma concentrations of cysteine, the main metabolite of N-acetylcysteine and a precursor of reduced glutathione, were greater in the groups receiving treatment (groups 2 and 3) than in group 1. Cysteine concentrations in lavage fluid were similar in the three groups. Concentrations of reduced glutathione were greater in both plasma and lavage fluid in group 2 than in group 1. These data suggest that N-acetylcysteine given by mouth is rapidly deacetylated to cysteine, with resulting increases in the concentrations of cysteine in plasma and of reduced glutathione in plasma and the airways, which thus temporarily increase the antioxidant capacity of the lung. Images PMID:1871695

  17. UVC Irradiation for Pathogen Reduction of Platelet Concentrates and Plasma.

    PubMed

    Seltsam, Axel; Müller, Thomas H

    2011-01-01

    Besides the current efforts devoted to microbial risk reduction, pathogen inactivation technologies promise reduction of the residual risk of known and emerging infectious agents. A novel pathogen reduction process for platelets, the THERAFLEX UV-Platelets system, has been developed and is under clinical evaluation for its efficacy and safety. In addition, proof of principle has been shown for UVC treatment of plasma units. The pathogen reduction process is based on application of UVC light of a specific wavelength (254 nm) combined with intense agitation of the blood units to ensure a uniform treatment of all blood compartments. Due to the different absorption characteristics of nucleic acids and proteins, UVC irradiation mainly affects the nucleic acid of pathogens and leukocytes while proteins are largely preserved. UVC treatment significantly reduces the infectivity of platelet units contaminated by disease-causing viruses and bacteria. In addition, it inactivates residual white blood cells in the blood components while preserving platelet function and coagulation factors. Since no photoactive compound needs to be added to the blood units, photoreagent-related adverse events are excluded. Because of its simple and rapid procedure without the need to change the established blood component preparation procedures, UVC-based pathogen inactivation could easily be implemented in existing blood banking procedures. PMID:21779205

  18. 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

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

    PubMed

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

    2013-10-01

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

  20. 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.

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

    PubMed

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

    2016-03-01

    OBJECTIVE To evaluate circadian and postprandial variations in plasma citrulline concentration in healthy dogs. ANIMALS 8 healthy Beagles. PROCEDURES 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. RESULTS 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). CONCLUSIONS AND CLINICAL RELEVANCE 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. PMID:26919600

  2. Identifying plasma glycerol concentration associated with urinary glycerol excretion in trained humans.

    PubMed

    Nelson, Jeff L; Harmon, Molly E; Robergs, Robert A

    2011-11-01

    Glycerol has been used as a means to legitimately hyperhydrate the body in an attempt to offset the deleterious effects of dehydration. It has the potential to mask blood doping practices and as a result has been added to the WADA prohibited substance list. The purpose of this study was to identify the plasma glycerol concentration coinciding with urinary glycerol excretion. Twelve healthy, trained male subjects completed five separate trials under resting conditions. For each trial, subjects consumed a different glycerol dose (0.025, 0.05, 0.10, 0.15, or 0.20 g glycerol/kg LBM) of a 5% glycerol solution in order to determine at what plasma glycerol concentration an increase in urine glycerol concentration becomes apparent. Based on regression analysis, plasma glycerol concentrations > 0.327 ± 0.190 mmol/L and a glycerol dose > 0.032 ± 0.010 g glycerol/kg LBM would be associated with urinary glycerol excretion. There were significant linear relationships between peak plasma glycerol concentration and time to reach peak plasma glycerol concentration to the ingested glycerol doses. Our findings illustrate the importance of considering the effect of urinary glycerol excretion on legitimate hyperhydration regimens as well as suggesting that it is possible to detect surreptitious use of glycerol as a masking agent through urinary analysis. PMID:22080901

  3. INFLUENCE OF GENDER, SEX HORMONES AND TEMPERATURE ON PLASMA IGF-I CONCENTRATIONS IN SUNSHINE BASS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasma insulin-like growth factor-I (IGF-I) concentrations in male and female sunshine bass were determined in March, early April and late April in outdoor ponds at a commercial farm. Growth and IGF-I concentrations in sunshine bass fed with estrogen, testosterone, methyl testosterone or a control ...

  4. 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

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

    USGS Publications Warehouse

    Guillette, L.J., Jr.; 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.

  6. Amiodarone concentrations in plasma and fat tissue during chronic treatment and related toxicity

    PubMed Central

    Lafuente-Lafuente, Carmelo; Alvarez, Jean-Claude; Leenhardt, Antoine; Mouly, Stéphane; Extramiana, Fabrice; Caulin, Charles; Funck-Brentano, Christian; Bergmann, Jean-François

    2009-01-01

    AIMS To determine if amiodarone, highly lipophilic, accumulates in excess with respect to dose in fat tissue during long-term administration, and study if plasma and fat tissue concentrations are correlated with adverse effects. METHODS Trough concentrations of amiodarone and N-desethyl-amiodarone were measured simultaneously in plasma and fat tissue, in 30 consecutive patients treated with amiodarone for 3 months to 12 years. Subcutaneous adipose tissue was obtained by needle aspiration from lumbar and abdominal areas. Concentrations were measured by liquid chromatography–tandem mass spectrometry. RESULTS Plasma levels of amiodarone and N-desethyl-amiodarone were significantly correlated with daily maintenance doses (R = 0.52, P = 0.003). Amiodarone concentrations in fat tissue were four to 226 times (mean 55) higher than in plasma, and well correlated with plasma levels (R = 0.68, P < 0.001). Concentrations of amiodarone and N-desethyl-amiodarone in adipose tissue did not significantly increase with higher total cumulated doses or longer treatment duration. Nine of 12 patients who had received amiodarone for ≥2 years developed clinically important adverse effects, predominantly hypothyroidism (n = 6), compared with two of 18 patients treated for less time (relative risk 6.75; 95% confidence interval 1.8, 26). The incidence of those adverse effects was not significantly associated with amiodarone concentrations, whether in plasma or in adipose tissue. CONCLUSIONS We found no evidence of excessive or unexpected accumulation of amiodarone in fat tissue on long-term administration. Late amiodarone adverse effects, particularly hypothyroidism, are associated with longer exposure times, but do not seem to be explained by higher concentrations in plasma or in fat tissue. PMID:19552745

  7. In Vitro Comparative Efficacy of Voriconazole and Itraconazole against Fluconazole-Susceptible and -Resistant Cryptococcus neoformans Isolates

    PubMed Central

    Nguyen, M. Hong; Yu, Christine Y.

    1998-01-01

    In vitro susceptibility testing for 50 clinical isolates of fluconazole-susceptible or -resistant Cryptococcus neoformans was performed with itraconazole and voriconazole. Voriconazole was more potent than itraconazole for fluconazole-susceptible isolates and as potent as itraconazole for fluconazole-susceptible dose-dependent isolates and for fluconazole-resistant isolates. For fluconazole-resistant isolates, the voriconazole and itraconazole MICs ranged from 1 to 2 μg/ml. PMID:9527812

  8. The plasma dilution factor: predicting how concentrations in plasma and serum are affected by blood volume variations and blood loss.

    PubMed

    Flordal, A

    1995-10-01

    To determine the effects of therapeutic interventions on plasma protein concentrations, it is often desirable to rule out nonspecific effects of hemodilution. Because red cells are restricted to the vascular space, the hematocrit (Hct) is a convenient marker. At the bedside--and even in scientific reports--a simple ratio of Hcts (obtained before and after the change in plasma volume) is often used to "correct" the value of interest. This is incorrect, and it may introduce a sizeable error. A new method, the plasma dilution factor (PDF), has been mathematically deduced. It accounts for the influence of any blood loss, plasma osmolality changes, and blood volume variations on plasma and serum concentrations. In an in vitro experiment, blood loss and osmolality and blood volume changes were simulated through the withdrawal of various volumes of blood, which were replaced with smaller, identical, or larger volumes of hypotonic, isotonic, or hypertonic solutions. The PDF accurately predicted changes in concentrations of albumin, fibrinogen, and antithrombin III. In contrast, the Hct ratio significantly underestimated the effects of dilution. Von Willebrand factor concentrations after hemodilution through dextran infusion in volunteers were the same as predicted by the PDF. In patients undergoing orthopedic surgery who were also given dextran, the postdilution von Willebrand factor concentrations were higher than predicted by the PDF. The Hct gave a false impression of a decrease in the volunteers that was not explained by hemodilution, and it failed to detect the von Willebrand factor response to trauma in the surgical patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7561443

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

    USGS Publications Warehouse

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

    1981-01-01

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

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

    SciTech Connect

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

    1981-06-01

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

  11. Diazepam and N-desmethyldiazepam concentrations in saliva, plasma and CSF.

    PubMed Central

    Hallstrom, C; Lader, M H

    1980-01-01

    1 Salivary and plasma diazepam and nordiazepam concentrations were measured in 51 paired samples from four experimental situations. In seven of the patients CSF samples were estimated. 2 Correlation of 0.89 (P less than 0.001) was observed between salivary and plasma diazepam and 0.81 (P less than 0.001) between salivary and plasma nordiazepam. 3 Mean salivary diazepam was 1.6% (+/- 0.3%) of the plasma diazepam. It was found to vary markedly in an acute dosage study. Mean salivary nordiazepam was 2.9% (+/- 1%) of the plasma measure and was dependent on salivary flow rate. 4 CSF diazepam was in equilibrium with unbound plasma diazepam and salivary diazepam. 5 Mean protein binding of diazepam in vitro was 99.3% with no variations as a function of concentration. 6 The results suggest salivary diazepam and nordiazepam measures to be of value in epidemiological studies. However, they do not predict accurately the plasma total or unbound drug concentration from a salivary sample in an individual. PMID:6769453

  12. Time to overcome fluconazole resistant Candida isolates: Solid lipid nanoparticles as a novel antifungal drug delivery system.

    PubMed

    Moazeni, Maryam; Kelidari, Hamid Reza; Saeedi, Majid; Morteza-Semnani, Ketayoun; Nabili, Mojtaba; Gohar, Atefeh Abdollahi; Akbari, Jafar; Lotfali, Ensieh; Nokhodchi, Ali

    2016-06-01

    Antifungal therapy results in complications in management due to changes in the patterns of epidemiology and drug susceptibility of invasive fungal infections. In this study, we prepared fluconazole-loaded solid lipid nanoparticles (FLZ-SLNs) and investigated the efficacy of the optimal formulation on fluconazole (FLZ)-resistant strains of several Candida species. FLZ-SLN was produced using probe ultrasonication techniques. The morphology of the obtained SLNs was characterized by field emission scanning electron microscopy. The minimum inhibitory concentrations for the new formulations against fluconazole-resistant strains of Candida were investigated using CLSI document M27-A3. The FLZ-SLNs presented a spherical shape with a mean diameter, zeta potential and entrapment efficiency of 84.8nm, -25mV and 89.6%, respectively. The drug release from FLZ-SLNs exhibited burst release behaviour at the initial stage (the first 30min) followed by a sustained release over 24h FLZ-resistant yeast strains behaved as susceptible strains after treatment with FLZ-SLNs (≤8μg/ml). The MIC50 drug concentrations were 2μg/ml, 1μg/ml and 2μg/ml for FLZ-resistant strains of Candida albicans, Candida parapsilosis and Candida glabrata, respectively. In this study, we evaluated novel delivery systems for combating Candida strains that exhibit low susceptibility against the conventional formulation of FLZ as a first-line treatment. PMID:26974361

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

    PubMed

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

    1985-08-01

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

  14. Association between plasma zinc concentration and zinc kinetic parameters in premenopausal women.

    PubMed

    Yokoi, Katsuhiko; Egger, Norman G; Ramanujam, V M Sadagopa; Alcock, Nancy W; Dayal, Hari H; Penland, James G; Sandstead, Harold H

    2003-11-01

    The objective of this study was to measure relationships between plasma zinc (Zn) concentrations and Zn kinetic parameters and to measure relationships of Zn status with taste acuity, food frequency, and hair Zn in humans. The subjects were 33 premenopausal women not taking oral contraceptives and dietary supplements containing iron and Zn. Main outcomes were plasma Zn concentrations, Zn kinetic parameters based on the three-compartment mammillary model using 67Zn as a tracer, electrical taste detection thresholds, and food frequencies. Lower plasma Zn was significantly (P < 0.01) associated with smaller sizes of the central and the lesser peripheral Zn pools, faster disappearance of tracer from plasma, and higher transfer rate constants from the lesser peripheral pool to the central pool and from the central pool to the greater peripheral pool. The break points in the plasma Zn-Zn kinetics relationship were found between 9.94 and 11.5 micromol/l plasma Zn. Smaller size of the lesser peripheral pool was associated with lower frequency of beef consumption and higher frequency of bran breakfast cereal consumption. Hypozincemic women with plasma Zn <10.7 micromol/l or 700 ng/ml had decreased thresholds of electrical stimulation for gustatory nerves. Our results based on Zn kinetics support the conventional cutoff value of plasma Zn (10.7 micromol/l or 700 ng/ml) between normal and low Zn status. PMID:12865259

  15. 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.

  16. Invitro Anti-mycotic Activity of Hydro Alcoholic Extracts of Some Indian Medicinal Plants against Fluconazole Resistant Candida albicans

    PubMed Central

    Varadarajan, Saranya; Malaisamy, Malaiyandi; Duraipandian, Chamundeeswari

    2015-01-01

    Background Candidiasis is one of the most common opportunistic infections caused by Candida albicans. Fluconazole is the drug of choice for prevention and management of this condition. However, the emergence of fluconazole resistant candidal strains has become a major concern. Many herbs like fenugreek, cinnamon, papaya, oregano, garlic are rich in phytochemical constituents known to express antimycotic activity. With the available information, the present research study was carried out to assess the invitro anti-mycotic activity of hydro alcoholic extracts of Trigonella foenum-graecum seeds, Cinnamomum verum bark and Carica papaya leaves and seeds against fluconazole resistant Candida albicans Materials and Methods Hydro alcoholic extracts of Trigonella foenum-graecum (seeds), Cinnamomum verum (bark), Carica papaya CO.2 strain (male and female leaves) and Carica papaya CO.2 strain (seeds) were prepared by maceration. The anti-mycotic activity of the prepared extracts against Candida albicans was assessed by agar well diffusion method. Three independent experiments were performed in triplicates and the mean and standard deviation were calculated. Minimum inhibitory concentration was determined. Results The results of the present study revealed that all the extracts exhibited anti-mycotic activity in a dose dependent manner and minimum inhibitory concentration of all the extracts was found to be 15.62 μg/ml. Conclusion The results of the present study shed light on the fact that plant extracts could be used not only as an alternate drug for management of fluconazole resistant candidiasis but also explored further for oral cancer prevention as a therapeutic adjunct. PMID:26436036

  17. Liver-to-plasma vaniprevir (MK-7009) concentration ratios in HCV-infected patients

    PubMed Central

    Wright, D Hamish; Caro, Luzelena; Cerra, Michael; Panorchan, Paul; Du, Lihong; Anderson, Melanie; Potthoff, Andrej; Nachbar, Robert B; Wagner, John; Manns, Michael P; Talal, Andrew H

    2016-01-01

    Background Some drugs that are actively taken up into the liver exhibit greater than dose proportional increases in plasma exposure, although human liver-to-plasma concentration ratios have rarely been evaluated. Understanding these relationships has implications for drug concentrations at the target site for certain classes of compounds, such as direct-acting antivirals, targeted towards HCV. Methods Treatment-experienced, chronic HCV non-cirrhotic patients (n=3) received vaniprevir (600 mg or 300 mg twice daily) on days 1–3 and (600 mg or 300 mg single dose) on day 4. Core needle biopsy was performed at 6 or 12 h post-dose on day 4. Blood samples were collected pre-dose on days 1 and 4, and for 24 h post-dose on day 4. The primary study objective was the hepatic concentration of vaniprevir at 6 and 12 h post-dose. Results Vaniprevir plasma pharmacokinetic parameters increased in a greater than dose-proportional manner between the 300 mg and 600 mg doses, with approximately fivefold increases in AUC0–12 and Cmax associated with a twofold increase in dose (AUC0–12, 10.6 µM/h to 59.5 µM/h; Cmax, 2.60 µM to 13.5 µM). In the 300 mg and 600 mg dose groups, mean liver concentrations of vaniprevir were 84.6 µM and 169 µM at 6 h post-dose, and 29.4 µM and 53.7 µM at 12 h post-dose. Liver concentrations were higher than plasma with liver-to-plasma concentration ratios of approximately 20–280. Conclusions These data confirm higher vaniprevir concentrations in human liver compared with plasma and demonstrate that measurement of human liver drug concentration using needle biopsy is feasible. PMID:25849338

  18. 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

  19. 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. PMID:25130711

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  2. Effects of clinically occurring chronic lameness in sheep on the concentrations of plasma noradrenaline and adrenaline.

    PubMed

    Ley, S J; Livingston, A; Waterman, A E

    1992-07-01

    Plasma adrenaline (AD) and noradrenaline (NA) concentrations were measured by high performance liquid chromatography with electrochemical detection in blood samples from control and lame sheep. The lame sheep suffered from naturally occurring foot rot and showed behavioural characteristics normally associated with chronic pain. The lame sheep were scored both for impairment of gait and pathology of the foot and divided into mild and severely affected groups. Both the mildly and severely lame group showed a significant increase in plasma AD and plasma NA which tended to persist even after clinical resolution of the condition. The measurement of plasma AD and NA may provide information which can be used to assess animals experiencing chronic pain, when taken in conjunction with other parameters, such as nociceptive thresholds and plasma hormone levels. PMID:1410809

  3. Pharmacokinetics and plasma concentrations of acetylsalicylic acid after intravenous, rectal, and intragastric administration to horses.

    PubMed

    Broome, Ted A; Brown, Murray P; Gronwall, Ronald R; Casey, Matthew F; Meritt, Kelly A

    2003-10-01

    Six healthy adult horses (5 mares and 1 stallion) were given a single dose of acetylsalicylic acid (ASA), 20 mg/kg of body weight, by intravenous (IV), rectal, and intragastric (IG) routes. Serial blood samples were collected via jugular venipuncture over a 36-h period, and plasma ASA and salicylic acid (SA) concentrations were determined by high-performance liquid chromatography. After IV administration, the mean elimination rate constant of ASA (+/- the standard error of the mean) was 1.32 +/- 0.09 h(-1), the mean elimination half-life was 0.53 +/- 0.04 h, the area under the plasma concentration-versus-time curve (AUC) was 2555 +/- 98 microg x min/mL, the plasma clearance was 472 +/- 18.9 mL/h/kg, and the volume of distribution at steady state was 0.22 +/- 0.01 L/kg. After rectal administration, the plasma concentration of ASA peaked at 5.05 +/- 0.80 microg/mL at 0.33 h, then decreased to undetectable levels by 4 h; the plasma concentration of SA peaked at 17.39 +/- 5.46 microg/mL at 2 h, then decreased to 1.92 +/- 0.25 microg/mL by 36 h. After rectal administration, the AUC for ASA was 439.4 +/- 94.55 microg x min/mL and the bioavailability was 0.17 +/- 0.037. After IG administration, the plasma concentration of ASA peaked at 1.26 +/- 0.10 microg/mL at 0.67 h, then declined to 0.37 +/- 0.37 microg/mL by 36 h; the plasma concentration of SA peaked at 23.90 +/- 4.94 microg/mL at 4 h and decreased to 0.85 +/- 0.31 microg/mL by 36 h. After IG administration, the AUC for ASA was 146.70 +/- 24.90 microg x min/mL and the bioavailability was 0.059 +/- 0.013. Administration of a single rectal dose of ASA of 20 mg/kg to horses results in higher peak plasma ASA concentrations and greater bioavailability than the same dose given IG. Plasma ASA concentrations after rectal administration should be sufficient to inhibit platelet thromboxane production, and doses lower than those suggested for IG administration may be adequate. PMID:14620867

  4. Plasma aldosterone and sweat sodium concentrations after exercise and heat acclimation

    NASA Technical Reports Server (NTRS)

    Kirby, C. R.; Convertino, V. A.

    1986-01-01

    The relationship between plasma aldosterone levels and sweat sodium excretion after chronic exercise and heat acclimation was investigated, using subjects exercised, at 40 C and 45 percent humidity, for 2 h/day on ten consecutive days at 45 percent of their maximal oxygen uptake. The data indicate that, following heat acclimation, plasma aldosterone concentrations decrease, and that the eccrine gland responsiveness to aldosterone, as represented by sweat sodium reabsorption, may be augmented through exercise and heat acclimation.

  5. Vulvovaginal candidiasis: species distribution, fluconazole resistance and drug efflux pump gene overexpression.

    PubMed

    Zhang, Jie-Yu; Liu, Jin-Hui; Liu, Fa-Di; Xia, Yan-Hua; Wang, Jing; Liu, Xi; Zhang, Zhi-Qin; Zhu, Na; Yan-Yan; Ying, Ying; Huang, Xiao-Tian

    2014-10-01

    The increasing incidence of vulvovaginal candidiasis (VVC) and the emergence of fluconazole resistance are an indisputable fact. However, little information is available regarding the correlation between fluconazole resistance in vaginal Candida albicans and the expression of drug efflux pump genes. In this study, we investigated the species distribution, fluconazole susceptibility profiles and the mechanisms of fluconazole resistance in Candida strains. In total, 785 clinical Candida isolates were collected from patients with VVC. C. albicans was the most frequently isolated species(n = 529) followed by C. glabrata (n = 164) and C. krusei (n = 57). Of all Candida isolates, 4.7% were resistant to fluconazole. We randomly selected 18 fluconazole resistant isolates of C. albicans to evaluate the expression of CDR1, CDR2, MDR1 and FLU1 genes. Compared with fluconazole-susceptible C. albicans isolates, CDR1 gene expression displayed 3.16-fold relative increase, which was statistically significant. CDR2, MDR1 and FLU1 overexpression was observed in several fluconazole-resistant C. albicans isolates, but statistical significance was not achieved. These results demonstrate a high frequency of non-albicans species (32.6%); however, C. albicans is the most common Candida species implicated in vaginitis, and this strain displays considerable fluconazole resistance. Meanwhile, our study further indicates that fluconazole resistance in C. albicans may correlate with CDR1 gene overexpression. PMID:24962255

  6. 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. PMID:26946249

  7. Leptin concentration in plasma and in milk during the interpartum period in the mare.

    PubMed

    Romagnoli, U; Macchi, E; Romano, G; Motta, M; Accornero, P; Baratta, M

    2007-01-01

    The aim of this work is to investigate on plasma profiles of leptin and estradiol 17beta during the interpartum period and leptin concentrations in the milk and in the colostrum during the period from parturition to the successive delivery in mare. Leptin plasma concentration varied from 5.1+/-2.3 ng/ml after the first parturition (week 0) to 3.0+/-0.7 at week 21 (p<0.05), then it increased to maximal level at week 49 (6.9+/-1.0 ng/ml, p<0.05). Leptin concentration in the colostrum and in the milk has been significantly (p<0.05) higher than that in plasma samples at week 1 (milk 8.8+/-2.3 versus plasma 5.2+/-0.6 ng/ml) and between week 12 and 17. This difference may be explained with a local leptin production at mammary level and supports a role of leptin in the mammary gland and/or in foal intestine. Estradiol 17beta increased from week 15 (17.9+/-2.3 pg/ml) up to 487.9+/-67.7 pg/ml at week 43. Plasma estradiol 17beta rise anticipated by 4 weeks plasma leptin increase and it does not seem to be positively correlated to leptin secretion. PMID:16524675

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

    PubMed

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

    1987-01-01

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

  9. Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis.

    PubMed

    Roos, Per M; Vesterberg, Olof; Syversen, Tore; Flaten, Trond Peder; Nordberg, Monica

    2013-02-01

    Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons. The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms. In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n = 17) of ALS patients diagnosed with quantitative electromyography. Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry. Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF. We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e.g. inward directed transport. A pattern of multiple toxic metals is seen in ALS CSF. The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS. PMID:23225075

  10. Garcinia xanthochymus Benzophenones Promote Hyphal Apoptosis and Potentiate Activity of Fluconazole against Candida albicans Biofilms.

    PubMed

    Jackson, Desmond N; Yang, Lin; Wu, ShiBiao; Kennelly, Edward J; Lipke, Peter N

    2015-10-01

    Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia xanthochymus fruits, showed multiple activities against Candida albicans biofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic, with MICs of 1 to 3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatidyl serine and DNA fragmentation, as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms, xanthochymol and garcinol caused the death of biofilm hyphae, with 50% effective concentrations (EC50s) of 30 to 50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50 from >1,024 μg/ml to 13 μg/ml. Therefore, xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis. PMID:26195512

  11. Association phenothiazine and laser on growth of C. tropicalis fluconazole-resistant

    NASA Astrophysics Data System (ADS)

    Gomes Júnior, Rafael Araújo; de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Santos, Gustavo M. P.; Sampaio, Fernando J. P.; Gesteira, Maria F. M.; Zanin, Fátima A. A.; Brugnera, Aldo; Pinheiro, Antônio Luiz B.; Vannier-Santos, Marcos A.

    2014-02-01

    Candidiasis is caused by Candida species found on the skin, gastrointestinal tract and mucous cavities of the humans and may be acute, chronic, localized or systemic. Alhough C. albicans is the species most often identified as responsible for this type of infection C. Tropicalis has been considered an emerging cause. The effect of the association of phenothiazine - PTZ and laser on fluconazole-resistant C.tropicalis growth was tested. 2.5 x 106 CFU/mL 100mg/mL of phenothiazine with the pre-irradiation time of 10 min were irradiated with laser light (660 nm; 4.8 and 12 J/cm2 (L1 and L2 respectively) 40 mW) followed by incubation in RPMI for 24h. The following conditions were tested: control (control), laser (L1 and L2), phenothiazine (F1 and F2), and PACT (F1L1 and F2L2). Statistically significant diferences were seen between groups (L-F +) and (F + L +) for both conditions of the laser, with a growth inhibition of the yeast around 67 and 51%, respectively, however, when using only the laser there was an increase of 18% in the survival of these cells. PACT's efficacy on fluconazole-resistant C. tropicalis depended on both the time of pre-irradiation and concentration of the PTZ.

  12. Comparative in vitro activities of fluconazole, voriconazole, and MXP-4509 against Romanian blood yeast isolates.

    PubMed

    Mareş, Mihai; Năstasă, Valentin; Ramona, Florina Moraru; Doroftei, Bogdan; Stefanache, Alina

    2011-12-01

    The aim of the study was to evaluate the antifungal activity of a new triazole formulation against 182 clinical isolates of yeasts recovered from blood cultures in three tertiary hospitals in Romania and to compare its activity with those of fluconazole and voriconazole. In vitro susceptibility was assessed by following the guidelines of AFST-EUCAST E. Def. 7.1. The distribution of minimum inhibitory concentrations (MICs) of MXP-4509 was very similar to that of voriconazole (MIC(50): 0.0312 mg/l vs. 0.0156 mg/l; MIC(90): 0.25 mg/l vs. 0.25 mg/l), but significantly different from that of fluconazole (MIC(50): 0.0312 mg/l vs. 0.5 mg/l; MIC(90): 0.25 mg/l vs. 32 mg/l). The new triazole MXP-4509 proved to have a good in vitro antifungal activity raising the interest for further pharmacological and microbiological investigations in order to assess its potential advantages for therapy. PMID:21805354

  13. Preparation of Fluconazole β-Cyclodextrin Complex Ocuserts: In Vitro and In Vivo Evaluation

    PubMed Central

    Abdul Ahad, Hindustan; Sreeramulu, J.; Padmaja, B. Suma; Reddy, M. Narasimha; Prakash, P. Guru

    2011-01-01

    The main purpose of the present study was to develop ocuserts of Fluconazole β-CD (beta-cyclodextrin) complex and to evaluate both in vitro and in vivo. Fluconazole was made complex with β-CD, and the release rate was controlled by HPMC K4M and ethyl cellulose polymers using dibutyl Phthalate as permeability enhancer. Drug-polymer interactions were studied by Fourier transform infrared spectroscopic studies. The formulated ocuserts were tested for physicochemical parameters of in vitro release and in vivo permeation in rabbits. The optimized formulations (F-5 and F-8) were subjected to stability studies. The formulated ocuserts were found to have good physical characters, thickness, diameter, uniformity in weight, folding endurance, less moisture absorption, and controlled release of drug both in vitro and in vivo. The optimized formulations retained their characteristics even after stability studies. The study clearly showed that this technique was an effective way of formulating ocuserts for retaining the drug concentration at the intended site of action for a sufficient period of time and to elicit the desired pharmacological response. PMID:22389846

  14. Garcinia xanthochymus Benzophenones Promote Hyphal Apoptosis and Potentiate Activity of Fluconazole against Candida albicans Biofilms

    PubMed Central

    Jackson, Desmond N.; Yang, Lin; Wu, ShiBiao; Kennelly, Edward J.

    2015-01-01

    Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia xanthochymus fruits, showed multiple activities against Candida albicans biofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic, with MICs of 1 to 3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatidyl serine and DNA fragmentation, as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms, xanthochymol and garcinol caused the death of biofilm hyphae, with 50% effective concentrations (EC50s) of 30 to 50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50 from >1,024 μg/ml to 13 μg/ml. Therefore, xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis. PMID:26195512

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

    PubMed Central

    HU, WEI; SHI, LEI; ZHOU, PANG-HU; ZHANG, XIAO-BIN

    2015-01-01

    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

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

    PubMed

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

    2009-01-01

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

  17. In vitro activities of voriconazole (UK-109, 496), fluconazole, itraconazole and amphotericin B against 132 non-albicans bloodstream yeast isolates (CANARI study).

    PubMed

    Swinne, D; Watelle, M; Van der Flaes, M; Nolard, N

    2004-06-01

    The aim was to evaluate the in vitro activity of voriconazole compared with those of amphotericin B, itraconazole and fluconazole against 132 bloodstream isolates of Candida non-albicans and Saccharomyces cerevisiae species. The minimal inhibitory concentrations (MICs) were determined by an adapted National Committee for Clinical Laboratory Standards (NCCLS) M27-A method using RPMI 1640 as test medium supplemented with 2% glucose. MIC end-points were determined with a spectrophotometer after incubation for 48 h at 35 degrees C. Optical density data were used for the calculation of the MIC end-points. For amphotericin B, the end-point was defined as the minimal antifungal concentration that exerts 90% inhibition compared with the control well growth. For the azoles, the end-points were determined at 50% inhibition of growth. Amphotericin B is highly active with 97% of isolates inhibited by < or =1 microg ml(-1). Decreased susceptibility or resistance to fluconazole was the rule among C. krusei, which is intrinsically resistant to fluconazole. For C. glabrata isolates, resistance to fluconazole and itraconazole was measured in 13% and 17% of the isolates respectively. Voriconazole was quite active in vitro against all the isolates with a MIC90% of < or =1 microg ml(-1) and we conclude that it may be useful in the treatment of non-albicans bloodstream infections. PMID:15189180

  18. Size at birth and plasma insulin-like growth factor-1 concentrations.

    PubMed Central

    Fall, C H; Pandit, A N; Law, C M; Yajnik, C S; Clark, P M; Breier, B; Osmond, C; Shiell, A W; Gluckman, P D; Barker, D J

    1995-01-01

    OBJECTIVE--To test the hypothesis that reduced fetal growth leads to altered plasma insulin-like growth factor-1 (IGF-1) concentrations in childhood. DESIGN--A follow up study of 4 year old children whose birth weights were recorded, and of 7 year old children whose weight, length, head circumference, and placental weight were measured at birth. SETTING--Pune, India, and Salisbury, England. SUBJECTS--200 children born during October 1987 to April 1989 in the King Edward Memorial Hospital, Pune, weighing over 2.0 kg at birth and not requiring special care, and 244 children born during July 1984 to February 1985 in the Salisbury Health District and still living there. MAIN OUTCOME MEASURE--Plasma IGF-1 concentrations. RESULTS--In both groups of children, and consistent with findings in other studies, plasma IGF-1 concentrations were higher in taller and heavier children, and higher in girls than boys. Allowing for sex and current size, concentrations were inversely related to birth weight (Pune p = 0.002; Salisbury p = 0.003). Thus at any level of weight or height, children of lower birth weight had higher IGF-1 concentrations. The highest concentrations were in children who were below average birth weight and above average weight or height when studied. Systolic blood pressures were higher in children with higher IGF-1 concentrations (Pune p = 0.01; Salisbury p = 0.04). CONCLUSIONS--Children of lower birth weight develop higher circulating concentrations of IGF-1 than expected for their height and weight. This is consistent with the hypothesis that under-nutrition in utero leads to reprogramming of the IGF-1 axis. The increase of plasma IGF-1 concentrations in low birthweight children may also be linked to postnatal catch-up growth. High IGF-1 concentrations may be one of the mechanisms linking reduced fetal growth and high blood pressure in later life. PMID:7492190

  19. Cytochrome P450 epoxygenase dependence of opioid analgesia: fluconazole does not interfere with remifentanil-mediated analgesia in human subjects.

    PubMed

    Oertel, B G; Vermehren, J; Huynh, T T; Doehring, A; Ferreiros, N; Zimmermann, M; Geisslinger, G; Lötsch, J

    2014-12-01

    Cytochrome P450 (CYP) inhibitors may reduce opioid analgesia by inhibiting CYP activity-dependent post-opioid receptor signaling pathways in the brain. This suggestion was predicated on observations of highly attenuated morphine antinociception in rodents after intracerebroventricular injection of fluconazole or carrying a neuron-specific deletion of the cytochrome P450 reductase. However, based on assessments of thermal and electrical pain tolerance, respiratory function, and side effects in 21 healthy volunteers, before and during steady-state concentrations of 1.5 and 3.0 ng/ml of remifentanil at the effect site (viz., the central nervous system), administration of 400 mg/day fluconazole for 8 days in a double-blind, placebo-controlled manner failed to attenuate opioid effects. Although CYP inhibitors such as fluconazole are unlikely to attenuate remifentanil analgesia in humans, extrapolation of the findings to other opioids is premature because differences among opioid effects, such as ligand-selective biased signaling at opioid receptors, leave the possibility that CYP-dependent opioid signaling in the brain might be limited to morphine and may not extend to remifentanil. PMID:25148377

  20. Psidium guajava L. and Psidium brownianum Mart ex DC.: Chemical composition and anti - Candida effect in association with fluconazole.

    PubMed

    Morais-Braga, Maria Flaviana B; Sales, Débora L; Carneiro, Joara Nalyda P; Machado, Antonio Júdson T; Dos Santos, Antonia Thassya L; de Freitas, Maria Audilene; Martins, Gioconda Morais de A Bezerra; Leite, Nadghia Figueiredo; de Matos, Yedda Maria L S; Tintino, Saulo R; Souza, Djair S L; Menezes, Irwin R A; Ribeiro-Filho, Jaime; Costa, José G M; Coutinho, Henrique D M

    2016-06-01

    The therapeutic combinations have been increasingly used against fungal resistance. Natural products have been evaluated in combination with pharmaceutical drugs in the search for new components able to work together in order to neutralize the multiple resistance mechanisms found in yeasts from the genus Candida. The aqueous and hydroethanolic extracts from Psidium brownianum Mart ex DC. and Psidium guajava L. species were evaluated for their potential to change the effect of commercial pharmaceutical drugs against Candida albicans and Candida tropicalis strains. The tests were performed according to the broth microdilution method. Plate readings were carried out by spectrophotometry, and the data generated the cell viability curve and IC50 of the extracts against the yeasts. A chemical analysis of all the extracts was performed for detection and characterization of the secondary metabolites. The total phenols were quantified in gallic acid eq/g of extract (GAE/g) and the phenolic composition of the extracts was determined by HPLC. Fluconazole and all extracts presented high Minimum Inhibitories Concentrations (MICs). However, when associated with the extracts at sub-inhibitory concentrations (MIC/16), fluconazole had its effect potentiated. A synergistic effect was observed in the combination of fluconazole with Psidium brownianum extracts against all Candida strains. However, for Psidium guajava extracts the synergistic effect was produced mainly against the Candida albicans LM77 and Candida tropicalis INCQS 400042 strains. The IC50 values of fluconazole ranged from 19.22 to 68.1 μg/mL when it was used alone, but from 2.2 to 45.4 μg/mL in the presence of the extracts. The qualitative chemical characterization demonstrated the presence of phenols, flavonoids and tannins among the secondary metabolites. The concentration of total phenols ranged from 49.25 to 80.77 GAE/g in the P. brownianum extracts and from 68.06 to 82.18 GAE/g in the P. guajava extracts

  1. 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. PMID:15465768

  2. 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. PMID:21984397

  3. What is the concentration of hydrogen peroxide in blood and plasma?

    PubMed

    Forman, Henry Jay; Bernardo, Angelito; Davies, Kelvin J A

    2016-08-01

    The concentration of hydrogen peroxide (H2O2) in blood and plasma is a measurement that has often been made, but the absolute values remain unsettled due the great variability of results actually published in the literature. As in every tissue, the concentration of H2O2 in blood and plasma is determined by the dynamics of its production versus its removal. The major sources of H2O2 in cells will only be briefly described as they are already well documented, The production of H2O2 in red blood cells will be described as it is less well known. But, the concentration of H2O2 within cells is more problematic. Intracellular H2O2 concentration has been estimated based on the kinetics of production and elimination, while its determination is technically difficult. Furthermore, compartmentalization and gradients result in its quantitation only as an average. The sources of extracellular H2O2, particularly in plasma, will also be described briefly. The major question addressed here however, is the actual concentration of H2O2 in plasma, which has been studied extensively, but still remains controversial. PMID:27173735

  4. Plasma concentrations after oral or intramuscular vitamin K1 in neonates.

    PubMed Central

    McNinch, A W; Upton, C; Samuels, M; Shearer, M J; McCarthy, P; Tripp, J H; L'E Orme, R

    1985-01-01

    One hundred and seven healthy, breast fed infants received 1 mg vitamin K1 either at birth (orally or intramuscularly) or with the first feed (orally). Venous blood samples collected in the next 24 hours were assayed for plasma vitamin K1. In babies given the vitamin orally at birth, the peak median concentration (73 ng/ml) occurred at four hours. By 24 hours median plasma concentrations had fallen to 23 ng/ml and 35 ng/ml in the groups fed vitamin K1 at birth or with the first feed, respectively; this difference was not, however, significant. Plasma concentrations after intramuscular injection exceeded those in the oral groups at all comparable times, with a peak median concentration of 1781 ng/ml at 12 hours falling to 444 ng/ml at 24 hours. Since median plasma vitamin K1 concentrations 24 hours after oral administration were some 100 times and 1000 times greater than previously estimated adult and newborn values respectively, this study supports giving vitamin K1 orally at birth to well, mature babies to protect against early haemorrhagic disease of the newborn. Further studies are needed to determine the optimum dose for protection over subsequent weeks. PMID:4051538

  5. Preparation and Characterisation of Fluconazole Vaginal Films for the Treatment of Vaginal Candidiasis

    PubMed Central

    Kumar, L.; Reddy, M. S.; Shirodkar, R. K.; Pai, G. K.; Krishna, V. T.; Verma, R.

    2013-01-01

    Objective of the present study was to develop and evaluate vaginal films with essential in vitro studies. Films were developed using hydroxypropyl methylcellulose as a polymer and formulations were coded. The developed films were evaluated with Fourier transform infrared spectroscopy, drug content, viscosity, surface pH, thickness, mechanical characterisation and in vitro drug release study. Fourier transform infrared spectroscopy results confirmed that there is no chemical interaction between drug and stabilisers/excipients. The batch variation was not more than 5% for average thickness and weight of the films. The drug content for the prepared formulation was in the range of 72.32±0.18% to 94.48±0.54%. Viscosity of the formulations increased with the increase in concentration of polymer. Mechanical characterisation revealed that tensile strength and percentage elongation of the films improved as there is increase in degree of substitution of the polymer, but the values of modulus decreased which confirmed that all the prepared films are soft in nature. The in vitro study indicated that 1 and 2% concentrations of polymer are the least concentrations to control the release of drug whereas the 4% concentration of polymer is a good and more effective concentration to control the release. Only one prepared formulation released the drug by following anomalous transport whereas other film formulations released the fluconazole by following Fickian diffusion mechanism. Prepared vaginal films may be an important alternative for the treatment of vaginal candidiasis, because these prepared films suggest the benefits of controlled release of fluconazole at the site of absorption. PMID:24403660

  6. Treatment of experimental cryptococcosis with SCH 39304 and fluconazole.

    PubMed Central

    Negroni, R; Costa, M R; Finquelievich, J L; Iovannitti, C; Agorio, I; Tiraboschi, I N; Loebenberg, D

    1991-01-01

    The efficacy of two triazoles, SCH 39304 and fluconazole, in the treatment of disseminated cryptococcosis in Wistar rats was determined. A total of 160 rats were inoculated intracardiacally with 2 x 10(5) cells of Cryptococcus neoformans. Both drugs were administered by gavage once daily, at three doses (8, 16, and 32 mg/kg/day). Two treatment schedules were followed: (i) treatment began 1 week after infection and continued for 3 weeks and (ii) prophylaxis treatment began 3 days before infection and continued an additional 3 weeks. Evaluation was based on (i) macroscopic examination of lungs, (ii) microscopic examination of brains and lungs, (iii) histopathology of brains and lungs, and (iv) determination of number of CFU in brains. The number of CFU was the best measure of activity. SCH 39304 was more active than fluconazole in both regimens, and, prophylactically, SCH 39304 was able to achieve biological cures. PMID:1929309

  7. The Possible Efficacy of Artichoke in Fluconazole Related Hepatotoxicity

    PubMed Central

    Toprak, Omer

    2014-01-01

    Although fluconazole related hepatotoxicity (FRH) is rare, mortal acute hepatic necrosis and jaundice were reported in immunocompromised states such as acquired immunodeficiency syndrome (AIDS) and bone marrow transplant (BMT). We present a case of a patient with multiple sclerosis who developed hepatotoxicity with the use of a single 150 mg fluconazole tablet for fungal vaginitis, 10 days after methylprednisolone pulse treatment. Our patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were decreased, 1200 U/L and 800 U/L, respectively, and bilirubin levels were consistent at 37 mg/dL. Artichoke which has anticholestatic and antioxidant properties was used by our patient. She consumed a 30 mg artichoke leaf extract tea 3 times a day. The bilirubin levels significantly declined at the end of the first week and all liver function tests were normalized within 2 months. PMID:25374729

  8. 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. PMID:23635368

  9. Fluconazole induced toxic epidermal necrolysis: a case report

    PubMed Central

    2009-01-01

    Drug induced toxic epidermal necrolysis and Stevens Johnson syndrome are more commonly associated with medications such as sulfonamides, penicillin, anticonvulsants, oxicam non-steroidal anti-inflammatory drugs, allopurinol and corticosteroids. Isolated instances secondary to drugs outside of the aforementioned classes have also been reported. We report a case of probable toxic epidermal necrolysis induced by fluconazole in a 52 year old woman. PMID:20062708

  10. 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

  11. Plasma brain natriuretic peptide concentrations in patients with valvular heart disease

    PubMed Central

    Stewart, Ralph A; Lee, Mildred; Gabriel, Ruvin; Van Pelt, Niels; Newby, David E; Kerr, Andrew J

    2016-01-01

    Objective Plasma brain natriuretic peptide (BNP) concentrations predict prognosis in patients with valvular heart disease (VHD), but it is unclear whether this directly relates to disease severity. We assessed the relationship between BNP and echocardiographic measures of disease severity in patients with VHD. Methods Plasma BNP concentrations were measured in patients with normal left ventricular (LV) systolic function and isolated VHD (mitral regurgitation (MR), n=33; aortic regurgitation (AR), n=39; aortic stenosis (AS), n=34; mitral stenosis (MS), n=30), and age-matched and sex-matched controls (n=39) immediately prior to exercise stress echocardiography. Results Compared with controls, patients with VHD had elevated plasma BNP concentrations (MR median 35 (IQR 23–52), AR 34 (22–45), AS 31 (22–60), MS 58 (34–90); controls 24 (16–33) pg/mL; p<0.01 for all). LV end diastolic volume index varied by valve lesion; (MR (mean 77±14), AR (91±28), AS (50±17), MS (43±11), controls (52±13) mL/m2; p<0.0001). There were no associations between LV volume and BNP. Left atrial (LA) area index varied (MR (18±4 cm2/m2), AR (12±2), AS (11±3), MS (19±6), controls (11±2); p<0.0001), but correlated with plasma BNP concentrations: MR (r=0.42, p=0.02), MS (r=0.86, p<0.0001), AR (r=0.53, p=0.001), AS (r=0.52, p=0.002). Higher plasma BNP concentrations were associated with increased pulmonary artery pressure and reduced exercise capacity. Despite adverse cardiac remodelling, 81 (60%) patients had a BNP concentration within the normal range. Conclusions Despite LV remodelling, plasma BNP concentrations are often normal in patients with VHD. Conversely, mild elevations of BNP occur with LA dilatation in the presence of normal LV. Plasma BNP concentrations should be interpreted with caution when assessing patients with VHD. PMID:27175283

  12. 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

  13. Ibuprofen Potentiates the In Vivo Antifungal Activity of Fluconazole against Candida albicans Murine Infection

    PubMed Central

    Miranda, Isabel M.; Silva-Dias, Ana; Silva, Ana P.; Rodrigues, Acácio G.; Pina-Vaz, Cidália

    2015-01-01

    Candida albicans is the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression. PMID:25845879

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

    PubMed Central

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

    2016-01-01

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

  15. Concentrations of carotenoids, retinol, and tocopherol in plasma, in response to ingestion of a meal.

    PubMed

    Brown, E D; Rose, A; Craft, N; Seidel, K E; Smith, J C

    1989-02-01

    Field studies and epidemiological surveys may necessitate obtaining a blood sample from a nonfasted subject for nutritional assessments. We measured the effect of a standardized test meal, eaten after an overnight fast, on the concentrations of seven carotenoid fractions, retinol, and tocopherol in plasma of eight healthy adults. The 790-calorie test meal did not alter the measured concentrations. We conclude that blood sampled up to 4 h after breakfast can be validly used for these measurements. PMID:2914382

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

    PubMed Central

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

    2010-01-01

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

  17. 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.

  18. The proton concentration in the vicinity of the Io plasma torus

    NASA Technical Reports Server (NTRS)

    Tokar, R. L.; Gurnett, D. A.; Bagenal, F.

    1982-01-01

    Observations of lightning-generated whistlers conducted with the aid of the Voyager 1 plasma wave instrument during the March, 1979 encounter of Jupiter have been employed in numerous studies involving Jupiters's inner magnetosphere. In an investigation carried out by Tokar et al. (1982), the Voyager whistler observations were combined with heavy ion charged particle measurements in the Io torus to determine the light ion charge concentration along the whistler propagation paths. In the investigation, simple models were used for the plasma distribution along the propagation paths. In the present study, an improved model is used for the plasma distribution in the inner magnetosphere. The adopted model treats a plasma in diffusive equilibrium under the action of gravitational, centrifugal, and ambipolar electric field forces.

  19. Blood plasma concentrations of endocrine disrupting chemicals in Hong Kong populations.

    PubMed

    Wan, H T; Leung, P Y; Zhao, Y G; Wei, X; Wong, M H; Wong, Chris K C

    2013-10-15

    In this study we report the human plasma concentrations of some common endocrine disrupting chemicals (EDCs) in the Hong Kong population. We have analyzed 153 plasma samples for the contaminants by methods involving labeled standards spiked into the samples. Quantification was performed using high performance liquid chromatography tandem mass spectrometry for bisphenol-A (BPA) and perfluorinated compounds (PFCs), and gas chromatography mass spectrometry methods for phthalates. We found BPA, several types of PFCs and phthalates in over 90% of the plasma samples. Perfluorooctane sulfonate (PFOS) was the dominant PFC, followed by perfluroroctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS). Eight out of ten phthalates were detected, with bis(2-ethylhexyl) phthalate (DEHP) as the most abundant, followed by bis(2-methoxyethyl) phthalate (DMEP) and dioctyl phthalate (DnOP). The levels of PFOS, PFOA, PFHxS and perfluorohexanoic acid (PFHxA) were significantly higher in the male plasma samples (p<0.05), while the mean plasma levels of DEHP and n-butyl benzyl phthalate (BBP) were significantly higher in the young age group (p<0.02). The presence of the selected EDCs in human blood plasma indicates common exposure routes among different population cohorts. Although the plasma levels of the EDCs were comparable to other countries, regular monitoring of human blood EDC contamination levels is necessary to provide a time-trend database for the estimation of exposure risk and to formulate appropriate public health policy. PMID:23411151

  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. Fish oils lower rat plasma and hepatic, but not immune cell alpha-tocopherol concentration.

    PubMed

    Alexander, D W; McGuire, S O; Cassity, N A; Fritsche, K L

    1995-10-01

    These studies were designed to measure the impact of different fish oil sources of dietary (n-3) polyunsaturated fatty acid on the alpha-tocopherol content of rat immune cells. In the first experiment, rats were fed diets containing either lard, corn oil, menhaden fish oil or cod liver oil. In the second study, sardine fish oil replaced corn oil. Dietary fat source did not significantly influence body weights or the yield of immune cells in either study. In both studies, plasma and liver alpha-tocopherol concentrations were significantly lower in (n-3) polyunsaturated fatty acid-fed rats than in rats fed lard. In the first study, immune cell alpha-tocopherol concentrations followed those observed in the plasma and liver. These concentrations closely paralleled the amount of RRR-alpha-tocopheryl acetate added to diets and not the total vitamin E present, which was the same for all treatment groups. However, in the second study, alpha-tocopherol concentration of immune cells was not significantly different among rats fed lard, menhaden fish oil, and sardine fish oil. In that study both the amount and form of vitamin E were carefully balanced across dietary treatment groups. In conclusion, despite having similar amounts of (n-3) polyunsaturated fatty acids, two out of three fish oils tested did not lower immune cell alpha-tocopherol concentration even in the face of significantly reduced plasma and liver alpha-tocopherol concentrations. PMID:7562101

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

    PubMed

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

    2000-06-01

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

  3. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. DIET QUALITY SCORES AND PLASMA CONCENTRATIONS OF MARKERS OF INFLAMMATION AND ENDOTHELIAL DYSFUNCTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endothelial dysfunction is one of the mechanisms linked to an increased risk of cardiovascular disease. We assessed the association between several diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction. Diet-quality scores on the Healthy Eating Index (H...

  6. 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

  7. Plasma amino acid concentrations in 36 dogs with histologically confirmed superficial necrolytic dermatitis.

    PubMed

    Outerbridge, Catherine A; Marks, Stanley L; Rogers, Quinton R

    2002-08-01

    Plasma amino acid concentrations were measured in 36 dogs diagnosed with superficial necrolytic dermatitis (SND) via skin biopsy. The median age of the dogs was 10 years, and 27 out of 36 (75%) were male. Twenty-two out of 36 (61%) of the dogs were accounted for by six breeds; West Highland white terriers (six), Shetland sheepdogs (five), cocker spaniels (four), Scottish terriers (three), Lhasa apsos (two) and Border collies (two). The mean concentration (+/- standard deviation) was calculated for each measured plasma amino acid and compared to previously documented concentrations of plasma amino acids measured in dogs with acute and chronic hepatitis. The ratio of branched chain amino acids to aromatic amino acids in the dogs with SND was 2.6, slightly lower than that in normal dogs. The mean plasma amino acid concentrations for dogs with SND were significantly lower than for dogs with acute and chronic hepatitis. A metabolic hepatopathy in which there is increased hepatic catabolism of amino acids is hypothesized to explain the hypoaminoacidaemia seen in SND. PMID:12174180

  8. Changes in plasma gonadotrophin and prolactin concentrations following castration of the pony stallion.

    PubMed

    Collingsworth, M G; Fuller, Z; Cox, J E; Argo, C M

    2001-03-15

    Concentrations of gonadotrophins and prolactin were recorded in pony stallions castrated during the early breeding season, to examine the regulatory role of the gonad at a time when testosterone has been postulated to exert positive feedback on LH secretion. Further, gonadotrophin concentrations in geldings are reported to return to values within the normal range of the entire stallion. In an attempt to characterize this species-specific reversal, the gonadotrophin concentrations of 6 male ponies castrated on 25 March were monitored for 4 months, and 4 stallions were used to generate control data. Blood samples were collected daily, from 3 d before to 10 d after castration (Day 0), and weekly thereafter until Day 122. The pituitary response to castration was immediate. Castration resulted in a previously unreported, dramatic (13-fold) but transient (3 d) surge in circulating concentrations of LH. Concentrations of LH and FSH increased in a logarithmically scaled (LH, R2 = 0.77; FSH, R2 = 0.93) manner over the subsequent 5 wk, during which temporal changes in concentrations of both hormones were strongly correlated (R2 = 0.97). The ratio of plasma gonadotrophin concentrations was consistent throughout (LH:FSH, 1.43 +/- 0.04). Maximal concentrations of LH (20.58 +/- 1.97 ng/mL, Day 34.8 +/- 3.2) were attained approximately 2 wk before the peak in FSH (16.99 +/- 1.97 ng/mL, Day 49.7 +/- 3.0). Plasma gonadotrophin concentrations exceeded those of entire stallions throughout the study. The equine testes inhibited LH secretion during the early breeding season, and no chronic decrease in plasma gonadotrophin concentrations was recorded. However, the LH surge evident for 3 d immediately afer castration, may be related to the dynamic seasonal interaction between gonadal steroids and the regulation of pituitary gonadotrophin release. PMID:11322243

  9. Decrease in the plasma von Willebrand factor concentration following glucose ingestion: the role of insulin sensitivity.

    PubMed

    von Känel, R; Nelesen, R A; Le, D T; Ziegler, M G; Dimsdale, J E

    2001-12-01

    Elevated plasma von Willebrand factor (vWF) concentration is thought to be associated with increased prevalence of cardiovascular events in the insulin resistance syndrome. We examined the effects of oral glucose challenge and accompanying metabolic and hemodynamic changes on vWF levels with respect to insulin sensitivity. Forty normotensive and hypertensive subjects (mean age +/- SD, 40 +/- 5 years) underwent a standard oral glucose tolerance test (OGTT). Plasma vWF antigen, glucose, insulin, catecholamines, and hemodynamics were measured at rest, and at 30, 60, 90, and 120 minutes after glucose intake. Insulin sensitivity was determined by the insulin sensitivity index (ISI(0,120)). Resting plasma vWF concentration was associated with screening systolic blood pressure (BP) (r =.43, P =.005). There were time effects for all variables of interest. While vWF antigen (P =.044), epinephrine (P =.003), and diastolic BP (P =.001) decreased after glucose challenge, norepinephrine (P =.009), systolic BP (P =.022), and heart rate (P <.001) increased. Decline in vWF (area under the curve) was associated with decrease in epinephrine (r =.46, P =.004) and with screening systolic BP (r =.45, P =.004). However, neither resting plasma vWF levels nor vWF decrease following glucose ingestion were significantly associated with the ISI(0,120.) The plasma vWF concentration decreases following glucose ingestion. While mechanisms underlying this phenomenon may relate to sympathetic nervous system function, they seem not related to insulin sensitivity. Endothelial dysfunction such as caused by hypertension rather than metabolic dysregulation per se may underlie the elevated plasma vWF concentration found with insulin resistance. PMID:11735092

  10. Antagonism of Fluconazole and a Proton Pump Inhibitor against Candida albicans

    PubMed Central

    Liu, Ning-Ning

    2015-01-01

    Hospitalized ill patients, at risk for invasive candidiasis, often receive multiple medications, including proton pump inhibitors (PPIs). The antifungal fluconazole perturbs the vacuolar proton ATPase. The PPI omeprazole antagonized Candida albicans growth inhibition by fluconazole. A C. albicans codon-adapted pHluorin, Ca.pHluorin, was generated to measure cytosolic pH. The fungal cytosol was acidified by omeprazole and realkalinized by coexposure to fluconazole. Vacuolar pH was alkalinized by fluconazole. Off-target effects of any medication on fungal pathogens may occur. PMID:26596946

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

    PubMed Central

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

    2009-01-01

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

  12. Increase in plasma leptin and Lep mRNA concentrations by food intake is dependent on insulin.

    PubMed

    Patel, B K; Koenig, J I; Kaplan, L M; Hooi, S C

    1998-05-01

    Obese (Lep) gene expression and leptin secretion are regulated by changes in food intake. However, the mechanism by which leptin concentrations are altered by fasting and feeding is unclear. Since these changes occur in parallel with changes in plasma insulin, it is possible that the changes observed are mediated by insulin. To test this hypothesis, we studied the role of insulin in the regulation of Lep gene expression in epididymal fat and leptin secretion during feeding. As shown previously, fasted animals showed significant reductions in Lep mRNA, plasma leptin, and plasma insulin concentrations. Conversely, feeding increased plasma insulin, Lep mRNA, and plasma leptin. In streptozotocin (STZ)-treated animals, plasma insulin concentrations were low. This was associated with low Lep mRNA and plasma leptin concentrations. Changes in food intake, whether fasting or feeding, did not significantly alter plasma insulin levels in STZ-treated animals. Under these circumstances, Lep mRNA and plasma leptin concentrations also remained low. Our results demonstrate that the decrease in Lep mRNA and plasma leptin during fasting and the increase with feeding are dependent on changes in the plasma insulin concentration. PMID:9591754

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

    PubMed

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

    1987-09-01

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

  14. Effects of CYP3A4 polymorphisms on the plasma concentration of voriconazole.

    PubMed

    He, H-R; Sun, J-Y; Ren, X-D; Wang, T-T; Zhai, Y-J; Chen, S-Y; Dong, Y-L; Lu, J

    2015-04-01

    Voriconazole is frequently utilized for the prevention and treatment of invasive fungal infections (IFIs), and is extensively metabolized by the cytochrome P450 (CYP) system. The impact of activity of the genes encoding CYP3A4, CYP3A5, and CYP2C9 on the pharmacokinetics of voriconazole cannot be ignored because, second to CYP2C19, they are the most important enzymes involved in voriconazole metabolism. The influence of genetic polymorphisms in CYP3A4, CYP3A5, and CYP2C9 on the plasma concentrations of voriconazole was evaluated in the present study. The study cohort comprised 158 patients with IFIs in whom 22 single-nucleotide polymorphisms (SNPs) in CYP3A4, CYP3A5, and CYP2C9 were genotyped using the Sequenom MassARRAY RS1000 system, and voriconazole plasma concentrations were measured by high-performance liquid chromatography (HPLC). 40, 91, and 27 patients presented with low (<1 mg/L), normal (1-4 mg/L), and high (>4 mg/L) plasma voriconazole concentrations, respectively. Correlation analysis between polymorphisms and the plasma voriconazole concentration revealed an association between the presence of the rs4646437 T allele and a higher plasma voriconazole concentration [p = 0.033, odds ratio (OR) = 2.832, 95% confidence interval (CI) = 1.086-7.384]. This study has identified a new SNP related to the metabolism of voriconazole, potentially providing novel insight into the influence of CYP3A4 on the pharmacokinetics of this antifungal agent. PMID:25515945

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

    PubMed

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

    2016-01-01

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

  16. 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.

  17. 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

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

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2016-07-01

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

  20. Plasma luteinizing hormone concentration in mares treated with gondotropin-releasing hormone and estradiol.

    PubMed

    Garcia, M C; Ginther, O J

    1975-11-01

    Three experiments were performed to study the luteinizing hormone (LH) and ovulatory responses to various doses and methods of administration of gonadotropin-releasing hormone (GnRH) in estrous pony mares and the influence of estradiol-17beta (E2-17beta) on LH response to GnRH treatment. In experiment 1, single injections of synthetic GnRH were subcutaneously given to 5 groups of estrous (day 2) mares (3 mares/group) on a body weight basis as follows: group A--isotonic saline solution; group B--GnRH, 0.14 mug/kg; group C--GnRH, 0.28 mug/kg; group D--KGnRH, 0.59 mug/kg; and group E--GnRH, 2.37 mug/kg. Significant increase of plasma LH concentration lasting for approximately 2 hours occurred only in mares of group E given the largest dose of GnRH (2.37 mug/kg). Plasma LH concentration increase at 1 hour after treatment approached significane (P less than 0.10) in mares of group D given the next smaller dose. In experiment 2, GnRH (2.37 mug/kg) was intravenously infused for 24 hours to a group of 6 mares (group F); 6 other mares (group G) were given saline solution infusion. Mean plasma LH concentration was increased at 3 hours, continued to increase until 6 hours, and remained at approximately the 6-hour concentration throughout the period of GnRH infusion. In the 3rd experiment, 3 groups of mares (4 mares/group) were subcutaneously given the following treatments on days 2 and 3 of estrus, respectively: group H--corn oil and saline solution; group I--corn oil and GnRH, 0.59 mug/kg; and group J--estradiol-17beta, 0.5 mg, and GnRH, 0.59 mug/kg. Plasma LH response was not seen in group H mares given corn oil and saline solution. Mean plasma LH concentration at 1 hour after administration of GnRH approached significance (P less than 0.10) in group I mares given corn oil and GnRH. For the mares in group J given E2-17beta and GnRH, E2-17beta pretreatment increased plasma LH after 24 horus; significnat increases of plasma LH concentration were seen from 1 to 6 hours after

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

    PubMed Central

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

    2010-01-01

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

  2. Low plasma concentrations of diet-derived antioxidants in association with microalbuminuria in Indigenous Australian populations.

    PubMed

    Rowley, Kevin; O'Dea, Kerin; Su, Qing; Jenkins, Alicia J; Best, James D

    2003-11-01

    Microalbuminuria is a risk factor for renal and cardiovascular diseases. Oxidant stress may contribute to vascular disease risk by promoting damage to renal and vascular tissues. This study examined the associations of plasma levels of diet-derived antioxidants with albuminuria in Australian population groups at high risk of renal and cardiovascular disease. Data on microalbuminuria and diet-derived plasma antioxidants were drawn from results of cross-sectional community-based risk factor surveys of Aboriginal and Torres Strait Islander peoples (n =698, 15 years and older). Prevalence of microalbuminuria ranged from 17-21%. After adjustment for age, gender, body mass index, diabetes, smoking status, plasma lipids and blood pressure, microalbuminuria was associated with significantly lower plasma concentrations of lycopene (-29%; P <0.001), beta-carotene (-22%; P <0.001), alpha-carotene (-22%; P <0.001) and cryptoxanthin (-17%; P <0.001) compared with normalbuminuric persons. Significant associations of microalbuminuria with plasma concentrations of alpha-tocopherol, retinol, lutein plus zeaxanthin and homocysteine were absent. The data are consistent with a protective effect of diets rich in carotenoids on vascular endothelium and/or renal tissues, and support the need for interventions to address affordable food supplies and dietary quality among Indigenous Australians. PMID:12826019

  3. No endogenous circadian rhythm in resting plasma Hsp72 concentration in humans

    PubMed Central

    Fortes, Matthew B.

    2008-01-01

    Extra-cellular (e) heat shock protein (Hsp)72 has been shown to be elevated in a number of clinical conditions and has been proposed as a potential diagnostic marker. From a methodological and diagnostic perspective, it is important to investigate if concentrations of eHsp72 fluctuate throughout the day; hence, the purpose of the study was to measure resting concentrations of plasma eHsp72 throughout a 24-h period. Blood samples were taken every hour from 1200–2100 hours and from 0700–1200 hours the following day from seven healthy recreationally active males. Participants remained in the laboratory throughout the trial, performed light sedentary activities and were provided with standardised meals and fluids. Physical activity was quantified throughout by the use of an accelerometer. Ethylenediaminetetraacetic acid blood samples were analysed for eHsp72 concentration using a commercially available high-sensitivity enzyme-linked immunosorbent assay (intra-assay coefficient of variation = 1.4%). One-way repeated measures analysis of variance revealed that measures of physiological stress such as heart rate, systolic and diastolic blood pressure remained stable throughout the trial and subjects remained sedentary throughout (mean activity energy expenditure above resting metabolic rate—35.7 ± 10.0 kcal∙h−1). Plasma Hsp72 concentration did not fluctuate significantly throughout the day and showed no apparent endogenous circadian rhythm in absolute (P = 0.367) or plasma volume change corrected data (P = 0.380). Individual coefficients of variation ranged from 3.8–7.7% (mean 5.4%). Mean Hsp72 concentration across all subjects and time points was 1.49 ± 0.08 ng∙ml−1. These data show that in a rested state, plasma eHsp72 concentration shows no apparent endogenous circadian rhythm. PMID:18839337

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

    SciTech Connect

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

    2006-01-15

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

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

    PubMed

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

    2013-08-01

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

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

    PubMed

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

    2016-01-01

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

  7. Hospital Specificity, Region Specificity, and Fluconazole Resistance of Candida albicans Bloodstream Isolates

    PubMed Central

    Pfaller, M. A.; Lockhart, S. R.; Pujol, C.; Swails-Wenger, J. A.; Messer, S. A.; Edmond, M. B.; Jones, R. N.; Wenzel, R. P.; Soll, D. R.

    1998-01-01

    In a survey of bloodstream infection (BSI) isolates across the continental United States, 162 Candida albicans isolates were fingerprinted with the species-specific probe Ca3 and the patterns were analyzed for relatedness with a computer-assisted system. The results demonstrate that particular BSI strains are more highly concentrated in particular geographic locales and that established BSI strains are endemic in some, but not all, hospitals in the study and undergo microevolution in hospital settings. The results, however, indicate no close genetic relationship among fluconazole-resistant BSI isolates in the collection, either from the same geographic locale or the same hospital. This study represents the first of three fingerprinting studies designed to analyze the origin, genetic relatedness, and drug resistance of Candida isolates responsible for BSI. PMID:9620370

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

    PubMed

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

    2015-12-01

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

  9. Clinically achievable plasma deferoxamine concentrations are therapeutic in a rat model of Pneumocystis carinii pneumonia.

    PubMed Central

    Merali, S; Chin, K; Del Angel, L; Grady, R W; Armstrong, M; Clarkson, A B

    1995-01-01

    The iron-chelating drug deferoxamine (DFO) has been shown to be active in animal models of Pneumocystis carinii pneumonia (PCP), with effective daily intraperitoneal bolus dosages being 400 and 1,000 mg of DFO mesylate kg of body weight-1 in mouse and rat models, respectively. Continuous infusion produced a moderately improved response in a rat model. The data reported here demonstrate that the response achieved by continuous infusion of 195 and 335 mg of DFO mesylate kg-1 day-1 in the rat model is associated with mean concentrations in plasma of 1.3 and 2.5 micrograms of DFO ml-1 and mean concentrations in lung tissue of 4.9 and 6.0 micrograms of DFO g of lung tissue-1, respectively. Since current clinical use of DFO mesylate for the treatment of iron overload produces higher concentrations in the plasma of patients, DFO may prove to be a useful anti-PCP treatment. The 2.4- to 3.8-fold higher DFO concentration observed in lung tissue compared with that observed in plasma may be important in the response of PCP to DFO. PMID:8540710

  10. Association of type 2 diabetes mellitus with plasma organochlorine compound concentrations.

    PubMed

    Eden, Paul R; Meek, Edward C; Wills, Robert W; Olsen, Eric V; Crow, J Allen; Chambers, Janice E

    2016-03-01

    The increased prevalence of type 2 diabetes mellitus (T2DM) is associated with obesity, age, and sedentary lifestyle, but exposure to some organochlorine (OC) compounds has also been recently implicated. The hypothesis tested is that higher concentrations of bioaccumulative OC compounds are associated with T2DM. Plasma samples were obtained from a cross-section of adult male and female Caucasians and African Americans, either with or without T2DM from two US Air Force medical facilities. A method of extracting OC compounds from human plasma using solid phase extraction was developed, and three OC compounds [p,p'-DDE (DDE), trans-nonachlor, and oxychlordane] were quantified by gas chromatography/mass spectrometry. Multivariable logistic regression modeling indicated that increasing body mass index (BMI) was associated with T2DM in Caucasians but not in African Americans, and African Americans were more likely to have T2DM than Caucasians with decreasing odds ratios as BMI increased. An association between T2DM and increasing plasma DDE (adjusted for age, base, race, and BMI) was observed. Increasing DDE concentrations were associated with T2DM in older individuals and those with lower BMIs. Thus, in this study sample there was a higher risk of T2DM with increasing DDE concentrations in older people of normal weight and relatively lower risk associated with increasing DDE concentrations in those who are overweight or obese. PMID:25335866